# Bangerter v. Secretary of Health and Human Services

> United States Court of Federal Claims · February 14, 2022

URL: https://www.frixlaw.com/law-library/cases/6221511

## Case

- **Court:** United States Court of Federal Claims
- **Decided:** February 14, 2022
- **Precedential status:** Published
- **Opinion:** Opinion
- **Judges:** Daniel T. Horner
- **Cited by:** 0 later opinions in the Frix Law Library

## Citator (automated)

- No negative treatment found by the automated citator. That is not the same as a confirmation that the case is good law; read the citing cases.
- Full citator and citing cases: https://www.frixlaw.com/law-library/cases/6221511

## How later opinions describe it (automated extraction)

- 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.”
- affirming special master's reliance on conclusions of IOM

## Opinion text

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

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Source: Frix Law Library, https://www.frixlaw.com/law-library/cases/6221511. Public record. Not legal advice.