Bangerter v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 15-1186V

Filed: January 18, 2022

PUBLISHED

Special Master Horner

MANDY BANGERTER, parent and

next friend of D.B., a minor,

Infantile Spasms; Tetanus,

Petitioner, diphtheria, acellular pertussis

v. (“DTaP”) vaccine;

Pneumococcal Conjugate

SECRETARY OF HEALTH AND Vaccine; Residual Effects and

HUMAN SERVICES, Complications

Respondent.

Richard Gage, Richard Gage, P.C., Cheyenne, WY, for petitioner.

Julia Marter Collison, U.S. Department of Justice, Washington, DC, for respondent.

DECISION 1

On October 13, 2015, petitioner filed a petition under the National Childhood

Vaccine Injury Act, 42 U.S.C. § 300aa-10-34 (2012), 2 alleging that her child, D.B.,

suffered infantile spasms following his receipt of various childhood vaccinations 3 on

February 14, 2014. (ECF No. 1.) For the reasons set forth below, I conclude that

petitioner is not entitled to compensation.

1 Because this decision contains a reasoned explanation for the special master’s action in this case, it will

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

Act of 2002. See 44 U.S.C. § 3501 note (2012) (Federal Management and Promotion of Electronic

Government Services). This means the decision will be available to anyone with access to the

Internet. In accordance with Vaccine Rule 18(b), petitioner has 14 days to identify and move to redact

medical or other information the disclosure of which would constitute an unwarranted invasion of privacy.

If the special master, upon review, agrees that the identified material fits within this definition, it will be

redacted from public access.

2 Within this decision, all citations to § 300aa will be the relevant sections of the Vaccine Act at 42 U.S.C.

§ 300aa-10-34.

3 Specifically, diphtheria, tetanus and acellular pertussis (“DTaP”), Hepatitis B, Inactivated Polio Vaccine

(“IPV”), Haemophilus Influenzae type B (“HIB”), Pneumococcal Conjugate 13-Valent, and Rotavirus.

(ECF No. 1.)

1

I. Applicable Statutory Scheme

Under the National Vaccine Injury Compensation Program, compensation

awards are made to individuals who have suffered injuries after receiving vaccines. In

general, to gain an award, a petitioner must make a number of factual demonstrations,

including showing that an individual received a vaccination covered by the statute;

received it in the United States; suffered a serious, long-standing injury; and has

received no previous award or settlement on account of the injury. Finally – and the key

question in most cases under the Program – the petitioner must also establish a causal

link between the vaccination and the injury. In some cases, the petitioner may simply

demonstrate the occurrence of what has been called a “Table Injury.” That is, it may be

shown that the vaccine recipient suffered an injury of the type enumerated in the

“Vaccine Injury Table,” corresponding to the vaccination in question, within an

applicable time period following the vaccination also specified in the Table. If so, the

Table Injury is presumed to have been caused by the vaccination, and the petitioner is

automatically entitled to compensation, unless it is affirmatively shown that the injury

was caused by some factor other than the vaccination. § 300aa-13(a)(1)(A); § 300 aa-

11(c)(1)(C)(i); § 300aa-14(a); § 300aa-13(a)(1)(B).

In many cases, however, the vaccine recipient may have suffered an injury not of

the type covered in the Vaccine Injury Table. In such instances, an alternative means

exists to demonstrate entitlement to a Program award. That is, the petitioner may gain

an award by showing that the recipient’s injury was “caused-in-fact” by the vaccination

in question. § 300aa-13(a)(1)(B); § 300aa-11(c)(1)(C)(ii). In such a situation, of course,

the presumptions available under the Vaccine Injury Table are inoperative. The burden

is on the petitioner to introduce evidence demonstrating that the vaccination actually

caused the injury in question. Althen v. Sec’y of Health & Human Servs., 418 F.3d

1274, 1278 (Fed. Cir. 2005); Hines v. Sec’ of Health & Human Servs., 940 F.2d 1518,

1525 (Fed. Cir. 1991).

The showing of “causation-in-fact” must satisfy the “preponderance of the

evidence” standard, the same standard ordinarily used in tort litigation. § 300aa-

13(a)(1)(A); see also Althen, 418 F.3d at 1279; Hines, 940 F.2d at 1525. Under that

standard, the petitioner must show that it is “more probable than not” that the

vaccination was the cause of the injury. Althen, 418 F.3d at 1279. The petitioner need

not show that the vaccination was the sole cause of the injury or condition, but must

demonstrate that the vaccination was at least a “substantial factor” in causing the

condition, and was a “but for” cause. Shyface v. Sec’y of Health & Human Servs., 165

F.3d 1344, 1352 (Fed. Cir. 1999). Thus, the petitioner must supply “proof of a logical

sequence of cause and effect showing that the vaccination was the reason for the

injury;” the logical sequence must be supported by “reputable medical or scientific

explanation, i.e., evidence in the form of scientific studies or expert medical testimony.”

Althen, 418 F.3d at 1278; Grant v. Sec’y of Health & Human Servs., 956 F.2d 1144,

1148 (Fed. Cir. 1992). A petitioner may not receive a Vaccine Program award based

solely on his or her assertions; rather, the petition must be supported by either medical

records or by the opinion of a competent physician. § 300aa-13(a)(1).

2

In what has become the predominant framing of this burden of proof, the Althen

court described the “causation-in-fact” standard, as follows:

Concisely stated, Althen’s burden is to show by preponderant evidence

that the vaccination brought about her 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 proximate temporal relationship

between vaccination and injury. If Althen satisfies this burden, she is

entitled to recover unless the [government] shows, also by a

preponderance of the evidence, that the injury was in fact caused by

factors unrelated to the vaccine.

Althen, 418 F.3d at 1278 (citations omitted). The Althen court noted that a petitioner

need not necessarily supply evidence from medical literature supporting petitioner’s

causation contention, so long as the petitioner supplies the medical opinion of an

expert. Id. at 1279-80. The court also indicated that, in finding causation, a Program

fact-finder may rely upon “circumstantial evidence,” which the court found to be

consistent with the “system created by Congress, in which close calls regarding

causation are resolved in favor of injured claimants.” Id. at 1280.

II. Procedural History

This case was initially assigned to Special Master Millman. (ECF No. 4.)

Thereafter, petitioner filed medical records, Exhibits 1-3, to support her claim. (ECF No.

8.) On January 19, 2016, an initial status conference was held during which Special

Master Millman ordered petitioner to file additional supportive documentation, including

affidavits from D.B.’s treating physicians. (ECF No. 9.) Special Master Millman noted

that she “does accept that the DTaP vaccination could have caused D.B.’s infantile

spasms,” however, her review of the records revealed that D.B.’s developmental delay

may have predated his receipt of the vaccinations at issue. (Id. at 1-2.) Additionally,

she noted that “even if petitioner can prove that the vaccines significantly aggravated

D.B.’s developmental delays, petitioner’s medical records do not show that D.B.

experienced more than six months of sequalae.” 4 (Id. at 2.)

Thereafter, petitioner filed additional records, Exhibits 4-8, and a letter from Dr.

Robert Leland, D.B.’s pediatrician, Exhibit 9. (ECF Nos. 10, 12, 14.) Petitioner also

filed additional medical records (Exs. 10, 11). (ECF Nos. 20, 31.) On June 23, 2017,

petitioner filed a preliminary opinion letter from Dr. Harum, a pediatric

4 Of note, it is undisputed that D.B. had Down syndrome prior to onset of his infantile spasms; however,

petitioner does not contend that this case constitutes a significant aggravation claim with respect to D.B.’s

preexisting developmental delay. (ECF No. 1; ECF No. 108, p. 1.) Rather, petitioner contends that D.B.’s

infantile spasms represent a separate condition from his developmental delay, but one which did also

affect his developmental progress. (Id.) The parties do disagree as to whether that condition was

caused-in-fact by his vaccinations and whether residual effects of that condition interfered with his

development for more than six months. However, petitioner’s arguments regarding the residual effects of

D.B.’s infantile spasms also go beyond allegations of developmental delay.

3

neurodevelopment specialist, indicating that D.B.’s development had been affected for

more than six months following his infantile spasms. (ECF No. 40; Exs. 12-13.)

Petitioner filed a full report by Dr. Harum (Ex. 15) and further records (Ex. 14) on August

9, 2017. (ECF No. 42.) Special Master Millman ordered petitioner to file a clarifying

report by Dr. Harum, which was filed on November 6, 2017, with accompanying

literature. (ECF Nos. 43-44; Ex. 16-19.) Additionally, on January 16, 2018, petitioner

filed an opinion from neurologist Dr. Marcel Kinsbourne, with accompanying curriculum

vitae and medical literature. (ECF No. 46; Exs. 20-23.)

Respondent filed his Rule 4(c) report on April 30, 2018, recommending against

compensation. (ECF No. 51.) Thereafter, petitioner filed a supplemental expert report

by Dr. Kinsbourne and additional medical literature on August 15, 2018. (ECF No. 54;

Ex. 24-38.) Additional medical records were filed in December of 2018. (ECF No. 60;

Ex. 39.) Respondent filed a responsive expert report and supporting literature from

neurologist Dr. Gregory L. Holmes on February 4, 2019. (ECF No. 61; Ex. A.)

Petitioner filed a further supplemental report and literature Dr. Kinsbourne on May 17,

2019. (ECF No. 67; Ex. 40-48.)

This case was then reassigned to my docket on June 6, 2019, due to Special

Master Millman’s retirement. (ECF No. 69.) Thereafter, the parties filed further

supplemental expert reports. (ECF No. 70; Ex. C and ECF No. 71; Exs. 49-51 and ECF

No. 72; Ex. D.) However, on December 30, 2019, petitioner filed a status report

indicating that, after filing five expert reports, petitioner did not “feel that filing additional

expert reports will be beneficial,” and requested a hearing. (ECF No. 74.) Respondent

agreed and a hearing was scheduled. (ECF Nos. 76-77.) Thereafter, the parties filed

substantial additional medical literature in the lead up to the entitlement hearing. 5 (ECF

Nos. 83, 89, 91, 94-97, 100; Exs. 52-92.)

5 As noted above, Special Master Millman, the previously assigned special master, had indicated during a

prior status conference her acceptance that the DTaP vaccine can cause infantile spasms. (ECF No. 9.)

Thus, for example, in a November 19, 2020 prehearing brief, petitioner cited, inter alia, a ruling by Special

Master Millman, in Kottenstette v. Sec’y of Health & Human Servs., in which she found that the petitioners

had demonstrated that infantile spasms can be caused by the DTaP vaccine. ECF No. 88, p. 9 (citing

No. 15-1016V, 2017 WL 6601878 (Fed. Cl. Spec. Mstr. Dec. 12, 2017).) However, on February 12, 2020,

and subsequent to Special Master Millman’s retirement, that ruling was vacated by the Court of Federal

Claims on the basis that she had applied an incorrect legal standard. Kottenstette, No. 15-1016V, 2020

WL 953484 (Fed. Cl. Feb. 12, 2020).

Due to the retirement of the previously assigned special master, the case had been reassigned to me

and, thus, was remanded to me for evaluation of petitioner’s theory consistent with the correct legal

standard. See id. On June 2, 2020, I issued a decision on remand reaching a different result from

Special Master Millman. See Kottenstette, No. 15-1016V, 2020 WL 4197301 (Fed. Cl. Spec. Mstr. June

2, 2020). In that decision I concluded that, although petitioners had demonstrated that the Tdap vaccine

can cause febrile seizures, there was not preponderant evidence that it can cause the specific disorder of

infantile spasms. Id. at *13-14. The outcome of my analysis then turned on factors related to Althen

prong two. Id. at *15-17. Because there was not preponderant evidence that the Kottenstette child

suffered a febrile seizure, I did not reach the question under Althen prong one of whether a single febrile

seizure could ultimately lead to the type of epileptic encephalopathy implicated by the condition of

infantile spasms. Id. at n. 37.

4

A two-day entitlement hearing was held on December 17 and 18, 2020. (See

ECF No.104-05, Transcript of Proceedings (“Tr”), filed 1/21/2021). Petitioner, D.B.’s

mother, and Jedidiah Bangerter, D.B.’s father, both testified. Petitioner also presented

testimony by Drs. Harum and Kinsbourne as well as by D.B.’s occupational therapist,

Sarah Nicholas. Respondent presented expert testimony from Dr. Holmes. Petitioner

filed a post-hearing brief on March 18, 2021, and respondent filed his response on May

12, 2021. (ECF Nos. 108-09.) Petitioner did not file any reply.

After the parties filed their post-hearing briefs, the Federal Circuit issued its

decision Wright v. Secretary of Health and Human Services, which interpreted the

statutory language pertaining to the Vaccine Act’s severity requirement (42 USC §

300aa-11(c)(1)(D)). No. 2021-1524, 2022 WL 38987 (Fed. Cir. Jan. 5, 2022). The

parties were given an opportunity to file supplemental briefs addressing this new

authority. The parties filed those briefs on January 14, 2022. (ECF Nos. 113-14.)

This case is now ripe for consideration. In total, petitioner has filed 92 numbered

exhibits, including medical records (Exs. 1-7, 10-11, 14, 39), expert and treater opinion

evidence (Ex. 8-9, 12-13, 15, 20, 23-24, 40, 49), and medical literature (Exs. 17-19, 25-

38, 41-48, 50-92). 6 Respondent filed responsive expert reports (Exs. A-D) and

supporting literature (Ex. A, Tabs 1-37, and Exs. E-L). 7 Although this decision does not

In response, petitioner in this case sought to supplement the record during the prehearing phase of

proceedings to address points raised in my own analysis of the Kottenstette case as compared to that of

Special Master Millman. These filings were permitted, even though many constituted late-filed evidence

pursuant to the prehearing order. At the close of the hearing, I noted: “the last point to address would be

during the prehearing status conference, we talked about the extent to which Mr. Gage wanted to add to

the record in light of Kottenstette, my decision is Kottenstette. It looks to me as though we've done that,

and I think Ms. Collison and Dr. Holmes have responded to the articles that Mr. Gage filed. So I just want

to confirm with everybody, do we have a complete record at this point?” (Tr. 356.) Both counsel

confirmed the record to be complete. (Tr. 356-57.) Ultimately, neither party further addressed

Kottenstette in their post-hearing briefs. (ECF Nos. 108-09.)

Subsequent to my decision on remand in Kottenstette, the Court of Federal Claims denied a further

motion for review and the Federal Circuit ultimately issued a decision in Kottenstette reversing the Court

of Federal Claims and reinstating Special Master Millman’s initial ruling in favor of entitlement. No. 15-

1016V, 2020 WL 4592590 (Fed. Cl. Jul. 27, 2020), rev’d 861 Fed.Appx. 433 (2021). However, the

Circuit’s analysis of the remand decision focused on the fact that it exceeded the scope of the remand by

including a reweighing of the evidence.

6However, quite a few exhibits were duplicated largely for purposes of adding highlighting to key

passages. Exhibits 41, 57-82, and 90, duplicate previously filed exhibits.

7 Some of respondent’s exhibits likewise overlap with exhibits previously filed by petitioner. For example,

in response to Dr. Kinsbourne’s reliance on studies by Bellman, Melchior, discussed extensively below,

Dr. Holmes refiled the same exhibits highlighting the passages he felt most significant and also filed a

related study, also discussed below, by Goodman. Dr. Kinsbourne later refiled the Goodman study in his

further report. Thus, the Bellman study has been filed as Exhibit A, Tab 16, in addition to being marked

as petitioner’s Exhibits 28, 65, and 90. The Melchior study has been filed as Exhibit A, Tab 17, as well as

being filed as petitioner’s Exhibits 34 and 71. The Goodman study has been filed as Exhibit A, Tab 18, as

well as being filed as petitioner’s Exhibit 42.

5

explicitly cite every article filed by the parties, each has been reviewed and the analysis

herein is based on the record as a whole.

III. Factual History

a. As Reflected by the Medical Records

D.B. was born on July 22, 2013 with Down syndrome and chronic lung disease.

(Ex. 1, p. 1-5; Ex. 39, pp. 6-8.) He was born preterm at 34 weeks and 6 days and spent

40 days in the NICU following delivery. (Ex. 1, p. 5; Ex. 10, p. 6.) He received the

Hepatitis B vaccine on the day of his birth. (Ex. 39, p. 10.) On September 3, 2013,

D.B., at six weeks old, had a well child visit with Dr. Joseph Horam at Cheyenne

Regional Medical Center. (Ex. 1, p. 4.) D.B. had feeding and reflux issues and needed

supplemental oxygen. (Id. at 5-6; Ex. 2, pp. 4-5.) D.B. was referred to physical and

occupational therapies and speech services. (Id. at 9; Ex. 2, p. 5.) Additionally, his

history of pulmonary hypertension was found to be resolved by October 18, 2013 by Dr.

Michael Schaffer. (Ex. 1, p. 10.) D.B. underwent two genetic screenings, which were

noted by Dr. Robert Leland, pediatrician, as normal. (Id. at 23.)

At two months old, D.B. was evaluated under the Peabody Developmental Motor

Scales. (Ex. 3.) In adjusting for his prematurity, D.B. tested, on a scale of zero to two,

a two on reflexes and a one on grasping and visual integration at the age of 29 days.

(Id. at 2.) He also had his initial occupational therapy exam on September 26, 2013.

(Id. at 19.) Overall, D.B. had low oral muscle tone which contributed to his difficulties

with feeding. Also, D.B. “continue[d] to demonstrate immature neurobehavioral cues

when overstimulated, including hiccoughing, arching, color change, stop sign, shutting

down, eye gaze aversion.” (Id. at 20.)

On September 27, 2013, D.B. saw Dr. Robert Leland for his 2-month well child

visit. (Ex. 1, p. 9.) At this visit, Dr. Leland noted that D.B.’s development was

appropriate. (Id. at 11.) He returned a month later for a follow up appointment and

complained of significant nocturnal choking. (Id. at 13.) D.B.’s GERD

(gastroesophageal reflux disease) worsened and he saw Dr. Leland again on November

7, 2013. (Id. at 16.) Additionally, Dr. Leland reported that D.B. experienced intermittent

stridor. (Id.) At the next follow up visit, Dr. Leland ordered nocturnal oximetry and sleep

study and referred D.B. to a gastroenterology specialist. (Id. at 18-19.) At his 4-month

check up on November 27, 2013, D.B. was assessed as healthy and his choking has

improved. (Id. at 23-24.) On December 20, 2013, D.B. received a Synagis injection,

which he tolerated well with no reaction at site. (Ex. 1, p. 25.) However, the next day,

D.B.’s dad called the hospital concerned with D.B.’s lethargy and lack of appetite

following injection. (Id. at 25-26.)

D.B. saw Dr. Leland on January 9, 2014 for concern of D.B.’s GERD and Down

syndrome. (Ex. 1, p. 27.) Dr. Leland noted that D.B. was now only on nocturnal

oxygen, and although there is a procedure, fundoplication, Dr. Leland opined that D.B.’s

reflux needs to be reviewed once again. (Id. at 28.)

6

On February 1, 2014, at the advice of the triage nurse on an after-hours call, D.B.

went to the emergency department at Cheyenne Regional Medical Center for a croupy

cough. (Ex. 1, pp. 32-33.) Dr. Daniel Possehn’s impression was that D.B. maybe had

bronchiolitis as evident by the coarse lung markings. (Id. at 34, 118; Ex. 4, p. 1.) Upon

his discharge from the emergency department, D.B. had a follow up appointment with

Dr. Carol Schiel, who assessed him with croup, an infection that causes the throat to

swell. (Ex. 1, pp. 37-39.) D.B. had a therapy session on January 30, 2014, where

D.B.’s mom reported that D.B. was able to roll over independent and the therapy noted

that D.B. “tolerates tummy well. Using good elbow prop up to 20 seconds with neck

extension.” (Ex. 3, p. 22.)

On February 14, 2014, D.B. returned to Dr. Leland for a six-month well child visit.

At this visit, Dr. Leland indicated that “[g]rowth parameters are noted and are

appropriate for age.” (Ex. 1, p. 43.) At this visit, D.B. received DTaP, HiB,

Pneumococcal, IPV, Hep B, and rotavirus vaccinations. (Id. at 44.) Three days later on

February 17, 2014, petitioner called Dr. Leland’s office to report that D.B. appeared to

be having seizures. (Ex. 1, p. 46.) Dr. Leland suspected infantile spasms and ordered

an EEG and consultation from Dr. Dingman, neurologist. (Id. at 47.) At this visit, Dr.

Leland did assess D.B. with otitis media. (Id. at 48.) He was treated with amoxicillin.

The next day on February 18, 2014, D.B. was seen at the hospital for seizures

and was admitted for infantile spasms. (Ex. 2, p. 7; Ex. 7, p. 6.) It was reported that

D.B. had onset of abnormal movements on February 14, 2014. (Ex. 2, p. 12.) The

attending physician, Dr. Kaitlin M. Widmer, noted that D.B. appeared to have met his

milestones as a six-month old. (Id.) D.B. had a neurology consult during his stay with

Dr. Jennifer Armstrong-Wells. (Id. at 16.) Her impression was that D.B. “is a 6 month

old boy with trisomy 21 and new abnormal spells. On video, these spells are classic for

infantile spasms.” (Id.) Dr. Andra L. Dingman examined D.B. in a follow up neuro

consult and after reviewing his EEG, wanted to proceed with ACTh 8 treatment. (Id. at

27.) D.B. was discharged on February 19, 2014 with a diagnosis of infantile spams,

with secondary diagnoses of Trisomy 21 and acute otitis media. (Id. at 8.) At

discharge, it was confirmed that D.B. experienced infantile spasms as there was

evidence of hypsarrhythmia 9 on his EEG. (Id.) D.B. was discharged home to wait for

insurance approval of ACTh treatment. (Id.)

8 “ACTh” stands for adrenocorticotropic hormone, an established treatment for infantile spasms.

(Nabbout et al., Infantile Spasms in Down Syndrome: Good Response to a Short Course of Vigabatrin,

42(12) EPILEPSIA 1580-1583 (2001) (Ex. 21, p. 4); Baram & Hatalski, Neuropeptide-mediated excitability:

a key triggering mechanism for seizure negation in the developing brain, 21(11) TRENDS. NEUROSCI. 1-9, 6

(1998) (Ex. 26); Tr. 200-01, 293-94.)

9 “Hypsarrhythmia” is an electroencephalographic abnormality sometimes observed in infants, with

random, high-voltage slow waves and spikes that arise from multiple foci and spread to all cortical areas.

Hypsarrhythmia, DORLAND’s ILLUSTRATED MEDICAL DICTIONARY ONLINE,

https://www.dorlandsonline.com/dorland/definition?id=24469, last accessed January 11, 2022.

7

The following day after discharge, D.B. had a therapy session. (Ex. 3, p. 24; Ex.

5, p. 1.) D.B.’s mom reported that he had lost some head control and was not rolling

over as much as before and noted that “this may be due to seizure activity.” (Ex. 3, p.

24.) During the session, D.B. was able to complete a roll three times. 10 (Id.)

On February 26, 2014, D.B. was admitted again to initiate ACTh treatment for his

infantile spasms. (Ex. 1, p. 52; Ex. 2, p. 59; Ex. 7, p. 64.) D.B.’s parent noted

regression in his milestones, including decreased smiling and babbling, and less neck

control, but he did not have any new types of spells. (Ex. 2, pp. 61, 67.) His brain MRI

noted mild brachycephaly and nonspecific fluid signal in the left mastoid air cells and

middle ear, but was otherwise a “negative MRI.” (Ex. 1, p. 57; Ex. 2, pp. 78, 99.) D.B.

was discharged on March 1, 2014 with a diagnosis of infantile spasms and secondary

diagnoses of leukopenia and Trisomy 21. (Ex. 2, p. 56.) It was noted that “[m]ost

spams will stop after the first week of ACTh treatment.” (Id. at 72.) At discharge, D.B.

was ordered to follow up with his PCP during his ACTh treatment. (Id. at 57.)

On March 6, 2014, D.B. was examined by Dr. Andrew Rose for a reevaluation of

infantile spasms. (Ex. 1, p. 58.) Dr. Rose indicated that D.B. was on ACTh therapy and

that D.B. had significant fluid retention. (Id. at 59.) D.B. saw Dr. Leland following his

stay at the hospital on the same day. (Ex. 1, p. 52.) Dr. Leland indicated that D.B.’s

EEG showed hypsarrhythmia and he was diagnosed with infantile spasms. (Id.) Dr.

Leland prescribed him with ACTh (twice a day for two weeks and then will be tapered

down) and ordered electroencephalograms coinciding with his therapy treatment. (Id.)

Additionally, Dr. Leland indicated that D.B.’s infantile spasms had “diminished

remarkably.” (Id. at 53.)

A couple of days later on March 10, 2014, D.B. visited Dr. Leland and reported

that after three days of ACTh, D.B. did not have any further spasms. 11 (Ex. 1, p. 60; Ex.

2, p. 171.) During a reevaluation with Dr. Rose on March 21, 2014, D.B. was noted to

be more interactive, but there were still some breathing issues. (Ex. 1, pp. 69-70.) Dr.

Rose indicated that the ECHO and EEG were normal and did not show any

hypsarrhythmia. (Ex. 1, pp. 69-70; Ex. 11, pp. 1-2.)

D.B. had a therapy session on March 27, 2014, where he was noted to show

developmental improvement by sitting independently for 2-3 seconds. (Ex. 3, p. 28; Ex.

5, p. 5.) He also met two of his ongoing short-term feeding goals. (Id.) D.B. was

responding to therapy, but still demonstrated low oral tone. (Ex. 3, p. 32.) The therapy

progress notes indicated that D.B. was being treated for his infantile seizures. (Id.)

D.B. continued working on his feeding issues with therapy. 12

10 D.B. had a similar therapy session on March 6, 2014 as well. (Ex. 3, pp. 26-27.)

11 D.B.’s parents also confirmed on the March 13, 2014 visit with Dr. Leland that D.B. has not had any

seizures. (Ex. 1, p. 63.) Dr. Andrew White, who interpreted D.B.’s EEG study on March 11, 2014, noted

that D.B. did not have any new spasms since March 3, 2014. (Ex. 2, p. 171; Ex. 7, p. 162.)

12The April 17, 2014 therapy records no longer indicated infantile seizures as part of D.B.’s assessment.

And during this session, D.B. was noted to show improvement through accepting solids from spoon. (Ex.

8

In a further reevaluation with Dr. Rose, on April 1, 2014, D.B.’s mother

(petitioner) reported that D.B. was “back to his normal self. Starting to hold head up,

makes noises, and sit up for a few seconds by himself.” (Ex. 1, p. 72.) D.B. had his last

ACTh dose on April 4, 2020. (Id. at 77.) His EEG performed on April 7, 2014, indicated

normal results. (Ex. 7, p. 166.) On April 8, 2014, D.B. saw Dr. Andra Dingman for a

follow up of his infantile spasms. (Ex. 7, p. 169.) By this visit, D.B. had stopped ACTh

treatment for a week and no spasms had occurred since March 3, 2014. (Id.) Dr.

Dingman noted that in the past week since stopping ACTh treatment, D.B.’s parents

reported that he regained his social skills, was smiling often, and showed improvement

with head control. (Id. at 170.) Dr. Dingman indicated that D.B. responded well to

ACTh and the infantile spasms were resolved with normalized EEG. (Id. at 173.)

However, Dr. Dingman noted that “specific developmental consequences for [D.B.] are

hard to predict at this point, but he is at higher risk of more developmental delays than if

he has not developed spasms.” (Id.)

On April 14, 2014, D.B. visited Dr. Leland due to worsening reflux and vomiting.

(Ex. 1, p. 80.) Although D.B. had reflux issues, prior to the onset of infantile spasms, he

had normal upper GI. (Id.) Dr. Leland planned to discuss with D.B.’s pediatric

gastroenterologist, Dr. Brumbaugh; however, scheduling did not permit D.B. to be seen

until May. (Id. at 80-81.) Over the next few days, D.B.’s symptoms continued to

worsen, and Dr. Leland assessed that he needed an endoscopy. (Id. at 82.) Dr. Leland

noted that “[i]t is unclear if his current symptoms [of poor feeding/intake and vomiting]

are related to his ongoing reflux.” (Id.) D.B. did manage to see Dr. David. E.

Brumbaugh on April 21, 2014. (Ex. 7, p. 198.) His impression was that D.B.’s reflux

now includes an onset of “more forceful emesis and decreased intake,” and suggested

that the ACTh therapy could increase risk for peptic disease and cortisol deficiency.

(Id.) Dr. Brumbaugh recommended D.B. stay at the hospital for monitoring due to his

high risk of severe dehydration. (Id.) D.B. went to the hospital and was admitted for

decreased oral intake. (Ex. 1, p. 85.) D.B. had an upper intestinal endoscopy with

biopsy on April 22, 2014. (Ex. 7, p. 249.) He was discharged on April 23, 2014. (Ex. 7,

p. 229.) Following his stay at Children’s hospital, D.B. saw Dr. Danae Stampfli on April

25, 2014. (Ex. 1, p. 85-86.) The plan was to monitor his intake.

D.B. continued to have feeding difficulties and saw Dr. Leland on June 3, 2014.

(Ex. 1, p. 87.) Dr. Leland noted that there was less refluxing and only mild choking.

D.B. was able to roll from his stomach to his back, sit independently (but tipped over),

and other activities. Dr. Leland stated however that “[w]hen he was on ACTh, his

weight went past the 95th percentile for a Down syndrome chart. Currently his weight is

falling midway between the 75th and 95th percentile.” (Id.)

Additionally, D.B. continued seeking testing for his bilateral hearing loss. (Ex. 7,

p. 345-46.) On July 3, 2014, D.B. was recommended for hearing aid fitting and

continued follow-up with audiology. (Id.) D.B. had “a bilateral mild sensorineural

hearing loss diagnosed shortly after being referred on his newborn hearing screen age.”

3, pp. 34-35.) He continued therapy, however, occasionally, he would experience vomiting and serious

reflux issues. (Id. at 36-44.)

9

(Id. at 346.) It was noted that “[d]evelopmentally, he is delayed although making gains.

He had significant regression while he had infantile spasms but has been regaining

skills and is almost back to his pre-seizure status.” (Id.) Dr. Kristina Kocsis indicated

that D.B.’s hearing loss was most likely caused by a non-syndromic gene rather than

being related to his Down syndrome. (Id.)

During his follow up visit on July 8, 2014, with Dr. Dingman regarding the infantile

spasms, it was noted that D.B. gained back the milestones that were lost after the onset

of spasms and continued making developmental gains. (Ex. 7, p. 351.) From a

developmental standpoint, D.B. was reported to be “doing well.” (Id. at 355.)

At his 12-month checkup, D.B. was still taking Prevacid and progressing slowly

regarding his feeding issues. Dr. Leland noted that “Mother is hesitant about

immunization as [D.B.’s] infantile spasms began the evening after his 3rd DTAP.” (Ex.

1, p. 90.) No additional vaccinations were administered at this appointment; and Dr.

Leland answered in the negative when asked if D.B. had a history of previous adverse

reactions to immunizations. (Id. at 91.) Also, by July 31, 2014, D.B. had met his goal in

occupational therapy in demonstrating age-appropriate oral skills in eating puree from a

spoon, propping on elbows in prone, and holding head up in play. (Ex. 3, p. 44.)

However, during this session, it was first noted as part of his assessment that D.B. had

delayed milestones. (Id. at 43.) Two months later, his progress notes specified that

D.B. demonstrated “low tone throughout and delayed milestones, consistent with Down

syndrome.” (Id. at 50.)

When D.B. was 14 months old, he experienced an upper respiratory infection

(“URI”) that lasted several weeks. (Ex. 1, pp. 94, 99.) A note left by RN Anna M.

Hernandez indicated that RN Hernandez notified that the DT vaccine is available for

D.B. and petitioner indicated that D.B. will probably receive it the following day on

December 5, 2014. There is no record of D.B. receiving this vaccine, and in fact during

a later appointment, Dr. Leland noted that D.B. still needs the DT vaccine. (Id. at 102.)

On December 12, 2014, Dr. Leland saw D.B. and noted that he “has two words

and eight signs. He sits well. He rolls both ways. He is not crawling, but he scoots on his

bottom to get where he wants to go. He is not pulling to stand yet.” (Ex. 1, p. 102; Ex. 4,

p. 3.) At this visit, D.B. received a diphtheria/tetanus (“DT”) immunization, and about

three days later, D.B. started experiencing vomiting and diarrhea. (Ex. 4, p. 6.) D.B.

returned to see Dr. Leland on December 22, 2014. (Id.) Dr. Leland noted the temporal

association with the immunizations but also noted that D.B.’s brother also experienced

the symptoms two days prior to D.B. (Id.) Additionally, Dr. Leland noted that D.B. is

less active than usual and ordered stool studies. (Id.) About four days later, D.B.’s

mom reported that D.B. was feeling better. The stool culture results were negative. (Id.

at 10.)

In January 2015, D.B. was still undergoing skilled occupational therapy to

address his difficulty with oral feeding, low oral tone, and signs of stress with

10

overstimulation. (Ex. 3, pp. 69-70.) He still had a “sensory and motor dysfunction with

swallowing thin liquids.” (Id. at 69.)

At his 18-month well child visit, Dr. Leland noted that D.B.’s behavior was normal

for his age. (Ex. 4, p. 14.) Dr. Leland indicated that D.B. could walk quickly, walk on

steps, scribble with crayon, play with building blocks, and feed using a spoon and cup.

(Id. at 16.) Additionally, regarding his mental development, D.B. had a 15-20 word

vocabulary and could form short sentences. (Id. at 17.) On February 17, 2015, D.B.

was sick with symptoms of URI, coughing, and vomiting. (Id. at 21.) His cough

persisted over the next couple of days. (Id. at 24.) D.B. had other episodes of URI. (Id.

at 29.) However, during his interval visit on May 8, 2015, Dr. Leland noted that D.B.

was making excellent progress despite his history of infantile spasms. (Id. at 33.)

At his two-year-old checkup, Dr. Leland indicated that D.B. was a healthy two-

year-old with normal growth and development. (Id. at 41.) He continued to make

progress, although D.B. was becoming ill often and petitioner expressed concern about

his immune status in January of 2016. (Id. at 64-65.) Dr. Leland indicated he would

order bloodwork and a recheck in six months (Id. at 65); however, no further pediatric

records have been filed. D.B. also continued with his skilled occupational therapy for

his Down syndrome and swallowing difficulties. (See generally Exs. 5, 14.) Petitioner

filed occupational therapy records through June of 2017, at which time D.B. was

approximately 47 months of age. (Ex. 14.)

b. As Reflected by Testimony/Affidavits

i. Petitioner Mandy Bangerter’s Testimony

Petitioner Mandy Bangerter is D.B.’s mother. (Tr. 61-62.) She explained that

prior to onset of his infantile spasms, D.B. received physical and occupational therapies

beginning at two months of age. (Tr. 62-63.) However, she characterized him as doing

well and as progressing each week. (Id.) D.B. never had any seizures prior to receipt

of his six-month vaccinations; however, he did have a history of reacting poorly to

vaccinations, including fever, sluggishness, and sleepiness. (Tr. 63.)

The evening of D.B.’s six-month checkup (a Friday), petitioner noticed that as

D.B. was waking, “his eyes were kind of like just staring forward.” (Tr. 68.) Although

she could not recall a specific temperature, petitioner does recall that D.B. did have a

“low-grade” fever. 13 (Tr. 67, 69.) This was the only instance of seizure activity

13Petitioner stressed that she had a habit and practice, dating back to the infancy of her older child, of

giving an initial dose of infant Tylenol upon returning home after vaccinations were administered to

prophylactically address anticipated fevers. (Tr. 63-64.) She would then subsequently check for fevers

and administer a second dose if a fever was present. (Tr. 86.) When asked how confident she was that

she administered an initial dose of Tylenol following D.B.’s six-month vaccinations on February 14, 2014,

petitioner testified that there is a “very high probability” that she did based on this habit and practice. (Tr.

85.) She also stressed that D.B. in particular had a history of fevers following vaccinations. (Tr. 86.)

Petitioner “would assume” that she administered a second dose of Tylenol on February 14, because she

does recall that D.B. had a fever; however, she cannot actually recall whether she did. (Tr. 98.)

11

petitioner observed that evening. (Tr. 71.) She acknowledged it was subtle, but still felt

that something was wrong and told her husband, Jedidiah, that she thought D.B. had a

seizure. (Tr. 70-71.) He did not agree at that time. (Id.)

The next morning, D.B. exhibited eye rolling as he awoke. (Tr. 72.) At that time

he was not yet exhibiting body movement during seizures. (Id.) By Saturday evening,

his body began to stiffen during the seizures. (Id.) By Sunday, movements were still

slight, but D.B. was twitching in addition to rolling his eyes. (Tr. 73.) Seizures occurred

when D.B. was transitioning from sleeping to waking. (Tr. 73.) Petitioner became

confident by Sunday evening that something was happening, because D.B.’s “arms

would kind of go out-wise, legs through midline, and his head kind of went rigid and

eyes moved.” (Id.)

By the time D.B. was taken to back to Dr. Leland on Monday, February 17, he

was no longer holding his head up and wasn’t moving around as much as usual. (Tr.

75.) His eye rolling and body movement during seizures had increased and would

result in fatigue. 14 Dr. Leland was able to observe D.B. as he was waking and

confirmed that he was experiencing seizure activity. (Tr. 75-76.) Petitioner could not

recall whether Dr. Leland referenced any specific term for the seizures, but he did refer

them to the children’s hospital. (Id.)

Petitioner recalled that after onset of his seizures, D.B. could not sit up or roll

over. (Tr. 77.) He stopped babbling and cooing and stopped being alert. (Id.)

“[E]ssentially over time, he had to continue to relearn everything from his therapists and

daily work and regiment that was set up.” (Id.) However, his seizures stopped within 32

days of starting his ACTh treatment. (Tr. 78.) D.B. was starting to sit up again by the

end of March. (Tr. 87-89.) By his first birthday, D.B. was able to hold his head up and

his gross motor skill issues had resolved; however, petitioner continued to be concerned

about his swallowing and difficulty holding a spoon. 15 (Tr. 91-92.) Petitioner also

explained, however, that D.B. experienced side effects from the ACTh treatment

including extreme weight gain, irritability, and reduced sleep. These symptoms did not

cease with the discontinuation of the ACTh and it took several more months for D.B. to

return to his normal demeanor. (Tr. 249-50.)

Petitioner indicated that a fever of about 101 degrees would prompt her to administer a second dose of

Tylenol. (Id.) She testified that the fever she recalls was not concerning at the time. (Tr. 254.) She

characterized it as “just a regular fever type pattern that he still gets to this day after receiving something.”

(Id.)

14Petitioner struggled to find an appropriate description on this point. She said he was “I don’t know –

very like tired and exhausted afterwards,” but specifically noted that she did not mean lethargic. (Tr. 75.)

15 During the hearing, respondent’s counsel showed petitioner a medical record from March 24, 2014

wherein petitioner is recorded as having reported that D.B. was “back to baseline.” (Tr. 87-89

(referencing Ex. 1, p. 71).) Petitioner could not recall what she would have said on that date, but disputed

the specific “back to baseline” reference insofar as she recalls D.B. was not back to sitting up by the end

of March. (Tr. 89.)

12

ii. Jedidiah Bangerter’s Testimony

Jedidiah Bangerter is D.B.’s father. (Tr. 101.) Mr. Bangerter’s testimony is

largely in agreement with that of petitioner. He noted that D.B. never had seizures prior

to his six-month vaccinations. (Tr. 101.) He was not present for D.B.’s six-month

checkup and vaccinations but was with D.B. later that evening. (Tr. 101-03.) He

explained that petitioner did raise a concern to him that D.B.’s eyes had begun getting

wide and staring off during the evening following his vaccinations, but agrees that he

dismissed that concern at the time. (Tr. 102-04.) He also agreed that the condition got

progressively worse the following Sunday. (Tr. 106.) Sunday is when Mr. Bangerter

also began to become concerned. (Id.) Mr. Bangerter indicated that by Monday D.B.

had stopped babbling and cooing, was lethargic, and wasn’t sitting as well. (Tr. 108-

09.) He observed that D.B.’s seizures stopped within a few days of his ACTh treatment

and that he has not had a seizure since. (Tr. 109.) He did, however, experience weight

gain and irritability caused by the treatment. (Id.) D.B. is currently doing well, though

he continues to have obstacles. (Tr. 109-10.) Mr. Bangerter testified that D.B. was just

returning to babbling and sitting up at his first birthday. He was starting to lose his

ACTh-related weight by his first birthday. (Tr. 111-12.)

iii. Robert Leland, M.D.

Dr. Robert Leland, D.B.’s pediatrician, drafted a letter regarding D.B.’s

developmental delays. (Ex. 9.) Dr. Leland noted that on the evening subsequent to

receiving his routine immunizations, D.B. developed infantile spasms and responded

well to ACTh treatment three days thereafter at Children’s Hospital Colorado. (Ex. 9, p.

1.) Dr. Leland opined that “[i]t is probable, although it cannot be proven scientifically,

that [D.B.], at 6 months after onset of infantile spasms, had additional developmental

delays beyond those which would have been associated with his Down’s syndrome.”

(Id.) Dr. Leland recommended further consultation from Dr. Francis Hickey.

iv. Sarah Nicholas, MOTR/L

Petitioner also provided a letter from D.B.’s occupational therapist, Sarah

Nicholas. (Ex. 8.) In her letter dated April 2, 2016, upon review of her notes from “just

before” D.B.’s vaccinations through the date of her letter, Ms. Nicholas indicated that

D.B. demonstrated “significant loss in motor skill during my therapy sessions at the time

of seizure activity [through] the treatment period for infantile seizures.” (Ex. 8, p. 1.)

Ms. Nicholas opined that D.B. returned to his skill level prior to onset of seizures around

June 5, 2014 and continued to improve slowly with respect to fine motor skills and

feeding skills. (Id.) Ms. Nicholas stated that D.B. “should have made greater gains,

compared to other children [she has] treated with Down syndrome,” but that she is

“unable to project exactly where he would be had he not had the seizure activity and

other medical complications, specifically, reflux.” (Id.)

During the hearing, Ms. Nicholas discussed her medical records extensively. (Tr.

157-174.) Ms. Nicholas confirmed that D.B. had feeding concerns and reflux prior to the

13

onset of infantile spasms. (Tr. 157, 178, 185.) She explained that children with Down

syndrome are more likely to have choking events because they have low muscle tone

and lack coordination. (Tr. 178.) She noted that prior to his infantile spasms, D.B.

“clearly had difficulty with coordination and suck, swallow, breath, although not to the

degree that he needed a feeding tube.” (Tr. 178 (discussing January 30, 2014 record at

Exhibit 3, p. 22).) She testified:

So as I went through these records today and I kind of skimmed over the

part about then we went to feeding, feeding and reflux were a significant

issue, not that the seizures weren’t, but for day-today life, dealing with reflux

was very, very difficult for [D.B.]. Feeding aversion and difficulty. And so, I

mean, I believed that he – reflux was also in his way of development.

(Tr. 185.)

With respect to developmental trajectory, Ms. Nicholas agreed that there is “wide

variability” among individual children and that the developmental gap seen among Down

syndrome children compared to other groups widens at about the two-year mark; she

stressed, however, that the developmental gap relates to the rate of milestone

acquisition rather than the order of developmental milestones that are achieved. (Tr.

179-81.) With regard to D.B., she agreed that he showed gains beyond his pre-seizure

level of development within five months of the end of his seizures. (Tr. 186.) However,

she testified that D.B. “had a period of months where he was not performing to the level

he was prior to the seizure, and then he started making gains again. But certainly, I

think if we had had those months, he would have been further along at this point, at the

end of October[.]” (Tr. 175.) Asked if she could attribute any of D.B.’s developmental

delays after June of 2014 to D.B.’s infantile spasms, she stated “I can’t point to anything

specific. I felt that he would have been further along in his development at his current

rate of development prior to the seizures compared to his rate of development after the

seizures.” (Tr. 186.)

IV. Expert Opinions

a. Petitioner’s Experts

i. Karen Harum, M.D.

Additionally, petitioner presented an opinion from Dr. Karen Harum from Clinic for

Special Children. (ECF No. 40; Ex. 12.) Dr. Harum is a neurodevelopmental

pediatrician at the Clinic for Special Children in Wilmington, North Carolina. Previously

she was a clinical assistant professor in the department of pediatrics at Eastern

Carolina School of Medicine and, before that, an instructor of neurology and

developmental pediatrics at the Kennedy Krieger Institute at Johns Hopkins University

School of Medicine. (Ex. 13, p. 1.) Dr. Harum obtained her medical degree at the

University of Miami School of Medicine in 1987 and completed a fellowship in

neurodevelopmental pediatrics at the Kennedy Krieger Institute. (Id. at 2.) She is board

certified in neurodevelopmental disabilities by the American Board of Pediatrics. (Id. at

14

3.) She was accepted without objection as an expert in pediatrics with a specialty in

pediatric development. 16 (Tr. 7-8.)

Regarding whether D.B. experienced residual effects following his recovery, Dr.

Harum opined that D.B.’s developmental progress was negatively affected for more

than six months after the onset of his infantile seizures. (Ex. 12, p. 1.) Using

developmental quotients (DQ) to measure his developmental progress in the areas of

fine motor, gross motor, and feeding skills, Dr. Harum indicated that D.B.’s scores were

dropping over time, even accounting for Down syndrome as an impediment. (Id. at 1.)

She explained that DQ “are calculated as a ratio of the age equivalent of the relevant

skill, over the actual age of the child.” (Ex. 15, p. 1.) From the records, Dr. Harum

summarized that at 6.5 months, D.B.’s DQ was 77 in gross motor skills and 61 in fine

motor skills, and at 16 months, his DQs were 37 and less than 50. (Ex. 15, p. 2.) From

that information, Dr. Harum opined that D.B. continued to decline for more than six

months following his injury and he did not entirely recover to his baseline before the

onset of his seizures until about 42 months of age. (Id.)

Dr. Harum opined that considering D.B.’s Down syndrome, his recovery should

not have lasted more than 12 months, and he should have returned to achieving DQ

levels at 60-77 by 19 months, not 42. (Ex. 15, p. 2.) Moreover, “developmental abilities

between infancy and two years of age are not expected to be greatly different between

typically developing children and children with DS.” (Ex. 16, p. 2.) Yet, Dr. Harum also

opined that D.B. was following the developmental trajectory for children with Down

syndrome aside from the residual deficits in hand ability and feeding difficulty. (Id. at 3.)

Specifically, she opined:

Putting into perspective the somewhat typical developmental trajectory for

Down syndrome, it appears that DB is not markedly different from his [Down

syndrome] peers, yet he is left with residual deficits in L hand ability and in

oropharyngeal motor skills that affect his feeding in a pervasive way.

From these data, we can therefore surmise that DB suffered residual effects

of the alleged injury for >6 months.

(Ex. 16, p. 3.)

During the hearing, Dr. Harum testified in accordance with her reports. (Tr. 5-

59.) Critically, however, for the few developmental quotients Dr. Harum calculated for

6.5, 8, 10, and 16 months, she did not disclose in her report the basis for those

calculations. (Ex. 16, p. 2.) During the hearing, she was not able to explain the basis

for those calculations. (Tr. 33.) Because D.B. suffered his infantile spasms at about six

16 Of note, however, although Dr. Harum stressed that she has a strong background in neurology and

neuroscience, when asked if she has ever practiced as a neurologist, she indicated “not as you conceive

of neurology, no.” (Tr. 21.)

15

months of age, these calculations served as the baseline premise for her entire opinion

regarding D.B.’s developmental trajectory.

ii. Marcel Kinsbourne, M.D.

With respect to causation, petitioner presented an expert opinion by neurologist

Marcel Kinsbourne, M.D. Dr. Kinsbourne served as a senior fellow at the Center for the

Study of Aging and Human Development at Duke University, an adjunct professor of

neurology at Boston University School of Medicine, a research professor at the Center

for Cognitive Studies at Tufts University, and a professor of psychology at New School

University. (Ex. 23.) Dr. Kinsbourne obtained his B.M.B. Ch. from Oxford University

Medical School in 1955 and his medical degree from State of North Carolina in 1967.

Dr. Kinsbourne has published over 400 medical articles. Dr. Kinsbourne was accepted

without objection as an expert in pediatric neurology. (Tr. 117.)

Beginning with his second report, 17 Dr. Kinsbourne addressed the question of

whether D.B.’s DTaP vaccination caused or triggered the onset of his infantile spasms.

(Ex. 24.) First, Dr. Kinsbourne opined that findings from the National Childhood

Encephalopathy Study (NCES) as later published by Bellman et al., support the idea

that the diphtheria, tetanus, and whole cell pertussis (“DTP”) vaccine can trigger onset

of infantile spasms within 6 days. (Ex. 24, p. 1 (citing Bellman et al., Infantile Spasms

and Pertussis Immunisation, The Lancet, 1031-34 (1983) (Ex. 28.)) He also cited an

earlier study by Melchior which he also suggests demonstrated an association between

onset of infantile spasms and DPT. (Id. (Melchior, Infantile spasms and early

immunization against whooping cough: Danish survey from 1970-1975, 52 ARCHIVES OF

DISEASE IN CHILDHOOD 137-37 (1977) (Ex. 34.)) Dr. Kinsbourne opined that D.B. had

cryptogenic infantile spasms, reporting that Bellman found children with cryptogenic

infantile spasms who received DPT vaccinations had more seizure onsets within the

first week. (Ex. 24, p. 2 (citing Bellman et al., supra, at Ex. 28).) Additionally, Dr.

Kinsbourne believed that a later onset of spasms would result in milder developmental

delays. (Id. at 2 (citing Arya et al., Epilepsy in children with Down syndrome, 13(1)

EPILEPTIC DISORD. 1-7 (2011) (Ex. 25.)) Although the vaccination at issue is DTaP

(acellular pertussis) and not DTP, Dr. Kinsbourne suggests that the mechanism is

similar and the pertussis toxin promotes proinflammatory cytokine output that triggers

seizures. (Id. at 3.) Relatedly, “[c]hildren with Down syndrome have been reported to

have cytokine excess in blood and brain.” (Id.)

17 Dr. Kinsbourne’s first report did not discuss vaccine causation. (Ex. 20.) Rather, it focused exclusively

on D.B.’s medical history and whether his infantile spasms had any lasting effect on his development

beyond the six-month mark. (Id.) However, during the hearing, Dr. Kinsbourne later deferred to Dr.

Harum’s opinion with respect to D.B.’s developmental course. (Tr. 236, 238.) On the question of residual

consequences, Dr. Kinsbourne explained in that first report that the adverse impact of infantile spasms on

child development depends on the duration of the spasms and subsequent treatment. (Ex. 20.)

Moreover, children with Down syndrome usually responds well to ACTh treatment, “[t]hat does mean,

however, that the developmental setback that Down syndrome children incur when they have had

infantile spasms is so readily compensated.” (Ex. 20, p. 2.) Using the DQs as summarized by Dr. Harum,

Dr. Kinsbourne is also of the opinion that the residual effects of the alleged vaccine injury lasted more

than six months. (Id. at 3.)

16

Second, Dr. Kinsbourne cited a theory for the mechanism of injury explored by

Baram and Hatalski, which he contended demonstrates developmental seizures,

including infantile spasms, can be provoked by injurious or stressful stimuli affecting

neuronal excitability via the release of corticotropin releasing hormone (“CRH”). 18 (Id. at

2; Ex. 40, pp. 3-4.) Dr. Kinsbourne opined that D.B. had a lower threshold for seizures

due to his Down syndrome and was “predisposed to react adversely to potentially

excitatory influences.” (Ex. 24, pp. 2-3.) Dr. Kinsbourne stated:

The development of Down syndrome changes in the brain, which is

prenatal, bestows a susceptibility to infantile spasms. Because this seizure

variant is age-dependent, when the brain has developed to the point that

neuronal circuitry can create spasms and hypsarrhythmia, the clinical onset

of the spasms can be triggered by immediately preceding events in the

already susceptible infant when s/he is within the applicable age range,

usually cited as being three to eight months.

(Id. at 2.)

Dr. Kinsbourne proposed that vaccinations activate the Toll-like receptors of the

innate immune system that would release cytokines that then trigger the seizures. (Id.

at 3-4.) He also noted that this process can be rapid and related that DTaP

vaccinations can trigger adverse reactions within the first 24 hours after administration.

(Id. at 4.) Thus, Dr. Kinsbourne opined that D.B.’s susceptibility to infantile spasms was

a first hit and the DTaP vaccination, acting as a trigger, was the second hit that resulted

in the onset of infantile spasms. (Ex. 40, pp. 2-3; Ex. 49, p. 2.) Dr. Kinsbourne opined

that both the immune response to vaccination and the stress associated with injection

would act on the endocrine system to elevate CRH consistent with the Baram

hypothesis. (Ex. 40, p. 4; Tr. 152-53 (discussing Jansen et al., Cortisol reactivity in

young infants,35 PSYCHONEUROENDOCRINOLOGY 329-38 (2010) (Ex. 86.))

During the hearing, Dr. Kinsbourne largely testified in accordance with his prior

reports (Tr. 115-240); however, he also introduced for the first time the alternative

suggestion that what D.B. initially suffered was not infantile spasms, but tonic/partial

seizures. (Tr. 123-24, 220-21 (citing Carrazana et al., Facilitation of Infantile Spasms by

Partial Seizures, 34(1) EPILEPSIA 97-109 (1993) (Ex. 92.)) He opined that it was these

seizures, rather than D.B.’s infantile spasms, that were vaccine-caused via

proinflammatory cytokines. (Tr. 135-37, 221-22.) He further opined that these initial

seizures transformed into infantile spasms. 19 (Tr. 135-37.)

18Petitioner filed two papers by Dr. Tallie Baram. Baram and Hatalski, Neuropeptide-mediated

excitability: a key triggering mechanism or seizure generation in the developing brain, 21(11) TRENDS

NEUROSCI. 471-76 (1998) (filed as Exhibits 26, 41, 63, and 76); Baram, et al, 31(5) Corticotropin-releasing

Hormone – induced Seizures in Infant Rates Originate in the Amygdala, ANN NEUROL. 488-94 (1992) (filed

as Exhibit 89).

19 While discussing the Carrazana paper (Ex. 92), which he testified represented “exactly what happened

with [D.B.],” Dr. Kinsbourne testified that “the vaccines surely triggered the partial seizures, not the

infantile spasms.” (Tr. 136 (emphasis added).) This would actually seem to represent a retraction of

17

b. Respondent’s Expert: Gregory Holmes, M.D., Ph.D.

Respondent provided a responsive report from Gregory Holmes, M.D. Dr.

Holmes is board certified in pediatrics, clinical neurophysiology, and psychiatry and

neurology with special qualification in child neurology. (Ex. B, p. 2.) Dr. Holmes

currently holds a teaching and chair position at the University of Vermont College of

Medicine as well as being a physician leader of neurology at the University of Vermont

Medical Center. (Ex. B, p. 1.) He obtained his medical degree from the University of

Virginia School of Medicine in 1974. (Id.) Like Dr. Kinsbourne, his curriculum vitae lists

hundreds of publications. (Ex. B.) Dr. Holmes was presented as an expert in pediatric

neurology with an additional specialty in seizure disorders; however, petitioner objected

to the designation of this specialty. 20 (Tr. 268-69.)

Citing to the Institute of Medicine, Dr. Holmes stated that there is no evidence to

support the notion that DTaP vaccination causes infantile spasms. (Ex. A, p. 10 (citing

the IOM report).) Similar to Dr. Kinsbourne, Dr. Holmes cited the prevalence of seizures

in patients with Down syndrome (1-13% for individuals with DS versus 1.5-5% for the

general population). (Ex. A, p. 9.) Dr. Holmes also noted that children with Down

syndrome and infantile spasms typically respond well to treatment and prompt treatment

results in better prognosis. (Id.) For infantile spasms to occur, there’s no need for a

trigger. (Ex. C, p. 3.) Therefore, D.B. had symptomatic infantile spasms that were

consistent with his Down syndrome, not cryptogenic infantile spasms. 21 (Ex. C, p. 2.)

According to Dr. Holmes, none of the studies Dr. Kinsbourne cited supports a

relationship between vaccination and infantile spasms with developmental delay. (Ex.

A, p. 11.) Additionally, there is no evidence that onset of infantile spasms later in life

reduces the developmental impact. (Id. at 11.) Dr. Holmes added that the materials Dr.

Kinsbourne relied on focused on DTP vaccinations while D.B. received the DTaP

vaccination, which is less reactogenic. (Id.) He insisted that relying on literature

referring to DTP vaccines rather than DTaP from 30 years ago is neither helpful nor

relevant. (Ex. D, p. 2.) Additionally, there is no evidence that DTaP vaccination causes

substantial portions of Dr. Kinsbourne’s prior reports and likely represents a veiled acknowledgement of

the fact that much of the evidence petitioner relies on that is specific to the modern acellular DTaP

vaccine (as opposed to the older whole cell DPT vaccine) relates to unitary post-vaccination seizures

rather than the specific seizure disorder of infantile spasms. For purposes of this decision, however, I

treat the direct causation of infantile spasms by vaccination and the indirect causation of infantile spasms

via partial seizures as theories presented in the alternative.

20 That objection is addressed in detail below in section V(d) and found to be unpersuasive.

21 Dr. Kinsbourne first opined that D.B.’s infantile spasms were cryptogenic, meaning of obscure or

unknown origin. (Ex. C, p. 2.) And although Dr. Holmes explained why he does not think the infantile

spasms are cryptogenic, he explained that categorizing the infantile spasms as cryptogenic does not

dictate outcome but only etiology, and here, “[w]hether one calls these idiopathic, cryptogenic, or

symptomatic is irrelevant in this case.” (Id.)

18

infantile spasms through proinflammatory cascades or activation of cytokines. 22 (Ex. D,

p. 3.) Regarding Dr. Kinsbourne’s two hit theory, Dr. Holmes stated that the medical

records do not support that D.B. had a slow development of susceptibility to infantile

spasms “that resulted in an ‘explosive reaction’ to the DTaP vaccine.” (Ex. C, p. 2.)

Additionally, Dr. Holmes opined that it is not biologically possible for onset of

infantile spasms to occur within 12 hours after vaccination. (Id. at 12.) Dr. Holmes

emphasized that the “interval between brain injury and the onset of infantile spasms

ranges from 6 weeks to 11 months.” (Id.) Dr. Holmes also stressed that there is “no

evidence that a later onset of infantile spasms the better the outcome,” stating that the

articles cited by Dr. Kinsbourne do not support this contention. (Ex. C, p. 2.) Moreover,

Dr. Holmes asserted that even accepting petitioner’s theory that a vaccine can trigger

infantile spasms in a predisposed child, there is no evidence predicting any effect on

outcome. (Ex. D, p. 2.)

Dr. Holmes also noted that, on review of the records, D.B. did not have any

adverse reactions to his first and second DTaP vaccinations and that D.B. was not

developing normally prior to the vaccination at issue. (Ex. A, pp. 2-3, Ex. D, p. 2.)

Additionally, the records indicated that D.B.’s spasms ceased in early March after ACTh

treatment and he regained certain skills. (Ex. A, p. 7.) Thus, Dr. Holmes concluded that

D.B. returned to baseline within a month of ACTh treatment and that his developmental

delays thereafter were consistent with his Down syndrome. (Id. at 9.) Dr. Holmes

opined that the developmental regression that occurred once D.B. recovered, as

evidenced in his EEG, cannot be linked to the infantile spasms, but that D.B. had other

chronic problems that contributed to his developmental issues. (Id. at 13.) Specifically,

he stated:

While it is clearly recognized that cognitive regression can occur with

infantile spasms in Down syndrome, the developmental regression that

occurred following the end of hypsarrhythmia and infantile spasms

obviously cannot be attributed to the infantile spasms. Even if there was

permanent damage following the short period of infantile spasms and

hypsarrhythmia, this would not explain the decline months following

remission of the condition. Dr. Kinsbourne does not provide an explanation

for why [D.B.] should decline following the cessation of infantile spasms.

(Ex. C, p. 3.) Dr. Holmes also testified in accordance with his written reports. (Tr.

261-354.)

22 Dr. Holmes provided an alternative mechanism, discussing the GABABR-mediated mechanism. (Ex. A,

p. 12.)

19

V. Discussion

a. Althen Prong One

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

demonstrating that the vaccine received can cause the type of injury alleged. Pafford v.

Sec’y of Health & Human Servs., 451 F.3d 1352, 1355–56 (Fed. Cir. 2006) (citations

omitted). To satisfy this prong, 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). Such a theory must only be “legally probable, not

medically or scientifically certain.” Id. at 549. However, 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 v.

Sec’y of Health & Human Servs., 440 F.3d 1317, 1325-26 (Fed. Cir. 2006)).

There is no dispute in this case that the DTaP vaccine can cause seizures in

some contexts. 23 (Tr. 118 (Kinsbourne); Tr. 344-45 (Holmes).) However, that is not the

question at issue in this case. The condition at issue in this case is not interchangeable

with other forms of epilepsy or seizure activity. D.B. suffered a specific seizure disorder

known as infantile spasms, the diagnosis of which is not disputed. And while Dr.

Holmes agrees on respondent’s behalf that a single seizure can be vaccine-caused, he

disagrees that vaccines cause any form of epilepsy and further stresses that infantile

spasms in particular are not “provoked” seizures. (Tr. 294-96; 344-45.)

The condition of “infantile spasms” (also referred to as epileptic spasms or “West

Syndrome”) represents an epileptic 24 encephalopathy. 25 (Lee & Ong, Epidemiology of

23 Dr. Holmes agreed that DTaP can cause febrile seizures, but disagreed that DTaP has been shown to

cause afebrile seizures. (Tr. 344-45.) In fact, while he agreed that vaccination in general can cause

febrile seizures, he noted that the question of whether they can cause afebrile seizures is generally

considered contentious. (Id.) In this case, petitioner has also filed a package insert for the DAPTACEL

vaccine, a DTaP vaccine manufactured by Sanofi Pasteur, that includes seizures occurring within three

days of vaccination as adverse reactions to the vaccine. (DAPTACEL package insert, supra, at Ex. 55.)

There is no evidence of record to indicate that D.B. was administered the DAPTACEL vaccine

specifically; however, for more detailed discussion of the DAPTACEL package insert, see n. 33, infra.

24 An epilepsy is “any of a group of syndromes characterized by paroxysmal transient disturbances of the

brain function that may be manifested as episodic impairment or loss of consciousness, abnormal motor

phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system. A single

episode is called a seizure (q.v.). Many types of epilepsy are combinations of different kinds of seizures.

Epilepsy is classified as either symptomatic or idiopathic according to whether the cause is known or

unknown. Both of these types may be further subdivided into partial and generalized types depending on

whether the seizures begin with localized, limited brain dysfunction or with widespread brain dysfunction.”

Epilepsy, DORLAND’S MEDICAL DICTIONARY ONLINE,

https://www.dorlandsonline.com/dorland/definition?id=16869 (last visited Jan. 11, 2022).

25 Broadly speaking, encephalopathy is defined as “any degenerative disease of the brain.”

Encephalopathy, DORLAND’S MEDICAL DICTIONARY ONLINE,

https://www.dorlandsonline.com/dorland/definition?id=16202 (last visited Jan. 11, 2022).

20

West syndrome in Singapore, 23 BRAIN & DEV. 584-85, 584 (2001) (Ex. A, Tab 15);

Ogawa, et al., Cytotoxic edema at onset in West syndrome of unknown etiology: A

longitudinal diffusion tensor imaging study, 59(2) EPILEPSIA 1-21, 1 (2018) (Ex. 43.))

Outwardly, it is characterized by “repetitive bursts of myoclonic 26 jerking of the head or

limbs.” (Bellman et al., supra, at Ex. 28, p. 1031.) However, the three cardinal features

of infantile spasms are: (1) encephalopathy; (2) epileptic spasms; and (3)

hypsarrhythmia. (Lee & Ong, supra, at Ex. A, Tab 15, p. 584; Ogawa et al., supra, at

Ex. 43, p. 1.) Infantile spasms are considered an age-dependent condition typically

occurring within the first year of life, most often between six to eight months of age.

(Osbourne et al., The underlying etiology of infantile spasms (West syndrome):

Information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary

causes of their classification, 51(10) Epilepsia 1-28, 2 (2010) (Ex. 48); Arya et al., supra,

at Ex. 25, p. 2.) Children with Down syndrome, like D.B., are more likely than the

general population to suffer epilepsies in general and infantile spasms is the most

common epilepsy among children with Down syndrome. (Arya et al., supra, at Ex. 25,

pp. 1-2.) The expert testimony in this case indicates that it is the hypsarrhythmia

underlying the condition – a key characteristic of infantile spams that can be clinically

silent apart from detection on EEG – that is primarily responsible for any lasting

damage. (Tr. 128-29, 235 (Dr. Kinsbourne); Tr. 272-78 (Dr. Holmes).)

In this case, Dr. Kinsbourne’s opinion suggests two different inquiries. First, Dr.

Kinsbourne is clearly of the view that there is evidence directly suggesting that certain

vaccines, including whole cell pertussis and diphtheria/tetanus vaccines, can trigger the

onset of infantile spasms. Second, Dr. Kinsbourne opines that infantile spasms can be

circumstantially evidenced as being vaccine-caused, either directly or via a partial

seizure. He indicates that in this case D.B. suffered an initial, vaccine-caused,

partial/tonic seizure that in turn developed into infantile spasms, thereby theorizing an

indirect causal relationship between vaccination and infantile spasms. On the whole,

Dr. Holmes is far more persuasive than Dr. Kinsbourne and petitioner has not met her

burden under Althen prong one under either theoretical approach.

i. Older literature is unpersuasive in suggesting any association

between vaccines and the development or onset of infantile

spasms

First, Dr. Kinsbourne is not persuasive in arguing that the medical literature

supports any association between the DTaP vaccination and infantile spasms. The

evidence he principally relies upon – two studies from the 1970’s and early 1980’s by

Melchior and Bellman respectively - are old and equivocal, presenting only very weak

evidence. (See Melchior, supra, at Ex. 34; Bellman et al., supra, at Ex. 28; Tr. 137-40.)

26 “Myoclonus” refers to “shocklike contractions of a portion of a muscle, an entire muscle, or a group of

muscles, restricted to one area of the body or appearing synchronously or asynchronously in several

areas. It may be part of a disease process (e.g., epileptic or post-anoxic myoclonus) or be a normal

physiologic response (e.g., nocturnal myoclonus).” Myoclonus, DORLAND’S MEDICAL DICTIONARY ONLINE,

https://www.dorlandsonline.com/dorland/definition?id=32802 (last visited Jan. 11, 2022).

21

More recent literature filed by Dr. Holmes refutes these older studies. To understand

why these older studies are not persuasive, it is worth discussing them at length.

According to the literature filed in this case, a possible link between pertussis

vaccination and infantile spasms was first proposed in 1964. (Melchior, supra, 34, p. 1.)

However, subsequent papers suggested that the possible association was merely a

coincidence of timing. (Id.) In April of 1970, Denmark changed its immunization

schedule for pertussis vaccination. Previously, the pertussis vaccine was typically

administered in Denmark as a triple combination at five, six, and 15 months of age.

After April of 1970, that schedule was advanced so that pertussis was administered as a

monovalent vaccine at five and nine weeks of age and then again at 10 months. (Id.)

However, immunization against diphtheria-tetanus-polio was still given at five, six and

15 months of age. (Id.) This provided an opportunity to examine whether the change in

the vaccine schedule would result in a statistically significant change in the typical age

of onset for infantile spasms. (Id.) J.C. Melchior published a survey study regarding

this question in the Archives of Disease in Childhood in 1977. (Id.)

Melchior compared 113 cases of infantile spasms diagnosed between April 1 of

1970 and March 31 of 1975 to 86 cases of infantile spasms occurring from 1957 to

1967. (Melchior, supra, at Ex. 34, p. 1.) Of the 113 cases from the early 1970’s, 40

were classified as cryptogenic, 60 of the subjects as symptomatic, and the remaining 13

reported as having an unclear etiology, but with immunization occurring prior to onset.

(Id. at 2.) Of those 13 subjects, six had seizures following either the first or second

dose of monovalent pertussis and seven had seizures following a combined diphtheria,

tetanus, and polio vaccination. (Id. (Table 2).) The conclusion reached by the study

was that: “A comparison of the age of onset of infantile spasms shows no significant

difference between the series of spasms before the new immunization programme and

after.” (Id. at 2.)

Despite these conclusions, Dr. Kinsbourne pointed out certain findings specific to

the pertussis vaccine. He noted that the Melchior study results demonstrate that:

12% of cases of infantile spasms had onset before age 2 months when DTP

had not yet been given by then, whereas 23% began before the child was

two months old when DTP had been given at 5 weeks. Melchior did not take

advantage of this opportunity to analyze the differential outcomes at age

two months statistically. He only compared the final outcomes of the two

subgroups, which did not differ significantly. 27

(Ex. 24, p. 2.)

Notably, however, Melchior did at least broadly address the concern raised by

Dr. Kinsbourne, explaining that if the pertussis component of the vaccine was isolated

27Although Dr. Kinsbourne references the vaccination at issue in Melchior as “DPT,” Melchior indicates

that the post-1970 vaccination schedule changed to administration of a monovalent pertussis vaccination.

(Melchior, supra, at Ex. 34, p. 1.)

22

as an etiologic factor, one would expect to see both an increase in incidence of infantile

spasms in the younger group and a decrease among the older group. (Id. at 2-3.) But

this was not observed in the data. Melchior noted that:

[o]f special interest is the occurrence of infantile spasms in 7 children,

developing within 2 weeks of the diphtheria-tetanus-polio immunization.

This seems to confirm the opinion that we are dealing mainly with a time-

coincidence and suggests that whatever immunization we administer in

the age groups between 1 and 2 months and 9 and 10 months, some

children will develop neurological disorders which are typically associated

with these age groups.

(Melchior, supra, at Ex. 34, p. 3.) Melchior characterized the possibility of a causal

connection between pertussis vaccination and infantile spasms as “very unlikely.” (Id.)

A figure from the study illustrates the point:

(Id. at 2.) Even while the increase at two months observed by Dr. Kinsbourne is visible,

this figure still shows that the overall distribution of onset of infantile spasms remained

substantially the same before and after the change in Denmark’s vaccination schedule.

Moreover, onset at 6-8 months of age among the 1970 series remained slightly above

the 1957 series even after pertussis was no longer administered at six months of age.

Subsequently, in 1983, Bellman et al., published a further study of 269 cases of

infantile spasms reported to the National Childhood Encephalopathy Study (“NCES”) in

23

Great Britain. (Bellman et al., supra, at Ex. 28, p. 1031.) Of those, 92 were classified

as symptomatic, 163 as cryptogenic, and a further 14 as “doubtful.” (Id.) Bellman

compared the immunized population to age-matched controls. (Id. at 1032.) Bellman

examined not only the DTP vaccine, but also a DT vaccine without any pertussis at all.

(Id.) Examining the pertussis vaccine, the Bellman study found no significant

association between spasms and the administration of a pertussis vaccine in either the

prior seven days or 28 days. (Bellman et al., supra, at Ex. 28, p. 1033.) However, they

did find that:

a small excess in the number of cases over that expected by comparison

with controls in 7 days after immunization with both DTP and DT vaccines

followed by a corresponding deficit in the next 3 weeks suggests that, in

some cases, immunization may trigger the onset of spasms or attract

attention to symptoms in children destined to show the condition overtly

within a short time.

(Id.) The authors allowed that the small excess in cases within seven days might speak

to vaccination being a “trigger” of spasms, but also indicated that it may be due to the

fact of vaccination attracting greater attention to symptoms displayed by children

destined to show the condition more overtly in a short time. (Id.) The latter explanation

was viewed as being in harmony with the prior Melchior study. (Id.)

In his second report, Dr. Kinsbourne sought to emphasize the “trigger” aspect of

the Bellman findings while waving away the Bellman study’s overall conclusion as to the

lack of any causal association as an “intuition as to destiny that cannot be tested.” (Ex.

24, p. 2.) However, the Bellman data was revisited in 1998 by Goodman et al.

(Goodman et al., Temporal relationship modeling: DTP or DT immunizations and

infantile spasms, 16(2/3) VACCINE 225-31 (1998) (Ex. A, Tab 18.)) The points stressed

by Goodman reveal this to be disingenuous. In the 1998 Goodman et al. follow up, the

authors cautioned against reading too much into the term “triggered.” They explained

that subsequent to the NCES, the U.S. Institute of Medicine (“IOM”) 28 had conducted its

own evaluation of the available data, including review of the Bellman data, and rejected

any causal association between DTP and infantile spasms. (Goodman et al., supra, at

Ex. A, Tab 18, p. 226.) They agreed with that conclusion. (Id. at 5-6.) To further clarify

the issue in light of the subsequent commentary, Goodman et al., reexamined the

Bellman data using three different statistical models – association (asking whether the

overall frequency of infantile spasms increases post-vaccination), temporal shift (asking

whether administration of a vaccine changes the timing of onset without necessarily

28 The Institute of Medicine (known as the National Academy of Medicine since 2015) is the medical arm

of the National Academy of Sciences. The National Academy of Sciences (“NAS”) was created by

Congress in 1863 to be an advisor to the federal government on scientific and technical matters (see An

Act to Incorporate the National Academy of Sciences, ch. 111, 12 Stat. 806 (1863)), and the Institute of

Medicine is an offshoot of the NAS established in 1970 to provide advice concerning medical issues.

When it enacted the Vaccine Act in 1986, Congress directed that the IOM conduct studies concerning

potential causal relationships between vaccines and illnesses. See § 300aa–1 note.

24

changing the overall frequency), and no-effect (asking how the studied period compares

to the expected rate). (Ex A, Tab 18, p. 1.)

The Goodman authors stressed that, consistent with the prior use of the term

“triggered” in Bellman, only the temporal shift model suggested any significant signal. 29

Because they specifically demonstrated that the associational model showed no

significant increase in cases of infantile spasms following vaccination, they cautioned

against any understanding of the term “trigger” to imply an association between

vaccination and infantile spasms. (Id. at 4-5.) The temporal shift among the “previously

normal” group was statistically significant, meaning that the cases demonstrated a

“significant” fit to the temporal shift model. (Id.) Nonetheless, the authors also

explained that “[t]he no effect model appears to be the best fitting of the three models

for the entire group of those with DTP or DT exposure.” (Id. (emphasis added).) This

means that “[t]here are no more immunizations given in the month prior to seizure onset

than would be expected.” (Id. at 6.) Thus, the authors reiterated the caution first

included in the Bellman article that the observed temporal shift may be due to increased

attention to symptoms. Specifically, they noted: “[a] temporal association with

immunization may be sought by parents for children who have no other apparent

antecedent factor for infantile spasms,” thus, “a fit to the temporal shift model for

previously normal cases may reflect a social or perceptual temporal shift, a biological

temporal shift, or a combination of both processes.” (Id.) The authors also cautioned

that the insidiousness of onset for infantile spasms makes it difficult to identify a precise

date of onset. (Id.)

Petitioner also relies on a 2011 retrospective analysis of vaccine-related seizures

conducted by von Spiczak et al., using the national German database of adverse events

following immunization. (von Spiczak, supra, at Ex. 36.) The authors indicated that the

risk for epilepsy following DTaP vaccination is not elevated, but noted instances where

epilepsy presents with its first seizure post-vaccination. (Id. at 2.) In their own review,

the authors gathered a cohort of 17 cases of infantile spasms, 10 of which were

apparently cryptogenic. (Id. at 10.) Among these subjects, they observed that for nine

out of the 17 their first seizure was “associated with the vaccination.” (Id. at 8.) They

noted that their findings may be consistent with the temporal shift observed in Goodman

but stressed that their study design did not test that hypothesis. (Id. at 10.) Thus, the

von Spiczak paper does not provide any further support for Goodman’s temporal shift or

serve to extend the Goodman findings to the DTaP vaccine at issue in this case. In

fact, citing both the Goodman study (discussed above) and Guggenheim study

(discussed below), von Spiczak explained that any causal relationship remains

controversial. (Id.) Additionally, Dr. Holmes was highly critical of this study for not

having any control group or disclosing the overall population. Based on his own

assumptions as to the relevant population, he estimates that it is likely these results

29 Only the results for the “previously normal” group demonstrated a temporal shift compared to controls

during the first week prior to vaccination as compared to the preceding three weeks. (Id.) When

examining the entire group of infantile spasm subjects against controls, Goodman explained that “[a]s the

odds ratio for the first week prior to seizure onset is not significantly greater than that for the subsequent

three weeks, there is no evidence for a fit to the temporal shift model.” (Id. at 5.)

25

would demonstrate an “extremely low” likelihood of vaccine-associated infantile spasms.

(Tr. 307-08.)

Dr. Holmes also stresses that this issue was also examined by the Institute of

Medicine in 2012. (Ex. A, p. 10 (citing Committee to Review Adverse Effects of

Vaccines, Institute of Medicine, Stratton et al., Diphtheria Toxoid--, Tetanus Toxoid--,

and Acellular Pertussis—Containing Vaccines, in ADVERSE EFFECTS OF VACCINES:

EVIDENCE AND CAUSALITY 525-97 (2011) (Ex. A, Tab 14.)) With respect to the specific

condition of infantile spasms and vaccinations containing tetanus and/or diphtheria

toxoids, the IOM committee reported three studies, the Goodman study discussed

above, the sole epidemiologic study examined, and a 1983 study by Pollock and Morris

and a 1996 study by Schmitt, both considered as potential mechanistic evidence. (IOM,

supra, Ex. A, Tab 14, pp. 537-38.) The committee was critical of the Goodman study as

lacking validity and precision to assess an association. In particular they were critical of

the study for not disclosing how control subjects were selected. They concluded that

the weight of epidemiologic evidence was insufficient or absent to assess any

association between infantile spasms and either diphtheria or tetanus toxoided vaccines

or acellular pertussis vaccines. (Id. at 538.) The committee’s discussion of Pollock and

Morris and Schmitt is limited to noting that they did not provide evidence beyond

temporality and these studies are not otherwise a part of the record of this case.

Ultimately, the committee concluded that the evidence is inadequate to accept or reject

a causal relationship. (Id. at 539.)

In his reports and during the hearing, Dr. Kinsbourne contended that the IOM’s

conclusion lacks value, because “[p]itching the selection criterion so high is appropriate

if one wishes to construct a ‘definitive picture.’ But that is far from the standard or goal in

Vaccine Court proceedings.” (Ex. 40, p. 1.) During the hearing, he characterized the

IOM’s report as “seriously irrelevant.” (Tr. 241-43.) In this case, the IOM examined the

Goodman study, which reviewed the same data as the Bellman study relied upon by Dr.

Kinsbourne, and concluded that, although it did contribute to the weight of epidemiologic

evidence, the study had flaws. That Dr. Kinsbourne disagrees with that criticism does

not automatically render it overly stringent. 30 In any event, the Goodman study has

30 Dr. Kinsbourne is correct to the extent that special masters are not bound by the IOM’s conclusions and

it has been previously observed, as Dr. Kinsbourne suggests, that the IOM employs a standard for finding

causation that is higher than what is required by petitioner’s burden of proof. E.g. Raymo v. Sec’y of

Health & Human Servs., No. 11-654V, 2014 WL 1092274, at *21, n.39 (Fed. Cl. Spec. Mstr. Feb. 24,

2014). Accordingly, IOM reports and findings should be approached with caution. However, his further

characterization of the report as “seriously irrelevant” based on the preponderant evidence standard goes

too far. First, the question is not whether the IOM itself employs a preponderant standard, but whether

the investigation and conclusions reflect reasonable medical and scientific rigor. Dr. Kinsbourne’s own

challenge to the quality of the IOM’s investigation must be weighed against Dr. Holmes’s competing

endorsement and the IOM should not be expected to cater specifically to this Program’s burden of proof

any more than the authors of any other study or article that includes a retrospective literature review.

Second, special masters apply the preponderant evidence standard to the record as a whole, not specific

pieces of evidence in isolation. The IOM report is not dispositive, but nor does it need to be dispositive to

constitute relevant evidence that must be evaluated in reaching a determination based on the record as a

whole. Numerous prior cases have demonstrated that special masters may account for IOM findings in

reaching their decisions. See, e.g., Crutchfield v. Sec’y Health & Human Servs., 125 Fed. Cl. 251, 262

26

been separately filed into the record of this case and I have reached my own conclusion

as to its weight. During the hearing I also asked Dr. Kinsbourne whether he knew the

IOM’s literature review to be in any way deficient. That is, I invited Dr. Kinsbourne to

draw my attention to any study he is aware of that was overlooked by the IOM in

reaching its conclusion. However, he indicated he had not considered that issue and

could not answer. 31 (Id.)

Standing alone, the findings from Melchior and Bellman do not provide significant

support for Dr. Kinsbourne’s causal opinion. While Bellman noted a small clustering of

cases within one week of vaccination, the overall result did not support a causal

relationship. Moreover, Dr. Kinsbourne is not persuasive in citing only a subset of data

from Melchior to reach the opposite conclusion as the study author. Thus, the overall

findings of these studies weigh against the conclusion that there is any causal

relationship between vaccination and infantile spasms. Nonetheless, Dr. Kinsbourne

cites Bellman et al., for the proposition that the DPT vaccine was shown to “trigger”

clinical onset of infantile spams, referring to it as “a trigger which changed the

(2014) (noting that “it was appropriate for the special master to consider the medical literature presented,

including the IOM report” and that “the court often has relied on the findings of the Institute of Medicine.”);

See also, Isaac v. Sec’y Health & Human Servs., 108 Fed. Cl. 743, 755 (2013), aff'd, 540 Fed. Appx. 999

(Mem.) (Fed. Cir. 2013) (affirming the special master's reliance on findings of the IOM); Porter v. Sec’y

Health & Human Servs., 663 F.3d 1242, 1252 (Fed.Cir.2011) (noting the special master's comment that

“IOM reports are favored, although not dispositive, in the Vaccine Act Program,” then affirming the special

master's decision); Cedillo v. Sec’y Health & Human Servs., No. 98–916V, 2010 WL 331968, at *94 (Fed.

Cl. Spec .Mstr. Feb. 12, 2009), mot. for rev. denied, 89 Fed. Cl. 158 (2009) (affirming special master's

reliance on conclusions of IOM), aff'd, 617 F.3d 1328 (Fed.Cir.2010); Rodriguez v. Sec’y Health & Human

Servs., 67 Fed. Cl. 409, 410 (2005) (relying on IOM report regarding vaccine causation of an injury);

Althen v. Sec’y Health & Human Servs., No. 00–170V, 2003 WL 21439669, at *11, n.28 (Fed. Cl. Spec.

Mstr. June 3, 2003) (“Due to the IOM's statutory charge, the scope of its review, and the cross-section of

experts making up the committee reviewing the adverse events associated with vaccines, the court

considers their determinations authoritative and subject to great deference.”), rev'd on other grounds, 58

Fed. Cl. 270, 272–74 (2003) (citing IOM reports frequently in support of various scientific propositions),

aff'd, 418 F.3d 1274 (Fed. Cir. 2005); Terran v. Sec’y Health & Human Servs., 41 Fed. Cl. 330, 337

(1998) (affirming special master's reliance on conclusions of IOM), aff'd, 195 F.3d 1302 (Fed. Cir.1999),

cert. denied, 531 U.S. 812 (2000); Cucuras v. Sec’y Health & Human Servs., 993 F.2d 1525, 1529 (Fed.

Cir. 1993) (noting that the special master had placed “a great deal of weight” on an IOM report in reaching

a decision, then affirming the special master's decision); Stroud v. Sec’y Health & Human Servs., 113

F.3d 1258 (Fed. Cir. 1997) (unpublished)(special master may rely upon an IOM report that neither party

filed as evidence); Ultimo v. Sec’y Health & Human Servs., 28 Fed. Cl. 148, 152 (1993) (proper for a

special master to rely on IOM report).

31 It should be noted that the IOM committee’s apparent decision to selectively cite from the relevant body

literature for its report does not a fortiori demonstrate bias against the finding of a causal relationship. For

example, the committee did not cite the Guggenheim article discussed below, which pre-dates the 2012

IOM report and casts further doubt on the Goodman findings that were discussed by the committee.

Especially given that the IOM committee did review the primary piece of evidence cited by Dr. Kinsbourne

– that is, the NCES data albeit as examined by Goodman rather than Bellman – Dr. Kinsbourne’s critique

would be much stronger if he were able to identify potentially persuasive evidence of a causal relationship

that represented a significant omission. The IOM committee’s conclusion that there is not sufficient

evidence to accept or reject a causal relationship is not inconsistent with the Goodman study’s overall

conclusion despite its additional finding as to a temporal shift.

27

subclinical to a clinical disorder.” (Tr. 139.) However, to the extent Bellman includes a

specific finding that provides some limited support for the notion of a vaccine-triggered

infantile spasms, passage of time has not borne out that hypothesis any further and, in

fact, subsequent studies have called the very premise into question.

Specifically, Dr. Holmes has filed studies from 2008 by Philippi et al., and

Guggenheim et al., which showed that infantile spasms actually develop over the

course of weeks to months. Philippi, et al, retrospectively examined 39 infants with

symptomatic infantile spasms. (Philippi et al., Electroencephalographic evolution of

hypsarrhythmia: Toward an early treatment option 49(11) EPILEPSIA 1859-1864, 1859

(2008) (Ex. A, Tab 29.)) After examining the serial EEGs available for these subjects,

they concluded that the evolution of the hypsarrhythmia underlying infantile spasms

occurs in three phases, each of which lasts several weeks. (Id. at 5.) They found that

mental deterioration due to infantile spasms begins 3-6 weeks prior to the onset of

hypsarrhythmia. (Id. at 6.) Guggenheim et al., examined 19 published cases of infantile

spasms. They examined the length of time between an encephalopathic event

experienced by a previously normal infant and the onset of infantile spasms.

(Guggenheim et al., Time Interval From a Brain Insult to the Onset of Infantile Spasms,

J. PEDIAT. NEUROL. 34-37, 34 (2007) (Ex. A, Tab 25.)) They found that the latency

between brain insult and onset of spasms ranged from six weeks to 11 months. (Id.)

Thus, they concluded:

[T]he results of our analysis preclude claims that the onset of infantile

spasms within hours or days of immunization indicates a causal

relationship, because such claims are based on the assumption that the

brain is injured by a toxin present in the product, or by some unspecified

aberrant immunologic process. Consequently, the observation that infantile

spasms occur with an average latency of 5.1 months after postnatal injury

is supportive of the already existing strong evidence that vaccine

administration is not a causative factor in this disorder, and reinforces the

generally held view that a close temporal association in occasional cases is

only coincidental.

(Id. at 3.). These findings also support Dr. Holmes’s emphasis throughout the

hearing that infantile spasms are not “provoked” seizures. (Tr. 294-95, 320-21,

323, 354.)

Even setting aside these subsequent studies, an additional issue with Dr.

Kinsbourne’s reliance on the Melchior and Bellman studies is the transition away from

the whole cell pertussis vaccines (“DPT”) studied by Melchior and Bellman toward

acellular formulations of pertussis-containing vaccines (“DTaP”) that are generally

considered to be much safer. This transition dates these studies and leaves them

further attenuated from current realities. Thus, for example, the 2011 von Spiczak

paper relied on by petitioner observes that there is no elevated risk of epilepsy following

DTaP vaccination. (von Spiczak, supra, at Ex. 36, p. 2.) Petitioner also cites a 2002

28

package insert for the DAPTACEL DTaP vaccine. 32 (DAPTACEL package insert, Ex.

55.) That insert identifies seizures occurring within three days of vaccination (with or

without fever) as adverse reactions but does not include infantile spasms as adverse

reactions among its Warnings and Precautions. (Id. at 4-5.) DAPTACEL discloses nine

clinical trials with 18,000 doses administered with only a single report of infantile

spasms reported. 33 (Id. at 6-14.)

Especially because Melchior and Bellman at best demonstrate statistical

observations and not mechanistic evidence, what is purportedly demonstrated with

respect to the DPT vaccine does not automatically translate to the DTaP vaccine. This

was a point stressed by Dr. Holmes during the hearing. (Tr. 309-10.) Dr. Kinsbourne

attempts to overcome this issue by suggesting that both DPT and DTaP vaccinations

promote similar proinflammatory cytokine output and further stressing that “I’ve never

seen any article that said they eliminated the reaction.” 34 (Ex. 24, p.3; Tr. 144.)

However, Dr. Kinsbourne is unpersuasive on this point for several reasons.

32 There is no evidence of record indicating what specific brand of vaccination D.B. received.

33 Petitioner highlights the fact that the contraindications include progressive neurological disorders

including infantile spasms and notes that the “Pertussis vaccine should not be administered to individuals

with such conditions until a treatment regimen has been established and the condition has stabilized.”

(DAPTACEL package insert , supra, at Ex. 55, p. 4.) According to Dr. Kinsborne, this is an

acknowledgement that the pertussis vaccine is more likely than other vaccines to cause seizures when

there is already brain inflammation present. (Tr. 145.) Dr. Holmes disagreed and stressed during the

hearing that this is not an indication that the vaccine causes infantile spasms. (Tr. 311-12.) For a more

detailed discussion of the information contained in package inserts, see Cottingham v. Sec’y of Health &

Human Servs., 15-1291V, 2021 WL 347020, *23-26 (Fed. Cl. Spec. Mstr. Jan. 7, 2021), vacated on other

grounds, 154 Fed. Cl. 790 (2021). In some prior cases, special masters have concluded broadly that

“[s]tatements contained in vaccine package inserts do not constitute reliable proof of causation, and

cannot be deemed admissions that the vaccines in question have the capacity to harm a particular

petitioner in a specific manner.” Sullivan v. Sec'y of Health & Human Servs., No. 10-398V, 2015 WL

1404957, at *20 (Fed. Cl. Feb. 13, 2015) (citing Werderitsh v. Sec'y of Health & Human Servs., No. 99–

319V, 2005 WL 3320041, at *8 (Fed. Cl. Spec. Mstr. Nov. 10, 2005); see also 21 C.F.R. § 600.80(l). The

Cottingham special master, however, further distinguished as more valuable information provided by the

clinical trials described by the package insert. 2021 WL 347020, *23-26. Here, as noted above, the

clinical trials do not appear to support infantile spasms as an adverse reaction to DAPTACEL, which is

consistent with the fact that only seizures, and not infantile spasms or epilepsies, are included among the

Warnings and Precautions despite the language of the contraindication. (DAPTACEL package insert,

supra, at Ex. 55, p. 4-5.) Additionally, while post marketing experience includes febrile convulsions,

grand mal convulsions, and partial seizures, infantile spasms were not reported. (Id. at 16.) The specific

basis for including uncontrolled epilepsies among the contraindications is not indicated (i.e. there is no

citation to either the clinical data or any other literature).

34 Of note, in Kottenstette the Federal Circuit has addressed a similar scenario wherein Dr. Kinsbourne

opined before a different special master that the Bellman and Melchior studies could be relied upon in the

context of the DTaP vaccine based on the notion that DTaP only imperfectly improved the safety of

pertussis immunizations. 861 Fed.Appx at 441-42. The Federal Circuit concluded that the special master

did not abuse her discretion by crediting Dr. Kinsbourne’s testimony as supporting reliance on the

Bellman and Melchior studies. Id. However, nothing in the Federal Circuit’s holding mandates the

outcome reached in that case. Moreover, the Federal Circuit stressed that the special master in

Kottenstette did not reach her conclusion based solely on the Bellman and Melchior studies. Id. at 441.

In that case, Dr. Kinsbourne relied on a different rationale. Whereas here he opines that the adverse

effect profile carries over based on the cytokines produced by the two vaccines, in Kottenstette he opined

29

First, he seeks to extend the Bellman and Melchior findings by relying in large

part on unrelated findings relating to unitary post-vaccination seizure events rather than

the infantile spasms examined by Bellman and Melchior. For example, in addition to the

package insert discussed above, he relies on a 2003 Canadian study be Le Saux et al.,

which examined post-vaccination febrile and afebrile seizures, but does not include

information regarding any form of epilepsy let alone infantile spasms specifically. (Tr.

141-42, 245; Le Saux et al., Decrease in Hospital Admissions for Febrile Seizures and

Reports of Hypotonic-Hyporesponsive Episodes Presenting to Hospital Emergency

Departments Since Switching to Acellular Pertussis Vaccine in Canada: A Report from

IMPACT, 112 PEDIATRICS 1-8 (2003) (Ex. 83.)) The idea that DTaP can cause isolated

seizures, especially febrile seizures, is not disputed in this case (Tr. 323-24, 344-45

(Holmes)) whereas even the more up to date literature filed by Dr. Kinsbourne (von

Spiczak) acknowledges the suggestion of a relationship between infantile spasms and

vaccinations to be controversial. (Ex. 36, p. 10) 35 Dr. Holmes likewise testified that

unitary seizures and infantile spasms cannot be conflated. (Tr. 309-10.)

that the toxoiding process that creates the acellular pertussis component of the vaccine is imperfect and

adverse events following DTaP can be attributed to direct effects of residual untoxoided pertussis toxin

within the vaccine. Kottenstette, 861 Fed.Appx. 436-37. In decisions dating back years, other special

masters have been critical of attempts to carry over statistical observations from one vaccine formulation

to the other. See, e.g., Taylor v. Sec'y of Health & Human Servs., No. 05-1133V, 2012 WL 4829293, at

*30 (Fed. Cl. Spec. Mstr. Sept. 20, 2012) (“[i]t is well established that, while pertussis toxin may be

capable of causing neurological damage, vaccination, especially modern-day vaccination with the

acellular form, is generally safe”) (emphasis added); Holmes v. Sec'y of Health & Human Servs., No. 08-

185V, 2011 WL 2600612, at *20 (Fed. Cl. Spec. Mstr. Apr. 26, 2011) (noting that expert in question had

previously attempted to extrapolate conclusions from studies involving DPT to DTaP vaccines), citing

Simon v. Sec'y of Health & Human Servs., No. 05-941V, 2007 WL 1772062, at *7 (Fed. Cl. Spec. Mstr.

June 1, 2007) (“the relative risks of an adverse event from a DPT vaccine found in those DPT related

epidemiologic studies do not attach to a DTaP vaccine”); Grace v. Sec'y of Health & Human Servs., No.

04-[redacted], 2006 WL 3499511, at *9 (Fed. Cl. Spec. Mstr. Nov. 30, 2006) (noting that “[t]he DTaP

version, in general, is believed by medical scientists to be much improved, and to be much less likely than

the DPT vaccine to cause neurologic reactions or other harmful side effects.”) Moreover, Dr.

Kinsbourne’s framing of the issue as requiring affirmative proof of an “elimination” of the risk is not really

consistent with how epidemiology functions or petitioner’s burden of proof. The question posed from an

epidemiologic standpoint would more likely be whether the incidences of infantile spasms following DTaP

vaccination remain statistically observable as compared to the general population or to controls. Dr.

Kinsbourne has not cited any evidence to suggest that they are. The von Spiczak paper from 2011

acknowledged the possibility, but explicitly indicated that they did not reach that question based on their

own data and otherwise observed based on other studies that the risk of epilepsies following DTaP

vaccine is not elevated. (von Spiczak, supra, at Ex. 36, p. 2.) The 2012 IOM report likewise indicated

that insufficient evidence is available to accept or reject a causal relationship between infantile spasms

and the DTaP vaccine. (IOM, supra, at Ex. A, Tab 14, p. 539.) In a cause-in-fact claim, it is petitioner’s

burden to affirmatively present a prima facie showing of vaccine causation. Petitioner cannot simply

assert ipse dixit that a specific vaccine formulation is unsafe and call on the respondent to prove a

negative.

35 To be clear, Dr. Kinsbourne did also opine that D.B. suffered a tonic seizure that was triggered by his

vaccination and then subsequently evolved into infantile spasms. (Tr. 135-37 (citing Carrazana et al.,

supra, at Ex. 92.)) That aspect of Dr. Kinsbourne’s opinion is addressed separately below. Here I note

only that comparison of the Bellman and Melchior studies to studies involving unitary seizures is not an

“apples to apples” comparison that could support extension of the earlier studies’ findings to other vaccine

formulations.

30

Additionally, even if there can be some intersection between neurology and

immunology, Dr. Kinsbourne is well outside his area of expertise in purporting to opine

as to the relative reactogenicity of different vaccine formulations based on their

immunogenicity. Nor is it clear from the face of the study he cites, which administered

pertussis toxin, rather than vaccines, to mice, how the study’s findings correlate to the

human response to different vaccine formulations. (Chen et al., Pertussis Toxin by

Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 cells, 178(10) J.

IMMUNOL. 1-13 (2007) (Ex. 30.)) By contrast, Dr. Holmes cites a study finding evidence

of lower reactogenicity among infants receiving DTaP vaccine compared to DPT (Stehr

et al.), as well as a competing mouse model study (Donnelly et al.), showing that the

whole cell pertussis vaccine, but not the acellular pertussis vaccine, produced

convulsive levels of proinflammatory cytokines. (Ex. A, p. 9 (citing Stehr, et. al, A

Comparative Efficacy Trial in Germany in Infants Who Received Either the

Lederle/Takeda Acellular Pertussis Component DTP (DTaP) Vaccine, the Lederle

Whole-Cell Component DTP Vaccine, or DT Vaccine, 101(1) PEDIATRICS 1-13, 9 (1998)

(Ex. A, Tab 21); Ex. A, p. 11-12 (citing Donnelly et al., Whole-Cell but Not Acellular

Pertussis Vaccines Induce Convulsive Activity in Mice: Evidence of a Role for Toxin-

Induced Interleukin-1β in a New Murine Model for Analysis of Neuronal Side Effects of

Vaccination, 69(7) INFECT. IMMUN. 4217-4223 (2001) (Ex. A, Tab 23.))

The record is not entirely without evidence consistent with Dr. Kinsbourne’s view

– most notably the temporal shift observed by Bellman. 36 On the whole, however, Dr.

Holmes was more persuasive in testifying that, although the initial investigation into

whether whole cell pertussis can be causally linked to infantile spasms may have been

justified, vaccinations are no longer viewed as a risk factor for the development of

infantile spasms. (Tr. 304-05.) As a general matter, it is true that petitioners in the

Vaccine Program are not required to present epidemiological evidence to establish their

causation burden under Althen. Moberly v. Sec'y of Health & Hum. Servs., 592 F.3d

1315, 1325 (Fed. Cir. 2010). Nonetheless, “[n]othing in Althen or Capizzano requires

the Special Master to ignore probative epidemiological evidence that undermines

petitioner’s theory.” D'Tiole v. Sec’y of Health & Human Servs., 726 F.App'x 809, 811

(Fed. Cir.) (citing Andreu, 569 F.3d at 1379 (“Although Althen and Capizzano make

clear that a claimant need not produce medical literature or epidemiological evidence to

establish causation under the Vaccine Act, where such evidence is submitted, the

Special Master can consider it in reaching an informed judgment as to whether a

particular vaccination likely caused a particular injury.”) (emphasis added))); Grant, 956

F.2d at 1148-49 (considering negative epidemiological studies). Here, given that Dr.

Kinsbourne also proposes a mechanism of injury, the lack of recognition of vaccinations

as risk factors for infantile spasms is not necessarily dispositive, though Dr.

Kinsbourne’s mechanistic theory does in turn rely partly on the above-discussed

literature. (Tr. 209.) At a minimum, however, it does provide important context in

evaluating Dr. Kinsbourne’s proposed mechanism, discussed below.

36In Kottestette, I previously characterized the temporal shift observed by Bellman as providing only

“scant” evidence. 2020 WL 4197301, at *14. However, the Philippi and Guggenheim studies discussed

above were not a part of the record of that case.

31

ii. Dr. Kinsbourne’s proposed mechanism is not supported by

preponderant evidence

Dr. Kinsbourne also purports to demonstrate a mechanism of injury. Specifically,

he proposes that the immune and stress responses to a vaccine injection may act on

the endocrine system to elevate corticotropin-releasing hormone (“CRH”) and provoke

infantile spasms. (Ex. 40, pp. 3-4; Tr. 152.) Alternatively, he suggests that vaccines

may cause partial seizures and that partial seizures may then evolve into infantile

spasms. (Tr. 135-37.) Dr. Kinsbourne cites several points that he urges as support for

this theory:

• The human brain depends on a balance between inhibition and excitation

of neuronal activity. The immature brain is more excitable than the adult

brain. (Tr. 145-47 (see also Baram & Hatalski, supra, at Ex. 26, p. 1).)

GABA is the principle inhibitory neurotransmitter in the mature central

nervous system. (Id.)

• Down syndrome constitutes a predisposition to react adversely to

excitatory influences. (Baram & Hatalski, supra, at Ex. 26, p. 3.)

• Cortez et al., demonstrated that infantile spasms can be caused in a

mouse model of Down syndrome using an injection of Baclofen. (Tr. 145-

47 (discussing Cortez et al., Infantile Spasms and Down Syndrome: A

New Animal Model, 65 PEDIATRIC RESEARCH 499-503 (2009) (Ex. 85.))

Because Baclofen enhances GABA function, Dr. Kinsbourne contends

that this study shows that infantile spasms operate via a GABA-mediated

mechanism. This result is counterintuitive because enhancing GABA,

which is inhibitory, would not be expected to cause seizures, which are

excitatory.

• However, according to Dr. Kinsbourne a further study by Cullinen et al.,

further demonstrates that the body’s stress response indirectly inhibits

GABA, raising overall excitation in the brain. (Tr. 149-51 (discussing

Cullinan et al., Functional role of local GABAergic influences on the HPA

axis, BRAIN STRUCT. FUNCT. (2008) (Ex. 87.))

• Epilepsies are inflammatory states and vaccines release cytokines via the

innate immune system. (Tr. 211.)

• Jansen et al., demonstrated that a heel stick causes a steroid reaction that

affects the hypothalamic-pituitary-adrenal axis, i.e., the HPA axis. (Tr.

152-53 (discussing Jansen et al., supra, at Ex. 86).)

• Baram and Hatalski developed a theory of infantile spasms that posits the

neurohormone corticotropin-releasing hormone (“CRH”) modulates

excitability in the developing brain and may account for the development

32

of seizures in response to stress or infection. (Baram & Hatalski, supra, at

Ex. 26, p. 6.)

• Carrazana et al., reported 16 cases of infantile spasms beginning in close

proximity to a partial seizure. (Tr. 135-36 (discussing Carrazana et al.,

supra, at Ex. 92.))

Pulling these points together, Dr. Kinsbourne opines that Down syndrome constitutes a

preexisting susceptibility or “first hit” and that vaccines can act as a “second hit.” The

vaccine creates two stresses, the production of cytokines as part of the immune

response and the pain of the needle. Acting upon the HPA axis via the stress response

to over produce CRH, vaccination can induce a seizure, whether infantile spasms or a

partial seizure. A partial seizure can then lead to infantile spasms. (Tr. 153, 214-15.)

This theory has significant flaws at nearly every step.

First, Dr. Kinsbourne is not persuasive in contending that the two-hit hypothesis

is an appropriate starting premise. Dr. Holmes distinguishes between Down syndrome

as including a lowered threshold for seizure and as constituting a “first hit” in the two-hit

hypothesis. (Tr. 298-300.) According to Dr. Holmes, the two-hit hypothesis involves the

cumulative effect of multiple brain injuries as contributing to status epilepticus. (Id.

(discussing Hoffman et al., Cognitive impairment following status epilepticus and

recurrent seizures during early development: support for the “two-hit” hypothesis,

Epilepsy & Behavior 873-77 (2004) (Ex. G); Koh et al., NBQX or Topiramate Treatment

after Perinatal Hypoxia-induced Seizures Prevents Later Increases in Seizure-induced

Neuronal Injury, 45(6) EPILEPSIA 569-575 (2004) (Ex. K)).) This is also consistent with

the way in which Arya et al., filed by petitioner, categorize infantile spams in the context

of Down syndrome as potentially being either cryptogenic or symptomatic depending on

the presence of other factors. (Arya et al., supra, at Ex. 25, p. 2.) Moreover, Dr.

Holmes explained that Guggenheim et al., demonstrates that even when there is an

identified first hit, such as hypoxia, onset of infantile spasms occurs months later and

without the necessity of a “second hit.” (Tr. 301-02 (discussing Guggenheim et al.,

supra, at Ex. A, Tab 25).) In fact, Dr. Kinsbourne himself acknowledges that a second

hit is not necessary to the manifestation of infantile spasms. (Tr. 208-09.)

Second, Dr. Holmes takes issue with Dr. Kinsbourne’s reliance on the mouse

studies by Cortez and Cullinen as well as upon the Baram hypothesis. (Tr. 315-17.)

With respect to all three, Dr. Holmes stressed that none of these studies relate their

findings to the context of vaccination. (Id.) Indeed, Baram only hypothesized that

triggers such as fever, hypoxia, or trauma might contribute to seizures. (Ex.41, pp. 1-2.)

With respect to the Cortez study, Dr. Holmes further stressed the point, also

acknowledged by Dr. Kinsbourne, that the animal model did not have spontaneous

spasms. (Tr. 315.) That is, Dr. Kinsbourne acknowledged that model of Down

syndrome did not demonstrate infantile spasms except through the manufactured

means of injecting Baclofen. Thus, Dr. Kinsbourne indicated that the model is

“incomplete,” and accepted that this was an “important point.” (Tr. 146.)

33

Dr. Holmes also explained that the Baram hypothesis comes from a long-

standing research interest of Dr. Tallie Baram in exploring whether the HPA axis could

contribute to the triggering of infantile spasms. It was based on two observations. On

the one hand, studies of the spinal fluid of children with infantile spasms found

decreased levels of ACTh. (Tr. 317.) The fact that ACTh is an effective treatment for

infantile spasms is well established. (Tr. 293-94.) On the other hand, an animal model

study showed that injecting CRH into the brains of young animals can cause seizures

(not infantile spasms). (Tr. 318.) According to Dr. Holmes, where the Baram

hypothesis failed was in trying to bridge the two observations by using ACTh to prevent

the CRH-induced seizures in the animal model. ACTh did not prevent the CRH-induced

seizures. Thus, while the theory once merited attention, he indicates that it has since

been abandoned. 37 (Id.)

In any event, assuming arguendo that infantile spasms are provoked by stress

hormones, Dr. Kinsbourne has also not supported the idea that any of this would be

triggered by vaccination. With respect to the stress response from a heel stick, he

acknowledges that the Jensen article is inadequate to provide any suggestion that its

findings of increased cortisol, which Dr. Holmes characterizes as mild, are clinically

significant. (Tr. 246, 316.) Dr. Kinsbourne also acknowledges that the only basis for

contending that infantile spasms are an inflammatory condition is his own assertion that

they have a pro-inflammatory trigger. In the absence of such a trigger, he would not

know if the condition was inflammatory. (Tr. 211-12, 213.) Confusingly, despite

positing that the pertussis in the vaccine can cause seizures via pro-inflammatory

cytokines, he also suggested that the Cortez mouse model suggests that you don’t

need a cytokine response to produce the elevated cortisol underlying the Baram

hypothesis. (Tr. 218, 221.) He does not know of any animal model study that shows

activation of the immune system causes infantile spasms and does not recall filing any

literature identifying proinflammatory cytokines as a mechanism for post-vaccination

infantile spasms. (Tr. 211-12, 213.) When asked during the hearing if any literature

posits vaccination as a second hit within the two-hit hypothesis, he referred to the

literature filed in this case demonstrating higher than expected incidences of infantile

spasms following vaccination. (Tr. 209.) However, for all the reasons discussed above,

that literature is not persuasive.

Finally, the ultimate lynch pin in Dr. Kinsbourne’s alternative theory for this case

is his reliance on the Carrazana article as demonstrating that a partial seizure can

introduce infantile spasms. This is the sole support on this record for Dr. Kinsbourne’s

assertion that partial seizures can develop into infantile spasms. In fact, Dr. Kinsbourne

testified that he cannot explain how a seizure can evolve into infantile spasms but for

his reliance on the Carrazana article. 38 (Tr. 221.) However, Dr. Holmes’s explanation

37In Kottenstette, I previously accepted Dr. Kinsbourne’s reliance on the Baram hypothesis to the extent

that it showed seizures can be triggered by stress. 2020 WL 4197301, at *14. In that case, there was no

expert testimony challenging the Baram hypothesis’s general acceptance.

38 There is a theory known as the “kindling theory” in which initial seizures are suspected to bring about

further seizures. Dr. Holmes explained, however, that the seizures involved in infantile spasms are not

consistent with the kindling theory. (Tr. 350-52 (discussing Ben-Ari & Holmes, Relevance of Basic

34

of the Carrazana article (he is among the authors) persuasively established that Dr.

Kinsbourne is misinterpreting that paper. (Tr. 286-90.)

Carrazana et al., is a report of 16 cases of infantile spasms in which the infantile

spasms were preceded by or concurrent with partial seizures. (Carrazana et al., supra,

at Ex. 92.) The authors suspected that the temporal proximity of the partial seizures to

the infantile spasms may be causally relevant. Specifically, Dr. Kinsbourne highlights

the following explanation: “‘[t]his group of patients supports a model in which the

spasms, though probably generated at a subcortical level, are facilitated or possibly

induced [by] focal discharges from cortical pathology.’” (Tr. 136 (quoting Carrazana et

al., supra, at Ex. 92, p. 1.) He opined that this article provides evidence that “[t]he

vaccines surely triggered the partial seizures, not the infantile spasms. The partial

seizures then transformed into infantile spasms.” (Tr. 136.)

Dr. Holmes explains, however, that all of the sixteen subjects had focal

abnormalities or lesions. This was a prerequisite to being included in the study. (Tr.

288-90.) Dr. Kinsbourne had not understood this as he denied that all of the Carrazana

subjects had focal abnormalities. (Tr. 222.) This is significant because Carrazana did

not identify partial seizures as causes of infantile spasms, but rather questioned in the

specific context of focal abnormalities whether the partial seizures, as manifestations of

the focal abnormality, were evidence that the infantile spasms were etiologically related

to the focal cortical lesion as opposed to the partial seizure. Dr. Holmes explained that

while Carrazana demonstrated that infantile spasms and focal seizures can occur at the

same age, the bilateral generalized infantile spasms and the focal seizure remain two

separate neuropathologic processes. (Tr. 287-88.) Dr. Holmes specifically testified that

“we clearly show that they're not having focal seizures that then propagate into infantile

spasms” (Tr. 290) and that “[b]y no means did that paper show that focal seizures cause

infantile spasms.” (Tr. 288.) Thus, the article stresses that as of its 1993 publication,

“the role of the coexisting cortical lesions, whether critical for development of the

spasms or merely coincidental, remains unknown” and that the paper instead suggests

“an important role for cortical structures in the generation of spasms.” (Carrazana et al.,

supra, at Ex. 92, p. 1.) Among these subjects, ACTh treatment was largely not effective

and many were considered surgical candidates, points which distinguish these subjects

from other patients with infantile spasms, including D.B. (Tr. 286-88; Carrazana et al.,

supra, at Ex. 92, p. 11.) That is, the Carrazana paper proposes an etiologic model for a

specific subset of symptomatic infantile spasms involving cortical pathology not relevant

to D.B.’s own history rather than any kind of causal relationship between partial seizures

and infantile spasms. (Carrazana et al., supra, at Ex. 92, p. 1.)

For all these reasons, even if setting aside the discussion of epidemiology in the

preceding section, Dr. Kinsbourne has not persuasively theorized that vaccines can in

themselves cause infantile spasms. Nor has he persuasively theorized that an initial

vaccine-caused partial seizure can cause or contribute to the onset of infantile spasms.

Research to Clinical Data: Good Answers, Wrong Questions!, 8(1) EPILEPSY CURRENTS, 19-22 (2008) (Ex.

E.)) In any event, Dr. Kinsbourne never specifically cited this theory.

35

b. Althen Prong Two

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; Grant,

956 F.2d at 1148. In establishing that a vaccine “did cause” injury, the opinions and

views of the injured party's treating physicians are entitled to some weight. Andreu, 569

F.3d at 1367; 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).

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. See 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”).

In this case, there is testimony indicating that D.B. had a fever during the evening

following his February 14, 2015 vaccinations. (Tr. 67, 69.) Additionally, there is

evidence that the DTaP vaccine can cause febrile seizures (Tr. 118 (Kinsbourne); 344-

45 (Holmes)), though Dr. Kinsbourne is not specifically relying on the presence of a

febrile seizure. (Tr. 222, 245-46). However, even if D.B. had initially experienced a

post-vaccination seizure separate from his infantile spasms, Dr. Kinsbourne has not

articulated how that one seizure could have developed into infantile spasms. As noted

above, Dr. Kinsbourne testified that he cannot explain how a seizure can evolve into

infantile spasms but for his reliance on the Carrazana article. (Tr. 221; Carrazana et al.,

supra, at Ex. 92.) Dr. Holmes was persuasive, however, in explaining that Dr.

Kinsbourne misinterpreted the Carrazana paper. (Tr. 222, 286-90.) Dr. Kinsbourne’s

reliance on the Carrazana paper is further attenuated in that Dr. Holmes suggests Dr.

Kinbourne is wrong to equate the tonic seizure he purports to identify in D.B.’s case with

a partial seizure as discussed in Carrazana. (Tr. 320.) Although Dr. Kinsbourne

opines that a focal injury is not necessary for a tonic seizure to occur, Carrazana

involved partial seizures manifesting from focal pathology and Dr. Kinsbourne

acknowledges D.B. had no focal injury. 39 (Tr. 221.) Dr. Kinsbourne also acknowledged

that what he proposes would constitute an unusual presentation. (Tr. 246.)

In any event, Dr. Kinsbourne is also not persuasive in opining that D.B. actually

experienced an initial partial or tonic seizure prior to onset of his infantile spasms. First,

none of D.B.’s treating physicians diagnosed him with any type of seizure other than

infantile spasms. In fact, D.B.’s treating neurologist (Dr. Armstrong-Wells) reviewed

39Dr. Kinsbourne nonetheless opined that inflammatory cytokines could have acted focally to cause a

tonic seizure (Tr. 221); however, the basis for this statement is not clear.

36

video footage of D.B.’s early seizures and concluded that they are “classic for infantile

spasms.” (Ex. 2, p. 16.) Moreover, no objective evidence supports Dr. Kinsbourne’s

assertion. Dr. Kinsbourne acknowledges there is no medical record evidence to

suggest that D.B. suffered focal seizures and that his opinion is based on descriptive

evidence only. (Tr. 225, 244.) Yet, he did not personally observe the seizures and,

again, his interpretation of these early seizures is directly contradicted by D.B.’s treating

neurologist. (Ex. 2, p. 16.) Second, Dr. Kinsbourne’s opinion is not consistent with the

onset of D.B.’s own seizures. Specifically, while Dr. Kinsbourne suggested D.B.’s initial

seizure was a tonic seizure because D.B. had body stiffness, D.B.’s parents were clear

and consistent in indicating that his initial seizure activity was limited to staring episodes

and that seizures inclusive of stiffness did not begin until the next day. 40 (Compare Tr.

220-21, 245 and Tr. 68, 72, 102-06.) Third, Dr. Holmes is persuasive in providing a

competing expert opinion, consistent with that of the treating neurologist, that the

description of onset provided by D.B.’s parents closely fits the pattern of onset of

infantile spams rather than tonic seizures. (Tr. 318-22.) Dr. Holmes further explained

that while the seizures seen in infantile spasms are a bit more prolonged than simple

myoclonus, they are not tonic. (Tr. 270-71, 280.) The fact that the spasms occur in

clusters is characteristic of the condition. (Id.)

Even setting aside the question of a partial or tonic seizure, the fact that D.B.’s

infantile spasms arose post-vaccination does not in itself provide meaningful evidence

supporting vaccine causation. Standing alone, a temporal association is not sufficient to

satisfy Althen prong two. Veryzer v. Sec’y of Health & Human Servs., 100 Fed. Cl. 344,

356 (2011) (explaining that a “temporal relationship alone will not demonstrate the

requisite causal link and that petitioner must posit a medical theory causally connecting

the vaccine and injury.”). Moreover, Dr. Holmes has raised reasons to doubt there is

any significance to the apparent temporality in this case. First, the condition of infantile

spasms in itself has an age-related onset (first year of life) that matches the onset in

D.B.’s case. (Ex. A, p. 9.) Relatedly, Dr. Kinsbourne acknowledges, consistent with Dr.

Holmes’s testimony that infantile spasms are not provoked seizures, that a specific

trigger is not necessary for the onset of infantile spasms and that they can present

40 Theoretically Dr. Kinsbourne could disagree that the initial staring episodes described by petitioner and

Mr. Bangerter were actually seizures at all; however, this is not his opinion. Dr. Kinsbourne confirmed

that his opinion is that the seizures began on the same day as the vaccinations. (Tr. 134, 153.) Notably,

Dr. Kinsbourne based his opinion in part on a description of D.B.’s seizure activity contained in the

medical records (Tr. 123-24; Ex. 1, p. 46); however, the record he relied upon is from February 17 and Dr.

Kinsbourne agrees that by that time D.B.’s seizure activity represented infantile spasms. (Tr. 124.) The

discrepancy between Dr. Kinsbourne’s assumption and fact witness testimony regarding the nature of

D.B.’s very first spasms on the evening of his vaccination also calls into question Dr. Kinsbourne’s

suggestion that onset of D.B.’s spasms was unusually abrupt. (Tr. 125-26.) In that regard, Dr. Holmes

clarifies that any one individual seizure is necessarily abrupt by the nature of seizures. (Tr. 346-48.)

Infantile spasms can be subtle enough to go unnoticed until they become more intense, but they can also

be noticed abruptly. (Tr. 345.)

37

spontaneously. (Tr. 196-97, 220.) Second, D.B.’s Down syndrome represented a

separate risk factor for the condition. 41 (Ex. A, p. 9.)

Given these factors, Dr. Kinsbourne is unpersuasive in dismissing the alternative

to vaccine-causation as an unbelievable “cosmic coincidence.” 42 (Tr. 227-28.) Without

any basis to connect the two events (vaccination and injury onset), Dr. Kinsbourne’s

apparent reticence in applying the term coincidence does not serve to fill that gap or

constitute actual evidence of causation. Dr. Kinsbourne is correct that coincidence

would not necessarily be a satisfying explanation in the context of a truly mysterious

injury with no other available explanation, but that is not the case here. That a child

predisposed to suffering infantile spasms, a condition that does not require a trigger to

manifest and has a known age-related period of onset, suffered that condition at the age

when that condition typically manifests in no way requires invocation of coincidence to

constitute a reasonable explanation for the occurrence of that injury.

Additionally, as discussed further with respect to Althen prong three, Dr. Holmes

is persuasive in demonstrating that clinically overt infantile spasms have a weeks-to-

months long latency period from initial insult, meaning that the cause-and-effect

relationship suggested by Dr. Kinsbourne in this specific case is implausible. While the

outward presentation of infantile spasms may appear sudden, Dr. Holmes explained

that:

[a] process this complex, this diffuse, this dramatic on EEG, just doesn’t

occur suddenly. Much different than someone that comes in who has status

epilepticus, who suddenly goes into a prolonged seizure. The brain is – the

arch of the EEG is remarkably dramatically abnormal from the very onset.

Infantile spasms is a beast of a different nature in that it does evolve slowly

. . . So the clinical aspect, at some point they have someone who notices

something . . . But infantile – the hypsarrhythmia didn’t start then, the

process evolved.

(Tr. 347-48.)

Finally, petitioner also contends that one of D.B.’s treating neurologists (Dr.

Chapman) “clearly linked the pertussis component of the DtaP vaccine to the seizures

when he advised that D.B. should not get another pertussis containing vaccine in the

future. The neurologist certainly accepted a cause and effect association between the

41Specifically, the prevalence of seizures among Down syndrome individuals is 1-13% compared to 1.5-

5% in the general population and infantile spasms are the most common type of seizure activity among

those with Down syndrome. (Ex. A, p. 9.)

42 Dr. Kinsbourne relies in part on the logic that the closer in time two events are, the more difficult it is to

attribute coincidence. (Tr. 227-28.) However, this is unpersuasive. Coincidences by definition have the

appearance of concurrence without necessarily suggesting a causal relationship. What Dr. Kinsbourne is

actually describing is a continuum between what can be viewed as coincidental and what is not even

perceived as potentially connected.

38

pertussis vaccine that D.B. received and his seizures.” (ECF No. 108, p. 9.)

Specifically, a note within D.B.’s primary care records reports that Dr. Leland “spoke

with Dr. Kevin Chapman at Children’s Neurology and he recommended the [patient] not

get the DTAP vaccine given his history, but rather the DT pediatric dose vaccine.” (Ex.

1, p. 97.)

While petitioner is not unreasonable in interpreting this notation as showing Dr.

Chapman to be open to an association between pertussis vaccination and seizures, a

precaution against future vaccination is not actually an opinion that D.B.’s prior condition

of infantile spasms was vaccine-caused. For example, the DAPTACEL package insert

filed by petitioner indicates that the DTaP vaccine is contraindicated in the context of

neurologic conditions such as infantile spasms without respect to the underlying cause

of the condition and without including infantile spasms among the known adverse

reactions to the vaccine. 43 (DAPTACEL package insert, supra, at Ex. 55, pp. 4-5.) In

contrast to Dr. Chapman’s precaution, D.B.’s neurology records do not record any view

by his neurology team that his infantile spasms were caused by any of his vaccinations.

Dr. Chapman’s precaution is not wholly without evidentiary value and I have considered

it; however, especially in light of petitioner’s failure to meet her burden under Althen

prongs one and three, it is not enough without more to carry petitioner’s burden under

Althen prong two.

c. Althen Prong Three

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 Fed.Appx. 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).

Petitioner’s failure to establish Althen prong one in this case necessarily means

she cannot establish Althen prong three. Dr. Holmes has persuasively explained that

due to the way in which infantile spasms develop, the initial onset of D.B.’s first spams

43 It is also worth noting that Dr. Chapman’s recommendation actually exceeds the contraindication

included in the DAPTACEL package insert in that the package insert indicates only that the vaccine is

contraindicated for neurologic conditions that are untreated or not yet stabilized. (DAPTACEL package

insert, supra, at Ex. 55, p. 4.) By the time Dr. Chapman was consulted for this precaution, D.B.’s infantile

spasms had completely resolved. For his part, Dr. Holmes indicates that he recommends that all of his

patients get all immunizations on schedule, including DTaP. (Tr. 323.)

39

could not be temporally related to a trigger occurring just hours earlier. The studies by

Philippi et al., and Guggenheim et al., show that infantile spasms actually develop over

the course of weeks to months. (Guggenheim et al., supra, at Ex. A, Tab 25; Philippi et

al., supra, at Ex. A, Tab 29.)) Guggenheim et al., further demonstrated that the latency

between an encephalopathic event and onset of infantile spasms was between six

weeks to 11 months. (Guggenheim et al., supra, at Ex. A, Tab 25, p. 34.) The

Guggenheim study explicitly refutes the temporal shift observed by Bellman within the

first week following vaccination. (Id.) In the interest of completeness, I do note that Dr.

Kinsbourne is persuasive in establishing that it is medically reasonable to attribute a

seizure occurring within three days of a DTaP vaccination to that vaccine. (See, e.g.,

DAPTACEL package insert, supra, at Ex. 55; Le Saux et al., supra, at Ex. 83.)

However, as discussed above, this is not consistent with what D.B. actually

experienced. Asked if the hypsarrhythmia underlying infantile spasms can develop

within one day, Dr. Kinsbourne indicated that he does not know. (Tr. 231.)

d. Weighing the Competing Expert Opinions

Where both parties 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, 118 S. Ct. 512, 139 L.Ed.2d 508 (1997)); see also Isaac v. Sec'y of

Health & Human Servs., No. 08–601V, 2012 WL 3609993, at *17 (Fed. Cl. Spec. Mstr.

July 30, 2012), mot. for review den'd, 108 Fed. Cl. 743 (2013), aff'd, 540 Fed. Appx. 999

(Fed. Cir. 2013) (citing Cedillo, 617 F.3d at 1339). 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. Moberly, 592 F.3d 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”).

In determining whether a particular expert's testimony was reliable or credible, a

special master may consider whether the expert is offering an opinion that exceeds the

expert's training or competence. Walton v. Sec'y of Health & Human Servs., No. 04–

503V, 2007 WL 1467307, at *17–18 (Fed. Cl. Spec. Mstr. Apr. 30, 2007)

(otolaryngologist not well suited to testify about disciplines other than her own

specialty). While all testimony of the experts offered at the entitlement hearing was

heard and considered, a special master may properly evaluate, and give appropriate

weight to, whether certain testimony is beyond a particular expert's purview. See, e.g.,

King v. Sec'y of Health & Human Servs., No. 03-584V, 2010 WL 892296, at *78–79

(Fed. Cl. Spec. Mstr. Mar. 12, 2010) (petitioner's expert far less qualified to offer opinion

40

on general causation issues pertaining to autism than specific issues pertaining to the

petitioner's actual medical history, given the nature of the expert's qualifications).

Here, Dr. Kinsbourne was accepted without objection as an expert in pediatric

neurology. (Tr. 117.) However, respondent stresses in his briefing his view that Dr.

Kinsbourne’s opinion is of “minimal value” based on several factors. (ECF No. 90, pp.

11-14.) Respondent stresses that Dr. Kinsbourne’s credentials do not include any

education, training, or expertise in pediatric immunology or seizure disorders. (Id. at

11.) He also stresses that Dr. Kinsbourne’s career has largely focused on

neuropsychology. (Id. at 11-12.) Respondent also argues that Dr. Kinsbourne’s

retirement in the 1990’s renders his clinical experience remote. (Id. at 12.) (Dr.

Kinsbourne took a nonmedical position with the New School in the early 1990’s which

ended after 20 years or about four to five years prior to the hearing in this case (Tr.

116).) Respondent cites a number of cases in which special masters have weighed the

specifics of Dr. Kinsbourne’s background in the context of assessing his opinion with

respect to pediatric epilepsy. 44 (ECF No. 109, pp. 12-13.)

I have previously been critical of Dr. Kinsbourne for opining beyond his area of

expertise and into the field of immunology. Kottenstette., 2020 WL 4197301 at *13-14,

review denied, decision aff'd, No. 15-1016V, 2020 WL 4592590 (Fed. Cl. July 27, 2020),

rev'd on other grounds, 861 Fed. Appx. 433 (Fed. Cir. 2021). However, I have also

declined to credit respondent’s arguments regarding Dr. Kinsbourne’s retirement in

some circumstances based on the specific contours of his testimony. Eilan v. Sec'y of

Health & Human Servs., No. 15-381V, 2021 WL 1085925, at *29-31 (Fed. Cl. Spec.

Mstr. Feb. 23, 2021). In this case Dr. Kinsbourne’s reliance on seemingly outdated

materials and his lack of any recent clinical experience relative to pediatric epilepsy

does dovetail with respondent’s criticism and does affect the weight of his testimony in

this case. Dr. Kinsbourne did have some notable experience in the 1950’s and 1960’s

at Great Ormond Hospital with respect to the early use of ACTh in the treatment of

infantile spasms (Tr. 200-01); however, that experience was limited and was decades

ago (Tr. 201-02). Dr. Kinsbourne acknowledged that it has been decades since he last

administered ACTh therapy to any patient. (Tr. 240.) Moreover, although Dr.

Kinsbourne’s CV reflects that he has an extensive publication history, it is unrevealing of

44

Specifically: Martin v. Sec’y of Health & Human Servs., No. 15-789V, 2020 WL 4197748, at *7, 31 (Fed.

Cl. Spec. Mstr. May 8, 2020), aff’d, Martin v. Sec’y of Health & Human Servs., No. 15-789V, slip op (Fed.

Cl. 2020) (“Dr. Kinsbourne . . . has no demonstrated research or treatment expertise in the matters in

dispute, and he relies on neurology expertise that has not been honed or refined, whether by clinical

practice or research, for nearly 30 years.”); Jaafar v. Sec’y of Health & Human Servs., No. 15-267V, 2018

WL 4519066, at *3 (Fed. Cl. Spec. Mstr. Aug. 10, 2018) (concluding that petitioner did not establish DTaP

vaccination caused infantile spasms and noting that “the most recent phase of [Dr. Kinsbourne’s] career

has had a shallower connection to pediatric neurology clinical care.”); Holmes, 2011 WL 2600612 at *20

(questioning Dr. Kinsbourne’s “clinical expertise in diagnosing and treating febrile seizures and epilepsy”);

Stone v. Sec’y of Health & Human Servs., No. 04-1041V, 2010 WL 1848220, at *8 (Fed. Cl. Spec. Mstr.

Apr. 15, 2010), review granted, judgment rev’d sub nom; Stone v. Sec’y of Health & Human Servs., 95

Fed. Cl. 233 (2010) (“The fact that for the past twenty-five years Dr. Kinsbourne has not focused his

practice, research or teachings in the field of seizure disorders, . . . significantly limited his ability to offer

reliable, persuasive, and cogent testimony in this case.”); Hoskins v. Sec’y of Health & Human Servs., No.

15-071V, 2017 WL 3379270, at *5 (Fed. Cl. Spec. Mstr. July 12, 2017).

41

any significant body of publications directly relevant to the condition of infantile spasms.

(Ex. 23, pp. 5-33.) It is also the case that key elements of Dr. Kinsbourne’s mechanistic

theory are grounded in immunology, a subject beyond his area of expertise. Although

immunology and neurology can intersect in the etiology of pediatric neurologic

conditions, Dr. Kinsbourne here is attempting to leverage immunologic concepts to

circumstantially establish a role for vaccines in the onset of infantile spasms in the face

of direct investigation of that possibility that has suggested the lack of such a role.

Moreover, his premise for leveraging evidence relating to different vaccine formulations

to the DTaP vaccine is to compare the relative reactogenicity of the different

formulations.

Dr. Holmes was also accepted as an expert in pediatric neurology; however,

petitioner did object to an additional designation of Dr. Holmes as having a specialty in

seizure disorders. (Tr. 268-69.) According to petitioner, Dr. Holmes’s practice “sounds

like a very general pediatric neurology practice.” (Id.) Petitioner stressed that all

pediatric neurologists see patients with seizures along with other things and that given

the broad description of his practice, he is not out of the ordinary for a pediatric

neurologist. (Id.) Petitioner is correct that Dr. Holmes described a full neurology

practice in which he devotes only a single day per week to epilepsies and sees only

about five or six infantile spasms patients per year. (Tr. 263, 266.)

Petitioner’s objection is unpersuasive, however, when viewing Dr. Holmes’s

background and credentials as a whole. In addition to his clinical practice, Dr. Holmes

has a long career in research relating to childhood epilepsies. (Tr. 263-64.) Dr. Holmes

has developed animal models and done in vivo and in vitro laboratory studies

addressing the effects of seizures and epilepsies on brain development. (Tr. 264.) His

curriculum vitae lists two ongoing research grants, both on the topic of seizures, as well

as 313 peer-reviewed articles of which well over 100 directly reference seizures. (Ex. B,

pp. 26, 33-59.) Dr. Holmes represents that he has developed an animal model of

infantile spasms and has published 19 studies specifically on infantile spasms. (Tr.

265-66.)

Even setting aside the specific designation of a specialty in seizure disorders and

treating both Dr. Kinsbourne and Dr. Holmes as pediatric neurologists generally,

comparison of the two experts’ curriculum vitae still shows that they are not on equal

footing with respect to their background in seizure disorders. (Compare Ex. B and Ex.

23.) Dr. Holmes has more, and much more up-to-date, experience, both clinically and

in research, regarding seizure disorders generally and infantile spasms in particular.

e. Pneumococcal and other vaccines

I note briefly that D.B. received a number of vaccines at his six-month check up

on February 14, 2014. Of those vaccinations, his DTaP vaccine garnered by far the

most attention in this case. Other than DTaP, only his pneumococcal vaccine was

invoked during the hearing. Specifically, while Dr. Kinsbourne excluded most of D.B.’s

other vaccinations, Dr. Kinsbourne did cite the pneumococcal vaccine in his causal

42

opinion. (Tr. 122-23, 203.) However, he acknowledged that the literature linking the

pneumococcal vaccine to seizures is less robust than the evidence regarding the DTaP

vaccine and that petitioner did not file any literature pertaining specifically to the

pneumococcal vaccine. (Tr. 203.) Here, I note in the interest of completeness that, in

light of the analysis above pertaining to the DTaP vaccine, there is likewise not

preponderant evidence that any of D.B.’s other February 14, 2014 vaccinations,

including his pneumococcal vaccine, causally contributed to his infantile spasms alone

or in combination with his DTaP vaccine.

f. Six months of Sequela

Even if petitioners did succeed in demonstrating that D.B.’s infantile spasms

were vaccine-related, a remaining question would be whether they also established that

D.B. suffered complications or residual effects of his condition lasting at least six

months. In order to state a claim for a vaccine-related injury under the Vaccine Act, a

vaccinee must have either:

(i) suffered the residual effects or complications of such illness, disability,

injury, or condition for more than 6 months after the administration of the

vaccine, or (ii) died from the administration of the vaccine, or (iii) suffered

such illness, disability, injury or condition from the vaccine which resulted

in inpatient hospitalization and surgical intervention.

§ 300aa-11(c)(1)(D).

In this case, however, following his successful treatment with ACTh, D.B. was

seizure free as of March 3, 2014. (Ex. 2, p. 171; Tr. 132-33.) Moreover, an EEG of

March 13, 2014, demonstrated resolution of D.B.’s hypsarrhythmia. 45 (Ex. 7, p. 166; Tr.

133-34.) This is less than six months following the vaccination(s) at issue. Moreover,

neurological exams conducted on February 18 and February 26, 2014, as well as an

MRI study performed on February 27, 2014, showed no evidence of neurological

damage. (Ex. 7, pp. 13-16 (February 18 exam); Ex. 7, pp. 67-69 (February 26 exam);

Ex. 2, pp. 77-78 (February 27 MRI); Tr. 131, 332-35). Around the time of his

vaccination, D.B. did experience some loss of milestones, namely a loss of head control

and some reduction of social response. (Tr. 162-63 (discussing Ex. 3, pp. 24-25); Ex. 2,

pp. 61, 67.) However, D.B.’s medical records and the testimony of his occupational

therapist confirm not only that he had regained these milestones within six months, but

also that he had resumed making progress beyond his prior baseline. (Tr. 186

(discussing Ex. 3, p. 41); see also Tr. 237-38 (Dr. Kinsbourne agreeing); Ex. 7, p. 351

(Dr. Dingman noting return of milestones and additional developmental gains as of July

8, 2014).) None of this is necessarily surprising as both neurology experts opined that it

is possible for infantile spasms to be transient and without lasting neurologic damage.

45While Dr. Kinsbourne identified some additional abnormality relative to the March 13, 2014 EEG, a later

April 7, 2014 EEG was entirely normal. (Ex. 7, p. 166.)

43

Petitioner’s neurology expert, Dr. Kinsbourne, explained that “infantile spams

usually have an adverse impact on child development, which may be massive and

permanent, but in favorable cases is minor and recoverable[;]” and the “severity of the

impact on development is in part mediated by the duration of the spasms and is

mitigated when the spasms are readily suppressed by treatment, notably ACTh.” (Ex.

20, p. 2.) Dr. Kinsbourne further explained that infantile spasms occurring in children

with Downs syndrome “are unusually responsive to treatment,” including treatment with

ACTh. (Ex. 20, p. 2 (citing Nabbout et al., Infantile Spasms in Down Syndrome: Good

Response to a Short Course of Vigabatrin, 42(12) Epilepsia 1580-1583 (2001) (Ex. 21,

p. 4)).) With regard to D.B.’s own recovery, Dr. Kinsbourne opined that D.B.’s response

to ACTh treatment was “specifically wonderful” and the fact that his final spasm was on

March 3 was “spectacular.” (Tr. 131.)

Dr. Holmes further explained that in infantile spasms the outward seizure activity

is merely the “tip of the iceberg.” (Tr. 272.) “The seizures come and go . . . [but] the

hypsarrhythmic EEG is there 24 hours a day, seven days a week.” (Id.) The

hypsarrhythmic activity is what accounts for regression. (Id.) For example, he

explained that the presence of visual agnosia is an indicator that hypsarrhythmia is

interfering with the processing of information in the brain. (Tr. 276-77, 330-31.) Where

infantile spasms lead to permanent effects, it is because prolonged periods of

hypsarrhythmia have prevented neuronal development and connectivity in different

parts of the brain critical to the developmental stage. (Tr. 277-78.) Even where there is

later some improvement, these deficits cannot be recouped because the critical

developmental period is inherently lost. (Id.) However, when the hypsarrhythmia is

resolved quickly, children do quite well. (Tr. 277.)

Consistent with Dr. Kinsbourne’s testimony, Dr. Holmes also cited a study by

Stafstrom, showing that children with Down syndrome who experience infantile spasms

tend to have good outcomes vis-à-vis regression. (Stafstrom, Epilepsy in Down

Syndrom: Clinical Aspects and Possible Mechanisms, 98 AM. J. ON MENTAL

RETARDATION 12-26 (1993) (Ex. A, Tab 7.)) Additionally, that study suggested that the

regression, if any, is limited to the period of the spasms and a little before. (Id.) An

additional article by Kivity et al., indicates that early intervention improves outcomes.

(Kivity et al., Long-term Cognitive Outcomes of a Cohort of Children with Cryptogenic

Infantile Spasms Treated with High-dose Adrenocorticotropic Hormone, 45(3) EPILEPSIA

255-262 (2004) (Ex. J.)) According to Dr. Holmes, “infantile spasms are pretty serious

and are associated with regression, but not all is lost if you treat these children, some of

them will do quite well, including those with Down syndrome.” (Tr. 292.) In his personal

experience, infantile spasms patients with Down syndrome do very well, especially with

ACTh therapy. (Tr. 293.)

For D.B., Dr. Holmes explained that his normal EEG within four weeks is “a

winner” and indicative of a very good prognosis. (Tr. 281.) He also noted that, while

D.B. did have a period of inattentiveness, he did not demonstrate the type of visual

agnosia that would indicate hypsarrhythmic damage. (Tr. 331.) Dr. Holmes agreed that

D.B. continues to face developmental challenges due to his Down syndrome, but these

44

are not due to his infantile spasms. (Tr. 342.) Dr. Holmes opined that D.B. is no worse

off now than he would have been but for his infantile spasms. (Id.)

Additionally, petitioner testified that as of his first birthday, D.B. was “very similar”

to what he had been like prior to his infantile spasms. (Tr. 91-92.) D.B. was born on

July 22, 2013, and the vaccinations at issue were administered February 14, 2014.

Accordingly, D.B.’s first birthday occurred less than six months after his alleged vaccine

injury. Petitioner recalled that he was sitting up, reaching for objects, could hold his

head up, and that his gross-motor coordination difficulties had resolved. (Id.) As of that

point, petitioner’s only concerns were that D.B. had difficulty grasping his spoon and

difficulty swallowing (Id.), two concerns addressed separately below.

Petitioner raises several different arguments for why D.B. did experience further

residual effects or complications beyond six months from vaccination. Petitioner

contends that even in the absence of permanent neurologic damage, D.B.’s infantile

spasms changed the trajectory of his development. (ECF No. 108, p. 2.) In effect,

petitioner argues that even the temporary period during which D.B.’s development was

stalled due to the infantile spasms carried an opportunity cost. Even if he returned to

and exceeded his baseline within six months, he would necessarily have been still

farther along in development but for the infantile spasms. (Id. at p. 6.) Additionally,

petitioner identifies two specific problems – difficulty swallowing and a left-hand fine

motor deficit – that have persisted indefinitely and which petitioner contends are direct

sequela of the infantile spasms. (ECF No. 108, p. 4) Also, a known side effect of ACTh

therapy is weight gain. Petitioner contends that D.B. gained significant weight due to

his ACTh therapy and that his weight did not normalize until sometime after his first

birthday and interfered with his development. (ECF No. 108, p. 1.) On the whole,

petitioner is not persuasive in demonstrating that D.B. suffered complications or residual

effects of his infantile spasms for greater than six months.

i. Developmental trajectory

Petitioner’s argument with respect to D.B.’s developmental trajectory has an

attractive logic. However, petitioner has not provided preponderant evidence

substantiating that D.B.’s brief period of infantile spasms resulted in a change in his

overall developmental trajectory beyond six months post-vaccination. Although there is

no debate that D.B. suffers developmental delay, D.B.’s contemporaneous medical

records do not attribute his developmental delays to his infantile spasms. Rather, D.B.’s

occupational therapist, Ms. Nicholas, consistently recorded in D.B.’s occupational

therapy records that his developmental delays were consistent with his Down syndrome

and further complicated by his ongoing reflux. (Ex. 3, passim.) However, during the

hearing she testified:

Q. Sure. So can you attribute any of [D.B.]’s delays -- developmental delays

that he experienced after June 2014 to his episode of infantile spasms that

ended in March of 2014?

45

A. I can’t point to anything specific. I felt that he would have been further

along in his development at his current rate of development prior to the

seizures compared to his rate of development after the seizures.

(Tr. 186.)

D.B.’s pediatrician, Dr. Leland, similarly provided a letter in which he stated: “It is

probable, although it cannot be proven scientifically, that [D.B.], at 6 months after onset

of infantile spasms, had additional developmental delays beyond those which would

have been associated with his Down’s syndrome.” (Ex. 9.) Dr. Leland deferred to a

specialist for any further insight into D.B.’s developmental trajectory. (Id.)

Standing alone,

This text is long and has been trimmed here. Open the source document for the complete record.