Mattus-Lang v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: August 31, 2022

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

SHANELLE MATTUS-LANG, *

as parent and legal representative *

of her minor son, D.J.W., * No. 15-113V

* Special Master Sanders

Petitioner, *

v. * Entitlement Decision; DTaP-IPV

* Vaccine; Seizure Disorder; Cognitive

SECRETARY OF HEALTH * Delay; Developmental Delay; Epileptic

AND HUMAN SERVICES, * Encephalopathy; Autism Spectrum

* Disorder (“ASD”); Doose Syndrome

Respondent. * (“MAE”)

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

Elizabeth Martin Muldowney, Sands Anderson, P.C., Richmond, VA, for Petitioner.

Camille M. Collett, United States Department of Justice, Washington, DC, for Respondent.

DECISION ON ENTITLEMENT 1

On February 4, 2015, Shanelle Mattus-Lang (“Petitioner”) filed a petition pursuant to the

National Vaccine Injury Compensation Program (“the Program”), 2 alleging that a diphtheria

tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine (“DTaP-IPV”)

administered on February 6, 2012, caused her minor child, D.J.W., to suffer from “a seizure

disorder with cognitive and developmental delays.” Pet. at 6, ECF No. 1. Respondent filed his

Rule 4(c) report on July 22, 2015, and argued that Petitioner was not entitled to compensation

without “an expert report” or “other reliable medical evidence supporting causation sufficient to

meet her burden of proof.” Resp’t’s Report at 10, ECF No. 18. The case proceeded to an

entitlement hearing that was held on October 4–5, 2018. Min. Entry, docketed Oct. 9, 2018. At the

1

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

the E-Government Act of 2002, 44 U.S.C. § 3501 note (2012) (Federal Management and Promotion of

Electronic Government Services). In accordance with Vaccine Rule 18(b), a party has 14 days to identify

and move to delete medical or other information that satisfies the criteria in § 300aa-12(d)(4)(B). Further,

consistent with the rule requirement, a motion for redaction must include a proposed redacted Decision. If,

upon review, I agree that the identified material fits within the requirements of that provision, such material

will be deleted from public access.

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).

1

time of the hearing, both Petitioner and Respondent agreed that the relevant claimed injury was

epileptic encephalopathy. 3 They also agreed that D.J.W. suffered from Doose syndrome. 4

During the course of the hearing, it was revealed that an Autism Spectrum Disorder 5

(“ASD”) evaluation was pending. The hearing continued based upon the epileptic

encephalopathy/Doose syndrome diagnosis, but the parties agreed that any subsequent autism

diagnosis may necessitate additional argument and/or evidence before an entitlement decision

could be rendered. In May of 2019, D.J.W. was diagnosed with autism. Pet’r’s Ex. 87 at 8, ECF

No. 97. On February 7, 2020, Petitioner filed a “[b]rief in support of her contention that she be

permitted to proceed in the [Program] on the claimed injury of epileptic encephalopathy despite

[D.J.W.’s] subsequent autism diagnosis.” Pet’r’s Mem. at 1, ECF No. 103. On April 20, 2020,

Respondent filed his response to Petitioner’s brief, including a motion for a decision dismissing

Petitioner’s claim. Resp’t’s Resp. at 1, ECF No. 110. Petitioner submitted a reply to Respondent’s

response on August 28, 2020. Pet’r’s Reply, ECF No. 112. On October 22, 2021, I issued an Order

explaining that, after a careful review of the evidence presented, I must afford Petitioner an

additional opportunity to provide expert argument and evidence “specifically and only as it relates

to D.J.W.’s ASD diagnosis.” ECF No. 113. The parties then filed an additional round of expert

reports and supporting medical literature. See Pet’r’s Exs. 88–136, ECF Nos. 114–15, 130, 133–

35; Resp’t’s Exs. D, D1–D29, E, E1–E15, ECF Nos. 119–22, 124–25.

There are two predicate issues in this case: (1) can the autism diagnosis be separated from

the epileptic encephalopathy diagnosis with respect to symptom onset and clinical presentation;

and (2) is there preponderant evidence that the seizures (and cognitive delay) suffered by D.J.W.

have an autoimmune etiology and therefore could be vaccine-caused? The success of Petitioner’s

claim hinges on an affirmative answer to both questions.

3

Epileptic encephalopathy “refers to a group of disorders in which the unremitting epileptic activity

contributes to progressive cerebral dysfunction.” Puneet Jain, et al., Diagnosis and Management of

Epileptic Encephalopathies in Children, EPILEPSY RES. TREAT. (July 22, 2013),

http://dx.doi.org/10.1155/2013/501981. The group of disorders includes Doose Syndrome/myoclonic

encephalopathy. See id. Epileptic is defined as “pertaining to or affected by epilepsy[.]” Dorland’s

Illustrated Medical Dictionary 1263, 633 (32nd ed. 2012) [hereinafter “Dorland’s”]. Epilepsy is “any of a

group of syndromes characterized by paroxysmal transient disturbances of the brain function that may be

manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or

sensory disturbances, or perturbation of the autonomic nervous system.” Dorland’s at 633. Encephalopathy

is “atrophy of the brain.” Id. at 612.

4

Doose syndrome is also known as myoclonic astatic epilepsy (“MAE”). MAE or Doose syndrome “is an

epilepsy syndrome of early childhood, most commonly appearing between ages [one] and [five] and

featuring generalized seizures. Children will experience drop attacks and staring seizures, sometimes

associated with falls. MAE is idiopathic[.]” Epilepsy Syndromes in Children, JOHNS HOPKINS MED.,

https://www.hopkinsmedicine.org/health/conditions-and-diseases/epilepsy/epilepsy-syndromes-in-

children (last visited Aug. 1, 2022). I use “Doose syndrome” and “MAE” interchangeably throughout this

Decision.

5

Autism Spectrum Disorder (“ASD”) as defined by the Diagnostic and Statistical Manual of Mental

Disorders – 5th Edition includes “qualitative difficulties with social communication and interaction and

restricted/repetitive behavior.” American Psychiatric Association. (2013). Diagnostic and Statistical

Manual of Mental Disorders: Fifth Edition (DSM-5). Arlington, VA.

2

After reviewing the entire record and considering both parties’ arguments, I find that

D.J.W.’s autism diagnosis cannot be separated from any encephalopathy diagnosis. All of the

evidence that Petitioner presented prior to the revelation of D.J.W.’s autism diagnosis was in

support of her argument that his developmental delays are the result of his vaccines. This was the

case even though Petitioner expressed a concern about autism around the same time as the alleged

vaccine-caused injuries. She continued to link all of D.J.W.’s symptoms together and argue

everything was vaccine-caused, even as his ASD evaluation was pending. Now that D.J.W. has

been diagnosed with autism, Petitioner continues to allege developmental delay as a vaccine-

caused injury. Petitioner cites other cases wherein a child experiencing seizures was also diagnosed

with autism, but for reasons explained below, those cases are not analogous to her claim. Those

cases are factually distinct with respect to the onset of symptoms and the alleged vaccine-caused

injuries. Furthermore, additional evidence cannot negate the fact that Petitioner’s own expert has

already provided the most definitive and unequivocal evidence against any argument for

comorbidity in this case.

I further find that notwithstanding the comorbidity issue, there is insufficient evidence that

D.J.W.’s seizures have an autoimmune etiology. D.J.W.’s relevant medical records have already

been filed, and the medical literature submitted provides sufficient context for the experts’

conclusions regarding the etiology and pathophysiology of D.J.W.’s condition. Petitioner asserted

that D.J.W. suffers from an autoimmune epileptic encephalopathy. It follows that without an

autoimmune response post vaccination, Petitioner’s proposed biological mechanism is

inapplicable. Petitioner’s expert did not present preponderant evidence of an autoimmune

encephalopathy in this case. Furthermore, Respondent’s expert Dr. Holmes’ assertion that Doose

syndrome is widely considered to have a genetic cause, is supported by writings authored by the

condition’s namesake. The testimony provided by Dr. Holmes was persuasive. Also, the parties’

arguments were crystalized in post-hearing briefings. Petitioner has failed to articulate a need for

further evidence or argument regarding D.J.W.’s condition in the form of expert testimony or

otherwise. Petitioner’s claim that D.J.W.’s injuries were vaccine-caused is therefore ripe for

consideration. In finding that the record is sufficiently developed, I further find that Respondent’s

motion to dismiss is moot. Rather than setting out the favorable inferences to Petitioner to

determine if the claim is viable pursuant to the motion to dismiss standard, I will instead apply the

preponderant standard under Althen, as articulated in Respondent’s motion to dismiss, to conclude

that Petitioner cannot prevail on the fully established record. Accordingly, Petitioner’s claim is

hereby DISMISSED.

I. Procedural History

Petitioner filed her petition for compensation on behalf of her minor child, D.J.W., on

February 4, 2015. Pet. at 1. On February 9, 2015, Petitioner submitted a notice of intent to file

exhibits on a compact disc. See Notice, ECF No. 5. Those exhibits included two affidavits, one

from Petitioner and the other from Petitioner’s mother, and several medical records. Pet’r’s Exs.

1–13. Petitioner filed additional medical records on April 17, 2015. Pet’r’s Exs. 12–15, ECF No.

9. On May 20, 2015, Petitioner submitted additional medical records and a statement of

completion. Pet’r’s Exs. 16–20, ECF Nos. 14–15.

3

Respondent filed his Rule 4(c) report on July 22, 2015, recommending that compensation

be denied. Resp’t’s Report at 10. Petitioner filed additional medical records on September 9, 2015.

Pet’r’s Exs. 21–22, ECF No. 21. On December 29, 2015, Petitioner submitted a second notice of

intent to file exhibits on a compact disc. See Notice, ECF No. 28; Pet’r’s Exs. 23–57. Those

exhibits included Petitioner’s expert report and curriculum vitae of Yuval Shafrir, M.D., along

with supporting medical literature. Pet’r’s Exs. 23–57. On June 1, 2016, Respondent filed his

responsive expert report from Gregory Holmes, M.D. Resp’t’s Ex. A, ECF No. 32.6

On October 20, 2016, Petitioner submitted an additional notice of intent to file exhibits on

a compact disc. See Notice, ECF No. 34. These exhibits included Petitioner’s supplemental expert

report from Dr. Shafrir and supporting medical literature. Pet’r’s Exs. 58–69. Respondent filed his

rebuttal expert report from Dr. Holmes on January 30, 2017. Resp’t’s Ex. C, ECF No. 36. This

case was reassigned to me on June 20, 2017. ECF Nos. 40–41.

On August 17, 2017, I scheduled this matter for an entitlement hearing to take place from

October 4–5, 2018. Order, ECF No. 45. Petitioner filed her pre-hearing brief on June 27, 2018.

Pet’r’s Br., ECF No. 48. Respondent submitted his pre-hearing response brief on July 27, 2018.

Resp’t’s Resp., ECF No. 49. The entitlement hearing was held as scheduled on October 4–5, 2018.

See Min. Entry, docketed Oct. 9, 2018.

Following the entitlement hearing, Petitioner submitted additional medical records

throughout 2019, including those pertaining to D.J.W.’s autism diagnosis. See, e.g., Pet’r’s Ex. 87,

ECF No. 97; Pet’r’s Exs. 78–82, 86, ECF Nos. 79, 84, 95. Petitioner filed her post-hearing

memorandum on February 7, 2020. Pet’r’s Mem. at 1. On April 24, 2020, Respondent filed his

response to Petitioner’s memorandum, including a motion for a decision dismissing Petitioner’s

claim. Resp’t’s Resp. at 1. Petitioner submitted a reply to Respondent’s response and motion on

August 28, 2020. Pet’r’s Reply.

On October 22, 2021, prior to ruling on Respondent’s motion to dismiss, I afforded

Petitioner a final opportunity to provide additional evidence regarding D.J.W.’s autism diagnosis.

ECF No. 113 at 1. Petitioner filed an expert report from Dr. Shafrir and supporting medical

literature on this limited issue on December 1, 2021. Pet’r’s Exs. 88–107, ECF Nos. 114–15.

Respondent filed a responsive expert report from Dr. Holmes and medical literature on March 1,

2022. Resp’t’s Exs. D, D1–D29, ECF Nos. 119–21. The same day, Respondent also filed an expert

report from Max Wiznitzer, M.D. Resp’t’s Ex. E, ECF No. 122.

On March 7, 2022, Petitioner filed a motion to strike the expert report of Dr. Wiznitzer.

ECF No. 123. Petitioner argued that Dr. Wiznitzer was not previously disclosed as an expert in

this case, and he did not testify at the hearing on entitlement held in October of 2018. Id. at 2–3.

Petitioner further argued that Dr. Wiznitzer’s report “is redundant and duplicative of Dr. Holmes’

opinions[.]” Id. at 3. She continued that Dr. Wiznitzer’s report “adds nothing more to the resolution

of [] this case other than to produce expert opinions without the opportunity for [P]etitioner to

rebut [] or cross examine the expert about these opinions.” Id. Petitioner argued this report would

6

Also on June 1, 2016, Respondent filed the curriculum vitae of Dr. Holmes. Resp’t’s Ex. B, ECF No. 31-

2. This exhibit was stricken from the record and does not appear to have been re-filed. See Non-PDF Order,

docketed June 1, 2016.

4

therefore be prejudicial to her case. Id. Respondent filed a response to Petitioner’s motion on

March 15, 2022. ECF No. 126. Respondent argued that “Petitioner has not cited, and [R]espondent

is not aware, of any authority that allows [P]etitioner to pick and choose the testimony

[R]espondent can offer or what evidence a special master will be allowed to consider[.]” Id. at 4.

Respondent further argued that Dr. Wiznitzer’s opinions are “well-within his expertise, his report

was timely filed, and it responds to the issues that were presented very late in the development of

this case[,]” namely D.J.W.’s autism diagnosis. Id. He further indicated that “[s]pecifically, Dr.

Wiznitzer responds to opinions introduced for the first time in Dr. Shafrir’s most recent

supplemental report.” Id. Respondent argued it would be prejudicial for Respondent to be

“prevented from providing a fulsome response . . . .” Id. The same day, Respondent filed the

medical literature referenced in Dr. Wiznitzer’s report. Resp’t’s Exs. E1–E15, ECF Nos. 124–25.

Petitioner filed a reply on March 22, 2022. ECF No. 127. Petitioner reiterated her arguments in

her original motion. See id.

I denied Petitioner’s motion to strike Dr. Wiznitzer’s expert report on March 29, 2022.

ECF No. 128. I indicated that “[i]n accordance with the applicable legal principles, I am required

to broadly allow the submission of evidence and will therefore afford Respondent an opportunity

to defend this case.” Id. at 1; see also 42 U.S.C. § 300aa-12(d)(2); Vaccine Rule 8(c). I also noted

that “when evaluating this case, I will assess Dr. Wiznitzer’s report in terms of its probative and

foundational value and assign appropriate weight.” ECF No. 128 at 1–2. On April 4, 2022,

Petitioner filed an unopposed motion to file a supplemental expert report in response to Drs.

Holmes’ and Wiznitzer’s reports, which I granted. ECF No. 129; Non-PDF Order, docketed Apr.

13, 2022.

Petitioner filed medical records on April 18, 2022. Pet’r’s Exs. 108–10, ECF No. 130.

Petitioner filed her supplemental expert report from Dr. Shafrir and supporting medical literature

on June 23, 2022. Pet’r’s Exs. 111–36, ECF Nos. 133–35.

II. Medical History

Petitioner’s son D.J.W. was born on February 27, 2007. Pet. at 1. Petitioner indicated that

her son “was developing normally” and had “received previous vaccinations without apparent

sequelae.” Id.; see also Pet’r’s Ex. 3 at 6–91. During the first eighteen months of his life, D.J.W.

had an unremarkable medical history but suffered from various childhood illnesses. See Pet’r’s

Ex. 3 at 6–91. D.J.W.’s medical records noted that he was healthy at his four, six, nine, twelve,

fifteen, and eighteen-month well-visits. Id. at 7–8, 17, 36, 59, 76, 99.

On October 24, 2007, D.J.W. presented to his pediatrician Juan Garona, M.D., with a

cough, ear pain, and rhinorrhea. 7 Id. at 25. He was diagnosed with an upper respiratory infection

(“URI”). Id. On December 11, 2007, D.J.W. returned to Dr. Garona with a two to three-day history

of right ear pain. Id. at 44. Dr. Garona diagnosed him with otitis media 8 and prescribed

7

Rhinorrhea is “the free discharge of a thin nasal mucus.” Dorland’s at 1640.

8

Otitis media is “inflammation of the middle ear; subtypes are distinguished by length of time from onset

(acute versus chronic) and by type of discharge (serous versus suppurative).” Dorland’s at 1351 (emphasis

in original).

5

Amoxicillin. 9 Id. D.J.W suffered from three additional URIs on June 12, 2008, February 24, 2009,

and May 13, 2009. Id. at 81–83, 117, 136–37.

On March 11, 2009, D.J.W. presented to his pediatrician for his two-year-old well-visit.

Id. at 125–29. During this visit, Dr. Garona noted that D.J.W. “r[an], thr[ew] a ball, kick[ed] a ball,

climb[ed] ladders, jump[ed], spoon fe[d him]self, shape[d] puzzles, ma[d]e [two to three-]word

sentences, follow[ed] most directions well, identifie[d] simple objects in a book, kn[ew] body

parts, [and was] appropriately sociable.” Id. at 127.

D.J.W. underwent blood work on February 9, 2010. Id. at 146. The lab results showed low

white blood cell count, hemoglobin, 10 and hematocrit. 11 Id. Nonetheless, Dr. Garona wrote that

D.J.W. continued to have normal growth and development at his three-year well-visit two months

later, on April 9, 2010. Id. at 149. He indicated that D.J.W. was taking iron supplements for his

mild anemia and had a history of mild Reactive Attachment Disorder (“RAD”). 12 Id. at 149–50.

Likewise, Dr. Garona wrote that D.J.W. was a “healthy [four] year old [] male growing

and developing normally[]” at his four-year-old well-visit on April 22, 2011. Id. at 156. Dr. Garona

noted D.J.W.’s “[history] of borderline anemia.” Id. at 160. Dr. Garona indicated that D.J.W. knew

his letters, that he engaged in make-believe play, that strangers could understand his speech, and

that his fine motor skills were normal for a child of his age. Id. at 157–59. During this visit, D.J.W.

received his measles, mumps, rubella (“MMR”) and varicella vaccinations. Id. at 160. Dr. Garona

noted that D.J.W. had “[n]o history of significant adverse reaction [to vaccinations].” Id.

D.J.W. presented to a new pediatrician, George Johnson, M.D., on February 6, 2012.

Pet’r’s Ex. 6 at 1. During this visit, D.J.W. received the DTaP-IPV vaccine in advance of him

starting school. Id.

On February 13, 2012, seven days post vaccination, D.J.W. presented to the emergency

room (“ER”) for a generalized seizure that occurred after he “[w]as playing on [a six-foot-tall

bunk] bed, then fell.” Pet’r’s Ex. 7 at 3, 7. The ER attending noted it was “unclear if [the] seizure

preceded [the] fall or [the] fall was followed by [the] seizure. From [his] parents’ history[, it was]

more likely [a] fall with head trauma and [then a] subsequent seizure.” Id. at 7. Petitioner reported

that D.J.W. experienced “[t]otal body shaking[]” with unresponsiveness, which “lasted

9

Amoxicillin is “a semisynthetic derivative of ampicillin effective against a broad spectrum of gram-

positive and gram-negative bacteria; used especially in the treatment of infections due to susceptible strains

of Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Neisseria gonorrhoeae, streptococci

(including Streptococcus faecalis and S. pneumoniae), and non-penicillinase-producing staphylococci.”

Dorland’s at 65.

10

Hemoglobin is “the red oxygen-carrying pigment of erythrocytes, formed by developing erythrocytes in

bone marrow. It is a type of hemoprotein that contains four heme groups and globin and has the property

of reversible oxygenation[.]” Dorland’s at 839.

11

Hematocrit is “the proportion of the volume of a blood sample that is red blood cells[.]” Dorland’s at

832.

12

Reactive Attachment Disorder (“RAD”) is “a mental disorder of infancy or early childhood, characterized

by notably unusual and developmentally inappropriate social relatedness, usually associated with grossly

pathologic care. It may be the inhibited type, with failure to initiate or respond to social interactions, or the

disinhibited type, with indiscriminate sociability or attachment.” Dorland’s at 552 (emphasis in original).

6

approximately [two] minutes.” Id. at 3, 6. Petitioner also indicated that D.J.W. “woke up and was

sluggish for a bit . . . [but had n]o vomiting or slurred speech.” Id. at 6. D.J.W.’s neurological

examination was normal. Id. A CT-scan was performed in the ER, which was unremarkable. Id. at

8. The ER attending noted that D.J.W.’s “[s]ugar was fine and [he wa]s afebrile.” Id. D.J.W. was

assessed with head trauma with a concussion and a seizure and was instructed to follow up with

neurology. Id.

On March 11, 2012, D.J.W. returned to the ER for concerns of another seizure. Id. at 33.

Petitioner reported D.J.W. experienced a loss of consciousness and that his “eyes flutter[ed]

backwards in the head, [he] f[e]ll backwards onto his buttocks, [but he had] no head trauma.” Id.

During this encounter, Petitioner reported that D.J.W. had suffered another seizure three days

prior, on March 8, 2012, and “was found on the bathroom floor unconscious but then rapidly

aroused.” Id. Petitioner reported that D.J.W. did not have a headache, fever, or chills. Id. The

attending pediatric neurologist recommended an outpatient workup, including an EEG 13 and MRI,

and did not prescribe medications. Id. at 34.

D.J.W. presented to another pediatrician, Laura Webb, M.D., on March 16, 2012. Pet’r’s

Ex. 8 at 4. Petitioner reported that D.J.W. had four seizures in the past month and was now “having

seizures every [three] days.” Id. at 4, 9. She also indicated that D.J.W. had been wetting the bed,

which was “not normal for him.” Id. Dr. Webb consulted with neurologist Dr. Sankar during this

appointment, who recommended starting D.J.W. on 10 mg/day of Keppra, an anti-seizure

medication. Id. at 8.

On March 19, 2012, D.J.W. presented to the ER after a one to two-minute generalized

tonic-clonic seizure (“GTC”), 14 which his father and brother witnessed. Pet’r’s Ex. 7 at 57. D.J.W.

had been on Keppra for three days. Id. The attending ER physician noted that D.J.W. was not

experiencing any “fever, chills, rash, cough, vomiting, diarrhea, or other complaints.” Id. His

neurological examination and CT scan were normal. Id. at 58. The attending pediatric neurologist

Ann Lewis, M.D., recommended increasing D.J.W.’s Keppra dose and instructed Petitioner to

schedule a follow-up with her for D.J.W.’s continued treatment. Id. at 59.

Petitioner sent an email to D.J.W.’s pediatrician Dr. Webb on March 22, 2012. Pet’r’s Ex.

8 at 15. Petitioner reported that D.J.W. was having seizures every three to four days. Id. She

expressed concerns about possible brain damage. Id. The same day, D.J.W. underwent an MRI of

his brain, which was normal. Pet’r’s Ex. 7 at 80–81.

On March 30, 2012, D.J.W. presented to Dr. Lewis for a pediatric neurology evaluation.

Pet’r’s Ex. 8 at 28. During this visit, Petitioner reported that D.J.W. “began having seizures in

February[, and she] wonder[ed] if it is related to his immunizations he received one week before

[the seizures began].” Id. at 29. Dr. Lewis wrote that D.J.W. “likely has an idiopathic localization

related epilepsy.” Id. at 30. Dr. Lewis increased D.J.W.’s Keppra dose to 6 ml two times per day,

13

D.J.W. underwent an EEG on March 21, 2012, which was normal. Pet’r’s Ex. 8 at 14.

14

A generalized tonic-clonic seizure (“GTC”) is “the seizure of grand mal epilepsy, consisting of a loss of

consciousness and generalized tonic convulsions followed by clonic convulsions.” Dorland’s at 1688.

Grand mal epilepsy is “a symptomatic form of epilepsy often preceded by an aura; characterized by loss of

consciousness with generalized tonic-clonic seizures[.]” Id. at 633.

7

added vitamin B6 to combat behavioral issues associated with D.J.W. taking anti-seizure

medication, and discussed switching him to Trileptal 15 if the Keppra was ineffective. Id.

Petitioner contacted Dr. Lewis via email on April 7, 2012, reporting that D.J.W.

experienced “another strong seizure.” Id. at 40. Dr. Lewis expressed that she did not think the

Keppra was working well enough for D.J.W. and switched his medication to Trileptal. Id. at 39.

Petitioner emailed Dr. Lewis again four days later, on April 11, 2012, reporting concerns with

D.J.W.’s cognition. Id. at 50. Petitioner wrote her concerns about his “mental health[, as h]e seems

to be much slower[]” and cannot remember his colors in Spanish. Id. On April 16, 2012, Dr. Lewis

noted that she did not “expect the seizures to be damaging [D.J.W.’s] brain[.]” Id. at 63. Petitioner

communicated with Dr. Lewis via email again on April 23–24, 2012, noting concerns of D.J.W.’s

“passing out” and staring spells. Id. at 69. Dr. Lewis instructed D.J.W. to stop using Trileptal and

she prescribed valproic acid. 16 Id. at 82.

D.J.W. presented to Dr. Webb for his five-year-old well-visit on April 28, 2012. Id. at 88.

Petitioner repeated concerns of D.J.W.’s cognitive decline and noted he was “forgetting things that

he used to know.” Id. Petitioner reported that D.J.W. ‘“passes out’ or seems like he is staring off

into space . . . [but] Dr. Lewis believes some of this may be [a] side effect of the medications vs.

new types of seizures.” Id.

On May 2, 2012, D.J.W. underwent a repeat EEG, which was abnormal. Id. at 103. The

testing revealed that D.J.W. had experienced a generalized epileptic disturbance with frontal

predominance. Id. Dr. Lewis was unable to distinguish whether this was “a truly generalized

disturbance or a frontal disturbance with rapid bilateral spread.” Id. at 141. Later that month, on

May 29, 2012, Petitioner emailed Dr. Lewis and noted a “serious decrease in [D.J.W.’s]

intelligence.” Id. at 132.

D.J.W. presented to Dr. Lewis for a follow-up on June 6, 2012. Id. at 140. Dr. Lewis noted

D.J.W.’s medication history to treat his seizures and wrote that despite the increased doses, she

was “not able to eliminate his seizures.” Id. Petitioner reported continued concerns with D.J.W.’s

cognitive issues, noting that D.J.W. was “talking slower, [wa]s less articulate[,] and seem[ed] to

have forgotten things that he knew before (more trouble counting and with letters).” Id. Dr. Lewis

again noted that she was not certain whether D.J.W.’s cognitive decline was “secondary to

medication side effects or symptomatic of an epileptic encephalopathy.” Id. at 141. She wrote that

“[t]here are still several possibilities for [D.J.W.’s] subtype of epilepsy including Lennox-Gastaut

[syndrome] 17 and Doose syndrome.” Id. Dr. Lewis discussed possible testing to look for an

15

Trileptal is the “trademark for preparation of oxcarbazepine.” Dorland’s at 1967. Oxcarbazepine is “an

anticonvulsant used in the treatment of partial seizures[.]” Id. at 1355.

16

Valproic acid is “a simple eight-carbon branched-chain fatty acid used as an anticonvulsant in the

treatment of epileptic seizures, particularly absence seizures[.]” Dorland’s at 2020.

17

Lennox-Gastaut syndrome is “an atypical form of absence epilepsy characterized by diffuse slow spike

waves, often with atonic, tonic, or clonic seizures and intellectual disability; there may also be other

neurologic abnormalities or multiple seizure types. Unlike typical absence epilepsy, it may persist into

adulthood.” Dorland’s at 1837.

8

immune-related etiology and proposed additional treatments, such as IVIG and the ketogenic

diet. 18 Id.

On July 11, 2012, after Petitioner reported the continued worsening of D.J.W.’s condition,

Dr. Lewis wrote that she “suspect[ed D.J.W. suffered from] epileptic encephalopathy.” Id. at 155.

The next day, on July 12, 2012, Dr. Lewis had D.J.W. admitted for a repeat EEG and bloodwork

to include antibody testing and a genetic epilepsy panel. Id. at 170. Dr. Lewis also started D.J.W.

on IVIG. Id. D.J.W.’s admission notes indicated that Petitioner “associate[d] the onset of

[D.J.W.’s] seizures to [his] vaccinations given one week prior.” Pet’r’s Ex. 7 at 95. D.J.W.’s repeat

EEG was unchanged from his previous EEG performed on May 2, 2012, which also showed

“diffuse delta slowing of the background, and a spike/wave burst during sleep.” Id. at 99. The

attending physician noted that “[t]his does not show progression (as can be seen with epileptic

encephalopathies such as Lennox Gastaut).” Id. at 101. D.J.W.’s repeat MRI was unremarkable.

Id. His genetic epilepsy panel also did not reveal any disease-causing mutations. Pet’r’s Ex. 9 at

13. D.J.W. responded well to IVIG and was discharged on July 14, 2012, in a stable condition with

medications including Keppra, Lamictal,19 and valproic acid. Pet’r’s Ex. 7 at 137. Dr. Lewis added

Clobazam 20 to D.J.W.’s prescribed medications on August 16, 2012. Pet’r’s Ex. 8 at 182–83.

On January 4, 2013, Petitioner contacted Dr. Webb via email and explained that D.J.W.

was “not getting any better[]” and was having seventy-five drop seizures a day. Id. at 275. She

also reported that D.J.W. experienced “a big seizure once every two weeks . . . last[ing] over [six]

minutes.” Id.

D.J.W. presented to another pediatric neurologist, Sharon McDaniel, M.D., on January 29,

2013, following the worsening of D.J.W.’s condition. Pet’r’s Ex. 18 at 1. Dr. McDaniel noted that

it was “difficult to classify [D.J.W.’s] epilepsy syndrome . . . [as h]e has some features compatible

with myoclonic-astatic epilepsy (Doose syndrome), although he has some atypical features []

including focal/multifocal epileptiform activity in addition to generalized discharges[.]” Id. at 8.

Dr. McDaniel adjusted D.J.W.’s medications and advised him to start the ketogenic diet. Id.

Petitioner spoke with Dr. Lewis regarding D.J.W.’s condition on November 1, 2013.

Pet’r’s Ex. 8 at 377. Petitioner reported that D.J.W. “has had a gradual increase in the frequency

of his big seizures[,]” in that they occurred every couple of weeks, increased to every week, and

then to every two to three days. Id. Dr. Lewis noted that Petitioner had not been checking D.J.W.’s

urine ketones to monitor his consistency with the ketogenic diet, so Dr. Lewis “c[ould not] use that

as a measure of change in [D.J.W.’s] compliance.” Id. Petitioner acknowledged that D.J.W. may

have cheated on this diet around Halloween. Id. Dr. Lewis wrote that if that was the case, D.J.W.

may take one to two weeks to return to baseline. Id.

18

The ketogenic diet is “a diet that contains a large amount of fat with minimal amounts of protein and

carbohydrate, in order to produce ketosis[.]” Dorland’s at 516.

19

Lamictal is the “trademark for a preparation of lamotrigine.” Dorland’s at 1000. Lamotrigine is “an

anticonvulsant used in the treatment of partial seizures in adult patients formerly treated with an enzyme-

inducing anticonvulsant (e.g., carbamazepine) and as an adjunct in the treatment of partial seizures in adults

with epilepsy and of generalized seizures associated with Lennox-Gastaut syndrome[.]” Id. at 1003.

20

Clobazam is “a benzodiazepine with anticonvulsant actions; administered orally as an adjunct in the

treatment of epilepsy.” Dorland’s at 373.

9

The next day, on November 2, 2013, D.J.W. returned to Dr. Webb with complaints of “an

increase in seizure activity resulting in multiple falls and hits to his head.” Id. at 385. D.J.W.’s

grandmother attended this appointment with him and noted that D.J.W. had been in a constant state

of staring for the past two days. Id. She also reported that D.J.W. could not walk or use the

bathroom by himself. Id. Dr. Webb advised D.J.W. to go to the ER to be monitored. Id. at 386.

During his hospitalization, D.J.W.’s mental status and neurological examination were normal.

Pet’r’s Ex. 7 at 208. D.J.W. was discharged home on November 4, 2013, and Clonazepam 21 was

added to his prescribed medications. Id. at 210.

D.J.W. underwent a repeat EEG on April 8, 2014. Pet’r’s Ex. 8 at 413. The results of the

EEG remained unchanged and showed generalized spike and wave complexes during D.J.W.’s

sleep. Id.

On June 25, 2014, D.J.W. returned to Dr. Lewis for a follow-up. Id. at 447. Dr. Lewis wrote

that “[o]verall, [D.J.W.] has done well with the ketogenic diet[,]” although “[h]e has had ups and

downs[.]” Id. at 448. She also noted that D.J.W.’s “seizures are much worse for about a week[]”

when he “cheats” on the ketogenic diet. Id. Dr. Lewis wrote that D.J.W. was experiencing a grand

mal seizure “every week (in [his] sleep), drop seizures [zero to two times a day] on a good day and

[ten to fifteen times a day] on a ‘bad day[,]’ and no absence/staring spells.” Id. She indicated that

D.J.W.’s “cognitive function ha[d] improved with his current level of seizure control (and [being]

off of valproic acid and benzos).” Id. at 450. Dr. Lewis noted D.J.W.’s difficulties with learning.

Id. at 448. She concluded that “Doose syndrome seems to be the most appropriate diagnosis[]” for

D.J.W.’s condition. Id. at 450. Dr. Lewis advised Petitioner to continue D.J.W.’s current

medications and ketogenic diet. Id.

D.J.W. attended follow ups with pediatrician Dr. Garona throughout 2018. See Pet’r’s Ex.

108 at 8–11, ECF No. 130. He also presented for neurology follow ups with various treaters for

his epileptic encephalopathy. Id. at 11–16. No cause of D.J.W.’s condition was identified absent

Petitioner’s self-reported concern that his injuries were vaccine-caused. See id. at 15, 20. A repeat

EEG performed on September 24–25, 2018, showed abnormal results. Id. at 7. The impression

included a “[d]iffusely slow background. Delta-range slowing is particularly prominent in the

frontal regions bilaterally hi [sic] again . . . multifocal epileptiform discharges . . . generalized

spike and slow-wave complexes . . . [and] bilateral, frontally predominant ‘paroxysmal fast

activity[.]’” Id. This study “suggest[ed] a severe underlying epileptogenic disturbance and is

consistent with [D.J.W.’s] diagnosis of epileptic encephalopathy.” Id.

On January 10, 2019, after years of continuous treatment for his Doose syndrome, D.J.W.

was seen by Aaron Nayfack, M.D., a developmental behavioral pediatrician, on referral from his

pediatrician. Pet’r’s Ex. 82 at 11, ECF No. 84. Dr. Nayfack recommended an Autism Spectrum

Disorder evaluation “following seizure activity at 5 years [old] and related regression in

functioning.” Pet’r’s Ex. 86 at 5, ECF No. 95. Dr. Nayfack noted that he “underst[oo]d the concern

for autism but [he was] not sure if it is the cause of [the] observed delays.” Pet’r’s Ex. 82 at 34.

He continued that D.J.W.’s “long seizure history is the main driver but [agreed] there is definitely

21

Clonazepam is “a benzodiazepine used as an anticonvulsant in the treatment of Lennox-Gastaut syndrome

and of atonic and myoclonic seizures and as an anti[-]panic agent in the treatment of panic disorders[.]”

Dorland’s at 373.

10

at least one secondary diagnoses [sic] to be considered. The main possibilities in [his] mind [we]re

autism, intellectual disability or both.” Id.

D.J.W. presented to clinical psychologist Carrie Silver, Ph.D., on May 22, 2019. Pet’r’s

Ex. 86 at 1. She noted under chief concerns: “[a] review of well[-]child checks from ages 2, 3[,]

and 4 reveal no developmental concerns.” Pet’r’s Ex. 87 at 1, ECF No. 97. Dr. Silver considered

all of D.J.W.’s symptoms in her assessment and wrote, “[s]ince seizures began at age 5, [D.J.W.]

has stalled in his development and regressed in many ways.” Id. She also noted that despite starting

a ketogenic diet, he continues to have seizures. Id. Dr. Silver wrote that the seizures “seem to also

coincide with memory loss of information [he] previously retained.” Id. at 2.

D.J.W. underwent testing to assess his intellectual functioning and was determined to be

within the extremely low range of ability in all five tested areas. Id. at 3–4. As a result, Dr. Silver

concluded that “[g]iven the full picture and review of available data, it is determined that [D.J.W.]

does meet [the] medical diagnostic criteria for an Autism Spectrum Disorder [diagnosis].” Id. at 7.

Specifically, Dr. Silver wrote that he “present[s] with behavioral aspects of an Autism Spectrum

Disorder including repetitive play patterns, rigidity[,] and hyposensitivity to pain. He has

substantial delays in imaginative and creative play[,] . . . tends to resist interacting with other

children[, and exhibits s]ome difficulty with conversation[.]” Id. D.J.W. was diagnosed at a Level

2 on the spectrum, indicating that he requires “substantial support.” Id.

On January 29, 2020, D.J.W. presented for a neurology follow-up with Jane MacLean,

M.D., and she noted his “[r]ecent diagnosis of ASD.” Pet’r’s Ex. 108 at 28. D.J.W. returned on

March 9, 2020, and was still “having a lot of seizure activity.” Id. at 33. The working diagnoses

included “Lennox-Gastaut syndrome, intractable, with status epilepticus[.]” Id. at 4. The same day,

March 9, 2020, D.J.W. had a follow-up with Dr. Nayfack. Pet’r’s Ex. 109 at 27, ECF No. 130. Dr.

Nayfack maintained his impression of “moderate [intellectual disability] and autism.” Id. at 28. He

based this assessment on D.J.W.’s “clinical impressions, parent report[s], and previous

evaluations[]” which noted “the core deficits we see in all children with autism, including difficulty

interacting socially[, . . .] communicating with others[,] and restrictive/repetitive behaviors.” Id. at

35. He noted that D.J.W. “demonstrate[d] some improvement with a school program that includes

speech, [occupational therapy,] and [adapted physical education].” Id. at 27. D.J.W. presented for

follow-ups throughout 2020. Pet’r’s Ex. 108 at 34–51. On December 16, 2020, D.J.W. was

diagnosed with asthma. Id. at 52. Dr. MacLean noted D.J.W.’s diagnoses of “refractory

generalized epilepsy with epileptic encephalopathy[,] intellectual disability[,] and [ASD]” on

November 9, 2021. Id. at 59. He continued to receive care for his conditions throughout 2021 and

2022. See id. at 52–67.

III. Expert Qualifications

a. Petitioner’s Expert, Dr. Yuval Shafrir, M.D.

Dr. Shafrir received his medical degree from the Sackler School of Medicine in Tel Aviv,

Israel in 1982. Pet’r’s Ex. 24 at 1. He completed his post-graduate training at the Chaim Sheba

Medical Center in Tel Hashomer, Israel, where he completed a rotating internship in 1983. Id. Dr.

Shafrir completed residencies in pediatrics at the Kaplan Hospital in Rehovot, Israel and the

11

Beilinson Medical Center in Petah Tikvah, Israel in 1984 and 1985, respectively. Id. He completed

an additional pediatric residency in the United States at North Shore University Hospital in

Manhasset, New York in 1988. Id. Dr. Shafrir also completed a pediatric neurology residency and

fellowship at the Washington University Medical Center in St. Louis, Missouri in 1991. Id. The

following year, in 1992, Dr. Shafrir completed a fellowship in pediatric neurophysiology and

epileptology at the Comprehensive Epilepsy Center at Miami Children’s Hospital. Id. He became

board certified in neurology and psychiatry with a special qualification in child neurology in 1993,

followed by neurophysiology in 1998. Id. at 2. Following active duty as a Major in the U.S.

Army’s Medical Department from 1993–1995, Dr. Shafrir was an attending child neurologist at

Georgetown University Hospital and Oklahoma University Health Science Center from 1995–

1999 and 1999–2000, respectively. Id. at 2–3. Dr. Shafrir served as an associate professor of

neurology and pediatrics while at both institutions. Id. at 3. Since 2000, Dr. Shafrir has practiced

in the field of pediatric neurology in private practice. Id. He currently serves as an assistant

professor of pediatrics at the University of Maryland School of Medicine. Id. He also teaches

residents at Sinai Hospital’s Department of Pediatrics. Id. Dr. Shafrir’s curriculum vitae includes

approximately twenty published articles and abstracts of which he is a listed author. See id. at 4–

7.

During the hearing, Dr. Shafrir stated that the “main focus” of his clinical practice involves

epilepsy. Tr. 72:16. He also noted that “in the last [twenty] years[, he has seen] a lot of patients

with more neurological problems . . . and then . . . autisms [sic].” Tr. 72:9–12. He stated that he

has also dealt with patients who have Doose syndrome of “both the easy variety and severe

variety.” Tr. 73:3–7. He also stated that he has testified many times in the Vaccine Program. Tr.

73:16–22.

Dr. Shafrir submitted two expert reports and testified during the hearing. See Pet’r’s Exs.

23, 58; Tr. 71:8–226:4. Dr. Shafrir was offered by Petitioner as an expert in pediatric neurology

without objection, and I recognized him as such. Tr. 73:23–25, 74:1–2. Following the entitlement

hearing, Dr. Shafrir submitted two supplemental expert reports. See Pet’r’s Exs. 88, 111.

b. Respondent’s Expert, Dr. Gregory Holmes, M.D.

Dr. Holmes received his medical degree from the University of Virginia School of

Medicine (“UVA”) in 1974, along with an honorary degree from Harvard University in

1996. Resp’t’s Ex. B at 1. He completed his post-graduate training at Yale University School of

Medicine, where he completed an internship in pediatrics in 1975 and a residency in pediatrics in

1976. Id. Dr. Holmes also completed a residency in neurology at UVA in 1979. Id. He is board

certified in pediatrics, psychiatry, neurology with special competence in child neurology, and

clinical neurophysiology. Id. He served as an associate professor of neurology and pediatrics at

Harvard Medical School from 1988–1996, before serving as a professor of neurology at the same

institution from 1996–2002. Id. at 2. Dr. Holmes was also a professor of neurology and pediatrics

at Dartmouth Medical School from 2002–2013. Id. He currently serves as a professor and

Chairman of Neurological Sciences at the University of Vermont College of Medicine, as well as

a professor of pediatrics. Id. Dr. Holmes served as the Director of the Clinical Neurophysiology

Laboratory and Epilepsy Program at the Children’s Hospital in Boston, Massachusetts for

12

approximately ten years, from 1988–1998. Id. Dr. Holmes’ curriculum vitae includes over six

hundred articles, reviews, and abstracts of which he is a listed author. See id. at 39–113.

During the hearing, he explained that as the Chairman of the Department of Neurological

Sciences, he “teach[es] students and train[s] physicians on seizure and seizure disorders, epilepsy,

and epileptic encephalopathy[.]” Tr. 240:21–25, 241:1. He also stated that throughout his clinical

practice, he has treated ten to fifteen patients with Doose syndrome. Tr. 242:8–12.

Dr. Holmes submitted two expert reports and testified during the hearing. See Resp’t’s Exs.

A, C; Tr. 239:18–312:11. Dr. Holmes was offered by Respondent as an expert in pediatric

neurology without objection, and I recognized him as such. Tr. 242:23–25, 243:1–4. Following

the entitlement hearing, Dr. Holmes submitted an additional expert report. See Resp’t’s Ex. D.

c. Respondent’s Expert, Dr. Max Wiznitzer, M.D.

Dr. Wiznitzer obtained his medical degree from Northwestern University in 1977. Resp’t’s

Ex. F at 1. He then completed a residency in pediatrics at Children’s Hospital Medical Center in

Cincinnati, Ohio, followed by fellowships at the Cincinnati Center for Developmental Disorders,

in pediatric neurology at the Children’s Hospital of Philadelphia, and in higher cortical functions

at the Albert Einstein College of Medicine. Id. at 1–2. He is currently a pediatric neurologist at

University Hospitals of Cleveland, as well as a professor of pediatrics and neurology at Case

Western University. Resp’t’s Ex. E at 1. He is board certified in pediatrics, psychiatry, neurology

(with a special qualification in child neurology), and neurodevelopmental disabilities. Id. He is a

part of the epilepsy group at University Hospitals Case Medical Center, UH Rainbow Babies, and

Children’s Hospital. Id. Dr. Wiznitzer has an active clinical practice interpreting EEGs and treating

pediatric patients who have seizure disorders and epileptic encephalopathies. Id. He serves on the

professional advisory board of the Autism Society of Ohio, is a child neurology liaison to the

American Academy of Pediatrics’ Autism Subcommittee, and is the American Academy of

Pediatrics’ neurology liaison to the Autism Treatment Network. Id. at 2. He is on the editorial

board of several journals, including the Journal of Child Neurology, Lancet Neurology, and

Pediatric Neurology. Id. He has authored or co-authored eleven textbook chapters and over eighty

scientific papers. Id. Dr. Wiznitzer submitted one written expert report in this case. See id.

IV. Petitioner’s Claim and Respondent’s Response

Petitioner alleged in the petition that D.J.W. suffered from “a seizure disorder with

cognitive and developmental delays, which were caused in fact by his receipt of the DTaP-IPV

vaccine.” Pet. at 6. As the case proceeded to the entitlement hearing, Petitioner further defined her

claim in a pre-hearing briefing and explained that D.J.W. suffers from an “autoimmune epileptic

encephalopathy that progressed into a severe epileptic syndrome with associated developmental

delay[,]” following his DTaP-IPV vaccinations. Pet’r’s Br. at 9. During the entitlement hearing,

Petitioner’s expert Dr. Shafrir opined that D.J.W. developed a “progressive and severe and

disabling epileptic encephalopathy.” Tr. 75:24–25. Dr. Shafrir continued that D.J.W. “has the

absolute typical epileptic encephalopathy in which the seizures is [sic] contributing to his cognitive

and neurological decline[,] and emotional decline and emotional symptoms, and we do[ not] have

any other cause other than the epilepsy itself to cause it.” Tr. 131:10–14. Dr. Shafrir concluded

13

that this encephalopathy “is more likely than not [to] have [an] immune basis,” and “that the

vaccine was the trigger.” Tr. 76:1–2.

Post hearing, D.J.W. was diagnosed with autism. See generally Pet’r’s Ex. 86. In her post-

hearing memorandum, Petitioner reiterated that her claim “is that D.J.W. suffered a vaccine injury,

namely epileptic encephalopathy (i.e.[,] Doose syndrome), via an autoimmune process.” Pet’r’s

Mem. at 11. She asserted that “petitioners in the National Vaccine Injury Compensation Program

have previously pursued claims based upon an encephalopathy by a covered vaccine that later

manifested developmental regression or even autism.” Id. at 11–12 (citing Wright v. Sec’y of

Health & Hum. Servs., No. 12-423V, 2015 WL 6665600, at *98 (Fed. Cl. Spec. Mstr. Sept. 21,

2015)). Petitioner argued that based on the reasoning in similar cases, “[her] claim is viable despite

an ASD diagnosis[,] and [P]etitioner should be permitted to proceed on this injury.” Pet’r’s Mem.

at 13.

Respondent addressed Petitioner’s memorandum with a response, including a motion to

dismiss, and asserted that “there is no credible evidence that vaccinations cause autism, and there

is no manner to proceed that excludes D.J.W.’s autism diagnosis from his epileptic

encephalopathy.” Resp’t’s Resp. at 11. He argued D.J.W. has autism and Doose syndrome, two

“conditions [that] are inherent encephalopathies of the brain and can be understood as generalized

brain disorders.” Id. at 8. Respondent continued that “the two entities are so intertwined that it is

impossible to separate them.” Id. at 9. Respondent noted that “Petitioner’s argument here that

[D.J.W.’s] ‘neurologic’ [sic] and other developmental problems, which have been subsequently

diagnosed as autism, are the product of a vaccine-aggravated epileptic encephalopathy is a tactical

approach to evade well-established precedent that vaccines do not cause autism.” Id. He argued

that Petitioner is now attempting to “recast [the] claim that a vaccine caused autism into an

encephalopathy claim based on the logic that the neurologic symptoms associated with an ASD

reflect an underlying brain injury.” Id. Respondent asserted that this is an autism injury case and

given the history of such claims in the Program, “the current record fails to provide evidence [of]

a reasonable basis for bringing, or moving forward with, this claim.” Id. at 12.

Petitioner argued in her reply to Respondent’s response that she is “not attempting to

recharacterizing [sic] an autism diagnosis as an encephalopathy as argued by [R]espondent[.]”

Pet’r’s Reply at 3. Petitioner emphasized that she is alleging only that D.J.W.’s encephalopathy is

vaccine caused. Id. She stated that “[t]he court is not required to find that [D.J.W.’s] subsequent

diagnosis of autism was or was not caused by the vaccination.” Id. Petitioner conceded that she

must address D.J.W.’s autism diagnosis. Id. at 3–4. She asserted that “additional expert testimony

[wa]s necessary and relevant to the determination as to the issue of whether [P]etitioner’s claim

that D.J.W.’s vaccine induced epileptic encephalopathy is separate and distinct from [his]

subsequent autism diagnosis.” Id. at 4. She reiterated that her claim is based on an encephalopathy

diagnosis, “and there is no dispute” between the parties that D.J.W. “developed epileptic

encephalopathy[] or unremitting epileptic activity that contributed to his severe and rapid cognitive

and behavioral impairments, after his vaccination with DTaP-IPV on February 6, 2012.” Id. at 3.

V. D.J.W.’s Diagnoses

a. Autism Spectrum Disorder

14

D.J.W. was diagnosed with ASD on May 22, 2019, at twelve years old. For several years

prior, Petitioner communicated to D.J.W.’s medical providers that she had “long been concerned

about a possible Autism Spectrum Disorder [diagnosis] further complicating [D.J.W.’s]

developmental functioning.” Pet’r’s Ex. 86 at 6. During D.J.W.’s ASD evaluation, Petitioner told

Dr. Silver that D.J.W.’s “onset of symptoms [] corresponds to seizure activity rather than prior to

the age of [five] while [he] was navigating earlier milestones.” Id. Petitioner testified during the

October 4, 2018 hearing, that she could not remember specific dates but that she asked D.J.W.’s

treaters about the cause of his cognitive symptoms after she “noticed his brother was developing

faster.” Tr. 33:5. She stated, “doctors sa[id] that the seizures could be causing delays but then also

that his delays could be caused by, you know, him having autism.” Tr. 34:9–11. Since the seizures

started “he[ had been] having a lot of activity while he[ is] sleeping, so even the ones that

[Petitioner was] not catching, he[ was] still having them, and those are causing, you know issues .

. . it[ is] very confusing, like we do[ not] – honestly do[ not] know what[ is] – what[ is] wrong with

[D.J.W.]” Tr. 35:6–11.

Petitioner’s expert testified after hearing Petitioner’s account and unequivocally ruled out

autism as a diagnosis or comorbidity. He stated, “first of all, [the child] does not have autism.” Tr.

146:11. Dr. Shafrir explained that his contention is largely based on the age of autism onset,

typically around or before the age of three. Tr. 146:12–13. D.J.W.’s symptoms consistent with

autism manifested “[a]fter the onset of his encephalopathy. Not before. And after the onset of his

seizures. Not before.” Tr. 148:12–14. He explained that autism “is a neurological manifestation of

multiple diseases and at least is — at least 150 conditions [] cause autism.” Tr. 146:23–25. When

asked if a patient can have autism concurrent with seizure disorders, Dr. Shafrir said no. Tr.

148:18–20. He stated that “seizure[s] cause autistic symptoms. That[ is] what happens. This is a

part of epileptic encephalopathy.” Tr. 148:20–21. Petitioner’s expert was clear, “[a]utism is not an

independent symptom that you have in addition to having epileptic encephalopathy

independently.” Tr. 149:2–4. Dr. Shafrir said that he “never heard anybody claim it anyway.” Tr.

149:4–5. Dr. Shafrir reiterated his position that “[a]utism is not an additional independent

diagnosis in a patient who have [sic] already known severe progressive — regressive epileptic

encephalopathy.” Tr. 150:13–15.

Dr. Shafrir submitted a post-hearing expert report following D.J.W.’s ASD diagnosis,

wherein Dr. Shafrir maintained that autism is not applicable in this case. See Pet’r’s Ex. 88 at 37.

He wrote that “D.J.W.’s clinical presentation, including his autistic symptoms can be fully

explained by the diagnosis of Doose syndrome.” Id. at 39. Dr. Shafrir cited to the CDC reference

on autism, 22 which states, “ASD begins before the age of [three] years.” Id. at 38; Pet’r’s Ex. 93

at 1, ECF No. 114. He highlighted that according to Dr. Silver, D.J.W.’s “development was

typical” and he had “no developmental concerns” prior to seizures that began at five-years-old.

Pet’r’s Ex. 88 at 38; see also Pet’r’s Ex. 86. Dr. Shafrir continued that Dr. Silver associated

D.J.W.’s stalled development and regression with these seizures. See Pet’r’s Ex. 88 at 31. He stated

definitively that “[ASD] never starts at the age of [twelve],” and described D.J.W.’s late diagnosis

as “a result of lack of knowledge, experience[,] and understanding of the nature of [ASD], as well

as the diagnostic process by the single psychologist who made the diagnosis.” Id. at 36, 45. Dr.

Shafrir continued his criticism of Dr. Silver and stated that she “failed to cover the entire diagnostic

22

Signs and Symptoms of Autism Spectrum Disorder, CENTERS FOR DISEASE CONTROL AND PREVENTION,

https://www.cdc.gov/ncbddd/autism.signs.html.

15

list in the DSM-V,” and she “contradicted her own scoring . . . which indicated that D.J.W. scored

below the cutoff for an autism spectrum disorder.” Id. at 46.

Respondent’s expert Dr. Holmes was not allowed to testify about the pending ASD

evaluation. 23 Dr. Holmes did note that D.J.W. had an atypical presentation of Doose syndrome

that would account for his symptoms, but he was not including in his assessment the behavioral

and cognitive delays that Petitioner expressed concern about. Tr. 314:1–6. Dr. Holmes also pushed

back on the implication from Dr. Shafrir that seizures can cause autistic-like symptoms. Dr.

Holmes then submitted a post hearing expert report in response to Dr. Shafrir and agreed with Dr.

Silver’s amended diagnosis, “autism spectrum disorder with severe intellectual impairment,

moderately severe language impairment, associated with Doose.” Resp’t’s Ex. D at 2. Dr. Holmes

also filed literature that discusses the “substantial evidence that genetics plays an important role in

[the development of] ASD.” Resp’t’s Ex. D2 at 1, ECF No. 119. 24

In response to Dr. Shafrir’s focus on the age of onset, Dr. Holmes submitted the 2018

consensus guidelines from the British Association for Psychopharmacology to note that the current

DSM-5 “does not specify an age of onset.” Resp’t’s Ex. D3 at 8, ECF No. 119. 25 The revision also

states that “symptoms must be present in the early developmental period,” but that “ASD may not

become fully apparent until later in life and enables the diagnosis of ASD [even into] adulthood.”

Id. The article continues that diagnosis should be conducted by a multi-disciplinary team of

professionals “trained in the assessment, diagnosis, and treatment of ASD using a combination of

diagnostic tools . . . .” Id. at 33. The authors identify speech and language therapists, clinical

psychologists, pediatricians, psychiatrists, and occupational therapists as ideal team members. Id.

Post hearing, Respondent filed an expert report from pediatric neurologist Dr. Max

Wiznitzer that directly addresses the late ASD diagnosis in this case. See Resp’t’s Ex. E. Dr.

Wiznitzer conceded that most children are symptomatic by age three, but noted that “there are

some, such as D.J.W., who have a developmental regression and become symptomatic after that

age and during the early childhood years.” Id. at 9. He noted that the DSM-5 now includes within

ASD: childhood disintegrative disorder, Asperger’s disorder, and pervasive developmental

disorder not otherwise specified. Id. Because one or more of these conditions is characterized by

a “clinically significant loss of previously acquired skills (before age [ten] years),” Dr. Wiznitzer

opined that “D.J.W.’s onset of ASD falls within the accepted age range of onset.” Id.

b. Doose Syndrome

23

D.J.W.’s upcoming ASD evaluation was not disclosed prior to the entitlement hearing, and instead was

revealed during the hearing. That was not the injury alleged in the petition or any subsequent pleadings,

and there was no testimony, written or otherwise, relating to an autism diagnosis in advance of the hearing

in this case.

24

A.W. Buckley & G.L. Holmes, Epilepsy and Autism, 6 COLD SPRING HARB PERSPECT MED. 1–18

(2016).

25

O.D. Howes, et al., Autism Spectrum Disorder: consensus guidelines on assessment, treatment and

research from the British Association for Psychopharmacology, 32(1) J. PSYCHOPHARMACOL. 3–29

(2018).

16

Dr. Shafrir opined during the hearing that D.J.W.’s encephalopathy was autoimmune in

nature and, more specifically, Doose syndrome with a “very early loss of cognitive function.” Tr.

76:8–9. Dr. Shafrir explained that D.J.W.’s Doose syndrome diagnosis is “based on [D.J.W.’s]

EEG and the predominance of [his] atonic seizures[.]” Tr. 90:10–11. He then equivocated and

noted that D.J.W.’s treaters “decided that it fits Doose the best, and — but, as I said, this is — this

is a — less than half of the patient with Doose that — they have some — I mean, it[ is] not there.”

Tr. 90:10–14. Dr. Shafrir continued, “I think that his diagnosis is Doose syndrome of the severe

variety with very early progression and severe neurological impairment, regression, cognitive

function, which appeared very early in his course.” Tr. 90:20–23. Dr. Shafrir maintained his

opinion (post hearing) that D.J.W. only has Doose syndrome, despite the ASD diagnosis. See

Pet’r’s Ex. 88.

Respondent’s expert Dr. Holmes agreed with D.J.W.’s diagnosis of epileptic

encephalopathy, but he was equivocal when asked specifically about Doose syndrome. Dr. Holmes

described the Doose syndrome in this case to be a typical case of a rare, unfavorable presentation

and outcome. Tr. 253:11. Dr. Holmes described D.J.W.’s first seizure:

[D.J.W.] was a healthy, normal child, four years old, who had a single seizure. He

fell when he was climbing up to the bed, hit his head, had a generalized tonic-clonic

seizure which lasted approx. [sic] — a couple of minutes. It was followed by a

postictal period. And then he returned to his baseline relatively quickly. And the

physicians in the emergency room were concerned about the head trauma part of it

and then did a CT scan, which was normal.

Tr. 256:4–11.

Dr. Holmes continued that D.J.W. “was then discharged home and did well with no

evidence of any type of encephalopathic process occurring until approximately one month later[,]”

when Petitioner believed D.J.W. had another seizure in the bathroom. Tr. 256:12–14. Petitioner

did not take D.J.W. to the hospital following the second seizure, but “a few days later, [there was]

another clear-cut generalized tonic-clonic seizure,” prompting an epilepsy classification after two

spontaneous seizures less than one month apart. See Tr. 256:17–18. Dr. Holmes opined that it

“would be extremely unusual in a child that has an autoimmune cause, for their first seizure to [be]

an isolated seizure.” Tr. 256:25, 257:1–2. Dr. Holmes noted D.J.W.’s normal EEG and that he

“demonstrated no signs of any type of encephalopathy.” Tr. 256:23–24.

Although there was no family history or positive genetic testing in D.J.W.’s case, Dr.

Holmes explained that “the prevalence of specifically myoclonic and astatic seizures among family

members is [significantly higher than the general population, but still] found to be only [two]

percent.” Tr. 254:5–8. He noted that D.J.W. had “[n]ormal development before onset. Never

neurometabolic or degenerative diseases. Mostly no neurological deficits at the onset of the

epilepsy.” Tr. 252:14–16. He continued that there were “[p]rimarily generalized myoclonic, astatic

or myoclonic-astatic seizures, short absences[,] and mostly generalized tonic-clonic seizures [and]

rarely focal seizures.” Tr. 252:18–21. Dr. Holmes also referred to the testimony of Petitioner’s

mother who indicated that “if [her grandson] did[ not] have a seizure before 7:00 a.m. that he was[

17

not] going to have one.” Tr. 269:24–25. Dr. Holmes referenced the Nabbout and Dulac article26 to

support his contention that D.J.W. suffers from a severe case of Doose syndrome. Resp’t’s Ex. A,

Tab 3, ECF No. 50. The authors wrote:

[MAE/Doose syndrome] affects previously normal children, mainly boys, with a

high incidence of familial incidence of familial antecedents of epilepsy. It begins

between 2 and 5 years of age, with some patients having a few earlier febrile

convulsions. Generalized tonic-clonic seizures are the only type of seizures during

the first few months of the disease. Then, myoclonic astatic seizures occur with

increasing frequency, causing the patient to fall several times a day. . . . Between 2

and 12 months after onset, the other half of the patients [with more severe

manifestation and less favorable outcome] have an epileptic encephalopathy with

mental deterioration, erratic myoclonus, and vibratory tonic seizures, especially on

early morning sleep, confusion, and, on EEG, slow activity with diffuse and nearly

continuous spike activity. This condition often lasts for weeks and even months,

with progressive worsening of cognitive functions, after which the patient is left

with mental retardation and tonic seizures, mainly in early morning sleep, between

4:00 a.m. and 6:00 a.m.

Id. at 4.

Dr. Holmes noted that as a syndrome, “[Doose] does[ not] have a strict criteria [sic].” Tr.

296:2. When diagnosing someone after a seizure, Dr. Holmes explained that you have to first rule

out a brain tumor and then “just wait and see because a lot of the children, — over 50 percent —,

especially if you have a normal EEG will not, — which [D.J.W.] did — he — would not go on to

have a second or a third seizure.” Tr. 306:19–22. Doose syndrome, “requires a number of features,

including multiple seizure types,” and “a certain pattern on the EEG with spike and wave activity.”

Tr. 307:10–13. In D.J.W.’s case, after the first seizure, there was eventually “a second seizure and

perhaps that third seizure where [he was found] on the bathroom floor where he just sort of

collapsed.” Tr. 306:25, 306:1. D.J.W. went on to have astatic seizures, “absence seizures where he

stare[d] and blink[ed,] and then he ha[d] generalized tonic-clonic seizures.” Tr. 307:7–9. Dr.

Holmes noted that “when all those things c[a]me together, [] I would have made the diagnosis of

Doose syndrome, and I would have told [Petitioner] that I think this is most likely genetic.” Tr.

307:14–16.

Dr. Holmes explained that although not common, “cognition stagnation and delay [] can

occur in Doose [patients] and especially [in] those children that have poorly controlled seizures.”

Tr. 313:13–16. He distinguished seizures in conjunction with Doose syndrome from Dr. Shafrir’s

discussion of autoimmune encephalitis. Tr. 248:18–249:8. Dr. Holmes clarified that encephalitis

(brain inflammation), that is caused by autoantibodies (an immune system response), can lead to

an encephalopathy (brain injury or dysfunction). Tr. 202:6–7, 13–14, 247:18–22. Dr. Holmes

testified that Dr. Shafrir’s reference to encephalitis is not relevant to this case because there is no

evidence that D.J.W. experienced brain inflammation. Tr. 266–68. Dr. Holmes noted on redirect

26

R. Nabbout & O. Dulac, Epileptic Encephalopathies: A Brief Overview, 20(6) J. CLIN. NEUROPHYSIOL.

393–97 (2003).

18

that in concluding that Doose syndrome accounted for all of D.J.W.’s symptoms, he was not

including D.J.W.’s behavioral delays. Tr. 314:1–6.

Dr. Wiznitzer confirmed that D.J.W. has Doose syndrome in his written report and opined

that the onset was following his first seizure reported on February 13, 2012. Resp’t’s Ex. E at 8.

He reiterated Dr. Shafrir’s contention that Doose syndrome has a genetic basis. Id. He noted that

since 2010, “over [thirty] genes have been linked to Doose syndrome.” Id. As a result, a recent

proposal has emerged to “redesignate [Doose syndrome as a] genetic generalized epilepsy with

MASs (myoclonic-atonic seizures), consistent with the familial genetic study conducted by Doose

and the recent identification of candidate genes.” Id.; Resp’t’s Ex. E7, ECF No. 124.27

c. Autoimmune Encephalopathy

Dr. Shafrir opined in his first expert report that D.J.W. suffered from an autoimmune

epileptic encephalopathy (Doose syndrome) that resulted from a vaccine-induced, immune

response. Pet’r’s Ex. 23 at 29. He discussed an article that “looked at the serum of autistic children”

and identified antibodies to a protein that “is part of the neuronal potassium channel.” Id.; Pet’r’s

Ex. 41, ECF No. 60. 28 Dr. Shafrir further explained that “[t]he only mechanism by which vaccines

can cause neurological symptoms is through [the] activation of the immune system.” Pet’r’s Ex.

58 at 6.

Petitioner’s causation theory hypothesizes that “[b]ecause of yet unidentified genetic

susceptibility, D.J.W. reacted abnormally to his fifth DTaP vaccination by an immune attack on

protein components of his brain, likely ion channels which control neuronal excitability[, and]

produced progressive encephalopathy.” Pet’r’s Ex. 88 at 39. Dr. Shafrir explained that the

encephalopathy manifested as seizures that continued to occur “because of the production of

autoantibodies against brain components,” via epitope spread and bystander activation. Id. In

support of his theory, Dr. Shafrir identified the late onset of D.J.W.’s Doose syndrome as evidence

that the temporal association between his vaccination and disease onset is not random. Id. Dr.

Shafrir also noted that “inflammation has been implicated in the pathophysiology of childhood

epileptic encephalopathies.” Id. at 40. He identified the “increased production of

inflammatory/epileptogenic cytokines in response to the DTaP vaccination” but noted that the

“literature regarding [the] cytokine response to immunization is still not well developed.” Id. Dr.

Shafrir explained this is because “[t]he effects of autoantibodies on brain activity are much easier

to study and characterize than the role of the cellular arm of the adaptive immune system and the

innate immune system, [involving] multiple components, including multiple cytokines.” Id. at 42.

He continued that “[t]hese multiple components by themselves are covered by genetic and

epigenetic mechanisms which are still poorly understood, and are regulated from mostly unknown

interactions of cytokines, chemokines, and cell receptors.” Id. Dr. Shafrir then noted that the DTaP

vaccine “contained several proteins, as well as [an] aluminum adjuvant[,] which are capable of

producing multiple cytokines, including those which were described in association with infantile

spasms and probably other epileptic encephalopathies.” Id.

27

H. Oguni, Epilepsy with myoclonic-atonic seizures, also known as Doose syndrome: Modification of the

diagnostic criteria, 36 EURO. J. PAEDIATRIC NEUROL. 37–50 (2022).

28

D.F. Obregon, et al., Potential Autoepitope with the Extracellular Region of Contactin-Associated

Protein-like 2 in Mice, 4(1) BRITISH J. MED. & MED. RES. 416–32 (2014).

19

In her pre-hearing submission, Petitioner described her causation theory as “well

established in medical literature.” Pet’r’s Br. at 18. She continued:

There is evidence to suggest that the onset of the seizure is caused by an

immunological mechanism. Through yet unidentified immunogenic traits, D.J.W.

experienced an autoimmune injury in his brain, which was most probably mediated

by either his innate and [sic] adaptive immune systems. The resultant autoimmune

encephalopathy produced D.J.W.’s epileptic syndrome and residual neurological

sequelae.

Id.

Dr. Shafrir testified that D.J.W.’s epileptic encephalopathy “more likely than not [has an]

immune basis, and it is more likely than not that the vaccine was the trigger for the autoimmune

process that caused it.” Tr. 76:1–3. When asked to describe the characteristics of autoimmune

encephalopathy, Dr. Shafrir did not provide specific factors. He stated that “we see them based on

the fact that there is [sic] some articles and it[ is] quite documented, and in many cases in which

autoimmune basis was found[,] and Doose syndrome itself in one case report and in similar cases

and in other case reports.” Tr. 76:15–18. When asked again for the evidence to support an

autoimmune phenomenon in Doose syndrome, Dr. Shafrir explained, “most [kids with Doose

syndrome] have problems before [onset], and – but it[ is] a generalized epilepsy that is associated

with somewhat similar epileptic phenomena and is associated with worsening of cognitive function

and are [sic] very severe.” Tr. 99:19–22. He later clarified, “there is no obvious relationship

between epilepsies and autoimmune disease.” Tr. 100:22–23.

Dr. Shafrir testified that Doose syndrome is “not genetically based,” and “there are articles

[that say] it is not.” Tr. 129:13–15; Pet’r’s Ex. 77, ECF No. 66.29 Dr. Shafrir testified that articles

support his contention that Doose syndrome has an autoimmune etiology. He asserted that the Sirsi

et al. article sought to “widen the spectrum of etiologies for MAE to include autoimmunity.”

Pet’r’s Ex. 77 at 1. The authors wrote that “a range of central and peripheral nervous system

disorders” can result from autoimmunity to voltage gated potassium channel complexes 30

(“VGKC”). Id. at 4. “The proposed mechanism of pathogenicity is [the] binding of antibodies to

transmembrane VGKCs which impair ion channel function leading to hyperexcitability.” Id. The

authors described case studies but conceded that “the incidence, and the spectrum of VGKC

autoimmunity in children is yet to be established.” Id. at 3. They further conceded that “there are

no cases of VGKC antibody mediated epilepsy presenting as a MAE.” Id. at 4. One of the study’s

stated limitations is that “multiple different intractable pediatric epilepsy syndromes [that] were

not specific to MAE” were included. Id. The authors noted that “[a]lthough MAE is a unique[,]

well-defined[,] electro-clinical syndrome, the underlying etiology is presumed to be genetic.” Id.

29

D. Sirsi, et al., Does Autoimmunity have a Role in Myoclonic Astatic Epilepsy? A Case Report of Voltage

Gated Potassium Channel Mediated Seizures, 1 ANN. CLIN. CASE REP. 1178–84 (2016).

30

Dorland’s defines a voltage-gated channel as “an ion channel that opens or closes in response to changes

in the electrical potential across the cell membrane.” Dorland’s at 337. The Sirsi et al. article is referring

specifically to potassium channel complexes “of the peripheral nervous system [that] play an important role

in synaptic transmission, conduction[,] and repolarization.” Pet’r’s Ex. 77 at 1.

20

Ultimately, they determined that “[c]ausality of MAE by VGKC antibodies needs further

investigation and cautious interpretation.” Id.

Dr. Shafrir first described molecular mimicry as “the suggested mechanism” in this case in

his written report. Pet’r’s Ex. 23 at 26. He asserted during his testimony that “molecular mimicry

is definitely a solid place to start.” Tr. 107:16–17. Dr. Shafrir defined molecular mimicry as “a

situation in which a part of the vaccine protein is similar to part of the target protein attacked by

the autoimmune disease, and the antibody that is produced in the vaccine are [sic] attacking the

protein that is similar in structure.” Tr. 106:14–18. He noted that bystander activation was another

mechanism that he “mention[ed]” Tr. 106:24–25. He defined bystander activation as “an activation

of other cells that are in the area of inflammation.” Tr. 106:25, 107:1. He continued with “the next

[mechanism that] is something called an epitope spread [where] there is – because of inflammation

that is caused by the immunoreaction, there is exposure of other parts of the molecule and the body

– that they[ are] not supposed to be exposed, and then the body produce [sic] antibodies against

them.” Tr. 107:2–6. Dr. Shafrir explained that he filed literature wherein the authors “look in

databases of protein structure[s] and they look at [the] database of epitope[s] and of proven

immune epitope[s] that were known to cause – to have antibodies against them, and they show that

there is sharing of those structural vaccine[s] with those epitopes.” Tr. 107:19–23.31 He conceded

that none of the articles that he filed mentioned the DTaP vaccine or the corresponding wild viruses

when discussing antibodies to the protein implicated in autoimmune epilepsy. Tr. 167:10–24.

When asked if there was any evidence of an autoimmune etiology in this case, Dr. Shafrir

noted that a “treating physician actually suspected an autoimmune process existent, and it[ is] more

or less [an] incomplete job.” Tr. 76:19–21. He opined that “the evaluation of autoimmune epilepsy

was minimal, including only anti-NMDA receptor and anti-GAD (glutamic acid dehydrogenase)

antibodies, measured only in the serum and not the [cerebrospinal fluid].” Pet’r’s Ex. 23 at 23. He

continued, that “[i]mmunosuppressant treatment was initiated relatively early,” but noted that

D.J.W.’s treatment “did not go beyond a single course of IVIG.” Id. Dr. Shafrir testified that no

one looked for “any overt immune abnormality.” Tr. 117:10–11. Dr. Shafrir acknowledged that

the medical records in this case did not contain “any generalized signs of autoimmunity.” Tr.

223:5–6. However, Dr. Shafrir asserted that in D.J.W.’s case, “he has Doose syndrome[,] and he

ha[d] abrupt onset, very rapid cognitive decline, and — lack of response to medication typical to

him.” Tr. 223:18–20. Dr. Shafrir also suggested that there was no attempt to determine if antibodies

were present or there were any signs of encephalitis. Tr. 117:12–16. He stated that the minor child

in this case “had nuances of progressive epileptic encephalopathies.” Tr. 125:2–3. According to

Dr. Shafrir, this is “completely different, but it[ is] the same mechanism” as autoimmune

encephalitis. Tr. 125:3–4.

Dr. Shafrir addressed the negative antibody testing in this case by discussing an article he

submitted entitled, Paediatric Autoimmune Encephalopathies: Clinical Features, Laboratory

Investigations and Outcomes in Patients, as evidence that the clinical presentation and response to

treatment was similar in patients with or without antibodies. Tr. 85:23–25, 86:1; Pet’r’s Ex. 67,

31

Dr. Shafrir did not cite to any particular article when making this statement.

21

ECF No. 63. 32 Dr. Shafrir explained this observation applies to “the autoimmune encephalitis in

those particular patients, but we have no reason to believe that it[ is] not — this does not exist in

other situation [sic], and it is a work in progress.” Tr. 86:7–10. He highlighted that the three

patients in the study had recently been vaccinated. However, Dr. Shafrir was reminded that all

three of these patients also had “prodromal symptoms with either fever and/or associated infectious

episodes.” Tr. 161:9–10. He admitted that D.J.W. did not have prodromal symptoms. Tr. 161:11–

13. He further admitted that D.J.W. “does not fit the severe acute autoimmune encephalitis that

[would lead] to [hospital] admission” seen in these types of cases. Tr. 163:6–7. However, Dr.

Shafrir noted that D.J.W.’s “clinical presentation led his doctors to order tests for autoimmune

encephalitis, so obviously his clinical presentation was compatible with this by the thinking of his

neurologists as autoimmune encephalitis.” Tr. 163:12–15. Dr. Shafrir noted D.J.W.’s

immunization “the week before” as the most important evidence of an autoimmune process in this

case. Tr. 176:10. He also noted D.J.W.’s “abrupt onset of epileptic encephalopathy with

uncontrolled seizure [sic] commingled with the other symptoms [a]s a reason to suspect

autoimmune encephalitis.” Tr. 176:25, 177:1–4. He asserted that D.J.W. does “have autoimmune

epilepsy. You can call it — so autoimmune encephalitis and autoimmune epilepsy can be both

called autoimmune encephalopathy.” Tr. 136:8–10. Dr. Shafrir admitted that it is not generally

accepted by the medical community that Doose syndrome is autoimmune. Tr. 137:16–18.

Following Dr. Shafrir’s direct and cross examinations, I asked him several questions to

clarify his previous testimony. He defined encephalitis generally as, “signs of inflammation in the

brain.” Tr. 201:5. I also asked for a definition 33 for encephalopathy. Dr. Shafrir defined

encephalopathy as, “any abnormal function of the brain, more or less.” Tr. 202:3–4. When asked

if his definition of the phrase ‘epileptic encephalopathy’ was consistent with the stand-alone

definition of each word, Dr. Shafrir did not agree. Tr. 205:8–15. He described epileptic

encephalopathy as an “independent term.” Tr. 204:15. He acknowledged that there is a formal,

medical definition of the term but he “cannot [tell me what it is] by heart.” Tr. 206:1–3. He

explained that “it has to do with that there is a contribute — the epileptic activity is producing

some of the patient’s neurological deficit that would not exist if the epileptic activity would not

exist.” Tr. 206:3–7. He described the deficit as consisting of “things that are not decisions but

cognitive problem [sic] typically and regression in behavior, psychiatric problems.” Tr. 204:20–

22.

Dr. Shafrir also clarified that Doose syndrome is not autoimmune encephalitis. Tr. 226:4.

He maintained that Doose syndrome does have an autoimmune etiology, and that it manifests as

an encephalopathy. Tr. 225:19–25, 226:1–4. After Petitioner’s testimony that D.J.W. suffered from

a fever following vaccination, Dr. Shafrir asserted that the fever was of no consequence due to its

common occurrence post vaccination. Tr. 232:10–12. Dr. Shafrir did not contend that evidence of

D.J.W.’s fever strengthened Petitioner’s argument for an autoimmune etiology. See Tr. 232:17.

32

Y. Hacohen, et al., Paediatric autoimmune encephalopathies: clinical features, laboratory investigations

and outcomes in patients with or without antibodies to known central nervous system autoantigens, 84 J.

NEUROL. NEUROSURG. PSYCHIATRY 748–55 (2013).

33

I also had Dr. Shafrir define epilepsy and autoimmune disease. He defined epilepsy as “having epileptic

seizures[.]” Tr. 202:17–18. He defined autoimmune disease as a condition where a patient’s own immune

system attacks a part of the patient’s body. Tr. 203:3–9.

22

Dr. Shafrir then admitted that the effect of making the DTP vaccine acellular was to

“remove the factors that were determined to cause a lot of side effects,” including those commonly

associated with autoimmune responses. Tr. 214:24–25. He went on to identify these side effects

as a “[v]ery high fever, febrile seizure, encephalopathies, things like that.” Tr. 215:2–3.

Dr. Holmes disagreed that the etiology of D.J.W.’s epileptic encephalopathy is

autoimmune. See, e.g., Tr. 255:23–24. The Sirsi et al. article that Dr. Shafrir relied on specifically

discussed patients with encephalopathy but who otherwise had “varying presentations including

acute encephalitis, status epilepticus, febrile infection related epilepsy syndrome (“FIRES”)[,] and

limbic encephalitis.” Pet’r’s Ex. 77 at 2. Dr. Holmes explained that Doose syndrome, by contrast,

is an inherent encephalopathy and defined “inherent” as a “disorder in which the child is born with

a predisposition to develop that syndrome.” Tr. 245:11–13. He noted that “head trauma can lead

[to] epilepsy.” Tr. 277:4–5. However, he did not believe that D.J.W.’s fall off of the ladder played

any part in his condition. Tr. 277:9. Dr. Holmes asserted that in the neurological community the

“consensus is that [Doose syndrome has] a genetic cause.” Tr. 247:1. He explained “that there

have been a number of genes identified in Doose syndrome, but the fact that it has a varying clinical

presentation suggests that it[ is] probably multifactorial or polygenetic in cause, so there may be

multiple genes that are coming together, unfortunately, in one child that leads to the epileptic

encephalopathy.” Tr. 250:21–25, 251:1. Doose’s Myoclonic-astatic epilepsy chapter 34 supports

Dr. Holmes’ contention. See Pet’r’s Ex. 63 at 4, ECF No. 63. Doose wrote, “[i]t has been

demonstrated that a genetic predisposition to seizures of early childhood onset is the decisive factor

in the pathogenesis of MAE.” Id. He continued, “[a] number of genetically distinct and partly

mutually independent factors, some of which are expressed by special EEG patterns, others by

certain clinical characteristics [], are interacting and mutually augmentative.” Id. Dr. Holmes also

cited Petitioner’s medical literature that reads, “MAE is an idiopathic[,] presumably genetic

epileptic syndrome[,] with variable prognosis and although most [] patients reach a seizure

remission, the cognitive development remains uncertain.” See Pet’r’s Ex. 61 at 140, ECF No. 63. 35

After Dr. Shafrir noted that physicians in this case considered an autoimmune etiology, Dr.

Holmes countered that although D.J.W. received immunotherapy initially, D.J.W.’s current

treatment plan does not involve steroids. Tr. 261:3–4. He stated he “[does] not believe [D.J.W.’s]

current physicians believe he has an autoimmune epilepsy.” Tr. 261:17–19.

Dr. Holmes discussed the hypothesis that VGKC autoantibodies can lead to MAE and

compared the child that had autoimmune seizure activity in the Sirsi et al. article to D.J.W. See Tr.

258–59; see also Pet’r’s Ex. 77.36 Dr. Holmes testified that “there are certain children with Doose

syndrome that can have an explosive onset of seizures, but it[ is] very unusual . . . for the child to

come in basically with this many seizures, this refractory[,] and really not a good description of

astatic seizures, which is part of the definition of Doose syndrome.” Tr. 259:18–23. The child in

the Sirsi et al. case study had a generalized tonic-clonic seizure and was taken to the hospital. Tr.

34

MAE is Doose syndrome; however, the author had the grace to not use his own name in his work and in

the chapter he authored. H. Doose, Myoclonic-astatic epilepsy, BENIGN LOCALIZED & GENERALIZED

EPILEPSIES OF EARLY CHILDHOOD Ch. 25 at 166 (R. Degen & F.E. Dreifuss eds., 1992).

35

M. Trivisano, et al., Myoclonic astatic epilepsy: An age-dependent epileptic syndrome with favorable

seizure outcome but variable cognitive evolution, 97 EPILEPSY RES. 133–41 (2011).

36

See D. Sirsi, et al., supra note 29.

23

258:9–10. In the hospital, the child “continued to have episodes [–] 5 to 45 seconds of staring, eye

fluttering[,] and clonic movements.” Tr. 258:12–14. He experienced frequent seizures that were

characterized by “bilateral upper extremity myoclonus, rapid eye fluttering, facial twitching[,] and

subtle head drop.” Tr. 259:8–10. This child’s treaters believed he may have autoimmune

encephalitis. Tr. 259:12–13. His antibody tests were negative, but “[h]e was treated with steroids

and improved rapidly.” Tr. 259:15–16. Dr. Holmes testified that the case of the boy with

autoimmune encephalitis “is quite different from [D.J.W.’s] case[.]” Tr. 259:17–18. He stated that

there are so many differences between the case study and D.J.W. that while he “understand[s] why

the authors [of the Sirsi et al. article] call this Doose syndrome, [he] would actually have some

trouble with that.” Tr. 260:1–3.

Dr. Holmes continued to distinguish this case from the case studies submitted. See, e.g.,

Pet’r’s Ex. 67 at 1;37 Resp’t’s Ex. C, Tab 5, ECF No. 54.38 Other patients with seizure disorders

that have an autoimmune etiology “present with amnesia, confusion, seizures and psychiatric

features, and some then develop a more generalized encephalopathy with a movement disorder.”

See Resp’t’s Ex. C, Tab 5 at 1; see also Tr. 267:4–7. Dr. Holmes described what it might look like

if there was evidence of autoantibodies in this case. He explained, “[i]t can look like a variety of

manifestations, but usually the children have more than an isolated seizure.” Tr. 277:20–21. For

example, Dr. Holmes testified that they “have changes in mental status, behavior, and

encephalopathy . . . they may or may not have MRI changes, . . . they often have EEG abnormalities

early on in the course.” Tr. 277:21–25.

Dr. Holmes testified that his opinion on D.J.W.’s condition is based on how he presented

in the initial days and months following his first seizure. Tr. 268:4–8. Dr. Holmes clarified that his

conclusions were not influenced by negative autoantibody testing. Tr. 268:2–8. Using the case

studies relied on by Dr. Shafrir and the criteria for diagnosing Doose syndrome, Dr. Holmes

concluded that D.J.W. suffered from severe Doose syndrome with seizures with no evidence of

encephalitis or an autoimmune etiology. See Tr. 267–70.

Dr. Wiznitzer discussed the von Spiczak et al.39 article that Dr. Shafrir relied on to support

an association between vaccination and the development of Doose syndrome. See Resp’t’s Ex. E

at 10; see also Pet’r’s Ex. 29 at 1, ECF No. 59. Dr. Wiznitzer noted in his post-hearing report that

“the authors unequivocally state the overall risk for seizures, however, is not increased within

[three] days following DTaP [vaccination],” and additionally, “the risk for epilepsies is not

elevated even though epilepsy may present with a seizure following vaccination.” Resp’t’s Ex. E

at 10; Pet’r’s Ex. 29 at 1.

Dr. Wiznitzer also discussed Dr. Shafrir’s reliance on the Kashiwagi et al. 40 article to

explain the role cytokines may have played in a vaccine-induced, pathological, immune response

37

See Y. Hacohen, et al., supra note 32, at 1.

38

See id.

39

S. von Spiczak, et al., A retrospective population-based study on seizures related to childhood

vaccination, 52(8) EPILEPSIA 1506–12 (2011).

40

Y. Kashiwagi, et al., Production of inflammatory cytokines in response to diphtheria-pertussis-tetanus

(DPT), haemophilus influenzae type b (Hib), and 7-valent pneumococcal (PCV7) vaccines, 10(3) HUMAN

VACCINES & IMMUNOTHERAPEUTICS 677–85 (2014).

24

in this case. Resp’t’s Ex. E at 11; Pet’r’s Ex. 102, ECF No. 115. Cytokine levels, Dr. Wiznitzer

asserted, peak approximately 24 hours post vaccination, and return to baseline within three days.

Resp’t’s Ex. E at 11. D.J.W.’s first known seizure occurred seven days post vaccination, well after

this three-day period. Id. Dr. Wiznitzer maintained the article, therefore, “does not show that any

elevation [of cytokines] in humans would be high enough to cross the blood brain barrier and enter

the brain,” during that relevant post-vaccination, one-week time period in D.J.W.’s case. Id.

d. Autism and Epilepsy

Dr. Holmes explained that “[a] common biological mechanism for childhood epilepsy and

comorbid ASD is suggested from their overlapping prevalence, which include subgroups of

epilepsy and autism genes that have similar phenotypic manifestations and biological functions.”

Resp’t’s Ex. D at 2. Dr. Holmes noted the “known association of ASD with epilepsy for over fifty

years, with the prevalence of epilepsy in ASD in some studies reaching almost 50%.” Id.; Resp’t’s

Ex. D2 at 1. 41 He cautioned that “[t]he high comorbidity rate between ASD and epilepsy and EEG

epileptiform activity does not mean that there is a causal relationship between the conditions.”

Resp’t’s Ex. D at 2. Furthermore, “[s]eizure frequency is not associated with ASD, suggesting that

treating seizures does not prevent ASD from emerging.” Id.

Dr. Wiznitzer filed literature in support of the connection between ASD and epilepsy. He

asserted that there is a known association between ASD and Doose syndrome and referred to the

Routier et al. 42 and Tang et al. 43 articles for the premise that “the ASD diagnosis may be related to

the developmental impact of the genetic causation beyond the effect of seizures and/or excessive

epileptiform activity.” Resp’t’s Ex. E at 9; Resp’t’s Exs. E3, E6, ECF No. 124. The Routier et al.

article identified “four strong candidate genes [that] have already been linked to [ASD],

[intellectual disability,] and neurodegenerative brain disease.” Resp’t’s Ex. E3 at 6. The authors

concluded that “all patients with epilepsy genes or genes reported in neurodevelopment disorders

showed [intellectual disability] and some presented later [with] ASD.” Id. They determined that

“this higher incidence of [intellectual disability] and ASD compared to the group with no identified

genes might be related to the direct developmental impact of these genes beyond seizures and EEG

impact.” Id.

Dr. Wiznitzer concluded that ASD also has a genetic cause because of its relationship to

Doose syndrome. Resp’t’s Ex. E at 9. The Tang et al. authors found that “[intellectual disability],

ASD, and epilepsy share causative genes and biological pathways including gene transcription

regulation, neurotransmission, and maintenance of synaptic structure.” Resp’t’s Ex. E6 at 10. They

continued that “[t]hese neurodevelopmental comorbidities may be a primary feature of the genetic

disease rather than secondary to [the] disturbance of brain function due to excessive epileptiform

activity (an epileptic encephalopathy).” Id.

41

A.W. Buckley & G.L. Holmes, supra note 24.

42

L. Routier, et al., Exome sequencing findings in 27 patients with myoclonic-atonic epilepsy: Is there a

major genetic factor? 96 CLIN. GEN. 254–60 (2019).

43

S. Tang, et al., Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures, 61 EPILEPSIA

995–1007 (2020).

25

VI. Analysis

A. D.J.W.’s Diagnoses

As a factual predicate to proving vaccine-causation, it is each petitioner’s burden to

demonstrate by a preponderant standard that the subject of the claim actually suffers from the

injury alleged to have been caused by the identified vaccination(s). See Hibbard v. Sec’y of Health

& Hum. Servs., 698 F.3d 1358, 1364–65 (Fed. Cir. 2012); Lombardi v. Sec’y of Health & Hum.

Servs., 656 F.3d 1343, 1353 (Fed. Cir. 2011); Broekelschen v. Sec’y of Health & Hum. Servs., 618

F.3d 1339, 1346 (Fed. Cir. 2010). D.J.W’s diagnoses are in dispute not only between the parties

in this case, but also between D.J.W.’s treaters and Petitioner’s own expert. Although the various

conditions asserted by medical professionals in this case may “present with many of the same

symptoms, their underlying causes are different and require different treatments.” See

Broekelschen, 618 F.3d at 1344. To decide if Petitioner is entitled to damages, “it [i]s appropriate

in this case—where virtually all of the evidence on causation [i]s dependent on the diagnosis of

[D.J.W.’s] condition—for [me] to determine the proper diagnosis before applying the Althen test.”

Id.; Althen v. Sec’y of the Dept. of Health & Hum. Servs, 418 F.3d 1274, 1278–79 (Fed. Cir. 2005).

Petitioner has alleged D.J.W. suffered from vaccine-caused epileptic encephalopathy and

developmental delay. Furthermore, she connects the two injuries by asserting that there is a linear

sequence of events from vaccination to seizures to delay.

There is no dispute that D.J.W. suffers from an epileptic encephalopathy. Petitioner alleges

that this encephalopathy is the cause of D.J.W.’s developmental delay. D.J.W. has also been

diagnosed with ASD. Petitioner’s expert asserts that D.J.W.’s ASD was misdiagnosed, and all of

his symptoms are explained by Doose syndrome. In her filings, Petitioner asserts that any autism

diagnosis is unrelated to her claim and D.J.W.’s alleged vaccine-caused injuries. Respondent

alleges that D.J.W.’s autism is the cause of the developmental delay. Respondent further asserts

that Doose syndrome does not account for all of D.J.W.’s symptoms and as the two conditions are

comorbidities, D.J.W. suffers from both ASD and Doose syndrome.

i. Autism Spectrum Disorder

D.J.W. was diagnosed with autism on May 22, 2019, by licensed clinical psychologist Dr.

Carrie Silver. He was referred to Dr. Silver by his treating developmental behavioral pediatrician

Dr. Nayfack. Dr. Silver opined that “[g]iven the full picture and review of available data, it is

determined that [D.J.W.] does meet medical diagnostic criteria for an Autism Spectrum Disorder.”

Pet’r’s Ex. 87 at 7. Furthermore, D.J.W.’s most recently filed medical records from a March of

2020 encounter with Dr. Nayfack note that “[t]esting confirmed moderate [intellectual disability]

and autism.” Pet’r’s Ex. 109 at 27. An additional record from a November 9, 2021 evaluation with

pediatric neurologist Dr. Jane MacLean lists epileptic encephalopathy, intellectual disability, and

autism spectrum disorder in D.J.W.’s past medical history. Pet’r’s Ex. 108 at 59. Dr. Shafrir

presents robust arguments that D.J.W. does not suffer from autism, but from an autistic-like delay

as a result of his epileptic encephalopathy. However, D.J.W.’s treaters have experience in

diagnosing and treating autism. Furthermore, they have access to his medical and school records

26

and his family and medical histories. Lastly, their interactions with D.J.W. over a period of several

years allow them to accurately diagnosis and treat his conditions.

The benefit of seeing a patient in person in addition to reviewing medical records cannot

be overstated. 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

v. Sec’y of Health & Hum. Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993)). 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). However, there is no presumption that medical records are accurate

and complete as to all the patient’s physical conditions. Kirby, 997 F.3d at 1383 (citing Cucuras,

993 F.2d at 1528). Contemporaneous medical records are generally found to be deserving of

greater evidentiary weight than oral testimony — especially where such testimony conflicts with

the record evidence. Cucuras, 993 F.2d at 1528; see also Murphy v. Sec’y of Health & Hum. Servs.,

23 Cl. Ct. 726, 733 (1991), aff’d per curiam, 968 F.2d 1226 (Fed. Cir. 1992), cert. denied, 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.”)); Althen, 418 F.3d at 1278, 1280; Andreu v.

Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1375–77 (Fed. Cir. 2009); Capizzano v. Sec’y of

Health & Hum. Servs., 440 F.3d 1317, 1326 (Fed. Cir. 2006) (“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.’”). 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. § 13(b)(1) (providing that

“[a]ny such diagnosis, conclusion, judgment, test result, report, or summary shall not be binding

on the special master or court”); Snyder v. Sec’y of Health & Hum. Servs., 88 Fed. Cl. 706, 746

n.67 (2009) (“there is nothing . . . that mandates that the testimony of a treating physician is

sacrosanct — that it must be accepted in its entirety and cannot be rebutted.”). Rather, special

masters must consider the entire record. § 13(b)(1).

Dr. Silver’s examination and ultimate opinion concerning D.J.W.’s autism diagnosis is the

result of behavioral evidence consistent with parental and treating physician suspicions. Despite

D.J.W.’s simultaneous epileptic encephalopathy diagnosis, his current treaters separately

recognize his autism diagnosis as reflected in his most current medical history. The experts in this

case have presented evidence in support of their respective positions that is probative. However,

Dr. Shafrir’s position must be weighed against Dr. Silver’s first-hand diagnosis, Dr. Nayfack’s

agreement, Drs. Holmes’ and Wiznitzer’s opinions, and the medical literature filed in this case.

Considering the entire record, Petitioner has not established it more likely than not that D.J.W.’s

autism was misdiagnosis. Therefore, I find preponderant evidence the D.J.W. suffers from autism.

ii. Developmental Delay

27

To prevail on her claim that vaccinations caused D.J.W.’s developmental delay, Petitioner

has to establish by a preponderance of the evidence that epileptic encephalopathy is the cause-in-

fact, despite D.J.W.’s autism diagnosis. See, e.g., Cedillo v. Sec’y of Health & Hum. Servs., No.

98-916V, 2009 WL 331968 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d, 89 Fed. Cl. 158 (2009),

aff’d, 617 F.3d 1328 (Fed. Cir. 2010); Hazlehurst v. Sec’y of Health & Hum. Servs., No. 03-654V,

2009 WL 332306 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d, 88 Fed. Cl. 473 (2009), aff’d, 604

F.3d 1343 (Fed. Cir. 2010); Snyder v. Sec’y of Health & Hum. Servs., No. 01-162V, 2009 WL

332044 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d, 88 Fed. Cl. 706 (2009); Dwyer v. Sec’y of

Health & Hum. Servs., No. 03-1202V, 2010 WL 892250 (Fed. Cl. Spec. Mstr. Mar. 12, 2010);

King v. Sec’y of Health & Hum. Servs., No. 03-584V, 2010 WL 892296 (Fed. Cl. Spec. Mstr. Mar.

12, 2010); Mead v. Sec’y of Health & Hum. Servs., No. 03-215V, 2010 WL 892248 (Fed. Cl. Spec.

Mstr. Mar. 12, 2010) (rejecting the contention raised in the Omnibus Autism Proceedings that

vaccines can cause ASD); see also Cunningham v. Sec’y of Health & Hum. Servs., No. 13-483V,

2017 WL 1174448, at *4 (Fed. Cl. Spec. Mstr. Jan. 25, 2017) (rejecting Petitioner’s attempt to

separate a case alleging an autoimmune encephalopathy vaccine injury with other vaccine-autism

cases because by doing so, it would create a step between vaccination and the end result of autism,

simply to allow for compensation where other autism cases have failed); Bushnell v. Sec’y of

Health & Hum. Servs., No. 02-1648V, 2015 WL 4099824 (Fed. Cl. Spec. Mstr. June 12, 2015)

(rejecting Petitioner’s contention that neurotoxins contained in vaccines aggravated a minor child’s

mitochondrial disorder, resulting in a regressive encephalopathy manifesting as autism. The Court

rejected the characterization of ASD as an encephalopathy or any other injury in an attempt to

circumvent the binding effect of the Omnibus Autism Proceedings decision).

Although Petitioner now argues that the injuries alleged in the petition are solely related to

epileptic encephalopathy, she acknowledges that D.J.W. has been diagnosed with autism. Pet’r’s

Mem. at 11. During his testimony, her own expert, Dr. Shafrir, conflated the clinical progression

of D.J.W.’s autism with the increasing frequency and severity of his seizures. In fact, he was

vehement that D.J.W. did not suffer from autism but displayed autistic symptoms as a direct result

of the vaccine-induced seizures. Following D.J.W.’s diagnosis, Dr. Shafrir maintained his position

and asserted that D.J.W. was misdiagnosed. In this case, Petitioner’s expert’s opinions provide

some of the best evidence against her current argument.

Petitioner argues that she does not wish to recast her claim, but Dr. Shafrir’s opinion that

D.J.W. does not have autism is antithetical to D.J.W.’s current medical record. There is no way to

reconcile Petitioner’s current argument that D.J.W. suffers from “epileptic encephalopathy with

developmental delay” and “also me[ets] the medical criteria for ASD[,]” Pet’r’s Mem. at 11, with

Petitioner’s expert’s opinion that “[a]utism is not an additional independent diagnosis in a patient

who have [sic] already known severe progressive — regressive epileptic encephalopathy.” Tr.

150:13–15. In fact, Petitioner’s own tacit acknowledgement that D.J.W does have autism

contradicts Dr. Shafrir’s final report where he reiterates that D.J.W. does not have autism. He

asserts that D.J.W.’s “epileptic encephalopathy caused severe regression in all developmental

aspects, including cognitive . . . [and] produced, among other things, the appearance of multiple

autistic features.” Pet’r’s Ex. 88 at 45. Dr. Shafrir’s assertion that epileptic encephalopathy cannot

co-exist with autism contradicts much of the evidence, including, most notably, the filed literature.

28

Alternatively, the ASD diagnosis strengthens Dr. Holmes’ argument that Doose syndrome

does not explain D.J.W.’s behavioral and cognitive changes. Dr. Holmes opined that an individual

could suffer from a severe case of Doose syndrome with accompanying seizures (epileptic

encephalopathy) and a comorbid cognitive delay (autism). The Routier et al. 44 and Tang et al.45

articles provide support for the premise that “the ASD diagnosis may be related to the

developmental impact of the genetic causation beyond the effect of seizures and/or excessive

epileptiform activity.” Resp’t’s Ex. E at 9. The Routier et al. article concludes that “all patients

with epilepsy genes or genes reported in neurodevelopment disorders showed [intellectual

disability] and some presented later [with] ASD.” See Resp’t’s Ex. E3.

Dr. Shafrir’s testimony that D.J.W.’s autistic-like symptoms, which we now know to be

autism, are a result of a vaccination, is also counter to a long line of Program cases that hold,

without exception, that autism is not caused by vaccination. See Cedillo, 617 F.3d at 1328.

Petitioner argues that other claims have been allowed to proceed on an alternative theory that

encephalopathy caused intellectual disability following an autism diagnosis. Petitioner relies on a

case where there is a developmental delay that clearly occurs within a different timeframe from

the seizure activity. Pet’r’s Mem. at 11; Wright, 2015 WL 6665600, at *98. She cites a case

wherein the claimant never alleges developmental delay as the injury caused by vaccination.46

Pet’r’s Mem. at 13–14; Moriarty v. Sec'y of Health & Hum. Servs., 844 F.3d 1322, 1324 (Fed. Cir.

2016). She also cites a case with clear evidence of encephalitis. Pet’r’s Mem. at 16; Mojabi v.

Sec’y of Health & Hum. Servs., No. 06-227V, 2012 WL 6869685 (Fed. Cl. Spec. Mstr. Dec. 13,

2012). All of those cases are distinguishable from the facts here. The cases Petitioner relies on that

were successful did not present evidence of autism symptoms that could not be parsed from those

of encephalopathy. That is, however, precisely what Petitioner did in this case. In her reply to

Respondent, Petitioner asserts “there is no dispute that D.J.W. developed epileptic encephalopathy,

or unremitting epileptic activity that contributed to his severe and rapid cognitive and behavioral

impairments, after his vaccination.” Pet’r’s Reply at 3. In the next paragraph, Petitioner asserts

that “[t]he court is not required to find that D.J.W.’s subsequent diagnosis of autism was or was

not caused by the vaccination.” Id.

Petitioner has made it clear since sharing her initial concern of D.J.W.’s developmental

delay with his physicians that the seizures and the regression occurred simultaneously. She has

consistently argued that D.J.W.’s seizure activity and delay were both the result of his vaccination.

Her current argument is that D.J.W.’s developmental delays resulted from seizures, which were

unrelated to his autism diagnosis. She does not explicitly reject Dr. Shafrir’s opinion that D.J.W.

was misdiagnosed. It is unclear, however, whether Petitioner agrees with Dr. Shafrir that D.J.W.

does not actually have ASD. She does not provide a legal argument to overcome the autism rulings

that rejected the argument that developmental delay can be both a manifestation of an autism

diagnosis and, independently, a result of vaccination. Indeed, this argument is not asserted in the

successful cases she cites for support. See Pet’r’s Mem. at 11–16. Further discussion of these cases

highlight why they are distinguishable.

44

See L. Routier, et al., supra note 42.

45

See S. Tang, et al., supra note 43.

46

In the present case, Petitioner raised a possible significant aggravation claim in her petition, but that was

never pursued. Petitioner’s most recent post hearing filing alleges only causation-in-fact.

29

Petitioner cites to the Wright case as an example of a successful claim involving a child

with autism who suffered from vaccine-caused encephalopathy. The child in that case suffered

from a seizure within hours of vaccination and the encephalopathy fit within the criteria for a Table

injury. Wright, 2015 WL 6665600, at *98. In this case, the time lapse of seven days between

D.J.W.’s vaccination and seizure precludes any claim based on a Table injury. See, e.g., Adams ex

rel. Adams v. Sec’y of Health & Hum. Servs., 76 Fed. Cl. 23, 41 (2007) (finding an infant who

developed a febrile seizure within 24 hours of receiving a pneumococcal vaccination was entitled

to compensation); Tembenis ex rel. estate of Tembenis v. Sec’y of Health & Hum. Servs., No. 03-

2820V, 2010 WL 5164324, at *1, 2, 4, 15 (Fed. Cl. Spec. Mstr. Nov. 29, 2010) (finding a vaccinee

who developed a fever and seizures within 12 hours of receiving a DTaP vaccination was entitled

to compensation); Teller v. Sec’y of Health & Hum. Servs., No. 06-804V, 2009 WL 255622, at *2,

5 (Fed. Cl. Spec. Mstr. Jan. 13, 2009) (finding a vaccinee who developed a fever and seizures

within 4 hours of receiving DTaP-IPV, Hepatitis B, pneumococcal, and Hib vaccinations was

entitled to compensation); Simon v. Sec’y of Health & Hum. Servs., No. 05-941V, 2007 WL

1772062, at *2, 25 (Fed. Cl. Spec. Mstr. June 1, 2007) (finding a vaccinee who developed a fever

and seizures within 12 hours of receiving a DTaP vaccination was entitled to compensation).

Petitioner also refers to Moriarty to argue that she can successfully bring a claim alleging

an encephalopathy despite a comorbid autism diagnosis. Moriarty v. Sec’y of Health & Hum.

Servs., 130 Fed. Cl. 573 (2017). Petitioner discusses this case in some detail, but she fails to

mention several significant distinguishing factors. Most importantly, in Moriarty, the child had

already exhibited “problems with her gross motor skills and language development and was

diagnosed with hypotonia and developmental delay” prior to the MMR vaccination at issue. See

Moriarty, 844 F.3d at 1324. Petitioners in that case were able to cleanly differentiate between the

developmental delay that their child had pre vaccination and the seizures that occurred post

vaccination. This distinction was also evidenced by the successful treatment of the seizures with a

ketogenic diet in that case, despite the continued developmental delay, i.e., autism. Id. at 1325. In

the present case, D.J.W.’s seizures continued with “a grand mal seizure every week, and drop

seizures up to 10–15 times a day as well as absence seizures daily,” despite a ketogenic diet. Pet.

at 8. The continued seizures were accompanied by “issues with learning.” Id.

The nature of the seizures in Moriarty is also distinguishable from that in this case, and

there is evidence that some treaters in Moriarty documented a belief that the MMR vaccination

was to blame for the seizures. Moriarty, 130 Fed. Cl. at 576. All of these factors are evidence that

the seizures in that case were not necessarily attributed to the child’s autism. This is also evidenced

by the petition itself. Petitioners in Moriarty alleged a seizure disorder and encephalopathy as the

injury, but they did not include developmental delay. In the present case, Petitioner maintains that

the autism diagnosis is separate from the encephalopathy, but she continues to assert that D.J.W.’s

developmental delay is a vaccine-caused injury and not a result of his autism. Moriarty is not

analogous to the present case and does not provide support for Petitioner’s claim that D.J.W.’s

autism diagnosis is separate from his encephalopathy.

The last case that Petitioner cites involves a child with encephalitis. Mojabi, 2012 WL

6869685, at *1. There is no evidence in this case that D.J.W. was diagnosed with encephalitis, and

Dr. Shafrir did not go as far as asserting that during his testimony. When asked what type of

autoimmune encephalitis is present in this case, Dr. Shafrir responded that D.J.W. has

30

“autoimmune epilepsy. You can call it — so autoimmune encephalitis and autoimmune epilepsy

can be both called autoimmune encephalopathy.” Tr. 136:8–10. He would not say that all three

conditions could be used interchangeably and clarified that, “I think we can use more accurately

autoimmune — auto — well, I mean, you can say that [he] have [sic] autoimmune epileptic

encephalopathy. I think that[ is] the best way we can describe it.” Tr. 136:12–15.

Petitioner asserts that vaccinations caused or contributed to her child’s developmental

delay, despite his autism diagnosis. Dr. Shafrir stated repeatedly that D.J.W.’s developmental

delay was a result of encephalopathy, and he does not have autism. Respondent’s experts have

explained, with supporting literature, that ASD and epileptic encephalopathy are comorbidities in

the absence of vaccination. D.J.W.’s medical record is consistent with the explanations provided

by Drs. Holmes and Wiznitzer. After considering the complete record, including Petitioner’s

pleadings, medical records, expert reports and testimony, and medical literature, 47 I do not find

preponderant evidence that D.J.W.’s developmental delay can be separated from his autism

diagnosis. Therefore, I do not find that Petitioner has identified developmental delay as an

actionable vaccine-caused injury in this case.

iii. Epileptic Encephalopathy

Although Petitioner alleges a linear causation theory that links D.J.W.’s vaccine to his

developmental delay via seizures, she also identifies epileptic encephalopathy as an actionable

injury. Petitioner originally asserted that D.J.W.’s vaccination initiated an autoimmune response

that resulted in seizures and ultimately epileptic encephalopathy, without regard for autism.

Petitioner asserts and is correct that D.J.W.’s encephalopathy is not in dispute. There is

disagreement, however, “on whether this can be caused by vaccination through an autoimmune

process.” Pet’r’s Reply at 3. Therefore, Petitioner does have a viable claim based on epileptic

encephalopathy, and my analysis will continue based on this injury. The entitlement hearing was

conducted under the same premise.

B. Applicable Legal Standards

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

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

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

causation is presumed.” Capizzano, 440 F.3d at 1320 ; see § 13(a)(1)(B). Second, where the alleged

47

While I have reviewed all of the information filed in this case, only those filings, records, and testimony

that are most relevant to the decision are discussed. Moriarty v. Sec'y of Health & Hum. Servs., 844 F.3d

1322, 1328 (Fed. Cir. 2016) (“[w]e generally presume that a special master considered the relevant record

evidence even though he does not explicitly reference such evidence in his decision.”) (citation omitted);

see also Paterek v. Sec'y of Health & Hum. Servs., 527 F. App'x 875, 884 (Fed. Cir. 2013) (“[f]inding

certain information not relevant does not lead to—and likely undermines—the conclusion that it was not

considered.”).

31

injury is not listed in the Vaccine Injury Table, a petitioner may demonstrate that she suffered an

“off-Table” injury. § 11(c)(1)(C)(ii). Petitioner does not assert a Table claim in this case.

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

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

in Althen. Althen requires that a petitioner establish by preponderant evidence that the vaccinations

she received caused her injury “by providing: (1) a medical theory causally connecting the

vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination

was the reason for the injury; and (3) a showing of a proximate temporal relationship between

vaccination and injury.” 418 F.3d at 1278.

Each of the Althen prongs requires a different showing. Under Althen prong one, petitioners

must provide a “reputable medical theory,” demonstrating that the vaccine received can cause the

type of injury alleged. Pafford v. Sec’y of Health & Hum. Servs., 451 F.3d 1352, 1355 (Fed. Cir.

2006) (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). Such a theory must only be “legally probable, not medically or

scientifically certain.” Knudsen, 35 F.3d at 549.

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.” Andreu, 569 F.3d 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). But this

does not negate or reduce a petitioner’s ultimate burden to establish her overall entitlement to

damages by preponderant evidence. W.C. v. Sec’y of Health & Hum. Servs., 704 F.3d 1352, 1356

(Fed. Cir. 2013) (citations omitted).

Establishing a sound and reliable medical theory connecting the vaccine to the injury often

requires a petitioner to present expert testimony in support of her claim. Lampe v. Sec’y of Health

& Hum. Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). The Supreme Court’s opinion in Daubert

v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993), requires that courts determine the

reliability of an expert opinion before it may be considered as evidence. “In short, the requirement

that an expert’s testimony pertain to ‘scientific knowledge’ establishes a standard of evidentiary

reliability.” Id. at 590 (citation omitted). Thus, for Vaccine Act claims, a “special master is entitled

to require some indicia of reliability to support the assertion of the expert witness.” Moberly v.

Sec’y of Health & Hum. Servs., 592 F.3d 1315, 1324 (Fed. Cir. 2010). The Daubert factors are

used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec’y of Health &

Hum. Servs., 94 Fed. Cl. 53, 66–67 (2010) (emphasis in original) (“[U]niquely 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.”).

Under Daubert, the 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

32

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 ex rel.

Terran v. Sec’y of Health & Hum. Servs., 195 F.3d 1302, 1316 n.2 (Fed. Cir. 1999) (citing

Daubert, 509 U.S. at 592–95). 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)).

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. 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). de Bazan, 539 F.3d at 1352; Shapiro

v. Sec’y of Health & Hum. Servs., 101 Fed. Cl. 532, 542 (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);

Koehn v. Sec’y of Health & Hum. Servs., No. 11-355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr.

May 30, 2013), mot. for review denied (Fed. Cl. 2013), aff’d, 773 F.3d 1239 (Fed. Cir. 2014). The

special master cannot infer causation from temporal proximity alone. See Thibaudeau v. Sec'y of

Health & Hum. Servs., 24 Cl. Ct. 400, 403–04 (1991); see also Grant v. Sec'y of Health & Hum.

Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992).

C. Althen Discussion

i. General Causation Theory (Althen prong one)

Dr. Shafrir wrote that “[t]he only mechanism by which vaccines can cause neurological

symptoms is through activation of the immune system.” Pet’r’s Ex. 58 at 6. Both experts testified

that D.J.W.’s condition was an atypical presentation of Doose syndrome, but Dr. Shafrir did not

present persuasive evidence of an autoimmune etiology. Dr. Shafrir’s discussion of encephalitis

gave a very clear example of an autoimmune process, but he was unable to connect that mechanism

with his theory in this case. Dr. Shafrir also confirmed that Doose syndrome is not autoimmune

encephalitis. Given the severe and acute nature of autoimmune encephalitis, its treatment course,

and clear markers for diagnosis, Dr. Shafrir did not persuasively explain why a discussion of

autoimmune encephalitis is instructive in this case.

During his testimony Dr. Shafrir made a passing reference to several different mechanisms,

including bystander activation and epitope spread, but stated that molecular mimicry “is definitely

a solid place to start.” Tr. 107:16–17. To explain molecular mimicry, he embarked upon a

meandering discussion about narcolepsy, adjuvants, and the whole cell pertussis vaccine. See Tr.

94–138. That testimony was tortuous and unhelpful to the facts and arguments in this case.

33

Therefore, it is not recounted in the summary of Dr. Shafrir’s opinion. In short, the whole cell

pertussis vaccine is no longer administered in the United States, and causation theories based on

the enhanced immune response produced by adjuvants have been largely unsuccessful in the

Program. See, e.g., Decker v. Sec’y of Health & Hum. Servs., No. 15-017V, 2020 WL 7889059, at

*32 (Fed. Cl. Spec. Mstr. Dec. 14, 2020) (reiterating that “[aluminum adjuvant induced

autoimmunity (“ASIA”)] is a theory that has been unsuccessfully argued [] in several previous

[P]rogram cases.”). Lastly, while there is substantial evidence that narcolepsy may be an

autoimmune disease, Dr. Shafrir, as with his encephalitis reference, did not present evidence that

narcolepsy is analogous to Doose syndrome. I, and other special masters, have repeatedly warned

petitioners that the mere mention of molecular mimicry is not a “get out of jail free card” in the

Program, entitling claimants to compensation, merely because it has scientific reliability as a

general matter. Johnson v. Sec’y of Health & Hum. Servs., No. 14-254V, 2018 WL 2051760, at

*26 (Fed. Cl. Spec. Mstr. Mar. 23, 2018) (“Petitioners cannot simply invoke the concept of

molecular mimicry and call it a day . . . . Rather, they need to offer reliable and persuasive medical

or scientific evidence of some kind . . . that suggests the vaccine components could interact with

self-structures as maintained.”); see also Haubner v. Sec’y of Health & Hum. Servs., No. 16-

1426V, 2021 WL 5614942, at *32 (Fed. Cl. Spec. Mstr. Oct. 22, 2021); Sheets v. Sec’y of Health

& Hum. Servs., No. 16-1173V, 2019 WL 2296212, at *17 (Fed. Cl. Spec. Mstr. Apr. 30, 2019).

This reasoning holds true for all biological mechanisms that are routinely presented in the Program.

Dr. Shafrir’s explanations of bystander activation and epitope spread were also superficial

and do not connect specifically to Doose syndrome. Petitioners are not required to identify specific

biological mechanisms to establish causation. Indeed, scientific and “objective confirmation” of

the medical theory with additional medical documentation is unnecessary. Althen, 418 F.3d at

1278–81; see also Moberly, 592 F.3d at 1322. However, as the Federal Circuit has made clear,

“simply identifying a ‘plausible’ theory of causation is insufficient for a petitioner to meet her

burden of proof.” LaLonde v. Sec’y of Health & Hum. Servs., 746 F.3d 1334, 1339 (Fed. Cir. 2014)

(citing Moberly, 592 F.3d at 1322). Rather, “[a] petitioner must provide a reputable medical or

scientific explanation that pertains specifically to the petitioner’s case.” Moberly, 592 F.3d at 1322.

Dr. Shafrir relied extensively and repeatedly on the Sirsi et al.48 article to provide support

for an autoimmune etiology for Doose syndrome. See Pet’r’s Ex. 77. Dr. Holmes did not dispute

that VGKC autoimmunity was a plausible pathogenesis for MAE; however, the Sirsi et al. article

makes no mention of vaccination as a catalyst for the body’s production of the relevant

autoantibodies. Furthermore, those authors noted cases of multiple different intractable pediatric

epilepsy syndromes, but there were no cases of VGKC antibody mediated epilepsy presenting as

MAE. See id. The authors also conceded that unlike other pediatric epilepsies, the etiology for

MAE is presumed to be genetic. Id. Dr. Shafrir, on the other hand, testified emphatically that Doose

syndrome does not have a genetic etiology, but even the medical literature that he filed belies that

assertion. See id.; see also Pet’r’s Ex. 61. 49 Dr. Shafrir conceded during his testimony that the

medical community has not generally accepted Doose syndrome as an autoimmune disease. Tr.

137:16–18. While the mechanism described in the Sirsi et al. article is currently a viable thought

experiment, that is not the standard for establishing causation in Program cases. See Pet’r’s Ex. 77.

The authors themselves stopped short of identifying their proposed mechanism as causative and

48

See D. Sirsi, et al., supra note 29.

49

See M. Trivisano, et al., supra note 35.

34

suggested that further research is warranted. See id. Even assuming arguendo that the articulation

of such a mechanism is sound and reliable, it is incomplete. Dr. Shafrir has not explained how

vaccines fit into this immune process. His opinion that vaccines could be the catalyst for an

untested, never-before-seen autoimmune etiology for a presumed genetic epileptic encephalopathy

is speculative at best.

Petitioner’s theory also includes a passing reference to increased cytokine production with

a disclaimer that this type of mechanism is hard to study and understand. Dr. Shafrir asserted that

“the persistence of the epileptic encephalopathy can be explained by several mechanisms including

epitope spread and persistence of autoimmune activity with cellular or humoral autoimmune

activity against adjacent proteins.” See Pet’r’s Ex. 88 at 39. This conclusion is an overbroad list of

complex immune processes and concepts without relation to the specific characteristics of

encephalopathy generally, or Doose syndrome specifically. Dr. Shafrir has not answered the

question of how epitope spread is causal here. He did not explain how the different processes of

cellular and humoral autoimmune activity interact during the pathogenesis of Doose syndrome

post vaccination. There is no answer to the question, “can the DTaP vaccine cause Doose

syndrome?” Evaluation of Petitioner’s biological mechanism pursuant to the Daubert factors lays

bare the theory’s deficiencies. The theory, as best articulated in the Sirsi et al. article, has not been

tested, and therefore, there is no known error rate or method to control error. Furthermore, the

theory (VGKC autoimmunity in MAE) or even the premise (MAE has an autoimmune etiology)

is not generally accepted by the relevant medical community.

Dr. Wiznitzer’s discussion of the von Spiczak et al.50 article, which illustrates that patients

are not more likely to develop epilepsy post DTaP vaccination even if they experience a seizure

shortly thereafter, is also persuasive evidence. See Pet’r’s Ex. 29. Studies that establish or negate

vaccine causation are extremely rare and not required in the Program. However, to the extent that

studies have been done to analyze statistically significant cases of injury post vaccination, they are

probative. It is worth noting that the von Spiczak et al. article is not significant in a vacuum. It is

consistent with other submitted evidence that Doose syndrome is not an autoimmune disease and

thus would be unlikely to result from vaccination via Petitioner’s proposed mechanism. In sum,

Petitioner has not presented preponderant evidence that a DTaP vaccination can cause Doose

syndrome via his proposed biological mechanism. She has not met her burden pursuant to Althen

prong one.

ii. Logical Sequence of Cause and Effect (Althen prong two)

Dr. Shafrir’s asserted biological mechanism begins with the premise that D.J.W.

experienced an abnormal reaction to his fifth DTaP vaccination, resulting in “an immune attack

on protein components of his brain.” Pet’r’s Ex. 88 at 39. The applicability of Petitioner’s causation

theory to the present case therefore hinges on an autoimmune etiology for D.J.W.’s Doose

syndrome. D.J.W.’s current treatment is not indicative of an autoimmune disease. Dr. Shafrir even

acknowledged that there was no evidence in D.J.W.’s medical record of general autoimmunity. Tr.

223:5–6. I am not persuaded by Dr. Shafrir’s heavy reliance on D.J.W.’s treaters’ initial

consideration of an autoimmune process, given the ultimate diagnosis and treatment regimen.

D.J.W. underwent cursory testing for an autoimmune etiology that did not yield definitive results.

50

See S. von Spiczak, et al., supra note 39.

35

D.J.W.’s treatment course of a single round of IVIG for autoimmune seizure activity was

ineffective and discontinued. Dr. Shafrir noted that Petitioner refused further IVIG treatment, but

the record does not reflect a concern from D.J.W.’s treaters that this directive significantly

hindered D.J.W’s treatment. While it is reasonable, given D.J.W.’s presentation, that medical

providers would initially administer IVIG, the cessation of this treatment without concern from

treaters is significant. Furthermore, as stated previously, Petitioner has not presented preponderant

evidence that Doose syndrome can ever result from vaccination.

Alternatively, Dr. Holmes opined that D.J.W.’s specific epileptic encephalopathy, Doose

syndrome, is an inherent condition. He further explained that there is no evidence of an

autoimmune etiology in this case and described what he would look for to diagnose a patient with

autoimmune seizure activity. Dr. Holmes identified several symptoms, including amnesia,

confusion, seizures and psychiatric features, a more generalized encephalopathy with a movement

disorder, MRI changes, and early EEG abnormalities. None of these additional factors were

present in D.J.W.’s case. Dr. Holmes’ use of case studies and other medical literature for support

also increases the credibility of his opinion. In particular, the literature that explains how the

medical community has come to believe that Doose syndrome has a genetic etiology, is persuasive.

See, e.g., Resp’t’s Ex. E7. 51 Dr. Holmes presented persuasive medical literature from Doose

himself to support his testimony that Doose syndrome is a multifactorial, genetic condition. See

Pet’r’s Ex. 63. Therefore, Petitioner has failed to establish by preponderant evidence that D.J.W.’s

epileptic encephalopathy has an autoimmune etiology. This, by Dr. Shafrir’s explicit admission,

is a necessary condition for Petitioner’s suggested biological mechanism of injury. Therefore, I

find Petitioner has failed to establish by a preponderant standard that the vaccine causation theory

presented is relevant to the injury suffered by D.J.W. Petitioner has not met her burden pursuant

to Althen prong two.

iii. Timing (Althen prong three)

Petitioner has failed to meet her burden with respect to Althen prong one. This makes it

difficult to determine an appropriate temporal relationship between vaccination and the alleged

injury pursuant to prong three. In this case, however, Dr. Shafrir stated that the seven-day period

between D.J.W.’s DTaP vaccination and his first seizure is compelling. Respondent’s experts

noted the same short interval as temporally proximate. However, as it has been settled in the

Program, a temporal relationship alone is not sufficient to establish causation. However, I find that

Petitioner’s assertion that a seven-day-interval would be sufficient time for an adaptive immune

response to develop post-vaccination to be appropriate. I find that Petitioner has therefore satisfied

her burden with respect to Althen prong three, to the extent that an autoimmune process could

develop within that time.

VII. Conclusion

Petitioner and her son have both been through immeasurable suffering and uncertainty

since this case was filed. The delay in clarifying his diagnosis, as well as other logistical and

administrative delays, have undoubtedly added to the stress. In the Program, the multifactorial

pathogenesis of many of the diseases that we see is frustrating and can be difficult for us to

51

See H. Oguni, supra note 27.

36

understand. That is why the expert opinions and supporting medical literature are so important in

helping me reach a decision. After a careful consideration of all the filed evidence in the record

(medical records, expert reports, and medical literature), along with the presented testimony, I find

that Petitioner has had an opportunity to present the case that D.J.W. developed a vaccine-caused,

autoimmune encephalopathy. This evidence was not submitted in contemplation of an autism

diagnosis (as Petitioner requested), and Petitioner had the opportunity to present her complete

argument at a hearing. This opportunity is further evinced by the fact that Petitioner’s expert did

not change his position at any point, including after the hearing, D.J.W.’s autism diagnosis, and

Respondent’s post-hearing expert opinions. Special masters possess discretion to decide whether

an evidentiary hearing will be held. 42 U.S.C. § 300aa-12(d)(3)(B)(v) (promulgated as Vaccine

Rule 8(c) & (d)); Kreizenbeck v. Sec’y of Health & Hum. Servs., 945 F.3d 1362, 1365 (Fed. Cir.

2018). Given Petitioner’s opportunity to present expert evidence pre hearing, at hearing, and post

hearing, I do not find an additional hearing is needed, largely due to Dr. Shafrir’s assertion that

D.J.W.’s autism was misdiagnosed and is therefore inconsequential. Based on the record in this

case, Petitioner has failed to present preponderant evidence that D.J.W.’s autism exists

independently from his epileptic encephalopathy, or that his encephalopathy has an autoimmune

pathogenesis and can therefore be vaccine-caused. I do not find that additional evidence would be

able to overcome the evidence already in the record on those two points. Accordingly, Petitioner

has failed to establish entitlement to compensation and her claim is hereby DISMISSED. The

Clerk of Court shall enter judgment accordingly.52

IT IS SO ORDERED.

s/Herbrina D. Sanders

Herbrina D. Sanders

Special Master

52

Pursuant to Vaccine Rule 11(a), entry of judgment is expedited by the parties’ joint filing of a notice

renouncing the right to seek review.

37