Nunez v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: March 29, 2019

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

JORDIA NUNEZ and JOHN DIAZ, * No. 14-863V

as legal representatives of J.J.D., *

an infant, deceased, * Special Master Sanders

*

Petitioners, * Hepatitis B (“HBV”) Vaccine; Rotavirus

* Vaccine; Diphtheria-Tetanus-acellular

v. * Pertussis (“DTaP”) Vaccine; Haemophilus

* Influenza Type B (“HiB”) Vaccine;

SECRETARY OF HEALTH * Inactivated Polio Vaccine (“IPV”);

AND HUMAN SERVICES, * Pneumococcal Conjugate Vaccine; Sudden

* Infant Death Syndrome (“SIDS”); Althen

Respondent. * Causation

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

Sylvia Chin-Caplan, Law Office of Sylvia Chin-Caplan, Boston, MA, for Petitioners.

Adriana R. Teitel, United States Department of Justice, Washington, D.C., for Respondent.

DECISION ON ENTITLEMENT1

On September 17, 2014, Jordia Nunez and John Diaz (“Petitioners”), as legal

representatives of J.J.D. (“J.J.”),2 a deceased infant, filed a petition pursuant to the National

Vaccine Injury Compensation Program.3 Petitioners alleged that the death of their minor son, J.J.,

was caused by “adverse effects” of hepatitis B virus (“HBV”); rotavirus; Diphtheria-Tetanus-

acellular Pertussis (“DTaP”); haemophilus influenza type B (“HiB”); inactivated polio (“IPV”);

and pneumococcal conjugate vaccines that he received on November 14, 2012. Pet. at 1, ECF No.

1; Amended Pet. at 1, ECF No. 21-1.

After carefully analyzing and weighing all the evidence and testimony presented in this

case in accordance with the applicable legal standards, the undersigned finds that Petitioners have

1

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

the E-Government Act of 2002, 44 U.S.C. § 3501 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), a party has 14 days to identify and move to delete

medical or other information that satisfies the criteria in § 300aa-12(d)(4)(B). Further, consistent with the

rule requirement, a motion for redaction must include a proposed redacted decision. If, upon review, the

undersigned agrees that the identified material fits within the requirements of that provision, such material

will be deleted from public access.

2

J.J.D. was referred to as “J.J.” throughout the hearing, despite the caption. J.J. will be used throughout

the opinion. Tr. at 10:15.

3

The Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, 42 U.S.C. §§ 300aa-

10 et seq. (hereinafter “Vaccine Act,” “the Act,” or “the Program”).

not met their legal burden. Petitioners have not provided preponderant evidence that the

vaccinations J.J. received on November 14, 2014, can cause SIDS generally, or that one or more

of them caused J.J. to succumb to SIDS. Accordingly, Petitioners are not entitled to compensation.

I. Procedural History

This case was originally assigned to Special Master Hamilton-Fieldman. See ECF No. 4.

Petitioners filed eleven exhibits consisting of medical records and affidavits. Pet’rs’ Exs. 1–11;

ECF No. 6-1–6.11. On February 3, 2015, Respondent filed his Rule 4(c) Report. ECF No. 11.

Respondent argued that Petitioners’ claim “lack[ed] any medical corroboration” and that

Petitioners had “not proffered any mechanism of injury to explain how [J.J.’s] death was vaccine-

related.” Id. at 5. Respondent also noted that “[n]o treating physician ha[d] ascribed [J.J’s] death

as being related to any of the vaccinations he received on November 14, 2012.” Id.

On June 19, 2015, Petitioners filed an amended petition, substituting initials for J.J.’s name

throughout the document and adding language alleging that J.J.’s death was “a result of the adverse

effects” of the vaccines he received. Amended Pet. at 1. The same day, Petitioners filed an expert

report authored by Dr. Douglas Miller. Pet’rs’ Ex. 12, ECF No. 21-2.

On November 19, 2015, Respondent filed two responsive expert reports, authored by Dr.

Christine McCusker and Dr. Rebecca Folkerth. Resp’t’s Exs. A, C, ECF Nos. 37-1, 41-1.

Thereafter, Petitioners filed a supplemental expert report authored by Dr. Miller on January 19,

2016. Pet’rs’ Ex. 37, ECF No. 44-1. Respondent filed supplemental responsive expert reports

authored by Dr. McCusker and Dr. Folkerth on April 11, 2016, and April 14, 2016, respectively.

Resp’t’s Exs. E, F, ECF Nos. 51-1, 56-1.

At a status conference held on May 10, 2016, the parties agreed to proceed to an entitlement

hearing. Order, ECF No. 58. Another status conference was held on October 18, 2016, and the

parties discussed the case in light of Special Master Hamilton-Fieldman’s August 29, 2016

decision denying entitlement in a similar case, Jewell v. Sec’y of Health and Human Servs., No.

11-138V, 2016 WL 5404165 (Fed. Cl. Spec. Mstr. Aug. 29, 2015). Order, ECF No. 59.

Ultimately, Petitioners admitted that their case bore many similarities to Jewell, but they requested

to proceed to a hearing. See id.; Pet’rs’ Stat. Rept., ECF No. 65.

The case was reassigned to the undersigned on January 10, 2017. See ECF Nos. 66–67.

At a status conference held on February 16, 2017, the parties discussed the case and the features

which Petitioners felt distinguished their case from Jewell. See Order, ECF No. 69. Petitioners

again requested that they and their expert be afforded an opportunity to testify at an entitlement

hearing. Id. Thereafter, Petitioners filed a second supplemental expert report authored by Dr.

Miller and a second affidavit authored by Petitioner Jordia Nunez (“Ms. Nunez”). Pet’rs’ Exs. 38–

39, ECF No. 71-1, 71-2.

An entitlement hearing was held in Washington, D.C., on February 22 and 23, 2018. The

parties timely filed post-hearing briefs. ECF Nos. 103, 106, 110. This matter is now ripe for a

decision.

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II. Factual Background

A. Medical Records

Ms. Nunez was in her early twenties when she became pregnant with twins in 2012. Pet’rs’

Ex. 5 at 24 (filed on compact disk; ECF No. 6). Ms. Nunez had previously given birth to a baby

girl in 2008 and had experienced preeclampsia and mild hypertension with that pregnancy. Id.

The 2012 pregnancy was considered high risk due to Ms. Nunez’s history and it being a twin

gestation, but an early workup for preeclampsia and hypertension was negative. Id. at 66, 82. Ms.

Nunez attended several prenatal appointments between March and July 2012. See id. at 23–99.

On July 10, 2012, Ms. Nunez was transported to Bronx Lebanon Hospital in pre-term labor. Pet’rs’

Ex. 2 at 5 (filed on compact disk; ECF No. 6). Ms. Nunez naturally delivered twins on July 11,

2012. Pet’rs’ Ex. 6 at 6 (filed on compact disk; ECF No. 6). J.J. and his twin sister were born at

approximately twenty-nine weeks and two days’ gestation. Id. at 8; Pet’rs’ Ex. 2 at 58. J.J.’s

Apgar scores4 were seven and eight at one minute and five minutes, respectively. Pet’rs’ Ex. 6 at

6. The twins were transferred to the neonatal intensive care unit (“NICU”) after birth due to their

prematurity. Id. at 6, 27; Pet’rs’ Ex. 2 at 58. Ms. Nunez was discharged from the hospital on July

13, 2012. Pet’rs’ Ex. 2 at 58.

J.J. had episodes of respiratory distress upon admission to the NICU, and he received nasal

continuous positive airway pressure (“NCPAP”) from July 11 through July 15, 2012. Pet’rs’ Ex.

6 at 29, 34, 36, 38, 40, 898–99. He remained in the NICU until August 31, 2012, when he was

discharged home in stable condition. Id. at 901.

On September 13, 2012, J.J. was seen by Dr. Yves Verna for his two-month well-baby

examination. Pet’rs’ Ex. 7 at 1–3 (filed on compact disk; ECF No. 6). Dr. Verna noted that J.J.

was taking vitamin supplements and that he was being breastfed approximately every twelve

hours, supplemented with cow’s milk formula as needed. Id. at 1. Dr. Verna wrote that J.J. was

“[w]ell-appearing, alert, well hydrated, and active” and that he was “[n]ot acutely ill.” Id. She

noted the following about J.J.’s growth and development: “Vocalizes, attentive to voices, has a

social smile, the gaze follows past the midline, lifts the head and chest off a surface, the head is

steady in an upright position, and the hands are open 50% of the time.” Id. at 2. J.J. received

rotavirus, DTaP, HiB, IPV, and pneumococcal conjugate vaccines during the visit. Id. at 3. J.J.’s

parents were instructed to give him Tylenol every four hours for 48 hours after vaccination. Id. at

2.

On November 14, 2012, J.J. was brought to Dr. Verna for his four-month well-baby

examination. Pet’rs’ Ex. 7 at 3–5. Dr. Verna documented that J.J. had “[n]o fever,” “[n]o cough,”

his “[a]ppetite [was] not decreased[,]” and he had “[n]o difficulty sucking.” Id. at 3. She also

documented that there were “[n]o parental concerns about hearing[,] vision[, or] behavior.” Id.

J.J. weighed 11 lbs. and measured 22.75 inches long with a head circumference of 39.5 cm. Id.

Those measurements put him at the low end of the normal range for weight and slightly under the

4

An Apgar score is “a numerical expression of the condition of a newborn infant . . . being the sum of

points gained on assessment of the heart rate, respiratory effort, muscle tone, reflex irritability, and color.”

Dorland’s Illustrated Medical Dictionary 1682 (32nd ed. 2012) [hereinafter “Dorland’s”]. Between seven

and ten is considered “[n]ormal [r]ange.” See Pet’rs’ Ex. 7 at 2.

3

normal range for body length and head circumference. Id. Dr. Verna wrote that J.J. was “[w]ell-

appearing, alert, well hydrated, and active.” Id. She noted the following about J.J.’s growth and

development: “Turns toward voices, visual track 180 degrees, laughs, no head lag when pulled to

sitting position, brings hands together, and reaches for objects.” Id. at 4. The physical examination

portion of the note reflects no abnormalities, including “[n]o nasal discharge seen.” Id. at 3. J.J.

received HBV, rotavirus, DTaP, HiB, IPV, and pneumococcal conjugate vaccines during the visit.

Id. at 5. The note reflects that the vaccines were administered between 5:40 p.m. and 6:24 p.m.

that evening. Id. at 4–5. J.J.’s parents were instructed to give him Tylenol every four hours for

48 hours after vaccination. Id. at 4.

The next morning, on November 15, 2012, a 911 call was made from Petitioners’ residence

at around 9:49 a.m. Pet’rs’ Ex. 8 at 1 (filed on compact disk; ECF No. 6). The caller described

J.J. and stated: “He’s not breathing.” Id. An ambulance was dispatched and arrived at Petitioners’

home at 9:53 a.m. Id. EMS crew members evaluated J.J. and found him to be unresponsive, with

non-reactive pupils and absent lung sounds. Id. at 3. The crew members documented that J.J.’s

skin color was either cyanotic5 or normal, and his skin temperature and condition were marked as

normal. Id. Crew members found no injuries on physical examination. Id. At both 9:55 a.m. and

10:00 a.m., J.J. was found to have no pulse or respiration. Id. In the ambulance, J.J. was treated

with a bag valve mask, oral/nasal airway support, CPR, and oxygen therapy. Id. Petitioners

reported to the EMS crew members that J.J. was last awake at 11:00 p.m. the night before. Id.

The ambulance left Petitioners’ home at 9:57 a.m. and arrived at the nearest hospital at 10:01 a.m.

Id. at 1. J.J. was pronounced dead at the hospital at 10:23 a.m. Pet’rs’ Ex. 9 at 12 (filed on compact

disk; ECF No. 6); Pet’rs’ Ex. 6 at 1.

The attending physician upon arrival at the hospital was Dr. Ye Aung. He and a resident

authored a note which includes a timeline of events provided by Petitioners. Pet’rs’ Ex. 9 at 15–

19. The note reflects that J.J. had received vaccinations in the previous evening and had been

given Tylenol. Id. at 16. Petitioners reported that J.J. “was a bit cranky,” that he was fed formula

around 9:30 p.m., and that he was put to bed at around 11:00 p.m. Id. Petitioners stated that the

next morning, Ms. Nunez awoke at around 8:30 a.m., found J.J. and his twin sister sleeping, and

took the older sister to school. Id. Mr. Diaz brought J.J.’s twin sister to the living room at

approximately 9:00 a.m. because she had awakened and J.J. remained sleeping. Id. Ms. Nunez

returned home at around 9:30 a.m. and checked on J.J. She saw that “his face [was] all blue and

unresponsive[.]” Id. Ms. Nunez “carried [J.J.] to the living room, called 911, and started a

cardiopulmonary resuscitation on him.” Id.

The note also includes a timeline that Petitioners provided to a social worker at the hospital.

Pet’rs’ Ex. 9 at 15. According to the note, Petitioners relayed that Ms. Nunez last checked on J.J.

and his twin sister at 11:00 p.m. the previous evening. Id. J.J. and his twin sister “slept thr[ough]

the night as always[.]” Id. The next morning, Ms. Nunez took her oldest daughter to school after

checking on the twins. Id. Mr. Diaz relayed that J.J.’s twin “started crying [and] he hurried up to

pick her up so she would not wake” J.J., who “appeared to be asleep[.]” Id. When Ms. Nunez

returned home, she observed Mr. Diaz and J.J.’s twin sleeping together, and she checked on J.J.

Id. At that point, Ms. Nunez “noticed [J.J.] was not breathing and screamed” for Mr. Diaz. Id.

5

Cyanosis is “a bluish discoloration, especially of the skin and mucous membranes due to excessive

concentration of deoxyhemoglobin in the blood.” Dorland’s at 452.

4

Ms. Nunez “tried blowing in [J.J.’s] mouth[,]” and Mr. Diaz “called the police.” Id. The note

reflects that the social worker contacted the authorities, but that child services “decline[d] to

[a]ccept the case[,] [c]iting [the] M.D. rul[ing]” that the cause of death was SIDS. Id.

An autopsy was performed on November 16, 2012, by Dr. James Gill. Pet’rs’ Ex. 10 (filed

on compact disk; ECF No. 6). Dr. Gill’s report reflects that J.J. was “a well-developed, well-

nourished, average-framed, 23[-inch-long], 14-pound” boy, with no evidence of recent injury. Id.

at 5. The head was “turned to the right on presentation.” Id. Dr. Gill noted bandages on the thighs,

commenting that there were “recent vaccinations.” Id. Dr. Gill indicated that the myocardium,

lungs, liver, kidneys, spleen, intestines, stomach, esophagus, laryngeal wall, thyroid gland, and

thymus gland were unremarkable, although petechiae6 were noted on the thymus gland.7 Id. at 1.

He noted a “[f]ocal epicardial hemorrhage” in the heart. Id. He also noted “[p]ancreas with

autolysis” and “[a]drenal glands with medullary congestion.” Id. A nasopharyngeal swab was

tested, but no influenza viruses were detected. Id. at 2.

Under a section of the report entitled “Final Diagnoses,” Dr. Gill wrote the following:

I. SUDDEN UNEXPECTED DEATH IN INFANT.

A. HISTORY OF PREMATURITY (26 [sic] WEEKS).

B. RECENT UPPER RESPIRATORY INFECTION.

C. RECENT IMMUNIZATIONS.

D. ONE OF A TWIN GESTATION.

E. CO-SLEEPING WITH TWIN IN CRIB.

F. BLOOD AND CSF CULTURES: NEGATIVE.

G. INFLUENZA STUDIES: NEGATIVE.

H. TOXICOLOGY POSITIVE FOR ACETAMINOPHEN.

I. METABOLIC STUDIES: NEGATIVE.

Id. at 3. Dr. Gill ruled that the “cause of death” was “Sudden Infant Death Syndrome” and the

“manner of death” was “natural.” Id.

An examination of the brain was performed by Dr. Hernando Mena on November 27, 2012.

Pet’rs’ Ex. 10 at 10. The brain weighed 618 grams. Id. Dr. Mena wrote that microscopic

examination revealed “recative [sic] astrocytes8 within the region of the raphe nucleus in the

midbrain and pons, and medullary inferior olivary nuclei. The intracranial dura reveals formation

of a subdural fibrovascular membrane with few hemosiderin-laden macrophages.” Id. The report

reflects two diagnoses: (1) “subdural hemorrhage, organized, cerebral convexities;” and (2)

“[g]liosis,9 brain stem nuclei.” Id.

6

A petechia is “a pinpoint, nonraised, perfectly-round, purplish red spot caused by intradermal or

submucous hemorrhage.” Dorland’s at 1422.

7

The thymus is a lymphoid organ. Dorland’s at 1925. It is the site where T lymphocytes are produced.

Id.

8

Astrocytes, also known collectively as astroglia, are neuroglial cells of ectodermal origin. Dorland’s at

169–70. They “appear to play a role in myelin formation, transport of material to neurons, and maintenance

of the ionic environment of neurons.” Id. at 1265.

9

Gliosis is “an excess of astroglia in damaged areas of the central nervous system.” Dorland’s at 784.

5

The accuracy of the medical records is not in dispute in the case. Both parties agree on the

date and circumstances surrounding J.J.’s vaccinations as represented in the medical records.

Additionally, J.J.’s medical history is not disputed by either party, although different conclusions

are drawn from symptoms and test results within the record. Both parties also agree that J.J.’s

cause of death was SIDS and that all the information noted in the autopsy report is accurate;

however, the significance of any objective finding may be in dispute.

B. Affidavits

Ms. Nunez filed two affidavits and Mr. Diaz filed one affidavit. Pet’rs’ Exs. 3–4, 39 (filed

on compact disk; ECF No. 6), ECF No. 71-2. The affidavits were consistent with the medical

records detailing Ms. Nunez’s pregnancy and the twins’ medical histories. Ms. Nunez wrote that

J.J. “had respiratory problems due to lung immaturity and was placed on a CPAP machine[, and

that h]e was also placed on antibiotics and in photo therapy for jaundice.” Pet’rs’ Ex. 3 at 2; see

also Pet’rs’ Ex. 4 at 2. Both parents also wrote that “[a]ll testing that was done on [J.J.] came back

normal” and he “was the healthier, stronger of the two” twins. Id. They wrote that J.J. was

discharged from the NICU on August 31, 2012, while his twin remained in the NICU until

September 7, 2012. Id. Ms. Nunez wrote that the twins “slept together at opposite ends of their

crib. When they were put to bed at night, they each had a light blanket that [she] tucked around

their waist. There were no pillows in their crib.” Pet’rs’ Ex. 39 at 1.

Ms. Nunez and Mr. Diaz both wrote that J.J. was examined and found to be “a healthy

baby” at his first well-baby visit on September 13, 2012. Pet’rs’ Ex. 3 at 2–3; Pet’rs’ Ex. 4 at 2.

They described a call to the pediatrician in October 2012 because J.J. “had a stuffy nose.” Pet’rs’

Ex. 3 at 3; Pet’rs’ Ex. 4 at 2. They wrote that Ms. Nunez “was told to use saline.” Id. After that,

Ms. Nunez wrote that J.J. “continued to thrive.” Pet’rs’ Ex. 3 at 3. Mr. Diaz wrote that J.J. “was

growing and getting stronger.” Pet’rs’ Ex. 4 at 2.

Both parents wrote that J.J. had his four-month visit with Dr. Verna on November 14, 2012,

at approximately 7:00 p.m. Pet’rs’ Ex. 3 at 3; Pet’rs’ Ex. 4 at 2. Both also wrote that J.J. and his

twin sister “had runny noses and productive coughs” on that date. Id. Ms. Nunez wrote that Dr.

Verna “did not perform a physical examination” on either twin and that “neither their ears [n]or

chests were checked.” Pet’rs’ Ex. 3 at 3. Mr. Diaz wrote that Ms. Nunez “pointed out [the

symptoms of runny nose and cough] to the doctor.” Pet’rs’ Ex. 4 at 2. The parents wrote that Dr.

Verna weighed, measured, and administered vaccinations to the twins. Pet’rs’ Ex. 3 at 3; Pet’rs’

Ex. 4 at 2.

Both parents wrote that they returned home at approximately 8:30 p.m. that evening.

Pet’rs’ Ex. 3 at 3; Pet’rs’ Ex. 4 at 3. J.J. was fed and given Tylenol because he “was fussy and his

nose was still running.” Id. Ms. Nunez added that J.J. “did not have any fever.” Pet’rs’ Ex. 3 at

3; see also Pet’rs’ Ex. 39 at 1. The parents wrote that J.J. was placed in a vibrating chair and fell

asleep at around 10:30 p.m. Pet’rs’ Ex. 3 at 3; Pet’rs’ Ex. 4 at 3. He was moved to his crib, which

he shared with his twin, at approximately 11:30 p.m. Id.

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Ms. Nunez wrote that J.J. usually “slept through the night from 11 p.m. until 8 a.m.” Pet’rs’

Ex. 3 at 3. Ms. Nunez described checking on J.J. and his twin sister the next morning at 8:00 a.m.,

when she found them both sleeping. Id.; Pet’rs’ Ex. 39 at 3. Mr. Diaz wrote that at around 9:15

a.m., he “heard that [J.J.’s twin] was up and immediately went in to get her so she would not wake

[J.J.] if he was still asleep.” Pet’rs’ Ex. 4 at 3. Mr. Diaz wrote that J.J. was still asleep at that time,

so he took J.J.’s twin out of the room to change and feed her. Id. Mr. Diaz also wrote that when

Ms. Nunez arrived home, she “immediately went in to check on [J.J.] since he never slept that

late.” Id. Ms. Nunez wrote that when she found J.J., his “eyes were open and his mouth was blue”

but he was warm. Pet’rs’ Ex. 3 at 4; see also Pet’rs’ Ex. 39 at 3. Mr. Diaz described J.J. in the

same manner. Pet’rs’ Ex. 4 at 3. Ms. Nunez wrote that she began CPR, which caused the “blueness

around his mouth [to go] away,” but “a lot of mucus [was] coming out of his mouth and nose.”

Pet’rs’ Ex. 3 at 4; see also Pet’rs’ Ex. 4 at 3. The parents wrote that an ambulance arrived around

15 minutes later, and J.J. was taken to the hospital where they were told he had died. Id.; Pet’rs’

Ex. 39 at 3.

C. Fact Testimony

Ms. Nunez did not initially describe J.J.’s health on the day of his four-month well-baby

visit during her testimony. On cross-examination and re-direct, both counsel referenced her

written statements describing J.J.’s “runny nose” and “productive cough” at the time of that visit.

Tr. 20:14–15, 22:5–10. Ms. Nunez affirmed those statements. Tr. 20:16, 22:11. Ms. Nunez then

testified that J.J. had a stuffy nose in October of 2012 that was “no longer stuffy on the day of his

appointment . . .” Tr. 22:14–22. She testified that his stuffy nose occurred in the beginning of

October, and she administered saline drops “for a couple of days” until J.J. “had just a runny nose,

[which] was from [her] giving him saline drops.” Tr. 23:14–23. She emphasized that the stuffy

nose from early October went away and was replaced by the runny nose, which “got better” with

time. Tr. 23:24–24:4. Ms. Nunez clarified that “he still had [the runny nose], but just not so often.”

Tr. at 24:6–7. She testified that on the day of his four-month appointment, his nose was “just

runny” with “very light, clear . . . mucus,” which she attributed to allergies. Tr. 22:18–21. She

stated that “he had a cough as well” during the appointment, but she said it was “less” of a cough

than when it started with the congestion in early October. Tr. 22:21–22, 24:10–16. Ms. Nunez

denied that she was “concerned about the stuffy nose, the runny nose[,] or the cough” on the day

of J.J.’s four-month visit. Tr. 24:19–21.

Ms. Nunez stated that, other than being “a bit cranky” and “[a] bit more fussy,” J.J. was

behaving normally and “it was just like another day” after his four-month appointment. Tr. at

14:16–22. She stated that J.J. was fed approximately twice before being put to bed. Tr. 14:23–

15:2. Ms. Nunez testified that J.J. was both breast- and bottle-fed. Tr. 21:20–23.

Ms. Nunez testified that J.J. and his twin sister slept together in one crib, lying with space

between them and their heads on opposite ends of the crib. Tr. 13:4–9. The crib contained a crib

sheet and a thin receiving blanket tucked “under [J.J.’s] waist [and] around his thighs and leg area.”

Tr. 15:3–12. There were no bumpers, blankets, bedding, stuffed animals, or pillows in the crib.

Tr. 15:10–11. Ms. Nunez testified that she never placed J.J. on his belly when putting him to sleep,

and J.J. was not yet able to roll over on his own. Tr. 15:23–16:8.

7

Ms. Nunez testified that she woke up at around 6:30 a.m. the next day to get J.J.’s older

sister ready for school. Tr. 17:1–3. She saw J.J. “sleeping on his back [in] the same position [she]

left him [i]n, [with] the blanket still . . . around his thighs [and] under his waist,” at approximately

6:45 a.m. Tr. 17:5–8.

Ms. Nunez’s testimony with respect to the chronology immediately following J.J.’s

vaccination and leading up to his death was consistent with the information provided in the

affidavits filed in this case. Ms. Nunez’s responses to questions regarding the severity of J.J.’s

symptoms on the date of his vaccination and his mobility were less clear. For example, Ms.

Nunez’s testimony regarding whether J.J. could successfully roll over or push up when he “would

try to roll his neck and just like push his hands . . . .” was inconsistent. Tr. 21:7–12. Also, Ms.

Nunez testified that she pointed out J.J.’s symptoms of cough and runny nose to the doctor on the

day of J.J.’s vaccinations, but she testified that she was not concerned about either at the time. Tr.

24:19–21.

III. Expert Review

A. Expert Qualifications

1. Petitioners’ Expert, Douglas C. Miller, M.D., Ph.D.

Petitioners’ expert, Dr. Douglas Miller, authored three expert reports and testified at the

entitlement hearing. Pet’rs’ Exs. 12, 37, 38, ECF Nos. 21-2, 44-1, 71-1; Tr. 26–122, 338–371. Dr.

Miller is a neuropathologist with experience in academia and forensic practice. Pet’rs’ Ex. 12 at

1. He is board certified in anatomic pathology and neuropathology. Id. He currently serves as a

clinical professor in the Department of Pathology and Anatomical Sciences at the University of

Missouri School of Medicine, where he has been employed since December 2007. Id.

Dr. Miller has published more than 150 articles and book chapters, co-authored a text-atlas

of neurology, and is the sole author of a surgical neuropathy text. Id. at 2. In addition to academia,

he has been a consultant neuropathologist for various hospitals and medical examiners. Id. He

currently serves as associate medical examiner as part of his duties at the University of Missouri,

where his office provides forensic autopsy services throughout the state. Id. His neuropathology

experience includes analysis of infant deaths where SIDS is suspected. Id. Dr. Miller testified

that in his current position, he completes “the neuropathology parts of autopsies” with residents.

Tr. 29:3–4. Dr. Miller has “been an expert witness in many legal cases, both civil and criminal,

including many infant deaths in which SIDS has been either suspected prior to autopsy or

suggested as an alternative diagnosis to one of traumatic brain injury.” Pet’rs’ Ex. 12 at 2. Dr.

Miller has testified three times in the United States Court of Federal Claims regarding potentially

vaccine-related injuries and deaths. Id.

Dr. Miller is not an immunologist. Tr. 87:10–12. Dr. Miller does not have educational or

clinical experience in pediatrics. Tr. 87:13–14. At the hearing, Petitioners did not seek to admit

Dr. Miller as an expert in any specific area. Respondent, however, did not object to Dr. Miller’s

testimony, and the undersigned did not limit his testimony. Based off Dr. Miller’s filed CV and

his testimony describing his research and practice areas, the record provides evidence that his

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expertise lies in neuropathology. Dr. Miller has also testified previously in the Program as an

expert in neuropathology, specifically in cases that alleged vaccine-caused SIDS. Jewell, 2017

WL 7259139; Boatmon v. Sec’y of Health and Human Servs., No. 13-611V, 2017 WL 3432329

(Fed. Cl. Spec. Mstr. Jul. 10, 2017); Copenhaver v. Sec’y of Health & Human Servs., No. 13-

1002V, 2016 WL 3456436 (Fed. Cl. Spec. Mstr. May 31, 2016); Lord v. Sec’y of Health & Human

Servs., No. 12-255V, 2016 WL 806818 (Fed. Cl. Spec. Mstr. Feb. 9, 2016).

2. Respondent’s Expert Rebecca D. Folkerth, M.D.

Dr. Rebecca Folkerth issued two reports in this case and testified at the entitlement hearing

on behalf of Respondent. Resp’t’s Exs. C, F, ECF Nos. 41-1, 56-1; Tr. 122–177. Dr. Folkerth

received her medical degree from the University of Louisville School of Medicine. Resp’t’s Ex.

C at 2. She completed her residency in anatomic pathology and a fellowship in neuropathology

before establishing a practice at Brigham and Women’s Hospital Department of Pathology. Id.

Dr. Folkerth holds board certifications in anatomic pathology, neuropathology, and cytopathology.

Id. Dr. Folkerth is a clinical associate professor at New York University School of Medicine in

the Forensic Medicine Department and the neuropathologist for the Office of the Chief Medical

Examiner in New York City. Tr. 124:7–10. She has written over 100 peer-reviewed articles

covering various issues in pathology. Resp’t’s Ex. C at 2.

The undersigned finds that Dr. Folkerth’s testimony was generally consistent with the

filings and essentially limited to a discussion of whether J.J.’s death was properly categorized as

SIDS. There was no disagreement between the parties that J.J.’s death was properly categorized

as SIDS, and on cross-examination, Dr. Folkerth was asked whether J.J. had a brainstem defect

that made him more vulnerable to SIDS. Dr. Folkerth stated that given his brainstem gliosis, “[i]t’s

probably likely, more likely than not” that J.J had a defective medullary serotonergic system. Tr.

134:3–6. She does not, however, believe that this is “necessarily indicative of a vulnerability to

SIDS.” Tr. 133:13–14. Instead, Dr. Folkerth opined that the gliosis “is a marker for whatever

leads to various apneic periods” and should be seen as “an indicator of some sort of previous mild

or chronic hypoxic ischemic changes.” Tr. 133:24–25.

3. Respondent’s Expert Dr. Christine McCusker, M.D.

Dr. Christine McCusker authored two expert reports and testified during the hearing on

behalf of Respondent. Resp’t’s Exs. A, E, ECF Nos. 37-1, 51-1; Tr. 178–337. She received her

Master of Science in Molecular Virology and Immunology and her M.D. from McMaster

University in Hamilton, Ontario. Resp’t’s Ex. B at 1, ECF No. 37-2; Tr. 178:25–179:1. Dr.

McCusker then completed a clinical fellowship in allergy and immunology at McGill University

in Montreal, Quebec. Id. at 2. She is board certified in pediatrics and currently works as a staff

physician in the Emergency Department and an associate professor in the Department of

Pediatrics, Division of Allergy and Immunology (Pediatric) of Montreal Children’s Hospital and

McGill University. Id. at 2–3.

Dr. McCusker has taught several courses at the undergraduate and graduate levels on

biochemistry, cytokines, and the development of the immune system in infancy. Tr. 181:20–182:3.

She has published peer-reviewed articles on pediatric immunology and specifically cytokine

9

activation. See Resp’t’s Ex. B. Dr. McCusker has testified previously in the Program, specifically

in cases that allege vaccine-caused SIDS. Jewell, 2017 WL 7259139; Boatmon, 2017 WL

3432329.

B. Sudden Infant Death Syndrome and the Triple Risk Model

Dr. Miller opined that “there is no evidence of any acute process in the brain which would

have been a cause of death” for J.J., such as meningitis. Pet’rs’ Ex. 12 at 4; see Tr. 33:22–24. Dr.

Miller stated that J.J.’s death was properly categorized as a SIDS death. Tr. 39:21–22. He

emphasized that “SIDS is a syndrome, not a disease[.]” Pet’rs’ Ex. 38 at 4. He testified that SIDS

“has lots of different potential causes, not all of which are fully understood.” Tr. 39:18–20. Dr.

Folkerth similarly noted that the medical examiner “designated the cause of death as ‘Sudden

Unexpected Death in Infancy.’” Resp’t’s Ex. C at 5. Dr. Folkerth further opined “that this case

falls into the category of SUDI/SIDS.”10 Id. at 6. Dr. McCusker also noted that the coroner ruled

that SIDS was the cause of death. Resp’t’s Ex. A at 2.

Dr. Miller opined that J.J. meets the criteria for the “Triple Risk Model” of SIDS, which

was “formulated by Dr. Hannah Kinney quite a few years ago.” Pet’rs’ Ex. 12 at 4 (citing Pet’rs’

Ex. 14, ECF No. 91-211). Dr. Folkerth agreed that “[t]he prevailing concept of SUDI/SIDS is that

proposed by Kinney and colleagues, [i.e.,] the ‘Triple Risk Model[.]’” Resp’t’s Ex. C at 5. Dr.

McCusker also discussed the Triple Risk Model in her reports and considered J.J.’s case under that

model. See Resp’t’s Ex. A at 2–3; Resp’t’s Ex. E at 2–6.

The Triple Risk Model, as described by Dr. Kinney and Dr. Filiano in a 1994 article,

proposes that “sudden death in SIDS results from the intersection of three overlapping factors: (1)

a vulnerable infant; (2) a critical developmental period in homeostatic control[;] and (3) an

exogenous stressor[ or stressors].” Pet’rs’ Ex. 14 at 1–2.12 Under the model, “an infant will die

of SIDS only if he/she possesses all three factors; the infant’s vulnerability lies latent until he/she

enters a critical developmental period and is subject to an exogenous stressor which matches the

infant’s underlying vulnerability and overwhelms an already compromised homeostatic system.”

Id. at 2. Furthermore, “death occurs only if all three factors intersect and only if the exogenous

stressor matches the specific vulnerability of the individual infant[.]” Id. at 3. Therefore, “the

infant may survive as ‘normal,’” despite an underlying vulnerability, “if the stressor is avoided, or

if the underlying vulnerability is ameliorated by therapeutic interventions.” Id.

10

Dr. Folkerth testified that “SUDI is a more generalized term” than SIDS. Tr. 129:23. She explained that

a death is classified as a “sudden unexpected death in infancy,” or SUDI, “any time an infant dies suddenly

and unexpectedly.” Tr. 129:9–12. She continued that the autopsy and related investigations may reveal

the cause for a subset of SUDI cases such that “they[ are] no longer an unexplained death.” Tr. 129:12–17.

However, if the death remains unexplained, then it is classified as a SIDS death. Tr. 129:17–22.

11

James J. Filiano & Hannah C. Kinney, A Perspective on Neuropathologic Findings in Victims of the

Sudden Infant Death Syndrome: The Triple-Risk Model, 65 BIOL. NEONATE 194 (1994).

12

When medical literature is referenced in this opinion, the undersigned will cite to the CM/ECF page

numbers of the filed documents rather than the page numbers of the articles as they appeared in the journals

or other original sources.

10

Dr. Kinney’s model favors “evidence [that] suggests that SIDS involves a convergence of

stressors that probably results in the asphyxia of a vulnerable infant who has . . . defective . . .

defense systems . . . .” Pet’rs’ Ex. 37, Tab C at 8, ECF No. 93-4.13 The research has not identified

“a universally accepted biologic explanation” for SIDS; however, the “current understanding . . .

reflects the simultaneous juxtaposition of multiple events that, when taken individually, are far

less powerful than the result of their chance combination.” Id.

1. Vulnerability under the Triple Risk Model

i. “Intrinsic Risk Factors” of Male Gender and Prematurity

Vulnerability is not clearly defined by any of the experts or the medical literature, but the

designation serves to identify the pool of infants that are more likely to suffer from SIDS using

their common traits. These traits, or intrinsic risks, are genetic or environmental in nature and

affect susceptibility, such as prenatal exposure to cigarettes and maturity at birth. Resp’t’s Ex. A,

Tab 5 at 2, ECF No. 38-5.14 The 1994 article by Dr. Kinney and Dr. Filiano considers such

“epidemiologic risk factors” in the discussion of “[t]he concept of the vulnerable infant.” Pet’rs’

Ex. 14 at 2. These types of factors “point to a suboptimal intrauterine environment[] and suggest

that the mechanisms for risk for SIDS develop in fetal life in at least some cases.” Id. Male infants

are also identified as potentially more vulnerable to SIDS. There is “mounting evidence” in studies

done with mice that “sexually dimorphic features in the brain[]” manifest as “differences in

brainstem-mediated 5-[hydroxytryptamine (“5-HT”)] function, with females’ brains apparently

relying less on 5-HT neurons in chemoreception and adapting more readily to the loss of 5-HT

function.” Pet’rs’ Ex. 20 at 11, ECF No. 91-8.15 These studies help to identify potential markers

for vulnerability, such as gender, and shed light on the biological systems that are affected in SIDS

cases, such as the brainstem. Id. Intrinsic risk factors also include identification markers that

indicate a statistically increased risk of SIDS, but the specific effect of the marker remains unclear,

such as the sub-Saharan African descent marker denoting race.16 Id. at 4.

Intrinsic risk factors were discussed by each expert in varying contexts. At times, intrinsic

factors were discussed in relation to infant vulnerability, and at other times they were considered

in combination with certain other “risk factors” that fall into the category of exogenous stressors.

See, e.g., Tr. 81; Pet’rs’ Ex. 37 at 6; Resp’t’s Ex. C at 5. Dr. McCusker also discussed intrinsic

risk factors as part of her “critical window” analysis. Resp’t’s Ex. E at 3–4. All the experts agreed

that J.J. was born prematurely and was a male, and that both of those facts increased his relative

risk of SIDS. Tr. 51: 16–23, 81:4–6, 134:24, 172:10–12, 208:13–14; Resp’t’s Ex. C at 5; Resp’t’s

Ex. E at 3–4. They do not all agree, however, on whether J.J. qualified as a “vulnerable infant”

under the Triple Risk Model. J.J.’s male gender and prematurity certainly did not cause him to

13

Hannah C. Kinney & Bradley T. Thach, The Sudden Infant Death Syndrome, 361 N. ENGL. J. MED. 795

(2009).

14

Felicia L. Trachtenberg et al., Risk Factor Changes for Sudden Infant Death Syndrome After Initiation of

Back-to-Sleep Campaign, 129 PEDIATRICS 630 (2012).

15

Hannah C. Kinney et al., The Brainstem and Serotonin in the Sudden Infant Death Syndrome, 4 ANN.

REV. PATHOL. 517 (2009).

16

The article designates “African-American” as a race, however, African-American is not a race. Pet’rs’

Ex. 20 at 4.

11

die from SIDS, but both are specifically identified by Dr. Kinney as risk factors that would have

statistically increased his chances of suffering from SIDS.

ii. Brainstem Defects

Dr. Miller testified that one major potential vulnerability under the Triple Risk Model is a

developmentally defective medulla. He explained that medical and scientific literature has shown

that “the brain structures responsible for regulation of respiration, including those that sense

increased blood carbon dioxide levels during sleep and respond[] to them with arousal and

increased (gasping) breathing, reside in the medulla in a network of nuclear structures which use

serotonin as their neurotransmitter.” Pet’rs’ Ex. 12 at 4 (citing Pet’rs’ Exs. 15–21, ECF Nos. 91-

3–917). He further explained that “there are several sets of neurons in the medulla in different

locations which have related but different functions” associated with “sensing how much carbon

dioxide there is in the blood” and stimulating respiratory drive and arousal from sleep. Tr. 43:11–

18. This “system of nerve cells . . . use[s] the transmitter serotonin” 5-HT.18 Tr. 43:9–11. He

also wrote that “[t]he arcuate nuclei are one important member of this network[.]” Pet’rs’ Ex. 12

at 4. In his testimony, Dr. Miller stated that based on what is known from animal data, the arcuate

nucleus is “the primary carbon dioxide sensor in the brain.” Tr. 43:23–25. Therefore, he opined

that “[a] critical structure to examine in the brain of a potential SIDS case is the arcuate nucleus in

the ventral medulla.” Pet’rs’ Ex. 12 at 4 (citing Pet’rs’ Ex. 13, ECF No. 91-119). Dr. Miller noted

that infants with defects in the brain structures responsible for respiratory regulation are thought

to make up as much as 70 percent of the SIDS population. Pet’rs’ Ex. 12 at 4; see also Pet’rs’ Ex.

20 at 6.

Dr. Miller explained that “[i]n an infant with such a defective brainstem, during the period

of early post-natal life before full maturation of brain systems that regulate heart rate, respiratory

activity, sleep, and related autonomic functions, one or more external ‘stressors’” can cause a life-

17

Pet’rs’ Ex. 15, Hannah C. Kinney et al., Medullary Serotonergic Network Deficiency in the Sudden Infant

Death Syndrome: Review of a 15-Year Study of a Single Dataset, 60 J. NEUROPATHOLOGY &

EXPERIMENTAL NEUROLOGY 228 (2001); Pet’rs’ Ex. 16, Hannah C. Kinney et al., Subtle Developmental

Abnormalities in the Inferior Olive: An Indicator of Prenatal Brainstem Injury in the Sudden Infant Death

Syndrome, 61 J. NEUROPATHOLOGY & EXPERIMENTAL NEUROLOGY 427 (2002); Pet’rs’ Ex. 17, Hannah

C. Kinney, Brainstem Mechanisms Underlying the Sudden Infant Death Syndrome: Evidence from Human

Pathologic Studies, 51 DEVELOPMENTAL PSYCHOBIOLOGY 223 (2009); Pet’rs’ Ex. 18, Hannah C. Kinney

et al., The Serotonergic Anatomy of the Developing Human Medulla Oblongata: Implications for Pediatric

Disorders of Homeostasis, 41 J. CHEMICAL NEUROANATOMY 182 (2011); Pet’rs’ Ex. 19, Kevin J.

Cummings et al., Postnatal Loss of Brainstem Serotonin Neurones Compromises the Ability of Neonatal

Rats to Survive Episodic Severe Hypoxia, 589 J. PHYSIOLOGY 5247 (2011); Pet’rs’ Ex. 20, Kinney et al.,

supra note 15; Pet’rs’ Ex. 21, David S. Paterson et al., Medullary Serotonin Defects and Respiratory

Dysfunction in Sudden Infant Death Syndrome, 168 RESPIRATORY PHYSIOLOGY NEUROBIOLOGY 133

(2009).

18

Dr. Miller explained in his testimony that serotonin is a synaptic neurotransmitter, “a chemical molecule

that neurons use to communicate from one cell to the next across a gap, which is called a synapse.” Tr.

47:9–11. Specifically, serotonin is “an excitatory synaptic transmitter,” which “is supposed to increase

activity” in the target neuron. Tr. 47:12–16.

19

James J. Filiano & Hannah C. Kinney, Arcuate Nucleus Hypoplasia in the Sudden Infant Death

Syndrome, 51 J. NEUROPATHOLOGY & EXPERIMENTAL NEUROLOGY 394 (1992).

12

threatening situation in one of two ways. Pet’rs’ Ex. 38 at 4. External stressors can “suppress the

normal homeostatic responses mediated by this medullary serotoninergic network, leading to a

failure of homeostasis and death.” Id. Alternatively, external stressors “can create a dangerous

situation, such as apnea, to which the medullary mechanisms which ought to respond by producing

arousal just fail to do so.” Id.

Dr. Miller explained that all humans “experience periods of apnea” during sleep, meaning

that there are periods where “we stop breathing in sleep.” Tr. 45:22–23. Normally, the period is

brief and a person wakes up, “or at least arouse[s] enough to breathe again.” Tr. 45:23–25. If

pillows or other objects are obstructing an infant’s face, the infant will re-inhale carbon dioxide-

rich air, which will lead to an increase in blood carbon dioxide levels. Tr. 46:9–19. Under normal

circumstances, if the body’s “level of CO2 rises above a safe level during sleep, the arcuate nuclei

should detect that[] and respond by signaling through their neurotransmitter serotonin to other

nuclei in the network to stimulate arousal and gasping respirations.” Pet’rs’ Ex. 38 at 4–5. Dr.

Miller wrote that it is “suppression of this network’s activity” that is thought to provoke SIDS in

a vulnerable infant. Id. at 5. Infants with “various different defects in the medulla,” particularly

where the “arousal mechanism, which is mediated by serotonin neurons, is defective,” will not

wake up. Tr. 46:25–47:3. As a result, carbon dioxide levels continue to rise, eventually leading

to death. Tr. 47:3–6. Dr. Miller explained that under the Triple Risk Model, “there are various

things which can cause stress on the brainstem functions, which then get no response or an

inadequate response” from the defective arousal mechanism when there is an apnea event. Tr.

46:1–7.

Dr. McCusker also acknowledged that studies suggest that infants who die of SIDS may

have “intrinsic defects in the autonomic nervous system with inadequate compensation[,] which

when stressed[,] can lead to death.” Resp’t’s Ex. E at 3 (citing Resp’t’s Ex. E, Tab 1, ECF No.

52-1;20 Tab 4, ECF No. 52-421). Dr. Folkerth did not explicitly discuss in her reports whether

brainstem defects or abnormalities can make an infant “vulnerable” under the Triple Risk Theory.

Instead, Dr. Folkerth wrote that “the finding by Dr. Kinney and others that a subset of infants dying

of SIDS . . . has brainstem abnormalities detected using research tools means only that there is a

biologically plausible basis for an intrinsic abnormality of the brainstem that leaves an infant at

risk for death when confronted by potential stressors[.]” Resp’t’s Ex. F at 2. She emphasized that

“a brainstem abnormality (such as arcuate nucleus hypoplasia)” is not required for a diagnosis of

SIDS. Id.

a. The Autopsy Procedure

Dr. Miller criticized the examination of the brain in this case, describing it as “suboptimal.”

Pet’rs’ Ex. 12 at 3. Dr. Miller explained that “[t]here is only one level of medulla available for

histological examination[.]” Id. Furthermore, he explained that “[t]he hippocampus section is

overly small, and at a rather more anterior level than is ideal for examination.”22 Id. at 3–4.

20

Kinney & Thach, supra note 13.

21

André Kahn et al., Sudden Infant Deaths: Stress, Arousal and SIDS, 75 EARLY HUM. DEV. S147 (2003).

22

Dr. Miller argued that sectioning all levels of the medulla would be “best practice[]” to rule out the

absence of the arcuate nucleus or hypoplasia in a SIDS autopsy. Pet’rs’ Ex. 37 at 2. In support of that

argument, he noted that experts retained by the Department of Health and Human Services have previously

13

Additionally, Dr. Miller wrote that the review of the hippocampus slide “is further limited by a

poor histological preparation, with the tissue in fragments, not in one piece.” Id. at 4. Finally, Dr.

Miller explained that “[t]here is only one other sample with any cerebral cortex, [and that sample

is] also small and inadequate.” Id. Dr. Miller noted that there is “more gliosis than Dr. Mena

described, including in the frontal cortex, in the frontal white matter, and in the cerebellar white

matter.” Id. Dr. Miller testified that “the gliosis didn’t happen the day [J.J.] died” and that it could

be evidence of prior episodes of adverse events. Tr. 92:24–25. He noted that “[g]liosis is a process

which takes days to evolve,” and that it can exist in a brain for “weeks or years.” 23 Tr. 92:25–

93:5.

Dr. Folkerth did not agree with Dr. Miller’s assessment that the brain examination was

“suboptimal,” because she explained that “only one level of the medulla is necessary to confirm

an impression of SUDI/SIDS.” Resp’t’s Ex. C at 6. She wrote that studies which have “detected

abnormalities in the medulla, principally of the serotonergic system,” rely on “research methods

(i.e., specialized biochemical, cell-counting, and other techniques)[] not available to forensic or

hospital pathology practitioners for diagnostic purposes.” Id. (emphasis in original). She also

wrote that “the lack of complete sectioning of the entire medulla in no way decreases the likelihood

that the child died of SUDI/SIDS[,]” and that “an examination of the entire medulla[]” is not

required to find a diagnosis of SIDS. Id. Dr. Folkerth opined that the brain sections available for

review were “adequate for the purposes of detecting alternate causes of death (such as encephalitis,

malformations, etc.).” Id. She concluded that “the sampling of the brain was within [the] standard

of care[.]” Resp’t’s Ex. F at 2.

b. J.J.’s Brain

Dr. Miller testified that the autopsy of the brain in this case showed “markers” of defects

associated with the medulla. Tr. 48:2–4. Dr. Miller opined that “the [arcuate] nuclei in the single

section available” from the examination performed in this case “are at least somewhat

hypoplastic,24 but this may just be due to the level of the section, as the nucleus varies in size from

level to level.” Pet’rs’ Ex. 12 at 4. He emphasized in his testimony that the single slide of medulla

available “has arcuate nuclei that in [his] judgment are too small,” and that the single slide is “the

only evidence [he] ha[s] to go on.” Tr. 115:22–24; see also Tr. 81: 9–14. He also noted that the

nucleus is “mildly gliotic,” which, he stated, “goes along with the gliosis Dr. Mena did record in

the adjacent inferior olivary nuclei.” Pet’rs’ Ex. 12 at 4. Based on his overall review of the autopsy

slides, Dr. Miller opined that “there is definite evidence of brainstem impairment in this infant,

opined that “the absence of any arcuate nuclei in a single section of medulla is insufficient evidence for a

brainstem defect[.]” Id. at 4. Dr. Miller opined that “[w]henever there are negative findings[,]” such as a

finding that there were no abnormalities, “one must ask about the adequacy of the examination[.]” Id. In

Dr. Miller’s opinion, the sampling Dr. Mena provided is not adequate. Id.

23

He noted that “there was gliosis, which is a sign of ongoing cellular damage[,] in several of the areas”

where serotonergic neurons exist, including the arcuate nuclei and the inferior olivary nuclei. Tr. 48:9–12.

He testified that additional areas of generalized gliosis were found in the brain, “including in the cerebral

hemispheres,” which, he testified, “indicat[es] that there had probably been prior episodes of perhaps lower

oxygen or higher carbon dioxide,” possibly related to J.J.’s prematurity. Tr. 48:19–24.

24

Hypoplasia is the “incomplete development or underdevelopment of an organ or tissue.” Dorland’s at

905.

14

especially of the medulla.” Id. Dr. Miller emphasized that “there is evidence in the autopsy that

[J.J.] had some of the brainstem defects reported as indicative of vulnerability to SIDS . . . and he

presumptively had a defective medullary serotoninergic system as the cause of his vulnerability.”

Pet’rs’ Ex. 37 at 6. Therefore, Dr. Miller opined that J.J.’s “maldeveloped or damaged medulla”

qualifies him as a “vulnerable infant” under the Triple Risk Model. Pet’rs’ Ex. 12 at 4. His

opinion was based in part on “the evidence of gliosis in the brain stem, and particularly in the

medulla.” Tr. 93:14–15. It was also based on his opinion that “in the slide that’s available of the

medulla, the arcuate nucleus is hypoplastic.” Tr. 94:10–12. Additionally, Dr. Miller testified that

he made a “statistical inference” based on the fact that 70 percent or more of infants who die from

SIDS “have defects in the serotonergic system in the medulla” at autopsy. Tr. 93:17–20.

Dr. Folkerth wrote in her report that “[a] single section of the medulla may or may not

show . . . aplasia or hypoplasia of the arcuate nucleus[.]” Resp’t’s Ex. C at 6. She did not provide

an opinion in her reports as to whether J.J. may have had a brain defect that would qualify him as

a vulnerable infant. She wrote only that “[t]he arcuate nucleus was present in the medulla.” Id. at

5. In her testimony, Dr. Folkerth opined that a single section of medulla is “adequate to exclude a

diagnosis of hypoplasia for the most part.” Tr. 131:22–25. She testified that she could not

remember and did not write anything down about the arcuate nuclei “appearing small or otherwise

abnormal” upon her review of the slide. Tr. 131:25–132:2. Therefore, she testified that she did

not “feel that there were enough grounds to say anything regarding arcuate hypoplasia,” and later

opined more definitively that she does not “think the arcuate nucleus is small.” Tr. 132:2–4,

137:10–11. Dr. Folkerth wrote in her report that the “[d]eep cerebral white matter had some

prominent reactive astrocytes.” Resp’t’s Ex. C at 5. Additionally, Dr. Folkerth noted that

“[s]ections of midbrain, pons, and medulla were notable for rare reactive astrocytes in the median

raphe[] and in the inferior olivary nucleus.” Id. Dr. Folkerth opined that “[g]liosis is a result of

any kind of injury,” and is therefore “not specific in the least.” Tr. 130:24–25. She agreed with

Dr. Miller’s assessment that “they’re sort of the scar cells of the brain,” noting that they can be

seen “following all sorts of processes,” such as “infection[, lack of] oxygen[,] or actual mechanical

trauma or seizures.” Tr. 131:2–10. Dr. Folkerth opined that gliosis does not “necessarily have a

lot of significance when [it is] very limited, as in this case.” Tr. 131:15–16. Dr. Folkerth further

opined that evidence of gliosis is “not necessarily indicative of a vulnerability to SIDS.” Tr.

133:13–14. She testified that gliosis is “a marker for whatever leads to various apneic periods that

result in gliosis.” Tr. 133:23–24.

Despite her opinions regarding the autopsy findings, Dr. Folkerth conceded that J.J. “could

very well have had, [and] probably did have[,] an intrinsic brain stem abnormality.” Tr. 159:1–3.

Dr. Folkerth testified that J.J.’s “brain stem was not studied to look for specific serotonergic

defects, so none of us in this room can say whether he had them or not.” Tr. 137:23–138:1.

Continuing, she testified that “based on the information we have [and] using the routine diagnostic

standards that we use, [she] think[s] [J.J.’s death] completely fits a SIDS picture.” Tr. 138:1–3.

Thus, she explained that “we’re sort of inferring that since J.J. died of SIDS and since most babies

who die of SIDS have a brain stem defect, more likely than not he did.” Tr. 168:25–169:2.

Dr. Folkerth wrote that a “vulnerable infant” under the model has “features such as

premature delivery, exposure to cigarette smoke, [or] male gender[,]” and she noted that both

prematurity and male gender are applicable in this case. Resp’t’s Ex. C at 5–7.

15

Based on all the evidence, the undersigned finds that it is more likely than not that J.J. had

a brain defect which, along with his male gender and prematurity, qualified him as a “vulnerable

infant” under the Triple Risk Model of SIDS. Dr. Miller persuasively opined that the arcuate

nuclei in the single section of medulla available for examination were “at least somewhat

hypoplastic[.]” Pet’rs’ Ex. 12 at 4. Dr. Folkerth agreed that, statistically, “[i]t’s probably likely,

more likely than not,” that J.J. had a defective medullary serotonergic system. 25 Tr. 134:4–6.

Ideally, multiple slides of the medulla would be available to the parties’ experts so that they could

determine definitively whether the arcuate nuclei were hypoplastic. However, as Dr. Folkerth

stated, the methods used to “detect[] abnormalities in the medulla, principally of the serotonergic

system,” are research methods which are “not available to forensic or hospital pathology

practitioners[.]” Resp’t’s Ex. C at 6. In Program cases involving infant deaths, petitioners must

rely on results from the procedures used by those practitioners,26 and it would be unfair to expect

hospital pathologists, while determining a cause of death, to replicate the type of comprehensive

examination done in research settings to study etiology. The Program does not ever require

medical certainty, and in this case, there is supporting evidence and the experts agree that

statistically speaking a condition is more likely than not present. It is enough for Petitioners to

establish it is more likely than not that J.J. had a defective brainstem and was a vulnerable infant

as defined by Dr. Kinney’s Triple Risk Model.

2. The Critical Development Period under the Triple Risk Model

The critical development period is defined by Dr. Kinney as the first year of life, with “the

peak age being between 2–4 months of age.” Resp’t’s Ex. E at 3. The window of time is significant

because it “coincides with progression both in brain and in lung development.” Id. at 3–4. All

three experts reviewed the medical records and concur that J.J. died from SIDS the day after his

receipt of four vaccines that were administered during his four-month well-baby examination.

This fits squarely within the critical development period and is not in dispute.

3. Exogenous Stressors under the Triple Risk Model

An exogenous stressor, or “extrinsic risk,” is “defined as a physical stressor around the

time of death that may increase the risk of SIDS for an already vulnerable infant.” Resp’t’s Ex.

A, Tab 5 at 2–3. Dr. McCusker cited Dr. Kinney’s findings from a 2012 study that found that

ninety-nine percent of SIDS infants “had at least 1 [intrinsic or extrinsic] risk factor.” Resp’t’s

Ex. A at 3 (citing Resp’t’s Ex. A, Tab 5 at 3). Dr. Kinney reported in that same study that “75%

[of SIDS infants] had at least 1 of each [extrinsic and intrinsic risk factor]” and “[t]he majority

25

Dr. Folkerth noted that she could not be certain without conducting a study such as the one Dr. Kinney

uses in her research. Tr. 134:7–11. Dr. Folkerth emphasized that “about 70 percent of SIDS infants do turn

out to have these abnormalities after [researchers] do research on them, but . . . that is not determined by

the routine standard neuropathologic examination that[ is] available . . . in medical examiners’ offices.” Tr.

134:12–18.

26

Dr. Folkerth testified that “the guidelines are sort of loose among all medical examiners’ offices about

exactly what should be submitted.” Tr. 132:11–14. Dr. Folkerth added that if she can include two sections

of the medulla, she will do so in order to “feel more sure that [she is] seeing . . . representational tissue.”

Tr. 132:14–17.

16

(57%) had at least 2 extrinsic risks and 1 intrinsic risk factor.” Resp’t’s Ex. A, Tab 5 at 3. Dr.

McCusker testified that “there is a suggestion that there is an increased frequency of sudden infant

death if there is more than one risk factor,” although the total number of risk factors “doesn’t

appear to . . . make a difference.” Tr. 268:23–269:5. She also noted that “you can have sudden

infant death with none” of the identified risk factors present. Tr. 269:9.

Dr. McCusker explained that “extrinsic factors,” which have been “identified through the

epidemiological studies,” are “those elements which may contribute to a change in the mechanics

of respiration, as opposed to the neurochemical.” Resp’t’s Ex. A at 3. She also described them as

“those factors that are consistent with hypoxia[-]generating conditions[.]” Resp’t’s Ex. E at 5,

(citing Pet’rs’ Ex. 37, Tab C27). She listed “prone or side sleeping, bed sharing, over-bundling,

soft bedding, [having one’s] face covered[,] upper respiratory tract infection[,] . . . parental,

especially maternal smoking[,] . . . bottle feeding[,] smoking in the home[,]” and “GE reflux” as

examples of external risk factors. Resp’t’s Ex. A at at 3, 9. She noted that “[h]igher ambient

temperatures” created by bundling or use of covers “are also considered risk factors for SIDS

[because they] inhibit[] respiratory drive and reduc[e] the normal heart-rate variability without

raising core body temperature.” Resp’t’s Ex. E at at 5 (citing Resp’t’s Ex. A, Tabs 1,28 4,29 15,30

ECF Nos.38-1, 38-4,39-5).

Dr. McCusker wrote that, “[i]n the case of [J.J.], he was co-sleeping, was known to be a

bottle[-]fed baby[,] and had symptoms of an upper respiratory tract infection.” Resp’t’s Ex. A

at 3 (emphasis in original); see also Resp’t’s Ex. E at 5 (Dr. McCusker’s second report, describing

bed sharing, bottle feeding, and “upper respiratory tract infection (per his parents)” as risk factors).

As discussed previously, Dr. McCusker also identified prematurity and male gender as risk factors

in J.J. Resp’t’s Ex. A at 9. Dr. Folkerth noted that J.J. “was born prematurely[] and had additional

known risk factors of a potentially unsafe sleeping environment (co-sleeping with his twin), and

male gender.” Resp’t’s Ex. C at 7. She also noted that Petitioners’ affidavits identified that J.J.

had a runny nose and cold, which she testified “probably represented a risk factor.” Tr. 135:5–7.

In contrast, Dr. Miller opined that some of the stressors which are generally accepted as

having an association with SIDS do not involve obstruction of an infant’s airway. For example,

he wrote that “[t]here is clear evidence that hyperthermia, whether from an overly warm external

environment . . . or fever, is another external stressor[.]” Pet’rs’ Ex. 37 at 6. Dr. Miller continued

that this condition is distinguished from the stressor of airflow obstruction seen with prone

sleeping, co-sleeping, or blanket use, and “it is unlikely to have its effect through any obstruction

of airflow.” Id. He further opined that “[t]here is equally clear evidence that [URIs] provoke

cytokine responses which have central nervous system [(“CNS”)] actions, not as inflammatory

mediators but as modifiers of synaptic activity[.]” Id.

Dr. Miller wrote that the majority of SIDS cases involve the presence of two or more

stressors. Pet’rs’ Ex. 38 at 5. He explained that the “stressors interact, and their combined effects

are likely to be multiplicative or geometric rather than just additive.” Id. However, Dr. Miller

27

Kinney & Thach, supra note 13.

28

Id.

29

Kahn et al., supra note 21.

30

Erwan Stéphan-Blanchard et. al., Heart Rate Variability in Sleeping Preterm Neonates Exposed to Cool

and Warm Thermal Conditions, 36 PLOS ONE 1 (2011).

17

emphasized that it “is impossible with present knowledge” to apportion the relative contribution

that each stressor would have had. Id. at 6. He wrote that “each would represent a substantial

contributing factor.” Id. Dr. Miller opined that “the most important potential external stressor”

for J.J. was the series of vaccinations he received on November 14, 2012. Pet’rs’ Ex. 12 at 4. He

asserted that J.J.’s only other risk factors were prematurity and male gender, which are both

intrinsic. Dr. Miller testified that there was no evidence of a URI or any other infection. Tr. 82:21–

23.

Dr. Gill’s autopsy report identified J.J.’s final diagnosis as SIDS. He then listed additional

information which, if not ultimately deemed relevant, was at least initially considered prior to

determining the cause of death. Dr. Gill’s list included intrinsic SIDS risk factors, extrinsic risk

factors, recent medical history, and test results. Pet’rs’ Ex. 10. Several of the items listed were

used to rule out other potential causes of death before SIDS could be considered, e.g., URI history,

influenza studies, and cerebrospinal fluid (“CSF”) cultures. Id. Other items were identified as

SIDS risks factors, such as J.J.’s prematurity and history of co-sleeping. Dr. Gill also listed J.J.’s

“recent immunizations”, but there is no indication of what, if any, significance Dr. Gill gave this

part of J.J.’s medical history. It is also unclear whether this line item was an example of something

that was ruled out as a cause (see influenza studies: negative) or identified as a possible

contributing risk factor (co-sleeping with twin).

i. Co-Sleeping

Dr. Miller wrote that “the data on the risks of co-sleeping” largely involve an infant

sleeping in the same bed or on a couch with an adult. Pet’rs’ Ex. 38 at 2. He explained that such

co-sleeping creates a “hazardous sleeping condition” because it may cause “accidental

asphyxiation of the infant when the adult rolls over in his or her sleep and smothers the child,

without awakening.” Id.

Dr. Miller explained that co-sleeping as a potential external stressor in this case is “almost

certainly a red herring, for two reasons[.]” Pet’rs’ Ex. 37 at 6. First, J.J. was sleeping with his

approximately equal-sized twin sister in a crib, as opposed to with an adult or older sibling in an

adult bed. Id. Dr. Miller noted J.J.’s “twin was not large enough to cause asphyxiation should the

two of them end up with one on top of the other[,]” and the crib “was large enough for them to be

entirely separate, so there was no chance for such an interaction to occur.” Pet’rs’ Ex. 38 at 2.

Second, the evidence suggests that his twin sister was removed from the crib before he experienced

the event which ultimately led to his death.31 Pet’rs’ Ex. 37 at 6.

In her testimony, Dr. Folkerth agreed that co-sleeping is “[p]robably not” a risk factor in

this case based on Ms. Nunez’s testimony that J.J. and his twin sister slept at opposite ends of the

crib. Tr. 177:11–16. Dr. McCusker similarly testified that based on Ms. Nunez’s testimony

regarding how the infants were sleeping at opposite ends of their crib, she “would say that this [co-

31

Based on the recorded temperature at the time of death, and with the disclaimer that “[e]stimating time

of death is admittedly quite imprecise,” Dr. Miller estimated that J.J. died only about an hour prior to the

time that his temperature was measured. Pet’rs’ Ex. 38 at 2. Dr. Miller noted that, based on the timeline

of events, J.J.’s twin had been removed from the crib well before that time, and thus co-sleeping was not a

risk factor contributing to J.J.’s death. Id.

18

sleeping] would not be considered a risk factor.” Tr. 284:13–20. Based on the record as a whole,

including Ms. Nunez’s testimony and Respondent’s experts’ ultimate concessions based on that

testimony, the undersigned finds that co-sleeping was not a relevant risk factor in this case.

ii. Bundling/Use of a Receiving Blanket in the Crib

Dr. Folkerth provided “soft bedding” and “hyperthermia/overbundling” as examples of

exogenous stressors under the Triple Risk Model. Resp’t’s Ex. C at 6. Dr. McCusker also

described two ways in which over-bundling is thought to be a risk factor for SIDS. Tr. 206:6–16.

She testified that a high ambient temperature can be a risk factor because it can affect the

sleep/wake cycle and respiratory rates. Tr. 206:6–11. Additionally, she explained that over-

bundling can create a situation where an infant’s startle reflex is compromised, such that if there

is a respiratory problem, the infant will not be able to startle himself awake. Tr. 206:14–22. Dr.

Miller noted that “[t]here is clear evidence that hyperthermia, whether from an overly warm

external environment . . . or fever, is another external stressor[,]” separate from the stressor of

airflow obstruction seen with blanket use. Pet’rs’ Ex. 37 at 6.

Dr. McCusker testified that the blanket tucked around J.J.’s legs was not “the equivalent

of bundling, but it is not recommended, because it’s considered an increased risk factor for sudden

infant death.” Tr. 288:4–6. Dr. McCusker testified that the Pediatric Task Force concluded that

“things should not . . . encircle the infant.” Tr. 287:13–14 (citing Resp’t’s Ex. A, Tab 7,32 ECF

No. 38-7). Specifically, Dr. McCusker read the following from the article: “Even if covered by a

sheet, it should not be placed under a sleeping infant.” Tr. 286:22–23. Dr. McCusker testified that

Ms. Nunez’s “description of having the blanket underneath the child . . . would be considered

something that would decrease the startle reflex.” Tr. 208:18–21. She testified that she “didn’t

appreciate that when [she] read the notes before, so that’s another sort of add-on” to her list of risk

factors in this case. Tr. 206:21–24.

Dr. McCusker’s late addition of the loosely tucked sheet as a risk factor in this case is not

persuasive. None of the experts testifying in this case suggested that the crib sheet led to

hyperthermia or asphyxiation in J.J. Additionally, the undersigned does not find that the Pediatric

Task Force considered a sheet loosely tucked underneath an infant’s legs to be a risk factor separate

from hyperthermia-inducing over bundling or mechanical obstruction. In the section that Dr.

McCusker referenced, the authors recommend that infants sleep on “a firm sleep surface,” and

more specifically, “[a] firm crib mattress, covered by a fitted sheet[.]” Resp’t’s Ex. A, Tab 7 at 3.

The sentence referenced by Dr. McCusker during her testimony appears in a paragraph regarding

such mattresses, which states in pertinent part:

Pillows or cushions should not be used as substitutes for mattresses or in addition

to a mattress. Soft materials or objects such as pillows, quilts, comforters, or

sheepskins, even if covered by a sheet, should not be placed under a sleeping infant.

Id. By leaving out the context of the sentence that she read, Dr. McCusker did not accurately

portray the authors’ concerns regarding the use of a sheet. Dr. McCusker conceded that there were

32

Task Force on Sudden Infant Death Syndrome, SIDS and Other Sleep-Related Infant Deaths: Expansion

of Recommendations for a Safe Infant Sleeping Environment, 128 PEDIATRICS 1030 (2011).

19

no other soft materials in the crib, other than the sheet. Tr. 287:20–24. Therefore, the undersigned

finds that the use of a receiving blanket in this case, based on Ms. Nunez’s description of how she

loosely tucked it around J.J.’s legs, was not a relevant risk factor for SIDS.

iii. Bottle Feeding

Dr. McCusker wrote that breastfeeding and pacifier use are considered “‘protective’ factors

in SIDS[,]” because infants with those factors “rouse more easily and more frequently compared

to those bottle fed.” Resp’t’s Ex. E at 5 (citing Tabs 4,33 16,34 17,35 ECF Nos. 52-4, 53-6, 53-7).

In her testimony, Dr. McCusker clarified that “[b]reast feeding is considered to be protective for

SIDS[, s]o bottle feeding is considered to be a risk factor.” Tr. 209:5–7. She was unable to answer

a question regarding whether a combination of breastfeeding and bottle feeding would change the

risk of SIDS. Tr. 309:23–310:5.

The risk associated with bottle feeding is very different than the exogenous stressors such

as prone sleeping or co-sleeping, which are associated with the “mechanics of respiration.”

Resp’t’s Ex. A at 3. Although breastfeeding’s protective effect was not explained, the literature

that Dr. McCusker filed reflects that “[b]reastfeeding is associated with a reduced risk of SIDS[,]”

and “[t]he protective effect of breastfeeding increases with exclusivity.” Resp’t’s Ex. A, Tab 736

at 5. This article notes that “any breastfeeding has been shown to be more protective against SIDS

than no breastfeeding.” Id. Therefore, bottle feeding does not appear to affirmatively contribute

to SIDS, like an unsafe sleeping position does. Instead, breastfeeding serves to help to protect

against SIDS. In this way, it is more like the intrinsic “risk factors” of prematurity or male gender

than exogenous stressors such as a dangerous sleeping environment. Ms. Nunez testified that J.J.

was fed with both breastmilk and formula. Tr. 21:20–21. Although exclusive breastfeeding may

have a protective effect, the undersigned found nothing in the literature to suggest that SIDS is in

any way caused by an infant’s having been partially (or exclusively) bottle fed. Because the

undersigned is considering potential causes of J.J.’s death in this case, the undersigned does not

find the fact that J.J. was partially bottle fed to be a significant factor in the analysis.

iv. Upper Respiratory Infection

a. URI as an Exogenous Stressor Generally – Cytokine Production vs.

Airway Obstruction

Dr. Miller testified that “one of the risk factors that [has] been statistically highly

important” in SIDS cases is having a mild infection. Tr. 53:7–9. He explained that the infection

can be either a mild or trivial URI or a gastrointestinal infection. Tr. 53:9–11. In his reports, Dr.

Miller wrote that “[a]mong the described external stressors[,] the presence of a URI is

prominent[,]” noting that studies have found URIs or other minor infections may be present in

anywhere from 20 percent to over 80 percent of SIDS cases. Pet’rs’ Ex. 38 at 4.

33

Kahn et al., supra note 21.

34

Bert Alm et al., Breastfeeding and Dummy Use Have a Protective Effect on Sudden Infant Death

Syndrome, 105 ACTA PAEDIATRICA 31 (2016).

35

Edwin A. Mitchell & Henry F. Kraus, Sudden Unexpected Death in Infancy: A Historical Perspective,

51 J. OF PAEDIATRICS AND CHILD HEALTH 108 (2015).

36

Task Force on Sudden Infant Death Syndrome, supra note 32.

20

Dr. Miller argued that “[t]he mechanism whereby [URIs or other minor] infections increase

the risk of a SIDS event . . . is believed to be mediated by cytokines.” Id. Dr. Miller explained

that the innate immune system produces cytokines, which both “promote the adaptive immune

system to react to the pathogens invading the body” and “mobiliz[e] more cells of the intrinsic

immune system to attack the pathogens.” Id. He opined that “[t]here is . . . clear evidence that

[URIs] provoke cytokine responses which have [CNS] actions, not as inflammatory mediators but

as modifiers of synaptic activity[.]” Pet’rs’ Ex. 37 at 6. He noted that IL-1, IL-6, and tumor

necrosis factor (“TNF”) are among the cytokines produced in response to infection. Pet’rs’ Ex. 38

at 4. Dr. Miller explained that some of these cytokines can cross the blood-brain barrier into CNS

tissues. Id. (citing Pet’rs’ Ex. 38, Tab D,37 ECF No. 94-2; Pet’rs’ Ex. 37, Tab M,38 ECF No. 93-

9). Dr. Miller wrote that the cytokines can mediate fever, produce “sick behaviors” such as

lethargy, excessive sleepiness, fussiness, crankiness, loss of appetite, and restlessness, and alter

sleep patterns. Pet’rs’ Ex. 38 at 4. Dr. Miller also wrote that the cytokine “actions which are

thought to lead to SIDS involve the[] suppression of the activity of the serotoninergic network[.]”

Id. This hypothesis is derived “from multiple published experimental animal studies which have

examined the functional responses and electrophysiological changes in serotoninergic medullary

neurons exposed to some of these relevant cytokines.” Id. (citing Pet’rs’ Ex. 38, Tabs 5,39 6,40 7,41

8,42 ECF Nos. 91-10, 92-1, 92-2, 94-3).

Dr. McCusker rejected Dr. Miller’s explanation of how a trivial URI increases the risk of

SIDS and wrote that “[c]ytokine production with respiratory or gastrointestinal infections have not

been defined as factors” in apneic episodes leading to SIDS. Resp’t’s Ex. E at 6. She further

wrote that “[t]here are no studies presented demonstrating that hypercapnia43 results from cytokine

release[.]” Id. at 5; see also Tr. 200:3–20 Dr. McCusker also testified that she is not aware of any

evidence that mild URIs create a risk factor for SIDS by causing a cytokine response in the

brainstem. Tr. 207:22–25.

Instead, Dr. McCusker argued that mild infection as a risk factor for SIDS “has to do with

[the] compromising of breathing.” Tr. 200:3–4. Specifically, she wrote that URIs “are sufficient

to interfere with normal infant respiration and act as a risk factor influencing gas exchange[.]”

Resp’t’s Ex. E at 5. Dr. McCusker explained that URIs “result in intermittent obstruction of the

37

Steven W. Threlkeld et al., Ovine Proinflammatory Cytokines Cross the Murine Blood-Brain Barrier by

a Common Saturable Transport Mechanism, 17 NEUROIMMUNOMODULATION 405 (2010).

38

William A. Banks et al., Bidirectional Transport of Interleukin-1 Alpha Across the Blood-Brain Barrier,

23 BRAIN RESEARCH BULLETIN 433 (1989).

39

Lauritz Stoltenberg et al., Changes in Apnea and Autoresuscitation in Piglets After Intravenous and

Intrathecal Interleukin-Iβ Injection, 22 J. PERINAT. MED. 421 (1994).

40

J. Frederik Frøen et al., Adverse Effects of Nicotine and Interleukin-1β on Autoresuscitation After Apnea

in Piglets: Implications for Sudden Infant Death Syndrome, 105 PEDIATRICS E52 (2000).

41

D. Brambilla et al., Interleukin-1 Inhibits Firing of Serotonergic Neurons in the Dorsal Raphe Nucleus

and Enhances GABAergic Inhibitory Post-synaptic Potentials, 26 EUR. J. NEUROSCI. 1862 (2007).

42

Alfredo Manfridi et al., Interleukin-18 Enhances Non-rapid Eye Movement Sleep when Microinjected

into the Dorsal Raphe Nucleus and Inhibits Serotonergic Neurons in Vitro, 18 EUR. J. NEUROSCI. 1041

(2003).

43

Hypercapnia is an excess of carbon dioxide in the blood. Dorlands at 887.

21

upper airway sufficient to affect the O2/CO2 balance in infants[.]” Resp’t’s Ex. A at 6 (citing

Pet’rs’ Ex. 26 at 9,44 ECF No. 92-4).

Dr. McCusker wrote that “[i]nfants are obligate nose breathers and have relatively small

nasal passages and airways.” Resp’t’s Ex. E at 5. Therefore, she explained, “[c]ongestion that

occurs with seemingly trivial upper respiratory tract infections results in increases in respiratory

effort and distress.” Id. Dr. McCusker noted that “[i]ncreases in carbon dioxide levels in affected

children have been documented in several studies.” Id. However, when discussing the articles

that she cited for that assertion, Dr. McCusker acknowledged that the studies were not looking at

increases in carbon dioxide levels and that “[t]here is no study that measures CO2 levels in SIDS

patients.” Tr. 275:9–10; see also Tr. 273–283.

Dr. McCusker also wrote that “[e]vidence suggests that the central functions of the

cytokines IL[-]1β, IL[-]6 and TNF[-]α at times of infection are to promote fever and to affect the

sleep architecture by increasing [non-rapid eye movement (“NREM”)] versus [rapid eye

movement (“REM”)] sleep resulting in more disturbed sleep with more frequent arousal . . .”

Resp’t’s Ex. A at 5 (citing Resp’t’s Ex. A, Tabs 19,45 20,46 21,47 ECF Nos. 39-9, 39-10, 40-1). She

discussed infant sleep patterns in her supplemental report and wrote that in infants, “NREM sleep

is associated with regular heart rate and respiratory patterns[, whereas] REM sleep is more

disorganized and considered ‘immature.’” Resp’t’s Ex. E at 4 (citing Resp’t’s Ex. E, Tab 11,48

ECF No. 53-1). She noted that although “the expression of the circadian rhythm and changes in

sleep wake cycles are specific to the infant period, there is no evidence that cytokines act

differently in infants[.]” Resp’t’s Ex. E at 4. Therefore, she opined that cytokine increases would

actually lead to increased arousal. Id.

On cross-examination, Dr. McCusker was asked about the Rognum et al.49 study,

specifically whether mild infection may trigger SIDS by cytokine interaction in a compromised

medullary system, and she disagreed with the hypothesis of the paper. Tr. 267:10–18. She then

noted that “infection can result in hypercapnia” and that the Rognum et al. paper “actually shows”

that “the presence of IL-6 may be related to the response to the infection or the stressor that the

baby is undergoing and not be related to actually a mechanistic causality association.” Tr. 268:5–

10. Dr. McCusker was asked again to clarify whether the study shows “the elevated IL-6 is related

to an infection, but that the elevated IL-6 does not necessarily relate to the impaired respiration.”

Tr. 268:11–13. She replied, “No. . . . what they say is that the presence of the IL-6 may be related

to the infection or may be related to the increase that – of the CNS in response [to] the stressor.”

Tr. 268:14–17. She did not elaborate further. The Rognum et al. study is also supported by the

44

Ingvar J. Rognum et al., Interleukin-6 and the Serotoninergic System of the Medulla Oblongata in the

Sudden Infant Death Syndrome, 118 ACTA NEUROPATHOL. 519 (2009).

45

James M Clinton et al., Biochemical Regulation of Sleep and Sleep Biomarkers, 7 J. CLINICAL SLEEP

MED. S38 (2011).

46

Charlene E. Gamaldo et al., The Sleep-Immunity Relationship, 30 NEUROLOGIC CLINICS 1313 (2012).

47

Nicolas Rohleder et al., Role of Interleukin-6 in Stress, Sleep, and Fatigue, 1261 ANNALS OF THE N.Y.

ACAD. OF SCI. 88 (2012).

48

Oskar G. Jenni & Mary A. Carskadon, Sleep Behavior and Sleep Regulation from Infancy through

Adolescence: Normative Aspects, 2 SLEEP MED. CLINICS 321 (2007).

49

Rognum et al., supra note 44.

22

2009 Kinney et al. study that found that “in infants who die unexpectedly of infection, the given

organism may precipitate a lethal cytokine cascade or toxic response.” Pet’rs’ Ex. 37, Tab C at

3.50

Dr. McCusker wrote that “[n]asal congestion associated with upper respiratory tract

infections can compromise infant respiration and increase carbon dioxide[,]” and that “‘noisy

breathing,’ as seen with nasal congestion or obstruction, positively correlates with sleep apnea.”

Resp’t’s Ex. E at 6 (citing Resp’t’s Ex. E, Tab 451). When questioned about the basis for her

mechanical hypothesis, Dr. McCusker stated that “[i]ncreased CO2 associated with upper

respiratory tract infections in infants is basic pediatrics.” Tr. 274:15–17. She emphasized that an

infant with a “stuffed up” nose will use “a lot of respiratory effort,” but there will be “no intake of

air,” which usually results in the infant waking up crying or upset. Tr. 200:10–16. She testified

that these infants “really do have a lot of difficulty getting their air in because the idea of breathing

through the mouth [does not] come naturally to these babies.” Tr. 200:16–20. She added that an

infant “making greater respiratory efforts” will have increased metabolic activity, which will also

“increase[] the risk of increasing carbon dioxide” in the body. Tr. 201:5–10. Dr. McCusker noted

that when a stuffy nose is obstructing the airway, “most of the time, suctioning is all [one] need[s]

to do and [the infant’s] oxygen comes right back up.”52 Tr. 202:17–19.

In response to Dr. McCusker’s arguments, Dr. Miller argued that “[t]here is no support in

the literature” for . . . a mechanical hypothesis[]” of URI as an external stressor, whereby

“mechanical obstruction of an infant’s nasal passages by mucus causes hypoxia and leads to

SIDS.” Pet’rs’ Ex. 38 at 5. Dr. Miller also disagreed with Dr. McCusker’s assertion that increased

cytokine activity would lead to increased arousal. Pet’rs’ Ex. 37 at 5. Dr. Miller opined that “this

mechanism might operate in normal infants[,]” whereas in “infants with defective medullary

serotonin networks . . . there cannot be a response to cytokines” as described because of the defect.

Id. He also emphasized that the mechanism described by Dr. McCusker in support of her assertion

would not be applicable in this case because infants such as J.J. “have not yet developed sleep

regulation by circadian rhythms[,]” and the article studied older children. Id. Dr. Miller

acknowledged that “over time[,] some cytokines can also stimulate the pituitary-adrenal axis to

drive greater production of serotonin in a healthy nervous system[.]” Pet’rs’ Ex. 38 at 6. However,

he emphasized that in a developmentally defective nervous system, this stimulation “ought not to

be regarded as an argument against the hypothesis that infection or vaccine-induced cytokine

responses can suppress the medullary serotoninergic network[.]” Id.

The role of cytokines stimulated by mild infection is central to Petitioners’ theory in this

case, because Dr. Miller compares the cytokine response in mild infection to that of vaccination to

explain his theory. The experts drastically diverge in their discussion at this point because Dr.

McCusker does not agree with the basis of Dr. Miller’s analogy: the mechanism by which a mild

50

Kinney & Thach, supra note 13.

51

Kahn et al., supra note 21.

52

Dr. McCusker testified that “[i]n more severe cases,” if an infant’s carbon dioxide level is “very, very

high,” they may “need assisted ventilation in order to get through that infection.” Tr. 202:19–24. Dr.

McCusker discussed bronchiolitis, where an infant’s upper and lower airways become obstructed, and noted

that even in such severe cases, “first-line management of bronchiolitis is upper airway suctioning.” Tr.

203:18–22.

23

infection can increase the risk of SIDS. Dr. Miller points to the Rognum et al.53 study which

“provides evidence for aberrant interactions in SIDS infants between IL-6 and the arcuate nucleus,

a key medullary 5-HT related region . . . potentially induced by the combined effect of prone

position and mild infection.” Pet’rs’ Ex 26 at 9. He then uses that same mechanism to argue that

a vaccine-initiated immune response is by its very nature similar to the immune response prompted

by an infection and, consequently, “[the mechanism] applies to all vaccines.” Tr. at 89:23.

b. URI as an Exogenous Stressor in this Case

Dr. Miller wrote that Petitioners’ descriptions of J.J. and his twin having “‘runny noses and

a productive’ cough” at the time of their visit to the pediatrician on November 14, 2012, “suggest

that J.J. had a URI[.]” Pet’rs’ Ex. 38 at 3. However, he noted that references to “runny noses and

productive coughs” come from Petitioners’ affidavits, which “were put together months after the

infant’s death[.]” Pet’rs’ Ex. 37 at 3.

Dr. Miller highlighted that neither the pediatrician’s note from the evening of November

14, 2012, nor the November 15, 2012 EMS and emergency department notes contain any

indication that Petitioners described a runny nose or recent URI symptoms at the time of J.J.’s

death. Pet’rs’ Ex. 37 at 3. Dr. Miller noted in his testimony that the pediatrician’s note contains

“a lot of specifics . . . in terms of physical examination that are mentioned that are all normal

findings, including . . . that there was no nasal discharge.” Tr. 32:14–16. He also emphasized that

the records from November 15, 2012, reflect only that J.J. was “cranky” after his vaccinations.

Pet’rs’ Ex. 37 at 4. Dr. Miller testified that he “tend[s] to go with medical records rather than

parent recollections” when the two conflict. Tr. 82:15–17. Therefore, Dr. Miller stated that “[f]or

the purposes of analyzing potential risk factors” in the Triple Risk Model, he “cannot agree that

there is any medical evidence [of] an URI in [J.J.] on the day before his death[.]” Pet’rs’ Ex. 37

at 4; see also Tr. 82:21–23.

Dr. Miller conceded that Dr. Gill’s autopsy report listed “recent upper respiratory

infection” under the “final diagnoses” section but noted that “recent immunizations” is noted on

the same list. Pet’rs’ Ex. 37 at 3–4. Therefore, Dr. Miller opined that, “[i]f the ME report is to be

regarded . . . as reliable as to the history of a recent URI as a contributing factor for SIDS . . . ,

[then the inclusion of] ‘[r]ecent immunizations’ directly under the diagnosis of the URI[ is]

presumably equally important as a potential contributor to death in this case.” Id. at 4. Dr. Miller

opined that if there were medical evidence of a mild infection in this case, “it would be an

additional risk factor.” Tr. 120:12–15. Dr. Miller opined that if J.J. did have a mild URI at the

time of vaccination, it may have “further increase[d] the risk of a SIDS event over the risk of

exposure to either stressor[, i.e., mild URI or vaccination,] alone.” Pet’rs’ Ex. 38 at 6. However,

he testified that such a finding would not change his analysis that the vaccines were still a

substantial contributing factor for the death. Tr. 120:21–23.

Dr. McCusker discussed URI as a risk factor for SIDS in this case without substantially

addressing the contradiction between the medical records and Petitioners’ affidavits. In both of

her reports, Dr. McCusker wrote that J.J.’s “parents reported nasal congestion, runny nose and

cough on the day and evening of November 14, 2012.” Resp’t’s Ex. A at 1; Resp’t’s Ex. E at 1.

53

Rognum et al., supra note 44.

24

In her first report, she opined that J.J. “had symptoms of an upper respiratory tract infection[,]”

among his risk factors for SIDS. Resp’t’s Ex. A at 3. In her second report, Dr. McCusker listed

“upper respiratory tract infection (per his parents)[]” as a risk factor in this case. Resp’t’s Ex. E at

5. In her testimony, Dr. McCusker indicated that she was “[p]erhaps . . . referring to the congestion

associated with the upper respiratory tract infection in October” when she included congestion in

her summary of symptoms on the evening of November 14, 2012. Tr. 262:15–23. She conceded

that there was no parental report nasal congestion on November 14, 2012. Tr. 263:1–4. However,

she nonetheless testified that “[t]he presence of the upper respiratory tract infection would be

considered a risk factor” in this case. Tr. 208:15–17. With regard to the absence of notation in

the medical records regarding URI symptoms on November 14, 2012, Dr. McCusker testified that

“on the balance of probabilities, in this situation, when the parents are clearly giving statements

related to runny nose and cough at the time of the vaccination, then you have to feel that there was

probably some runny nose and cough.” Tr. 265:15–19. Dr. Folkerth summarized in her report

that the father reported “runny noses and productive coughs,” but she acknowledged that “the

doctor’s note for that visit describes no fever or cough or other abnormality.” Resp’t’s Ex. C at 3.

She did not list URI among the risk factors for SIDS in this case. See id. at 7.

Discussing the “final diagnoses” section of the autopsy report, Dr. Folkerth was asked

about the significance of the nine listed items underneath “sudden unexpected death in infant.” Tr.

169:16–21. Dr. Folkerth agreed that it is “[g]enerally true” that each listed item under the final

diagnosis is relevant to the cause of death. Tr. 169:19–22. However, she testified that the office

where the autopsy was performed, which is the same office where she now works, receives all the

medical records of an infant prior to autopsy. Tr. 172:19–20. Therefore, she opined that the

medical examiner, Dr. Gill, “was listing some of the historical [data]—the things that were known

about the baby’s history as things to be ruled out as possible historical significance to the child,”

and not necessarily items which he felt were related to the SIDS diagnosis. Tr. 170:4–7.

There is contradicting evidence in the record regarding whether J.J. was exhibiting

symptoms consistent with a URI on the day of his death. The medical records do not document

any type of infection or note that J.J. suffered any symptoms. However, the affidavits in this case

state that J.J. was suffering from runny nose and cough. Additionally, Ms. Nunez testified that on

the day of J.J.’s four-month pediatrician appointment, she was not concerned by his symptoms.

Tr. 24:19–21. She stated that J.J.’s nose was “no longer stuffy” as it had been in October when he

suffered from congestion, and his cough “was getting better.”54 Tr. 22:18, 24:16. She explained

that his nose was “just runny” with no congestion, and there was only a “very light, clear, like

mucus or just clear from the allergies.” Tr. 22:19–21. Based on the medical record and the

testimony provided by Ms. Nunez, the undersigned finds that it is more likely than not that J.J. had

a runny nose but was not suffering from a URI on the evening that he received the vaccines at

issue in this case.

C. Vaccination as a Risk Factor for SIDS

54

Furthermore, she testified that she was instructed about how to decongest J.J.’s nostrils with saline when

he had a stuffy nose in the beginning of October 2012. Tr. 23. Therefore, it is most plausible that if J.J.

had congestion on the evening when he received his vaccines, Ms. Nunez would have been able to remedy

the stuffiness such that J.J.’s airway would not be obstructed.

25

Dr. Miller wrote that he has seen “well over a dozen” cases of SIDS death within 48 hours

of vaccination as part of his regular work as a neuropathologist and as an expert in the Vaccine

Program. Pet’rs’ Ex. 12 at 5. Dr. Miller explained that “the peak age for SIDS is between 2 and

4 months of post-natal age, corresponding to ages at which infants now receive their first and

second rounds of multiple vaccinations.” Pet’rs’ Ex. 12 at 5; see also Pet’rs’ Ex. 1555 at 2 (“Ninety

percent of SIDS occurs in the first 6 months of life, with a peak at 2–4 months[.]”). He noted that

such a correlation “raises a suspicion that vaccinations may trigger SIDS[,]” a suspicion which he

emphasized is recognized in some medical literature. Pet’rs’ Ex. 12 at 5 (citing Pet’rs’ Exs. 30–

33,56 ECF Nos. 92-8, 92-9, 92-10, 93-1). Dr. Miller acknowledged that no single piece of medical

literature sets forth his theory of causation. Tr. 96:7–10. Dr. Miller testified that “Dr. Kinney has

never evaluated vaccinations one way or the other.” Tr. 94:23–24.

Dr. Folkerth testified that she has never seen a case where she would attribute a death to

vaccination, other than acute immediate reactions. Tr. 173:2–15. Dr. McCusker testified that she

does not believe that any vaccine, under any circumstance, could result in SIDS. Tr. 332:16–20.

1. Epidemiological Studies

The 1991 Adverse Effects of Pertussis and Rubella Report concludes that “evidence does

not indicate a causal relation[ship] between DPT vaccine and SIDS.” Pet’rs’ Ex. 34 at 18 (filed

on compact disk; ECF No. 22).57 The 2012 Adverse Effects of Vaccines Report, however, held

that “evidence is inadequate to accept or reject a causal relationship between diphtheria toxoid-,

tetanus toxoid-, or acellular pertussis-containing vaccine and ITP.” Pet’rs’ Ex. 35 at 62 (filed on

compact disk; ECF No. 22).58

In the 2000 article by Jonville-Bera et al.,59 the authors “conducted a multicentre case-

control study in the 28 French ‘SIDS Centers.’” Resp’t’s Ex. A, Tab 25 at 1, ECF No. 40-5. The

authors selected 114 cases based on deaths labeled as a SIDS death of an infant between 30 and

90 days old. Id. The study’s authors selected 341 living controls (approximately three per case of

SIDS), who were “matched for sex [and] gestational age[.]” Id. The controls were also “born

immediately after the victim in the same maternity unit.” Id. The study’s authors found that

“vaccination does not constitute a risk factor for early SIDS[.]” Id. at 4. However, they noted

55

Kinney et al., supra note 17.

56

Pet’rs’ Ex. 30, Rüdiger von Kries et al., Sudden and Unexpected Deaths After the Administration of

Hexavalent Vaccines (Diphtheria, Tetanus, Pertussis, Poliomyelitis, Hepatitis B, Haemophilius Influenzae

Type b): is there a signal?, 164 Eur. J. Pediatrics 61 (2005); Pet’rs’ Ex. 31, B. Zinka et al., Letter to the

Editor: Unexplained Cases of Sudden Infant Death Shortly After Hexavalent Vaccination, 24 VACCINE

5779 (2006); Pet’rs’ Ex. 32, Giulia Ottaviani et al., Sudden Infant Death Syndrome (SIDS) Shortly After

Hexavalent Vaccination: Another Pathology in Suspected SIDS?, 448 VIRCHOWS ARCHIV 100 (2006);

Pet’rs’ Ex. 33, Giuseppe Traversa et al., Sudden Unexpected Deaths and Vaccinations During the First

Two Years of Life in Italy: A Case Series Study, 6 PLOS ONE e16363 (2011).

57

INSTITUTE OF MEDICINE, ADVERSE EFFECTS OF PERTUSSIS & RUBELLA VACCINES 125–43 (Christopher

P. Howson et al. eds., National Academy Press 1991).

58

INSTITUTE OF MEDICINE, ADVERSE EFFECTS OF VACCINES. EVIDENCE AND CAUSALITY 581–82

(Kathleen Stratton et al. eds., National Academy Press 2011).

59

Annie-Pierre Jonville-Bera et al., Sudden Unexpected Death in Infants Under 3 Months of Age and

Vaccination Status—a Case-control Study, 51 BRITISH J. CLINICAL PHARMACOLOGY 271 (2000).

26

several biases which “might explain a failure to demonstrate a risk[,]” including a selection bias

affecting the representativeness of the cases. Id. at 5. Dr. McCusker wrote that the authors “found

that vaccination was not an independent risk factor for SIDS.” Resp’t’s Ex. A at 7.

The 2007 article by Vennemann et al.60 examined “[n]ine case-control[] studies” which

examined a potential association between immunization and SIDS. Resp’t’s Ex. A, Tab 24 at 1,

ECF No. 40-4. The authors found that “[i]mmunisations are associated with a halving of the risk

of SIDS[]” and that they should thus “be part of the SIDS prevention campaigns.” Id. The authors

noted that “[t]here are biological reasons why this association may be causal, but other factors,

such as the healthy vaccine effect, may be important.” Id.

The 2010 paper authored by Traversa et al.61 studied “whether the immunisation with

hexavalent vaccines increased the short[-]term risk of [sudden unexplained death] in infants” in

Italy. Pet’rs’ Ex. 33 at 1. The authors considered a population of “around 3 million infants

vaccinated in Italy” between 1999 and 2004, of which “1.5 million received hexavalent

vaccines[.]” Id. For that population, events of sudden infant death were identified using death

certificates, and vaccination history was “retrieved from immunisation registries.” Id. A case

series design was utilized, which focused on varying intervals of risk periods between zero and

fourteen days after vaccination. Id. The authors concluded that the relative risks of sudden

unexplained death “for any vaccines and any risk periods, even when greater than 1, were almost

an order of magnitude lower than the estimates” of another study conducted in Germany. 62 Id.

They found that “[t]he limited increase in [relative risks] found in Italy appears confined to the

first dose and may be partly explained by a residual uncontrolled confounding effect of age.” Id.

Dr. Miller emphasized that there was “a statistically significant increased risk of sudden

death” following the first doses of several vaccinations, although he acknowledged that the authors

did not find such a risk after second doses. Tr. 79:12–14. In contrast, Dr. McCusker emphasized

the authors’ acknowledged limitation of “the confounding effect of age[.]” Resp’t’s Ex. A at 7.

Dr. McCusker also noted that the “association was not seen in older infants with subsequent

vaccination.” Id. Furthermore, she noted that the authors of that study, “as in others,” found a

lower immunization rate among sudden unexplained death cases when compared with controls,

which she opined “support[s] the concept of the ‘healthy vaccinee effect’ where vaccination

appears to reduce the risk of SID[S].” Id.

Dr. McCusker used many of the studies to support her position that “there is no evidence

for a role of vaccination in SIDS in the epidemiologic literature.” Id. at 9. She wrote that “[w]ell

designed publications . . . increase the strength of evidence against a causal association for SIDS

and vaccines providing strong epidemiological evidence for temporal association only.” Id. at 7

60

M.M.T. Vennemann et al., Sudden Infant Death Syndrome: No Increased Risk After Immunisation, 25

VACCINE 336 (2007).

61

Traversa et al., supra note 56.

62

The referenced study was filed as Petitioners’ Exhibit 30 and will be discussed below.

27

(citing Resp’t’s Ex. A, Tabs 24,63 28;64 Pet’rs’ Ex 33;65 ). She wrote that those “studies were

designed to be sufficiently powered to evaluate associations for rare events.” Id. She did not

elaborate further on what made the studies well designed or why she felt they were “sufficiently

powered.” See id.

Dr. McCusker wrote that the findings in the Toro et al.66 study “suggest[] that vaccination

was a protective measure for children at risk for SIDS[]” because the incidence of SIDS lowered

when children were vaccinated. Resp’t’s Ex. A at 7 (citing Resp’t’s Ex. A, Tab 26, ECF No. 40-

6). Dr. McCusker also referred to the article by Moro et al.,67 which looked at “the mortality data

in the [Vaccine Adverse Event Reporting System (“VAERS”)] dataset.” Id. (citing Resp’t’s Ex.

A, Tab 27, ECF No. 40-7). She wrote that the authors “found no difference in frequency or patterns

of SIDS compared with the expected frequency in the population.” Id.

Dr. Miller testified that there have been “more than several” epidemiological studies which

have looked at the potential role of vaccination in sudden infant death and noted that some have

found an increased incidence and some have not. Tr. 79:19–22. Dr. Miller also acknowledged

that some medical literature reflects no relationship between vaccines and SIDS. Pet’rs’ Ex. 12 at

5 (citing Pet’rs’ Exs. 34,68 3569). However, Dr. Miller opined that “none of the epidemiological

studies on this question have been appropriately done with quality neuropathological

examinations[, which are] the necessary foundation for any quality study.” Id. Dr. Miller wrote

that he has previously “detailed and testified as to the inadequacies of virtually all of the

epidemiological studies” which have considered possible relationships between vaccinations and

SIDS. Pet’rs’ Ex. 37 at 8. He declined to “consider any of [the studies] in detail” in his report,

id., and stated that “[m]ultiple published re-analyses of epidemiological studies which originally

claimed to show no statistically significant relationship between vaccinations and SIDS have

shown major defects in how those studies were constructed and/or analyzed[,]” but he averred that

there “are too many to cite[.]” Pet’rs’ Ex. 12 at 5. Dr. Miller concluded that none of the studies

“are convincing that there is no relationship between vaccinations and SIDS in . . . those [infants]

with defective medullary 5-HT networks,” which is central to his causation theory. Pet’rs’ Ex. 37

at 8. Dr. Miller noted that “no test exists in living children[]” for such a vulnerability, which

limited the ability to study it adequately. Id.

The 2012 paper by Kuhnert et al.70 reexamined three previously published case-control

studies. Resp’t’s Ex. A, Tab 28. The three reexamined studies were: the German study on sudden

infant death (GeSID) by Vennemann et al.; the Confidential Enquiry into Still Births and Deaths

63

Vennemann et al., supra note 60.

64

Kuhnert et al., Reanalyses of Case-control Studies Examining the Temporal Association Between Sudden

Infant Death Syndrome and Vaccination, 30 VACCINE 2349 (2012).

65

Traversa et al., supra note 56.

66

Klára Toro et al., Change in Immunisation Schedule and Sudden Infant Death Syndrome in Hungary, 42

FEMS IMMUNOLOGY AND MED. MICROBIOLOGY 119 (2004).

67

Pedro L. Moro et al., Deaths reported to the Vaccine Adverse Event Reporting System (VAERS), United

States, 1997–2013, 61 VACCINES 980 (2015).

68

Howson et al. (eds.), supra note 57.

69

Stratton et al. (eds.), supra note 58.

70

Kuhnert et al., supra note 64.

28

in Infancy (CESDI) study by Fleming et al.; and the New Zealand Cot Death (NZCD) study by

Mitchell et al. Dr. McCusker described the Kuhnert report as “one of the more definitive studies.”

Tr. 245:25–246:1. Dr. McCusker also noted that the authors of this study found that “the healthy

vaccine effect” discussed in the Vennemann et al. paper “was basically an overcall.” Tr. 249:7–8.

Ultimately, the Kuhnert authors did not find an association between vaccination and sudden infant

death and she acknowledged that “there wasn’t a benefit to vaccination” either. Tr. 249:7–10.

Dr. Miller testified that the Kuhnert et al. study has several issues, including use of non-

vaccinated individuals as controls. Tr. 35114–352:7. He also opined that “when you start

manipulating data over and over again,” as he posited was done in that study, “all sorts of biases

that just distort [the] study” are introduced. Tr. 353:12–13. He opined that based on that

manipulation, he does not view the study as “statistically reliable.” Tr. 353:14–15.

2. Case Reports

Dr. Miller briefly reviewed several articles where there was a temporal correlation found

between vaccination and SIDS. Tr. 77:10–79:1 (discussing Pet’rs’ Exs. 30,71 31,72 3273). He did

not draw any specific conclusions from these studies but stated that the authors in one study were

“looking for a signal . . . [that there was] something happening after vaccination that led to

SIDS…”; in another, authors were “concern[ed] that this new vaccine schedule and this new

combination of vaccines might be dangerous . . .” Tr. 77:19–22, 78:3–10.

Dr. McCusker testified that “a case report is the lowest strength of evidence” in

epidemiology. Tr. 244:7–9. She explained that a case series then groups together five or six case

reports “all with the same or similar story” and suggests that “maybe there’s something going on.”

Tr. 244:11–14. She continued that “in order to really define whether or not there . . . may be an

association that’s greater than just time, you need to design a better study.” Tr. 17–21 Dr.

McCusker testified that the “best study” is a “randomized control trial [where] you enroll all

children that are born and half get vaccinated and the other half don’t[, and then] you follow them

forward and you see if there’s any difference in sudden infant death between the two groups.” Tr.

244:22–245:3. However, such a study cannot be ethically conducted “because there are so many

benefits associated with vaccination.” Tr. 245:4–5. Dr. McCusker noted that cohort studies or

case control studies are the next best options. Tr. 245:8–9.

Dr. McCusker discussed the Moro et al. article that analyzes deaths reported to the VAERS,

including “child reports with available death certificates/autopsy reports [that listed] sudden infant

death syndrome (n = 544 [44%]).” Tr. 251:9–21 (citing Resp’t’s Ex A, Tab 2774 at 1). She testified

that Moro “found that there was no concerning pattern noted amongst the death reports with respect

to vaccinations in SIDS in that the frequency of death in the reported group was not different from

the frequency in the general population.” Tr. 251:25–252:4. Dr. McCusker acknowledged that

71

Kries et al., supra note 56.

72

Zinka et al., supra note 56.

73

Ottaviani et al., supra note 56. Dr. Miller conceded that the Ottovani case report, where an infant died

within an hour or so after vaccination, would fall outside of a timeline that he would consider suspicious of

causation. Tr. 111:6–11.

74

Moro et al., supra note 67.

29

VAERS relies on self-reporting but testified that “since the event in this situation is death, you

would expect it to be more often reported rather than not.” Tr. 252:8–10.

Regarding an article by Zinka et al.,75 Dr. McCusker wrote that “5 autopsies in children

who died within 1–2 days of vaccination showed a significant element of brain oedema [sic]

associated with cellular infiltration of unknown etiology and in one case necrosis of the

cerebellum.” Resp’t’s Ex. A at 6 (citing Pet’rs’ Ex. 31). She explained that “the authors noted

that this would represent a significant increase (13 fold) in SIDS deaths in the local region in

Germany” if the deaths were classified as SIDS. Id. at 6–7. Dr. McCusker explained that the

authors of that study “suggested [the need to conduct] a study to examine, in a larger population,

the frequency of SIDS and hexavalent vaccination.” Id. She noted that a 2007 “large case[-

]control study also from Germany showed no association with vaccination and SIDS.” Id. at 7

(citing Resp’t’s Ex. A, Tab 2476).

D. Proposed Biological Mechanism for a Causal Role of Vaccines in SIDS

As was articulated in Boatmon, a previous SIDS claim in the Program, “[t]he question

arises as whether the cytokine response stimulated by vaccination can have the same effect as a

mild or trivial infection in a baby who presumably has a defect in the medullary 5-HT system.”

Boatmon, 2017 WL 3432329, at *12.

Dr. Miller began to answer this question by concluding that “the same mechanisms can be

presumed to be involved[]” in vaccination-related SIDS as are involved in infection-related SIDS.

Pet’rs’ Ex. 38 at 4. He explained that vaccinations “provoke a reaction from the innate immune

system, just as if they were an actual infection.” Id. Dr. Miller emphasized that vaccinations

“provoke cytokine production[;] that’s what they’re designed to do.” Tr. 85:6–7. He noted that

“it’s irrelevant” in terms of the type of vaccine received, but he explained that data suggest that

“[i]t may be relevant in terms of how many vaccines” are received, because there may be a “more

vigorous . . . cytokine response” when more vaccines are added. Tr. 119:25–120:6. Dr. Miller

stressed that a minor viral URI “elicit[s] the same cytokine response as a vaccination.” Pet’rs’ Ex.

12 at 5 (citing Pet’rs’ Ex. 29,77 ECF No. 92-7).

Dr. Miller testified that when the immune system detects “what it perceives as a foreign

antigen,” multiple cytokines are produced. Tr. 67:23–68:1. Dr. Miller explained that therefore

“vaccinations lead, inevitably and as a natural event, to the production of circulating cytokines

including IL[-]2, IL-6, and IL[-1β] (and likely others)[.]” Pet’rs’ Ex. 37 at 6. He explained that

“these cytokines can cross from the blood into the brain, where they can have synaptic modulatory

effects which produce multiple physiological changes, including fever and suppression of

medullary 5-HT activity.” Id. Dr. Miller emphasized that “in an infant with an already defective

5[-H]T system,” the suppression of medullary 5-HT activity caused by those cytokines “may be

enough in any given situation of apnea or hypercapnia to produce a failure of arousal and increased

respiration, leading then to death.” Id. at 6–7.

75

Zinka et al., supra note 56.

76

Vennemann et al., supra note 60.

77

Ashild Vege & Torleiv Ole Rognum, Sudden infant death syndrome, infection and inflammatory

responses, 42 FEMS IMMUNOLOGY MED. MICROBIOLOGY 3 (2004).

30

Dr. Miller wrote that one recent study on the “potential relationships between SIDS, sleep,

and infantile febrile seizures has re-emphasized the importance of the defects in the medullary

serotoninergic system and network[.]” Pet’rs’ Ex. 12 at 5 (citing Pet’rs’ Ex. 36,78 ECF No. 93-2).

That study looked at “factors which interact with this underlying defect” to produce either SIDS

or sudden death after a seizure, including “fever, high body temperature from environmental

causes, maternal smoking, prematurity, male sex, [URIs], and sleep position[.]” Id. Dr. Miller

noted that the “study does not mention, and does not deal with, the issue of vaccinations,” but he

opined that “it is clear . . . that the elevations in cytokines produced by vaccinations act through

the same pathways, and often the same molecules, as several of the quoted risk factors, especially

infections.” Id. Therefore, Dr. Miller opined that it is “probable that vaccinations elicit cytokine

production which can suppress arousal and breathing responses, and that this suppression can cross

a fatal threshold when the infant in question is vulnerable because of an already defective

medullary serotonin system.” Id.

1. Evidence Regarding Cytokines in the Brain

Dr. Miller acknowledged the role of some cytokines as neuromodulators but argued that

cytokines “can get to [parts of the brain] directly by some mechanisms or may act at the interface

of the brain with the rest of the world, which is called the blood-brain barrier.” Tr. at 56:2–6. Dr.

Miller then stated that cytokines IL-1β and IL-6 have “been found to be elevated in post-mortem

specimens from SIDS patients.” Pet’rs’ Ex. 12 at 4 (citing Pet’rs’ Exs. 25,79 26,80 27,81 ECF Nos.

92-3, 92-4, 92-5).

Dr. McCusker responded that cytokines “that are found in the CNS are more likely than

not intrinsically produced by the CNS, and [are] not coming from the peripheral functioning

immune system.” Tr. 334:19–22. She explained that “normal brains under normal physiologic

conditions produce cytokines,” which are referred to as neurokines “because they are operating as

signaling molecules from neuron to neuron.” Tr. 195:18–23. Dr. McCusker wrote that cytokines

are released by microglial cells in the brain, and production can increase when those cells are

exposed to psychological or other stressors, such as acute brain injury or neurodegeneration.

Resp’t’s Ex. A at 4 (citing Resp’t’s Ex. A, Tabs 13,82 15,83 1684). Dr. McCusker testified that “if

our bodies would allow cytokines to sort of flood into the CNS, we would end up with a lot of

trouble.” Tr. 336:8–10.

78

Toke Hoppenbrouwers, Sudden Infant Death Syndrome, Sleep, and Seizures, 30 J. of Child Neurology

904 (2015).

79

Hazim Kadhim et al., Distinct Cytokine Profile in SIDS Brain. A Common Denominator in a

Multifactorial Syndrome?, 61 NEUROLOGY 1256 (2003).

80

Rognum et al., supra note 44.

81

Hazim Kadhim et al., Interleukin-2 as a Neuromodulator Possibly Implicated in the Physiopathology of

Sudden Infant Death Syndrome, 480 NEUROSCIENCE LETTERS 122 (2010).

82

Noga Ron-Harel et al., Brain Homeostasis is Maintained by “Danger” Signals Stimulating a Supportive

Immune Response Within the Brain’s Borders, 25 BRAIN, BEHAVIOR, AND IMMUNITY 1036 (2011).

83

Hugo O. Besedovsky & Adrianna del Rey, Central and Peripheral Cytokines Mediate Immune-brain

Connectivity, 36 NEUROCHEMICAL RES. 1 (2011).

84

Yun Su et al., Predator Exposure-induced Cerebral Interleukins are Modulated Heterogeneously by

Behavioral Asymmetry, 135 IMMUNOLOGY LETTERS 158 (2011).

31

i. Cytokines Constitutively Expressed in the Brain

Dr. Miller described how cytokines in the brain “have depressive effects on the serotonin

system in the medulla and can suppress whatever arousal mechanisms might remain in an infant

with a maldeveloped or damaged medulla.” Pet’rs’ Ex. 12 at 4.

Dr. McCusker pointed out that “cytokines have also been shown to be constitutively

expressed by cells of the brain and play distinct roles in normal brain homeostasis[.]” Resp’t’s Ex.

A at 4. She opined that those cytokines “are not considered ‘proinflammatory,’” like those in the

peripheral immune system. Id. She continued that “[n]ormal brain function requires [the] release

of cytokines[,]” which she explained “play essential roles in neuroprotection and

neuromodulation.” Id. (citing Resp’t’s Ex. A, Tab 14,85 ECF No. 39-4). Citing an article authored

by Dr. Kinney, Dr. McCusker opined that “the presence of the increased cytokines [in the brain of

infants who died of SIDS] is considered to occur in response to the inciting event of

hypoxia/hypercapnia[,] rather than represent[ing] an element etiologically linked to the respiratory

failure in the vulnerable child.” Id. at 5.

In her reports, Dr. McCusker also wrote that “there is significant evidence in the medical

literature that cytokines play important roles in both maint[aining] homeostasis in the brain and in

alerting the system to potential danger.” Id. She explained that “in children experiencing a

premortal event, cytokines involved in neuroprotection would be released in an attempt to ‘save’

the system.” Id. at 5–6. Therefore, she opined that the “differences in IL[-]6 and IL[-]6R levels

seen in SIDS children are likely a marker of the acute brain injury prior to death[,] and the presence

of cytokines in the brain of SID[S] patients represent[s] normal physiologic responses to the

stressors associated with their terminal events.” Id. at 6.

Dr. McCusker agreed with Respondent’s counsel that the articles filed by Petitioners “look

at more the expression of a cytokine as opposed to the effect of the cytokine.” Tr. 242:14–18. She

reiterated that the function of cytokines in the CNS is different than their function in the peripheral

body. Tr. 242:23–25. She testified that IL-1β is involved in sleep and arousal cycles and that

without IL-6, “you don’t lay down long-term memories properly.” Tr. 242:19–23.

Dr. McCusker admitted that she could not answer a question regarding how many

cytokines would be necessary to affect the brain of an infant with a defect in the medullary

serotonergic network, as opposed to a normal brain. Tr. 333:16–21. Dr. McCusker testified that

she was assuming that the brain of an infant who dies from SIDS is able to properly regulate

cytokines, as a baseline. Tr. 336:18–20. She testified that she has “no evidence that says that

[such brains] operate differently, with the exception that the receptor changes that are found in the

IL-6 system do[] suggest that they are less sensitive to the presence of the cytokines.” Tr. 336:22–

337:1. Dr. McCusker testified that this type of intrinsic defect would work against the idea of

cytokines overwhelming the brain, because such a brain would be less sensitive to the presence of

cytokines. Tr. 337:2–9.

85

Shamsudheen Moidunny et al., Interleukin-6-type Cytokines in Neuroprotection and Neuromodulation:

Oncostatin M, but not Leukemia Inhibitory Factor, Requires Neuronal Adenosine A1 Receptor Function,

114 J. OF NEUROCHEMISTRY 1667 (2010).

32

ii. Circulating Cytokines

Dr. McCusker testified that a person does not “have massive amounts of circulating

cytokines, except in the case of a cytokine storm.” Tr. 192:24–193:1. Cytokine storm is “the

classic example of cytokines going rogue,” where the body experiences “uncontrolled cytokine

release.” Tr. 189:16–20. Dr. McCusker testified that this results in “multi-system effects,” such

as “kidney shutdown, . . . liver failure, . . . failure of the bone marrow to produce white blood cells

and red blood cells[,] or pulmonary compromise because of pulmonary inflammation.” Tr. 190:2–

8. However, Dr. McCusker testified that “even in a cytokine storm, the effects of this massive

release of cytokines on the CNS is actually much less than in the rest of the body.” Tr. 190:9–11.

She testified that “most of the effects of this massive release of cytokines are seen in the systemic

immune system, systemic body, and not as much in the CNS.” Tr. 190:16–18. Dr. McCusker

explained that “people can die of cytokine storm,” and “over three or four days you see their

immune systems just go crazy and they’ll die within a week or two if you can’t shut down the

system.” Tr. 109:19–24.

Dr. McCusker contrasted the multisystem failure that occurs during a cytokine storm to a

“normal coordinated immune response.” Tr. 190:25–191:1. Dr. McCusker wrote that cytokine

production in the body is subject to “diurnal variations” but acknowledged that “[v]accination is

predicted to activate immune responses in part through cytokine up[-]regulation.” Resp’t’s Ex. A

at 4 (citing Resp’t’s Ex. A, Tab 10,86 ECF No. 38-10). During this response, Dr. McCusker

continued, the peripheral immune system produces and releases cytokines, “but there is no

evidence to suggest that the levels are sufficient to influence the brain . . . .” Id. She testified that

cytokines “have a very short half[-]life” and do not “live very long from the time that they’re

released.” Tr. 192:3–5. Dr. McCusker explained that they “are rapidly either taken up by a cell

which has a receptor[] and/or they are degraded by protease in the serum.” Tr. 192:6–8.

Additionally, Dr. McCusker testified that “as cytokines start to go up, so does the production of

the off switches,” or the “decoy receptor[s,]” which she explained “basically pull[] away and

trap[]” the cytokines “so that you do not get excessive inflammation.” Tr. 192:9–18. Dr.

McCusker concluded that “to get from the thigh or the draining lymph node and to put those

cytokines as implicated in a death in the CNS is just biologically not tenable, given our current

understanding of cytokine biology.” Tr. 335:2–6.

iii. Crossing the Blood-Brain Barrier

Dr. Miller testified that “there are at least two ways, and maybe more,” that cytokines can

enter the brain. Tr. 112:21–24. First, he explained that “[t]here are areas in the brain which lack

a blood-brain barrier normally,” such that “circulating molecules can cross into the brain just by

diffusion.” Tr. 112:24–113:8. Alternatively, “there is an active transport system” where cytokines

in the blood “come up against brain endothelial cells and can be grabbed and transported into the

central nervous system across the blood-brain barrier.” Tr. 113:12–16. He testified that “it’s an

energy-dependent process and it’s a saturable process.” Tr. 113:16–17. Dr. Miller described a

paper by Banks et al.,87 which “demonstrated that radiolabeled IL[-1α which was] injected

86

Aroon D. Hingorani et al., Acute Systemic Inflammation Impairs Endothelium-dependent Dilatation in

Humans, 102 CIRCULATION 994 (2000).

87

Banks et al., supra note 38.

33

intravenously crossed into the brain, with different concentrations in different neuroanatomic

structures[.]” Pet’rs’ Ex. 37 at 8 (citing Pet’rs’ Ex. 37, Tab M, ECF No. 93-9). He noted that the

“kinetics [were] indicative of a transport mechanism across the [blood-brain barrier].” Id. Dr.

Miller testified that such a system “is well documented now to exist” but acknowledged that “[w]e

don’t know a whole lot about that system.” Tr. 113:25–114:2. Dr. Miller noted that the process

of active transport does not distribute cytokines everywhere and it is “probably . . . somewhat

selective so that different places in the brain have receptors and pumps for different cytokines.”

Tr. 114:5–7. He noted that “the medulla is probably one of the places” where the process works.

Tr. 114:3–4. Dr. Miller testified that the transport process is not dependent upon inflammation or

elevated temperature. Tr. 114:8–10. He further noted that researchers believe “that the fever

comes about only after cytokines have reached the hypothalamus.” Tr. 114:12–14.

Dr. McCusker explained that there is “tight coordination between the peripheral system

and the brain system.” Tr. 195:4–7 (discussing Resp’t’s Ex. A, Tab 1388). She testified that the

blood-brain barrier was once thought to be essentially impermeable, but it is now understood that

it “is a very metabolically active site, which allows for [the] regulation of messaging from . . .

outside of the CNS, the rest of the body, and the brain.” Tr. 193:19–194:4. However, Dr.

McCusker emphasized that “this messaging is not willy-nilly[;] it’s also regulated and tightly

controlled so that messages that are being passed from the periphery into the brain . . . actually

follow[] a path to signal a specific event.” Tr. 194:5–10. She emphasized that cytokines are not

“flooding into the brain and going everywhere;” instead, there are “specific pathways that are taken

to signal in the CNS.” Tr. 194:13–16. Dr. McCusker noted that with every known mechanism by

which cytokines can cross the blood-brain barrier, they do not “just flood into the brain.” Tr.

327:19–20. She testified that the cytokines may require active transport, whereby specific

receptors would bind with certain cytokines at the blood-brain barrier. Tr. 328:6–11.

Dr. Miller clarified that he does not believe that the brain “gets flooded with cytokines

under most circumstances,” including “in the circumstances that lead to SIDS.” Tr. 367:23–25.

Instead, Dr. Miller explained that, in his opinion, “very small quantities can tip a balance” in the

brain of a vulnerable infant. Tr. 368:11–17. He noted that a vulnerable infant’s 5-HT system is

“already in peril” and therefore, amounts that may not otherwise cause a problem in the brain “can

be enough to tip the balance over and lead to catastrophe.” Tr. 368:15–17.

Dr. Miller testified that there are “just no data” on how long IL-1β can stay active in the

brain once transported across the blood-brain barrier. Tr. 370:18–21. He explained that “it’s an

experiment that would be impossible to do in humans, for ethical reasons,” and that “it would be

very difficult to do it in most animal models, because we don’t have a really good animal model

where we can predict there’s going to be SIDS.” Tr. 371:8–14.

2. Evidence Regarding Whether Cytokines Can Have an Effect on the Medullary

Serotonin System

Dr. Miller explained that studies look at the effects of one or two cytokines at a time

“because the data will be too confusing” if researchers attempt to “look at a soup of multiple

cytokines.” Tr. 68:1–4. Dr. Miller testified that the published literature primarily considers IL-1,

88

Ron-Harel et al., supra note 82.

34

IL-6, and TNF. Tr. 68:4–6. He described experiments which have shown that certain cytokines,

especially IL-1β and IL-6, “have depressive effects on the serotonin system in the medulla and can

suppress whatever arousal mechanisms might remain in an infant with a maldeveloped or damaged

medulla.” Pet’rs’ Ex. 12 at 4 (citing Pet’rs’ Exs. 22,89 23,90 2491); see also Tr. 72:10–16. As noted

previously, serotonin neurons “mediate arousal from apnea.” Tr. 76:22. Therefore, Dr. Miller

explained, when IL-1β is introduced, “recovery from apnea, sensing elevated levels of carbon

dioxide in the blood, [and] producing arousal and gasping respirations are all suppressed” when

compared with situations where the cytokine is not present. Tr. 73:8–14.

Dr. Miller noted that there are not very good animal models for SIDS in general. Tr.

103:16–18. He emphasized that the piglets in the Stoltenberg and Frøen studies, discussed below,

were “normal,” whereas “[a]n animal model of SIDS would hopefully be a spontaneous model in

which you have some strain of animals which predictably die at a certain age of what appears to

be from a full pathologic examination at death to be SIDS.”92 Tr. 103:19–104:10. He explained

that the studies involving piglets looked “at the question of recovery from apnea” and “whether

those cytokines, [IL-1β] in particular, suppress the serotonin system.” Tr. 103:23–104:1.

Although he opined that the studies “can have applicability to understanding what may be

happening in SIDS,” he explained that they are “not . . . animal model[s] of SIDS, per se.” Tr.

104:4

Dr. McCusker concluded that the three animal studies and three post mortem studies cited

by Petitioners’ expert “do not show evidence for the role of cytokines, either those constitutively

expressed in the brain or those found in the peripheral immune system, in suppressing the arousal

mechanisms of the ‘maldeveloped or damaged medulla’ . . . as claimed by Petitioners’ [e]xpert.”

Resp’t’s Ex. A at 8. Dr. McCusker repeatedly emphasized that “the dose required to induce

[apnea] in the newborn piglets was supra-therapeutic.” Resp’t’s Ex. E at 7. Dr. McCusker noted

that the Stoltenberg et al. study and “the follow up work” by Frøen et al. showed “the effect of

supratherapeutic doses of IL[-]1β was detectable only in the neonatal animals and did not occur

in animals older than 10–15 days.” Resp’t’s Ex. A at 7 (citing Pet’rs’ Exs. 22,93 2394) (emphasis

in original). She also emphasized that the authors of the Frøen et al. study “noted that similar

experiments using IL[-]6 had no effect on respiration.” Id.

89

Stoltenberg et al., supra note 39.

90

Frøen et al., supra note 40.

91

Brambilla et al., supra note 41.

92

Dr. Miller noted that “[p]igs mature far faster than human infants and so do their brains.” Pet’rs’ 37 at

8. Therefore, “[n]eonatal piglets may represent a reasonable model for human infants at the ages at which

SIDS is observed[.]” Id. He emphasized that “the brains of piglets aged 13–14 days are explicitly

comparable to those of human infants aged 2–4 months.” Id. Dr. Miller conceded that, “like all animal

models[,] there are aspects of the model system that more or less closely mimic the human disease[,]

whereas other aspects [d]o not.” Id. However, the purpose of using very young piglets in the Frøen and

Stoltenberg studies “was to find an animal model [of] something like a 2[-]month[-]old human[.]” Id. Dr.

McCusker testified that “you could argue back and forth” about whether a piglet aged six to ten days is

comparable to a two-to-four-month old infant. Tr. 326:2–6.

93

Stoltenberg et al., supra note 39.

94

Frøen et al., supra note 40.

35

Dr. McCusker wrote in her report that the “literature demonstrates that cytokines IL[-]1β,

IL[-]6 and TNF[-]α play important roles in the architecture of sleep and arousal and are

constitutively expressed in the brain.” Id. at 8. She wrote that “[s]ystemic cytokine release can

induce fever and changes in sleep patterns.” Id. However, Dr. McCusker opined that the changes

caused by cytokines “affect the development of REM sleep resulting in greater frequency of

arousal found in NREM sleep.” Id. Therefore, Dr. McCusker argued that “increases in IL[-]1β

would affect sleep architecture to decrease deep REM sleep and increase NREM associated with

more frequent and easy arousal.” Id. In other words, she opined that the “hypothesis that systemic

cytokine[] release reduces the capacity for arousal in at risk infants[,] leading to SIDS[,]” is

unsupported. Id.

Dr. McCusker argued that if Dr. Miller’s theory that “vaccine[s] induced significant

increases in the cytokine IL[-1]β” in J.J.’s brain were true, “the resulting effect would most likely

have been increased arousal.” Id. at 5. She wrote that although “low levels [of IL-1β] may promote

NREM sleep, high levels have been shown to promote arousal.” Id. (citing Pet’rs’ Ex. 2495). She

also wrote that “[e]vidence suggests that the central functions of the cytokines IL[-]1β, IL[-]6 and

TNF[-]α at times of infection are to promote fever and to affect the sleep architecture by increasing

NREM versus REM sleep resulting in more disturbed sleep with more frequent arousal[,] while

permitting the maintenance of increased body temperature.” Resp’t’s Ex. A at 5 (citing Resp’t’s

Ex. A, Tabs 19,96 20,97 2198). Dr. McCusker wrote that “cytokine activation would be protective

. . . rather than pathologically linked to failure to arouse.” Resp’t’s Ex. A at 5 (citing Resp’t’s Ex.

A, Tab 17,99 ECF No. 39-7). She wrote that this is because “immune stimulation results in

increased in TPH2, which increases 5-HT and augment[s] the protective arousal mechanism.” Id.

i. Stoltenberg et al. – Pet’rs’ Ex. 22100

Dr. Miller testified that in the Stoltenberg et al. study, apnea was induced in the piglets and

the study looked at how quickly they recovered. Tr. 64:6–8. Dr. Miller testified that some of the

piglets were injected with IL-1β, either in the blood or into the cerebrospinal fluid, and those

piglets’ recovery times were compared with piglets which were “not manipulated with any other

drugs or any other chemicals” other than those inducing the apnea. Tr. 64:8–15. Dr. Miller

testified that the IL-1β “produce[d] delayed recovery and impaired recovery from apnea.” Tr.

64:13–15.

Dr. McCusker emphasized that when this study was conducted in 1994, the authors

“thought that the blood-brain barrier was impermeable and that any presence of cytokines in the

brain must mean that there was an infection or an insult to the brain.” Tr. 215:10–14. Therefore,

95

Brambilla et al., supra note 41.

96

Clinton et al., supra note 45.

97

Gamaldo et al., supra note 46.

98

Rohleder et al., supra note 47.

99

Guo-Lin Chen & Gregory M. Miller, Advances in Tryptophan Hydroxylase-2 Gene Expression

Regulation: New Insights into Serotonin-stress Interaction and Clinical Implications, 159B AM. J. MED.

GENETICS NEUROPSYCHIATRY GENETICS 152 (2012).

100

Stoltenberg et al., supra note 39.

36

she opined that the authors “were looking for why [they were] finding these cytokines in the CNS.”

Tr. 215:17–18.

Dr. McCusker acknowledged that the piglets’ apnea events were prolonged but noted that

“they really needed to use high doses” of IL-1β to find results, also referring to them as “massive

doses.” Tr. 215:21–216:16. She testified that “doses are important with cytokines.” Tr. 216:6–7.

Dr. McCusker testified that even in a cytokine storm, “which is the worst release of cytokines that

we can think of,” the levels of cytokines are lower than what was administered to the piglets in the

study. Tr. 216:8–11. Therefore, she opined, the levels are “way over what you would see in a

vaccine response[] and/or any kind of normal routine infection response.” Tr. 216:13–15.

Additionally, Dr. McCusker opined that the authors “had to use really young piglets,

because they found that if the piglets were older than ten days, they no longer could induce this

[apnea] event.” Tr. 216:17–20. Dr. McCusker opined that a 10-day-old piglet, depending on

which literature one looks at, approximately equates to an infant who is “just under two months”

old. Tr. 217:7–11. Therefore, she criticized the study because it was not “even dealing with piglets

in the risk time that you would see for sudden infant death.” Tr. 217:18–20.

Dr. McCusker opined that “if we did the exact same thing with insulin,” or if one injected

“1,000 times the dose” of insulin that normally circulates, “you would kill the animal.” Tr. 216:23–

217:1. Therefore, Dr. McCusker opined that “to say it’s physiologically relevant is problematic.”

Tr. 217:2–3. She testified that the authors “actually say that in their article. It’s not like they’re

hiding anything.” Tr. 217:3–4.

ii. Frøen et al. – Pet’rs’ Ex. 23101

Dr. Miller also testified about the Frøen et al. study. Tr. 64:16–65:4. He explained that

the purpose of that study was to look at the effects of nicotine and IL-1β on the piglets’ recovery

from apnea episodes. Tr. 64:20–25. Dr. Miller testified that the study’s authors found that IL-1β

“inhibited recovery” and that if nicotine and IL-1β were both present, “it was even worse.” Tr.

65:1–4.

Dr. McCusker testified that the authors of the Frøen et al. study “managed to dial back the

dose [of IL-1β] a little bit,” when compared with the Stoltenberg et al. study. Tr. 218:5–6. She

testified that although the dose was “cut . . . in half . . . it’s still over 1,000 times more [than] what

you see in the blood.” Tr. 218:6–7. Therefore, she opined that “they still needed a ton of cytokine

in order to see any effect.” Tr. 218:15–16. Additionally, Dr. McCusker noted that the authors

“tried to do the same thing with IL-6,” because “IL-6 is the [cytokine] that[ is] really found in the

brain of [infants who die from] SIDS,” but that the authors could not “find any effect of giving

high dose of IL-6 on this model.” Tr. 218:14–23.

iii. Brambilla et al. – Pet’rs’ Ex. 24102

101

Frøen et al., supra note 40.

102

Brambilla et al., supra note 41.

37

Dr. Miller explained that the authors of the Brambilla et al. study used “brain slices,” or

“very thin slices of living tissue,” from rat brains to study the effect of IL-1β on the serotonin

system. Tr. 74:8–15. The tissue was kept in a bath to keep it alive, and the activity of the cells

was monitored. Tr. 74:11–14. Dr. Miller testified that the authors “took the relevant areas of

serotonergic neurons in the brain stem of these rats” and added IL-1β to the bath solution. Tr.

74:16–19. When that happened, Dr. Miller testified, the activity of the serotonin system was

suppressed, whereas the activity of gamma-aminobutyric acid (“GABA”),103 “which is the

inhibitory system that kind of interacts with the serotonin system,” increased. Tr. 74:20–24.

Therefore, Dr. Miller testified, “the net effect was even more suppression.” Tr. 74:24–25. He

noted that although arousal cannot be observed in brain slices, “these are the neurons that mediate

arousal,” so the inference is that in a whole living animal “there would have been less arousal.”

Tr. 75:2–6.

Dr. McCusker testified that “the relative significance [of the findings in the Brambilla et

al. study] is not clear, because of the massive amounts of IL-1[β] that was required” to have an

effect on the studied brains. Tr. 226:23–227:1. She noted that the article admits that “[t]he precise

effects of IL-1[β] on vigilant states are complex[] and depend on dose and timing administration.”

Tr. 227:2–7; see Pet’rs’ Ex. 24 at 6. Dr. McCusker testified that IL-1β, when injected

intracerebroventricularly,104 “increases NREM sleep across an effective dose range of 2.5 to 10

nanograms,” which is “significantly” above the picogram level. Tr. 227:7–13. She also testified

that “doses greater than 10 nanograms, when injected intracerebroventricularly, disrupt NREM

sleep and promote arousal.” Tr. 227:11–13.

Dr. McCusker testified that the Brambilla study used “supratherapeutic doses” and

analogized that “[i]nsulin in these level differences would kill you.” Tr. 227:14–17. She

emphasized that “a constant dose of 25ng/ml of IL[-]1β was required to demonstrate any effects

on the neurons[]” and argued that “there is no evidence that extremely high levels of IL[-]1β

needed to suppress the in vitro GABAnergic responses are achieved via peripheral vaccination.”

Resp’t’s Ex. A at 8. In contrast, Dr. McCusker wrote that “only picogram amounts of IL[-]6 w[ere]

detectable and IL[-]1β was undetectable in the peripheral circulation[]” for children after

vaccination in the Kashiwagi et al. study. Id.

Although Dr. Miller acknowledged that the Brambilla et al. study used 25,000 picograms

of IL-1β per millimeter, he noted that the amount was “potentially . . . diluted by a lot” due to the

culture system used to bathe the brain slices in that study, “which is a continuously running bath.”

Tr. 344:1–6. He noted that the amounts measured in the blood of vaccinated subjects studied in

the Kashigawa et al. study were “on the same order of magnitude,” and “certainly not thousands

of times different,” despite the lack of IL-1β data in those subjects. Tr. 346:19–347:1.

103

Serotonergic dorsal raphe nucleus neurons are inhibited by GABA. Pet’rs’ Ex. 24 at 1. “GABA plays

a crucial role in shaping the state-dependent firing and neurotransmitter release of serotonergic neurons,

which are highly active during wakefulness, reduce their activity during NREM sleep and are almost silent

during REM sleep.” Id. at 1–2.

104

Intracerebroventricular is within the ventricles of the brain. Dorlands at 953.

38

iv. Kadhim et al. – Pet’rs’ Exs. 25105 and 27106 and Resp’t’s Ex. H107

Dr. Miller discussed a 2003 study authored by Kadhim et al., which looked at cytokines in

the brain of infants who died from SIDS. Tr. 58:12–15 (discussing Kadhim et al., supra note 79).

He testified that IL-1β “was found in the arcuate nuclei, [which is] the same nuclei that can

sometimes be deficient in SIDS babies, and in the . . . dorsal vagal nuclei.” Tr. 58:24–59:1. Dr.

Miller testified that this “elevated immune activity” was not found in the brains of infants who

died from other causes. Tr. 59:11–14.

Dr. McCusker emphasized that in Table 1 of that study, “cytokine staining was elevated in

the . . . brains of children who had SIDS and had evidence of infection, but also . . . in children

who had SIDS without evidence of infection.” Tr. 213:4–8. Based on that data, Dr. McCusker

opined that IL-1β “is unregulated in the brains of SIDS [infants], regardless of a history of

infection.” Tr. 213:9–11. She testified that “if, as Dr. Miller is suggesting . . . with infection and/or

vaccination, the increase of cytokines isn’t is [sic] coming from . . . the signaling in the peripheral

immune system, you would expect to see a difference based on whether or not [the infant] . . . had

evidence of infection.” Tr. 213:13–18. Dr. McCusker emphasized that there is no difference

between the two in the chart. Tr. 213:18–19. Therefore, in her opinion, the data shows that

“cytokines [ and] neurokines, are constitutively expressed in brains.” Tr. 213: 20–22.

Furthermore, she opined that the cytokines are “a response marker,” increased in response to the

stressor which leads to the terminal event, “as opposed to a causative marker.” Tr. 213:24–214:3.

Therefore, Dr. McCusker opined that the Kadhim et al. study supports the IL-1β increase, “but it

doesn’t support that a peripheral immune response can induce that increase.” Tr. 214:13–15. Dr.

McCusker testified that IL-1β may be up-regulated in the brain of infants who died from SIDS

because “there is disordered sleep and respiration, and the body is trying to reorder it.” Tr. 230:9–

13. She testified that such a hypothesis is “as reasonable . . . as anything, based on this series of

articles.” Tr. 230:13–14.

Dr. McCusker wrote that the 2010 Kadhim et al. article compared IL-2 levels in the brains

of infants who died from SIDS to the brains of infants who died of other causes, and “showed no

difference in expression in” IL-2. Resp’t’s Ex. A at 8 (citing Kadhim et al., supra note 71). She

wrote that the authors of that study “hypothesize that IL[-]2, like the cytokines IL[-]1β, TNF[-]α

and IL[-]6, may be expressed in normally functioning brains of infants.” Id. Dr. McCusker

testified that IL-2 was increased in the brain of infants who died from SIDS but criticized that the

Kadhim et al. article does not “talk about what the cytokine is doing there, or whether it’s

implicated [in SIDS]. . . [or] . . . try and draw . . . a line that says it’s doing anything damaging in

the CNS following vaccin[ation], is just not there.” Tr. 242:5–12.

105

Kadhim et al., supra note 79.

106

Kadhim et al., supra note 81.

107

Hazim Kadhim et al., Selective Expression of a Neuromodulatory Cytokine (IL-2) in Specific Brainstem

Neurovegetative Centers: A Possible Final Common Neuro-molecular Pathway in Dying Patients, 78

MEDICAL HYPOTHESES 793 (2012).

39

During her testimony, Dr. McCusker also discussed a third article authored by Kadhim. Tr. 236:2–

8.108 She explained that this 2012 Kadhim study “actually looked at the brains of adults who died

and found the exact same signaling that they found in the SIDS brains,” which suggested that the

signaling is “probably related to sort of what’s happening in a terminal brain event as opposed to

being specific for SIDS.” Tr. 236:3–8.

v. Rognum et al. – Pet’rs’ Ex. 26109

Dr. Miller discussed the Rognum et al. study, entered as Petitioners’ Exhibit 26. Tr. 59:15–

16. He explained that the authors “were testing the hypothesis that the IL-6 receptors and the

gp130 expression would be altered in the medulla in SIDS patients.” Tr. 60:4–7. He testified that

the authors found increased amounts of IL-6 receptors in the arcuate nucleus in infants who died

from SIDS when compared with those infants in the control group. Tr. 60:8–12. The authors

concluded that “aberrant interactions in SIDS infants between IL-6 and the arcuate nucleus may

contribute to impaired responses to hypercapnia generated by infection combined with

rebreathing.” Pet’rs’ Ex. 26 at 9. Dr. Miller concluded that “it means that in SIDS babies who

have defects in those nuclei, there is a change in the expression of the cytokine, or in the binding

of this cytokine, and its receptors, compared to . . . normal infants who have died of something

else.” Tr. 61:22–62:3.

Dr. McCusker also discussed the Rognum et al. study. Dr. McCusker wrote that the authors

of that study “postulate from [their] data that the role of infection in SIDS is likely due to mild

upper respiratory tract infections influencing respiration resulting in increased CO2 levels in

infants rather than the influence of the infection on brain cytokine levels.” Resp’t’s Ex. A at 8

(emphasis in original).110 Dr. McCusker testified that the Rognum et al. study was done because

there was conflicting literature on whether IL-6 was associated with the brain of infants who died

from SIDS. Tr. 231:5–12. She noted that “part of the theory for the presence of the IL-6 was this

idea that mild infection[s] release[] cytokines, and so maybe that’s why there’s more IL-6 in the

brains of SIDS patients with infection.” Tr. 231:13–17.

Dr. McCusker testified that the authors “compared children whose final diagnosis was

SIDS to a control group, a couple of control groups, and within the SIDS diagnosis, they looked

at children who ha[d] evidence of mild infection versus those that did not.” Tr. 231:19–23. She

testified that the authors found the presence of infection made “no difference in the IL-6 levels” in

the brain of infants who died of SIDS, “suggesting that IL-6 in those children’s brains was not

there specifically because of the infection.” Tr. 231:24–232:3. More importantly, Dr. McCusker

explained that gp130 is a “key co-factor, a key protein that needs to be there . . . functioning, in

108

Petitioners objected to the introduction of this article, which Dr. McCusker stated that she did not rely

upon while writing her reports but found “later on” while “scanning the literature for new articles” in an

effort to keep up to date for future testimony in Vaccine Program cases. Tr. 237:5–19. Dr. Miller

acknowledged that the article “came up in another case in which [he] testified in December,” so he is

“loosely aware” of it but had not “had a chance to review it in detail.” Tr. 238:6–8. Dr. Miller opined that

the article was “sort of sprung on us in December.” Tr. 238:9.

109

Rognum et al., supra note 44.

110

But the abstract of this study says “[m]ild infection may trigger sudden death in the vulnerable infant by

cytokine interactions with a compromised medullary serotonergic (5HT) system[.]” Pet’rs’ Ex. 26 at 1.

40

order for that signal to go through.” Tr. 232:17–19. The authors noted in the study that “[i]t is

essential that gp130 be present on the cell membrane for IL-6 to elicit neuronal responses.” Pet’rs’

Ex. 26 at 8. Dr. McCusker put this relationship in context and explained that “there was a

disconnect between the IL-6 receptor expression and the gp130 expression” in the brain of infants

who died from SIDS, “such that the signaling was going to be dysregulated, meaning that if the

IL-6 bound to the IL-6 receptor, there was no gp130 to transmit the signal on.” Tr. 232:20–25.

Therefore, if infection and vaccination “can flood the brain with IL-6,” then the brain cells would

be “unable to respond to it [and] it would be as if it didn’t exist there, because it can’t signal

through IL-6.” Tr. 233:1–6. She explained that “the IL-6 might be there because the brain is

producing it in response to the stressor that it’s feeling as it’s dying, and the receptors that are

supposed to respond to it can’t[,] so it keeps producing more because that’s the right response to

IL-6, but the receptors can’t hear it.” Tr. 233:1–617–25.

Although Dr. McCusker acknowledged that the “hypothesis of the paper” was that SIDS

may be triggered by mild infections due to cytokine interaction with a compromised medullary

serotonergic system, she testified that she disagreed with such a conclusion. Tr. 267:10–18. Dr.

McCusker opined that the conclusion of the paper is that IL-6 “may be related to the response to

the infection or the stressor that the baby is undergoing, and not be related to actually a mechanistic

causality association.” Tr. 268:7–10. Dr. McCusker testified that the authors do not “think that

their thesis at the beginning of [the paper] is supported by the data that they showed.” Tr. 270:21–

23.

3. Evidence Regarding Whether Cytokines Are Produced in Response to

Vaccination

Dr. Miller testified that cytokines “can start to appear pretty rapidly” after vaccination. Tr.

83:18. More specifically, he testified that they can appear within “just a few hours.” Tr. 83:18–

19. He noted that the literature has generally considered cytokine levels 24 or more hours after

vaccination, but that “certainly 12 hours is enough for them to be detectable.” Tr. 83:19–23.

Dr. McCusker wrote that when an immune response is initiated, “cytokines are often

released in the local environment and are part of the initial cascade of inflammation at the site of

infection or trauma.” Resp’t’s Ex. A at 3–4. She opined that “[m]ost cytokine events occur locally

and do not generate significant systemic signaling.” Id. at 3. Instead, she opined that they “are

usually transient and tightly regulated.” Id. at 4 (citing Resp’t’s Ex. A, Tab 10111). However, she

wrote that “[a]n example of systemic effects of cytokines is the induction of fever[.]” Id. at 3.

Dr. McCusker wrote that “[v]accination results in the production and release of multiple

cytokines in a tightly regulated manner.” Resp’t’s Ex. E at 6. Furthermore, “cytokines may have

different effects depending upon the location of their release, [and therefore] the concentration and

duration of activity . . . are important considerations.” Id. at 7.

111

Lucile Capuron & Andrew H. Miller, Immune System to Brain Signaling: Neuropsychopharmacological

Implications, 130 PHARMACOLOGY & THERAPEUTICS 226 (2011).

41

Dr. McCusker wrote about two studies of post-vaccination cytokine levels. Resp’t’s Ex.

A at 4 (citing Resp’t’s Ex. A, Tabs 11,112 12,113 ECF Nos. 39-1, 39-2). She opined that the studies

“suggest that cytokines are produced and released by the peripheral immune system during

vaccination[,]” but that “there is no evidence to suggest that the levels are sufficient to influence

the brain serotonergic pathways[.]” Id.

Dr. McCusker acknowledged that one of the studies showed serum IL-6 levels were similar

in infants with influenza infection and those evaluated within 48 hours after vaccination. Id. at 6

(citing Resp’t’s Ex. A, Tab 12). However, she noted that the “serum cytokine levels were

independent of signs of CNS activity such as fever.” Id. Therefore, Dr. McCusker argued that the

study’s “findings show that UR[Is] and vaccination do not represent pathophysiologically

equivalent events in children with SIDS.” Id.

In support of his theory that vaccinations cause an infection-like cytokine response in the

body, Dr. Miller also cited the study authored by Kashiwagi et al. Pet’rs’ Ex. 37, Tab K, 114 ECF

No. 93-7. The authors studied in-vitro peripheral blood mononuclear cells (“PBMCs”) after

stimulation with vaccine components, as well as serum samples obtained from vaccine recipients.

Id. The study revealed measurable levels of the cytokines IL-1β, TNF-α, IL-6, and G-CSF in the

PBMCs. Id. at 3, Figure 1. With the exception of IL-1β, the authors also found detectable amounts

of those same cytokines in the serum of vaccinated subjects, at similar levels regardless of whether

a vaccine recipient developed a fever after vaccination. Id. at 6, Table 2. When compared with

the levels of subjects who did not receive vaccines, the authors found higher levels of IL-6, IL-10,

IL-12, G-CSF, IFN-γ, and TNF-α in all vaccine recipients, whether they were febrile or non-

febrile. Id. at 5. The cytokine levels of vaccine recipients were also compared with patients with

acute infections, and the authors found similar cytokine levels in the two groups. Id. at 5–6.

Dr. Miller emphasized in his testimony that “there were very few if any differences

between people who were sick with the flu and people who had been vaccinated,” in terms of

cytokines present in the blood. Tr. 71:12–16. He noted that the cytokines produced by the in vitro

cells were also similar, with the exception that “significant quantities” of IL-1β could be detected

in the cultures, whereas “only trivial quantities” of that cytokine could be detected in the blood of

vaccinated or ill patients. Tr. 71:17–21. However, Dr. Miller testified that the authors “think[]

that they just missed the peak of [IL-1β] production because it’s earlier than the time they sampled

the blood.” Tr. 71:22–25; see also Tr. 66:12–18.

Dr. McCusker explained that the authors of the Kashiwagi et al. study “[o]f course” found

that cytokines were up-regulated in response to vaccination and noted that “[t]hat’s what’s

supposed to happen.” Tr. 221:8–10. However, she explained that “we expect them to act locally,

we do not expect them to go systemic.” Tr. 221:15–16. She opined that the cytokine response

seen in the in vitro PBMCs “would be the equivalent of what is happening, and even that’s not

true, but of what is happening in the lymph node next to the site of vaccination, because it’s a

112

Hingorani et al., supra note 86.

113

Yasuyo Kashiwagi et al., Production of Inflammatory Cytokines in Response to Diphtheria-pertussis-

tetanus (DPT), Haemophilus Influenzae Type b (Hib), and 7-valent Pneumococcal (PCV7) Vaccines, 10

HUM. VACCINES & IMMUNOTHERAPEUTICS 677 (2014).

114

Id.

42

contained environment, and you’re having the cells being stimulated by the presence of the vaccine

components.” Tr. 219:23–220:2. She testified that “if you think about the lymph node as a pond,

you could see those levels” which are reflected in the study. Tr. 220:10–11. However, she

explained that “when you talk about those levels in the peripheral circulation, it’s like you open

the dam, and now those cytokines fall out into the rushing stream of the systemic circulation.” Tr.

220:12–14. Therefore, the concentration measured in the lymph is “diluted by the circulating

blood volume,” and the “levels are going to go way down.” Tr. 220:15–18. Additionally, Dr.

McCusker criticized the study because cytokines “operate over very short distances[] and they

have a very short half[-]life . . . most of the conversation is going to be in the cells next to them[.]”

Tr. 220:21–24. Therefore, she opined that “what happens in the dish” is not equivalent to “what’s

going to get up to the brain.” Tr. 221:5–6. Dr. McCusker testified that “you’re not going to get

this massive amount of cytokine running up to the brain.” Tr. 221:17–18.

Based on her analysis of the cytokine response in the PBMCs, Dr. McCusker opined that

it was “[n]ot a surprise” that there were “not too much [sic] cytokines in the peripheral circulation.”

Tr. 221:14–16. She noted that the authors measured serum cytokine levels in picograms, which

she testified are “tiny.” Tr. 225:16–17. Additionally, Dr. McCusker specifically noted that IL-1β

was “undetectable” in the patients’ serum. Tr. 224:18–20. She agreed with Dr. Miller that “the

obvious limitation” in the Kashiwagi et al. study “is the fact that the cytokine levels were measured

. . . between 24 and 48 hours after the vaccine,” which is beyond the time frame relevant to this

case. Tr. 225:20–25. However, she testified that “even if you look at the cytokine levels that [the

authors] report . . . in the dish, you’re still looking at picogram amounts.” Tr. 226:1–3. Therefore,

she testified that the amounts are “still well below what was needed in the Stoltenberg and Frøen

articles” to prolong apneas. Tr. 226:3–5.

Dr. Miller and Dr. McCusker both testified about the significance of the unit of

measurement used to describe the cytokine levels described in these studies.115 Dr. Miller testified

that a picomole is “10 to the minus 12 moles.” Tr. 357:6. A mole, he explained, is a quantity that

is “6.02 times 10 to the 23rd power” molecules. Tr. 357:11–13. He explained that these are

“really, really small quantities, not something that we are familiar with in every day life.” Tr.

358:16–18. He emphasized that the amount could not be measured outside of a laboratory. Tr.

358:19–22.

After providing this context, Dr. Miller countered Dr. McCusker, stating “things that are

in picogram quantities are hardly something you can characterize as massive.” Tr. 346:18–20. Dr.

Miller testified that in the in vitro experiments in the Kashigawa et al. study, the highest number

of cytokines the authors found for IL-1β was 510 picograms per milliliter. Tr. 342:13–20. Dr.

Miller then compared the amount produced in the Kashiwagi et al. study to the amount injected

into piglets to study the effect of cytokines on apnea and autoresuscitation. He testified that in the

Stoltenberg et al. study,116 “[t]he intravenous injections used IL-1β at 20 picomoles” and “you

have to do a conversion.” Tr. 340:21–341:18. Dr. Miller then explained that the conversion is

115

Dr. Miller testified that he relied on Graphpad for his calculations. Tr. 339:2–5.

116

Stoltenberg et al., supra note 39.

43

done using “the molecular weight of IL-1β . . . [which] is 17.5 kilodaltons.117” Tr. 341:5–9. He

stated that “[t]wenty picomoles is the same as 350 picograms.” Tr. 341:10–12. “And then for the

intrathecal injections, they used half, so they used 10 picomoles, which is 175 picograms. Tr.

342:7–9. Dr. Miller concluded that 175 picograms per milliliter were introduced by intrathecal

injection and 350 picograms per milliliter were introduced intravenously. Tr. 341:2–343:1.

Regarding the Frøen et al. study,118 he testified that “something like 367 picograms per injection”

were used in the piglet studies. Tr. 343:21–22. Dr. Miller clarified his point that the cytokines

described in the Kashiwagi, Stoltenberg,

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