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In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 15-792V

Filed: April 15, 2022

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HEATHE HELLER and JENNA HELLER, 

parents of H.H., a minor, 

 Petitioners,

v.

SECRETARY OF HEALTH AND

HUMAN SERVICES,

 Respondent.

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TO BE PUBLISHED

Aicardi–Goutières syndrome (AGS);

Type I Interferonopathy; Pentacel 

vaccine; influenza vaccine; Prevnar 

vaccine; insufficient proof of causation

Margaret Guerra, Margaret M. Guerra, Attorney at Law, Fort Worth, TX, for Petitioners

Adriana Teitel, U.S. Department of Justice, Washington, DC, for Respondent

DECISION ON ENTITLEMENT1

Oler, Special Master: 

On July 27, 2015, Heathe Heller (“Mr. Heller”) and Jenna Heller (“Mrs. Heller”) 

(collectively “Petitioners”) filed a petition for compensation under the National Vaccine Injury 

Compensation Program, 42 U.S.C. § 300aa-10, et seq.

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(the “Vaccine Act” or “Program”) alleging, 

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

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

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

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

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

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

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

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

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

of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa 

(2012).
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in part, that as a result of his October 17, 2013 vaccinations with influenza and Prevnar3and his 

October 23, 2013 vaccination with Pentacel,4 H.H. experienced either the onset or the significant 

aggravation of his degenerative neurologic disorder.

For the reasons discussed in this decision, I find that H.H.’s vaccinations did not cause or 

significantly aggravate his condition.

I. Procedural History

On July 27, 2015, Heathe and Jenna Heller, on behalf of their minor son, H.H. filed a 

petition5seeking compensation under the Vaccine Act, alleging that H.H. suffered from dystonia 

and encephalopathy as a result of the influenza (“flu”) and Prevnar vaccines he received on 

October 17, 2013, and/or the DTaP-IPV-Hib (Pentacel) vaccination he received on October 23, 

2013. Pet. at 1.

Petitioners filed medical records on August 3, 2015. ECF No. 10. Petitioners filed 

additional medical records, affidavits, and expert reports from Dr. Leslie Hollis and Dr. Warren 

Marks on October 9, 2015. ECF No. 14. Petitioner filed additional medical records on November 

9, 2015 (ECF No. 16) as well as a statement of completion on November 9, 2015 (ECF No. 17).

On February 1, 2016, Respondent filed his Rule 4(c) Report, asserting that the case was 

not appropriate for compensation and should be dismissed. Resp’t’s Rep. ECF No. 21.

Petitioners filed additional affidavits and exhibits on March 21, 2016. ECF No. 28. 

Petitioner also submitted a supplemental expert report from Dr. Hollis on the same date. Id.

On July 8, 2016, Special Master Hastings held a status conference. ECF No. 35. Special 

Master Hastings stated to Petitioners’ counsel that “as this case proceeds, it is imperative that all 

the evidence is identified in a manner that does not cause confusion.” See Scheduling Order of 

July 8, 2016, ECF No. 35 at 1. Accordingly, Special Master Hastings ordered Petitioners to renumber and re-file all of Petitioner’s exhibits that had been filed previously. Id. Special Master 

Hastings noted that “the numbering of these re-filed exhibits shall commence with exhibit number 

48, followed by consecutive exhibits numbers thereafter.” Id.

Accordingly, Petitioners refiled all previously submitted medical records, affidavits, and 

expert reports on August 26, 2016. Exs. 48-93, ECF Nos. 40-46.

3 Prevnar is a “trademark for a preparation of pneumococcal 7-valent conjugate vaccine.” Prevnar, 

Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=40909& 

searchterm=Prevnar (last accessed April 13, 2022).

4 Pentacel is a “trademark for a combination preparation of diphtheria and tetanus toxoids and acellular 

pertussis vaccine adsorbed, poliovirus vaccine inactivated, and Haemophilus b conjugate (tetanus toxoid 

conjugate) vaccine.” Dorland’s Med. Dictionary Online, Pentacel, https://www.dorlandsonline.com/

dorland/definition?id=37544&searchterm=Pentacel (last accessed April 13, 2022).

5 Petitioners filed an amended Petition on November 9, 2015. ECF No. 15.
3

On December 14, 2016, Respondent filed an expert report from Dr. Kristin Barañano. Ex. 

A, ECF No. 52. Respondent filed Dr. Barañano’s CV at Exhibit B. On the same date, Respondent 

filed the medical literature associated with Dr. Barañano’s report. Exs. A-1 – A-5, ECF No. 52. 

On August 25, 2017, Petitioners filed a supplemental expert report from Dr. Warren Marks. 

Ex. 94, ECF No. 54. 

This case was reassigned to my docket on December 5, 2017. ECF No. 59. Petitioners filed 

additional medical records on March 6, 2018. Ex. 95, ECF No. 61.

On August 17, 2018, Respondent filed a supplemental expert report from Dr. Barañano. 

Ex. C, ECF No. 67. Respondent filed the medical literature associated with Dr. Barañano’s report 

as Exhibit C-1 on the same date.

On April 29, 2019, Respondent filed an expert report from Dr. Stephen McGeady. Ex. D, 

ECF No. 70. Respondent filed Dr. McGeady’s CV at Exhibit E.6 Respondent filed the medical 

literature associated with Dr. McGeady’s report on the same day. Exs. D-1 – D-12, ECF No. 71.

On December 31, 2019, the parties filed their pre-hearing submissions. ECF Nos. 75-76. 

Pre-hearing briefs were filed on January 8, 2020. ECF Nos. 78-79. 

On January 8, 2020, Respondent filed two additional pieces of medical literature. Exs. F, 

G, ECF No. 81.

I held an entitlement hearing on January 22, 2020. ECF No. 88. At the conclusion of the 

hearing, I held a status conference with the parties during which several items were discussed. See

Scheduling Order of January 29, 2020, ECF No. 86. I directed Petitioners’ counsel to file several 

documents, including: 

1. Any emails and/or records from Dr. Yanick Crow, including the results of the genetic 

testing done by Dr. Crow.

2. Any medical records from the Panama clinic where H.H. underwent multiple stem cell 

treatments as referenced in Ex. 96, pg. 36.

3. Medical records from H.H’s Boston Children’s Hospital visit.

4. Medical records and/or genetic testing results from Atlanta.

5. Any additional photos or videos of H.H. from Halloween 2013.

6. A status report identifying the specific dates of the video clips in Ex. 47.

7. Additional medical records from H.H.’s most recent visits with Dr. Warren Marks.

8. A status report informing the Court as to whether Petitioners wished to file additional 

expert reports.7

6 Respondent re-filed Dr. McGeady’s CV on April 14, 2020. Ex. I, ECF No. 90.
4

Id. at 1-2. In addition, Respondent was ordered to file an updated CV for Dr. Barañano and Dr. 

McGeady, and the parties were ordered to file medical literature summaries by March 31, 2020.8

Id. at 2. 

Petitioners filed a status report on April 14, 2020, stating that they had employed Dr. 

Lawrence Steinman to provide an additional expert report. Petitioners’ Status Report of April 14, 

2020, ECF No. 92. Petitioners stated that they had only been able to retrieve some of the medical 

records that were requested in my January 29, 2020 order, and filed these on the same day. Exs. 

97-100, ECF No. 93.

On July 24, 2020, Petitioners filed an expert report from Dr. Steinman. Ex. 101, ECF No. 

95. Petitioners filed the medical literature associated with Dr. Steinman’s report on the same date. 

Exs. 101-1 – 101-20, ECF No. 101. 

On December 1, 2020, Respondent filed a rebuttal expert report from Dr. McGeady. Ex. J, 

ECF No. 104.

On February 12, 2021, Petitioners filed a supplemental expert report from Dr. Steinman. 

Ex. 99,9 ECF No. 108 (hereinafter “Second Steinman Rep.”).

On May 15, 2021, Petitioners filed their post-hearing brief. ECF No. 113. Respondent filed 

a response on July 8, 2021. ECF No. 116. Petitioners filed a reply on July 15, 2021. ECF No. 118.

On August 9, 2021, the parties filed a joint status report indicating that the record was 

complete. ECF No. 119. 

On March 15, 2022, my law clerk emailed the parties in order to inform Petitioners’ counsel 

that one exhibit referenced during the hearing (a letter from Sheri Huling to Petitioners’ counsel 

which served as the basis for Ms. Huling’s affidavit) had not been filed into the record. That same 

day, I entered an order directing Petitioners to file the letter as soon as practicable See Non-PDF

Informational Communication of March 15, 2022. Petitioners filed on the letter on March 23, 

2022. Ex. 102; ECF No. 120.

This matter is now ripe for adjudication. 

7 At the conclusion of the entitlement hearing after we went off the record, I informed Petitioners’ counsel 

that the record, as it currently stood, did not enable Petitioners to meet their burden. I suggested that 

Petitioners’ counsel consider retaining an additional expert neurologist so that Petitioners may be afforded 

a full and fair opportunity to prosecute their case.

8 This additional documentation filed on April 14, 2020. ECF No. 90.

9 Petitioners inadvertently labeled this report as Exhibit 99. Exhibit 99 is already a medical record. To avoid 

confusion, I have referred to this report as “Second Steinman Rep.” in this decision.
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II. Medical Records

A. Relevant Pre-Vaccination History 

H.H. was born on July 14, 2012. Ex. 48 at 1. H.H. was delivered vaginally with no 

complications. Ex. 49 at 5.

On July 18, 2012, H.H. was seen by Dr. Leslie Hollis at Wise Pediatrics for a newborn 

visit. Ex. 49 at 5. H.H. was noted as meeting all his newborn milestones: raising his head when 

prone, making eye contact/regarding faces, startling to noise, following to midline and equal 

movements. Id. H.H. was sleeping three to four hours at a time, and his parents indicated no 

concerns at this visit. Id. Dr. Hollis noted no abnormalities. Id. at 5-6. H.H. was scheduled to return 

in one week for a weight check. Id. at 6.

On July 23, 2012, H.H. visited Dr. Hollis at Wise Pediatrics to follow up on an abnormal 

newborn screen “possibly indicating a VLCAD deficiency.”10 Ex. 49 at 7. Dr. Hollis noted that 

H.H. “has been doing very well. Weight gain and breastfeeding going well.” Id. H.H. was observed 

as “playful, alert and aware” and Dr. Hollis found no abnormalities upon examination. Id. Dr. 

Hollis ordered a Texas newborn screen, a plasma acylcarnitine profile, and a urine organic acids 

test. Id.

On July 27, 2012, H.H. visited Dr. Hollis at Wise Pediatrics for a two-week well child visit. 

Ex. 49 at 9. His parents had no concerns at this visit. Id. Dr. Hollis observed no abnormalities upon 

examination. Id. H.H.’s Texas Newborn Screen was canceled at this visit. Id. at 10. H.H. was next 

scheduled to return for his two-month wellness check.

On August 1, 2012, RN Michelle Johns from Wise Pediatrics left a voicemail for Mrs. 

Heller, indicating that H.H.’s second PKU (Phenylketonuria) screening was normal. Ex. 49 at 11. 

On August 8, 2012, LVN Cozby called Mrs. Heller to inform her that the rest of H.H.’s 

labs returned normal results. Ex. 49 at 14. 

On August 16, 2012, RN Johns called Mrs. Heller and left her a voicemail informing her 

that “State is requiring a referral to Dr. Basinger[, a] metabolic geneticist since [H.H.’s] first [PKU 

screening] was abnormal.” Ex. 49 at 15. Petitioner called back the same day to confirm an 

appointment with Dr. Basinger. Id. at 16.

On August 23, 2012, Dr. Heather Crawford sent a letter to Dr. Hollis noting that H.H was 

under evaluation for a VLCAD deficiency, which could cause hypoglycemia, cardiomyopathy, 

elevated ammonia levels, abnormal liver function tests, and death should H.H. have prolonged 

10 A VLCAD deficiency “is a condition in which the body is unable to properly breakdown certain fats 

(called very long-chain fatty acids) into energy, particularly during periods without food (fasting).” National 

Institutes of Health, National Center for Advancing Translational Sciences, VLCAD Deficiency, https://

rarediseases.info.nih.gov/diseases/5508/vlcad-deficiency#:~:text=VLCAD%20deficiency%20is%20a%20 

condition,periods%20without%20food%20(fasting) (last accessed April 8, 2022).
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fasting or poor dietary intake due to illness. Ex. 89 at 14. She noted that H.H.’s blood glucose 

needed to be maintained at about 70 mg/dL. Id.

On September 18, 2012, H.H. visited Dr. Hollis at Wise Pediatrics for his two-month wellchild visit. Ex. 49 at 18. H.H.’s parents had no concerns at this visit. Id. H.H. was recorded as 

meeting all his developmental milestones: grasping a rattle, presenting a social smile, cooing, 

responding to a bell, following past midline, and parent/child interaction. Id. H.H. weight 11.7 

pounds. Id. Dr. Hollis noted no abnormalities upon examination. Id. at 18-19. H.H. received his 

Prevnar-13, Hepatitis B, Pentacel, and Rotarix vaccines at this visit. Id. at 19. H.H. was next 

scheduled to be seen for his four-month well child appointment. Id.

On November 14, 2012, H.H. was seen by Dr. Hollis at Wise Pediatrics for his four-month 

well child visit. Ex. 49 at 21. H.H. was noted to be sleeping “more than 10 hours per night”. Id.

His parents voiced no concerns at this visit. Id. H.H. was noted to be meeting all his developmental 

milestones: raising his body on his hands, steady head control when held upright, no head lag when 

pulling to sit, rolling “prone to supine”, grasping his rattle, playing with his hands/bringing his 

hands together, turning to sound, following objects 180 degrees, and laughing/squealing. Id. H.H. 

weighed 14.06 pounds. Id. Dr. Hollis observed no abnormalities upon examination. Id. at 22. H.H. 

received his Prevnar-13, Pentacel, and Rotateq vaccinations at this visit. Id. H.H. was next 

scheduled to return for his six-month well child visit. Id.

On January 23, 2013, H.H. was seen by Dr. Hollis at Wise Pediatrics for his six-month 

well visit. Ex. 49 at 26. H.H. was noted to be meeting all his developmental milestones: rolling 

over both ways, sitting with minimal support, no head lag when pulling to sit, bearing weight, 

transferring objects from hand to hand, laughing/babbling and imitating sounds, turning towards 

voices, “raking raisin”, looking “for yarn” and reaching for objects/working for toys. Id. at 27. 

H.H. weight 16.87 pounds at this visit. Id. Dr. Hollis noted no abnormalities upon examination. 

Id. at 27-28. H.H. received his Prevnar-13, HiB, Pediarix, Rotateq, and flu vaccinations at this 

appointment. Id. at 28. Dr. Hollis noted that H.H. had “no problems with previous immunizations.” 

Id. H.H. was next scheduled to be seen for his nine-month well child visit. Id.

On April 16, 2013, H.H. visited Dr. Hollis at Wise Pediatrics for his nine-month well visit. 

Ex. 49 at 28. By this point, H.H. had begun eating solid foods, including fruits, Cheerios, and 

yogurt. Id. He was sleeping more than ten hours per night and his parents had no concerns. Id.

H.H. was noted to be meeting all his developmental milestones: Sitting well, crawling, pulling to 

stand and cruising, using a pincer grasp, banging two toys together, finger feeding, babbling 

mama/dada, playing peek-a-boo, indicating his wants, and waving bye-bye. Id. Dr. Hollis noted 

no abnormalities upon examination. Id. at 28-29. H.H. weighed 18.77 pounds at this visit. Id. at 

29. H.H. was next scheduled to be seen for his 12-month well child visit. Id.

On July 18, 2013, H.H. was seen by Dr. Hollis at Wise Pediatrics for his 12-month well 

child visit. Ex. 49 at 33. By this time, H.H. had switched to whole milk from formula, was eating 

solids to include meats and Gerber Graduates, and was sleeping more than ten hours per night. Id.

His parents had no concerns at this visit. Id. H.H. was noted to be meeting all his developmental 

milestones: pulling to stand/standing alone for 2-3 seconds, walking with support and taking a few 

steps, precise pincer grasp, had a 1–3-word vocabulary, using Mama/Dada specifically, drinking 
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from a cup, understanding “no” and imitating actions. Id. H.H. weighed 21.34 pounds at this visit. 

Dr. Hollis noted no abnormalities upon examination. Id. at 33-34. H.H. received his MMRV and 

Hepatitis A vaccinations at this visit. Id. at 34. H.H. was next scheduled to be seen for his 15-

month well child visit. Id.

On July 29, 2013, H.H. was seen by Dr. Hollis at Wise Pediatrics for a sick child visit. Ex. 

49 at 36. Under HPI, Dr. Hollis stated that “Pt has been running fever to 102 for the [past] 3 days. 

Mom is also sick. He has had nasal congestion for 2 weeks.” Id. H.H. was diagnosed with purulent 

rhinitis and prescribed Augmentin. Id.

On September 13, 2013, Petitioner called Wise Pediatrics and stated that she was concerned 

with H.H. “not walking and right foot turned inward.” Ex. 49 at 37. LVN Cozby noted that H.H. 

was scheduled for an appointment in one month and advised Petitioner, per Dr. Hollis, to wait until 

that appointment to be seen. Id.

B. Post-Vaccination History

On October 17, 2013, H.H. visited Dr. Hollis at Wise Pediatrics for his 15-month well visit. 

Ex. 49 at 1. At this visit, H.H. was noted as meeting all of his developmental milestones: Walking 

alone, crawling up stairs, self-feeding with fingers, using a fork and spoon, talking with a three to 

six word vocabulary, understanding simple commands, rolling/tossing a ball, stooping to recover 

a toy, and indicating his wants without crying. Id. Upon physical exam, Dr. Hollis noted no 

abnormalities. Id. H.H. received his influenza and Prevnar-13 vaccines at this appointment, 

although he did not receive Pentacel.

11 Id. Dr. Hollis discussed H.H.’s development, growth and 

nutrition with Petitioner. Id. at 2. H.H. was next scheduled to return for his 18-month well child 

visit. Id. at 2. 

On October 23, 2013, H.H. was seen by Nurse practitioner Ariane Segura. Ex. 49 at 3. H.H. 

received his Pentacel vaccination at this visit. Id.

On November 11, 2013, H.H. visited Dr. Hollis at Wise Pediatrics for a sick child visit. 

Ex. 49 at 41. In the HPI, Dr. Hollis stated “Pt has been fussy for the last week. He has run fever to 

101.5. His energy level is decreased. Pts development has regressed in the last month. He has 

stopped crawl[]ing. He is not wanting to play with toys. He will throw toys and food.” Id. H.H. 

was noted to be “playful, alert and aware” and in no respiratory distress. Id. Dr. Hollis observed 

no abnormalities until she conducted a neurologic examination. She noted that H.H.’s reflexes 

were “Brisk, 3+” and his tone was “hypotonic”. Id. A rapid strep throat test was negative and a 

CBC returned normal results. Id. at 41-42. H.H. was diagnosed with a developmental delay and 

acute pharyngitis. Id. at 42. He was referred to neurology “ASAP” for evaluation. Id. Petitioner 

was instructed to try throat lozenges, fluids, and rest to treat the pharyngitis. Id.

On November 12, 2013, H.H. visited Dr. Heather Crawford at Cook Children’s Hospital, 

Department of Clinical and Metabolic Genetics, for “new problem of loss of milestones, elevated 

11 Mrs. Heller testified at the entitlement hearing that Wise Pediatrics was out of the Pentacel vaccine, and 

she was told to return to get that vaccine at a later date. Tr. at 17.
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liver enzymes.” Ex. 50 at 1. H.H. was observed to be “healthy-appearing, well-nourished, and 

well-developed” and in no distress. Id. He was “active and alert and [with a] normal mood.” Id.

Upon examination, no abnormalities were found in an examination of his head, eyes, ears, nose, 

throat, neck, chest, heart, abdomen, back, skin, hair and genitals. Id. at 1-2. Upon an examination 

of H.H.’s musculoskeletal systems, Dr. Crawford noted that H.H. had “normal strength and 

hypertonicity (noted in lower extremities especially at the ankles). Id. at 2. She stated that “his heel 

cords appear somewhat tight and he may require AFOs at some point in the future.” Id. A 

neurologic exam revealed that H.H. was “not walking yet” and was “not speaking yet.” Id. Dr. 

Crawford also noted that H.H. had “elevated transaminases” but she “would like to repeat those 

[tests] once his minor illness has passed.” H.H. was diagnosed as “a 16 month old who now 

presents with a new history of developmental delay with loss of some developmental milestones.” 

Id. Dr. Crawford ordered a “baseline genetic and metabolic workup to include looking for 

chromosomal abnormalities and disorders of fat and protein metabolism.” Id. Additionally, she 

ordered an “MRI of the brain to make sure that the gross anatomy of the brain is normal.” Id. She 

recommended that Petitioners start H.H. in physical and speech therapy while the cause of his 

developmental delay was diagnosed. Id. Concerning his “elevated transaminases”, Dr. Crawford 

stated that if they were still elevated in a month, she would “expand our evaluation to include an 

abdominal ultrasound to evaluate the liver and possible evaluate for lysosomal disorders if his 

regression persists.” Id.

On November 14, 2013, Dr. Crawford sent a note to Dr. Hollis, providing the details of 

H.H.’s visit on November 12, 2013. Ex. 50 at 4. Dr. Crawford stated that:

H.H. is a 16 month old male who is being referred again for an evaluation for 

developmental delay and possible regression of milestones. He was initially seen 

in the metabolic genetics clinic after an abnormal newborn screen for possible 

VLCAD deficiency. However, follow up testing including a skin biopsy to look at 

fat metabolism proved to be negative. He was then cleared for that screening test 

with no follow up recommended at that time. However, I was contacted by his PCP, 

Dr. Hollis, who was concerned about his development. She stated that he was sitting 

at 6 months, crawling at 7 months and took a few steps at 10 months. He apparently 

had 3 words at 12 months. Parents now state that he does not take any steps [] nor 

does he pull to stand anymore. He now has no words. They also feel that his affect 

is not normal in that he does not laugh spontaneously or much at all. He has been 

sick with a virus this last couple weeks. He has not had any major illnesses or

hospitalizations since birth.

Id. Dr. Crawford’s notes indicate that H.H. was diagnosed with a developmental delay, specifically 

a slight delay in gross motor function and fine motor function/ADLs, and a significant delay in 

language functioning. Id.

On the same date, H.H. was admitted to the hospital with worsening symptoms. Ex. 51 at 

5. Dr. Michael Aalbers, a neurologist, admitted H.H. to the hospital with “progressive dysarthria,12

12 Dysarthria is “a speech disorder consisting of imperfect articulation due to loss of muscular control after 

damage to the central or peripheral nervous system.” Dysarthria, Dorland’s Med. Dictionary Online, https:// 
9

trouble swallowing, and a fairly dramatic spastic diplegia in the lower extremities.” Id. at 8. A CT 

scan demonstrated “mild volume loss with no evidence of upper motor neuron injury.” Id. Dr. 

Aalbers also noted that there was “no evidence of bony malformation, [or] concerns for acute 

transverse myelitis.” Id. It was noted that H.H. was constipated but had “appropriate bowel and 

bladder symptoms.” Id.

After being admitted, H.H. underwent a lumbar puncture to “rule out demyelinating disease 

versus metabolic etiologies versus dopa-responsive dystonia.” Ex. 52 at 5. The lumbar puncture 

revealed no significant results.

On November 15, 2013, H.H. underwent a brain MRI. Ex. 51 at 1. The clinical indication 

was “acute onset spastic diplegia.” Id. Dr. Hayden Head interpreted the MRI. His impression was 

“Mild enlargement of subarachnoid spaces. If the head circumference is enlarged and/or has been 

rapidly increasing, the findings would be in keeping with benign enlargement of subarachnoid 

spaces of infancy, in the appropriate clinical setting. If not, mild diffuse parenchymal volume loss 

should be considered.” Id. Dr. Head noted that H.H.’s MRI was “otherwise unremarkable.”

On November 16, 2013, H.H. was discharged from the hospital. His discharge summary 

stated: 

[H.H.] presented to the emergency department and upon evaluation by Dr. Aalbers 

of neurology was found to have significant dystonic posturing of the lower 

extremities, prompting his admission. He was admitted to the floor in stable status. 

The workup included an MRI of the brain, which was within normal limits. An 

MRI of the complete spine was significant only for a fatty film, suggesting a 

possible tethered cord.

 

Ex. 51 at 5. Dr. Michael Perry, H.H.’s discharging physician, stated that “during admission, 

[H.H.’s] irritability decreased significantly, and he was able to feed fairly well.” Id. H.H. was 

treated with Sinemet for “presumptive dopa-responsive dystonia” and seemed to respond to the 

treatment. Id. Dr. Perry noted that confirmation of diagnoses would depend on CSF results. Id.

H.H.’s family was instructed to call the hospital if H.H. had increased irritability, increased tone, 

intolerance to medication, or any other concerns. Id. at 6. 

On November 21, 2013, Dr. Elisabeth Brockie, DO, of Quest Diagnostics – Dallas 

provided lab results for H.H.’s lactate and plasma acylcarnitine. Ex. 50 at 54. She noted that 

“several very-long-chain and long-chain-hydroxy acylcarnitine species were minimally to mildly 

elevated” in the sample she tested. Id. She noted that the results were “not sufficient” to rule out a 

mitochondrial fatty acid disorder. Id. She noted that these results have been seen in “liver disease, 

some mitochondrial disorders, metabolic stress, certain glycogen storage disorders, and 

generalized sickness of not metabolic origin.” Id. An amino acids lab result reported on the same

day showed “elevated” amino acids but did “not suggest a specific inherited metabolic disorder.” 

Id. at 56. 

www.dorlandsonline.com/dorland/definition?id=15144&searchterm=dysarthria (last accessed April 8, 

2022).
10

On November 22, 2013, H.H. was seen by Dr. Aalbers at Cook Children’s Hospital. Ex. 

52 at 8. Problems reviewed included “cough, spinal cord disease, dystonia, screening finding, 

speech delay and delayed milestone.” Id. In the patient history, Dr. Aalbers noted that H.H. was at 

the clinic “emergently secondary to concerns of rapidly advancing metabolic neurodegenerative 

disease” and that since his discharge from the hospital on November 16, 2013, H.H. had 

progressively lost meaningful use of his right hand. Id. at 9. Upon examination, Dr. Aalbers found 

no abnormalities in H.H.’s eyes, ears, nose, mouth, throat, heart, respiratory systems, 

gastrointestinal symptoms, musculoskeletal systems, or skin. Upon conducting a neurologic 

examination, Dr. Aalbers noted that H.H. had “weakness, trouble walking, and poor attention.” Id.

at 10. H.H.’s mental status was described as “somnolent.” Id. His grasp of language was considered 

“dysfluent and dysarthric” and his “fund of knowledge” was “delayed for age. Id. During a motor 

exam, Dr. Aalbers observed the following:

Motor spastic, rigidity, hypotonic axial, hypertonia appendicular, and dystonia

diffuse and normal bulk and no focal weakness; Patient has internal rotation and 

supination with dystonic posturing of the thumb in the right hand that was not 

present 4 days ago with intermittent scissoring of the lower extremities dystonic 

spastic posturing of the feet with plantarflexion striatal toes bilaterally patient has 

appropriate head[] control with increased tone and cogwheeling on the right but 

good range of motion of his fingers.

Id. at 10. Finally, in examining H.H.’s spine, Dr. Aalbers observed “no tenderness and decreased 

ROM” in H.H.’s cervical spine. Id. Dr. Aalbers’ initial impression was “rapidly progressive 

ascending dystonia with encephalopathy – Concern for mitochondrial disease versus lysosomal 

storage disease/inborn error of metabolism.” Id. at 11. Dr. Aalbers also provided his impression of 

H.H.’s testing from his hospital stay (November 14, 2013 – November 16, 2013): 

In the interim the patient was admitted to the hospital with subsequent concerns for 

rapidly progressive dysarthria choking with exacerbation dystonic posturing in the 

lower extremities. Patient matter and lumbar puncture which demonstrated no 

evidence of pleocytosis with normal lactate pyruvate urine organic acids and repeat 

[] acylcarnitine profile.

Subsequent neuroimaging demonstrates numerous white matter hyperintensities 

particularly along the insula bilaterally however this is still within the normal range 

of normal myelination for [a] 16- month-old, there is perhaps mild volume loss in 

the midline particularly midline stratum without signal change.

MRI of his lower spine demonstrates a mildly tethered cord that would not explain 

the dystonia or striatal toe [but] may explain the constipation rapid exag[g]eration 

of symptoms.

Id. at 11. Dr. Aalbers noted that “within a week [of his discharge, H.H. developed] increased 

encephalopathy and now has los[t] meaningful[] use of his right hand with cogwheeling of his left 

despite being on 25 100 mg of Sinemet secondary to a working diagnosis of rapidly progressive 
11

to responsive dystonia.” Id. A metabolic geneticist did not suspect that H.H. had a “fatty acids 

oxidation disorder based on the fibroblast and repeated carnitine profiles” and an EEG 

demonstrated “no evidence of epilep[t]iform [discharges].” Id. Dr. Aalbers’ differential diagnosis 

was “rapidly progressive primary mitochondrial disease.” Id. Dr. Aalbers stated that he would 

order testing for lysosomal storage diseases, and “full scale mitochondrial studies.” Id. H.H.’s 

parents were instructed to continue Sinemet 25 100 and observe H.H. for worsening 

encephalopathy or new symptoms. Id.

That same date, H.H. underwent an EEG. Ex. 52 at 47. Dr. Howard Kelfer, interpreting the 

EEG, stated that “this tracing, recorded while awake and during sleep, is mildly abnormal. The 

background activity is somewhat slow for age. The findings are indicative of a mild to moderate 

diffuse disturbance of brain function. There is no definite epileptiform activity.” Id.

On November 23, 2013, Dr. Thomas Lohmann provided the results of H.H.’s genetic 

testing conducted using a microarray analysis, stating that “no deletions or duplications of known 

or potential clinical significance were detected by microarray analysis.” Ex. 50 at 61.

On November 27, 2013, Medical Neurogenetics Laboratories (“MNG Labs”) provided the 

results of the testing ordered by Dr. Aalbers. Ex. 52 at 19. Under “neurotransmitter metabolics”, 

H.H.’s 5-Hydroxindoleacetic acid was slightly elevated, with a value of 215 mnol/L (reference 

range 67-189 nmol/L). Id. Dr. Keith Hyland, Ph.D, interpreting the results stated that “this is 

unlikely to be of any clinical significance.” Id. at 20. Under “tetrahydrobiopterin and neopterin 

profile”, H.H.’s neopterin was extremely elevated, with a value greater than 300 nmol/L (reference 

range 8-33 nmol/L). Id. H.H.’s tetrahydrobiopterin was also extremely elevated at 118 nmol/L 

(reference range 9-33 nmol/L). Dr. Hyland noted that “elevations of neopterin and 

tetrahydrobiopterin have been described in the Aicardi-Goutieres syndrome” and “we have also 

noted a similar abnormal pterin pattern in HIV infection.” Id. All other testing was normal. Id. at 

19-20, 23. 

On December 3, 2013, H.H. was seen by Dr. Aalbers for “neurological regression.” Ex. 52 

at 25. Dr. Aalbers noted generally the same problems he had observed during H.H.’s November 

22, 2013 visit. Id. at 25-26. Under “Impression”, Dr. Aalbers stated that H.H.’s diagnosis was 

“rapidly progressive dystonia and encephalopathy” with “concern for possible Accardi-Gutierres 

[sic]”. Id. at 28. Dr. Aalbers stated that H.H had:

Rapidly progressive dystonia, now with lo[ss of] meaningful [use] of his left hand 

and spastic dystonic scissoring of the lower extremities. In the interim [h]is 

neurotransmitter results surprisingly showed marked elevation to biopterin in the 

option which is commonly seen in patients with inflammatory encephalitis such as

[] AGS. Of concern the patient had previously unexplained transient elevations of 

liver enzymes which is consistent with AGS as is progressive encephalopathy and 

dystonia spasticity.

Id. at 28. Dr. Aalbers also noted that H.H.’s MRI was “confusing”, noting that “there are patchy 

white matter hyperintensities throughout however given his chronological age patchy 

hypomyelination can be normal.” Id.
12

To confirm the diagnosis, Dr. Aalbers arranged for HIV testing, repeat of H.H.’s 

neurotransmitters studies, and planned to contact experts in AGS. Id. H.H. was referred to Dr. 

Heather Crawford for additional genetic testing in connection with AGS. Id.

On December 3, 2013, H.H. was seen by Dr. Crawford at Cook Children’s Hospital, 

Department of Clinical and Metabolic Genetics for a follow up evaluation for “developmental 

regression with dystonia.” Ex. 50 at 11. No abnormalities were found upon an evaluation of H.H.’s 

head, eyes, ears, nose, mouth throat, neck, genitals, back, skin, or hair. Id. at 11-12. A 

musculoskeletal exam revealed that H.H. had “normal strength and hypertonicity (noted in lower 

extremities especially at the ankles, feet held inward position); Pt now holds hand in a fist when 

trying to reach for objects and when crawling, then afterward hand relaxes when trying to hold a 

bottle.” Id. at 11. A neurologic exam revealed that H.H. was “not walking yet” and “not speaking 

yet.” Id. H.H. was assessed as “a 16 month old who now presents with a new history of 

developmental regression and onset of progressive dystonia in the last 2-3 months.” Id. at 12. He 

was diagnosed with delayed milestones, unspecified encephalopathy, speech delay (“expressive

language disorder”), and dystonia (“unspecified extrapyramidal disease and abnormal movement 

disorder”). Id.

In the discussion notes, Dr. Crawford stated: 

[H.H.] continues to have dystonia in the lower extremities, however his hands are 

now becoming involved. He is still unable to crawl or pull [to] stand. He is now 

having difficulties sitting alone. His clinical picture is very concerning for either a 

metabolic or neurogenetic disorder. He had CSF studies done that included 

neurotransmitters which showed an extremely elevated neopterin and 

tetrahydrobiopterin. The lab's interpretation stated that only Aicardi-Goutières 

syndrome and HIV infection would cause such high values. Dr. Aalbers and myself 

have discussed this case at length. He does not have the typical presentation of AGS 

as he does not have any calcifications in the brain and did not present with 

thrombocytopenia, hepatosplenomegaly with elevated liver enzymes after birth. 

However, there are milder presentation[s] of this syndrome where the calcification 

can develop after 1-2 year of age. Therefore, this disorder remains on our 

differential. I got permission from the family to contact a Dr. Yanick Crow in 

England who is a world expert on AGS to get his opinion.

Id. Dr. Crawford recommended that the lumbar puncture be repeated, as well as a test for IFNalpha in the CSF. Id. She stated that, aside from AGS, “mitochondrial disorders are still in the 

differential as he has had an elevated lactate in the past, however repeat was normal.” Id. Dr. 

Crawford ordered sequencing of H.H.’s mitochondrial genome and stated that “ [S]ince his 

differential is still so wide at this point, we will proceed with whole exome sequencing which will 

include the mitochondrial genome. This will also look at the 5 genes known to be associated with

Aicardi-Goutieres syndrome.” Id. Dr. Crawford encouraged “intensive therapies to help condition 

his muscles and help with regaining milestones.” Finally, Dr. Crawford ordered additional 

biochemical labs for diagnostic purposes. Id.
13

On December 4, 2013, Dr. Crawford sent a note to Dr. Hollis, providing the details of 

H.H.’s visit on December 3, 2013. Ex. 50 at 14. Dr. Crawford stated that:

[H.H.] was last seen in the metabolic genetics clinic on 11/12/2013. At that time, 

some metabolic labs were ordered as well as PT and ST. However, 2 days after our 

clinic visit, parents felt that he was worsening. They felt he had difficulty 

swallowing, increase[d] tone in his legs and increased irritability.

Id. Dr. Crawford noted that H.H. was admitted to the hospital on November 14, 2013 by Dr. 

Aalbers in the neurology department. She stated that:

[Dr. Aalbers] felt that he had significant dystonic posturing of his lower extremities. 

This led to an emergent MRI of the brain and a lumbar puncture for CSF studies. 

He also had some other metabolic labs drawn during that admission. His irritability 

improved and he was feeding well by time of discharge on Saturday 11/16/13. He 

was started on sinemet during this admission due to the suspicion of doparesponsive dystonia. There was a slight improvement in his tone by discharge from 

the hospital.

Id. Dr. Crawford further noted that: 

Since discharge from the hospital, he continues to get physical therapy. Parents felt 

that he was [sleepier] and the increased tone has returned to his legs. His hands 

appear to be affected as the parents state that he does not use them as much as before 

and he seems frustrated when trying to use his hands, but he is not able to open 

them up to use them. Id.

Dr. Crawford noted that “[H.H.] was seen back in clinic by Dr. Aalbers on 11/22/13 and he felt 

that his right hand was more dystonic.” Id. A swallow study conducted in the hospital returned 

normal results, and an EEG did not demonstrate any seizure activity although “there was mildly 

slow background activity.” Id. Dr. Crawford noted that “CSF neurotransmitter studies done on 

11/14/13 returned and were abnormal. The neopterin and tetrahydrobiopterin were significantly 

elevated.” Id. Lab testing revealed “several long chain acylcarnitine elevated right at the cutoff 

ranges” and a “pattern of mildly elevated acids not in a pattern for specific disorder.” Id. at 15. A 

brain MRI revealed “mild cerebral volume loss, myelination normal for his age.” Id. Dr. 

Crawford’s notes again indicated that H.H. was diagnosed with a developmental delay, specifically 

a slight delay in gross motor function and fine motor function/ADLs, and a significant delay in 

language functioning. Id.

On December 9, 2013, H.H. underwent an EEG which returned normal findings. Ex. 52 at 

45. 

On December 18, 2013, H.H. was seen by Dr. Richard Roberts at Cook Children’s Hospital 

Neuroscience Center for a consultation regarding his tethered spinal cord. Ex. 53 at 1. In the HPI, 

Dr. Roberts noted that H.H. was a 
14

16-month-old patient who was referred to neurosurgery for findings of a tethered 

spinal cord on MRI. The patient was initially worked up for rapid onset of

developmental delay and hypertonia and a possible loss of motor skills. In the 

course of workup the patient had [an] MRI which showed a thickened and fat 

infiltrated filum terminale. The patient also suffers from constipation. Prior to the 

rapid neurologic changes the patient also dragged his right foot.

Id. Dr. Roberts explained the benefits and risks of surgical release of tethered spinal cord to H.H.’s 

parents, who indicated they wished to proceed with surgery. Id. 

On December 19, 2013, H.H. underwent surgery to release his tethered spinal cord. Ex. 53 

at 7. During surgery Dr. Roberts collected cerebrospinal fluid to be tested by neurology. Id. at 8. 

Dr. Roberts noted that the procedure was successful and H.H. tolerated the procedure well. Id. He 

was taken to recovery in stable condition. Id.

Following surgery, H.H. was seen by Dr. Aalbers. Ex. 55 at 1. Dr. Aalbers noted that the 

lumbar puncture showed “remarkably high elevations of biopterin and neopterin; the highest 

neopterin levels we have ever seen.” Id. Dr. Aalbers noted that the differential diagnosis in a patient 

with new-onset dystonia and significantly elevated neopterin levels was likely “Aicardi-

[Goutières] syndrome.” Id. H.H.’s brain MRI was “completely normal”, but in the interim, he 

continued to regress developmentally and was no longer using his arms. Id. Dr. Aalbers also wrote 

that H.H.’s elevations of his liver enzymes (325 for the AST and 472 for the ALT) were also 

indicative of possible AGS. Id. He noted that H.H. had been “intermittently lethargic, tired more 

so than usual over the last 3 or 4 months without significant weight gain.” Id. at 2. 

Dr. Aalbers laid out next steps for H.H.’s treatment. Ex. 55 at 3. He ordered an ultrasound 

of H.H.’s liver and spleen, noting that “fluctuating liver inflammation and spleen inflammation 

can be consistent with Aicardi-Goutieres syndrome with subsequent resolution of the syndrome.” 

Id. at 3-4. Dr. Aalbers also ordered a repeat EEG, noting that “patients can have stages of 

encephalopathy that come and go, which may explain why his abnormal EEG subsequently 

improved, and now that he is having progressive upper extremity symptoms, the EEG would again 

be abnormal.” Id. at 4.

Dr. Aalbers noted that AGS was incredibly rare. Ex. 55 at 4. He discussed that H.H.’s 

thallium levels were elevated and this could “inhibit glutathione levels and cause similar symptoms 

of encephalopathy” to AGS. Id. Dr. Aalbers recommended that H.H.’s parents discontinue all 

homeopathic medications until thallium levels could be resolved. Id. In the context of AGS, Dr. 

Aalbers noted that H.H. was likely in the early onset of the disease and repeat imaging could now 

show evidence of early-onset leukodystrophy. Id. He also ordered testing for H.H.’s CSF interferon 

alpha. Id. 

Accordingly, H.H. underwent an EEG on the same date. Ex. 53 at 12. Dr. Fernando Acosta, 

interpreting the results, stated that “this is an abnormal EEG due to mild generalized background 

slowing. This may be consistent with an encephalopathic state. No electrographic nor 

electroclinical seizures were recorded.” Id.
15

On December 20, 2013, while still in the hospital, H.H. was seen by Lori Thompson, CPNP 

for a consultation regarding his elevated transaminases. Ex. 54 at 1. In the history of present illness

section, Ms. Thompson noted that H.H. had a “complex past medical history,” including 

“abnormal newborn screening, concern[s] for a possible VLCAD”, and “metabolic genetics.” Id. 

Ms. Thompson noted that the workup thus far had been “within normal limits.” Id. She noted an 

unremarkable family history. Id. Upon a musculoskeletal examination, she noted “diminished deep 

tendon reflexes over lower extremities, spastic tone. His tone is spastic, dynamic, dystonic, and 

posture has hypotonia.” Id. 

In the medical history, Ms. Thompson noted that H.H. “was a normally developing male 

until approximately 15 months of age and he began losing milestones. He cannot walk, sit up, roll

over. He lost his verbal skills, but he is able to babble and is being followed by neurology for 

progressive dystonia.” Ex. 54 at 1. She noted that AGS was a concern and that H.H. was being 

“worked up by neurology” and by gastroenterology to follow his liver transaminases and evaluate 

for the source of the elevation. Id.

On January 2, 2014, NMG labs reported the results of the repeat neurotransmitter studies 

ordered by Dr. Aalbers on December 3, 2013. Ex. 52 at 71. H.H.’s neopterin was elevated, with a 

value of 270 nmol/L (reference range 7-65 nmol/L), while his tetrahydrobiopterin was also 

elevated, with a value of 69 nmol/L (reference range 18-58 nmol/L). Id. Dr. Hyland, interpreting 

the results stated that “the concentrations of tetrahydrobiopterin and neopterin were above our 

reference ranges. Elevations of neopterin and tetrahydrobiopterin have been described in []

Aicardi-Goutières syndrome.” Id. at 72. 

On January 6, 2014, MNG labs reported no abnormalities in H.H.’s sialic acid metabolism. 

Ex. 52 at 69. 

On January 14, 2014, H.H.’s HIV testing was returned as “non-reactive.” Ex. 52 at 39. His 

urine sample contained elevated 3-hydroxybutyrate, elevated 3-hydroxyisobutyric, elevated 2-et30hpropionic, elevated methylsuccinic, and low 3-OH-3-methylgutaric. Id. at 40-41. 

On January 16, 2014, H.H. visited Dr. Samson Cantu at Cook’s Children’s Hospital for his 

abnormal liver enzymes. Ex. 55 at 9. Dr. Cantu noted that H.H. had a history of tethered cord 

repair, hypertonia, elevated liver enzymes all of unclear etiology. “Pt has had an extensive workup thus far with inconclusive findings. Since release from hospital he has had no jaundice, and

increased bruisability .... He has intermittent constipation responsive to miralax.” Id. Dr. Cantu 

also noted that H.H.’s liver ultrasound was normal. Id. Upon examination, Dr. Cantu observed 

H.H. as developmentally delayed. Id. at 11. All other systems were normal, including H.H.’s back 

following surgery. Id. Dr. Cantu planned to repeat the liver panel, check H.H.’s CK level and 

potentially perform a liver biopsy, depending on the results of the liver panel. Id.

On January 17, 2014, Quest Diagnostics returned the labs ordered by Dr. Cantu. Ex. 80 at 

8. Under “hepatic function panel”, H.H.’s globulin was measured low at 1.7 g/dL (reference range 

2.1-3.5 g/dL), leading to a high albumin/globulin ratio of 2.8 g/dL (reference range 1.0-2.5 g/dL). 

Id. His indirect bilirubin was low at 0.1 mg/dL (reference range 0.2-0.8 mg/dL). Id. His AST was 
16

high at 117 u/L (reference range 3-56 u/L), and his ALT was high at 129 u/L (reference range 5-

30 u/L). Id.

On February 4, 2014, H.H. was seen by Dr. Warren Marks to review the results of his 

testing with genetics and neurology. Ex. 56 at 1. Dr. Marks indicated to H.H.’s father that H.H.’s 

likely diagnosis was AGS and they were awaiting genetic confirmation. Id.

On the same day, H.H. visited Dr. Crawford at Cook Children’s Hospital, Department of 

Clinical and Metabolic Genetics to discuss his disease and diagnosis. Ex. 50 at 23. Dr. Crawford 

stated that “[H.H.] has had 2 lumbar punctures that showed an elevated neopterin. This is seen 

only in Aicardi-Goutieres syndrome (AGS) and HIV infection. We ruled out HIV infection and 

pursued testing for AGS...” Id. at 24. Dr. Crawford noted that blood testing and CSF both “showed 

elevated levels of IFN-alpha which is diagnostic for AGS.” Id. In discussing H.H.’s possible 

diagnosis with his family, Dr. Crawford stated that 

[H.H.] appears to be hav[ing] a later-onset presentation for AGS as he presents after 

a long period of normal development. He then presented with developmental 

regression and developed progressive dystonia that is characteristic of the disease. 

This disease can lead to a severe encephalopathy that can result in severe 

intellect[u]al disability and physical disabilities. There is a spectrum for this 

disease, so ther[e] are milder cases that have been reported in the literature

depending on which gene is involved. Typica[l]ly, these children have a regression 

phase, followed by irritability, then a slow progressive encephalopathy phase. 

These children[] typically develop peripheral spasticity, truncal hypotonia, dystonic 

posturing upper limbs and poor head control, all of which [H.H.] is currently 

displaying.

Id. Dr. Crawford noted that Dr. Crow’s lab in England was working on DNA testing to determine 

which of H.H.’s genes were involved in his disease. Id. She noted that AGS is “now known to be 

associated with mutation in 6 different genes.” Id. Dr. Crawford stated that “there are currently no 

treatments known to affect or slow disease progression” and the H.H. would need “to continue 

aggressive therapies due to his hypotonia and dystonia.” Id.

Regarding AGS in particular, Dr. Crawford noted that it is an “autosomal recessive 

disorder, therefore recurrence risks for future pregnancies is 25%.... Therefore, if DNA testing 

confirms [H.H.] is affected, parents are obligate carriers.” Id.

On March 6, 2014, Petitioner received the results of H.H.’s genetic testing. Ex. 50 at 40. 

Only one significant mutation was found, a VLCAD deficiency in the gene ACADVL. Id. at 42.

On the same date, H.H. was seen by Dr. Marks for evaluation. Ex. 56 at 18. Dr. Marks

noted that H.H.’s eyes were “clear and anicteric and non cooperative with fundoscopic testing.” 

Id. He observed H.H. to be “awake (but not very interactive)” and that he was nonverbal. Id. Upon 

conducting a motor examination, Dr. Marks noted “motor spastic, rigidity, hypotonic axial, 

hypertonia appendicular, and dystonia diffuse (and severe generalized dystonic posturing - trunk 

and extremities with rigidity).” Id. He was non-ambulatory, and had decreased range of motion in 
17

his spine. Id. Dr. Marks noted that the diagnosis for H.H. was still “possible AGS” but “with 

negative genetic markers thus far.” Id. at 19. Dr. Marks also considered a retroviral infection as a 

possible cause. Id. He noted that H.H. suffered from extreme irritability and ordered further testing. 

Id.

On March 13, 2014, H.H. was seen by Dr. Kenneth Collins for an infectious diseases 

consultation. Ex. 57 at 1. Dr. Collins noted that he was “consulted because [H.H.] is being referred 

to the infectious diseases clinic over the next couple of weeks for possible retroviral infection 

causing developmental delay.” Id. Under medical history, Dr. Collins noted that H.H.’s “mother 

reports that she breastfed consistently until 10/09[/2013]. Within a day or 2 of stopping 

breastfeeding he seemed to trip and fall when he was crawling.” Id. Dr. Collins noted that HH.’s 

mother reported that H.H. was “completely normal” at his 15-month checkup. Id. Following the 

checkup, she “stopped breastfeeding, and within a week he was falling. About 8 days later, after 

stopping breastfeeding, he got his 15-month shots. After that time he developed increased inability 

to crawl and this progressed over the next couple of months.” Id. Under a review of systems, Dr. 

Collins noted that after H.H. “started falling in mid-October his parents noticed that he had a fever 

for about a week, with a red throat that resolved.” Id.

Upon examination, Dr. Collins noted that H.H. was irritable, made good eye contact, and 

appeared hypertonic. Ex. 57 at 2. His impression was “progressive dystonia with regression of 

developmental milestones from 10/2013 through the end of 12/2013, with no improvement in 

milestones since then. He is now not eating very well and requires a G button” Id. at 3. He also 

had “continuous elevation in liver enzymes with negative hepatitis, cytomegalovirus, and EpsteinBarr virus serologies.” Id. Dr. Collins wanted to recheck H.H. for HIV, but he thought it was 

unlikely that this was the explanation for H.H.’s condition. 

On the same date, H.H. was evaluated for placement of a G button. Ex. 58 at 1. It was noted 

that “over the last 2 weeks, he is refusing to eat or drink very much. He maybe drinks 6-10 ounces 

of PediaSure per day and not really eating unless mom forces him to.” Id. H.H. was also 

dehydrated, urinating 2 times per day “in the last 5 days.” Id. He had also lost three pounds since 

his 15-month checkup. Id.

On March 15, 2014, H.H. underwent surgery for insertion of a gastrostomy tube. Ex. 59 at 

1. H.H. was noted as tolerating the procedure well and the operation was successful. Id. at 2.

On March 25, 2014, H.H. was seen for a lumbar puncture for diagnostic studies. Ex. 56 at 

38. Dr. Marks noted that H.H.’s working diagnosis “has been Aicardi-Goutieres syndrome versus 

retroviral infection based on his markedly elevated CSF neopterin levels.” Id. Various samples 

were taken for neurotransmitter and other testing. Id.

On March 27, 2014, Dr. Marks received the results of H.H.’s updated neurotransmitter 

testing. Ex. 56 at 358. H.H.’s neopterin was extremely elevated at 239 nmol/L (reference range 7-

65 nmol/L) and his tetrahydrobiopterin was also elevated at 75 nmol/L (reference range 18-58 

nmol/L). Id. Dr. Hyland, the Ph.D. who interpreted the testing, noted that these findings were 

consistent with a diagnosis of AGS. Id. at 363.
18

On March 31, 2014, H.H. was seen by Dr. Jason Kennedy at Cook Children’s Hospital, 

Department of Orthopedics Services for neuromuscular decline. Ex. 60 at 1. Dr. Kennedy noted 

that H.H. suffered from a “yet undiagnosed neuromuscular decline.” Id. Interpreting an AP pelvis 

radiograph, Dr. Kennedy noted that H.H. had “encased tone throughout his upper and lower 

extremities” and could “achieve a plantigrade position of the feet.” Id. He noted that H.H. had 

“increased tone at his hip abductors and [had] increased neck-shaft angles on the x-ray” and his 

“Shenton’s lines appear[ed] intact.” Id. Dr. Kennedy ordered a repeat AP pelvis radiograph in six 

months. Id.

On April 17, 2014, H.H. visited Dr. Cantu. Ex. 61 at 12. Dr. Cantu noted that H.H. had a 

“history of hypotonia of unclear etiology” and that he had an “extensive work-up by neurology 

with unclear diagnosis, although it has been suggested he may have a variant of Aicardi.” Id. at 

13. H.H.’s parents reported that “over the past few weeks, he has begun to [spit]-up/reflux much 

more often” and that they were concerned with his level of reflux. Id.

On April 22, 2014, H.H. visited Dr. Marks for follow up regarding neurological regression. 

Ex. 56 at 329. Dr. Marks noted that H.H. did “not have words at 19 months” and his “affect has 

become more flat.” Id. at 330. He was diagnosed with “progressive encephalopathy and dystonia 

with loss of milestones and worsening dystonia. Interferonopathy with elevated [sic] neopterin 

clinically suggestive of Aicardi-Goutiere[s] Syndrome.” Id. at 333. 

On May 21, 2014, H.H. was seen by Dr. Kyriacos Panayides because the neurology 

department wanted a port added to his G button for IVIG treatments. Ex. 59 at 4. The medical 

records note that H.H. was throwing up about thirty minutes after feeding. Id. He had pain during 

feedings and was irritable at night. Id. A pH probe study was scheduled to attempt to locate the 

source of the issue; H.H. had no fever or associated symptoms. Id. Dr. Panayides diagnosed H.H. 

with “gastroesophageal reflux that is not responding to medical treatment.” Id. He ordered a UGI 

study, noting that “if there is horrid reflux, a fundoplication will be performed at the same time as 

the port. If the UGI is equivocal then a formal pH probe study will be done when the port is placed.” 

Id. 

On May 23, 2014, H.H. was seen by Dr. Jane Keng for consultation regarding feeding 

intolerance, vomiting and pain behaviors. Ex. 62 at 1. Nurse notes from that date indicate that the 

reflux was not acidic in nature. Ex. 63 at 1. Dr. Keng noted that H.H.’s CBC was normal, sodium 

was 147, and his bicarbonate was 21. Id. at 2. She noted that his AST was elevated at 119 and his 

ALT was elevated at 125. Id. Dr. Keng’s impression was that the intolerance, pain, and vomiting 

may be due to gastroesophageal reflux disease and she suggested that H.H. be placed on external 

pain medication rather than IV morphine. Id.

On June 23, 2014, H.H. was admitted to the hospital for a follow up with Dr. Marks after 

placement of his gastronomy feeding tube. Ex. 56 at 325. A review of his mental status noted that 

he was “awake (but not very interactive).” Id. at 328. He was nonverbal. Id. A motor system exam 

revealed “motor spastic, rigidity, hypotonic axial, hypertonia appendicular (and severe generalized 

dystonic posturing – trunk and extremities with rigidity).” Id. His reflexes were “1+ equal 

throughout and brisk throughout.” His plantar reflex was “upgoing bilaterally (spontaneous 

extensor responses).” Id. H.H. was “unable to perform heel-to-shin bilaterally.” Id. He was noted 
19

to have “prominent scissoring.” Id. He was non-ambulatory and had decreased range of motion in 

his spine. Id. His abdominal surgical wound was partially healed. Id. He was assessed with 

“progressive encephalopathy and dystonia with loss of milestones and worsening dystonia. 

Interferonopathy with elevated neopterin clinically suggestive of Aicardi-Goutiere[s] Syndrome 

but with negative genetic testing by two different labs.” Id. Dr. Marks stated that because of the 

negative genetic testing, he was “inclined to try several months of IVIG treatment.” Id. He noted 

however, that after a literature review, it did “not appear that IVIG, steroids, [or] azathioprine 

[would be] particularly effective” if H.H. did in fact have AGS. Id. at 329. Nevertheless, H.H. 

began IVIG treatments in June 2014 which lasted for six months. Id.

On October 6, 2014, H.H visited Dr. Kennedy for a follow up. Ex. 60 at 25. Dr. Kennedy 

discussed with H.H.’s parents that H.H. had “neuromuscular hip dysplasia and increasing 

migration.” Id. Dr. Kennedy suggested Botox in the gastrocsoleus complex as treatment. Id.

On November 3, 2014, H.H. was seen for a lumbar puncture and Botox injections. Ex. 56 

at 84. In a patient history obtained from H.H.’s mother, it was noted that H.H. developed “sudden 

regression after vaccines at 15 mo[nths] old.” Id. at 104. Nurse notes from that date also indicate 

that H.H. suffered from an “autoimmune response to vaccines.” Id. at 106. The notes from the 

procedure indicate that H.H. “has laboratory findings consistent with Aicardi-Goutières 

syndrome.” Id. Dr. Marks noted that H.H. had “been on 6 months of IVIG therapy and is here for 

follow [] up studies.” Id. Labs conducted that same day revealed that H.H.’s IGG serum was 

elevated at 2280 mg/dL (reference range 407-1009 mg/dL) and his CSF IGG/albumin ratio was 

elevated at 0.26 (reference range 0.09-0.25). Id. at 92. His neopterin was extremely elevated at 300 

nmol/L (reference range 7-65 nmol/L) and his tetrahydrobiopterin was elevated at 87 nmol/L 

(reference range 18-50 nmol/L). Id. at 93. 

On February 4, 2015, H.H. was seen by Dr. Michel Fayad at Boston Children’s Hospital. 

Ex. 97 at 3. It was noted that H.H. had a history of regression at the age of 15 months and “the 

regression happened around the time of his immunizations.” Id. at 2. Dr. Fayad noted that neither 

metabolic work-ups or genetic work-ups showed any results and the possibility of an autoimmune 

process was still something to look into. Id. at 3. Upon examination, he noted that H.H. was unable 

to sit, crawl, or roll over, but socially he was “very interactive.” Id. at 2.

On March 6, 2015, Dr. Marks provided a letter stating that he was the “pediatric neurologist 

caring for [H.H.].” Ex. 56 at 294. He stated that H.H. had been seen in the neurology clinic for 

“autoimmune encephalitis” and that “he has received IVIG infusions.” Id. Dr. Marks also noted 

that H.H. “has a gastrostomy tube for feeding.” Id. at 33. 

On March 20, 2015, H.H. was seen by Dr. Lesley Hall, Dr. Miriam Bloom, Dr. Sally Evans, 

Dr. Adeline Vanderver, and Amy Fizzino, MGC at the Myelin Disorders Clinic. Ex. 81 at 1. In 

summarizing the visit, Dr. Vanderver noted that H.H. was seen “in the context of developmental 

delay, dystonia, abnormal MRI and elevated CSF interferon/neopterin/tetrahydrobiopterin with a 

clinical diagnosis of Aicardi Goutieres Syndrome, but negative genetic testing and no visible 

intracranial calcifications on an early CT scan.” Id. In summarizing H.H.’s clinical picture, Dr. 

Vanderver noted that:
20

[H.H.] [h]ad been fine until about 15 months of life, hitting all milestones on time. 

In late October he had his 15-month vaccination (dTaP, flu, pneumonia). 

Approximately a week later his crawling was deteriorating. He also had a fever of 

about 102. Two weeks later he had rapid decline of motor function over 4 days, 

with loss of ability to crawl, sit, talk, or use his arms purposefully. He was 

extremely irritable. Per parents recollection he was not encephalopathic.

Id. Dr. Vanderver further noted that IVIG treatments beginning in June 2014 and lasting six months 

“did not seem to improve things significantly.” Id. Dr. Vanderver noted that since that time, H.H. 

had been “fairly stable” and possibly even showed improvement in August 2014, “where he started 

to try to support himself in sitting and reaching for objects” as well as trying to use language. Id.

at 2. Dr. Vanderver noted that H.H. does, however, continue to have significant crying and 

apparent discomfort. Id. Family history, birth history, and social history were reviewed and found 

to be unremarkable in relation to H.H.’s symptoms. Id. at 3-4. 

Upon examination, Dr. Vanderver noted that H.H.’s sleep was “poor” with multiple 

awakenings during the night with crying. Ex. 80 at 2. H.H. also presented with sweating and a 

faster respiratory rate while crying. Id. His parents estimated that he cried about thirty percent of 

the day. Id. H.H. had dystonic posturing and crying, occasionally with...myoclonic jerks. Id. His 

neurologic examination showed that H.H. was able to “briefly regard” the examiner, but he had 

“no vocalizations with communicative intent and did not demonstrate receptive skills” during the 

examination. Id. at 4. Dr. Vanderver’s impression was “developmental delay, dystonia, and 

encephalopathy.” Id. at 6. Dr. Vanderver planned to follow up with Dr. Crow (AGS expert) to 

facilitate genetic resolution of H.H.’s suspected heritable interferonopathy. Id.

On April 1, 2015, H.H. was seen by Dr. Eric Hubli for an enlarged soft palate. Ex. 76 at 

23. Dr. Hubli did not see signs of an enlarge palate, but saw signs of a possible upper airway issues 

for which he recommended a pulmonary evaluation. Id. at 26. 

On April 2, 2015, H.H. visited Dr. Michelle Marcincuk for a sleep consultation due to his 

persistent snoring. Ex. 72 at 13-14. In the HPI, Dr. Marcincuk noted the following was “reported 

by parent”: “Pt got vaccines about 1.5 years ago. Within 3 [] months had dev regression.” Id. at 

14. She noted that per H.H.’s mother, genetic testing was negative. She noted that Dr. Hubli (seen 

on April 1, 2015) believed he had low muscle tone and currently suffered from dysphagia due to 

low muscle tone. Id. Upon examination, she noted that his affect was “consistent with 

encephalopathy” and that he suffered from hypotonia and spasticity. Id. Dr. Marcincuk diagnosed 

H.H. with obstructive sleep apnea and hypertrophy of his tonsils and adenoids. Id. Dr. Marcincuk 

explained to H.H.’s parents that corrective surgery would likely be required. Id.

On April 14, 2015, H.H. was seen by Dr. Sami Hadeed for complaints of stridor. Ex. 69 at 

21. In the patient history, Dr. Hadeed completed notes, which summarized a history provided by 

Mrs. Heller. These notes indicate that H.H. was “reportedly in perfect health until 15 months of 

age when he developed neurological problems that his parents attributed to immunization. [H]e 

was subsequently diagnosed with autoimmune encephalitis.” Id. at 22. H.H.’s parents stated that 

H.H. had “noisy breathing” since birth, but this had gotten “markedly worse since he developed 

neurological problems specially since December.” Id. H.H. had been seen by Dr. Marcincuk, who 
21

diagnosed him with tonsillar and adenoidal hypertrophy, and recommended a tonsillectomy and 

adenoidectomy, along with a flexible fiberoptic bronchoscopy. Id. Upon examination of H.H.’s 

lungs, Dr. Hadeed noted “retractions, intercostal retractions, subcostal retractions, and strider 

inspiratory and clear to auscultation and no distress.” Id. at 24. A review of H.H.’s musculoskeletal 

systems indicated “contractures”, and an examination of his reflexes showed abnormalities of his 

deep tendon reflexes. Id. Dr. Hadeed assessed H.H.’s stridor as secondary to pharyngomalacia and 

his snoring as suggestive of a severe obstructive sleep apnea. Id. at 25.

On April 23, 2015, H.H. was seen by Dr. Cantu for a follow up of his feeding problem and 

gastroesophageal reflux disease. Ex. 80 at 23. In the history of present illness, Dr. Cantu noted that 

H.H. had a history of developmental delay, static encephalopathy, swallow dysfunction, and 

gastrostomy-tube dependence. Id. Per H.H.’s mother, he was gaining weight well. Id. at 24. H.H. 

was in a wheelchair. Id. at 25. 

On April 27, 2015, H.H. was seen for a follow up with Dr. Kennedy. Ex. 60 at 14. In 

interpreting an AP pelvis radiograph, Dr. Kennedy noted that H.H. “appeared to have more wellseated hips today” and his tone was “much improved.” Id.

On April 28, 2015, H.H. was admitted to the hospital for several procedures. Ex. 72 at 1. 

H.H. first underwent a bronchoscopy. Ex. 69 at 19. The procedure went well, and H.H. was 

diagnosed with moderate to severe pharyngomalacia and moderate laryngomalacia. Id.

On the same date, H.H. underwent a successful tonsillectomy and adenoidectomy. Ex. 69 

at 41, Ex. 72 at 4. He was admitted to the PICU following the procedure. Id. A physical exam the 

next day revealed hypotonia and abnormal deep tendon reflexes. Id. It was also noted that he had 

a swallow dysfunction. Id. at 45. An examination by Dr. Hadeed revealed that H.H. was in severe 

pain but calmed down following administration of morphine. Ex. 70 at 13. In the HPI, Dr. Hadeed 

noted that H.H. had suffered from autoimmune encephalitis since 15 months of age. Id.

On April 29, 2015, labs were taken, measuring H.H.’s hemoglobin to be high, with a value 

of 13.2 g/dL (reference range 11.5-13.0 g/dL). Ex. 72 at 9. His sodium bicarbonate was also high, 

measuring at 7220 mm3(reference range 1500-5000 mm3). His Eosinophils and Eosinophil Count 

Test (EOC) was low, measuring at 10 mm3(reference range 30-800 mm3). Id. In the interpretation 

section of the results, it was noted that these findings were consistent with methicillin resistant 

staphylococcus aureus. Id. at 10. 

On the same date, H.H. underwent an allergy panel. Ex. 77 at 1-2. H.H was noted to be 

allergic to cow’s milk. Id. at 2. 

On April 30, 2015, H.H. was discharged from the hospital. Ex. 72 at 1. He was scheduled 

for a sleep study a month later to observe if further surgery was needed. Id. at 2.

On May 3, 2015, H.H. was admitted to the hospital emergency room with fever, lethargy, 

poor perfusion, mild hypoxemia and concern for sepsis. Ex. 69 at 1. Under pertinent medical 

history during triage, nurse notes indicated that H.H. suffered from dystonia and encephalopathy, 

along with “auto immune response to vaccines”, among other conditions. Ex. 71 at 14. H.H. was 
22

given IV broad-spectrum antibiotics and admitted to the intensive care unit for further evaluation 

and treatment. Id. While in the hospital, H.H. was treated for parainfluenza bronchitis, sepsis 

syndrome, hypoxemia secondary to bronchitis, acute respiratory distress secondary to bronchitis, 

acute respiratory failure, fever secondary to bronchitis, and severe pharyngomalcia. Id. His 

hospital discharge records indicate that he suffered from autoimmune encephalitis and 

encephalopathy and developmental delay secondary to autoimmune encephalitis. Id.

On June 24, 2015, H.H. was seen by Dr. Marks for a follow up appointment. Ex. 56 at 389. 

His condition was largely unchanged. Id. at 389-391. At this point he was standing, albeit with 

“max support.” Id. at 389. 

On November 2, 2015, H.H. was seen by Dr. Kennedy for follow up of his hip dysplasia. 

Ex. 95 at 67-68. His parents reported that they were able to get him on a horse for therapy and that 

he was scissoring less. Id. at 68. Dr. Kennedy noted that his tone was increased throughout and he 

had had good response to Botox, which may be useful to try again. Id. at 71.

On February 29, 2016, H.H. was seen by Dr. Kennedy for hip tightness. Ex. 95 at 59-60. 

H.H. was non ambulatory and was extremely inflexible. Id. at 61-62. Dr. Kennedy recommended 

Botox injections. Id. at 62.

On March 4, 2016, H.H. was seen by Dr. Marc Mazade at the infectious diseases clinic as 

a new patient. Ex. 95 at 54, 57. It was noted that H.H. “stopped vaccines after 15 months due to 

neurologic condition that developed after vaccine administration.” Id. at 56. The following patient 

history was obtained from Mrs. Heller and entered into the notes section of the record by Dr. 

Mazade:

[H.H.] is a now 3-year-old boy who was seen by Dr. Whitworth in pediatric 

infectious diseases consultation as an inpatient on March 14, 2014 in regard to 

dystonia and progressive developmental delay. He has subsequently been 

diagnosed with encephalitis of an autoimmune nature presumably due to 

vaccinations two weeks previously. He is referred back to Infectious diseases now 

for possible recurrent C difficile infection. ... His immunizations are on hold due 

to the concern for immunologically mediated neurologic injury.

Id. at 57. 

On May 18, 2016, H.H. was seen by Dr. Marks at the spasticity clinic Ex. 95 at 49. H.H. 

was noted to be wheelchair bound, keeping his hands loosely fisted throughout the exam. Id. at 53. 

His mother reported that normally he was able to open them easily. Id. Dr. Marks noted “dystonictype UE movements present. LEs scissor when he is lifted. Id.

On July 7, 2016, H.H. received Botox injections in his hips. Ex. 95 at 223. The procedure 

was uneventful and H.H. was discharged home. Id.

On August 29, 2016, H.H. was seen by Dr. Kennedy for a follow up exam following a 

Botox injection. Ex. 95 at 41-42. Dr. Kennedy noted that H.H. had “further migration of 
23

progression of his neuromuscular hip dysplasia” and corrective surgery would soon likely be 

required. Id. at 45. 

On November 1, 2016, H.H. was seen by Dr. Abigail Collins at the Neurology Clinic at 

Children’s Hospital Colorado for treatment with medical marijuana. Ex. 98 at 1. H.H. was still 

wheelchair-bound at this time. Id. at 3. It was noted that H.H. had not been treated with 

immunomodulatory therapies to address his ongoing inflammation. Id. at 5. A physical exam was 

largely unchanged from previous exams, although it was noted that H.H. was having difficulty 

with lateral tongue movements. Id. Dr. Collins suggested continuing a trial of medical marijuana 

for tone. Id. at 6. She also strongly recommended that H.H, undergo immune-mediated treatments 

(such as steroids or Rituximab) after her review of the medical records. Id.

On December 5, 2016, H.H. was seen by Dr. Kennedy following treatment in “Colorado 

for treatment with distilled cannabinoids for his overall spasticity and neurologic function.” Id. at 

38. Dr. Kennedy noted that he continued to have decreased range of motion to his hips, most 

notably to his right hip. Id. at 39. H.H. had no issues with his spine. Id. Dr. Kennedy discussed 

surgery for bilateral adductor releases and bilateral proximal femoral varus derotational 

osteotomies with H.H.’s parents. Id. at 40. H.H. was scheduled for surgery on December 8, 2016. 

Id.

On December 8, 2016, H.H. underwent surgery for bilateral adductor releases and bilateral 

varus derotational osteotomies of the femora. Ex. 95 at 199. The procedure was uneventful and 

H.H. was discharged home on December 12, 2016. 

On December 21, 2016, H.H. visited Dr. Kennedy for a follow up after his hip surgery. Ex. 

95 at 31. This was his first visit post-surgery. Id. at 34. Dr. Kennedy observed no complications 

from his surgery and explained that H.H. could begin gentle therapy. Id. at 34-35. 

On January 16 , 2017, H.H. again visited Dr. Kennedy for a follow up after his hip surgery. 

Ex. 95 at 27. At this point, he had no weight bearing restrictions, but was still reluctant to fully 

extend his hips. Id. at 30-31. H.H. was noted to be healing well and improving gradually with his 

flexibility. Id.

On February 27, 2017, H.H. had another follow-up with Dr. Kennedy after his hip surgery. 

Ex. 95 at 22. H.H.’s examination was fairly unremarkable and his mother reported continued 

improvement in stretching of his lower extremities. Id. Dr. Kennedy noted that H.H. had tightness 

in his “gastrocs”, but as he continued to improve, this should resolve. Id. at 26.

On May 1, 2017, H.H. visited Dr. Marks. Ex. 95 at 17. The medical record noted that he 

stopped receiving vaccines “after 15 months due to [a] neurologic condition that developed after 

vaccine administration.” Id. at 18. H.H.’s mother clarified that he was up to date on all vaccines 

except those normally received at four years old. Id.

On May 22, 2017, H.H. visited Dr. Marks for a follow-up 5.5 months post hip surgery. Ex. 

95 at 15. He was noted to be “doing better” and making progress on his hip flexion contractures. 

Id. at 16. Dr. Marks scheduled a follow up appointment for four months later. Id.
24

On June 26, 2017, labs ordered by Dr. Marks found H.H.’s glucose elevated at 121 mg/dL 

(reference range 60-115 mg/dL). Ex. 95 at 77. A neurotransmitter study ordered the same date (but 

reported on August 7, 2017) found H.H.’s neopterin levels to be normal, at 47 nmol/L (reference 

range 7-65 nmol/L) and his tetrahydrobiopterin to be normal as well at 26 nmol/L (reference range 

18-50 nmol/L). Id. at 78. All other results were also within normal ranges. Id. at 77-92. 

That same day, H.H. underwent an MRI of his brain. Ex. 95 at 147. The MRI indicated that 

H.H. had lost white matter volume over the past three years. Id. The corpus callosum was complete 

but “quite thin”. Id. There was also “increased abnormal T2/FLAIR hyperintensity in the 

periventricular white matter, extending into the centrum semiovale in the frontal regions and in the 

periventricular white matter.” Id. Dr. Hayden Head, interpreting these results, noted that these 

findings were concerning for a cerebral neurodegenerative process. Id. at 148. Finally, it was noted 

that H.H.’s “maxillary sinuses are nearly completely opacified. There is also opacification of most 

of the bilateral mastoid air cells.” Id. Dr. Head requested clinical correlation for sinusitis and ear 

infection. Id. at 148.

On July 9, 2017, H.H. was seen by Dr. Jian Tong at Cook Children’s Emergency 

Department with complaints of seizure. Ex. 95 at 105. The seizure started with “eyes twitching 

then full body twitching upon ambulance arrival.” Id. Upon arrival of EMS, H.H. had “lip 

smacking and eye rolling...and he also began to develop [] right upper extremity and then left 

upper extremity tonic-clonic twitching.” Id. at 114. He had no history of seizures. Id. at 105. Under 

medical history, it was noted that H.H suffered from “vaccine dystonia.” Id. The seizure lasted 

approximately one hour and H.H. was reportedly playful and active prior to symptoms. Id. He had 

no fever prior to the seizure. Id. Upon arrival at the emergency department, H.H. had a fever of 

103o F, a white blood cell count of 21, and hypoxia, with O2 saturation 86% on room air. H.H. was 

intubated. Id. Upon admission, H.H. was chemically sedated and paralyzed. Id. at 110. His O2 

saturation was 97% on mechanical ventilation. Id. He had “coarse breathing sounds bilaterally.” 

Id. He was also tachycardic. Id.

While still in the hospital, H.H. was seen by Dr. Ryan Meyer, who noted that H.H. had a 

past medical history “significant for autoimmune encephalopathy thought to be vaccination related 

with severe dystonia” at normal baseline prior to the onset of seizure. Ex. 95 at 114. Dr. Meyer 

noted that a blood gas was obtained which revealed a pH of 6.97 and a CO2 of 111. Id. H.H. was 

transferred to the PICU and continued to receive ventilation. Id. 

Later that day, an electroencephalogram was conducted by Dr. Adrian Lacy. Ex. 95 at 126-

27. Dr. Lacy noted that H.H. was “a 4-year-old patient with a prior history of developmental delay 

and dystonia, who is admitted with febrile seizure, manifesting with right face and arm clonus and 

right eye deviation, as well as impaired mental status.” Id. at 126. Upon examination, Dr. Lacy 

observed that “The hypersomnolence and generalized slowing seen in states of maximal 

stimulation during the recording are reflective of diffuse nonspecific neuronal dysfunction as may 

be seen in multiple encephalopathic or sedated states.” Id. at 127.

On July 10, 2017, Dr. Meyer observed significant improvement in H.H.’s condition. Ex. 

95 at 133. An EEG taken overnight showed no seizure activity and no epileptiform activity. Id.
25

Dr. Lacy, also examining H.H. that day, stated that H.H. appeared to return to his prior baseline. 

Id. at 134. Under impression, Dr. Lacy wrote:

This is a very interesting almost 5-year-old patient with a prior history of acute 

encephalopathy with dystonia occurring at approximately 16 months of age, which 

has been previously associated with vaccinations by parents, although the

significance of this is unclear, who has had extensive testing and have some 

chemical parameters consistent with Aicardi Goutieres syndrome, for which the 

range of onset and symptomatology may be relatively wide. However, the patient 

does not have any gene mutations associated with this syndrome, and variants of 

uncertain significance in his whole exome sequencing have not been shown to be 

associated. He is being treated symptomatically for his dystonia, and recent

neuroimaging shows progressive white matter volume loss consistent with an 

ongoing neurodegenerative process of uncertain origin.... The origin of the seizure 

at this time is of uncertain cause, but the patient was not known to have fever prior 

to the onset of seizure, and has not had fever since, has no evidence for encephalitis 

currently by examination or by spinal fluid study. EEG is strongly suggestive of 

postictal slowing in the left posterior temporal region, which is strongly concordant 

with the patient's seizure semiology.

Id. at 135.

On July 11, 2017, H.H. was discharged from the hospital. Ex. 95 at 130. In the discharge 

summary, it was noted that:

[H.H.’s] condition and new changes were discussed extensively with his attending 

neurologist, Dr. Warren Marks. The management of Aicardi-Goutieres syndrome 

is unclear, but it is felt by world-wide authorities that rituximab and other B-cell 

immunotherapy is not effective. The management of seizures is not different with 

Aicardi-Goutieres syndrome than with epilepsy syndromes. The plan arrived at in 

discussion with Dr. Marks and family was for the patient to be discharged home 

with Diastat to be used as rescue if needed, continue seizure precautions and first 

aid and ER warnings, repeat EEG following discharge at baseline to evaluate for 

need for initiation of antiepileptic therapy, and Dr. Marks will seek authorization 

for a new medication, which is designed to inhibit the JAK-1 pathway, and 

experimental use for AGS.

Id. at 131. 

On August 23, 2017, H.H. was seen by Dr. Kennedy for a follow up appointment. Ex. 95 

at 6. Dr. Kennedy noted H.H. liked to attempt standing. Id. at 10. He had had stem cell treatment 

done in Panama, though H.H.’s mother reported no effect as of yet. Id. At the time, Petitioner was 

still awaiting news from Dr. Vanderver or Dr. Crow regarding H.H.’s molecular diagnosis. Id.

On October 2, 2017, H.H. was seen by Dr. Kennedy for a follow up after his hip surgery. 

Ex. 95 at 1. He was noted to be comfortable and his hip flexion contractures were improving. Id.
26

at 5. Dr. Kennedy noted that H.H. was not progressing towards ambulation at this point, although 

he had “wide, symmetric abduction of the hips and [was] continuing to improve.” Id.

On November 29, 2017, H.H. visited Dr. Marks. Ex. 96 at 98. H.H.’s mother stated that at 

the time, the only medication he was on was Botox. Id. at 101. She denied any new concerns 

regarding H.H.’s condition. Id. at 102. Upon examination, Dr. Marks noted that H.H.’s hypertonia 

seemed improved since his last visit. Id. He had bilateral Achilles contractures and his hips were 

“very tight.” Id. He was “attentive and cooperative” and engaged well with others. Id. Dr. Marks’ 

assessment was “progressive encephalopathy and primary dystonia with loss of milestones and 

worsening dystonia” and “interferonopathy with elevated neopterin clinically consistent [with] 

Aicardi-Goutiere[s] Syndrome or other autoimmune mediated event.” Id.

On October 1, 2018, H.H. was seen by Dr. Marks for planned Botox injections in his lower 

extremities. Ex. 96 at 1-2. Dr. Marks described H.H.’s condition as “autoimmune [encephalitis] –

presumed Aicardi Goutiere[s] syndrome.” Id. at 2. 

On December 10, 2018, H.H. was seen by Dr. Marks for a neurologic exam. Ex. 96 at 5. 

Dr. Marks noted that per his parents, H.H. had been less active since he received Botox injections, 

with intermittent dilated pupils and coolness of his extremities. Id. H.H. was observed to be 

somnolent and nonverbal. Id. His pupils were pharmacologically dilated and he had generalized 

truncal hypotonia. Id. He had increased reflexes and bilateral striatal toes. Id. at 6. Dr. Marks noted 

that H.H.’s dystonia was worsening. Id. Regarding AGS, Dr. Marks noted that H.H. had “negative 

genetic testing by two different labs for all seven known AGS genes – however that only covers 

95% of AGS cases.” Id.

On January 10, 2018, H.H. was seen by Dr. Kennedy for a pre-op discussion regarding his 

G button and removal of hardware. Ex. 96 at 69. H.H.’s mother reported that he was “tight” in his 

adductors. Id. Upon examination, his neurological condition was largely unchanged. Id. Upon a 

musculoskeletal examination, Dr. Kennedy noted that H.H.’s hip flexion contractures were 

improving, and that his ankles could be “fatigued to a neutral positioning.” Id. at 73. H.H.’s 

radiographs showed that he had “well-seated” hips. Id. 

On January 23, 2019, H.H. was seen by Dr. Marks. Ex. 96 at 10. Dr. Marks noted that H.H. 

was deteriorating with motor regression – “severe quadriparesis dystonia/spasticity with bulbar 

involvement.” Id. Dr. Marks noted that H.H. was “more alert” and his extremities seemed cool 

rather than warm. Id. His examination was largely unchanged from December 10, 2018. Id. at 11-

12. Dr. Marks noted that H.H. did not have independent sitting and no standing, and that he 

appeared lethargic. Id. at 11-12.

Dr. Marks noted that H.H.’s dystonia was currently being treated symptomatically. Ex. 96 

at 13. He stated that the “best plan would be a JAK 1/2 inhibitor”, noting that he had discussed the 

idea with Dr. Janik Crow and Dr. Vanderver (CHOP). Id. He also stated that “JAK 1/2 inhibition 

would appear [to be] the best treatment even if [H.H.’s injury was] triggered by [an] immune 

response to external stimulus such as immunization.” Id.
27

On the same date, H.H. was seen for an MRI of the brain. Ex. 96 at 15. Dr. Hayden Head, 

interpreting, found “cerebral white matter volume diffusely moderately diminished, with 

associated continued thinning of the corpus callosum.” Id. at 16. He also noted a “persistent thin 

band of abnormal T2/FLAIR hyperintensity in the periventricular white matter” and “abnormal 

T2/FLAIR hyperintensity with suspected volume loss of bilateral insula.” Id. Further, “the third 

ventricle [was] substantially larger, while still maintaining a non-obstructed appearance.” Id. “The 

lateral ventricles and fourth ventricle [were] mildly larger. The subarachnoid spaces and cerebella 

fissures [were] newly prominent.” Id. Trace fluid was noted in the mastoid air cells, “markedly 

decreased” from H.H.’s previous MRI. Id. Dr. Head’s impression was “enlargement of ventricles 

and subarachnoid spaces” and he was concerned for progressive neurodegeneration. Id. He also 

noted that there was “no significant change of already existing abnormalities” and that “for 

Aicardi-Goutieres syndrome, the severity of findings is quite mild.” Id.

H.H.’s neurotransmitters were also measured at this visit. Ex. 96 at 14. His neopterin was 

elevated at 176 nmol/L and his tetrahydrobiopterin was also elevated at 42 nmol/L.

On July 22, 2019, H.H. visited Dr. Shirley Tetteh at Cook Children’s Hospital Emergency 

Department. Ex. 96 at 17. H.H. presented with “seizure-like activity” at home, for which his home 

health nurse administered two doses of Diastat. Id. at 18. His mother stated that his seizure lasted 

for about four hours and H.H. was febrile approximately two hours into the seizure. Id. Per the ED 

nurse’s note, H.H. was actively seizing upon arrival. Id. Dr. Tetteh also noted that three weeks 

prior, H.H. had received his third regimen of stem cell treatment in Panama. Id. H.H. was admitted 

to the hospital. Id. Upon examination, it was noted that H.H. “appeared thin” and had increased 

tone in both his upper body and lower body. Id. at 39-40. He also had abnormal muscle tone. Id.

at 40. H.H. was admitted to the hospital on the same date. Id. at 17. 

On September 4, 2019, H.H. was seen by Dr. Marks and his MA, Ms. Kim Sunday. Ex. 96 

at 56. His examination was largely unchanged from his neurological baseline. Id. at 58-60. 

No additional medical records pertinent to this decision have been filed.

III. Petitioners’ Affidavits and Testimony

A. Affidavits 

1. Heathe Heller

Mr. Heller is H.H.’s father. He testified that H.H. was born with no complications and was 

otherwise healthy prior to his October 17 and 23, 2013 vaccinations. Ex. 64 at 1-2. H.H. was 

developmentally on track for a 15-month old child. Id. at 2. H.H was “able to walk with one hand 

assistance, crawl on his own, and climb.” Id. H.H. was also able to say some words like “Mama” 

and “Dada”, and interact with family members by waving, kissing, and playing with the family 

dog. Id.

The first time Mr. Heller noticed a change in H.H.’s health and behavior was one week 

after his 15-month checkup where he had received his vaccinations and flu shot. Ex. 64 at 2. H.H. 
28

lost the ability to do many of the things he had been able to do prior, including crawling, feeding

himself, talking, waving, and standing. Id. H.H. also seemed to be more irritable, and in a lot of 

pain. Id. In early November of 2013, Mr. Heller remembered that H.H. ran a fever of 102o F for 

two days and was recommended by Dr. Hollis to see a neurologist. Id. In December 2013, H.H.

was referred to many specialists and had many tests and procedures performed. Id. H.H. still does 

not have a diagnosis but has general diagnoses of dystonia and encephalopathy. Id. at 2-3. 

2. Jenna Heller

Mrs. Heller gave birth to H.H. with no complications and he was a healthy child who 

experienced normal minor illnesses. Ex. 65 at 1-2. H.H. was a happy, outgoing, and energetic 

child; he liked to play with golf clubs, hit golf balls, and play with the family dog. Id. at 2. Mrs. 

Heller took H.H. to his 15-month vaccinations in October 2013, where he received his influenza 

and DTaP vaccinations. Id. About a week after his vaccinations, H.H. ran a fever and his overall 

health declined. Mrs. Heller took H.H. to Dr. Leslie Hollis, who referred him to specialists at Cook 

Children’s Hospital. Id. Doctors and specialists have not been able to determine H.H.’s diagnosis

but he is being treated for dystonia and encephalopathy. Id. Mrs. Heller stated that “The only 

possible cause for H.H.’s drastic and significant decline in health is a complication resulting from 

the vaccinations he received at fifteen months, based on the timing and the severity of his 

problems.” Id. at 3. It is devastating to see H.H. unable to do the things he used to love so much. 

Id. H.H. is now in a wheelchair and requires a feeding tube to eat. Id. 

3. Angela Kleinhans

Ms. Kleinhans is H.H.’s aunt. Ex. 92 at 1. Ms. Kleinhans stated that her daughter, H.H.’s 

cousin, suffered from a vaccine reaction at her four month vaccinations so she has been aware of 

potential side effects ever since. Id. at 2. Ms. Kleinhans stated that H.H. regressed so severely she 

immediately thought it was related to his vaccinations. Id. Ms. Kleinhans also recalled that H.H. 

was a very normal baby and met his milestones on time. Id. Ms. Kleinhans noted that “The 

weekend after H.H. received his 15 months vaccinations he came down with a really high fever.... 

A few days [after October 23, 2013] he got sick and he was never the same again.” Id. Ms. 

Kleinhans remembered receiving a call from Mrs. Heller to come to her house the weekend of 

November 1st because she was worried about H.H. and he was now “doing this limp thing with his 

leg.” Id. Ms. Kleinhans stated she saw H.H. two times each week after this date and saw H.H. 

rapidly declining, from walking to limping, to crawling, and then crawling with his right leg 

dragging behind him. Id. at 3. Ms. Kleinhans recalled that the family believed he had simply 

injured his leg, but around November 8, 2013, Ms. Kleinhans saw that H.H. could no longer crawl 

or sit up. Id. Ms. Kleinhans next recalled that H.H.’s hands “started turning in” and he could no 

longer hold his head up on his own. Id. Ms. Kleinhans stated the Hellers took H.H. to the doctor 

around November 13, 2013 and in the ensuing weeks, H.H. lost all speech, he would gag on all 

food he ate, and he lost all motor skills. Id.

4. Sheri Huling

Ms. Huling signed her affidavit on March 21, 2016. Ex. 91. Ms. Huling is H.H.’s great aunt 

and had worked as a pediatric physical therapist for 35 years as the time she signed her affidavit. 
29

Id. at 2. Ms. Huling noted that H.H. was crawling, standing, and was able to take steps between 

furniture before his vaccine on October 23, 2013. Id. Ms. Huling stated that a few weeks prior to 

his October 23, 2013 vaccination, she noticed some tightness in his right heel cord that she directed 

Mrs. Heller to bring up at H.H.’s next appointment. Id. Ms. Huling recommended some stretches 

for Mrs. Heller to do with H.H. Id. Because H.H. was bearing weight on both legs, Ms. Huling 

was not concerned. Id.

Ms. Huling next saw H.H. on October 31, 2013 for Halloween and noticed him fall over 

when in a sitting position, and fall on a separate occasion when he was standing. Id. Ms. Huling 

described a distinct memory where H.H. was standing in the family driveway as other children 

were boarding a hayride and noticed H.H. “just falling down while standing.” Id. at 2-3. Ms. Huling 

described receiving a call from Mrs. Heller on November 14, 2013. Id. at 3. Mrs. Heller was very

concerned because H.H. was unable to sit up or crawl and wanted Ms. Huling to see him so she 

knew what to do. Id. Within two minutes of seeing H.H., Ms. Huling averred that she knew there 

was a “serious neurological insult.” Id. Ms. Huling noted that H.H.’s trunk “was so hypotonic he 

would just bend over forward while sitting on the floor and then could not right himself with his 

arms.” Id. H.H.’s arms also could not support his body to crawl. Id. Everyone left for Cook 

Children’s Hospital immediately. Id. H.H. continued to deteriorate over the next few months and 

is now wheelchair dependent. Id.

Ms. Huling testified at the January 22, 2020 entitlement hearing noting discrepancies 

between this affidavit and a letter she wrote to Ms. Guerra which served as the basis for her 

affidavit. See Tr. at 205-07. Ms. Huling’s letter to Ms. Guerra was filed as Exhibit 102. In this 

letter, Ms. Huling stated that H.H. was crawling, standing, and taking steps between furniture prior 

to his vaccine on October 17, 2013. Ex. 102 at 1. After his pneumonia and flu vaccine on October 

17, 2013, H.H. and Mrs. Heller visited Ms. Huling. Ms. Huling noticed that “over the last few days

[H.H.] was having some trouble cruising around furniture and taking steps and [Mrs. Heller] asked 

me to take a look at him from a therapist perspective.” Id. at 1 (emphasis added). Ms. Huling 

noticed that H.H. had right heel cord tightness that was alarming and told Mrs. Heller to bring this 

matter up at H.H.’s next visit on October 23, 2013. Id. Ms. Huling next saw H.H. on Halloween 

and noted worsening tightness in his right heel cord and described two instances where he fell 

while sitting and standing. Id. The other details provided are similar to what was stated in her 

affidavit. See generally id.; see generally Ex. 91. 

B. Testimony

1. Heathe Heller

Mr. Heller testified at the January 22, 2020 entitlement hearing. Mr. Heller is a gas and oil 

consultant in Midland, Texas. Tr. at 95-96. Mr. Heller described H.H.’s first year of life as fun 

because he was such a playful child. Id. at 96. Mr. Heller did not accompany Mrs. Heller to the 

vaccination appointments but his first recollection of something being wrong was when H.H. 

began dragging his leg. Id. at 98. Mr. Heller also testified that he noticed something “was different” 

on Halloween but couldn’t pinpoint a specific date regarding when H.H.’s leg dragging began. Id.

at 99. After Halloween, Mr. Heller remembered that H.H. would be playing, get tired, and lay 

down; at some point the other leg started to give out as well. Id. at 100. Mr. Heller was not present 
30

when Mrs. Heller drove to “Aunt Sher[i]’s” but remembered being at Cook’s Hospital emergency 

room and talking to Dr. Aalbers. Id.

Mr. Heller testified that none of the doctors H.H. has seen have been able to give him a 

diagnosis. Tr. at 103. H.H. is currently dependent on someone at all times. Id. at 104. H.H. now 

has a full-time nurse and is able to go to school. Id. After the Hellers had another child, Mrs. Heller 

spent more time with their new baby to breast feed him, so Mr. Heller slept with H.H. from 2013-

2017, until they moved to Midland and got his own room. Id. at 105-06. 

2. Jenna Heller

Mrs. Heller testified at the January 22, 2020 entitlement hearing. Mrs. Heller is a licensed 

professional counselor (LPC), working in the court system as a parenting coordinator and 

performing custody evaluations for custody cases. Tr. at 7. Petitioners and their family moved to 

Midland, Texas in 2017 for Mr. Heller’s work. Id. at 8. Petitioners have three sons, including H.H. 

Id. H.H. was born with no complications but had an abnormal newborn screening with elevated 

liver enzymes, which was resolved. Id. at 9. H.H. had some testing performed for his elevated liver 

enzymes but the results ended up being negative. Id. at 10-11. 

Regarding H.H.’s first year of life, Mrs. Heller testified she was a paranoid mom but had 

no issues with H.H. Tr. at 11. Mrs. Heller took H.H. to Dr. Leslie Hollis for his 15-month checkup 

and had concerns about whether his language skills were on track and also with him being “pigeontoed.” Id. at 13. Mrs. Heller stated she could not remember if it was his right leg or both legs that 

turned inward. Id.

I asked Mrs. Heller about a phone call she made before H.H.’s 15-month appointment about 

her concern about his ability to walk. Tr. at 15. Mrs. Heller stated she thought H.H. should be able 

to walk more independently by 15 months but he would take a few steps and resume crawling. Id.

at 15. Mrs. Heller confirmed that she was concerned about his right foot turning inward on this 

phone call as well. Id. at 15-16. Dr. Hollis assured Mrs. Heller that H.H. was developmentally in 

range during the 15-month checkup and was meeting the appropriate milestones. Id. at 16. 

Mrs. Heller testified that H.H. received two vaccinations on October 17, 2013, the flu and 

pneumonia shots, and that the office had run out of Tdap vaccines so they scheduled for Mrs. 

Heller and H.H. to return the following week to get the Pentacel vaccination. Tr. at 17. Mrs. Heller 

said she noticed that H.H. had a fever the weekend after the vaccinations and slept the whole time. 

Id. at 18. The following week was the week of Halloween which is when Mrs. Heller noticed he 

was dragging his right foot and leg. Id. at 18-19. Mrs. Heller also remember arguing with Mr. 

Heller because he noticed it first and thought H.H. had fallen and injured himself. Id. On 

Halloween, other people noticed something off with H.H. because he typically stood with his 

friends who are around the same age as he is, but he would just fall over and sit. Id. at 19-20. Over 

the weekend, Mrs. Heller testified that his other leg started to drag as well, prompting Mrs. Heller 

to call and schedule an appointment with Dr. Hollis. Id. at 20. Dr. Hollis “had no clue... what was 

going on” but said H.H. needed to see a geneticist right away and got an appointment with Dr. 

Heather Crawford. Id. at 21. 
31

H.H.’s first appointment with Dr. Crawford was on November 5, 2013.13 Tr. at 21. Dr. 

Crawford knew something was wrong but did not feel like H.H. needed to be admitted; she

instructed Mrs. Heller to see Dr. Hollis if he worsened. Id. at 22. During this appointment, Mrs. 

Heller stated that H.H. could no longer crawl. Id. He could crawl during the weekend but one leg 

dragged behind, which is why Mrs. Heller thought it could have been an injury. Id. at 23. 

Between the two appointments with Dr. Crawford, H.H. went from being unable to crawl, 

to being unable to sit up. Tr. at 24. Mrs. Heller immediately contacted her aunt, Sheri Huling, and 

drove H.H. out to Decatur, Texas, where Ms. Huling lived. Id. at 24-25. Mrs. Huling did “some of 

her PT things to try to figure out” what was wrong, and told them to go to Cook’s ER. Id. at 25. 

Ms. Huling and Mrs. Heller’s mother drove them to Cook’s [Hospital] emergency department. Id.

Ms. Huling said something about H.H. not bending his legs, they were straight and scissoring, and 

had a tight right (or left) heel cord, like a ballerina. Id. Dr. Aalbers was the neurologist on call at 

the hospital so he is the one who observed H.H. upon arrival. Id. Dr. Aalbers believed H.H. was 

experiencing dopamine responsive dystonia (DRD), and prescribed H.H. dopamine. Id. at 26, 27. 

Mrs. Heller stated that the dopamine made H.H. very sick and did not help him at all. Mrs. Heller 

remembered reporting back to Dr. Aalbers that the dopamine was not working around two weeks 

after their visit. Id. at 28. Mrs. Heller testified that at some point, Dr. Aalbers called to inform her 

that H.H.’s “brain cells are dying at a really rapid rate, and we don’t know why.” Id. at 28. The 

next steps for H.H. was to have his whole genetic exome sequenced, which Dr. Crawford said 

would take two to four months. Id. at 28-29. H.H. continued to get worse; he could pick up food 

at one point but would bite his fingers when they were in his mouth. Id. at 29. At some point, H.H. 

couldn’t bring the food to his mouth anymore and it would fall out of his hands prior to it reaching 

his mouth. Id. H.H. was also not sleeping much at the time and was crying all the time; only over 

time did the Hellers discover it was because he was in pain. Id. at 30. 

Around three years, ago, in 2017, there was a huge turn around and it was “kind of like he 

came out of this fog.” Tr. at 30. Dr. Hollis informed them that H.H. probably had a massive 

migraine all the time and was cramping. Id. at 30-31. Somewhere around December 2013 or 

January 2014, doctors were able to tell the Hellers that H.H.’s neopterin and tetrahydrobiopterin 

levels were too high, and medical research could only find levels that high in HIV or AGS patients. 

Id. at 31. Drs. Aalbers and Crawford explained that AGS was a very rare genetic disorder, more 

common in Amish communities. Id. at 32. Mrs. Heller testified that she emailed Dr. Crow to get 

H.H. tested for AGS around Christmas; Dr. Marks had told the Hellers about Dr. Crow and he was 

the most specialized researcher of AGS. Id. H.H.’s first round of testing was negative and there 

were six or seven known mutations of AGS at the time. Id. at 33. Another gene was discovered 

after the petition was filed but H.H. was still negative for the new gene. Id. at 33-34. 

H.H. continued to worsen and was given a G tube for his dehydration and eating issues. Tr. 

at 34. H.H. had a consultation with Dr. Suzanne Whitworth, who asked whether H.H. had any 

changes in his diet, to which Mrs. Heller informed her that she had weaned H.H. completely off 

breastfeeding on October 9, 2013. Id. at 34, 37. Mrs. Heller clarified that H.H. did not deteriorate 

after being weaned off of breastmilk but after his vaccinations. Id. at 37. Mrs. Heller also disputed 

13 Later in her testimony, Mrs. Heller recognized that she had shifted these events one week forward. Tr. at 

86.
32

Dr. Whitworth’s notation that H.H. started falling in mid-October and a “red throat and fever” that 

lasted about a week. Id. at 40-41; see also Ex. 57 at 1. Mrs. Heller clarified she does not recall a 

red or sore throat. Id. at 41-42. 

Under Dr. Marks’ care, H.H. was immediately tested for AGS genes and he was started on 

Baclofen. Tr. at 43. H.H. also had Botox injections and prescribed Thianicol and Clonidine. Id. at 

43-44. Mrs. Heller testified that all these various treatments did not help or alleviate H.H.’s

symptoms. Id. at 45. 

Mrs. Heller said she found out about vaccine injuries from her sister-in-law, whose

daughter had a vaccine reaction. Tr. at 46. Mrs. Heller said it was always in the back of their minds 

because there were so many different avenues for them to pursue. Id. She kept suggesting things 

to Dr. Marks so she must have mentioned the vaccinations as some point but Mrs. Heller doesn’t 

know specifically when. Id. at 46. Dr. Marks would always call H.H.’s condition AGS-like and be 

very vague. Id. at 47-48. Mrs. Heller recalled travelling to Boston and seeing a neurologist there 

who told her he had never seen a patient like H.H. before. Id. at 49. Mrs. Heller then recalled going 

to DC to do additional genetic testing, but the testing was also negative. Id. at 50. 

Mrs. Heller testified that before the petition was filed, Drs. Marks and Crow were still 

doing some testing but Dr. Marks told the Hellers that he believed that the vaccines triggered and 

induced H.H.’s condition. Tr. at 51-52. H.H. had been repeatedly tested for the genes associated 

with AGS which came back negative. Id. at 53. In 2015 (she later stated that it was during 2016-

2017), Mrs. Heller recalled H.H. coming out of a fog; within six months, his eyes were brighter 

and seemed happier and would snuggle with his family members and move his arms to reach for 

people. Id. at 53-54. The Hellers returned to Dr. Marks during this time, who was surprised at 

H.H.’s improvement. Id. at 54-55.

Mrs. Heller testified that the first two years of H.H.’s condition were horrible but the last 

two years (2017-2019) have been amazing. Id. at 55. The Hellers slept with H.H. until they had a 

second child and they slept in entirely separate rooms. Id. at 56. The Hellers’ second child grew 

up travelling with H.H. and going to all of this medical appointments. Id. Their second child had 

to grow up quickly as a result. Id.

Regarding the November 11, 2013 visit with Dr. Hollis, the medical record notes that H.H. 

had been fussy for the past week and had been experiencing developmental regression over the 

last month. Tr. at 60-61. Mrs. Heller denied this record indicated H.H.’s developmental regression 

began around October 11, 2013. Id. at 61. 

Because there was some confusion with the timeline, Mrs. Heller then recounted what 

occurred from her September 13, 2013 phone call to the November 11, 2013 appointment with Dr. 

Hollis. Tr. at 63-66. Of note, Mrs. Heller stated that at some point after his vaccinations, H.H. ran 

a fever and on a Monday morning, they went to see Dr. Hollis; on a Tuesday, they had an 

appointment with Dr. Crawford; on Thursday, they went to Ms. Huling’s house and went to the 

hospital. Id. at 65-66. Mrs. Heller also recalled having an argument with Mr. Heller the week of 

Halloween because other people had noticed H.H. having issues. Id. at 66. Mrs. Heller testified 

that all she could remember was H.H. slept throughout the weekend and “[b]y Halloween, he was 
33

not running a fever anymore, because I wouldn’t have let him around his little buddies, his friends.” 

Id.at 68. Between Halloween and when he was seen by Dr. Hollis, H.H. must have only 

experienced leg dragging, otherwise she would have sought medical attention sooner. Id. at 68-69. 

Mrs. Heller’s concern grew only when he was unable to sit up “that Monday morning.” Id. at 69. 

There was a dramatic change between Monday and Thursday; H.H.’s legs were stiff, and his torso 

was hypotonic. Id. Mrs. Heller was unsure if his fever occurred the weekend after his October 17, 

2013 vaccinations or after the October 23,2013 vaccination. Id. at 70-71. Mrs. Heller testified that 

around Halloween, H.H. could stand and he tried to play with his friends but he would fall over 

and it “presented more like maybe at that time a virus kind of thing.” Id. at 72. The leg symptoms 

occurred in his right leg and transferred to his left, then torso, arms, grasping, and the mouth was 

last. Id. at 72-73. This progression lasted until the end of 2013, leaving H.H. nonverbal and unable 

to chew. Id. at 73. 

Mrs. Heller testified that H.H. now sees seven therapists, once or twice per week, and

regularly sees Drs. Marks and Hollis. Tr. at 87. H.H. has also had the same teacher for the past 2.5 

years. Id. H.H. is able to communicate through his eyes, he can watch television, and he is happy 

most of time. Id. at 87-88. H.H. still cannot move independently but he can move his arms to grab 

people’s faces. Id. at 89. 

3. Sue Sewell

Ms. Sewell is Mrs. Heller’s mother, grandmother to H.H. Tr. at 108-09. Ms. Sewell is now 

retired but was a registered nurse, and worked as the chief nursing officer at a hospital in Decatur. 

Id. at 109. Decatur is not far, so Ms. Sewell made almost weekly visits to the Hellers. Id. at 109-

10. Ms. Sewell accompanied Mrs. Heller to the October 17, 2013 appointment with Dr. Hollis 

where H.H. received two vaccinations. Id. at 111. Ms. Sewell stated she remembered H.H. could 

walk about two to three steps unassisted. Id. at 112. She also stated she did not remember any 

conversation at the appointment regarding the turning inwards of H.H.’s right leg. Id.

Ms. Sewell testified that the weekend before Halloween, around October 26th, H.H. was 

sleeping for many hours and she thought it was strange. Tr. at 113. She brought it up to Mrs. Heller 

but they weren’t sure if it was an issue they should be concerned about. Id. Ms. Sewell also noticed 

that H.H.’s legs did not really support him, and he kept falling over. Id. Ms. Sewell stated her 

daughter, Mrs. Heller, would call nearly every day expressing concern that H.H. was not standing 

anymore. Id. at 115. H.H. would try to feed himself but would end up biting his finger, 

demonstrating he couldn’t coordinate his movements. Id.

On November 7, 2013,14 Ms. Sewell recommended Mrs. Heller take H.H. to her sister, 

Sheri Huling, or Aunt Sheri, because she had been a pediatric physical therapist for 30 years. Tr. 

at 115-16. Aunt Sheri did some tests with H.H., including putting him on all fours and having him 

crawl to Mrs. Heller, but he couldn’t do these things. H.H.’s arms would collapse and he couldn’t 

move towards Mrs. Heller. Id. at 116. Aunt Sheri told them they needed to go Cook’s (Hospital) 

immediately and Aunt Sheri drove them because they were in shock. Id. at 117. Ms. Sewell 

14 Again, this testimony shifted the visit to Cook’s Hospital forward. It is documented in the medical 

records that H.H. did not visit the hospital on November 7, 2013.
34

accompanied Mrs. Heller to H.H.’s medical appointments when Mr. Heller could not. Id. The 

Hellers’ lives have changed dramatically because of all the doctors they tried to take H.H. to, 

around the country. Id. at 118-19. H.H. has never been able to get a diagnosis from any doctor. Id.

at 119. 

4. Sheri Huling

Ms. Huling is H.H.’s great aunt, Mrs. Heller’s aunt, and Ms. Sewell’s sister. Tr. at 124. 

Ms. Huling was a physical therapist for 38 years. Id. at 125. She received her degree from the 

University of Texas Health Science Center. Id. Ms. Huling saw H.H. approximately every month 

during his first year of life. Id. at 126. Ms. Huling had no concerns with H.H.’s early development. 

Id. at 126-27. 

Ms. Huling remembered Halloween very distinctly. Tr. at 128. The family was preparing 

to go on a hay ride, and H.H. was standing in the driveway and just fell over. Id. Ms. Huling 

examined him after he fell over and noticed his right ankle was tight. Id. Ms. Huling told Mrs. 

Heller to inform his pediatrician. Id.

Ms. Huling received a phone call from Mrs. Heller on November 7, 2013,15 asking if she 

could bring H.H. over. Tr. at 129. Mrs. Heller stated on the phone that H.H. kept falling over and 

could not sit upright. Id. H.H. could not crawl and Ms. Huling told them to immediately go to 

Cook’s hospital. Id. at 129. Ms. Huling’s first impression was that H.H. was experiencing some 

type of encephalopathy because his problems appeared to be neurological. Id. at 130. 

Ms. Huling testified about her affidavit (Ex. 91). Tr. at 130-34. Ms. Huling’s affidavit 

stated she saw H.H. on November 14, 2021, but Ms. Huling stated she saw H.H. the same day he 

went to Cook’s Hospital, and that her affidavit had an error. Id. at 134. 

From a therapist’s perspective, Ms. Huling stated H.H. would need constant care the rest 

of his life. Id. at 135. H.H. has made some improvements, as he has been able to feed without a 

tube and can play some games. Id. at 136. Ms. Huling testified that she did not remember if Mrs. 

Heller called her in September 2013 regarding the turning in of H.H.’s right leg. 

Ms. Huling clarified that she saw H.H. after his October 17, 2013 vaccinations and noticed 

the right heel tightness then. Id. at 139. Ms. Huling stated it was specifically “the week before the 

23rd... I think it was the week before the 23rd.” Id. Ms. Huling was brought back to the stand to 

confirm that she observed H.H. have right heel cord tightness before the October 23, 2013 

vaccination. Id. at 205. Ms. Huling wrote a letter to Petitioner’s counsel to prepare her affidavit. 

Id. Ms. Huling noted that H.H. exhibited normal crawling, pulling and standing, cruising, and 

performed other physical acts prior to his October 17, 2013 vaccination and she had video footage 

of it. Id. at 206. After the pneumonia and flu vaccines, Mrs. Heller and Ms. Huling noticed some 

changes, and Ms. Huling instructed Mrs. Heller to bring up the right heel cord tightness when she 

15 Ms. Huling also shifted the date of this visit forward approximately one week from its occurrence.
35

returned on October 23, 2013. Id. at 207. Ms. Huling’s letter to Petitioner’s counsel was admitted 

into the record as Exhibit 97.16

IV. Expert Opinions and Qualifications

A. Petitioners’ Expert: Dr. Leslie Hollis

1. Qualifications

Dr. Hollis submitted a printout of her website’s “about me” page as her CV, in conjunction 

with her affidavit. Ex. 66 at 4. Dr. Hollis received her medical degree from the University of 

Oklahoma and performed her pediatric residency at [Baylor] Scott & White [Medical Center]. Id.

2. Affidavits

Dr. Hollis, H.H.’s treating pediatrician, filed two affidavits in this case. Exs. 66 (hereinafter 

“First Hollis Affidavit”) and 90 (hereinafter “Second Hollis Affidavit”). In her first affidavit, Dr. 

Hollis stated she has been H.H.’s treating pediatrician since his birth on July 14, 2012. First Hollis 

Affidavit at 2. Dr. Hollis noted that H.H. was a healthy patient with no major issues; he had an 

abnormal newborn screen which was retested and came back normal. Id. Dr. Hollis examined H.H. 

on November 11, 2013, after he had been experiencing a fever of 101.5o. Id. She noted that at this 

appointment, H.H. had noticeably less energy and his development “had been regressing over the 

last month.” Id. at 2. Dr. Hollis referred H.H. to Dr. Heather Crawford, a metabolic genetics 

specialist, and to an appointment with Dr. Brian Aalbers, a pediatric neurologist, for his 

developmental issues. Id. Dr. Hollis continued to treat H.H. along with his other doctors. Id. It is 

Dr. Hollis’ opinion that H.H.’s “rapid decline can be attributed to receiving the vaccinations on 

October 17, 2013 and October 23, 2013.” Id. at 3. 

Dr. Hollis’ second affidavit added a few more details regarding her history of treating H.H. 

See generally Second Hollis Affidavit. Dr. Hollis stated that “H.H. has dystonia and neurological 

impairment that manifested itself at 16 months of age.” Id. at 2. Dr. Hollis noted that H.H. was 

assessed at 12 months of age and was within the normal developmental range for his age group. 

Id. At his 15-month wellness check, Dr. Hollis noted that 

he was taking a few steps independently between objects. His mom had noted his 

foot possibly turning in 1 week prior to his appointment. The child was observed to 

bear weight on both feet, and no significant intoeing was noted when he was trying 

to walk. In my medical opinion, H.H. was still well within the developmentally 

acceptable range for his age.

Id. Dr. Hollis next saw H.H. on November 11, 2013, where H.H.’s mother reported that his 

development had been regressing over the last month; he stopped crawling, playing with toys and 

eating table food. Id. Dr. Hollis immediately referred H.H. to neurology for evaluation of his 

16 Because Petitioners did not file this letter, I prompted them to do so after the hearing. See informal 

communication remark dated 3/15/2022; ECF No. 120. The letter was received as Ex. 102.
36

developmental regression. Id. Dr. Hollis further added that H.H.’s decline was severe and rapid 

after his 15 month vaccinations and it was her opinion that H.H. will have “neurological and 

physical suffering for the rest of his life.” Id. at 3. 

B. Petitioners’ Expert: Dr. Warren Marks

1. Qualifications

Dr. Marks submitted a printout of his Cook Children’s Hospital physician page as his CV. 

Ex. 67 at 6-7. Dr. Marks received his medical degree from Texas Tech University School of 

Medicine and completed his residency and fellowship at the University of Oklahoma College of 

Medicine. Id. at 6. Dr. Marks is board certified in neurology with a special qualification in child 

neurology. Id. Dr. Marks has published two papers and 10 abstracts. Id. at 6-7. I recognized Dr. 

Marks as an expert in pediatric neurology. Tr. at 146. 

2. Affidavit and Expert Report

Dr. Marks filed one affidavit and one expert report in this case. Exs. 67 (hereinafter “Marks 

Affidavit”) and 94 (hereinafter “Marks Expert Report”). In his affidavit, Dr. Marks noted that his 

care of H.H. began on February 4, 2014, and that he had been treating H.H. for rapidly progressing 

dystonia with encephalopathy. Marks Affidavit at 2. H.H.’s other symptoms included: acute 

constipation, abnormal liver enzymes, encephalopathy, cough, dystonia, speech delay, and delayed 

milestones. Id. Dr. Marks has performed many work-ups over the years and has ruled out over 20 

different possible causes of H.H.’s condition, to include AGS, GBS, lysosomal storage disease, 

Creutzfeldt-Jakob disease, heavy metal poisonings, Epstein-Barr virus, enteroviruses, and 

cytomegaloviruses. Id. Testing done on H.H. includes extensive lab work, exome sequencing and 

lumbar punctures. Id. Most testing was performed at Cook Children’s Medical Center though 

testing for AGS was performed in England and France. Id. Dr. Marks opined that the start of H.H.’s 

symptoms began after the receipt of his fifteen month vaccinations.17 Id. Dr. Marks further opined

that there is no other explanation for why H.H. developed severe and rapidly progressing dystonia 

with encephalopathy at 15 months, other than his exposure to his 15 month vaccinations. Id. at 3-

4. Dr. Marks provided a theory as to how H.H.’s exposure to his vaccines caused his condition:

Essentially, H.H. was exposed to an antigen in the influenza or DTaP vaccines that 

triggered a neurological deterioration and an abnormal movement disorder, 

specifically dystonic posturing in his lower extremities which has rapidly 

progressed throughout his body. Unfortunately, this Influenza or DTaP antigen 

must have been similar to a “self” antigen in H.H.’s neurological structure, so that 

a neurological deterioration also occurred. H.H.’s lab results showed elevated 

levels of neopterin a marker of immune system activation, and tetrahydrobiopterin, 

an enzyme used to produce serotonin, dopamine and other neurotransmitters. 

Elevated levels of these enzymes have caused the interferonopathy, an up17 It should be noted that Dr. Marks did not observe or treat H.H. until he was more than 18 months old. 
37

regulation of type-1 interferons, consequently resulting in his current symptomatic 

state. The increase in interferons creates a sense that the body is under attack from 

an outside source, but in H.H.’s case, there is no such source so the cause is only 

neurological in nature H.H.’s neurological status has since stabilized, but still has 

persistent increases in his interferon levels. This stabilization of his neurological 

status, which was hyperactive post-immunization is indicative of the cause being 

derived from the vaccinations.... Based on the timing of his vaccine inoculation 

and the development of his symptoms thereafter, this theory makes complete sense 

as a probable cause for his symptoms since there is no other explanation for the 

sudden development or rapidly progressive dystonia with encephalopathy due to 

the increased interferon levels in an otherwise previously healthy individual with 

no other environmental exposures.

Id. at 4-5. Dr. Marks also opined that H.H. will suffer from dystonia and encephalopathy for the 

remainder of his life and will require extensive continued medical treatment. Id. at 5. 

Dr. Marks’ expert report was filed in response to Dr. Barañano’s first expert report. Ex. 94 

at 1. Dr. Marks clarified that H.H. had been tested for the IFIH1 gene and was negative. Id. He 

also confirmed that H.H. was negative for all known AGS genes and other non-genetic 

inflammatory disorders like Lyme disease. Id. Dr. Marks’ report indicated that H.H.’s CSF 

neopterin levels were normal, indicating the immune activation process may be normalizing but 

extensive CNS damage has been done. Id. H.H.’s MRI in July 2017 also revealed no intracranial 

calcifications or injury to the basal ganglia consistent with AGS. Id. Dr. Marks’ concluded that 

there are two realistic options for H.H. at this point: he is one of the very rare cases of AGS without 

a known genetic marker or he has an AGS-like interferonopathy triggered by “external immune 

stimulating condition such as immunization.” Id. Given his normalizing neopterin levels, “I would 

favor the latter.” Id.

2. Testimony

Dr. Marks testified at the January 22, 2020 entitlement hearing. Dr. Marks has practiced in 

the field of pediatric neurology for 40 years and specializes in movement disorders, rehabilitation, 

and neuromuscular disorders. Tr. at 140. Dr. Marks is H.H.’s treating pediatric neurologist. Id. at 

141-42. Dr. Marks’ first visit with H.H. was in February 2014. Id. at 142. When Dr. Marks saw 

H.H. on February 4, 2014, there was a presumptive diagnosis of Aicardi-Goutières syndrome based 

on elevated neopterin levels in his spinal fluid. Id. at 146. 

Dr. Marks testified that AGS is “a disorder of interferon activity... it’s an immune mediated 

disorder that typically result[s] in neurologic regression with dystonia, intracranial

calcifications,... seizures... almost always have a skin rash of some kind.” Tr. at 147-48. H.H. did 

not have a skin rash or calcifications on his neuroimaging. Id. at 148-49. AGS patients are also 

more likely to have seizures. Id.at 149. With a working diagnosis of AGS, Dr. Marks sent H.H.’s 

testing to be done by Medical Neurogenetics in Atlanta, which has a neurotransmitter gene panel 

test for AGS. Id. at 149-50. H.H. was tested against then six known genes for AGS. Id. at 150. A 

seventh gene was identified but H.H. tested negative for all seven genes. Id.
38

Dr. Marks had discussions with Dr. Yanick Crow, the world’s expert in AGS. Tr. at 150. 

Samples were sent to France, where Dr. Crow’s research lab was located. Id. Dr. Crow confirmed 

H.H.’s interferon levels were elevated. Id. H.H.’s entire genome was sequenced to find genes that 

would explain his dystonia, AGS, and other symptoms, but this testing did not provide an 

explanation for H.H.’s condition. Id. at 151. Dr. Marks gave H.H. a diagnosis of an “AGS-like” 

disease because H.H. has many of the clinical manifestations of AGS but no genetic markers. Id.

Dr. Marks testified that he cannot prove H.H. does not have AGS, but noted that there is clinical 

evidence to suggest it is not AGS as well. Id. The most recent terminology he has used to describe 

H.H.’s condition is dystonia with interferonopathy. Id. at 153. An interferonopathy means H.H. 

has an elevated level of interferon. Id.

Dr. Marks stated vaccinations are meant to cause an immune response and H.H.’s

symptoms began shortly after immunization. Tr. at 153-54. Dr. Marks additionally testified that 

“it’s not unique for vaccine to cause immune responses that produce neurologic injury. GuillainBarre has been well known to be associated with vaccines off and on.” Id. at 154. Dr. Marks stated 

that H.H. has had elevated interferon levels for six years, with some fluctuation, but it otherwise 

indicates that there is a persistent immunologic response or a genetic defect. Id. at 155. 

Dr. Marks also discussed H.H.’s case with Dr. Vanderver, the American expert on AGS, 

and had the Hellers see her while she was working at Children’s National Hospital in Washington, 

DC. Tr. at 156-57. Dr. Marks testified that Dr. Vanderver was not convinced H.H. had AGS and 

H.H. could not participate in any trials because he did not have any genetic markers for the disease. 

Id. Regarding H.H.’s current condition, Dr. Marks opined that H.H. has stopped regressing and 

has been clinically stable for the last year because he has not lost any skills. Id. at 157. 

Dr. Marks opined in favor of vaccine causation for several reasons. First, H.H. was a 

normally developing child prior to his 15-month vaccinations. Tr. at 158. Second, there is a 

temporal correlation between vaccination and H.H.’s deterioration. Id. at 159. Finally, H.H. has 

no known no genetic marker that would explain his condition. Id.

For the 5% subset of AGS patients who do not a known genetic marker for AGS, they are 

given the AGS diagnosis because they have other signs, like calcifications in the brain or skin rash. 

Tr. at 160-61. H.H.’s onset at 15-months of age is significant in that later onset cases of AGS tend 

to be milder. Id. at 161. Another difference in H.H.’s presentation is that he seems to have 

stabilized; if this were a “triggered reaction,” it makes sense that it should wane over time. Id. Dr. 

Marks opined that he did not expect an AGS patient to make improvements; it is a “relentlessly 

progressive disorder.” Id. at 164. 

Dr. Marks examined H.H. one day prior to the entitlement hearing and observed that he 

was stable. Tr. at 166-67. Dr. Marks noted his condition had not changed; H.H. still has very severe 

dystonia but he has a communication device that helps him interact and he is much less irritable. 

Id. at 167. Dr. Marks confirmed his belief that either H.H. has a rare case of AGS without a known 

genetic marker or he has an AGS-like interferonopathy “triggered by external immune stimulating

conditions such as immunization.” Id. at 170. Dr. Marks also testified that he does not know why 

the vaccines were able to trigger such a sustained reaction, as he is not an immunologist. Id. at 

170-71. Even in viral mediated diseases like Guillain Barré syndrome, the response is not sustained 
39

over time. Id. Dr. Marks did not identify a specific vaccine he believed was more likely to be 

causal. Id. at 173. Dr. Marks used Guillain Barré syndrome as a model when discussing the medical 

appropriate time frame for when an immune mediate disease should develop, usually one to two

weeks after immune stimulus. Id. at 175-76. 

Dr. Marks communicated with Drs. Crow and Vanderver mostly at conference meetings or 

phone calls. Tr. at 177-78. Dr. Marks confirmed that Dr. Vanderver was unsure what condition 

H.H. had but she noted that she believed H.H. likely has an inherited interferonopathy. Id. at 179. 

Dr. Marks also confirmed that there was no literature submitted to support his proposed theory of 

molecular mimicry in this type of case. Id. at 187. But Dr. Marks stated his theory was not specific 

to molecular mimicry, just that an immune response was triggered as a result of the vaccinations 

H.H. received. Id. at 188. We know that vaccines trigger an immune response, and on occasion, 

“the immune system just goes wild.” Id. at 193. Dr. Marks testified that in his conversations with 

Dr. Crow, Dr. Crow believed that AGS was the most logical diagnosis even though they could not 

identify which gene caused H.H.’s condition. Id. at 203-04. 

Dr. Marks testified that H.H.’s condition started when H.H. had a fever and was irritable. 

Tr. at 195. I also asked Dr. Marks if I find onset of H.H.’s condition was prior to his 15-month 

vaccinations, would his theory change. Id. Dr. Marks opined that the vaccinations could cause a 

fever to develop which could be “enough to trigger an irreversible neurologic decline.” Id. at 196-

97. 

C. Petitioners’ Expert: Dr. Lawrence Steinman

1. Qualifications

Petitioner filed Dr. Steinman’s CV on July 24, 2020. Ex. 101, Tab 1. Dr. Steinman received 

his medical degree from Harvard University and was a NIH Fellow in Chemical Neurobiology at 

Harvard Medical School. Id. at 1. Dr. Steinman completed his residency in pediatrics and pediatric 

and adult neurology at Stanford University Hospital. Id. Dr. Steinman is the GA Zimmermann 

Chair as Professor of Neurological Sciences, Neurology, and Pediatrics. Id. Dr. Steinman is board 

certified in neurology and is involved in the American Academy of Neurology as a fellow, the

American Neurological Association, the American Association of Immunologists, and the Clinical 

Immunology Society. Id. at 2. Dr. Steinman has over 40 patents (not limited to U.S. patents). Id.

at 2-3. Dr. Steinman has published nearly 600 articles. Id. at 5-48. 

1. Post-Hearing Expert Reports

Petitioners filed two reports from Dr. Lawrence Steinman. Exs. 101 (hereinafter “First 

Steinman Rep.”) and 99 (hereinafter “Second Steinman Rep.”). In his first report, Dr. Steinman 

stated that his theory focuses on “how the components of the [Pentacel] vaccine can drive an 

interferon response. It is not a theory based on molecular mimicry.” First Steinman Rep. at 9. There 

are two types of interferons have different receptors but share common signaling pathways 

including JAK and STAT molecules. Id. Type 1 interferons break down into other subtypes, 

whereas Type 2 interferons are only broken down to gamma interferon. Id. The Pentacel vaccine 

consists of many different components, including DTaP-IPV, ActHIB, and H. influenzae type b 
40

bound to tetanus toxoid. Id. at 11. The pertussis toxin “induces immune responses to both gammainterferon and to type 1 interferon.” Id. at 12. 

The Pentacel vaccine also contains alum, which activates the NALRP3 inflammasome, 

“which plays a role in inducing interferonopathies.” First Steinman Rep. at 12. There are a number 

of interferon responsive neuroinflammatory conditions such as multiple sclerosis (MS) and its 

animal model, experimental autoimmune encephalomyelitis (EAE), and these conditions are tied 

to strong activation of innate immunity induced by the NLRP3 inflammasome. Id. Dr. Steinman 

also coauthored a paper about how Type 1 IFNs and type II IFN mediate both regulation and 

inflammation in MS, neuromyelitis optica, and EAE; however “the underlying mechanism for 

these Janus-like activities of type I and II IFNs in neuroinflammation remain unclear.” Id. at 14. 

Dr. Steinman noted that “[a]lthough endogenous type I IFN signaling provides a protective 

response to neuroinflammation, we find that when IFFN-g signaling is ablated, type I IFNs drive 

inflammation, resulting in exacerbated EAE. Id.

Dr. Steinman stated that although H.H. does not have an ADAR-1 mutation, a vaccine 

could still trigger his interferonopathy. First Steinman Rep. at 14. Dr. Steinman cited to Dr. Crow’s 

paper (Ref. 18) which states that: 

Indeed, considering a putative role of physical stressors, note should be made of 

the cold dependency of the skin lesions seen in the type I interferonopathies and of 

a striking temporal relationship between the onset of ADAR1-related bilateral 

striatal necrosis and preceding infection. Whether vaccination represents a disease 

trigger is an important, and currently unanswered, question. Meanwhile, the 

possibility of a “cumulative” genetic burden contributing to cellular pathology is 

notable in light of recently published data on the group of type I interferonopathies 

caused by loss-of-function mutations in proteasome subunits.

Id.; see also Rodero & Crow, Type I interferon–mediated monogenic autoinflammation: The type

I interferonopathies, a conceptual overview, 213 J. EXP. MED. 12, 2527-38, 2351-52 (2016) (filed 

as Ex. 101, Tab 18) (hereinafter “Rodero & Crow”). Dr. Steinman opined that the onset of H.H.’s 

neuroinflammation within three weeks of the Pentacel vaccination is consistent with references 18 

and 19. Id. at 15. Dr. Steinman further opined that the Pentacel vaccine significantly aggravated 

H.H.’s prior condition which included the mild intorsion of his foot prior to the vaccination. Id. at 

16. 

Dr. Steinman filed a second expert report in response to Dr. McGeady’s report. Ex. 99. Dr. 

Steinman stated that both experts agree that the genetic basis for H.H.’s interferonopathy remains 

elusive, however the diagnosis of an interferonopathy is akin to AGS. Id. at 2. Where Drs. 

McGeady and Steinman disagree is whether the Pentacel vaccine can trigger a “physiologic 

amount of type I interferon.” Id. Dr. Steinman clarified that he believes that the vaccine is merely 

a trigger for an interferon response. Id. The overproduction of interferon type 1 “can be explained 

by the references which show that there is a resistance in some forms of neuroinflammation to the 

normal beneficial response of interferon. So unchecked interferon production can drive 

neuroinflammation.” Id.
41

Dr. Steinman added that if H.H. did have an underlying AGS condition, the Pentacel 

vaccine would have worsened his neuroinflammation. Second Steinman Rep. at 3. Dr. Steinman 

reiterated that it does not matter if H.H. had neurological symptoms prior to his 15-month 

vaccinations, just that the Pentacel vaccine on October 23, 2013 caused neuroinflammation, which 

could have significantly aggravated his condition, or caused his condition. Id. at 4. 

D. Respondent’s Expert, Dr. Stephen McGeady: 

1. Qualifications

Respondent filed an updated curriculum vitae for Dr. McGeady on April 4, 2020. Ex. I. Dr. 

McGeady received his medical degree from Creighton University and completed his residency in 

pediatrics at St. Christopher’s Hospital in Philadelphia, and his fellowship at Duke University in 

psychiatry and allergy. Id. Dr. McGeady is currently a professor of pediatrics at Jefferson Medical 

College and is the Emeritus Chief of the Allergy, Asthma & Immunology Division at duPont 

Hospital for Children. Id. Dr. McGeady is board certified in pediatrics and allergy/immunology. 

Id. Dr. McGeady has published at least 66 peer reviewed papers and 93 abstracts. Id. at 2-7, 7-13. 

I recognized Dr. McGeady as an expert in pediatric immunology and pediatrics. Tr. at 213. 

2. Expert Reports

Dr. McGeady filed two expert reports in this case. Exs. D (hereinafter “First McGeady 

Rep.”) and J (hereinafter “Second McGeady Rep.”). In Dr. McGeady’s first report, he noted that 

H.H. lacked some clinical features of AGS, such as calcification in the basal ganglia, chilblainlike skin lesions, and pleocytosis in the CSF. First McGeady Rep. at 4. However, AGS literature 

stated intracranial calcification should not be considered a prerequisite for an AGS diagnosis. Id.

Dr. McGeady also disagreed with Drs. Hollis and Marks’ assessment that H.H.’s normal 

development until 15-16 months is incongruous with AGS. Id. at 4-5. H.H.’s fever is also 

consistent with 405 of subjects in the Rice paper. Id. at 5. Markedly high neopterin and biopterin 

levels are typically only seen in two disorders, AGS and congenital HIV. Id. Dr. McGeady also 

noted that Dr. Vanderver believed H.H. has a “suspected heritable interferonopathy”, which is 

consistent with AGS and inconsistent with an adverse vaccine reaction. Id. at 6; see also Ex. 81 at 

10. 

Dr. McGeady also opined regarding Dr. Marks’ proposed causal theory. First McGeady 

Rep. at 7-10. Dr. McGeady stated that there are six possible metabolic lesions that have been 

proposed to account for the excess production and/or accumulation of interferon alpha and none 

of these mechanisms is “dependent upon immune activation alone.” Id. at 8. Dr. McGeady also 

noted that H.H.’s medical history does not include any localized reaction to any of the vaccines he 

received, which indicates no excessive reaction was produced. Id. at 9. Additionally, H.H. had 

elevated transaminase levels, which are associated with AGS but have not been associated in cases 

of patients who developed encephalopathies after vaccination. Id.

Dr. McGeady also pointed out Mrs. Heller’s 9/13/2013 phone call regarding H.H.’s 

inturning of his right foot and inability to walk; he opined this may have been the first mention of 

H.H. losing skills. Id. at 10. Dr. McGeady also addressed Dr. Hollis’ affidavit which broadly stated 
42

she had never seen a similar loss of skills in a previously normal child, and based on the timing, 

believed that H.H.’s condition was caused by his immunizations. Id. at 11. Dr. McGeady reiterated

that H.H.’s lack of genetic markers does not rule out AGS, considering his clinical and laboratory 

findings. Id.

3. Testimony

Dr. McGeady provided testimony on molecular mimicry and testified that it is “intuitively 

appealing” but in reality, almost never happens. Tr. at 214-15. There are many mimics widespread 

in nature but there are not many autoimmune diseases linked to molecular mimicry in a frequency 

one expects if molecular mimicry were real. Id. at 215-16. There are two accepted examples of 

molecular mimicry, which include GBS and campylobacteria and more recently, narcolepsy with 

the 2010 H1N1 flu. Id. at 216. There is no literature or case reports linking the flu and/or DTaP

vaccine to a Type 1 interferonopathy. Id. at 217. Nor are the viruses of these vaccines known to 

cause a Type 1 interferonopathy. Id. at 218. Dr. McGeady testified that the only know causes of a 

Type 1 interferonopathy are a genetic predisposition or intrauterine viral infections. Id. at 218-19. 

In the case of an intrauterine viral infection, a Type 1 interferonopathy is caused when a 

viral infection is “particularly persistent” like the HIV virus in a pregnant woman. Tr. at 220. The 

fetus become infected as well and starts to produce large quantities of Type 1 interferon; the fetus 

is extremely susceptible to the adverse effects of Type 1 interferonopathy and becomes badly 

damaged as a result. Id. Both viral causation and genetically predisposed babies look similar even 

when different etiologies exist. Id. Dr. McGeady testified that even if molecular mimicry were a 

viable theory, he does not believe vaccinations could have triggered this kind of response. Id. at 

223. Any triggered reaction could have an intense activation however “it gets damped down 

quickly.” Id. Only in hereditary interferonopathies are there no breaks. Id. H.H.’s neopterin levels

have fluctuated over the years but there are no active organisms in the vaccines he’s received that 

could cause this kind of neopterin production. Id. at 223-224. Molecular mimicry cannot explain 

“something that perpetuates over six years.” Id. at 224. Molecular mimicry also pertains to the 

adaptive immune system and there was no evidence of H.H. having an adaptive immune response, 

or localized reaction, to the vaccinations. Id. at 224-25. 

Dr. McGeady testified that he believed that H.H.’s lack of genetic markers does not mean 

he does not have AGS; he noted that new genes and sub mutations are still being identified. Tr. at 

228-29. Dr. McGeady opined that AGS is the condition most consistent with H.H.’s presentation. 

Id. at 233. Dr. McGeady also testified that H.H.’s improvement is not inconsistent with AGS; some 

patients have normal intellectual capacity and have courses that stabilize. Id. at 234.

4. Post-Hearing Report

Dr. McGeady’s second report was filed in response to Dr. Steinman’s first expert report 

(Ex. 101). Dr. McGeady opined that Dr. Steinman’s proposed mechanism regarding how the 

Pentacel vaccine caused H.H.’s condition is not consistent with what is known regarding type I

interferonopathies. Second McGeady Rep. at 1. 
43

Dr. Steinman proposed that the Pentacel vaccine activated H.H.’s innate immune system 

and the subsequent production of type I interferon and other inflammatory cytokines caused 

damage to H.H.’s central nervous system. Second McGeady Rep. at 1. Dr. McGeady argued that 

Dr. Steinman’s theory does not explain how this reaction caused elevation in interferon levels for 

the past six years. Id. Vaccines are meant to trigger an immune reaction however, to trigger a 

cytokine storm that is perpetuated over a number of years is unpersuasive. Id. at 2. Only in an 

inherited interferonopathy are interferon levels elevated for the length of time seen in H.H. Id.

Dr. McGeady addressed Dr. Steinman’s second theory, that the Pentacel vaccine 

significantly aggravated a pre-existing condition. Second McGeady Rep. at 1. Type I interferons

are produced by the innate immune system and are present in measurable quantities within 12 

hours following a viral exposure. Id. Interferon production promptly decreases following a nonprogressive provocation, thus “it would be expected that an acute injury to the CNS due to 

excessive type I interferon would appear sooner than several weeks following the immunization if 

vaccines are to be suspected as the initiating event.” Id. H.H. suffered from many febrile illnesses 

(on 12/10/2012, 5/20/2013, 7/29/2013, and 11/11/2013); these would have been suspected 

initiating events as well. Id.

Dr. McGeady opined that the persistent elevations of interferon alpha and other markers of 

type I interferonopathy cannot be the result of H.H.’s October 17 and 23, 2013 vaccinations. 

Second McGeady Rep. at 3. Dr. McGeady reiterated that Dr. Steinman’s theory does not account 

for the chronic overproduction of type I interferon. Id. Congenital type I interferonopathies do 

produce enduring excess amounts of cytokines, as seen in H.H. Id.

E. Respondent’s Expert, Dr. Kristin Barañano

1. Qualifications

Respondent filed an updated curriculum vitae for Dr. Barañano on April 14, 2020. Ex. H. 

Dr. Barañano received her medical degree and a Ph.D. in neuroscience from Johns Hopkins 

University School of Medicine. Id. at 1. Dr. Barañano completed residencies in pediatrics and 

pediatric neurology at Johns Hopkins University School of Medicine and was a research and 

clinical fellow in neurogenetics at the Kennedy Krieger Institute. Id. Dr. Barañano is currently an 

Assistant Professor of Neurology at Johns Hopkins School of Medicine and is Medical Staff at the 

Kennedy Krieger Institute. Id. Dr. Barañano has published papers, case reports, book chapters and 

editorials. Id. at 2-3. Dr. Barañano is board certified in neurology, with special qualification in 

child neurology. Id. at 4. I recognized Dr. Barañano as an expert in pediatric neurology and 

neurogenetics. Tr. at 252. 

2. Expert Reports

Dr. Barañano filed two reports in this case. Exs. A (hereinafter “First Barañano Rep.”) and 

C (hereinafter “Second Barañano Rep.”). In Dr. Barañano’s first report, she provided a typical 

presentation of AGS but cited to AGS case studies that demonstrated a wide spectrum on onset 

and presentations. First Barañano Rep. at 3. In Dr. Crow’s 2015 paper, 8.6% of patients presented 

after one year of age, and this occurrence was more common with certain AGS-associated genes. 
44

Id. at 3-4. Dr. Barañano also identified Mrs. Heller’s 9/13/2013 phone call as onset of neurological 

symptoms with the in-turning of H.H.’s right foot and right heel cord tightness. Id. at 5. Dr. 

Barañano testified that H.H. had a fever in between his vaccinations; onset of AGS symptoms is

often described in association with a febrile illness. Id. According to Dr. Barañano, H.H.’s clinical 

presentation is entirely consistent with AGS and it is more likely that a genetic disorder like AGS 

explains H.H.’s neurologic condition, rather than a molecular mimicry-like process triggered by 

the vaccination. Id. It is Dr. Barañano’s opinion that H.H.’s clinical picture is consistent with AGS, 

with his elevated liver enzymes, high CSF neopterin and biopterin levels, elevated interferon-alpha 

levels in blood and CSF. Id. at 5-6.

In Dr. Barañano’s second report, she opined that normalized neopterin levels are reported 

in 25% of AGS cases. Second Barañano Rep. at 1. The normalization of H.H.’s neopterin levels 

does not provide support that this was a vaccine-mediated process. Id. It remains Dr. Barañano’s 

opinion that H.H. falls into the 5% of AGS cases where a genetic marker has not been identified. 

Id.

3. Testimony

Dr. Barañano provided a summary of AGS. Tr. at 253-54. When cells break down in our 

body and release DNA products, such as nucleotides, the immune system is activated to clean up 

the nucleotides. Id. at 253. In AGS, patients with the known AGS genes sense aberrant nucleotides 

and attack its own body and nucleotides. Id. at 254. There are classical traits in AGS patients, 

namely calcifications in the brain, white matter abnormalities, and skin lesions, however over time, 

a greater spectrum of AGS phenotypes have been discovered, including children with later onset 

and even some adult patients. Id. at 254-55. Dr. Barañano treats a number of AGS patients, 

including one with a later onset. Id. at 255. AGS is generally an autosomal recessive gene; if H.H.’s 

parents were carriers, there would be a 25% chance with each pregnancy of having an affected 

child. Id. at 256. 

Interferon alpha is not tested in the United States, so other doctors, like Dr. Crow, will run 

the tests. Tr. at 261-62. Dr. Barañano’s understanding is that interferon alpha is “essentially 

thought to be pathognomonic for AGS” meaning it goes hand in hand with the diagnosis of AGS. 

Id. at 262. With more patients who are confirmed with the genetic markers for AGS, we have seen 

more and more AGS phenotypes, thus calcifications are not considered mandatory for an AGS

diagnosis. Id. at 262-63. 

Dr. Barañano discussed exhibit 83, a case study of children who have the confirmed gene 

for AGS but do not have calcifications. Id. at 263. Dr. Barañano stated that a definite genetic 

diagnosis only happens in 25-40% of cases. Id. at 264. Whole genome sequencing is a 

breakthrough but “not the end all, be all.” Id. at 264. Dr. Barañano opined that she has not yet seen 

a report regarding testing for the seventh AGS gene, and would have also recommended a 

chromosomal microarray. Id. at 264-65. Dr. Barañano also stated that Dr. Vanderver’s research 

program offers whole genome sequencing so her diagnostic rate is around 85%. Id. at 266. There 

are improvements in genetic testing but there are still limitations. Id. Of 20,000 genes, only 5,000

are in the online Mendelian Inheritance in Man database. Id. at 267. 
45

Dr. Barañano reiterated that H.H.’s onset at 15-16 months of age did not affect her opinion 

that AGS is still the best clinical diagnosis at this time. Tr. at 268. H.H.’s irritability is consistent 

with the onset of neurological symptoms. Id. The clinical course for AGS involves acute 

neurologic symptoms followed by a period of stabilization. Dr. Barañano disagreed with Dr. 

Marks’ assessment that AGS is a relentlessly progressive neurodegenerative disorder. Id. at 270. 

Dr. Barañano added that the nervous system’s normal programming is to make developmental 

progress, so if you superimpose a neurodegenerative process on that, a child plateaus and starts 

losing skills, but if the disease has stabilized, a child’s underlying developmental process can 

continue forward even though he remains severely impaired; thus improvement is not inconsistent 

with AGS. Id. at 271. 

Dr. Barañano confirmed that to the best of her knowledge there is no literature that 

discusses the flu or Pentacel vaccines causing a Type 1 interferonopathy. Id. at 271-72. Dr. 

Barañano also testified that other interferonopathies exist but AGS presents in the central nervous 

system, affecting the brain, whereas other interferonopathies are more systemic. Id. at 273-74. Dr. 

Barañano also stated that skin rashes were seen in 40% of AGS cases so it is not a universal finding. 

Id. at 277. In short, there is nothing in H.H.’s presentation that is inconsistent with AGS. Id. at 

293. However, without a genetic confirmation, Dr. Barañano cannot say definitively that H.H. has 

AGS, just that it is the most likely diagnosis. Id. at 296. 

V. Applicable Law

A. Petitioner’s Burden in Vaccine Program Cases

Under the Vaccine Act, when a petitioner suffers an alleged injury that is not listed in the 

Vaccine Injury Table, a petitioner may demonstrate that he suffered an “off-Table” injury. 

§ 11(c)(1)(C)(ii). 

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

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

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

petitioner establish by preponderant evidence that the vaccination he received caused his injury 

“by providing: (1) a medical theory causally connecting the vaccination and the injury; (2) a logical 

sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a 

showing of a proximate temporal relationship between vaccination and injury.” Id. at 1278. 

Under the first prong of Althen, petitioners must provide a “reputable medical theory,”

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

1355-56 (citations omitted). To satisfy this prong, a petitioner’s theory must be based on a “sound 

and reliable medical or scientific explanation.” Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 

543, 548 (Fed. Cir. 1994). Proof that the proffered medical theory is reasonable, plausible, or 

possible does not satisfy a petitioner’s burden. Boatmon v. Sec’y of Health & Hum. Servs., 941 

F.3d 1351, 1359-60 (Fed. Cir. Nov. 7, 2019). 

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

epidemiological studies, demonstration of a specific mechanism, or a generally accepted medical 
46

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

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

special masters are “entitled to require some indicia of reliability to support the assertion of the 

expert witness.” Boatmon, 941 F.3d at 1360, quoting Moberly v. Sec’y of Health & Hum. Servs., 

592 F.3d 1315, 1324 (Fed. Cir. 2010). Special Masters, despite their expertise, are not empowered 

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

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

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

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

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

Health & Hum. Servs., 121 Fed. Cl. 230, 245 (2015), vacated on other grounds, 844 F.3d 1363 

(Fed. Cir. 2017); see also Hock v. Sec’y of Health & Hum. Servs., No. 17-168V, 2020 U.S. Claims 

LEXIS 2202 at *52 (Fed. Cl. Spec. Mstr. Sept. 30, 2020).

The second Althen prong requires proof of a logical sequence of cause and effect, usually 

supported by facts derived from a petitioner’s medical records. Althen, 418 F.3d at 1278; Andreu, 

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

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

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

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

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

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

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

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

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

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

court”). As with expert testimony offered to establish a theory of causation, the opinions or 

diagnoses of treating physicians are only as trustworthy as the reasonableness of their suppositions 

or bases. The views of treating physicians should also be weighed against other, contrary evidence 

also present in the record. Hibbard v. Sec’y of Health & Hum. Servs., 100 Fed. Cl. 742, 749 (2011), 

aff’d, 698 F.3d 1355 (Fed. Cir. 2012); Caves v. Sec’y of Health & Hum. Servs., No. 06-522V, 2011 

WL 1935813, at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011), mot. for review den’d, 100 Fed. Cl. 344, 

356 (2011), aff’d without opinion, 475 Fed. App’x 765 (Fed. Cir. 2012).

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

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

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

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

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

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

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

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

Hum. Servs., 101 Fed. Cl. 532, 542 (2011), recons. den’d after remand, 105 Fed. Cl. 353 (2012), 

aff’d mem., 503 F. App’x 952 (Fed. Cir. 2013); Koehn v. Sec’y of Health & Hum. Servs., No. 11-
47

355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review den’d (Fed. Cl. 

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

The Vaccine Act defines significant aggravation as “any change for the worse in a 

preexisting condition which results in markedly greater disability, pain, or illness accompanied by 

substantial deterioration of health.” § 300aa-33(4). In Loving, the United States Court of Federal 

Claims established the governing six-part test for off-Table significant aggravations. Petitioner 

must prove by a preponderance of the evidence:

(1) The person’s condition prior to administration of the vaccine, (2) the person’s 

current condition (or the condition following the vaccination if that is also 

pertinent), (3) whether the person’s current condition constitutes a ‘significant 

aggravation’ of the person’s condition prior to vaccination, (4) a medical theory 

causally connecting such a significant worsened condition to the vaccination, (5) a 

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

for the significant aggravation, and (6) a showing of a proximate temporal 

relationship between the vaccination and the significant aggravation.

Loving v. Sec’y of Health & Hum. Servs., 86 Fed. Cl. 135, 144 (2009); see also W.C. v. Sec’y of 

Health & Human Servs., 704 F.3d 1352, 1357 (Fed. Cir. 2013) (adopting this as the proper legal 

standard for significant aggravation claims brought under the Vaccine Act). Loving prongs four, 

five, and six are derived from the Federal Circuit’s test for off-Table actual causation cases. Althen 

v. Sec’y of Health & Hum. Servs., 17 F.3d 374 (Fed. Cir. 1994).

In Sharpe, the Federal Circuit clarified the Loving prongs and what is required by 

petitioners to successfully demonstrate a causation-in-fact significant aggravation claim. Sharpe 

v. Sec’y of Health & Hum. Servs., 964 F.3d 1072 (Fed. Cir. 2020). Loving prong three only requires 

a comparison of a petitioner’s current, post-vaccination condition with his pre-existing prevaccination condition. Sharpe at 1082; Whitecotton v. Sec’y of Health & Hum. Servs., 81 F.3d 

1099 (Fed. Cir. 1996). A petitioner is not required to demonstrate an expected outcome or that his

post-vaccination condition was worse than such an expected outcome. Sharpe at 1081. Further, a 

petitioner is not required “to disprove that a pre-existing genetic mutation caused [his] significant 

aggravation.” Sharpe at 1087.

Under Loving prong four, a petitioner need only provide a “medical theory causally 

connecting [petitioner’s] significantly worsened condition to the vaccination.” Sharpe at 1083; see 

also Loving, 86 Fed. Cl. at 144. In other words, petitioner is required to present a medically reliable

theory demonstrating that a vaccine “can cause a significant worsening” of the condition. Sharpe

at 1083 (citing to Pafford ex. rel. Pafford v. Sec’y of Health & Hum. Servs., 451 F.3d 1352, 1356-

57 (Fed. Cir. 2006). A petitioner may be able to establish a prima facie case under Loving prong 

four without eliminating a pre-existing condition as the cause of her significantly aggravated 

injury. Id.; citing Walther v. Sec’y of Health & Hum. Servs., 485 F. 3d 1146, 1151 (Fed. Cir. 2007) 

(noting that “the government bears the burden of establishing alterative causation. . . . once 

petitioner has established a prima facie case”).
48

Loving prong five requires a petitioner to show “a logical sequence of cause and effect 

showing that the vaccination was the reason for the significant aggravation.” Loving, 86 Fed. Cl. 

at 144. In other words, petitioner must show that the vaccinations “did” cause a worsening of 

[petitioner’s underlying disorder]. Id.

In determining whether a petitioner is entitled to compensation, a special master must 

consider the entire record and is not bound by any particular piece of evidence. § 13(b)(1) (stating 

that a special master is not bound by any “diagnosis, conclusion, judgment, test result, report, or 

summary” contained in the record). Furthermore, a petitioner is not required to present medical 

literature or epidemiological evidence to establish any Althen prong. The special master essentially 

must weigh and evaluate opposing evidence in deciding whether a petitioner has met their burden 

of proof. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1380 (Fed. Cir. 2009); see also

Grant v. Sec’y of Health & Hum. Servs., 956 F.2d 1144, 1149 (Fed. Cir. 1992).

B. Law Governing Analysis of Fact Evidence

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

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

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

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

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

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

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

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

contemporaneous medical records and testimony. See Burns v. Sec’y of Health & Hum. Servs., 3 

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

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

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

determination is evidenced by a rational determination).

Medical records created contemporaneously with the events they describe are generally 

trustworthy because they “contain information supplied to or by health professionals to facilitate 

diagnosis and treatment of medical conditions,” where “accuracy has an extra premium.” Kirby v. 

Sec’y of Health & Hum. Servs., 997 F.3d 1378 (Fed. Cir. 2021) citing Cucuras, 993 F.2d at 1528. 

This presumption is based on the linked proposition that (i) sick people visit medical professionals; 

(ii) sick people honestly report their health problems to those professionals; and (iii) medical 

professionals record what they are told or observe when examining their patients in as accurate a 

manner as possible, so that they are aware of enough relevant facts to make appropriate treatment 

decisions. Sanchez v. Sec’y of Health & Hum. Servs., No. 11-685V, 2013 WL 1880825 at *2 (Fed. 

Cl. Spec. Mstr. Apr. 10, 2013) mot. for rev. denied, 142 Fed. Cl. 247, 251-52 (2019), vacated on

other grounds and remanded, 809 Fed. Appx. 843 (Fed. Cir. Apr. 7, 2020).

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

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

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

are generally found to be deserving of greater evidentiary weight than oral testimony -- especially 
49

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

Murphy v. Sec’y of Health & Hum. Servs., 23 Cl. Ct. 726, 733 (1991), aff’d per curiam, 968 F.2d 

1226 (Fed. Cir. 1992), cert. den’d, Murphy v. Sullivan, 506 U.S. 974 (1992) (citing United States 

v. U.S. Gypsum Co., 333 U.S. 364, 396 (1947) (“[i]t has generally been held that oral testimony 

which is in conflict with contemporaneous documents is entitled to little evidentiary weight.”)).

However, there are situations in which compelling oral testimony may be more persuasive 

than written records, such as where records are deemed to be incomplete or inaccurate. Campbell

v. Sec’y of Health & Hum. Servs., 69 Fed. Cl. 775, 779 (2006) (“like any norm based upon common 

sense and experience, this rule should not be treated as an absolute and must yield where the factual 

predicates for its application are weak or lacking”); Lowrie, 2005 WL 6117475 at *19 (“[w]ritten 

records which are, themselves, inconsistent, should be accorded less deference than those which 

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

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

be afforded. Andreu, 569 F.3d at 1379; Bradley v. Sec’y of Health & Hum. Servs., 991 F.2d 1570, 

1575 (Fed. Cir. 1993).

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

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

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

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

accuracy and completeness of medical records, the Court of Federal Claims has listed four possible 

explanations for inconsistencies between contemporaneously created medical records and later 

testimony: (1) a person’s failure to recount to the medical professional everything that happened 

during the relevant time period; (2) the medical professional’s failure to document everything 

reported to her or him; (3) a person’s faulty recollection of the events when presenting testimony; 

or (4) a person’s purposeful recounting of symptoms that did not exist. LaLonde v. Sec’y of Health 

& Hum. Servs., 110 Fed. Cl. 184, 203-04 (2013), aff’d, 746 F.3d 1334 (Fed. Cir. 2014). In making 

a determination regarding whether to afford greater weight to contemporaneous medical records 

or other evidence, such as testimony at hearing, there must be evidence that this decision was the 

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

C. Analysis of Expert Testimony

Establishing a sound and reliable medical theory connecting the vaccine to the injury often 

requires petitioners to present expert testimony in support of their claim. Lampe v. Sec’y of Health 

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

evaluated according to the factors for analyzing scientific reliability set forth in Daubert v. Merrell 

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

617 F.3d 1328, 1339 (Fed. Cir. 2010) (citing Terran v. Sec’y of Health & Hum. Servs., 195 F.3d 

1302, 1316 (Fed. Cir. 1999). “The Daubert factors for analyzing the reliability of testimony are: 

(1) whether a theory or technique can be (and has been) tested; (2) whether the theory or technique 

has been subjected to peer review and publication; (3) whether there is a known or potential rate 

of error and whether there are standards for controlling the error; and (4) whether the theory or 

technique enjoys general acceptance within a relevant scientific community.” Terran, 195 F.3d at 

1316 n.2 (citing Daubert, 509 U.S. at 592-95).
50

The Daubert factors play a slightly different role in Vaccine Program cases than they do 

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

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

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

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

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

expert testimony already admitted”). 

Respondent frequently offers one or more experts of his own in order to rebut petitioners’

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

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

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

Lampe, 219 F.3d at 1362). However, nothing requires the acceptance of an expert’s conclusion 

“connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too 

great an analytical gap between the data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743 

(quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)). A “special master is entitled to 

require some indicia of reliability to support the assertion of the expert witness.” Moberly, 592 

F.3d at 1324. Weighing the relative persuasiveness of competing expert testimony, based on a 

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

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

reliability of expert testimony often turn on credibility determinations”).

D. Consideration of Medical Literature

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

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

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

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

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

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

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

2015).

VI. Analysis

A. Diagnosis

In Broekelschen v. Sec’y of Health and Human Servs., 618 F.3d 1339, 1346 (Fed. Cir. 

2010), the Federal Circuit recognized that in some circumstances, the special master may “first 

determine which injury was best supported by the evidence presented in the record before applying 

the Althen test.” 

1. There is Preponderant Evidence that H.H. has Aicardi Goutières syndrome or a 

Similar Type I Interferonopathy due to a Congenital Abnormality in an 

Unidentified Gene
51

Aicardi-Goutières syndrome is a “rare genetic disorder most consistently affecting the 

brain and the skin.” Crow et al., Characterization of Human Disease Phenotypes Associated with 

Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1, AM J

MED GENET Part A 167A:296–312 (2014) (filed as Ex. A4) (hereinafter “Crow 2014”). Dr. Marks 

described AGS as “a disorder of interferon activity, so ... it’s an immune mediated disorder that 

typically result[s] in neurologic regression with dystonia, intracranial calcifications.” Tr. at 147. 

There are currently seven gene mutations known to cause AGS. La Piana et al., Neuroradiologic 

patterns and novel imagining findings in Aicardi-Goutières syndrome, 86 NEUROLOGY 28-35 

(2015) (filed as Ex. D, Tab 3) (hereinafter “La Piana”). Rice noted that “Some individuals with 

AGS do not harbor mutations in any of these ... genes.” Rice et al., Gain-of-function mutations in 

IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I 

interferon signaling, 46 NATURE GENETICS 5, 503-10 (2014) (filed as Ex. A, Tab 5) (hereinafter 

“Rice 2014”). La Piana noted that “[b]rain calcification, leukoencephalopathy,18 and cerebral 

atrophy are the classic hallmarks of the disease and have suggested the diagnosis of AGS in the 

majority of cases.” La Piana at 28.

The condition was first recognized in 1984 by French pediatric neurologists, Jean Aicardi 

and Françoise Goutières. Rice et al., Clinical and Molecular Phenotype of Aicardi-Goutières

Syndrome, 81 AMERICAN JOURNAL OF HUMAN GENETICS 713-25 (2007) (filed as Ex. C, Tab 1) 

(hereinafter “Rice 2007”). However, since 1984, “the spectrum of disease resulting from mutations 

in the AGS-related genes has broadened, in part due to the advent of the new sequencing 

technologies.” Crow 2014 at 300. Dr. Crow noted that AGS patients consistently demonstrated 

“increased levels of interferon activity in the cerebrospinal fluid and serum and an increased 

expression of interferon-stimulated genes (ISGs) in peripheral blood.” Id. at 301. Dr. Crow goes

on to note that “[t]hese observations are important in identifying AGS as an inflammatory disorder 

associated with the induction of a type I interferon mediated innate immune response, likely driven 

by endogenously-derived nucleic acids.” Id.

Several factors suggest that H.H. more likely than not, has AGS or a similar genetic 

disorder.

a. H.H.’s Clinical Presentation

H.H. presented with the rapid onset of encephalopathy with the development of spasticity19

18 Leukoencephalopathy is “any of a group of diseases affecting the white matter of the brain, especially of 

the cerebral hemispheres, and occurring as a rule in infants and children.” Leukoencephalopathy, Dorland’s 

Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=28070&searchterm= 

leukoencephalopathy (last accessed March 12, 2022).

19 Spasticity is “the state of being spastic.” Spastic is defined as “hypertonic, so that the muscles are stiff 

and the movements awkward.” Spastic, Dorland’s Med. Dictionary Online, https://www.dorlandsonline. 

com/dorland/definition?id=46356&searchterm=spasticity (last accessed March 14, 2022).
52

and dystonia,20 which Dr. Barañano described as “entirely consistent with a clinical diagnosis of 

AGS.” First Barañano Rep. at 5. Dr. Barañano further opined that “clinically, [H.H.] has behaved 

like an AGS patient with stabilization of [his] irritability.” Tr. at 292.

Dr. McGeady opined that H.H. had “evidence of leukodystrophy21 and thinning of the 

corpus callosum, which are described in AGS.” First McGeady Rep. at 4. See Ex. 95 at 135, 147. 

In support of this point, Rice et al. noted that “[c]ortical atrophy was a common feature in later 

scans, and a number of children demonstrated significant brain-stem and cerebellar atrophy. 

Thinning and, in one subject, complete absence of the corpus callosum were also observed.” Rice 

2007 at 719.

Several of H.H.’s treating physicians also agreed that H.H.’s clinical presentation was 

suggestive of or consistent with AGS. Dr. Aalbers, one of H.H.’s treating neurologists, noted that 

H.H.’s progressive encephalopathy, dystonia, and spasticity were all consistent with AGS. Ex. 52 

at 28.

Dr. Heather Crawford, a metabolic geneticist, saw H.H. on February 4, 2014. She noted in 

the medical records that H.H. presented “with developmental regression and developed 

progressive dystonia that is characteristic of [AGS].” Ex. 50 at 24. Dr. Crawford further stated that 

H.H. “appears to ... have a later-onset presentation for AGS as he presented after a long period of 

normal development.” Id. In discussing the natural history of AGS with Petitioners, Dr. Crawford 

told them that:

Typically, these children have a regression phase, followed by irritability, then a 

slow progressive encephalopathy phase. These children typically develop 

peripheral spasticity, truncal hypotonia, dystonic posturing [of the] upper limbs and 

poor head control, all of which [H.H.] is currently displaying. ... Seizures are also 

observed in up to 50% of affected [children].

Id. The progression of H.H.’s disease was consistent with Dr. Crawford’s description. Although 

H.H. had not developed seizures at the time of this conversation, he had his first seizure on July 9, 

2017. See Ex. 95 at 130.

Dr. Vanderver assessed H.H. in March of 2015 upon referral from Dr. Marks. See Ex. 81 

at 1-10. Dr Marks described Dr. Vanderver stating, “she's probably the United States' expert on ... 

AGS.” Tr. at 156.

Dr. Vanderver noted in her final report:

20 Dystonia is “[a] syndrome of abnormal muscle contraction that produces repetitive involuntary twisting 

movements and abnormal posturing of the neck, trunk, face, and extremities.” Stedman’s Medical 

Dictionary, 28th ed. 2006 (p. 602).

21 Leukodystrophy is “any of various types of neurodegeneration involving disturbance of the white matter 

of the brain. See also adrenoleukodystrophy and leukoencephalopathy.” Leukodystrophy, Dorland’s Med. 

Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=28066&searchterm=

leukodystrophy (last accessed March 14, 2022).
53

[H.H.] is seen in the context of developmental delay, dystonia, abnormal MRI and 

elevated CSF interferon/neopterin/tetrahydrobiopterin with clinical diagnosis of 

Aicardi Goutieres Syndrome but negative genetic testing and no evidence of visible 

intracranial calcifications on an early CT scan.

Ex. 81 at 1. In the “diagnostic and treatment plan” section, Dr. Vanderver indicated an intent to 

collaborate with Dr. Crow “to facilitate genetic resolution of [H.H.]’s suspected heritable 

interferonopathy.” Id. at 6.

b. Elevated Liver Enzymes

Several of H.H.’s treating physicians noted that H.H. had elevated liver enzymes, which is 

also consistent with a diagnosis of AGS.

H.H. visited Dr. Crawford on November 12, 2013. During this visit, Dr. Crawford noted 

that some of H.H.’s lab values were high. Specifically, his AST (aspartate transaminase) was 353, 

his ALT (alanine transaminase) was 400, and his AP (alkaline phosphatase) was 232. Ex. 50 at 4.

Dr. Crawford noted that H.H.’s transaminases (liver enzymes) were elevated. Id. at 6.

On December 17, 2013, Dr. Aalbers stated in the medical record that “[o]f concern the 

patient had previously unexplained transient elevations of liver enzymes which is consistent with 

AGS...” Ex. 52 at 28.

During H.H.’s hospital admission to address his tethered cord on December 18, 2013, Dr. 

Richard Roberts remarked that his liver enzymes were as follows: AST, 325; ALT, 472, “raising 

the concern for possible Aicardi-Goutieres syndrome, a very rare and progressive encephalitic 

disease of childhood.” Ex. 55 at 1.

On May 23, 2014, H.H. visited Dr. Jane Keng, who noted that his AST was elevated at 119 

and his ALT was elevated at 125. Ex. 63 at 2.

The concerns regarding H.H.’s elevated transaminases noted by several of his treating 

physicians are also supported by the medical literature. Rice et al. collected clinical data from 123 

patients with a confirmed AGS gene mutation. The authors noted that 15 of the 123 AGS patients 

“demonstrated liver involvement, with hepatosplenomegaly and/or raised transaminase levels.” 

Rice 2007 at 718. Livingston & Crow similarly noted liver dysfunction in a subset of AGS 

children. Livingston & Crow at 3.

The fact that H.H. had intermittently elevated liver enzyme levels is certainly not diagnostic 

of AGS, but these levels do provide support for his diagnosis with that condition.

c. Elevated Interferon Alpha/Neopterin Levels

In examining H.H.’s presentation and evolving clinical picture, one of the most striking 

aspects of it is his high neopterin and interferon alpha levels. As early as 2003, Dr. Crow stated 
54

that “an increase of CSF IFN-[alpha] in the absence of infection is currently considered a marker 

for the condition.” Crow et al., Cree encephalitis is allelic with Aicardi-Goutières syndrome: 

implications for the pathogenesis of disorders of interferon alpha metabolism, 40 JOURNAL OF 

MEDICAL GENETICS 3, 183-87, 184 (2003) (filed as Ex. D, Tab 5) (hereinafter “Crow 2003”). In 

2014, Crow et al. noted that “[p]atients with AGS consistently demonstrate increased levels of 

interferon activity in the cerebrospinal fluid and serum ... and an increased expression of 

interferon-stimulated genes (ISGs) in peripheral blood ... a so-called interferon signature.” Crow 

2014 at 301. 

Livingston & Crow additionally support the importance of this “interferon signature”; they 

describe that 

[t]he detection of elevated levels of interferon α in the CSF and blood of patients 

with AGS was recognized soon after the disorder was described. More recently, 

evidence for abnormal interferon activity in AGS has been demonstrated by 

identifying an “interferon signature” in peripheral blood. The interferon signature 

measures the expression of interferon stimulated genes and has been identified in 

almost 100% of patients with mutations in TREX1, RNASEH2A, RNASEH2C, 

SAMHD1, ADAR1, and IFIH1. 

Livingston & Crow at 5.

H.H.’s neopterin levels were high on 11/14/2013, (Ex. 96 at 7), 12/19/2013 (Ex. 96 at 7), 

11/14/2014 (Ex. 56 at 94), 4/17/2014 (Ex. 56 at 323). In fact, Dr. Richard Roberts assessed H.H. 

in December of 2013. He noted that H.H.’s lumbar puncture “showed remarkably high elevations 

of biopterin and neopterin: the highest neopterin levels we have ever seen.” Ex. 55 at 1 (emphasis 

added). H.H.’s levels remained elevated through 2017 when they returned to the normal range only 

to become elevated again when they were tested in 2019.

On February 4, 2014, Dr. Heather Crawford noted that H.H.’s elevated neopterin levels are

“only seen in Aicardi-Goutieres syndrome (AGS) and HIV infection.” Ex. 50 at 24 (emphasis 

added). H.H. tested negative for HIV. Ex. 52 at 75. H.H.’s blood was sent to England and his CSF 

was sent to France for interferon alpha testing. Dr. Crawford noted that “[b]oth CSF and blood 

showed elevated levels of INF-alpha which is diagnostic for AGS.” Ex. 50 at 24 (emphasis 

added).

During the entitlement hearing, I asked whether you could see elevated neopterin levels in 

a viral infection other than HIV. Dr. Barañano testified as follows:

You could. So ... for example, they looked at patients who had encephalitis and, 

meningoencephalitis, and with herpes virus infections, they would see elevated 

neopterin. There's a very terrible brain stem encephalitis that can be caused by an 

enterovirus, and so it's been reported in that situation. But these are clinical settings 

where patients would have fever. They would have lot of white cells in their spinal 

fluid. They would ... have very different imaging abnormalities on their MRI that 

would point to some kind of infectious picture going on. 
55

Tr. at 293-94.

H.H. also had his interferon alpha levels in both the blood and CSF tested in England and 

France. The French results revealed elevated levels of interferon alpha in the serum on two 

different dates: January 15, 2014 and March 25, 2014; the levels were 18 and 9, respectively, with 

˂ 2 being normal. Ex. 56 at 357.

After the extensive testing performed in this case, there was no explanation for H.H.’s 

elevated neopterin and interferon alpha levels other than AGS. Ultimately, Dr. Barañano opined 

that “based on his clinical course and his biochemical abnormalities, the most leading, the most 

likely diagnosis right now is suspected AGS.” Tr. at 279.

Petitioners argue that H.H. does not have AGS because his clinical presentation is lacking 

“five major characteristics” that should be present in order to render an AGS diagnosis. See Pet’rs’ 

Post-Hearing Brief at 13. Petitioners note that H.H. does not have one of the seven genetic 

mutations known to cause AGS; he did not have calcifications on MRI; he had no known damage 

to his basal ganglia; his neopterin levels did not normalize; and his rapid decline occurred after 12 

months of age. Id. I will discuss each of these points, in turn.

d. Genetic Mutation

Because H.H. does not have one of the seven identified genes known to cause AGS, 

diagnosis in this case has been challenging. Livingston and Crow have noted that “[m]utations in 

these [seven] genes account for around 95% of patients with classical AGS.” Livingston & Crow 

at 2. This means that five percent of AGS cases are associated with an unidentified genetic 

mutation. Second Barañano Rep. at 1. Dr. McGeady agreed, noting that the “identification of 

genetic mutations causing AGS is a work in progress.” First McGeady Rep. at 6.

The fact that H.H. does not have a gene currently identified with AGS is Petitioners’

strongest argument that he does not have the disease. 

Petitioners also argue that H.H. did not exhibit four other “major characteristics” that have 

been observed in other patients with AGS. At the outset, I note that our understanding of AGS has 

evolved as physician-scientists have conducted additional research. This additional research has 

led those who study the disease to recognize that “the range of phenotypes associated with 

mutations” of AGS genes “is much broader than previously realized.” Crow & Manel, AicardiGoutières syndrome and the type I interferonopathies, 15 NATURE REVIEWS IMMUNOLOGY 429-

40, 429 (2015) (filed as Ex. D1) (hereinafter “Crow & Manel”). Crow & Manel recognized that

“patients with mutations in the AGS-associated genes frequently lack one or more, sometimes

even all, of the original diagnostic criteria outlined by Aicardi and Goutières in their 1984 paper.”

Id. at 430 (emphasis added). Similarly, Livingston & Crow noted that “[a]s more patients harboring 

mutations in these genes have been described, in particular facilitated by the advent of whole 

exome sequencing, a remarkably broad spectrum of associated neurologic phenotypes has been 

revealed.” Livingston & Crow, Neurologic Phenotypes Associated with Mutations in TREX1, 

RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1: Aicardi–Goutières 
56

Syndrome and Beyond, NEUROPEDIATRICS, DOI http://dx.doi.org/10.1055/s-0036-1592307 ISSN 

0174-304X, 1-6 (2016) (filed as Ex. A, Tab 1) (hereinafter “Livingston & Crow”). Finally, Crow 

and Manel noted that 

although the AGS diagnostic label still has a useful clinical purpose, there are many 

patients who do not fit this paradigm as initially delineated. Hence, we are now 

tending towards the use of the generic term ‘type I interferonopathy’ to refer to this 

group of monogenic diseases in which a constitutive upregulation of type I IFN 

production is considered directly relevant to pathogenesis.

Crow & Manel at 430. It is important to consider this expanded understanding of the AGS 

phenotype in analyzing H.H.’s presentation.

e. Calcifications

Brain calcifications are consistently recognized as a feature usually present in children with

AGS. The fact that H.H. did not have brain calcifications supports Petitioners’ position that AGS 

is not his proper diagnosis. As Dr. Barañano noted in her testimony, “if he had calcifications, we 

would not be having this hearing.” Tr. at 280.

Although brain calcifications are typical of most AGS patients, some do not have them. 

Dr. McGeady opined that “[w]hile calcification of the CNS are not described in HH’s MRI studies, 

the authors of the 2007 report of Rice et al. state "this feature (i.e. intracranial calcification) should 

not be considered prerequisite for the diagnosis of AGS” since it is variably present. Id.; See Rice 

at 721.

Similarly, Dr. Barañano noted that “it’s become well established that calcifications are not 

required for ... a definitive genetic diagnosis of AGS.” Tr. at 279.

f. Basal Ganglia Damage

In his letter submitted on August 25, 2017, Dr. Marks stated that “On his most recent July 

2017 MRI scan, there is diffuse atrophy but there are no intracranial calcifications or physical 

injury to the basal ganglia damage, two of the common findings in AGS.” Second Marks Rep. at 

1.

It is not clear that damage to the basal ganglia is a “major characteristic” of an AGS 

diagnosis. Petitioners did not cite to any authority for this proposition except for the opinion of Dr. 

Marks. In examining the medical literature, Crow & Manel provide a chart that summarizes the 

“major clinical features associated with genetically distinct type I interferonopathies”. Crow & 

Manel at 434. Under “neurological phenotypes”, Crow & Manel list, “developmental delay”, 

“intracranial calcification”, “white matter disease”, “cerebral atrophy”, and “spastic paraparesis”. 

Id.
57

La Piana et al. note that “[b]asal ganglia atrophy was documented in cases with bilateral 

striatal necrosis.” La Piana at 30. It is unclear if this is the damage to which Dr. Marks referred. If 

so, it does not appear to be a common feature of the disease. 

Additionally, Dr. Barañano briefly discussed this issue at the entitlement hearing; she 

testified that “the basal ganglia damage is seen in a subset of patients especially those with a 

particular mutation in something called ADAR.” Tr. at 280. She noted that it is not universally 

seen in all cases of AGS. Id. Of note, mutations on the ADAR gene account for approximately 7% 

of AGS cases, according to Dr. Crow’s data. See Crow 2014 at 301. Based on the above, I do not 

find that basal ganglia damage is a major characteristic of AGS, as argued by Petitioners in their 

post hearing brief.

g. Normalization of Neopterin Levels

In his letter filed into the record on August 25, 2017, Dr. Marks stated that “HH has had 

persistently biomarkers for intrathecal interferon production until his most recent testing 

performed in July 2017 which revealed normal levels of CSF neopterin, a marker for interferon 

production.” Marks Expert Report at 1. Dr. Marks cited this normalization of neopterin as a basis 

to opine that he favored vaccine causation over AGS because of H.H.’s “waning immune 

response.” Id.

However, H.H.’s neopterin levels changed by the time of the entitlement hearing. While it 

is true that his levels were in the normal range on August 7, 2017 (Ex. 95 at 78), they were again 

elevated on January 23, 2019. Ex. 96 at 14; Ex. 96 at 115.

In their post-hearing brief, Petitioners argue that “H.H.’s presentation showed ... 3) no 

normalization of neopterin levels”. Pet’rs’ Post-Hearing Brief at 13. Petitioners further argued that 

a normalization of neopterin constitutes one of the five major characteristics of an AGS diagnosis. 

Id. It is unclear whether Petitioners misstated their position, as they later argue in their brief that 

H.H.’s neopterin levels normalized in July 2017. They stated that “H.H. has persistently shown 

biomarkers for intrthecal [sic] interferon production until his most recent testing performed in July 

2017, which revealed normal levels of CFS neopterin, a marker for interferon production.” Pet’rs’ 

Post-Hearing Brief at 16.

Dr. Marks testified at hearing with respect to H.H.’s neopterin levels. He stated, “So in 

2017, the levels had dropped down some, and then ... with the last one, they actually went back 

up again. Now ... admittedly, that's known to happen in AGS. The ... interferon levels can 

fluctuate some over time.” Tr. at 176. Dr. Marks’ testimony does not ascribe great significance to 

H.H.’s drop in neopterin levels in 2017 and subsequent re-elevation in 2019. Although he did not 

mention it at hearing, apparently he no longer believes that H.H.’s neopterin normalization

suggests vaccine causation, as that level is again elevated.

Further, the medical literature filed in this case does not provide compelling support for 

the point that it is characteristic for AGS patients to experience normalization in neopterin levels.

In fact, Crow et al. note that their data “clearly demonstrate that an interferon signature persists 

long term in most patients, indicative of an ongoing inflammatory process.” Crow 2014 at 309. 
58

Accordingly, I do not credit Petitioners’ position that normalization of neopterin is characteristic 

of AGS. In fact, the persistent elevation of H.H.’s neopterin levels lends support for an AGS 

diagnosis.

h. Onset of AGS after 12 Months of Age

Petitioners correctly note that most children who develop AGS do so within the first year 

of life. They go on to argue that because H.H. developed normally until he was approximately 15 

months-old, this suggests that AGS is not his correct diagnosis. 

Both Dr. McGeady and Dr. Barañano opined that there is variability in AGS presentation 

which includes onset after the first year of life. Dr. McGeady specifically opined that “a period of 

normal development before the onset of symptoms in AGS is described in some cases and should 

not be considered as a finding implicating the vaccines.” First McGeady Rep. at 4-5.

The medical literature supports the fact that while onset of “typical” cases of AGS occurs 

in the first year of life, it is well recognized that children can develop onset after this time. See e.g., 

Orcesi et al., Aicardi–Goutières syndrome presenting atypically as a sub-acute

leukoencephalopathy, 12 EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY, 408-11 (2008) (filed 

as Ex. A2) (describing a case of Aicardi–Goutières syndrome in a 16-month-old child with 

previously normal development); see also D’Arrigo (same). Livingston & Crow also described a 

case of later onset AGS. They discussed a child

who showed completely normal development until the age of 15 months, at which 

time he could walk and had 6 to 10 words. After this point, he developed 

intermittent posturing and rigidity of his legs, and then of the upper extremities. He 

also developed exaggerated startle. He subsequently experienced a relentless loss 

of motor and intellectual skills, and by the age of 24 months, he was unable to sit 

unsupported and had lost the ability to swallow. Between 15 months and 4 years of 

age, he demonstrated a fluctuating pattern of poor sleep, with persistent whining 

and crying. 

Livingston & Crow at 3.

Finally, Crow et al. studied 325 children with AGS and observed that “[t]wenty-eight 

patients (8.6%) presented after the age of 1 year, with 35% and 30% of patients with mutations in 

ADAR and IFIH1, respectively, demonstrating the onset of disease after this age.” Crow 2014 at 

303. Crow’s data suggest that later onset is associated primarily with mutations in two specific 

AGS genes.

Ultimately, the fact that H.H. developed symptoms consistent with AGS at 15 months does 

show his clinical course is not a typical presentation of the disease. At the same time, this point 

does not provide persuasive evidence that H.H. does not have AGS, as cases of later onset are 

reported in the medical literature.

i. Neurologic Stabilization/Improvement
59

Although not specifically alleged by Petitioners in their post hearing brief, Dr. Marks 

discussed H.H.’s neurologic stabilization and improvement as support for the fact that he does not 

have AGS.

In his affidavit, Dr. Marks opined as follows: “H.H.’s neurological status has since 

stabilized, but [he] still has persistent increases in his interferon levels. This stabilization of his 

neurological status, which was hyperactive post-immunization is indicative of the cause being 

derived from the vaccinations.” Marks Affidavit at 4-5. At hearing, Dr. Marks described AGS as 

a “relentlessly progressive disorder.” Tr. at 164. He opined that H.H.’s improvement in function 

is not expected in an AGS patient. Id.

Dr. Barañano disagreed with Dr. Marks on this point. She testified that “based on [her]

clinical experience and understanding of the literature, what is the most common clinical course is 

to have the acute neurologic symptoms followed by a period of stabilization.” Tr. at 270. “it's well 

established that AGS is not necessarily a relentlessly progressive neurodegenerative disorder. So 

I would respectfully disagree with Dr. Marks in his assessment ... of that.” Id.

Dr. McGeady disagreed with Dr. Marks as well. He opined that “stabilization of the 

neurologic status of AGS patients is a characteristic of the disease, and should not be considered 

evidence against that diagnosis.” First McGeady Rep. at 7.

The medical literature supports the opinions of Drs. Barañano and McGeady. For example, 

Crow et al. noted that “[b]eyond an initial encephalopathic phase, generally lasting several months, 

continued neurological deterioration was not obvious in most patients; indeed, some parents 

reported a slow but steady acquisition of new skills over time.” Crow 2014 at 309. Rice et al. 

similarly observed that the majority of children presented with “subacute onset of a severe 

encephalopathy, characterized by irritability, inconsolable crying, intermittent sterile pryexias ... 

and a loss of skills. These episodes usually lasted several months, beyond which time the condition 

stabilized. Thereafter no further disease progression was generally observed.” Rice 2007 at 718.

Finally, Livingston & Crow noted that 

Although initially considered a neurodegenerative, progressive disease, as more 

patients have been studied longitudinally, this point has come into question. In our 

opinion, the most classical clinical course is of a period of several months of 

neurologic regression in infancy associated with progressive radiological changes. 

For most patients, the disease then stabilizes, leaving the child with profound 

disabilities. 

Livingston & Crow at 4-5. The fact that H.H.’s condition stabilized and even showed some 

improvement is consistent with a diagnosis of AGS.

Dr. Barañano testified at the entitlement hearing regarding the question of diagnosis. She 

opined that “[H.H.] has something like AGS that in my experience we will eventually find the 

genetic underpinnings of his disorder.” Tr. at 296. Dr. Steinman agreed. He opined that “the 
60

diagnosis is an interferonopathy akin to AGS” and noted that “the genetic basis of the disease has 

not been shown at the time I wrote Ex 101.” Second Steinman Rep. at 2. Dr. Vanderver, one of the 

nations’ leading authorities on AGS, treated H.H. in March of 2015. Dr. Vanderver noted that H.H. 

had a “suspected heritable interferonopathy.” Ex. 81 at 6. Ultimately, in considering the evidence 

presented on this issue, I find the opinions of Dr. Barañano, Dr. McGeady, Dr. Vanderver, and Dr. 

Steinman to be persuasive. H.H., more likely than not, has AGS or a similar genetic 

interferonopathy. 

2. H.H.’s Aicardi Goutières Syndrome/Genetic Type I Interferonopathy

Manifested around the Time of his October 17, 2013 Vaccinations and before 

his October 23, 2013 Vaccination

On September 13, 2013, Mrs. Heller called Wise Pediatrics. The note from this phone call 

reads as follows: “mom concerned with pt not walking and rt foot turned inward has appt in one 

month, questions if needs to be seen earlier than scheduled appt, discussed development per Dr. 

Hollis, will wait till scheduled to be seen.” Ex. 49 at 37. There is no mention of this issue in the 

notes from the 15-month well visit on October 17, 2013. Id. at 39. At the entitlement hearing, Mrs. 

Heller testified that H.H. had appeared “pigeon-toed” when she called Wise Pediatrics, but that his

feet were not turned in during the 15-month appointment. Tr. at 13-14. Dr. Hollis assessed him as 

a well child.22 Id.

The experts did not provide a persuasive opinion regarding this evidence. Dr. Barañano 

opined “there is evidence that his onset of symptoms began prior to the vaccine administration.” 

Second Barañano Rep. at 1. Dr. McGeady stated that “It is not possible to know with certainty 

why the concerns expressed in the phone contact of 9/13/2013 were not addressed in the office 

visit of 10/17/2013, if only to dismiss them.” Second McGeady Rep. at 2. Dr. Steinman opined: “I 

personally do not think that H.H. had pre-existing evidence of a neurologic problem, unless the 

turning of the right foot inward was the earliest manifestation of dystonia. Whether or not there 

was a subtle form of an underlying problem prior to October 17, 2013 is a point that cannot easily 

be resolved.” First Steinman Rep. at 5.

Although there may be a relation between this documented concern in September involving 

H.H.’s right foot, and the onset of his type I interferonopathy (which also first manifested in his 

right foot/leg), I do not find there is sufficient evidence to draw this connection. In particular, none 

of the experts explained why or how H.H. would begin to demonstrate signs of his genetic disorder 

and then improve. This point is especially confounding given H.H.’s rapid and relentless decline 

once his disease process started. As such, I find there is not preponderant evidence that the 

inturning of H.H.’s right foot in September of 2013 constituted the onset of his condition. 

22 Dr. Hollis filed a supplemental affidavit on August 26, 2016. Ex. 90. In it, she stated that she examined 

H.H. on October 17, 2013, and noted that he was “taking a few steps independently between objects.” Id.

at 2. Dr. Hollis then wrote that “His mom had noted his foot possibly turning in 1 week prior to his 

appointment.” Id. I assume that “one week” is a typo and Dr. Hollis meant to write one month. In making 

this assumption, I have credited the contemporaneously created medical records over an affidavit created 

years after the fact.
61

On November 11, 2013, Mrs. Heller brought H.H. to visit Dr. Hollis. In the history of 

present illness section of the record, Dr. Hollis noted that “Pt has been fussy for the last week. He 

has run fever to 101.5. His energy level is decreased. Pts development has regressed in the last 

month.” Ex. 49 at 41. This record is the medical record most contemporaneous to the onset of 

H.H.’s condition; it suggests that H.H. had regressed in the last month, or since mid-October of 

2013.

The fact witnesses consistently testified at the entitlement hearing that H.H. was not 

himself on Halloween. Mrs. Heller testified that he began dragging his right foot that week. Tr. at 

19. Mrs. Heller also testified that he fell on Halloween. Id. at 19-20. Ms. Sewell testified that H.H. 

began falling around October 26, 2013. Id. at 113-14. Ms. Huling also saw H.H. fall on Halloween. 

Id. at 128.

On March 14, 2014, H.H. was evaluated at an infectious diseases consultation. Dr. Kenneth 

Colina noted as follows:

[H.H.] is a 20-month-old ... who has developed progressive developmental delay 

over the last 5 months, relatively acutely. His mother reports that she breastfed him 

constantly until 10/9. Within a day or 2 of stopping breastfeeding he seemed to trip 

and fall when he was crawling. She reports that he was completely normal at his 

15-month checkup, walking and talking, and very active and playful. She then 

stopped breastfeeding, and within a week he was falling. About 8 days later after 

stopping breastfeeding, he got his 15-month shots.

Ex. 57 at 1. The “review of systems” section noted that “after he started falling in mid-October his 

parents noticed that he had a fever for about a week, with a red throat that resolved.” Id.

This record does contain some inconsistencies. For instance, it is not clear whether H.H. 

was falling before his 15 month appointment or not. Mrs. Heller testified that H.H. did not trip and 

fall within one or two days of the date she stopped breastfeeding. Tr. at 39. However, several points 

in this record are accurate. First, Mrs. Heller did stop breastfeeding on approximately October 9, 

2013. She discussed this matter at the entitlement hearing, testifying that, “I wanted my kids two 

years apart, so I decided to wean him at the beginning of October so I could start trying again...” 

Tr. at 37. Mrs. Heller testified that she wanted H.H. to be completely weaned by 15 months. Id. at 

37-38. She additionally stated, “there's probably no question that I quit breast-feeding the week 

before vaccines ...” Id. at 60. It is also true that eight days after October 9 is October 17, 2013, the 

date H.H. received his flu and Prevnar vaccines. Ultimately, this record does support that H.H. 

started falling in mid-October, although the term “mid-October” is not precise.

Mrs. Heller took H.H. to see her aunt, Sheri Huling, early in the week of October 20, 2013. 

As of the date she drafted her letter, Ms. Huling had been a practicing pediatric physical therapist 

for 35 years. Ex. 102 at 1.23 According to Ms. Huling, H.H.

23 Ms. Huling testified at the entitlement hearing that her affidavit (Ex. 91) was not entirely accurate. The 

affidavit noted that “[a] few weeks prior to H.H.’s 10-23-13 visit with his pediatrician, I noted some 
62

had the pneumonia and flu vaccine[s] on 10-17-13, and I saw him the following 

week. His mom had noticed that over the last few days he was having some trouble 

cruising around furniture and taking steps and she asked me to take a look at him 

from a therapist perspective. I noted some tightness in his right heel [] cord that was 

alarming. I advised her of some stretches to do and then told her to make sure and 

call this to the attention of her physician on his next visit which was to be 10-23-

13.

Ex. 102 at 1. This visit with Ms. Huling took place either Sunday, October 20, 2013, Monday the 

21st, or Tuesday the 22nd, as it was the “next week” after the October 17 vaccinations and before 

H.H.’s visit on October 23rd. This places onset of H.H.’s difficulty walking to a few days before 

this visit, or around the date the first two vaccines were administered. Ms. Huling went on to note 

that when she saw H.H. on Halloween, she noted “worsening in his tightness in [the] right heel [] 

cord.” Id. Ms. Huling stated that she observed H.H. fall once while seated and once while standing 

on October 31, 2013. Id.

The right heel cord tightness that Ms. Huling observed is also documented in the medical 

records. Dr. Crawford evaluated H.H. on November 12, 2013. During this visit, she noted that 

H.H.’s “heel cords appear somewhat tight and he may require AFOs [ankle-foot orthosis]24 at some 

point in the future.” Ex. 50 at 2. The physical exam section of this record indicates that H.H. had 

“hypertonicity (noted in lower extremities especially at the ankles).” Id. at 5. Dr. Crawford 

recommended that H.H. attend physical therapy. Id. at 6.

H.H.’s clinical picture worsened by the time of his next visit with Dr. Crawford on 

December 3, 2013. Dr. Crawford noted that H.H. had “hypertonicity (noted in lower extremities 

especially at the ankles, feet held inward position). Pt now holds hand in a fist when trying to reach 

for objects and when crawling...” Ex. 50 at 11.

During a physical therapy session on June 26, 2014, the physical therapist noted that H.H. 

had several abnormal exam findings, to include “bilateral Achilles contractures”. Ex. 95 at 145. 

Ultimately, Ms. Huling noted that H.H. had a tight right heel cord – an observation that she 

described as “alarming.” She noticed this tightness sometime in the days after H.H. received his 

October 17, 2013 vaccinations, and before he received the Pentacel vaccine on October 23, 2013.

The medical records also document this finding, and associate the tightness with his disease 

tightness in his right heel [] cord that I suggested should be mentioned to his pediatrician.” Ex. 91 at 2 

(emphasis added). Ms. Huling testified that before signing her affidavit, she had prepared a letter (filed as 

Ex. 102) outlining her memory of the events surrounding the onset of H.H.’s condition. Tr. at 205-07. Ms. 

Huling specifically referenced H.H.’s heel cord tightness and testified that she noticed it a few days before 

the October 23, 2013 vaccination. See Tr. at 206-07.

24 An ankle-foot orthosis is “any orthotic device for the lower limb that encloses the ankle and foot and does 

not extend above the knee; often there is a cuff or other device in the region of the knee or upper calf to 

take weight off the limb.” Ankle-foot orthosis, Dorland’s Med. Dictionary Online, https://

www.dorlandsonline.com/dorland/definition?id=95032 (last accessed March 28, 2022).
63

progression. I find Ms. Huling’s description to be compelling evidence that is also supported by 

other medical records. See Ex. 49 at 41 (medical record from November 11, 2013, noting that 

H.H.’s development had regressed in the last month); Ex. 57 at 1 (stating that H.H. began falling 

in mid-October). Accordingly, I find there is preponderant evidence that the onset of H.H.’s 

condition began close-in-time to his October 17, 2013 vaccinations and before he received the 

Pentacel vaccine.

In sum, I have found the evidence preponderantly supports the fact that H.H. has a genetic 

type I interferonopathy that is either AGS or is AGS-like. Although I am unable to make a specific 

finding as to whether H.H. began to develop signs of his type I interferonopathy before or after the 

flu and pneumonia vaccines, I have not analyzed whether these vaccines either caused or 

significantly aggravated H.H.’s condition because Dr. Steinman only offered an opinion with 

respect to the Pentacel vaccine. My finding that H.H. began to show signs of his type I 

interferonopathy before he received the Pentacel vaccine makes the analysis more pointed. It 

means that the Pentacel vaccine did not cause H.H.’s condition, but instead, raises the question as 

to whether the Pentacel vaccine caused the significant aggravation of H.H.’s genetic condition that 

had already begun to manifest. See Locane v. Sec’y of Health & Hum. Servs., 685 F.3d 1375, 1381

(Fed. Cir. 2012) (stating that if “the illness was present before the vaccine was administered, 

logically, the vaccine could not have caused the illness.”).

B. Loving Prong One: H.H.’s Condition prior to the October 23, 2013 Vaccination

with Pentacel

H.H. developed normally up until the time surrounding his October 17, 2013 vaccinations. 

Right around this time, he began to have difficulty cruising around furniture and walking. His right 

heel cord was tight. Ms. Huling observed this tightness before H.H. received his October 23, 2013 

Pentacel vaccine.

C. Loving Prong Two: H.H.’s Condition after the October 23, 2013 Vaccination with 

Pentacel

After the October 23, 2013 vaccination, H.H.’s walking/cruising continued to deteriorate. 

He began dragging his right foot, and then falling. He lost the ability to bear weight on his legs 

and to crawl. H.H. developed rapid and progressively worsening encephalopathy, spasticity, and 

dystonia. His neopterin levels were dramatically elevated and have remained elevated through 

2019, with a return to normal levels for a period of time in 2017. Although H.H.’s condition 

stabilized, he cannot sit unassisted, cannot eat without a G-tube, and requires 24 hour medical care.

D. Loving Prong Three: Did H.H. Experience a Significant Aggravation of his

Condition?

H.H.’s deterioration is consistent with the Vaccine Act’s definition of significant 

aggravation resulting in markedly greater disability, pain, or illness accompanied by substantial 

deterioration of health. § 33(4). Therefore, this leaves the question of whether the significant 

aggravation of H.H.’s condition was vaccine-related.
64

E. Loving Prong Four/Althen Prong One: Petitioners have not Established a Reliable 

and Reputable Theory Concerning How the Vaccinations H.H. Received Can 

Cause a Significant Aggravation of AGS/a type I Interferonopathy

Under Loving prong four/Althen prong one, the causation theory must relate to the injury 

alleged. Thus, Petitioners must provide a “reputable” medical or scientific explanation, 

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

1355-56. The theory must be based on a “sound and reliable medical or scientific explanation.” 

Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). It must only be 

“legally probable, not medically or scientifically certain.” Id. at 549. 

Dr. Steinman emphasized that the Pentacel vaccine was causative and did not provide a 

theory involving either the flu or pneumonia vaccines (See First Steinman Rep. at 8, where Dr. 

Steinman noted that “Petitioner herein provides a theory on how the components of the October 

2013 vaccine induced activation of both type 1 interferon and type II interferon, known as gamma 

interferon. I shall focus on the Pentacel vaccine...”; First Steinman Rep. at 11, Dr. Steinman stated,

“I shall show that Pentacel causes increases in both type 1 interferons and in the type 2 interferon, 

known as gamma-interferon.”; First Steinman Rep. at 12, Dr. Steinman discussed the importance 

of alum in Pentacel; First Steinman Rep. at 13, Dr. Steinman noted that “Induction of type 1 and 

type 2 interferon by Pentacel could worsen neuroinflammation and this more likely than not 

occurred in H.H.”; First Steinman Rep. at 14, Dr. Steinman stated that “I have provided a 

mechanistic basis for how Pentacel can trigger a type 1 and type 2 interferon response and how 

the NALRP3 inflamm[a]some can be triggered by the components of Pentacel.”; See First 

Steinman Rep. at 15-16 for more examples). Because I have found that H.H. developed signs of 

his interferonopathy before he received the Pentacel vaccine, I will analyze whether the Pentacel 

vaccine can cause a significant aggravation of H.H.’s interferonopathy.

Dr. Barañano defined an interferonopathy as a “class of disorders where there is 

dysregulation of the control of the levels of interferon alpha in the immune system.” Tr. at 272.

They are thought to occur “as a result of the failure to appropriately regulate the metabolism of 

nucleic acids.” Tr. at 221. This gives continued stimulation to type I interferons. Id. Dr. McGeady 

testified that “in the hereditary interferonopathies, there [are] no breaks. The ... interferon just 

keeps getting produced more and more over ... an extended period of time.” Id. at 223. He further 

opined that, “In the case of HH, the control mechanisms failed, apparently from a genetically 

determined dysregulation of nucleic acid metabolism, and exceedingly large amounts of interferon 

alpha were produced and allowed to persist for an extended period of time.” Second McGeady 

Rep. at 2. This explains both the elevated levels and the persistence of these elevated levels. Id.

Type I interferonopathies are inherited genetic disorders. Tr. at 272, 287. This point is 

supported by the medical literature filed in this case. See e.g., Rodero & Crow, describing “the 

grouping of Mendelian disorders associated with an up-regulation of type I interferon signaling as 

a novel set of human inborn errors of immunity.” Rodero & Crow at 2527.
65

Dr. Steinman opined that the Pentacel vaccine activated H.H.’s immune system resulting 

in the production of type 1 and type 2 interferons, which led to the worsening of his 

neuroinflammation. First Steinman Rep. at 11-13.

25

In support of this theory, Dr. Steinman discussed literature describing the production of 

type 1 and type 2 interferons in response to components of the Pentacel vaccine.

He cited Fadugba et al., Immune Responses to Pertussis Antigens in Infants and Toddlers 

after Immunization with Multicomponent Acellular Pertussis Vaccine, 21 CLINICAL AND VACCINE 

IMMUNOLOGY 12 (2014) 1613-19 (filed as Ex. 101, Tab 12) (hereinafter “Fadugba”). Fadugba 

studied the antibody, cell-mediated, and cytokine responses to B. pertussis antigens in children 

who received a primary DTaP vaccination at two, four, and six months, and a booster vaccination 

at 15 to 18 months. The authors noted that: “One month after booster vaccination, ... our study 

revealed significant increase in gamma interferon (IFN-gamma) production in response to the 

[pertussis toxin] and [fimbriae] antigens, a significant increase in IL-2 production with the 

[pertussis toxin], [filamentous hemagglutinin], and [pertactin] antigens, and a lack of significant 

interleukin-4 (IL-4) secretion with any of the antigen.” Fadugba at 1613. Fadugba does stand for 

the proposition that DTaP vaccination results in an increase in gamma interferon, albeit these levels 

were not measured until one month after the booster vaccination. 

Dr. Steinman also cited to the Kooijman article. See Kooijman et al., Vaccine antigens 

modulate the innate response of monocytes to Al(OH)3, PLOS ONE, https://doi.org/10.1371/ 

journal.pone.0197885, 1-22 (2018) (filed as Ex. 101, Tab 13) (hereinafter “Kooijman”). Kooijman

“compared the innate immune responses induced by Al(OH)3 [aluminum hydroxide] alone versus 

that of a licensed combination DTaP vaccine containing Al(OH)3, using cytokine analysis,

transcriptomics and proteomics, to determine unique, shared and potential synergistic or

antagonistic effects of adjuvant and antigen components.” Kooijman at 2. Kooijman noted that 

“After 24 hours of stimulation, both Al(OH)3 and DTaP-stimulated monocytes showed a trend 

towards increased gene expression of the type I interferon IFNβ.” Id. at 13.

Dr. Steinman also discussed “the importance of alum in Pentacel in activating []the 

NALRP3 inflamm[a]some, which plays a key role in inducing interferonopathies.” First Steinman 

Rep. at 12. Dr. Steinman cited to the Li article. Li et al., Cutting Edge: Inflammasome Activation 

by Alum and Alum's Adjuvant Effect Are Mediated by NLRP3, 181 JIMMUNOL 17-21 (2008) (filed 

as Ex. 101, Tab 14) (hereinafter “Li”). In this study, mice were vaccinated with one-tenth of a 

human dose of the DT/TT vaccine, and then boosted two weeks later. On days 14, 28, and 56,

blood samples were collected. Li at 18. Li described that “inflammasome activation by alum and 

alum’s adjuvanticity are mediated by NLRP3 and ASC.” Li at 18. In concluding, the authors noted 

that “[o]ur results identified for the first time NLRP3 as an important player in alum’s adjuvant 

25 Although at hearing Dr. Marks opined that H.H.’s vaccines caused him to develop an interferonopathy

via molecular mimicry, Petitioners appear to have abandoned that theory in their post hearing brief. See

Petr’s’ Post-Hearing Brief at 12-13, 15-16. Indeed, as discussed in section VI F, Dr. Marks was unable to 

provide a persuasive causation opinion. Although not analyzed in this decision, I do not find that Dr. Marks’ 

opinion on molecular mimicry constitutes a sound and reliable theory in this case. 
66

effect and indicate an important role for the inflammasome in the development of adaptive 

immunity. The ability to activate the inflammasome must be one of the properties to be considered 

during the development of new generation vaccines.” Id. at 20-21.

While vaccines may activate the inflammasome, Dr. Steinman has not presented a link 

between such activation and the development of AGS or a similar type I interferonopathy. Indeed, 

Crow & Manel noted that “to our knowledge, a possible engagement of the inflammasome in 

patients with AGS has not been investigated.” Crow & Manel at 431.

Dr. Steinman also cited to two articles discussing Experimental Autoimmune Encephalitis 

(EAE) and Multiple Sclerosis for the proposition that inflammasome activation can worsen 

neuroinflammation. Inoue et al., Mechanism to develop inflammasome-independent and 

interferon-β-resistant EAE with neuronal damages, 19 NAT NEUROSCI. 12, 1599-1609 (2016) 

(filed as Ex. 101, Tab 15); Axtell et al., Type I Interferons: Beneficial in Th1 and Detrimental in 

Th17 Autoimmunity, 44 CLIN REV ALLERGY IMMUNOL. 2, 114-20 (2013) (filed as Ex. 101, Tab 

16).

Dr. McGeady disagreed with Petitioners’ causation theory, noting that the vaccines “are 

not related to the central nervous system (CNS) pathology which occurred in the child.” Second

McGeady Rep. at 1. He cited two main reasons for this opinion. First, Petitioners’ theory does not 

explain how vaccination caused H.H.’s innate immune response to be so “massively exaggerated 

as demonstrated by the elevated levels of interferon alpha in the blood and cerebrospinal fluid 

(CSF) of HH.” Id. Second, Dr. Steinman did not explain how H.H.’s interferon alpha levels 

remained elevated for years after vaccination. Id.

Dr. McGeady agreed that vaccination “would be expected to generate a physiologic amount 

of type I interferon and other pro-inflammatory cytokines”. Second McGeady Rep. at 2. However, 

he noted that interferon production “promptly decreases” after a non-progressive provocation such 

as vaccination. Id. In further substantiation of this opinion, Dr. McGeady noted that interferons are 

“biologically potent molecules excessive amounts of which can cause the acute illness called 

“cytokine storm”, and their production and metabolism are regulated closely in achieving 

homeostasis.” Id. Dr. Marks and Dr. Barañano were similarly unable to identify any medical 

literature that suggests that vaccination can caused substantially elevated levels of interferon alpha. 

Tr. at 193, 289.

Dr. McGeady is persuasive with respect to this point. While the literature cited by Dr. 

Steinman does demonstrate that vaccination causes the production of some amount of interferon, 

it does not suggest that these levels are excessive. In fact, both Fadugba and Kooijman discuss 

normal innate immune responses after vaccination. Neither article suggests that interferon 

production post-DTaP vaccination is anything resembling H.H.’s interferon alpha levels, which 

one provider described as “the highest neopterin levels we have ever seen.”

26 Ex. 55 at 1.

26 As Dr. Marks noted at the entitlement heating: “neopterin is a marker for interferon activity.” Tr. at 194. 
67

Petitioners’ theory is equally unpersuasive in preponderantly establishing that vaccination 

can cause persistently elevated levels of interferon alpha. With respect to this point, Dr. McGeady 

testified as follows: 

here you have a youngster who in 2013 has high levels of neopterin in his spinal 

fluid. In 2017, he’s back to normal again, and in 2019, he’s way up again. So it's 

that constant up and down. There’s no living organism in any of the vaccines that 

he received. So what could possibly keep that process going on for that long a 

period of time? 

Tr. at 223-24. Dr. Steinman claimed that the continuous production of type I interferon can be 

explained by the medical literature, which shows “that there is a resistance in some forms of 

neuroinflammation to the normal beneficial response of interferon.” First Steinman Rep. at 14. Dr. 

Steinman’s opinion seems to be that the beneficial type of interferon that would normally modulate 

an interferon response was absent or deficient in H.H., and as a result, his immune system 

continuously produced type I interferon, which resulted in disease. Id.

Naves et al. discusses the interplay between type I and type II interferons. Naves et al., The 

Interdependent, Overlapping, and Differential Roles of Type I and II IFNs in the Pathogenesis of 

Experimental Autoimmune Encephalomyelitis, 191 J IMMUNOL, 2967-77 (2013) (filed as Ex. 101, 

Tab 17) (hereinafter “Naves”). The authors state, “In summary, our data reveal that cooperative 

signaling from type I and II IFNs is necessary to restrain the pathogenesis in EAE. Loss and 

perhaps imbalance of either IFN signal aggravates inflammation and results in exacerbated 

disease.” Naves at 2975. This article does support the principle that imbalance in interferon 

signaling aggravates disease in EAE. EAE is the animal model for MS; it is not an 

interferonopathy. It is difficult to see how this point is persuasive in the case at bar when it involves 

an entirely different disease. I find that Petitioners have not provided a sound and reliable medical 

theory explaining how vaccination causes the chronic overproduction of interferon.

I also note that there appears to be no published medical literature (to include case reports) 

indicating that the flu, pneumonia, or Pentacel vaccines can cause or exacerbate a type I 

interferonopathy. See Tr. at 217, 272. Dr. McGeady testified that there is also no literature 

suggesting the live viruses associated with these vaccines could cause one of these conditions. Id.

at 218.

Dr. Steinman pointed to the Rodero & Crow article as providing support for his theory. In 

discussing type I interferonopathies and the ADAR-1 mutation, Rodero & Crow stated that 

“[w]hether vaccination represents a disease trigger is an important, and currently unanswered, 

question.” Rodero & Crow at 2532. This statement suggests that vaccination as a potential trigger 

for a type I interferonopathy involving an ADAR-1 mutation could be an area of study at some 

point in the future. This statement does not provide persuasive evidence in support of Petitioners’ 

theory in this case.

Petitioners are not required to present medical literature or epidemiological evidence to 

establish the first Althen prong. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1380 

(Fed. Cir. 2009). However, as the Federal Circuit noted in Andreu, “a claimant's theory of
68

causation must be supported by a ‘reputable medical or scientific

explanation.’” Andreu, 569 F.3d at 1379 (quoting Althen, 418 F.3d at 1278). Petitioners have not 

presented such a reputable explanation in this case; as such, they have failed to present 

preponderant evidence in support of Loving prong four/Althen prong one.

F. Loving Prong Five/Althen Prong Two: Petitioners have not Established a Logical 

Sequence of Cause and Effect between H.H.’s Vaccinations and the Significant 

Aggravation of his Condition

Loving prong five/Althen prong two requires the Petitioners to provide a logical sequence 

of cause and effect demonstrating that vaccination did cause a worsening of H.H.’s pre-existing 

condition. Althen, 418 F.3d at 1278; Andreu, 569 F.3d at 1375–77; Grant, 956 F.2d at 1148.

Althen’s second prong is not without meaning. Capizzano, 440 F.3d at 1327.

1. Petitioners have not Presented Evidence in Support of Vaccine Causation

Petitioners have not presented evidence demonstrating that H.H. experienced a vaccineassociated significant aggravation of his interferonopathy, signs of which had already begun to 

manifest by the time he received his Pentacel vaccine. They do not point to any testing or clinical 

signs that suggest vaccine causation. Instead, they assert that because H.H.’s deterioration occurred 

close-in-time to his vaccinations, and because no alternate explanation exists, then the vaccines 

“did cause” a significant aggravation of H.H.’s condition. This showing is insufficient. See

Moberly, 592 F.3d at 1323 (citing Althen, 418 F.3d at 1278) (stating that “neither a mere showing 

of a proximate temporal relationship between vaccine and injury, nor a simplistic elimination of 

other potential causes of the injury suffices, without more, to meet the burden of showing actual 

causation.”).

2. The Medical Record Evidence Indicates the Vaccines did not Cause or 

Significantly Aggravate H.H.’s Condition

Not only have Petitioners failed to present evidence from H.H.’s medical records which 

supports vaccine causation, but the records contain evidence supporting the opposite position –

that the vaccines H.H. received did not affect his condition.

Dr. McGeady noted that H.H.'s clinical history does not indicate that he experienced a 

severe local reaction at the vaccine injection sites. Dr. McGeady opined that “[w]hile interferon 

alpha is principally produced by the plasmacytoid dendritic cells and monocytes/macrophages that 

might migrate to regional lymphoid tissue, the absence of local reaction after several prior 

immunizations suggests that no excessive or untoward reaction was produced.” First McGeady 

Rep. at 9. He further opined that this exaggerated interferon release could cause a cytokine storm. 

There is certainly no evidence in the record that H.H. experienced this type of reaction.27

27 There is medical record evidence indicating that H.H. had a fever at his November 11, 2013 visit with 

Dr. Hollis. See Ex. 49 at 41 (noting that “Pt has been fussy for the last week. He has run fever to 101.5.”).

This record places onset of fever one week prior to this appointment, or on approximately November 4, 
69

Petitioners’ causation theory also does not explain how the vaccines caused an elevation in 

H.H.’s transaminases. Several of H.H.’s treating physicians noted that H.H. had elevated liver 

enzymes. During his visit with Dr. Crawford on November 12, 2013, H.H.’s AST was 353, and 

his ALT was 400. Ex. 50 at 4. On December 18, 2013, H.H.’s liver enzymes were again elevated. 

His AST was 325, and his ALT was 472. Ex. 55 at 1. On May 23, 2014, H.H.’s was 119 and his 

ALT was 125. Ex. 63 at 2. H.H.’s treating physicians have drawn a connection between the 

abnormally elevated levels and the onset of his disease process, indicating these levels were 

suggestive of AGS. While elevated liver enzymes are consistent with AGS, there has been no 

evidence presented in this case that they are consistent with a vaccine reaction. In short, Petitioners 

have not explained how this finding fits into their causation theory. Dr. McGeady opined that there 

is no medical literature supporting such a connection. First McGeady Rep. at 9. Dr. Barañano 

agreed. Tr. at 294. The fact that a vaccine reaction does not explain H.H.’s elevated liver enzymes 

suggests that the vaccines did not cause or significantly aggravate his condition.

3. Treating Physicians

Several of H.H.’s treating doctors opined that the vaccines he received caused his 

condition. In weighing evidence, special masters are expected to consider the views of treating 

doctors. Capizzano, 440 F.3d at 1326. The views of treating doctors about the appropriate 

diagnosis are often persuasive because the doctors have direct experience with the patient whom 

they are diagnosing. See McCulloch v. Sec’y of Health & Hum. Servs., No. 09-293V, 2015 WL 

3640610, at *20 (Fed. Cl. Spec. Mstr. May 22, 2015). However, the opinions of treating physicians

are not sacrosanct. Snyder v. Sec'y of Health & Human Servs., 88 Fed.Cl. 706, 745 n.67 (2009). 

These opinions are only as trustworthy as the reasonableness of their suppositions or bases.

Dr. Hollis is H.H.’s pediatrician. She opined as follows: “It seems to me that [H.H.’s] rapid 

decline can be attributed to receiving the vaccinations on October 17, 2013 and October 23, 2013.” 

Ex. 66 at 3. Dr. Hollis based her opinion on the fact that H.H. was previously healthy, and because 

of that, a “severe and rapid developmental regression is unusual” in these circumstances, and that 

many diagnoses have been ruled out by his medical team. Id. Dr. Hollis did not provide any 

additional information to support her opinion. She did not articulate a theory of causation. Under 

these circumstances, although I have considered Dr. Hollis’ opinion, I have not given it great 

weight.

Dr. Marks is H.H.’s treating neurologist. Dr. Marks opined that the vaccines H.H. received 

caused his condition. He stated that

It is also my opinion that considering the commencement of H.H.’s symptoms 

occurred after the receipt of his fifteen (15) month vaccinations, the fact that his 

symptoms have persisted, and the lack of any other explanation for why he has 

developed severe and rapidly progressing dystonia with encephalopathy at this age, 

I have concluded that H.H.’s exposure to the fifteen (15) month vaccines was within 

2013. This is 18 days after the flu and pneumonia vaccines and 12 days after Pentacel vaccine, too long for 

a fever associated with vaccination. 
70

a reasonable medical probability, the most likely trigger for him to develop rapidly 

progressing dystonia with encephalopathy to this degree.

Ex. 67 at 3-4. Dr. Marks’ theory of causation is that H.H.’s vaccines caused him to develop a type 

I interferonopathy via molecular mimicry between a component of one of the vaccines and a self 

antigen. Id. at 4-5. Dr. Marks was unable to provide persuasive testimony at the entitlement hearing 

in support of this opinion.

Q. And in your first report, which is Exhibit 67, and I will just quote it from Page 

4, Paragraph 8 for the paraphrase, you propose an antigen in the influenza or DTaP 

vaccine must have been similar to a self-antigen in HH’s neurological structure. 

Can you be any more specific what in the vaccine you think was involved?

A. No. I’m – I’m not – I’m not an expert in -- in vaccines. I’m not an expert in 

vaccine manufacture. This was -- this was the hypothesis of a clinical neurologist 

looking for some way to explain what was going on. Okay.

Tr. at 172. When asked whether he could identify anything beyond his opinion that supports a 

vaccine-caused AGS-like disease, he testified:

No. And, again, it doesn’t even -- it doesn’t even really have to be mimicry. It just 

has to be something that triggers an immune response, so mimicry was my way of 

explaining it as much to me and -- and to the family. But that doesn’t necessarily 

have to be the theory. It’s – it’s one idea.

Id. at 187. Dr. Marks testified concerning his causation theory by addressing several of my 

questions:

THE COURT: So you just testified that the theory in this case doesn’t have to be 

one of molecular mimicry but is something that triggers an immune response. I do 

need to hear a theory as to how either the Pentacel or the flu vaccine caused the 

issues that HH has experienced. ... And so ... what is your most succinct way ... 

of articulating that ... theory?

THE WITNESS: So if you think of molecular mimicry as an antigen which is --

which is what’s presented to the body, okay -- being similar to something that the 

body doesn't recognize. Then you might -- it might be a little more specific.

And I still think it's – it’s a logical theory that there's something in the vaccine that 

-- that clearly the body has recognized as foreign. That's the whole -- to give a 

vaccine is -- is to do that.

So you are -- vaccines, in general, basically, work by mimicry or by -- or by 

introducing something real to the body that the body should recognize as a[] foreign 

substance. And in this case, basically, the immune system has gone wild to -- in 

response to the immune presentation. So it’s – it’s -- it is a foreign antigen to the 
71

body. Okay. Whether -- whether it -- regardless of which vaccine it is, the -- the 

goal of the vaccine is -- is to introduce this -- this negative antigen, this foreign 

substance to the body, so create an immune response to it.

And on occasion, the immune system just goes wild. That – that’s known to happen. 

And in this case, it's the interferon system that seems to have gotten out of control.

THE COURT: But what specifically about Pentacel or flu caused that to happen?

THE WITNESS: Well, again, it -- it -- it is the -- it is whatever -- it -- it could be 

antigen. It could be the binding agent. The – I’m -- I – I’m not an expert on vaccines 

and -- and how they're made and all the things that go into them.

Tr. at 188-90. Dr Marks’ inability to persuasively articulate a theory of causation caused me to 

afford his opinion less weight.28

In support of his causation opinion, Dr. Marks highlighted the fact that H.H.’s neurologic 

status stabilized after his rapid decline. He stated that “[t]his stabilization ... which was 

hyperactive post-immunization is indicative of the cause being derived from the vaccinations.” Ex. 

67 at 4-5. After analyzing this issue earlier in the decision, I concluded that H.H.’s stabilization is 

consistent with a diagnosis of AGS. Indeed the medical literature makes this point clear. The fact 

that Dr. Marks based his opinion, in part, on an incorrect premise, has further reduced the value of 

this opinion in supporting Petitioners’ case.

Dr. Marks additionally pointed to H.H.’s normalization of neopterin levels in July of 2017 

as a reason to tip the scales in favor of vaccine causation. He stated, 

With 95% of patients having a known genetic marker, we are left with two 

essentially equal possibilities for H.H.’s condition. Either he is one of the very rare 

cases of AGS without a known genetic marker or an AGS-like interferonopathy 

triggered by external immune stimulating condition such as immunization. Given 

the waning immune response based on his most recent neopterin levels, I would 

favor the latter.

Ex. 94 at 1. At the time Dr. Marks drafted this opinion it was true that H.H.’s neopterin levels had 

normalized. However, by the time of the entitlement hearing, they were again elevated. Dr. Marks 

never reconciled his opinion expressed in exhibit 94, that the waning immune response tipped the 

scales in favor of vaccine causation where there were “essentially equal possibilities for H.H.’s 

condition”, with this new information available at trial.

I also note that neither Dr. Hollis nor Dr. Marks considered that onset of H.H.’s 

interferonopathy took place around the time of the flu and pneumonia vaccines and before H.H. 

received the Pentacel vaccine. While I do not fault either doctor on this point as my findings are 

28 I additionally note that Petitioners have since abandoned this molecular mimicry theory in place of the 

one proposed by Dr. Steinman.
72

articulated for the first time in this decision, I do find that it diminishes the persuasive value of 

their opinions. See Mosley v. Sec’y of Health & Hum. Servs., No. 08-724V, 2015 WL 2354316, at 

*18-19 (Fed. Cl. Spec. Mstr. Apr. 27, 2015) (affording the opinions of treating physicians less 

weight because they either did not consider how onset of TM one day after vaccination impacted 

their opinion or did not explain the basis for their opinion).

Ultimately, I have considered the opinions of Dr. Marks and Dr. Hollis, two of H.H.’s 

treating physicians, in arriving at my determination that there is not preponderant evidence that 

H.H.’s vaccinations did cause or significantly aggravate his condition. For the reasons articulated 

in this decision, I am not persuaded by these opinions, and instead have credited the opinions of 

Dr. Barañano and Dr. McGeady, who have opined that H.H. suffers from a genetic type I

interferonopathy the onset of which was unrelated to and unaffected by vaccination. See Locane,

685 F.3d 1375. Petitioners have failed to meet their burden under Loving prong five/Althen prong 

two.

G. Loving Prong Six/Althen Prong Three: Petitioners have not Established an 

Appropriate Temporal Relationship between H.H.’s Vaccinations and the 

Significant Aggravation of his Condition

The final Loving prong requires Petitionersto establish a “proximate temporal relationship” 

between the significant aggravation of A.S.’s condition and the vaccines he received. Loving at 

144; see also Althen, 418 F.3d at 1281. Petitioners must offer “preponderant proof that the onset 

of symptoms occurred within a timeframe which, given the medical understanding of the 

disorder’s etiology, it is medically acceptable to infer causation.” de Bazan v. Sec’y of Health & 

Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). 

The timing prong contains two parts. First, Petitioners must establish the “timeframe for 

which it is medically acceptable to infer causation” and second, they must demonstrate that the 

onset of the disease occurred in this period. Shapiro v. Secʼy of Health & Hum. Servs., 101 Fed. 

Cl. 532, 542-43 (2011), recons. denied after remand on other grounds, 105 Fed. Cl. 353 (2012), 

aff’d without op., 503 F. App’x 952 (Fed. Cir. 2013). I will address the question of onset first.

1. The Onset of H.H.’s Interferonopathy

Dr. Steinman opined that H.H.’s disease course began three weeks after his receipt of the 

Pentacel vaccine. He stated that “[n]ot until three weeks after the Pentacel immunization on 

October 23, 2013 was there any symptomatology related to an interferonopathy.” First Steinman 

Rep. at 16. This forms the premise for his opinion regarding the appropriateness of the onset 

interval. However, my determination in this case is contrary to Dr. Steinman’s; I found that H.H. 

began to develop heel cord tightness around the time he received his October 17, 2013 

vaccinations, and before he received the Pentacel vaccine, and further, that this heel cord tightness 

constituted a physical sign of his type I interferonopathy.

2. Medically-Acceptable Timeframe
73

With respect to the medically-acceptable onset interval, Dr. Steinman opined that “[t]he 

onset of neuroinflammation within 3 weeks of the October 23, 2013 immunizations with Pentacel 

is consistent with references 18 and 19, which cover related neuroinflammatory conditions of the 

peripheral (19) and central nervous systems (20). H.H. has a condition involving the central 

nervous system primarily.” First Steinman Rep. at 15. He then went on to state “A showing of a 

proximate temporal relationship between vaccination and injury” is met from similar studies on 

other neuroinflammatory conditions linking neuroinflammation and immunization, with onset at 

approximately 3 weeks post-Pentacel vaccine. See References 17–18.” Id. at 16. Although it 

appears that Dr. Steinman is relying on references 19 and 20 in support of his timing position (and 

not 17 and 18), I have examined references 17-20 in an abundance of caution.

Reference 17, Naves et al., discussed earlier in this decision, does not support the position 

that an interferonopathy would begin or become significantly aggravated either the same day or 

within one or two days after a trigger.

Reference 18 is an article by Rodero & Crow. This article does not discuss the onset 

timeframe of a type I interferonopathy.

Reference 19 is a paper by Schonberger that is oft-cited in the Vaccine Program. 

Schonberger et al., Guillain Barre Syndrome following vaccination in the National Influenza 

Immunization Program, United States, 1976-1977, 110 AMERICAN JOURNAL OF EPIDEMIOLOGY 2, 

105-23, (1979) (filed as Ex. 101, Tab 19) (hereinafter “Schonberger”). Schonberger demonstrates 

that the swine flu vaccine can cause Guillain Barré syndrome (GBS), a demyelinating disease of 

the peripheral nervous system. The increased risk for developing GBS after swine flu vaccination 

was concentrated within the five weeks after vaccination. Schonberger at 105.

Through his reference to this article, Dr. Steinman appears to opine that the findings from 

Schonberger regarding onset of GBS after swine flu vaccination are analogous to the onset of a 

type I interferonopathy after Pentacel vaccine. I do not find this position to be persuasive.

Chief Special Master Corcoran addressed Dr. Steinman’s reliance on Schonberger in a 

different case. See Rowan v. Sec’y of Health & Hum. Servs., No. 17-760V, 2020 WL 2954954, at

*16 (Fed. Cl. Spec. Mstr. Apr. 28, 2020). The Chief Special Master noted that Schonberger “loses 

persuasive heft when offered in disparate contexts, such as when invoked to prove a CNS injury 

(rather than peripheral nerve injury) was vaccine-caused.” See, e.g., L.Z. v. Sec’y of Health &

Hum. Servs., No. 14-920V, 2018 WL 5784525, at *18 n.18 (Fed. Cl. Spec. Mstr. Aug. 24,

2018) (“[p]etitioner’s evidentiary showing regarding the timing prong is similarly deficient based 

on the scientific literature submitted” because it relied on the Schonberger study on GBS, which 

was “distinguishable from MS”); see also Jones v. Sec’y of Health & Hum. Servs., No. 15-1239V,

2018 WL 7139212, at *16 (Fed. Cl. Spec. Mstr. Dec. 21, 2018) (“Schonberger’s timeframe [ ] is 

much less persuasive when used by way of analogy to a different condition that purportedly 

resulted from different vaccines”).

Not only is a type I interferonopathy a different condition than GBS, but the underlying 

theory of causation in GBS generally implicates molecular mimicry, a causation theory involving 

the adaptive immune system that has been eschewed by Dr. Steinman in this case. (“The theory 
74

here focuses on how the components of the vaccine can drive an interferon response. It is not a 

theory based on molecular mimicry...”) First Steinman Rep. at 9. Accordingly, the fact that swine 

flu vaccine can cause GBS via molecular mimicry in three weeks does not advance Petitioners’

position that the Pentacel vaccine significantly aggravated H.H.’s type I interferonopathy.

Finally, reference 20 is a paper by Bennetto and Scolding. See Bennetto & Scolding, 

Inflammatory/Post-Infectious Encephalomyelitis, 75 J NEUROL NEUROSURG PSYCHIATRY, i22-i28, 

doi: 10.1136/jnnp.2003.034256 (2004) (filed as Ex. 101, Tab 20) (hereinafter “Bennetto & 

Scolding”). In this article, the authors discuss acute disseminated encephalomyelitis (ADEM) and 

its link to various infections and immunizations. Bennetto & Scolding state that “[t]he timing of 

the first symptoms varies slightly with the precipitant: typically 1–14 days after non-neural 

vaccines, ... and 1–3 weeks (or more) after rabies inoculation.” Id. at 3. The authors further note 

that “[i]n the case of post-infectious ADEM, molecular mimicry between virus and myelin 

antigens may be responsible for initiating disease...” Bennetto & Scolding at 6. ADEM is a 

demyelinating disease of the central nervous system. It is an entirely different condition than a 

type I interferonopathy. Bennetto & Scolding briefly discuss the mechanism of molecular mimicry, 

which is not at play in this case. In short, this article does not advance Petitioners’ position in 

articulating a timeframe after vaccination for which it is medically acceptable to infer that H.H.’s 

vaccines caused the significant aggravation of his inherited type I interferonopathy.

In sum, I do not find that H.H.’s type I interferonopathy either began or was significantly 

aggravated three weeks after the Pentacel vaccine, or that Petitioners have preponderantly 

established that three weeks post vaccination is a medically acceptable onset interval. For these 

reasons, Petitioners have not met their burden to provide preponderant evidence with respect to 

Loving prong six/Althen prong three.

VII. CONCLUSION

Petitioners have experienced great suffering as a result of H.H.’s condition. However, in 

order to find they are entitled to compensation they must preponderantly demonstrate that the 

vaccines caused or significantly aggravated H.H.’s condition. Based on the evidence presented in 

this case, I conclude that Petitioners have not made such a showing. Their petition is therefore 

DISMISSED. The clerk shall enter judgment accordingly.29

IT IS SO ORDERED. 

s/ Katherine E. Oler

Katherine E. Oler

Special Master

29 Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment by each filing (either jointly 

or separately) a notice renouncing their right to seek review.