Court Opinion

ID: 4377785
Source: CourtListenerOpinion
Date Created: 2019-03-15 20:01:49.680464+00
Date Added: 2024-06-11T14:22:05.597647
License: Public Domain

In the United States Court of Federal Claims
                                     OFFICE OF SPECIAL MASTERS
                                               No. 14-65V
                                            (to be published)

*************************
HEIDI SHARPE, as legal representative *                                   Special Master Corcoran
of her minor child, L.M.,             *
                                      *
                                      *                                   Filed: November 5, 2018
                      Petitioner,     *
                                      *                                   Diptheria-Tetanus-Acellular
               v.                     *                                   Pertussis (“DTaP”) Vaccine;
                                      *                                   DYNC1H1 Mutation; Significant
SECRETARY OF HEALTH AND               *                                   Aggravation; Encephalopathy.
HUMAN SERVICES,                       *
                                      *
                      Respondent.     *
                                      *
*************************

Curtis Webb, Twin Falls, ID, for Petitioner.

Amy Kokot, U.S. Dep’t of Justice, Washington, DC, for Respondent.

                                        ENTITLEMENT DECISION1
        Heidi Sharpe, as legal representative of her child, L.M., filed a petition on January 27,
2014, seeking compensation under the National Vaccine Injury Compensation Program (“Vaccine
Program”).2 Pet. at 1, ECF No. 1. In her petition, Ms. Sharpe alleged that the diphtheria-tetanus-
acellular pertussis (“DTaP”) and other vaccinations administered to L.M. on February 10, 2011,
caused L.M. to suffer: (1) a Table injury in which her underlying brain malformation/white matter
deficiency/other genetic mutation constituted an encephalopathy that was significantly aggravated

1
  This Decision will be posted on the United States Court of Federal Claims’ website in accordance with the E-
Government Act of 2002, 44 U.S.C. § 3501 (2012). This means the Decision will be available to anyone with access
to the internet. As provided by 42 U.S.C. § 300aa-12(d)(4)(B), however, the parties may object to the published
Decision’s inclusion of certain kinds of confidential information. Specifically, under Vaccine Rule 18(b), each party
has fourteen (14) days within which to request redaction “of any information furnished by that party: (1) that is a trade
secret or commercial or financial in substance and is privileged or confidential; or (2) that includes medical files or
similar files, the disclosure of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b).
Otherwise, the entire Decision will be available in its current form. Id.
2
 The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, 42 U.S.C. §§ 300aa-
10–34 (2012) (hereinafter “Vaccine Act” or “the Act”). Individual section references hereafter shall refer to § 300aa
of the Act.
by the DTaP vaccine, and/or (2) an off-Table injury resulting from the February 10th vaccines she
received significantly aggravating the same constellation of underlying conditions. Id. at 2.

        An entitlement hearing was held in this matter on March 13–14, 2018. For the reasons
stated in more detail below, I hereby DENY an award of damages in this case. Because it was
incontrovertibly demonstrated that L.M. possessed a genetic mutation associated with the
seizures/spasms disorder she was diagnosed with after vaccination, the success of Petitioner’s
claim turned on whether the vaccines L.M. received significantly aggravated the sequelae of that
mutation. But Petitioner did not successfully establish that the vaccines did so (or that they could
specifically worsen the expected course of an individual with the precise mutation possessed by
L.M.). Petitioner’s alternative Table claim of significant aggravation of a preexisting
“encephalopathy” also failed, because it relied on a legally untenable construction of the relevant
portions of that Table claim’s definitions.

I.       Factual Background

         Pre-Vaccination History

        L.M. was born at term on July 26, 2010. Ex. 1 at 5. At six months of age (and prior to her
February 10, 2011 vaccinations), her development, motor skills, and responsiveness were deemed
normal. Ex. 2 at 6. Her parents have also confirmed in witness statements that her overall
development was normal at this point, and that she seemed a healthy and happy baby. See, e.g.,
Ex. 12 at 2 (affidavit of Richard Moore, L.M.’s father). Prior to this time, L.M. had received several
childhood vaccines—Pediarix (DTaP, hepatitis B, and inactivated polio), haemophilus influenzae
type B, pneumococcal conjugate, and rotavirus—on two occasions (her two-month well-child visit
on September 20, 2010, and her next well-child evaluation on November 18, 2010) without
incident. Ex. 1 at 100–01, Ex. 2 at 4–5, 30.

        At a January 17, 2011 well-child visit, Petitioner informed L.M.’s pediatrician that L.M.
had developed symptoms of an upper respiratory infection (“URI”)3 and a rash; she was diagnosed
with a viral exanthema,4 but was otherwise deemed healthy. Ex. 2 at 6. Vaccinations that were
scheduled to be given at this time were postponed due to her illness. Id. at 7. The next day, Ms.
Sharpe brought L.M. to Central Montana Medical Center’s emergency room in Lewistown,
Montana, reporting “inconsolable crying” for one hour after leaving L.M. under the care of
Petitioner’s thirteen-year-old daughter, although her exam was normal. Ex. 3 at 8. Two weeks

3
  This record also states that Ms. Sharpe “took [L.M.] to [the] ER 2 days ago. Dx’d with [v]iral URI.” Ex. 2 at 6. The
filed medical records, however, do not document a January 15, 2011 ER visit. See, e.g., Ex. 3 at 1–2; Ex. 4 at 1 (listing
L.M.’s emergency room visits and hospital admissions).
4
 A disease featuring prominent skin eruptions or rashes. Dorland’s Illustrated Medical Dictionary 656 (32nd ed.
2012) (hereinafter “Dorland’s”).

                                                           2
later, in early February 2011, Petitioner brought L.M. to her pediatrician’s office with complaints
of congestion and “thick green nasal drainage for [six] weeks.” Ex. 2 at 8. L.M. was diagnosed
with congestion and received an antibiotic. Id.

       February 2011 Vaccinations and Alleged Reaction

        At about 4:00 pm on February 10, 2011, L.M. received another dose of Pediarix, plus the
ActHIB (HIB) and Prevnar (Pneumococcal Conjugate) vaccines. Ex. 2 at 30. By 7:00 pm that
evening, Petitioner purports, L.M. had developed a fever and became flushed and floppy. Ex. 11
at 3 (affidavit of Ms. Sharpe). The next day, Ms. Sharpe phoned L.M.’s pediatrician, Dr. Annette
Comes, and (consistent with her affidavit) reported that after vaccination, L.M. had “developed a
fever and [was] whimpery [and] wak[ing] up ‘screaming.’” Ex. 2 at 19. Petitioner specifically
observed that L.M. had not reacted to the vaccines she had received the prior fall. Id; see also Ex.
11 at 3. L.M.’s doctor proposed “that this [was] most likely not related to the injections,” and
attributed L.M.’s symptoms to a possible viral illness (also consistent with the medical record,
given what Petitioner reported to pediatricians less than two weeks before). Ex. 2 at 19. Petitioner
was instructed to administer alternating doses of ibuprofen and Tylenol, and to bring L.M. in for a
doctor’s visit the following Monday (February 14, 2011) if she did not appear to improve. Id.

        Ms. Sharpe contends that L.M. did not improve that weekend, but continued to run a high
fever and to display floppiness and an uncharacteristic disinterestedness. Ex. 11 at 4. She avers
that she thereafter called the ER twice about her concerns, but was rebuffed (id. at 4)—although
no records confirm these calls. See Ex. 74 at 17–18 (no calls from Ms. Sharpe to ER on February
12 or 13). On February 15, 2011, however, Petitioner brought L.M. to the ER, reporting that L.M.
had “suddenly become ‘stiff all over’ [and] unresponsive” after an episode lasting approximately
thirty seconds. Ex. 3 at 13.

         During that episode, L.M. had no fever or other identifiable URI symptoms. Ex. 3 at 13.
The record from this visit notes that L.M. had experienced a fever related to the vaccinations from
four days prior, but downplays the extent to which Petitioner at the time associated L.M.’s prior
illness with her presenting condition. See id. The record from this visit also reveals that Petitioner
reported to treaters at this time that the month before (January 2011) L.M. had similarly
experienced an “unexplained episode of sudden flaccidity [and] unresponsiveness” for
approximately thirty seconds, followed by several minutes of crying and irritability. Id. at 13.
L.M.’s temperature at the ER was 97.5 degrees Fahrenheit, she was alert and playful, and although
a “bit listless,” she displayed few other alarming clinical symptoms. Id. at 12–14. However, L.M.
was also noted to have “floppy” motor control and skills, poor head control, and “pupils that were
equal and reactive bilaterally.” Id. at 16.

                                                  3
        The afternoon of February 15th, L.M. had a second seizure event at 3:30 pm. Ex. 3 at 18.
A nurse observed L.M. to be “staring off into space” and unresponsive to touch or grasp. Id. At
this point, Dr. Comes contacted St. Vincent Hospital in Billings, Montana, to arrange L.M.’s
transfer, after noting that her unresponsiveness and listlessness could indicate a possible seizure.
Ex. 4 at 7; Ex. 13 at 18. That evening, L.M. was transferred to St. Vincent via ambulance, and
records from her admission suggest that EMTs detected an additional episode of tonic stiffening
as they prepared to effect the transfer. Ex. 4 at 3, 5. Upon arrival at St. Vincent, the admitting
physician noted that L.M. had been well “until about a month ago,” when episodes in which she
“blanked out” were first observed, along with head bobbing and eye crossing. Id. at 3. The history
from this initial record also notes that after L.M. was brought to the ER in Lewistown, she would
“not focus or track except briefly and mainly then only to the left,” and the initial assessment
expressed uncertainty as to whether L.M.’s condition was the product of seizures, sleepiness, or
the phenobarbital she had received just before being transferred to St. Vincent. Id. at 3–4.

        St. Vincent had a larger neurologic evaluating staff and better facilities than Central
Montana Medical Center, and L.M. there received a neurologic work-up the next day (February
16, 2011). The pediatric neurologist who saw L.M., Dr. Tarif Bakdash, confirmed in his intake
history that she had experienced three seizures in the last twenty-four hours, and that the third had
features resembling infantile spasms. Ex. 4 at 5. But that same record also characterized L.M. as
“being hypotonic or floppy” since birth, and noted a history of gastroesophageal reflux disease
(“GERD”). Id. Petitioner also informed Dr. Bakdash of L.M.’s two-day fever after vaccination,
but added that “a few days later she was fine.” Id. Dr. Bakdash’s neurologic exam noted that L.M.’s
reflexes were “one out of four,” and that she was “hypotonic throughout.” Id. at 6. His initial
impression was that L.M. was suffering from “generalized seizure pattern and infantile spasms.”
Id. Dr. Bakdash expressed his preliminary assessment that L.M. could likely be discharged shortly,
although he ordered some additional testing for confirmation of his views. Id.

        The next day, February 16, 2011, L.M. received a magnetic resonance imaging (“MRI”) of
her brain, performed without contrast,5 with three different imaging sequences performed. Ex. 5
at 3; see generally Ex. 69.6 The radiologist responsible for the MRI observed “no evidence of
migrational abnormality,” no “acute ischemia or infarction,” typical brain parenchyma, and

5
 When an MRI is performed with contrast, a dye containing gadolinium is intravenously injected into the body. This
dye can help enhance certain details in MRI images, including disruption of the blood-brain barrier and the age of
brain lesions. Mayo Clinic, MRI, https://www mayoclinic.org/tests-procedures/mri/about/pac-20384768; Bender v.
Sec’y of Health & Human Servs., No. 11-693V, 2018 WL 3679637, at 2* n.6 (Fed. Cl. Spec. Mstr. July 2, 2018).
6
 Specifically, the following imaging sequences were performed: a sagittal spin echo T1; an axial T2 with diffusion
weighted images; and a coronal FLAIR. Ex. 5 at 3. Axial images show transverse or (horizontal) “slices;” sagittal
images run vertically (perpendicular to axial images) and show a lateral view; and coronal images show a frontal
vertical perspective. University of Wisconsin School of Medicine and Public Health—Department of Radiology,
Neuroradiology             Learning          Module—Imaging             Techniques:          The           Basics,
https://sites.google.com/a/wisc.edu/neuroradiology/image-acquisition/the-basics (2011).

                                                        4
nothing else alarming, deeming the overall results “unremarkable.” Ex. 5 at 3. The overall normal
and unremarkable character of this MRI was confirmed on L.M.’s discharge. Id. at 7.

        Treaters also performed an electroencephalogram (“EEG”) for L.M. on February 16th,
however, which revealed hypsarrhythmia,7 a primary clinical characteristic of infantile spasms.
Ex. 4 at 9. This confirmed Dr. Bakdash’s initial impression that infantile spasms/West syndrome
was the proper diagnosis, and he maintained the phenobarbital treatments initiated for L.M. right
before her arrival at St. Vincent. Id. at 7–8. L.M. experienced no additional seizures at St. Vincent,
and was discharged on February 17th. Id. The discharge summary records Petitioner’s earlier-
referenced recollection that L.M. had previously experienced episodes of “‘spacing out’ when she
would have a strange look on her face and seemed unresponsive,” although the record does not
specify when. Id.

       By the time of discharge, L.M. had returned to her pre-hospitalization baseline (with some
generalized hypotonia). Ex. 4 at 8. However, she was taken back to the ER at Central Montana
Medical Center in Lewistown on March 21, 2011, with complaints of ongoing seizures and URI
symptoms. Ex. 3 at 56–57. The treater’s impression was that L.M. was “somewhat floppy” with
“loose muscle tone” and continued to have five to six seizures daily but otherwise showed “[n]o
other obvious abnormalities.” Ex. 3 at 57.

        L.M.’s Health After Infantile Spasms Diagnosis

        L.M.’s subsequent medical history documents significant developmental difficulties in the
course of dealing with her West syndrome symptoms. Dr. Comes’s notes from February 21, 2011
post-hospitalization follow-up visit, for example, show that L.M. had “poor eye contact” and “poor
head control.” Ex. 2 at 10. Dr. Comes made similar observations at an April 11, 2011 visit, when
she noted that L.M.’s eyes “don’t really focus on anything,” that she had “[n]o interactive smile,”
and that she “really didn’t have good head control at all.” Id. at 14. A physical therapist’s
assessment from March 15, 2011, echoed such findings, describing L.M.’s poor muscle tone and
difficulties holding up her head. Ex. 13 at 3–4.

        Around this time period, L.M. was seen by Dr. Bakdash on several occasions. See, e.g.,
Ex. 7 at 1–8. A follow-up EEG performed on April 18, 2011, confirmed her hypsarrhythmia, as
well as new onset seizure activity in the left temporal region, for which L.M. was prescribed
Keppra. Id. at 4–5. Dr. Bakdash’s assessments in this period did not always corroborate
Petitioner’s assertions of post-vaccination progressive developmental decline. For example, a
February 22, 2011 record noted that L.M. did “reach out for things,” that she held her head up
when placed on her stomach, and that she was “looking at things and tracking them.” Ex. 7 at 2.

7
 “An electro-encephalographic abnormality sometimes observed in infants, with random, high-voltage slow waves
and spikes that arise from multiple foci and spread to all cortical areas.” Dorland’s at 908.

                                                     5
He later noted L.M.’s persistent developmental delays and motor limitations (see, e.g., Ex. 7 at 4),
but overall seems to have viewed her delay as “static in nature” rather than progressive. Id. at 6
(July 12, 2011), 8 (November 8, 2011), 11 (March 14, 2012).

        As of November 8, 2011, Dr. Bakdash’s differential diagnosis for L.M. continued to
include infantile spasms, complex partial seizures, and global developmental delay. Ex. 7 at 8.
Other specialists evaluating L.M. that year proposed other explanations for her symptoms. For
example, on October 27, 2011, Laura Nicholson, M.D., a developmental and behavioral
pediatrician, diagnosed L.M. with static encephalopathy with epilepsy. Ex. 10 at 355–58. Based
upon an examination of L.M. and a review of her history, Dr. Nicholson concluded that L.M.’s
condition appeared metabolic, “with a sudden onset with the stress of the six month shots, recurrent
regression with illness . . . [i]t looks like a mitochondrial disorder . . . but the initial labs do not
show acidosis.” Id. at 357–58. In an e-mail to Samuel P. Yang, M.D., a geneticist, Dr. Nicholson
stated that L.M. “was fine until six months of age and then became neurologically devastated after
a fever with her six-month shots. She has infantile spasms, extreme hypotonia, [and] severe
neurological regression.” Id. at 80.

        Dr. Yang thereafter examined L.M. on December 8, 2011. Ex. 10 at 13–15. The history
from this visit states that “[c]oncern developed around the time [L.M.] was six months old
following an illness and vaccinations when she became ‘hypotonic and hot.’” Id. at 13. Dr. Yang
observed that although L.M.’s EEG was consistent with infantile spasms, her clinical picture and
lack of response to steroids were “more typical for complex partial seizures.” Id. at 14. He
proposed that L.M. might have a cerebral folate deficiency, and recommended treatments aimed
at addressing the deficiency. Id. at 14–15.

        L.M. had improved by March 14, 2012, when she next saw Dr. Bakdash. Ex. 7 at 11–12.
In the wake of treating L.M.’s possible cerebral folate deficiency, her generalized seizures had
ceased, and an EEG now showed no hypsarrhythmic changes—and Ms. Sharpe indicated that L.M.
appeared to experience fewer seizures since the new treatment was initiated. Id. at 11. At that time,
L.M. was receiving physical, occupational, and speech therapies. Id. On May 1, 2012, Dr. Yang
noted that L.M.’s seizure frequency had “decreased dramatically,” and that her infantile spasms
occurred only once or twice per week. Ex. 10 at 19. Her diagnoses now included cerebral folate
deficiency, infantile spasms, global developmental delay, and esotropia.8 Id.

        At present, L.M. continues to experience seizures and developmental delays. Petitioner
alleges that, at 7 years and 5 months of age, L.M. can crawl, as well as walk with a walker when
aided (someone needs to direct her and catch her if she stumbles). Tr. at 60–61. She takes the
anticonvulsant Tegretol and a low dose of CBD oil (medical marijuana) to control her seizures.
Tr. at 64. In her prehearing submission, Petitioner asserts that L.M. experiences “occasional

8
 Esotropia is a condition in which one eye deviates towards the other; in other words, the individual goes “cross-
eyed.” Dorland’s at 648.

                                                        6
breakthrough seizures” even during periods of relatively good health, has a poorly coordinated
grasp, suffers from cortical visual impairments, and is nonverbal, though she can use a few signs
to express ideas such as “hungry,” “thirsty,” “I want,” “yes,” and “no.” Pet’r’s Pre-Hr’g Brief at
12, dated Dec. 12, 2017, ECF No. 73 (“Pet. Brief”).

       Evidence of Genetic Basis for Petitioner’s Symptoms

         Some time after this case’s initiation, evidence potentially shedding light on the cause of
 L.M.’s seizures and related symptoms was uncovered. Specifically, on January 12, 2016, genetic
 testing performed by Ambry Genetics (a company that provides clinical diagnostics testing
 services for genetic diseases, including full exome sequencing) revealed that L.M. is
 “heterozygous for the alteration in the DYNC1H1 [dynein cytoplasmic 1 heavy chain 1] gene
 [hereinafter, the “DYNC gene”].” Ex. 42 (ECF No. 54-1) at 37; see also Ex. R at 2, dated May
 1, 2017, ECF No. 67-1 (“Descartes Rep.”) (stating specifically that L.M. “is heterozygous for
 the alteration c.3278T>C (p.F1093S) in DYNC1H1 in exon 13”). These records conclude that
 “[c]ollectively, the evidence supports the likelihood that the alteration in the DYNC1H1 gene
 [hereinafter, the “DYNC mutation”] is the cause of [L.M.’s] clinical symptoms.” Ex. 42 at 38
 (emphasis added); see also id. at 40 (“[b]ased on the available evidence, the clinical overlap of
 this gene with [L.M.’s] reported phenotype is positive. [L.M.’s] overlapping features include
 infantile spasms, intellectual disability, ongoing refractory epilepsy, and diffuse hypotonia”).
 The Ambry Genetics report also references an unidentified “female patient” who Ambry Genetics
 had previously determined possessed the same mutation and had experienced a phenotypic
 outcome very similar to L.M.’s course. Id. at 41.

         In the course of setting forth the above, the Ambry Genetics test results report includes a
 brief description of many items of literature reviewing the phenotypic outcomes associated with
 DYNC mutation variants. Ex. 42 at 39–40. It summarizes these studies by noting that “[n]o clear
 genotype-phenotype correlations have emerged, although alterations associated with
 malformations of cortical development tend to cluster in the motor domain, whereas alterations
 associated with SMA-LED [Spinal muscular atrophy with lower extremity predominance] tend
 to cluster in the stem domain.” Id. at 40. Nevertheless, the Ambry Genetics results make note of
 reported occurrences that were inconsistent with the mutation’s location as predictive of
 phenotype. Id.

        On February 12, 2016, L.M.’s geneticist documented L.M.’s overall symptomatic
 condition as characterized by epilepsy, global developmental delay with absent speech,
 hypotonia, and mental retardation. Id. at 31–32.

                                                 7
II.      Witness Testimony

         A.       Fact Witnesses

        At hearing, both of L.M.’s parents—Ms. Sharpe and Richard Moore9—testified. See Tr.
at 5–91. These two witnesses also provided affidavits (see Ex. 11; Ex. 12), and their testimony was
largely consistent with their written statements.

                  1.       Ms. Sharpe

        Ms. Sharpe noted that L.M. had few problems early in her life, although she did suffer from
GERD. Tr. at 6–7. The month before receiving the vaccines at issue, L.M. saw her pediatrician,
where “nothing major” was noted. Id. at 9. Ms. Sharpe emphasized that L.M.’s development in
January 2011 remained normal, and she seemed to be a happy baby. Id. at 10–11, 15. She also
acknowledged that L.M. had a cold that January 2011 prior to receiving the vaccines, and received
antibiotics for it, but noted that it was not accompanied by fever. Id. at 15–16.

       Respondent questioned Ms. Sharpe about certain pre-vaccination records that could be
construed as evidence of seizure-like activity. When asked about “episodes” of unresponsiveness
mentioned in a February 15, 2011 record, Ms. Sharpe stated that she did not recall any such
episodes.10 Tr. at 12–13. When questioned later about the February 15th hospital visit notes, Ms.
Sharpe again denied the accuracy of the record, stressing her view that L.M. had never had such
seizures prior to vaccination. Id. at 69. She also denied informing treaters that L.M. had been
floppy or hypotonic since her birth. Id. at 70.

        Ms. Sharpe was also asked about the January 18, 2011 visit to Dr. Comes, when L.M. was
described as crying inconsolably—a characterization Ms. Sharpe disputed. Tr. at 70–72. In her
recollection, this visit was mainly attributable to an incident in which her older daughter had failed

9
 Many of the medical records refer to Mr. Moore as “Richard Hanson.” See, e.g., Ex. 4 at 2. As Mr. Moore explained
at hearing, he was known by this name at the time of L.M.’s vaccination, but subsequently changed his name for
personal reasons relating to his discovery of his biologic parent. Tr. at 74–75.
10
   Respondent’s questions about possible episodes in January 2011 during which L.M. “became limp and unresponsive
for about 30 seconds and then cried for several minutes” and “spaced out, had a strange look in her eyes and was
unresponsive for several seconds” (Tr. at 12–13) seem to reference notes from Petitioner’s February 15, 2011 ER visit,
which reflect that, according to Ms. Sharpe, “a month ago [L.M.] had unexplained episode of sudden flaccidity [and]
unresponsiveness for [about] 30 sec[onds], then crying [and] irritable for several minutes,” as well as “a few other
episodes of ‘spacing out’ where she had a strange look in her eye and was not responsive for several seconds.” Ex. 3
at 13, 15.

                                                          8
to watch L.M. carefully while babysitting, and the behavior L.M. displayed was not, in Ms.
Sharpe’s view, comparable to L.M.’s later seizure activity. Id. at 72.

         As Ms. Sharpe recalled, L.M. received the vaccines in question on the afternoon of
February 10, 2011. Tr. at 17. Immediately after receiving the vaccines, L.M. cried and then quickly
fell asleep, appearing flushed. Id. at 17–19. Later that afternoon toward evening she had trouble
waking up and seemed feverish. Id. By 7:00 p.m., L.M. had a fever of 102 to 103 degrees
Fahrenheit, and she was floppy and lethargic before falling asleep. Id. at 19–21.

        Concerned about L.M.’s condition, Ms. Sharpe called Dr. Comes’s office twice in the early
hours of February 11, 2011. Tr. at 22–23. In particular, the pain relievers she was administering to
L.M. were not effective in reducing her temperature, and L.M. was resistant to waking. Id. at 23,
25–26. Treaters, however, were dismissive of her concerns. Id. at 24. Ms. Sharpe called the
pediatrician again at noon that day, informing the office that L.M. had woken up screaming and
seemed uncomfortable and irritable—very different from how she had been before receiving
vaccines the previous day—but the pediatrician’s office again seemed not to deem L.M.’s
condition significant, simply advising Ms. Sharpe simply to make an appointment to bring L.M.
in on a later date. Id. at 26–29, 30–31.

        Over the next few days, Ms. Sharpe testified, L.M. remained in a distressed condition. Tr.
at 32. She did not, however, opt to bring L.M. in for a visit, maintaining that a nurse had made her
feel that she was overreacting and that Dr. Comes’s office was otherwise booked up. Id. at 33–34.
On February 15, 2011, however, Ms. Sharpe observed L.M.’s head fall back and her body go stiff,
with her color drained out, although she did not check L.M.’s temperature at this time. Id. at 34–
35, 37. She then decided to take L.M. to the ER in Lewistown. Id. at 36. By the time they arrived,
L.M. had begun to “come around,” although she remained unresponsive and continued to resist
waking. Id. at 38, 39–40, 46–47. At hearing, Petitioner expressed concerns about the quality of
care L.M. received initially, and noted that after Mr. Moore arrived, he helped her press upon
treating staff their shared view that L.M. should be transferred to a more up-to-date facility in
Billings. Id. at 45–47, 49–50.

        Ms. Sharpe testified that, prior to transfer, L.M. was administered an IV and drugs
(treatment steps that Ms. Sharpe felt the ER had improperly failed to provide initially). Tr. at 50–
51. During this period, L.M. remained unresponsive, resisted feeding, and would not hold up her
head. Id. at 53–54. She was no better by the time they arrived in Billings that evening. Id. at 54.
During the time L.M. was hospitalized at St. Vincent Hospital, Ms. Sharpe recalled, L.M. showed
some improvement but was still “floppy,” and experienced additional seizures despite medication.
Id. at 57, 58–59.

                                                 9
       Finally, Ms. Sharpe testified about L.M.’s current state of health. L.M. has trouble walking
without assistance (especially outside of the home) and has a limited vocabulary, although her
head control has improved. Tr. at 59–62. She also continues to experience seizures to varying
degrees of severity, although medication helps control them. Id. at 63–64.

                2.      Mr. Moore

        Mr. Moore testified that he worked on-site in the oil extraction industry in North Dakota at
the time period relevant to this case, and was thus often away from the home he shared with Ms.
Sharpe for several days at a time. Tr. at 75. He was in North Dakota around February 14–15, 2011,
and had been there for several days. Id. at 76, 81. Prior to his departure for this shift, L.M. appeared
to him a normal baby, who responded properly to her parents, had good head control, and could
sit up. Id. at 77–79. He acknowledged that L.M. appeared to be developing a cold prior to his
departure, but characterized it as nothing out of the ordinary. Id. at 80. Mr. Moore did not recall
any instance prior to vaccination in which L.M. appeared unresponsive to him. Id.

        Mr. Moore learned of L.M.’s post-vaccination problems while he was working away from
home, after being contacted by Ms. Sharpe. Tr. at 81. He largely corroborated Ms. Sharpe’s
testimony about L.M.’s condition from February 11–15, 2011. Id. at 81–82. He was called while
in North Dakota after Ms. Sharpe took L.M. to the ER in Lewistown, and immediately travelled
back to Montana. Id. at 83–84. At the ER, Mr. Moore observed L.M. to be what he characterized
as “catatonic” and nonresponsive, resisting any of his efforts to get her to react to his presence. Id.
at 85–86.

        Similar to Ms. Sharpe, Mr. Moore described his frustration arising from the perception that
ER treaters were not adequately caring for L.M., and that more skilled neurologic expertise was
required to ascertain the nature and cause of L.M.’s condition. Tr. at 86–87. Therefore, he and Ms.
Sharpe concurred that L.M. needed to be transported to St. Vincent Hospital, and conveyed that
request to ER treaters in Lewiston. After going to Billings, Mr. Moore indicated, L.M. appeared
to him roughly the same as she had upon his arrival, and that since that time she has never returned
to her pre-vaccination condition. Id. at 88.

       B.       Expert Witnesses

                1.      Dr. Robert Shuman

        Dr. Shuman testified at hearing and prepared three written reports for Petitioner. See
Ex. 17, ECF No. 16-1, dated October 2, 2014 (“Shuman First Rep.”); Ex. 28, ECF No. 29-1, dated
June 8, 2015 (“Shuman Second Rep.”); Ex. 68, ECF No. 72-1, dated December 10, 2017 (“Shuman
Third Rep.”). Dr. Shuman overall opined that L.M. suffered from a preexisting, structural brain

                                                  10
deformity that, as a result of the vaccines she received, caused an interference in her brainstem
activity that resulted in seizures. Tr. at 127.

        Dr. Shuman is a pediatric neuropathologist with special expertise in child neurology. Tr.
at 92–93. He received his M.D. from Stanford University. Ex. 19 at 1, ECF No. 16-3 (“Shuman
CV”). He completed a residency in pediatrics at the University of Colorado, a residency in
pathology at the University of Washington, and a residency in child neurology at the University
of Kentucky. Id. At various points, he has served as a professor of neurology, neuropathology, and
pediatric neuropathology at the University of Pittsburgh, the University of Nebraska, and the
University of Oklahoma. Id. at 1–2; Tr. at 92–93. He is board certified in pathology,
neuropathology, and child neurology, but not pediatrics. Tr. at 94; Shuman CV at 2.

        Dr. Shuman acknowledged his particular interest in neuroimaging processes, like MRIs,
stressing the degree to which this kind of testing had increased the reach of the field of pathology
and revolutionized its capabilities. Tr. at 95. Because of his interest in such technological
advancements, his career focus over time shifted to imaging instead of a clinical, patient-oriented
practice. Id. at 96. Dr. Shuman possesses a certification from the American Society of
Neuroimaging. Id. at 98. He retired from medical practice in 2006, and has not had a clinical
practice since that time (and has therefore not had the occasion to review any MRIs for purposes
of treatment, although he routinely views them in the context of serving as an expert—his primary
source of income today). Id. at 97, 137, 139–40.

        The core of Dr. Shuman’s testimony and opinion was his interpretation of L.M.’s various
MRIs, which he proposed demonstrated the existence and extent of an underlying encephalopathic
condition. Overall, he stressed that (a) L.M. had a thin corpus callosum,11 (b) L.M.’s ventricles
were large and malformed, and (c) there were “irregular densities” in the white matter around the
ventricles and under the cerebral cortex, all of which were suggestive to Dr. Shuman of a white
matter disease of some kind or other cerebral malformation. Tr. at 101–02.

        First, Dr. Shuman discussed the MRI obtained on February 16, 2011, after L.M. was taken
to St. Vincent Hospital. See Ex. 69 at 2. This MRI is a sagittal image12 showing the entirety of
L.M.’s cranium, and in Dr. Shuman’s interpretation evidenced the thin nature of L.M.’s corpus
callosum. Tr. at 103, 105. The axial T2 image13 obtained on the same date revealed that L.M.’s
lateral ventricles were unevenly shaped—in particular, the left was shaped differently than the

11
   Corpus callosum is the “arched mass of white matter” located in the longitudinal fissure of the cerebrum. Dorland’s
at 417, 709, 711.
12
     See supra note 6.
13
  A T2 image, as distinguished from a T1 image, “excites water.” Tr. at 106. Dr. Shuman explained that this shows
the presence of cerebrospinal fluid. Id.

                                                         11
right, which appeared normal. Id. at 107–08. Dr. Shuman could not attribute this discrepancy solely
to the positioning of the particular image. Id. at 107. His conclusion was that the ventricles, taken
together, were overly large, asymmetric, and abnormal. Id. at 108.

        In addition to such observations about structural deficiencies, Dr. Shuman reached other
conclusions from these initial MRI images. He pointed out what he deemed striations in the white
matter, which he deemed consistent with “perinatal teloleukoencephalopathy” (“PNTLE”), a white
matter deficiency condition.14 Tr. at 108–09. This alleged white matter deficiency he characterized
as “part of the preexistent encephalopathy of [L.M.]’s genetic disease.” Id. at 110. However, on
cross-examination Dr. Shuman later admitted that this alleged white matter deficiency was not
evidence of an acute brain injury (whether caused by a vaccine directly or by vaccine-induced
epileptic activity), although he noted that an MRI would not reveal epileptic activity generally. Id.
at 152.

         Dr. Shuman next turned to the second set of MRI images, obtained in April 2011 (two
months post-vaccination). Tr. at 110 (discussing Ex. 69 at 4). In his reading, these new images
revealed “essentially no change in [L.M.]’s preexisting encephalopathic state,” thus corroborating
his interpretation of the initial images. Id. at 111. In fact, in Dr. Shuman’s opinion, this set of
images revealed the existence of a “static encephalopathy.” Id. at 112. Finally, Dr. Shuman
reviewed the third set of images, obtained on May 22, 2012 (over a year after the second set). Id.
at 115 (discussing Ex. 69 at 6). He asserted that they were “pretty good” evidence of the structural
abnormalities and white matter deficiencies that he maintained could be seen in the initial imaging
sets, as well as the static nature of L.M.’s underlying encephalopathy. Id. at 115–16, 369.

        Based on his review of these MRIs, Dr. Shuman opined (as mentioned above) that
concurrent with L.M.’s purported structural deficiencies, she suffered from a specific kind of white
matter deficiency: PNTLE. Tr. at 140. Dr. Shuman admitted, however, that the term was somewhat
medically outdated and was subsumed within the concept of “white matter deficiency,” although
he stressed that PNTLE and white matter deficiency are “gradation[s] of the same disease.” Id. at
141, 142, 162. He allowed that any PNTLE/white matter deficiency from which L.M. suffered was
fairly mild, as corroborated by the MRI findings, and agreed that his interpretation of these MRI
findings was not echoed by the radiologists who performed them. Id. at 143, 144, 162–63.

         In advancing PNTLE as a reasonable diagnostic explanation for L.M.’s white matter
deficiency, Dr. Shuman claimed there is support in the literature establishing that this
condition/diagnosis is recognized, although his own personal experience also led him to propose
it. Tr. at 141 (discussing J. Volpe, Neurology of the Newborn (4th ed. 2001), excerpts filed as Ex.

14
  Dr. Shuman defined a perinatal teloleukoencephalopathy as “a generalized insufficiency of the formation of white
matter or the destruction of precursors of the white matter form cells” that leads to “blunting of the lateral ventricular
angle [and . . .] dilatation of the lateral ventricle.” Tr. at 109–10.

                                                           12
23, Ex. 26A, Ex. 26B (ECF Nos. 17-5; 17-8; 17-9); L. Woodward, et al., Neonatal MRI to Predict
Neurodevelopmental Outcomes in Preterm Infants, 355 New England J. Med. 685 (2006), filed as
Ex. 25 (ECF No. 17-7)). He acknowledged, however, that the literature’s reference to PNTLE did
not precisely match or describe the PNTLE he observed from the MRIs. Id. at 141–42. In a similar
vein, Dr. Shuman pointed to images from an article involving the effects of the DYNC mutation
that he maintained were similar to what he observed in L.M.’s MRIs (and thus confirmed his
overall view about the nature of her brain abnormalities). Id. at 116 (discussing M. Scoto, et al.,
Novel Mutations Expand the Clinic Spectrum of DYNC1H1-Associated Spinal Muscular Atrophy,
84 Neurology 668, 676 (2015), filed as Ex. 70; Ex. 72 (ECF Nos. 72-3; 72-5) (“Scoto”)). The child
mentioned in Scoto was, Dr. Shuman maintained, about the same age as L.M., and Scoto’s authors
had identified similar abnormalities in her MRI. Id. at 118. The child from Scoto also had similar
debilitating symptoms, such as gait deficiencies and related motor issues. Id. at 122.15

        Dr. Shuman defined the structural abnormalities and white matter deficiencies he observed
as a preexisting encephalopathy. In his view, alterations in brain structure, if also accompanied by
resulting abnormal function (such as head control or motor problems) as well as other evidence of
brainstem issues (such as resting loss of muscle tone), could evidence encephalopathy. Tr. at 118,
119, 120, 126–27. He speculated that the abnormal function that L.M. already displays would only
continue as she ages. Id. at 119. Even though the encephalopathy was only discovered after
vaccination, the abnormalities in brain structure and white matter content were enough to
constitute an “encephalopathic precondition.” Id. at 100. However, Dr. Shuman admitted that had
a pre-vaccination MRI been performed and revealed nothing, then his conclusions about
preexisting encephalopathy would lack foundation. Id. at 149.16

        After an extensive discussion of his conclusions drawn from L.M.’s MRIs, Dr. Shuman
turned to the putative role the vaccines L.M. received in February 2011 played in exacerbating her
brain abnormalities/white matter deficiency. Dr. Shuman maintained that the vaccines precipitated
her seizures (although he did not maintain that the vaccines caused the preexisting abnormalities
themselves). Tr. at 161. He found the close temporal relationship between the date of vaccination
and seizure onset particular significant, characterizing it as “too close to ignore.” Id. at 133. He
deemed her health good prior to vaccination (except for her documented GERD and a URI). Id.
at 99–100. After vaccination, by contrast, Dr. Shuman described Ms. Sharpe’s observations of
L.M.—even before she was taken to the Lewistown E.R.—as documented medical evidence of her

15
 On cross-examination, however, Dr. Shuman acknowledged that Scoto’s authors had (correctly) identified the same
DYNC mutation relevant in this case as the actual cause of the observed structural malformations. Tr. at 152.
16
  Although Dr. Shuman’s opinion is premised on the determination that L.M. had a preexisting static/structural
encephalopathy, he maintained that even if this were not the case, he would still propose that, at a minimum, L.M. had
a “genetic propensity” to react to the vaccinations in light of her DYNC mutation, noting that a structural brain
malformation was not a prerequisite to injury. Tr. at 169–70, 171.

                                                         13
profound developmental change.17 Id. at 122–24. He specifically identified likely onset as the
hours after vaccination, when L.M.’s lack of responsiveness was first evident to Ms. Sharpe. Id. at
144.

        In support of his statements about the causal relationship between vaccination and L.M.’s
symptoms, Dr. Shuman referenced the “National Childhood Encephalopathy Study” performed in
the United Kingdom in the late 1970s. See Richard Alderslade et al., The National Childhood
Encephalopathy Study: A Report on 1000 Serious Cases of Serious Neurological Disorders in
Infants and Young Children from the NCES Research Team, Reports from the Comm. on Safety
of Med. & Joint Comm. on Vaccination & Immunisation (1981), filed as Ex. 36a; Ex. 36b (ECF
Nos. 31-8; 31-9) (“UK Study”). In the UK Study, researchers queried whether the pertussis vaccine
can cause neurological harm to young children. Id. at 141. Based on an examination of the
vaccination records of one thousand children between the ages of two and thirty-five months who
had been hospitalized with diagnoses such as encephalopathy and West syndrome, the researchers
concluded that the “DTP vaccine probably can cause acute neurological reactions.” Id. at 107, 138,
141.

        Dr. Shuman maintained that the UK Study established an association between “serious
neurologic illness” and vaccines like DPT.18 Tr. at 128. In his view, the UK Study, as well as other
scientific literature, showed a connection specifically between whole cell pertussis (contained in
the DPT vaccine) and incidence of infantile spasms. Id. at 369–70 (discussing D.L. Miller, et al.,
Pertussis Immunization and Serious Acute Neurological Illness in Children, 282 British Med. J.
1595 (1981), filed as Ex. 35, ECF No. 31-7 (“Miller”); UK Study).19 He admitted, however, that
the UK Study was dated, especially in light of recent scientific developments and changes to the
pertussis component in childhood vaccines (and that there was nothing more recent to which he
could point associating vaccines with infantile spasms). Id. at 160. Thus, the UK Study did not
address the more recent acellular pertussis vaccine forms (which, he acknowledged, had been
successfully implemented to reduce the risks observed in the UK Study associated with the whole
cell version), although he disputed that introduction of the acellular pertussis component

17
   Dr. Shuman in his testimony attempted to bulwark Ms. Sharpe’s assertion that L.M. was in fact feverish not long
after vaccination to a greater degree than she reported at the time, noting that because an axillary, or underarm,
thermometer was used (which would imprecisely underestimate actual body temperature), L.M.’s temperature was
likely even higher than 103 degrees Fahrenheit. Tr. at 125. He later characterized this initial fever as an important
piece of evidence linking the vaccinations L.M. experienced to her subsequent seizures and developmental problems.
Id. at 167–68.
18
  The DPT vaccine covers diphtheria, pertussis, and tetanus. Liable v. Sec’y of Health & Human Servs., No. 98-120V,
2000 WL 1517672, at *1 (Fed. Cl. Spec. Mstr. Sept. 7. 2000). See Analysis § I(C), infra, for an explanation for the
difference between the DPT vaccine and the DTaP vaccine that L.M. received.
19
  On cross-examination, Dr. Shuman admitted that Table VIII in Miller was general in application, referencing “all
serious neurologic illnesses” as opposed to infantile spasms specifically. Tr. at 374–75.

                                                         14
completely eliminated all risk. Id. at 129–30, 158.20 He noted further that the package inserts for
the vaccines in question also revealed manufacturer awareness of possible adverse effects, the risk
of which was multiplied when, as here, several vaccines were administered at the same time. Id.
at 130.

         Dr. Shuman referenced an article filed by Respondent as actually supporting his view about
the association between infantile spasms and vaccines. Tr. at 370–71 (discussing M. Bellman, et
al., Infantile Spasms and Pertussis Immunisation, Lancet 1031 (1983), filed as Ex. J, ECF No. 34-
2 (“Bellman”)). He claimed that Bellman affirmatively established that the risk of developing a
spasm disorder is heightened in the days immediately after vaccination. Id. at 370–71. Bellman
itself does not facially seem to support this conclusion, however, because its authors conclude that
their data supports the increased incidence of spasms onset in first seven days after vaccination as
only applying to trigger cases, i.e., those in which vaccines may have triggered an otherwise
inevitable neurological event. Bellman at 1033. Bellman thus asserts that pertussis is not a direct
cause of infantile spasms for children with normal brains but may precipitate onset in children “in
whom [infantile spasms] is already destined to develop.” Id.

        Dr. Shuman nevertheless maintained that Bellman’s authors had relied upon a “specious
argument” to manufacture the result they wanted, discounting data which was contrary to their
desired findings by claiming that the affected individuals had a susceptibility to a seizure disorder.
Tr. at 371–72. In effect, he maintained that the reduced incidence of post-vaccination spasms onset
on a longer timeframe was misused by Bellman’s authors to explain away the significance of a
dramatic increase in risk in the shorter timeframe. Id. at 372–73. When cross-examined about
Bellman—and in particular the fact that the conclusions it allegedly reached about vaccine
causation of infantile spasms were not corroborated in any other subsequent literature filed in the
case—Dr. Shuman maintained that such studies were likely wrong (although he did not specify
how, and lacks the kind of epidemiologic credentials necessary to make such sweeping assertions).
Id. at 373, 375–76.21

       Despite his admitted lack of direct experience in immunologic matters, Dr. Shuman made
some effort to provide a more detailed explanation for the mechanism by which he theorized
vaccines could interact with the preexisting static encephalopathy he proposed characterized

20
   Dr. Shuman also admitted that the UK Study did not take into account the subsequent discovery of the DYNC
mutation’s relationship to the kind of injury L.M. had experienced, although he suggested that the study could be
updated in light of such discoveries (and implicitly that the outcome of such updating might not be contrary to the
original’s determinations). Tr. at 160.
21
  Respondent also cross-examined Dr. Shuman as to whether Bellman actually provided a better way of understanding
the UK Study’s conclusions, revealing that the pertussis vaccine is not a direct causal factor of seizure disorders (as
opposed to a precipitating factor of individualized seizures). But Dr. Shuman claimed that the premise of such
questioning was wrong. Tr. at 376–77.

                                                          15
L.M.’s condition. As he reasoned, a person like L.M. with structural brain abnormalities and a
form of white matter deficiency would be vulnerable to “decompensation” if hit with the
immunologic stress of vaccination. Tr. at 131. Thus, L.M.’s preexisting state and dysfunction was
primed for further reaction. Id. at 132. Dr. Shuman was a bit more specific about the mechanism
of causation on cross-examination, maintaining that it was likely a reaction to the pertussis toxin
purportedly in the DTaP component of the Pediarix vaccine,22 which would stimulate her immune
system to overproduce cytokines and other immunologic substances. Id. at 150.

        Besides the above, Dr. Shuman also attempted to offer an explanation for the medical
reasonableness of the timeframe in which L.M.’s seizure disorder and subsequent sequelae
occurred. He referenced her February 2011 neurologic evaluation as revealing the presence of her
disorder, noting that West syndrome could appear suddenly, but that its timing in comparison to
the vaccinations she had received (given her preexisting encephalopathy) was not just coincidental.
Tr. at 133–34. He admitted that there were some references in the record to L.M. having
experienced seizure-like activity before the vaccines were administered, but maintained that there
was no prior medical record evidence corroborating that these events had actually occurred (and
thus suggesting, without elaboration, that they likely had not). Id. at 145–48. He acknowledged,
however, that Ms. Sharpe and Mr. Moore might not have understood such prior occasions to
constitute seizures. Id. at 149.

        Dr. Shuman dismissed suggestions by Respondent’s counsel that an identifiable alternative
cause for L.M.’s symptoms post-vaccination existed. In so doing, he did not contest that L.M. may
have suffered from a URI prior to vaccination, but maintained that it could not have constituted
enough of a “hit” to trigger the level of reaction that he opined the vaccines had caused. Tr. at 164.
For this view, Dr. Shuman relied on Ms. Sharpe’s contention that the URI had likely cleared by
the time of vaccination—leaving only the vaccines as possibly causal. Id. at 165.

        Dr. Shuman also briefly addressed the significance of the DYNC mutation as possibly
providing a better explanation for the cause of L.M.’s seizures and developmental problems—a
concept that did not initially figure into his opinion (because the Ambry Genetics testing results
were obtain after his first two reports). He did not dispute that L.M. carries the mutation, as well
as the more general point that some kind of genetic mutation or irregularity likely explained the
structural abnormalities and white matter deficiency that he observed from L.M.’s MRI images.
Tr. at 121–22. However (and anticipating Dr. Boles’s opinion), he proposed that the precise
location of the mutation on the greater gene itself was relevant to the expected “consequences” of
the mutation. Id. Ultimately, he deferred to Dr. Boles on these matters, given that they were outside
of his expertise. His final expert report (filed after the discovery of L.M.’s DYNC mutation)

22
  Pediarix consists of DTaP, hepatitis B, and inactivated polio virus vaccines. See Centers for Disease Control &
Prevention, Pediarix Vaccine: Questions and Answers, https://www.cdc.gov/vaccines/vpd/hepb/hcp/faqs-hcp-
pediarix html.

                                                       16
offered his own analysis of the genetic component to this case, which largely echoed Dr. Boles’s
emphasis on the importance of location (stem versus stalk) of a DYNC mutation in predicting
outcome. Shuman Third Rep. at 6.

       On cross-examination, Dr. Shuman acknowledged that his opinion lacked a basis for the
conclusion that L.M.’s seizure disorder/developmental problems were worsened by vaccination
beyond what would otherwise have been expected given her alleged encephalopathic brain
malformation/white matter deficiency. Tr. at 151.

       2.      Dr. Richard Boles

       Dr. Boles filed one report in this case and testified at hearing. Ex. 57, dated December 25,
2016, ECF No. 61-1 (“Boles Rep.”). His opinion accepts the fact that L.M. had the DYNC mutation
and that it played a role in her seizure disorder and related condition, but maintains that the
vaccines she received worsened her overall course. Tr. at 183.

        As reflected in his curriculum vitae, Dr. Boles received his B.S. from the University of
Arizona and his M.D. at the University of California Los Angeles (“UCLA”). Ex. 58 at 2, ECF
No. 61-2. He completed a pediatrics residency at Harbor-UCLA Medical Center, followed by a
genetics fellowship at Yale University. Id. Dr. Boles served as a professor of clinical pediatrics at
the University of Southern California from 1993 until 2014. Id. at 2. He is board certified in clinical
genetics and clinical biochemical genetics. Id. at 1. He specializes in clinical genetics and metabolic
diseases. Tr. at 172. He has worked for biotech companies but is largely today in private practice,
where he “treats people with energy disorder[s].” Id. at 225. Dr. Boles’s ample expertise in genetics
is offset by his admitted lack of expertise in immunology. See id. at 207–08, 225.

        In his reports and testimony, Dr. Boles discussed at length the nature of L.M.’s DYNC
mutation. He agreed she possessed the mutation before the vaccinations at issue, and that it likely
was present at her birth. Tr. at 217. He defined it as a “missense” mutation (id. at 173), meaning
one that causes a gene to code for a different amino acid than normal. Dorland’s at 1169. He also
allowed that the DYNC mutation explained some of L.M.’s spasms and other symptoms. Tr. at
179, 193–94 (“I’m concurring with [Ambry’s] decision that [the DYNC mutation genetic
variant]’s pathogenic”). He nevertheless maintained that certain features of the mutation
bulwarked his view that vaccination likely exacerbated L.M.’s condition.

        In particular, Dr. Boles opined that the precise location of the DYNC mutation on the
DYNC chromosomal protein chain was critical in determining the symptoms an individual would
experience when the mutation is expressed. Here, he identified the gene’s tail or stem domain—
specifically its “dynein complex-binding domain”—as the likely location of L.M.’s mutation,
relying on a graphic from one of Petitioner’s filed items of literature to illustrate his point. Boles

                                                  17
Rep. at 9; Tr. at 173–74 (discussing A. Strickland, et al., Mutation Screen Reveals Novel Variants
and Expands the Phenotypes Associated with DYNC1H1, 262 J. Neurology 2124, 2137 (2015),
filed as Ex. 82, ECF No. 85-8 (“Strickland”)).

        Strickland’s authors screened over one thousand cases of individuals suffering from
motoneuron and related diseases in search in instances in DYNC mutations, locating thirteen
patients possessing some form of DYNC mutation. Strickland at 2126. The mutations were
distributed across the length of the gene (which Strickland noted to be “one of the largest genes in
the human genome”) but the pathogenic versions were grouped in the “functional domains” of the
gene, suggesting to its authors that “there are regions that are more susceptible to mutation-induced
dysfunction.” Id. at 2131. In particular, Strickland observed (based upon its thirteen-patient sample
group) that “intellectual disability mutations are clustered microtubule binding regions”—which
Dr. Boles maintained was not the location of L.M.’s mutation. Id.; Tr. at 173–76.

         Dr. Boles acknowledged that the terms “stem” and “tail” were not consistently used in the
literature in discussing the location of the DYNC mutation, but that for purposes of his analysis
what mattered was that the relevant mutation was not found in the section of the gene responsible
for motor function. Tr. at 173. A missense mutation found only in the “complex binding domain”
of the gene, by contrast, would be less severe than otherwise possible, claiming that he was
unaware of any contrary circumstances. Id. at 176–77, 181, 365. This was consistent with his
report, in which he concluded that an individual with a DYNC mutation located in the motor end
of the gene was far more likely to experience a severe outcome than one with a mutation in the
stem.23 Boles Rep. at 10.

        As additional support for this proposition, Dr. Boles referenced Scoto, observing that the
DYNC mutation for the child in question was located outside of the gene domain responsible for
motor function. Tr. at 175–76. He also relied upon other items of literature filed, plus case reports.
Id. at 181–82 (discussing Strickland at 8; S. Gandomi, et al., Exome Sequencing Identifies Five
Mutations in the DYNC1H1 Gene Associated with Severe Neurological Phenotypes (2014), filed
as Ex. 83, ECF No. 85-9 (finding that “mutations in the motor domain and MTBD appear to be
associated with more severe neurological phenotypes”)). And he claimed that the “vast majority

23
   Dr. Boles in fact attempted to cast this point as statistically significant, maintaining that DYNC mutations located
“in the dynein complex-binding domain [are] 23 times more likely to result in either developmental delay and/or
epilepsy than is mutation in the DYNC1H1 gene outside of this domain.” Boles Rep. at 10. As a basis for this assertion,
he performed his own statistical analysis of the thirteen individual cases discussed in the Strickland plus five more
taken from another item of literature. Id. Of course, such a small sample size—eighteen cases total—greatly
undermines the degree to which it can be characterized as statistically significant. See D. Kaye & D. Freedman,
Reference Guide on Statistics, in Reference Manual on Scientific Evidence 211, 264 (3rd ed. 2011); see also Jewell v.
Sec’y of Health & Human Servs., No. 11-138V, 2016 WL 5404165, at *10 (Fed. Cl. Spec. Mstr. Aug. 29, 2016) (expert
opining that two studies utilizing sample sizes of 6 and 420, respectively, would need to be much larger to identify a
statistically significant risk factor).

                                                         18
of the mutations in the dynein binding or dimerization domain [the area where monomers combine
to form polymers]24” were generally more likely to be severe than tail/stem-located mutations, Tr.
at 366–67.

        Dr. Boles spent much time in his testimony (particularly during Petitioner’s rebuttal case)
attacking the argument of Respondent’s genetic expert, Dr. Maria Descartes, that a DYNC
mutation in the stem/tail region of the gene could also be severe in phenotypic outcome and/or
consistent with L.M.’s course. Tr. at 363–67. In particular, he claimed that two articles offered to
show that L.M.’s illness course was consistent with others bearing the DYNC mutation involved
mutations located “outside the dimerization domain,” thus decreasing their relevance to
understanding L.M.’s condition. Id. at 364 (discussing H. Hoang, et al., DYNC1H1 Mutations
Associated with Neurological Diseases Compromise Processivity of Dyenin-Dynactin-Cargo
Adaptor Complexes, 114 Proceedings of the Nat’l Acad. Of Sci. 1597 (2017), filed as Ex. U, ECF
No. 70-2 (“Hoang”); M. Willemsen, et al., Mutations in DYNC1H1 Cause Severe Intellectual
Disability with Neuronal Migration Defects, 49 J. Med. Genetics 179 (2012), filed as Ex. FF, ECF
No. 71-6 (“Willemsen”)). He also took issue with accepting the Ambry Genetics prognosis for
L.M.’s expected outcome, noting that the test results report did not identify the location of the
mutation (and therefore, presumably, missed the importance of that distinction in characterizing
expected outcome). Id. at 196 (discussing Ex. 42 at 41; Ex. 57 at 8).

        Another item of literature offered by Respondent did not involve a missense mutation. Tr.
at 365; K. Poirier, et al., Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A Cause
Malformations of Cortical Development and Microcephaly, 45 Nat’l Genetics (2013), filed as Ex.
W, ECF No. 70-4. Only Strickland featured a DYNC mutation in the same location of the gene as
that Dr. Boles alleged occurred with L.M., but he maintained that the symptoms of the affected
child were more like attention deficit/hyperactivity disorder rather than the “severe intellectual
cognitive problem” that L.M. has. Tr. at 365.

        L.M.’s receipt of vaccines greatly amplified and worsened the expected, comparatively
milder course otherwise attributable to her mutation, Dr. Boles opined. To support this contention,
Dr. Boles relied upon both general and specific points. Broadly, he maintained, the field of genetics
recognizes that a particular mutation can never be solely responsible for all resulting aspects of a
disease it might cause. Tr. at 180. Genetic factors associated with certain outcomes were in his
view better thought of as posing risk than “predisposition.” Id. at 183. Rather, in Dr. Boles’s
experience, an outside environmental factor was more commonly a primary disease trigger even
in the context of genetic factors relevant to the illness. Id. at 184. He cited twin studies as
corroborative proof of the impact of environment even in the context of shared genetic similarities.
Id. at 180–81.

24
     See Dorland’s at 520, 562.

                                                 19
        Vaccines could, Dr. Boles reasoned, constitute a sufficient “environmental insult” to
exacerbate the effects of an underlying mutation. Tr. at 188, 220. He noted in his report that the
entire purpose of vaccines was to “evoke an immunologic response,” and therefore there was “no
rational reason” to exclude vaccines as possible environmental factors that could spark the
pathogenesis of a seizure disorder later resulting in more severe symptoms like developmental
regression. Boles Rep. at 11. Indeed, he claimed that “80 percent or more” of instances in which a
person like L.M. would experience a seizure disorder would be after an “immunological trigger.”
Tr. at 210. He did not, however, offer literature specifically addressing the propensity of any
vaccine to exacerbate a disease otherwise attributable to a genetic mutation, and this component
of his overall opinion had a conclusory character to it, relying more on his ipse dixit than
independent evidence. See, e.g., Boles Rep. at 11 (“I find it very difficult to believe that the above
neurological changes are unrelated to the temporally‐associated vaccination. The possibility of this
all being due to coincidence exceeds belief”).

         Dr. Boles also attempted to rebut Respondent’s argument that (as evidenced in the Ambry
Genetics test results report) another individual who possessed the same DYNC mutation had
experienced a course very comparable to L.M., maintaining that there were no more than vague
references in literature to this individual that prevented the conclusion that the disease course was
similar. Tr. at 182–83. He even denied that there was evidence at all that the two patients’ courses
were comparable (while admitting that both had infantile spasm disorders accompanied by severe
developmental/intellectual difficulties). Id. at 200, 367–68. And (somewhat contrary to his overall
assertion that mutation location predicted phenotypic outcome) he purported that the genetic
testing could not possibly determine the predicted severity of course for someone with the mutation
in the first place. Id. at 199.

        Dr. Boles struggled to offer reliable scientific or medical proof associating vaccines of any
kind with the sparking of a seizure disorder connected to the DYNC mutation or some other
comparable genetic mutation. Tr. at 204. At best, he referenced familiarity with literature
pertaining to instances in which an underlying metabolic disorder was believed to have interacted
with vaccines like the measles-mumps-rubella (“MMR”) or DTaP,25 leading to
illness/developmental disorders. Id. at 203–04, 208. He also proposed that it was reasonable to
expect that an individual with the DYNC mutation also likely had energy production dysfunction
due to concurrent metabolic problems, although he added that his opinion did not depend upon the
finding that L.M. did in fact have an underlying metabolic disorder (and the record contains no
such corroborative findings in any event). Id. at 222–24. He admitted as well that a number of
other possible triggers (such as fasting and over-exercise) could spark a similar pathogenic process

25
  Dr. Boles admitted he could not pinpoint which specific vaccine received by L.M. was causal of her illness, but
proposed awareness that the MMR and DTaP had been implicated in other contexts. Tr. at 207–09.

                                                       20
in a person susceptible for genetic reasons to a seizure disorder, with a direct wild virus infection
the most likely culprit in the majority of cases. Id. at 212–13.

       As noted, Dr. Boles affirmatively opined that L.M.’s overall course of disease (which he
admitted would have involved some seizures and other sequelae attributable to the DYNC
mutation) was worse than what she would have experienced absent vaccination. Tr. at 191–92,
201. For support, he referenced his own personal experience treating a set of twins with a
predisposing genetic mutation (not the DYNC mutation). Id. at 185–86, 202. Both experienced a
stomach virus, but the twin with the more acute infection had a more severe course of infantile
spasms and resulting developmental difficulties than the other. Id. at 185–86. The disparity, in his
view, could only be attributable to a different response to an environmental factor. Id. at 187. He
acknowledged, however, that the Ambry Genetics report and other genetic testing records made
no reference to vaccination as having played a role in L.M.’s disease course, although he
questioned whether Ambry would have been informed of the vaccinations in the first place. Id. at
206.

        Dr. Boles also defended the timing of onset of L.M.’s post-vaccine reaction as reasonable.
He deemed her “dramatic deterioration” as occurring within three hours of receipt of the vaccines,
terming that timeframe “hard to ignore.” Tr. at 185. When pressed on cross-examination for the
basis for this pronouncement, however, Dr. Boles acknowledged that he relied mainly on the
statements of Ms. Sharpe about the deterioration she alleges to have observed in a three-hour
window (although he added that he would still deem a timeframe of 12 or even 24 hours to be
alarmingly short). Id. at 216–17. He also referenced his own personal experience with individuals
that he deemed susceptible to a vaccine reaction, stating that it was not uncommon for them to
experience a short timeframe after a vaccine trigger. Id. at 215.

        Finally, Dr. Boles made some effort to harmonize his testimony on causation with that of
Dr. Shuman’s (which focused on purported preexisting brain structure abnormalities—and
significantly was mostly based on reports filed prior to the discovery of L.M.’s DYNC mutation).
He maintained that his opinion was not dependent on a finding of static/structural encephalopathy,
although Dr. Shuman’s opinion strengthened his own conclusions, since what he termed brain
“migrational defects”26 could be seen in conjunction with DYNC mutations. Tr. at 219, 221.
However, he acknowledged uncertainty as to whether the DYNC mutation would in fact manifest
with the brain abnormalities and/or white matter deficiencies pointed to in Dr. Shuman’s
testimony. Id. at 220–21.

26
   Neuronal migration disorders occur when neurons fail to migrate from their locations at birth to their proper neural
circuits. National Institute of Neurological Disorders and Stroke, Neuronal Migration Disorders Information Page,
https://www.ninds nih.gov/disorders/all-disorders/neuronal-migration-disorders-information-page (June 18, 2018);
see also Ellis v. Sec’y of Health & Human Servs., No. 13-336V, slip op. at 5 (Fed. Cl. Spec. Mstr. Sept. 6, 2018).

                                                         21
       3.      Dr. Maria Descartes

       Dr. Descartes prepared one expert report and testified at hearing for respondent. See
Descartes Rep. She opined that L.M.’s DYNC mutation was the cause of her seizure disorder and
developmental problems. Tr. at 240.

        As shown in her curriculum vitae, Dr. Descartes received her A.S., B.S., and M.D. from
the University of Puerto Rico. Ex. S at 1, ECF No. 67-2. She completed a residency in pediatrics
at San Juan City Hospital in Puerto Rico, followed by a fellowship in genetics at Baylor College
of Medicine in Houston, Texas. Id. at 2. Dr. Descartes is currently a professor of genetics and
pediatrics at the University of Alabama Birmingham (“UAB”). Tr. at 234. She is board certified
in generics and pediatrics, among other things. Id. at 236. She has treated numerous children and
adults with genetic disorders in her career, and also participated in clinical trials for new treatments
and drugs. Id. at 235, 236. She has also published writings on the topic of medical genetics. Id. at
236–37. Dr. Descartes is a participant in UAB’s undiagnosed disease program as well, within
which she mostly assists in evaluating pediatric patients. Id. at 237–38.

        Dr. Descartes’s testimony began with an explanation of some core genetic concepts. She
described genes as “inheritable units” that code the production of different kinds of proteins
serving a variety of purposes, from inheritable traits (eye and hair color) to “housekeeping” jobs
within the human body. Tr. at 240–42. An individual’s “genotype” is their genetic composition,
while their “phenotype” embodies the characteristics produced (in part) by that composition. Id.
at 246. She defined an exon as the coding part of a gene that is transcribed for production of a
particular protein. Id. at 248. Dr. Descartes took special effort to explain the concept of
“conservation” in a genetic context, testifying that a “conserved” genetic sequence is one that has
been maintained in evolution from lower species to higher/vertebrate species, thereby signifying
its biologic importance. Id. at 246–47.

        Dr. Descartes also explained what genetic mutations are. Any variation in a genetic
sequence can result in a “faulty product,” as she put it. Tr. at 243. A missense mutation is one
where a particular genetic variance results in the production of an amino acid/protein sequence
different from what would otherwise occur. Id. at 250. A “de novo” mutation is one that has not
been inherited from a parent. Id. at 244–45. Such genetic variants occur in part as cells divide and
replicate to make new ones, or may be environmentally-triggered, in the process of turning on and
off (as certain genes perform their function only at certain times in life, such as during an infant’s
development). Id. at 245–46. The “location” of a particular mutation is simply the place in the
protein chain forming the gene where the mutation occurs. Id. at 244.

       Turning to this case, Dr. Descartes explained that the DYNC mutation impacted the
function of a gene intended to code the production of dynein, a protein important to cell function

                                                  22
(particularly aiding in intercellular communication or the movement of internal organelles). Tr. at
247. She characterized the DYNC gene as evolutionarily conserved and therefore critical to
biologic development. Id. at 258. Dynein, she explained, is important to early brain development,
but continues to be relevant thereafter to brain functioning (and thus the genes responsible for its
coding do not simply shut down later in life). Id. at 248, 275–76. In concordance with the Ambry
Genetics test results description, Dr. Descartes noted that the specific mutation in question (one of
fifty known variants of DYNC mutations) was located at exon 13, and caused the production of
phenylalanine to be replaced by serine. Id. at 249, 250.

       Dr. Descartes characterized L.M.’s version of the mutation as particularly rare—and,
because it was de novo, serious, as de novo mutations are more commonly associated with negative
outcomes. Tr. at 252, 280. However, she also acknowledged that it could not be predicted in
advance with complete certainty what any outcomes would be for individuals bearing DYNC
mutations, and that the possession of certain mutations was not necessarily determinative of
outcome. Id. at 253, 275, 279, 280.

        In response to Dr. Boles, Dr. Descartes devoted a large portion of her testimony and expert
reports to rebutting Petitioner’s proposition that the precise location of the DYNC mutation was
significant. She admitted that L.M.’s mutation was located in the gene’s stem/tail location.
Descartes Rep. at 3. However, although Dr. Descartes acknowledged that mutations in that location
were viewed by the relevant literature as generally resulting in polyneuropathic symptoms, while
mutations found in the gene’s stalk/motor domain were associated with more severe intellectual
deficits (i.e., cortical malformation, seizure disorders, etc.), she disputed that stem/tail mutations
were invariably associated only with more benign outcomes. Tr. at 254, 261, 283–84, 289. In her
view, a range of outcomes was always possible regardless of mutation location. Id. at 266–68. In
so proposing, she maintained that it was the mutation itself that mattered more than its location,
given the overall significance of the DYNC gene’s function. Id. at 258 (“the gene has all these
regions that are very important. They are not static”).

       To support her opinion, Dr. Descartes referenced several instances in medical literature in
which the location of a DYNC mutation was discussed. See generally Tr. at 262–66. For example,
she mentioned a case report involving one patient with a de novo DYNC mutation in the stem/tail
region of the gene who experienced severe intellectual deficits and late onset epilepsy but not the
neuropathic symptoms that Dr. Boles had argued were characteristic of tail mutations. Id. at 262
(discussing Hoang at 16, Table S1). Hoang (published two years after Strickland) specifically
reviewed fourteen individual cases of DYNC mutations in humans, plus three in mice that resulted
in motor and sensory defects. In discussing this particular case of a tail-located mutation, Hoang’s
authors observed that “[r]emarkably, the tail mutation with the strongest effect on processive
movements of the dynein-dynactin-BICD2N complex in our study—K129I—is the one farthest

                                                 23
away from the motor domain.” Id. at 9 (emphasis added).27 Hoang overall is more tentative in
embracing the interpretation of Strickland Dr. Boles proposes, emphasizing that overall too much
remains unknown about the possible mutations (not all of which are even pathogenic) or the
mechanisms effected thereby. Id. at 1597, 1603 (“the dynamic changes within the motor complex
[resulting from mutation] . . . are only partially understood”).

        In another piece of literature evaluating the association between the DYNC mutation and
polyneuropathies, a patient with a DYNC mutation in the stalk/motor function region experienced
only mild intellectual delay (contrary to what Dr. Boles argued would be expected for a mutation
in that location of the gene). Tr. at 263 (discussing C. Fiorillo, et al., Novel Dynein DYNC1H1
Neck and Motor Domain Mutations Link Distal SMA and Abnormal Cortical Development, 35
Human Mutation 298 (2014), filed as Ex. CC, ECF No. 71-3). Dr. Descartes admitted on cross-
examination that DYNC mutations in the stalk/motor function region of the gene would in most
cases result in more severe outcomes, but persisted in maintaining that location was overall not a
robust predictor. Id. at 284.

        Turning to the medical records, Dr. Descartes reviewed L.M.’s condition, relating it to the
preexisting DYNC mutation. She characterized L.M. as having severe intellectual disabilities,
along with evident cortical and brain malformation. Tr. at 259. This outcome was, in Dr.
Descartes’s view, consistent with her mutation. Id. at 254. She could not say if the mutation in this
case resulted in a presentation more or less severe than what others similarly situated would face—
but cited the existence of another person who experienced the DYNC mutation but a similar
outcome as evidence that the “pathogenic mutation” was the most likely explanation for L.M.’s
symptoms. Id. at 259; see also id. at 256, 284, and 286.

        This individual is only glancingly referenced in the Ambry Genetics report on L.M.’s
DYNC mutation. Ex. 42 at 41 (describing L.M.’s mutation as “previously detected internally at
Ambry Genetics in a female patient with a history of infantile spasms, intellectual disability,
autism spectrum disorder, reduced muscle tone in all extremities, and gray matter heterotopia on
MRI”). However, the relevant patient was discussed with somewhat more specificity in a
subsequent article. Tr. at 256–57, 268, 270, 288; K. Helbig, et al., Diagnostic Exome Sequencing
Provides a Molecular Diagnosis for a Significant Proportion of Patients with Epilepsy, 18
Genetics in Med. 898 (2016), filed as Ex. OO, ECF No. 90-1 (“Helbig”). Dr. Descartes testified
that she had personally telephoned Ambry Genetics to inquire about the similar patient, whereupon
an Ambry Genetics representative informed her that this patient had been reported in the Helbig
article. Tr. at 272. That child possessed a DYNC mutation identical to L.M.’s—including
location—and a highly similar phenotypic presentation (infantile spasms coupled with a

27
  In discussing the effect of tail mutations, Hoang’s authors also noted that “many sites along the [DYNC] tail are
involved in regulating motor activity,” further diminishing the reliability of the stem/tail versus stalk/motor mutation
distinction urged by Dr. Boles. Hoang at 9.

                                                          24
subsequent epileptic encephalopathy). Tr. at 270; Helbig at 11 (Table 3, Patient ID 32).28 Dr.
Descartes admitted that there was no way to determine if the second child had faced the same
environmental factors that arguably affected the outcome of L.M.’s mutation (including
vaccination). Id. at 287. She nevertheless stressed that articles like Helbig recognized the
commonalities between the DYNC mutation and the kinds of symptoms L.M. experienced. Id.
at 269–70.

         Dr. Descartes spent some time in her testimony discussing the putative causal role
vaccination may have played in L.M.’s subsequent illness. She asserted that she was not aware of
literature establishing any connection between the DYNC mutation and vaccination. Tr. at 284–
85. She did allow that a wild virus infection could constitute an environmental factor that might
interact with the sequelae primarily stemming from a genetic variant, due to a reduced tolerance
to infection. Id. at 285. But she disclaimed the ability to opine on whether a vaccine could impact
the symptomatic course caused otherwise by a mutation absent more specific, reliable studies on
the subject. Id.

        Dr. Descartes more affirmatively denied that L.M.’s outcome was worse than what would
have been expected absent vaccination. Tr. at 259. In support, she referenced the Willemsen article,
which discusses the overall severe outcomes associated with the DYNC mutation regardless of the
mutation’s precise location. Id. at 259–60. Willemsen evaluated the phenotypic outcome for two
patients who possessed a DYNC mutation—one in the stem domain, the other in the motor domain.
Willemsen at 181 Fig. 2. Although the phenotypes were not identical, they both featured
intellectual disability, and were deemed sufficiently similar to conclude that “de novo mutations
in [DYNC] causes variable phenotypes including severe [intellectual disability] with variable
neuronal migration defects, and peripheral neuropathy.” Id. at 179. In citing Willemsen, she also
noted that one of the two referenced individuals in that article had experienced brain malformations
much like Dr. Shuman observed in the L.M.’s MRIs, along with intellectual deficits and
neuropathic symptoms. Tr. at 259–60 (discussing Willemsen at 4). And she cited the patient
discussed in Strickland as evidencing the severity of DYNC mutation outcomes and how
comparable those outcomes were to L.M.’s experience. Tr. at 260 (discussing Strickland at 6).

28
   Ex. OO was not filed before hearing, nor was it referenced in Dr. Descartes’s report, although Dr. Descartes did in
her report mention the similar patient when discussing the Ambry Genetics test results report. See Descartes Rep. at
3. During cross-examination of Dr. Descartes, Petitioner’s counsel pointed these factors out in arguing that the exhibit
should not be admitted in evidence. I nevertheless have allowed it in, based upon the general understanding that late-
filed evidence, if relevant to the claim, is routinely permitted into the record in the Vaccine Program. Tr. at 272–74. I
maintain that holding herein—and note in addition that since the Ambry Genetics testing report unquestionably
references the similarly-situated child in the first place, the relevance of the subsequent document (which merely
provides more details about the other child) is self-evident, and outweighs whatever slight prejudicial effect its late
filing might have. The parties expressly agreed not to file post-trial briefs (tr. at 378), and Petitioner never filed
anything after hearing in response to this exhibit.

                                                          25
       4.      Dr. John Zempel

        Dr. Zempel, a pediatric neurologist, prepared two reports and was Respondent’s second
expert witness to testify. See Ex. B, ECF No. 21-1 (“Zempel First Rep”); Ex. I, ECF No. 34-1
(“Zempel Second Rep.”). He offered the opinion that L.M.’s seizure disorder reflected a “classic
presentation” that could not be credibly linked to her vaccinations other than temporally. Tr.
at 322.

        Dr. Zempel received his B.S. from the University of Wisconsin-Madison, followed by his
M.D. and Ph.D. from Washington University in St. Louis. Ex. C at 1, ECF No. 21-2. He completed
residencies in pediatrics, adult neurology, and child neurology, as well as fellowships in pediatric
epilepsy and clinic neurophysiology. Id. at 2. He is board certified in neurology, child neurology,
and psychiatry, and was previously also board certified in pediatrics, though he acknowledged that
he has not maintained that certification. Tr. at 297. Dr. Zempel divides his professional time
between clinical work (inpatient neurology exams involving children with epilepsy and infantile
spasm disorders) and teaching at Washington University Medical School, publishing, and acting
as a peer reviewer for medical journals. Id. at 293–94, 296. He estimates that in his clinical practice
he routinely sees between eight and twenty patients per day, and he had examined a patient with
infantile spasms disorder within a month of his hearing testimony. Id. at 297.

        Like Dr. Descartes, Dr. Zempel began by defining certain terms relevant to L.M.’s
condition. In his view, the classic term “seizure disorder” was being displaced by the more precise
concept of “epileptic encephalopathy,” which he defined as including seizures as a symptom
attributable to some other, larger “underlying problem in brain function.” Tr. at 299 (“[t]he seizures
are not the disease”). That brain dysfunction could include other symptoms in addition to seizures,
such as developmental regression or delay. Dr. Zempel characterized West syndrome (infantile
spasm disorder) as “one of the prime epileptic encephalopathies that involve infants.” Id. at 298–
99.

        Dr. Zempel also reviewed his understanding of the term “encephalopathy.” He defined it
to mean some kind of brain disease, whether short or long-term. Tr. at 298. He rejected the concept
of a “structural encephalopathy” proposed by Dr. Shuman, however, positing that the proper way
to characterize a brain malformation such as that allegedly present in L.M. was to call it a
“structural abnormality.” Id. at 300. Dr. Zempel differentiated epileptic encephalopathies from an
acute encephalopathy, emphasizing that children diagnosed with a spasm disorder that would fall
within the category of an epileptic encephalopathy, despite the severity of such a condition, do not
suffer from the inability to function normally in many respects that a child suffering from a severe
acute encephalopathy would experience. Id. at 298, 317.

                                                  26
        As Dr. Zempel explained, infantile spasms disorder (named for its classic temporal
presentation in infancy) can feature a variety of seizures.29 Tr. at 300–01. Its clinical definition,
however, also requires evidence of hypsarrhythmia corroborated by EEG readings, as well as
evidence of developmental delay. Id. at 302. It is a progressive condition, and can present first
with spasms or be uncovered by EEG absent spasms. Id. at 352–53. Because “the syndrome of
infantile spasms is more than just the spasms,” seizures alone are not, in Dr. Zempel’s view, an
alarming occurrence capable of leading to “long-term neurodevelopmental problems.” Id. at 336,
337 (“I don’t stress out” when presented with a child experiencing a cluster of overnight seizures,
assuming they can be controlled with treatment), 338. Because its initial presentation is not clear-
cut in children, it can be difficult for parents to recognize seizure activity as a precursor. Id. at 301–
02.

        Dr. Zempel went on to discuss the possible known causes of infantile spasms,
differentiating between symptomatic (where a cause is known) and cryptogenic (spasms similar to
the symptomatic kind but where no etiology is understood). Tr. at 304–05. Symptomatic spasms
can be caused by brain malformation, stroke or other brain injury (often occurring prenatally), a
metabolic disorder, or can have a genetic origin attributable to a chromosomal abnormality such
as Down syndrome.30 Id. at 303. EEGs and neuroimaging can aid treaters in identifying if a spasm
disorder’s source is attributable to brain abnormalities. Id. at 304. Advances in genetic testing have
also helped establish certain genetic variants as a potential underlying source of a spasm disorder,
thereby reducing the number of such disorders deemed cryptogenic. Id. at 306–07, 359–60. Dr.
Zempel stressed the importance of trying to identify the source of such infantile spasms, given
how few causes could be directly treated (meaning that in all other cases the priority of treatment
would be limited to controlling the symptoms). Id. at 305.

       Based upon a review of the medical record, Dr. Zempel agreed that L.M. suffers from West
syndrome. Tr. at 309. But he took issue with Dr. Shuman’s assertion that L.M. had PNTLE or any
other white matter deficiency. He asserted that PNTLE was not a commonly-employed diagnostic
term, maintaining that it was subsumed within the category of periventricular leukomalacia
(“PVL”), an “all too common complication of extreme prematurity” that was notably severe
(especially in comparison to L.M.’s presentation). Id. at 310.31 PVL is often detectable from

29
  In so testifying, Dr. Zempel distinguished between generalized seizures, which affect the whole body, and partial
seizures, which affect only a certain area, such as one limb or the face. Tr. at 300. He also distinguished between
different seizures patterns: clonic seizures involve jerking movements; tonic seizures involve stiffening of the body;
and myoclonic seizures feature “lightning-quick jerks.” Id.
30
   Down syndrome results from trisomy of chromosome 21 and presents with moderate to severe developmental
disabilities and distinctive facial characteristics. Dorland’s at 1828.
31
  Importantly, L.M. was born at term (Ex. 1 at 5), yet Dr. Shuman continued to suggest that she suffers from PNTLE
or PVL in spite of his concession that these conditions are strongly correlated with prematurity. Tr. at 163.

                                                         27
prenatal screening ultrasounds, and can be confirmed when an at-risk child approaches term by
MRI. Id. at 311.

        Here, however, Dr. Zempel disputed that L.M.’s MRIs supported a PVL, PNTLE, or white
matter deficiency diagnosis, noting that his opinion (informed by his own viewing of the relevant
MRIs) was echoed by the treating neuroradiologist who performed the MRIs at the relevant time.
Tr. at 311; see generally Ex. 69. He agreed that L.M.’s ventricles appeared “a little bit generous”
in size, but opined that most neuroradiologists would not deem them abnormal, adding that the
treaters who actually performed the MRIs at issue did not themselves include “ventriculomegaly”
in their recorded findings. Id. at 312. He therefore disputed that L.M.’s post-vaccination spasms
and sequelae could be attributed to brain abnormality.32

         Dr. Zempel also questioned Dr. Shuman’s assertion that L.M. experienced any other form
of pre-vaccination encephalopathy. In his view, the only “clinically significant” evidence of an
existing encephalopathy would be proof that an infant “doesn’t function well.” Tr. at 317, 319
(“one good indication of whether someone is severely encephalopathic is whether they can
function as a baby or as a human”). But his reading of the record did not support that conclusion.
Id. at 317. Thus, despite her parents’ understandable concerns that L.M. receive the highest quality
care, and their valid bases for seeking medical intervention on February 15, 2011, L.M.’s treaters
did not deem her initial presentation severe. Id. at 319. Dr. Comes, L.M.’s pediatrician, seems to
have concurred, and Dr. Zempel also found significant the fact that L.M. did not present in a coma
and was otherwise not thought to require immediate transfer to St. Vincent Hospital (despite the
views of Mr. Moore and Ms. Sharpe that a transfer was necessary). Id. at 318–19. And thereafter,
once L.M. received a neurologic evaluation, she was discharged and allowed to go home. Id.
at 322.33

       In testifying whether the medical record established that L.M. had experienced an
encephalopathy, Dr. Zempel discussed the relevance of fever. He agreed with Dr. Shuman that
L.M.’s temperature reading of 103 degrees Fahrenheit (as provided by Ms. Sharpe) was high
regardless of the manner in which it was taken, and could reflect a vaccine reaction. Tr. at 320.
But Dr. Zempel denied that fever is strongly associated with an existing encephalopathy,34 and

32
  Dr. Zempel, did, however, acknowledge that the structural issues pointed to by Dr. Shuman could constitute “a sign
that [L.M.]’s brain development hasn’t been normal,” even though he discounted any such developmental problems
as causative of her post-vaccination spasms and developmental problems. Tr. at 359.
33
  Because Dr. Zempel did not accept the contention that L.M. had experienced any form of encephalopathy before
receiving the vaccinations at issue, he rejected the contention that L.M.’s underlying condition was significantly
aggravated by those same vaccines. Tr. at 322.
34
  Dr. Zempel accepted Petitioner’s counsel’s point on cross-examination that a fever could in certain cases be high
enough to precipitate brain injury, although he also noted that infants have better tolerance of such high temperatures,
and otherwise disputed the concept that L.M. may have merely experienced a “transient” encephalopathy. Tr. at 348–
49.

                                                          28
noted that L.M.’s overall presentation at the time she was first taken to the ER did not seem any
more severe than when she had been treated for URIs and associated congestion in the early weeks
of 2011 prior to vaccination. Id. at 319–20. He also admitted on cross-examination that L.M. had
displayed a concerning reduced responsiveness at the time of the fever, but disputed that such
elements together amounted to evidence of acute encephalopathy meriting hospitalization. Id. at
343–44, 350. And he allowed that certain conditions also known to have a genetic cause, like
Dravet syndrome,35 could be provoked by a febrile-caused seizure (which in turn could have a
vaccination as the trigger), but argued that not enough is known about such illnesses to say whether
vaccination is the primary cause of the condition’s progression or simply an event temporally
coincidental to an increase in symptoms (especially given that children received certain vaccines
at the same age as when Dravet symptoms are known to present and/or expand). Id. at 353–56.

        Dr. Zempel next attacked Petitioner’s theory that vaccination could trigger (or exacerbate)
an infantile spasms disorder. He maintained that no persuasive or reliable data associates vaccines
with infantile spasms. Tr. at 322–23. Indeed, in his view it would be rare that any external “inciting
factor” would cause infantile spasms. Id. at 329. Dr. Zempel discounted the evidentiary value of
the UK Study given its age, noting that it was performed before imaging or genetic testing of the
kind used today to identify etiologies for epileptic encephalopathies was possible, and also that it
involved a vaccine component (whole cell pertussis) that has since been mostly abandoned. Id. at
323, 325. By contrast, studies like Bellman (performed not long after the UK Study) did not find
the same association between vaccines and infantile spasms. Id. at 325.

         In Dr. Zempel’s view, Petitioner’s case fared no better on the “did cause” side of her claim.
Based on his overall reading of the medical records, he termed L.M.’s history to constitute a
“classic presentation” of an infantile spasm disorder only temporally coinciding with the vaccines
she received in February 2011. Tr. at 322. The course of her illness from before vaccination to the
present was in his opinion consistent with “treatment-nonresponsive” individuals suffering from
infantile spasms. Id. at 334. He agreed that there was no evidence of developmental delay prior to
vaccination, and that the records from L.M.’s immediate post-vaccination treatment did suggest
some differences in her motor presentation. Id. at 340, 342–43. He also acknowledged that some
records from L.M.’s time at St. Vincent Hospital revealed reduced responsiveness to parental
contact, but noted that those same records revealed that contemporaneous treaters attributed such
behaviors to drug reactions (administered in response to her seizure activity) or simple sleepiness.
Id. at 345–46. He emphasized that reduced responsiveness could not simply be seen as a presenting
symptom for developmental decline, given the number of possible factors that could explain it
(especially given the context of emergency hospitalization of an infant). Id. at 346–47.

35
  Dravet syndrome is a rare seizure condition, also called Severe Myoclonic Epilepsy of Infancy, linked to mutations
in the SCN1A gene. Faoro v. Sec’y of Health & Human Servs., 127 Fed. Cl. 61, 63–64 (2016).

                                                        29
        Dr. Zempel sought to identify record evidence he felt supported the conclusion that L.M.’s
seizure activity likely preceded her receipt of the vaccines at issue. He allowed that L.M.’s GERD
symptoms could have resembled spasms, but nevertheless maintained that the records otherwise
contained references to incidents suggesting a pre-vaccination onset (although he did not dispute
that Ms. Sharpe had properly recognized L.M.’s condition as a reason to bring her to the ER on
February 15th). Tr. at 313–14 (discussing Ex. 3 at 15; Ex. 4 at 3), 321, 335–36, 339–40. In fact,
he questioned whether the histories provided by Ms. Sharpe and Mr. Moore to treaters of pre-
vaccination incidents described GERD symptoms at all. Id. at 315–16. He also pointed out items
in the medical record that suggested L.M. had poor muscle tone before being vaccinated as well
(the kind of symptom Petitioner has argued is evidence of vaccine causality). Id. at 340. Dr. Zempel
emphasized that as a treater he would generally want to inquire of parents if the seizure activity
that prompted them to seek medical intervention predated the reason for their visit, noting that
parents often only realize after the most recent (and alarming) seizure event that prior, milder
occurrences were related. Id. at 314–15, 317 (pointing out how common it is for parents only to
recognize that seizure activity has been ongoing after a “larger sentinel event”).

        Finally, Dr. Zempel directed some of his testimony to the issue of the DYNC mutation and
its bearing on the causation question.36 In his view, the fact that the mutation in question occurred
in connection with the DYNC gene—understood to have been conserved through evolution and
thus highly important—was strong proof that it was more likely the cause of L.M.’s condition
(since an error in an important gene’s coding function would be expected to be more calamitous).
Tr. at 327. In addition, and as the Ambry Genetics report first revealed, another child like L.M.
with the same DYNC mutation experienced a similar outcome, underscoring the mutation’s role
in causation. Id. at 327–28. The temporal relationship between the vaccinations at issue, he added,
did not reduce the greater likelihood that L.M.’s condition was mostly attributable to the mutation,
stressing that the age-dependent component of infantile spasms meant that their onset would
always be temporally coincidental to the administration of certain childhood vaccines. Id. at 329.
And he dismissed the contention that vaccines could significantly aggravate a condition with a
genetic source, comparing the DYNC mutation at issue in this case to what is known about Dravet
syndrome (caused by a different genetic mutation); the overall course of the latter, he testified, is
not affected by vaccination, even if a vaccine can cause a transient symptomatic spike (for
example, due to a fever induced by the vaccine). Id. at 330–33.

III.     Procedural History

       As noted above, the case was filed in January 2014, with the petition amended on October
7, 2014, and again on May 27, 2015. See Pet.; Am. Pet., ECF No. 15; Second Am. Pet., ECF

36
  Dr. Zempel is not a geneticist, and so I give his comments on this topic less weight than those of Drs. Descartes or
Boles. At the same time, however, Dr. Zempel’s expertise on the subject of infantile spasms does give him a basis for
discussing known causes of the condition, including genetic etiologies—and his background in diagnosing and treating
the relevant injury far exceeds that of any other expert testifying in this case.

                                                         30
No. 26. In the months following the filing of the petition in this case, Petitioner filed medical
records, affidavits, and an expert in support of her claim. Respondent subsequently filed a Rule
4(c) Report on November 14, 2014, arguing that compensation was not appropriate in this case.
Respondent also filed an expert report on January 16, 2015, which supported this conclusion.
Thereafter, Petitioner filed a supplemental expert report on June 10, 2015, and Respondent
submitted a responsive expert report on September 30, 2015. In addition, and as addressed in detail
below, Petitioner also filed a “Motion for a Determination of Law Governing Petitioner’s Table
Significant Aggravation Claim,” on February 26, 2016.

        The entitlement hearing was held in March 2018. The parties did not elect to file post-trial
briefs. Tr. at 378.

IV.      Applicable Legal Standards

         A.       Claimant’s Burden in Vaccine Program Cases

        To receive compensation in the Vaccine Program, a petitioner must prove either: (1) that
he suffered a “Table Injury”—i.e., an injury falling within the Vaccine Injury Table, corresponding
to one of the vaccinations in question and also occurring within a statutorily-prescribed period of
time—or, in the alternative, (2) that his illnesses were actually caused by a vaccine (a “Non-Table
Injury”). See Sections 13(a)(1)(A), 11(c)(1), and 14(a), as amended by 42 C.F.R. § 100.3; see also
Shalala v. Whitecotton, 514 U.S. 268, 270 (1995) (quoting 42 U.S.C. § 11(c)(1)(C)(i)); Moberly
v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1321 (Fed. Cir. 2010); Capizzano v. Sec’y of
Health & Human Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006).37 Petitioner in this case asserts
both types of claims.

        For both Table and Non-Table claims, Vaccine Program petitioners bear a “preponderance
of the evidence” burden of proof. Section 13(1)(a). That is, a petitioner must offer evidence that
leads the “trier of fact to believe that the existence of a fact is more probable than its nonexistence
before [he] may find in favor of the party who has the burden to persuade the judge of the fact’s
existence.” Moberly, 592 F.3d at 1322 n.2; see also Snowbank Enter. v. United States, 6 Cl. Ct.
476, 486 (1984) (mere conjecture or speculation is insufficient under a preponderance standard).
A petitioner may not receive a Vaccine Program award based solely on his assertions; rather, the

37
  Decisions of special masters (some of which I reference in this ruling) constitute persuasive but not binding
authority. Hanlon v. Sec’y of Health & Human Servs., 40 Fed. Cl. 625, 630 (1998). By contrast, Federal Circuit rulings
concerning legal issues are binding on special masters. Guillory v. Sec’y of Health & Human Servs., 59 Fed. Cl. 121,
124 (2003), aff’d, 104 F. App’x 712 (Fed. Cir. 2004); see also Spooner v. Sec’y of Health & Human Servs., No. 13-
159V, 2014 WL 504728, at *7 n.12 (Fed. Cl. Spec. Mstr. Jan. 16, 2014).

                                                         31
petition must be supported by either medical records or by the opinion of a competent physician.
Section 13(a)(1).

       When a Table Injury claim is successfully established, causation is presumed. 42 C.F.R.
§ 100.3. Table claims must satisfy with evidence the specific elements of the relevant claim,
including the definitions of terms set in the Qualifications and Aids to Interpretation (the “QAI”).
Section 14(b). Case law underscores that, to obtain the benefit of the presumption of causation
associated with a Table claim, the claim’s requirements must be strictly construed. Miller v. Sec’y
of Health & Human Servs., No. 02-235V, 2015 WL 5456093, at *24 (Fed. Cl. Spec. Mstr. Aug.
18, 2015) (requiring petitioner to satisfy the “strict Table definition” of encephalopathy).

        For a non-Table claim, proof of medical certainty is not required. Bunting v. Sec’y of Health
& Human Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). In such circumstances, a petitioner must
demonstrate that the vaccine was “not only [the] but-for cause of the injury but also a substantial
factor in bringing about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health
& Human Servs., 165 F.3d 1344, 1352–53 (Fed. Cir. 1999)); Pafford v. Sec’y of Health & Human
Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). A petitioner asserting a non-Table claim must satisfy
all three of the elements established by the Federal Circuit in Althen v. Secretary of Health &
Human Services: “(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
1274, 1278 (Fed. Cir. 2005).

        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, 451 F.3d at 1355–56 (citations omitted). To satisfy this prong, the
petitioner’s theory must be based on a “sound and reliable medical or scientific explanation.”
Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). Such a theory
must only be “legally probable, not medically or scientifically certain.” Id. at 549.

        Petitioners may satisfy the first Althen prong without resort to medical literature,
epidemiological studies, demonstration of a specific mechanism, or a generally accepted medical
theory. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1378–79 (Fed. Cir. 2009)
(citing Capizzano, 440 F.3d at 1325–26). Special masters, despite their expertise, are not
empowered by statute to conclusively resolve what are essentially thorny scientific and medical
questions, and thus scientific evidence offered to establish Althen prong one is viewed “not through
the lens of the laboratorian, but instead from the vantage point of the Vaccine Act’s preponderant
evidence standard.” Id. at 1380. Accordingly, special masters must take care not to increase the
burden placed on petitioners in offering a scientific theory linking vaccine to injury. Contreras v.

                                                 32
Sec’y of Health & Human Servs., 121 Fed. Cl. 230, 245 (2015), vacated on other grounds, 844
F.3d 1363 (Fed. Cir. 2017).

        In discussing the evidentiary standard applicable to the first Althen prong, many decisions
of the Court of Federal Claims and Federal Circuit have emphasized that petitioners need only
establish a causation theory’s biologic plausibility (and thus need not do so with preponderant
proof). Tarsell v. United States, 133 Fed. Cl. 782, 792–93 (2017) (special master committed legal
error by requiring petitioner to establish first Althen prong by preponderance; that standard applied
only to second prong and petitioner’s overall burden); Contreras, 121 Fed. Cl. at 245
(“[p]lausibility . . . in many cases may be enough to satisfy Althen prong one” (emphasis in
original)); see also Andreu, 569 F.3d at 1375. At the same time, there is contrary authority from
the Federal Circuit suggesting that the preponderance standard applied when evaluating a
claimant’s overall success in a Vaccine Act claim also bears on the first Althen prong. See, e.g.,
Broekelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1350 (Fed. Cir. 2010) (affirming
special master’s determination that expert “had not provided a ‘reliable medical or scientific
explanation’ sufficient to prove by a preponderance of the evidence a medical theory linking the
[relevant vaccine to relevant injury]”) (emphasis added). Regardless, one thing remains: petitioners
always have the ultimate burden of establishing their Vaccine Act claim overall with preponderant
evidence. W.C. v. Sec’y of Health & Human Servs., 704 F.3d 1352, 1356 (Fed. Cir. 2013) (citations
omitted); Tarsell, 133 Fed. Cl. at 793 (noting that Moberly “addresses the petitioner’s overall
burden of proving causation-in-fact under the Vaccine Act” by a preponderance).

        The second Althen prong requires proof of a logical sequence of cause and effect, usually
supported by facts derived from a petitioner’s medical records. Althen, 418 F.3d at 1278; Andreu,
569 F.3d at 1375–77; Capizzano, 440 F.3d at 1326; Grant v. Sec’y of Health & Human Servs., 956
F.2d 1144, 1148 (Fed. Cir. 1992). In establishing that a vaccine “did cause” injury, the opinions
and views of the injured party’s treating physicians are entitled to some weight. Andreu, 569 F.3d
at 1367; Capizzano, 440 F.3d at 1326 (“medical records and medical opinion testimony are favored
in vaccine cases, as treating physicians are likely to be in the best position to determine whether a
‘logical sequence of cause and effect show[s] that the vaccination was the reason for the injury’”)
(quoting Althen, 418 F.3d at 1280). Medical records are generally viewed as particularly
trustworthy evidence, since they are created contemporaneously with the treatment of the patient.
Cucuras v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).

        However, medical records and/or statements of a treating physician’s views do not per se
bind the special master to adopt the conclusions of such an individual, even if they must be
considered and carefully evaluated. Section 13(b)(1) (providing that “[a]ny such diagnosis,
conclusion, judgment, test result, report, or summary shall not be binding on the special master or
court”); Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 746 n.67 (2009) (“there is
nothing . . . that mandates that the testimony of a treating physician is sacrosanct—that it must be

                                                 33
accepted in its entirety and cannot be rebutted”). As with expert testimony offered to establish a
theory of causation, the opinions or diagnoses of treating physicians are only as trustworthy as the
reasonableness of their suppositions or bases. The views of treating physicians should also be
weighed against other, contrary evidence also present in the record—including conflicting
opinions among such individuals. Hibbard v. Sec’y of Health & Human Servs., 100 Fed. Cl. 742,
749 (2011) (not arbitrary or capricious for special master to weigh competing treating physicians’
conclusions against each other), aff’d, 698 F.3d 1355 (Fed. Cir. 2012); Caves v. Sec’y of Health &
Human Servs., 100 Fed. Cl. 119, 136 (2011), aff’d, 463 F. App’x 932 (Fed. Cir. 2012); Veryzer v.
Sec’y of Health & Human Servs., No. 06-522V, 2011 WL 1935813, at *17 (Fed. Cl. Spec. Mstr.
Apr. 29, 2011), mot. for review denied, 100 Fed. Cl. 344, 356 (2011), aff’d without opinion, 475
F. App’x 765 (Fed. Cir. 2012).

        The third Althen prong requires establishing a “proximate temporal relationship” between
the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been equated to the
phrase “medically-acceptable temporal relationship.” Id. A petitioner must offer “preponderant
proof that the onset of symptoms occurred within a timeframe which, given the medical
understanding of the disorder’s etiology, it is medically acceptable to infer causation.” Bazan v.
Sec’y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for what
is a medically acceptable timeframe must also coincide with the theory of how the relevant vaccine
can cause an injury (Althen prong one’s requirement). Id. at 1352; Shapiro v. Sec’y of Health &
Human Servs., 101 Fed. Cl. 532, 542 (2011), recons. denied after remand, 105 Fed. Cl. 353 (2012),
aff’d mem., 2013 WL 1896173 (Fed. Cir. 2013); Koehn v. Sec’y of Health & Human Servs., No.
11-355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review denied (Fed.
Cl. Dec. 3, 2013), aff’d, 773 F.3d 1239 (Fed. Cir. 2014).

       B.      Standard for Significant Aggravation Claim

        In this matter, Petitioner maintains that the relevant vaccines significantly aggravated
L.M.’s preexisting genetic mutation or other brain malformation/white matter deficiency. Where
a petitioner so alleges, the Althen test is expanded, and the petitioner has additional evidentiary
burdens to satisfy. See generally Loving v. Sec’y of Health & Human Servs., 86 Fed. Cl. 135, 144
(2009). In Loving, the Court of Federal Claims combined the Althen test with the test from
Whitecotton v. Secretary of Health & Human Services, 81 F.3d 1099, 1107 (Fed. Cir. 1996), which
related to on-Table significant aggravation cases. The resultant “significant aggravation” test has
six components, which are:

       (1) the person’s condition prior to administration of the vaccine, (2) the person’s current
       condition (or the condition following the vaccination if that is also pertinent), (3) whether
       the person’s current condition constitutes a ‘significant aggravation’ of the person's
       condition prior to vaccination, (4) a medical theory causally connecting such a

                                                34
         significantly worsened condition to the vaccination, (5) a logical sequence of cause and
         effect showing that the vaccination was the reason for the significant aggravation, and (6)
         a showing of a proximate temporal relationship between the vaccination and the
         significant aggravation.

Loving, 86 Fed. Cl. at 144; see also W.C., 704 F.3d at 1357 (holding that “the Loving case provides
the correct framework for evaluating off-table significant aggravation claims”). In effect, the last
three prongs of the Loving test correspond to the three Althen prongs.

        Subsumed within the Loving analysis is the requirement to evaluate the likely natural
course of an injured party’s preexisting disease, in order to determine whether the vaccine made
the petitioner worse than he would have been but for the vaccination. Locane v. Sec’y of Health &
Human Servs., 685 F.3d 1375, 1381–82 (Fed. Cir. 2012) (upholding special master’s determination
that petitioner had failed to carry her burden of proof in establishing that her preexisting injury
was worsened by the relevant vaccine); Hennessey v. Sec’y of Health & Human Servs., No. 01-
190V, 2009 WL 1709053, at *41–42 (Fed. Cl. Spec. Mstr. May 29, 2009), mot. for review denied,
91 Fed. Cl 126 (2010). The critical point of examination is thus “whether the change for the worse
in [petitioner’s] clinical presentation was aggravation or a natural progression” of the underlying
condition. Hennessey, 2009 WL 1709053, at *42.38 The Federal Circuit has upheld the
determinations of special masters that worsening was not demonstrated by a petitioner in
connection with establishing her overall preponderant burden of proof for a non-Table causation-
in-fact claim. See, e.g., Snyder/Harris v. Sec’y of Health & Human Servs., 553 F. App’x 994, 999-
1000 (Fed. Cir. 2014); Locane, 685 F.3d at 1381–82.39

        Application of Loving’s “worsening” requirement has been the occasion for some disparate
holdings by special masters as well as the Court, especially due to the problems posed when
evaluating the impact of a preexisting genetic condition that likely played some role in an injured
party’s post-vaccination health. In some cases, the mere fact that an injured party was literally

38
   The legislative history of the Vaccine Act strongly supports interpreting “significant aggravation” as requiring a
claimant to establish that a vaccine rendered a preexisting condition qualitatively worse than it would have been
otherwise—not simply that the affected individual experienced a post-vaccination symptom that contrasts with the
individual’s comparatively better pre-vaccination health. See H.R. Rep. No. 99-908, at 15 (1986) (“This [significant
aggravation] provision does not include compensation for conditions which might legitimately be described as pre-
existing (e.g., a child with monthly seizures who, after vaccination, has seizures every three and a half weeks), but is
meant to encompass serious deterioration (e.g., a child with monthly seizures who, after vaccination, has seizures on
a daily basis” (emphasis added)).
39
  This is consistent with the fact (well recognized by controlling precedent) that evidence of “worsening” relevant to
Respondent’s alternative cause burden may reasonably by evaluated by a special master in determining the success of
a petitioner’s prima facie showing. Snyder/Harris, 553 F. App’x at 1000, quoting Stone, 676 F.3d at 1380 (“no
evidence should be embargoed from the special master’s consideration simply because it is also relevant to another
inquiry under the statute”); see also Bazan, 539 F.3d at 1353 (“[t]he government, like any defendant, is permitted to
offer evidence to demonstrate the inadequacy of the petitioner’s evidence on a requisite element of the petitioner’s
case-in-chief”).

                                                          35
“worse” than she was immediately prior to the vaccination at issue has been viewed as sufficient
to satisfy this prong. See, e.g., Paluck v. Sec’y of Health & Human Servs., 113 Fed. Cl. 210, 232
(2013), aff’d, 786 F.3d 1373 (Fed. Cir. 2015).

        In other instances, however, the mere fact a vaccine might “trigger” a transient negative
response in an individual with an underlying condition has not been deemed proof of worsening if
that individual would be expected to experience a similar overall course regardless. Faoro v. Sec’y
of Health &Human Servs., No. 10-704V, 2016 WL 675491, at *27 (Fed. Cl. Spec. Mstr. Jan. 29,
2016), mot. for review denied, 128 Fed. Cl. 61 (Fed. Cl. Apr. 11, 2016) (finding that “the
vaccinations would not have changed her clinical course and thus, the vaccinations did not
significantly aggravate her preexisting condition”). This point has been emphasized in a
subcategory of Program cases involving the claim that a child’s Dravet syndrome was significantly
aggravated by vaccination. Faoro, 2016 WL 675491, at *1. In such cases, special masters have
repeatedly determined that petitioners failed to show that a child’s expected outcome would have
been different but-for the vaccination—even though it was not disputed that the child’s first major
seizure had been triggered by vaccination. Id. at *2 (“[a]lthough H.E.F.’s vaccinations may have
caused a low-grade fever or otherwise triggered her first seizure, neither the initial seizure nor her
vaccinations caused or significantly aggravated her Dravet syndrome and resulting neurological
complications”); see also Snyder/Harris, 553 F. App’x 994 (special master was not arbitrary in
finding that petitioners’ expert failed to show that the child’s outcome would have been different
had he not received the vaccinations at issue).

        In Barclay v. Secretary of Health & Human Services, 122 Fed. Cl. 189 (2015), however,
the Court of Federal Claims called into question whether Loving was the appropriate framework
in cases where a genetic basis for an injured party’s disease is undisputed. There, Judge Bruggink
discussed the fact that “how the genetic abnormality is taken into account” heavily impacted
application of the Loving factors. Barclay, 122 Fed. Cl. at 193. The Court noted that in a case
where a child unquestionably possessed a preexisting genetic mutation associated with a particular
outcome (in Barclay, the SCN1A mutation and its association with Dravet syndrome), the
petitioner would logically seek to argue that the vaccine at issue had aggravated the child’s pre-
vaccination health (which in Barclay involved no manifestation of seizure activity at all prior to
vaccination) by attempting to prove that the vaccine had made the child’s future seizures and
developmental delay “more severe.” Id. at 198. The alternative was untenable; the genetic factor
was too persuasively associated with seizure activity to rule it out, and the fact that the vaccine
(through causing a fever due to its stimulation of the innate immune system) might have directly
caused initial seizure activity was “insufficient to establish liability” based simply on the fact that
the child thereafter recovered (if briefly) from it. Id.

        As a result, Barclay suggested that the Loving analysis might actually not be an “ideal fit”
for cases involving a genetic mutation. Instead, a better way to approach such a case would simply

                                                  36
be to evaluate Respondent’s success in carrying his counter-burden of establishing that a “factor
unrelated” to the vaccine was the cause of injury. Barclay, 122 Fed. Cl. at 193 (citing Knudsen, 35
F.3d at 547). Doing so would avoid requiring a petitioner to establish a disease prognosis in light
of the preexisting genetic mutation (which Barclay deemed to constitute a heightening of the
Petitioner’s underlying burden of proof). Barclay, 122 Fed. Cl. at 198–99.

       C.      Law Governing Factual Determinations

        The process for making determinations in Vaccine Program cases regarding factual issues
begins with consideration of the medical records. Section 11(c)(2). The special master is required
to consider “all [] relevant medical and scientific evidence contained in the record,” including “any
diagnosis, conclusion, medical judgment, or autopsy or coroner’s report which is contained in the
record regarding the nature, causation, and aggravation of the petitioner’s illness, disability, injury,
condition, or death,” as well as “the results of any diagnostic or evaluative test which are contained
in the record and the summaries and conclusions.” Section 13(b)(1)(A). The special master is then
required to weigh the evidence presented, including contemporaneous medical records and
testimony. See Burns v. Sec’y of Health & Human Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (it is
within the special master’s discretion to determine whether to afford greater weight to
contemporaneous medical records than to other evidence, such as oral testimony surrounding the
events in question that was given at a later date, provided that such a determination is evidenced
by a rational determination).

        Medical records that are created contemporaneously with the events they describe are
presumed to be accurate and “complete” (i.e., presenting all relevant information on a patient’s
health problems). Cucuras, 993 F.2d at 1528; Doe/70 v. Sec’y of Health & Human Servs., 95 Fed.
Cl. 598, 608 (2010) (“[g]iven the inconsistencies between petitioner’s testimony and his
contemporaneous medical records, the special master’s decision to rely on petitioner’s medical
records was rational and consistent with applicable law”); Rickett v. Sec’y of Health & Human
Servs., 468 F. App’x 952 (Fed. Cir. 2011) (non-precedential opinion). This presumption is based
on the linked propositions that (i) sick people visit medical professionals; (ii) sick people honestly
report their health problems to those professionals; and (iii) medical professionals record what they
are told or observe when examining their patients in as accurate a manner as possible, so that they
are aware of enough relevant facts to make appropriate treatment decisions. Sanchez v. Sec’y of
Health & Human Servs., No. 11-685V, 2013 WL 1880825, at *2 (Fed. Cl. Spec. Mstr. Apr. 10,
2013); Cucuras v. Sec’y of Health & Human Servs., 26 Cl. Ct. 537, 543 (1992), aff’d, 993 F.2d
1525 (Fed. Cir. 1993) (“[i]t strains reason to conclude that petitioners would fail to accurately
report the onset of their daughter’s symptoms. It is equally unlikely that pediatric neurologists,
who are trained in taking medical histories concerning the onset of neurologically significant
symptoms, would consistently but erroneously report the onset of seizures a week after they in fact
occurred”).

                                                  37
        Accordingly, if the medical records are clear, consistent, and complete, then they should
be afforded substantial weight. Lowrie v. Sec’y of Health & Human Servs., No. 03-1585V, 2005
WL 6117475, at *20 (Fed. Cl. Spec. Mstr. Dec. 12, 2005). Indeed, contemporaneous medical
records are generally found to be deserving of greater evidentiary weight than oral testimony—
especially where such testimony conflicts with the record evidence. Cucuras, 993 F.2d at 1528;
see also Murphy v. Sec’y of Health & Human Servs., 23 Cl. Ct. 726, 733 (1991), aff’d, 968 F.2d
1226 (Fed. Cir.), cert. denied sub nom. Murphy v. Sullivan, 506 U.S. 974 (1992) (citing United
States v. United States Gypsum Co., 333 U.S. 364, 396 (1947) (“[i]t has generally been held that
oral testimony which is in conflict with contemporaneous documents is entitled to little evidentiary
weight.”)).

        However, there are situations in which compelling oral testimony may be more persuasive
than written records, such as where records are deemed to be incomplete or inaccurate. Campbell
v. Sec’y of Health & Human Servs., 69 Fed. Cl. 775, 779 (2006) (“like any norm based upon
common sense and experience, this rule should not be treated as an absolute and must yield where
the factual predicates for its application are weak or lacking”); Lowrie, 2005 WL 6117475, at *19
(“[w]ritten records which are, themselves, inconsistent, should be accorded less deference than
those which are internally consistent”) (quoting Murphy, 23 Cl. Ct. at 733). Ultimately, a
determination regarding a witness’s credibility is needed when determining the weight that such
testimony should be afforded. Andreu, 569 F.3d at 1379; Bradley v. Sec’y of Health & Human
Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

         When witness testimony is offered to overcome the presumption of accuracy afforded to
contemporaneous medical records, such testimony must be “consistent, clear, cogent, and
compelling.” Sanchez, 2013 WL 1880825, at *3 (citing Blutstein v. Sec’y of Health & Human
Servs., No. 90-2808V, 1998 WL 408611, at *5 (Fed. Cl. Spec. Mstr. June 30, 1998)). In
determining the accuracy and completeness of medical records, the Court of Federal Claims has
listed four possible explanations for inconsistencies between contemporaneously created medical
records and later testimony: (1) a person’s failure to recount to the medical professional everything
that happened during the relevant time period; (2) the medical professional’s failure to document
everything reported to her or him; (3) a person’s faulty recollection of the events when presenting
testimony; or (4) a person’s purposeful recounting of symptoms that did not exist. La Londe v.
Sec’y Health & Human Servs., 110 Fed. Cl. 184, 203–04 (2013), aff’d, 746 F.3d 1334 (Fed. Cir.
2014). In making a determination regarding whether to afford greater weight to contemporaneous
medical records over contrary testimony, there must be evidence that this decision was the result
of a rational determination. Burns, 3 F.3d at 417.

       D.      Analysis of Expert Testimony

                                                 38
        Establishing a sound and reliable medical theory often requires a petitioner to present
expert testimony in support of his claim. Lampe v. Sec’y of Health & Human Servs., 219 F.3d
1357, 1361 (Fed. Cir. 2000). Vaccine Program expert testimony is usually evaluated according to
the factors for analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharmaceuticals,
Inc., 509 U.S. 579, 594–96 (1993). See Cedillo v. Sec’y of Health & Human Servs., 617 F.3d 1328,
1339 (Fed. Cir. 2010) (citing Terran v. Sec’y of Health & Human Servs., 195 F.3d 1302, 1316
(Fed. Cir. 1999)). “The Daubert factors for analyzing the reliability of testimony are: (1) whether
a theory or technique can be (and has been) tested; (2) whether the theory or technique has been
subjected to peer review and publication; (3) whether there is a known or potential rate of error
and whether there are standards for controlling the error; and (4) whether the theory or technique
enjoys general acceptance within a relevant scientific community.” Terran, 195 F.3d at 1316 n.2
(citing Daubert, 509 U.S. at 592–95).

         The Daubert factors play a slightly different role in Vaccine Program cases than they do
when applied in other federal judicial fora (such as the district courts). Daubert factors are usually
employed by judges (in the performance of their evidentiary gatekeeper roles) to exclude evidence
that is unreliable and/or could confuse a jury. In Vaccine Program cases, by contrast, these factors
are used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec’y of Health
& Human Servs., 94 Fed. Cl. 53, 66–67 (2010) (“uniquely in this Circuit, the Daubert factors have
been employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness of
expert testimony already admitted”). The flexible use of the Daubert factors to evaluate the
persuasiveness and reliability of expert testimony has routinely been upheld. See, e.g., Snyder, 88
Fed. Cl. at 742–45. In this matter (as in numerous other Vaccine Program cases), Daubert has not
been employed at the threshold, to determine what evidence should be admitted, but instead to
determine whether expert testimony offered is reliable and/or persuasive.

        Respondent frequently offers one or more experts of his own in order to rebut a petitioner’s
case. Where both sides offer expert testimony, a special master’s decision may be “based on the
credibility of the experts and the relative persuasiveness of their competing theories.”
Broekelschen, 618 F.3d at 1347 (citing Lampe, 219 F.3d at 1362). However, nothing requires the
acceptance of an expert’s conclusion “connected to existing data only by the ipse dixit of the
expert,” especially if “there is simply too great an analytical gap between the data and the opinion
proffered.” Snyder, 88 Fed. Cl. at 743 (quoting Gen. Elec. Co. v. Joiner, 522 U.S. 146 (1997)); see
also Isaac v. Sec’y of Health & Human Servs., No. 08-601V, 2012 WL 3609993, at *17 (Fed. Cl.
Spec. Mstr. July 30, 2012), mot. for review denied, 108 Fed. Cl. 743 (2013), aff’d, 540 F. App’x
999 (Fed. Cir. 2013) (citing Cedillo, 617 F.3d at 1339).

                                                 39
       E.      Consideration of Medical Literature

        Both parties relied on medical and scientific literature in this case in support of their
respective positions. I have reviewed all of the medical literature submitted in this case, although
my decision does not discuss each filed article in detail. Moriarty v. Sec’y of Health & Human
Servs., No. 2015-5072, 2016 WL 1358616, at *5 (Fed. Cir. Apr. 6, 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).

                                            ANALYSIS

I.     Overview of Law Pertaining to Specific Injuries Alleged

       A.      Infantile Spasms

        Petitioners seeking an entitlement award on the basis of the claim that a vaccine
precipitated a child’s seizure disorder have succeeded. Many of these cases involve the DTaP
vaccine or its predecessor, the DPT vaccine (the differences between which are discussed below),
as well as the pneumococcal vaccine. E.g., Graves v. Sec’y of Health & Human Servs., 101 Fed.
Cl. 310 (2011) (reversing special master’s denial of entitlement; pneumococcal vaccine caused
seizure activity resulting in child’s death even in absence of fever); Kottenstette v. Sec’y of Health
& Human Servs., No. 15-1016, 2017 WL 6601878 (Fed. Cl. Spec. Mstr. Dec. 12, 2017) (vaccines
(including DTaP and pneumococcal) caused infantile spasms disorder); but see Arango v. Sec’y of
Health & Human Servs., No. 09-318V, 2012 WL 4018028 (Fed. Cl. Spec. Mstr. Aug. 23, 2012)
(DTaP and pneumococcal vaccines, among others, not causal of infantile spasms disorder,
rejecting both Table and non-Table claims), mot. for review denied, 109 Fed. Cl. 335 (2013). L.M.
received both such vaccines in February 2011, before the ER visit alleged to have been the first
instance in which she experienced a seizure.

        There is no real dispute in this case as to the elements of West syndrome/infantile spasms.
As explained by Dr. Zempel and reflected in the filed medical literature, West syndrome is a form
of seizure disorder experienced by infants and characterized by seizures (the spasms) plus
hypsarrhythmia and subsequent developmental problems. A. Arzimanoglou, et al., Epilepsy in
Children: Ch. 3—Infantile Spasms and Related Syndromes 1–32 (3rd Ed. 2004), filed as Ex. F,
ECF No. 21-5 (“Arzimanglou”); Tr. at 300–02, 352–53. Spasms are “often associated with
developmental arrest or regression,” and “[m]any infants become severely disabled, physically and
intellectually, even when no underlying cause is found.” A. Lux, et al., The United Infantile Spasms
Study (UKISS) Comparing Vigabatrin with Prednisolone or Tetracosactide at 14 Days; A
Multicentre, Randomised Trial, 364 Lancet 1773, 1773 (2004), filed as Ex. 30, ECF No. 31-2. On
average, onset of spasms occurs at five months of age. Id. at 1775. While the etiology of West

                                                 40
syndrome is often unknown, known causes include enzyme deficiencies, perinatal maternal drug
abuse, meningitis, and cerebral palsy. Andrew L. Lux et al., The United Kingdom Infantile Spasms
Study (UKISS) Comparing Vigabatrin with Prednisolone or Tetracosactide at 14 Days; A
Multicentre, Randomised Trial, 4 Lancet Neurology 712, 716 (2005), filed as Ex. 31, ECF No. 31-
3.40

        However, cases in which a child is found to have possessed a preexisting genetic mutation
known to be associated with phenotypes involving seizure disorders are a different matter entirely.
The weight of such authority goes against the conclusion that any vaccine could significantly
aggravate the expected course of disease—even where it was not disputed that the vaccine might
nevertheless be responsible for triggering an initial seizure. See generally Oliver v. Sec’y of Health
& Human Servs., No. 10-394V, 2017 WL 747846 (Fed. Cl. Spec. Mstr. Feb. 1, 2017) (vaccines,
including DTaP and pneumococcal, did not significantly aggravate underlying mutation associated
with seizure disorder, although fever attributable to vaccination was trigger for initial seizures),
mot. for review denied, 133 Fed. Cl. 341 (2017), aff’d, 900 F.3d 1357 (Aug. 17, 2018); Faoro,
2016 WL 675491 (vaccines including pneumococcal and DTaP did not significantly aggravate
child’s SCN1A mutation resulting in seizures and developmental delay); Barclay v. Sec’y of
Health & Human Servs., No. 07-605V, 2014 WL 7891493 (Fed. Cl. Spec. Mstr. Dec. 15, 2014)
(DTaP vaccine did not significantly aggravate Dravet syndrome otherwise attributable to SCN1A
mutation), mot. for review denied, 122 Fed. Cl. 189; Taylor v. Sec’y of Health & Human Servs.,
No. 05-1133V, 2012 WL 4829293 (Fed. Cl. Spec. Mstr. Sept. 20, 2012) (same), mot. for review
denied, 108 Fed. Cl. 807 (2013); Snyder v. Sec’y of Health & Human Servs., No. 07-59V, 2011
WL 3022544 (Fed. Cl. Spec. Mstr. May 27, 2011), mot. for review granted, 102 Fed. Cl. 305
(2011), rev’d, 553 Fed. App’x 994 (Fed. Cir. 2014) (same).41

       The overlap between such cases and the present action is striking. All involve
circumstances in which a child’s preexisting genetic mutation was acknowledged by the petitioner,

40
  Exhibits 30 and 31 discuss the same scientific study, but provide different analytical angles. Both provided distinct
and useful background information on West syndrome/infantile spasms.
41
   Even though it established the framework for a significant aggravation claim, Loving is an outlier in finding that the
DTaP vaccine did significantly aggravate a child’s infantile spasms predating vaccination. There, however (and unlike
the present case), it was not established that the child in question had any genetic mutation specifically associated with
a phenotypic presentation consistent with the child’s disease course. The child’s spasm disorder also already existed
at the time of vaccination, allowing the Court to focus on the pure question of whether vaccination altered the expected
course of his disorder. Loving, 86 Fed. Cl. at 137. In this context, the Court found significant the fact that the DTaP
vaccine was specifically contraindicated for individuals already diagnosed with a seizure disorder. Id. at 138.
Otherwise, the case turned on the timing in which the exacerbation occurred, as well as the extent to which conclusions
could be drawn about a systemic response to vaccination from a record that did not contain evidence of the child’s
post-vaccination reaction. Id. at 148–52. Here, by contrast, the record is well-developed with respect to (at least)
L.M.’s post-vaccination health, and timing is less of a dispositive issue given the predominance of questions raised
about her preexisting DYNC mutation, which is understood to be associated with her specific presentation.

                                                           41
but nevertheless alleged to have been affected by vaccination—whether because the vaccine
triggered a fever which produced a seizure and thereby “unmasked” the genetic variant, or more
generally because vaccination was an environmental factor that interacted with the child’s immune
system sufficient to complicate his otherwise expected outcome. See generally Oliver, 2017 WL
747846, at *1 n.3 (collecting fifteen Vaccine Program decisions rejecting the theory that a seizure
disorder was triggered in a child with a preexisting genetic mutation). However, it is also the case
that almost all of these parallel cases involve a specific genetic mutation (the SCN1A mutation)
known to be associated with a phenotype consistent with what the injured child experienced, and
that reliable medical research had demonstrated that this mutation produced the same outcome
regardless of whether a child experienced a “triggering” seizure that unmasked its pathologic
character. There is no dispute herein that L.M’s mutation is not an SCN1A variant (although its
similar expected phenotypic outcome means that SCN1A cases have some bearing on this case’s
resolution).

       B.      Encephalopathy

        The kind of facts supportive of a finding that an injured party experienced an
encephalopathy depend on whether the petitioner advances a Table or non-Table claim. As
discussed in more detail below, the requirements of establishing a Table encephalopathy are
precise and quite rigorous. The Table’s definition of the term “simply does not encompass every
type of brain dysfunction to which the broader meaning of ‘encephalopathy’ applies.” Wright v.
Sec’y of Health & Human Servs., No. 12–423V, 2015 WL 6665600, at *6 (Fed. Cl. Spec. Mstr.
Sept. 21, 2015); Fester v. Sec’y of Health & Human Servs., No. 10–243V, 2013 WL 5367670,
at *21, n. 5 (Fed. Cl. Spec. Mstr. Aug. 27, 2013). By contrast, a claim involving a non-Table
encephalopathy can be based on more expansive understanding of the term. As noted by former
Chief Special Master Vowell, the term encephalopathy, “as commonly used in the medical
community, encompasses a much broader class of injuries than the more stringent definition of
acute encephalopathy found in the QAI [qualifications and aids to interpretation].” Wright, 2015
WL 6665600, at *5 (citing Waddell v. Sec’y of Health & Human Servs., No. 10-316V, 2012 WL
4829291, at *6 (Fed. Cl. Spec. Mstr. Sept. 19, 2012)).

       C.      Injury-Causing Capacity of Pertussis, DPT, and DTaP Vaccines

        In finding that a child’s spasms were caused by vaccination, a few cases in the Vaccine
Program involving a pertussis-containing vaccine elide differences in the formulation of such
vaccines, assuming that their pathogenic capabilities are indistinguishable for purposes of
determining entitlement. See, e.g., Kottenstette, 2017 WL 6601878, at *13–14 (because the injured
child’s spasms would have qualified her for inclusion in studies involving the DPT vaccine, the
findings of those studies (which associated the DTP vaccine with spasms) applied to her even
though she received the DTaP vaccine). However, there is a significant distinction between the

                                                42
DPT vaccine and the subsequent forms that use the acellular version of pertussis—and it bears
directly on the propensity of the version of pertussis vaccine most commonly administered today
to promote seizures.

        The Pediarix combined vaccine that L.M. received in 2011 included DTaP, a component
of which is intended to immunize against infection by the Bordetella pertussis bacterium that
causes whooping cough, “an acute contagious infection of the upper respiratory tract, seen in
young children.” Dorland’s at 1421. The version of the pertussis vaccine that was previously
widely administered was a “whole cell” vaccine, meaning a “suspension[] of the entire B. pertussis
organism that has been inactivated.” Pertussis, World Health Organization (May 21, 2015).42 The
acellular version, by contrast—which L.M. received—is formulated from antigens isolated from
the Bordetella pertussis bacterium (including inactivated pertussis toxin as well as other protein
components of the bacterium) and then purified or detoxified. See Grace v. Sec’y of Health &
Human Servs., No. 04-[redacted], 2006 WL 3499511, at *9 (Fed. Cl. Spec. Mstr. Nov. 30, 2006).
It was developed specifically to address certain adverse reactions that had been observed in
connection with the whole cell version’s administration.

        In a decision from approximately twelve years ago, former Special Master Hastings took
the above into account in noting that “[t]he DTaP version, in general, is believed by medical
scientists to be much improved, and to be much less likely than the DPT vaccine to cause
neurologic reactions or other harmful side effects.” Grace, 2006 WL 3499511, at *9. As a result,
the expert in that case improperly relied on findings pertinent to DPT in attempting to establish
that a child’s infantile spasms were attributable to DTaP vaccine (a claim that Special Master
Hastings rejected, albeit not solely for this reason). Id. at *13–14.

        Subsequent decisions have underscored that the DTaP vaccine’s injury-causing potential
cannot be conflated with findings pertinent only to the DPT whole-cell version.43 See, e.g., Taylor
v. Sec’y of Health & Human Servs., No. 05-1133V, 2012 WL 4829293, at *30 (Fed. Cl. Spec.
Mstr. Sept. 20, 2012) (“[i]t is well established that, while pertussis toxin may be capable of causing
neurological damage, vaccination, especially modern-day vaccination with the acellular form, is
generally safe”) (emphasis added). Special masters have therefore been critical of expert attempts
to apply medical or scientific research pertaining to the DPT vaccine to the TDaP form. Holmes v.

42
     https://www.who.int/biologicals/vaccines/pertussis/en.
43
  Importantly, it is not even the case that medical science has established an association between infantile spasms and
the older, whole-cell pertussis vaccine. See Taylor, 2012 WL 4829293, at *1 (“decades of epidemiological research
into the issues presented in this case—whether pertussis vaccination causes West Syndrome—has not yielded reliable
evidence of a causal link”). As a result, there is a lengthy set of special masters decisions stretching back over 25 years
that do not find petitioners succeeded in connecting infantile spasms to the pertussis vaccine. See generally Grace,
2006 WL 3499511, at *12 (citations omitted). While those decisions do not control the outcome of this case or even
reflect evidence before me, their holdings involved an evidentiary weighing process similar to that I am called upon
to perform herein (and even similar evidence), and I thus take some limited note of them.

                                                              43
Sec’y of Health & Human Servs., No. 08-185V, 2011 WL 2600612, at *20 (Fed. Cl. Spec. Mstr.
Apr. 26, 2011) (noting that expert in question had previously attempted to extrapolate conclusions
from studies involving DPT to TDaP vaccines), citing Simon v. Sec’y of Health & Human Servs.,
No. 05-941V, 2007 WL 1772062, at *7 (Fed. Cl. Spec. Mstr. June 1, 2007) (“the relative risks of
an adverse event from a DPT vaccine found in those DPT related epidemiologic studies do not
attach to a DTaP vaccine”). Such decisions have also specifically noted that certain literature or
studies that Petitioner’s experts herein rely on, like the UK Study, are not reliable scientific
evidence supporting causation. See, e.g., Taylor, 2012 WL 4829293, at *28 (UK Study only
revealed a “temporal shift” in which an increased incidence of reported cases of infantile spasms
was observed closer in time to vaccination than later, but that this increase could be attributed
merely to parental vigilance or an underlying causal genetic factor); Simon, 2007 WL 1772062,
at *7.

II.     Petitioner’s Table Claim

        A.       Petitioner’s Proposed Table Claim Interpretation is Legally Untenable

        Ms. Sharpe’s Table claim alleges that L.M. “suffered a significant aggravation of a pre-
existing encephalopathy,” with the first manifestation of that aggravation occurring within three
days of L.M.’s receipt of the DTaP vaccine44 on February 10, 2011. Pet. Brief at 15. Applying the
relevant terms as they are set forth in the Table, to prevail on her Table significant aggravation
claim Ms. Sharpe must demonstrate that: (a) L.M. experienced an “encephalopathy” prior to
receipt of the DTaP vaccine on February 10, 2011; (b) L.M. suffered a significant aggravation of
that encephalopathy after vaccination; and (c) the first symptom or manifestation of the significant
aggravation of L.M.’s encephalopathy occurred within seventy-two hours after her February 10,
2011 DTaP vaccination. Sections 11(c)(1)(C)(i), 14(a), 33(4); 42 C.F.R. § 100.3(a) (2017).

        Before addressing if Petitioner can meet this definition, there is a preliminary matter to
resolve: what is the proper Table definition for “encephalopathy” in the context of a claim alleging
significant aggravation? See generally “Motion for a Determination of Law Governing Petitioner’s
Table Significant Aggravation Claim,” dated February 26, 2016, ECF No. 40 (“Table Mot.”), and
accompanying memorandum of law, ECF No. 41 (“Memo.”). Petitioner raised this issue well
before hearing, but I ultimately deferred its resolution, since the proof that would be offered for
Petitioner’s non-Table claim would be the same. I am now prepared to rule on this pending
question of law.

44
   Of the vaccines administered to L.M. in February 2011, only the DTaP vaccine can be the basis for a Table claim
alleging significant aggravation of a preexisting encephalopathy.

                                                       44
       The Table defines encephalopathy in the following manner:

       (2) Encephalopathy. A vaccine recipient shall be considered to have suffered an
           encephalopathy if an injury meeting the description below of an acute encephalopathy
           occurs within the applicable time period and results in a chronic encephalopathy, as
           described in paragraph (d) of this section.

           (i) Acute encephalopathy.

              (A) For children less than 18 months of age who present:

                  (1) Without a seizure, an acute encephalopathy is indicated by a significantly
                      decreased level of consciousness that lasts at least 24 hours.
                  (2) Following a seizure, an acute encephalopathy is demonstrated by a
                      significantly decreased level of consciousness that lasts at least 24 hours
                      and cannot be attributed to a postictal state—from a seizure or a medication.

42 C.F.R. §§ 100.3(c)(2)(i)(A)(1–2) (2017).
                                                  ***

              (C) The following clinical features in themselves do not demonstrate an acute
                 encephalopathy or a significant change in either mental status or level of
                 consciousness: Sleepiness, irritability (fussiness), high-pitched and unusual
                 screaming, poor feeding, persistent inconsolable crying, bulging fontanelle, or
                 symptoms of dementia.
              (D) Seizures in themselves are not sufficient to constitute a diagnosis of
                 encephalopathy and in the absence of other evidence of an acute
                 encephalopathy seizures shall not be viewed as the      first   symptom      or
                 manifestation of an acute encephalopathy.

42 C.F.R. §§ 100.3(c)(2)(i)(C–D) (2017).

                                                  ***

       (1) Chronic Encephalopathy.

           (i) A chronic encephalopathy occurs when a change in mental or neurologic status,
               first manifested during the applicable Table time period as an acute encephalopathy
               or encephalitis, persists for at least 6 months from the first symptom or

                                               45
               manifestation of onset or of significant aggravation of an acute encephalopathy or
               encephalitis.

42 C.F.R. § 100.3(d)(1)(i) (2017).
                                                   ***

       (4) Significantly decreased level of consciousness is indicated by the presence of one or
           more of the following clinical signs:

           (i) Decreased or absent response to environment (responds, if at all, only to loud voice
                or painful stimuli);
           (ii) Decreased or absent eye contact (does not fix gaze upon family members or other
                individuals); or
           (iii) Inconsistent or absent responses to external stimuli (does not recognize familiar
                people or things).

42 C.F.R. §§ 100.4(d)(4)(i–iii) (2017).

        Petitioner, however, argues that the “common, ordinary, and accepted meaning” of
“encephalopathy” should be used when deciding her Table significant aggravation claim, rather
than the above definition, “because the language of 42 CFR 100.3(b)(2) limits its [QAI] application
to onset cases.” Table Mot. at 2 (citing Waddell v. Sec’y of Health and Human Services, No. 10-
315V, 2012 WL 4829291, at *8 (Fed. Cl. Spec. Mstr. Sept. 19, 2012) (special master should use
the ordinary meaning of ‘encephalopathy’ because the statute and regulations do not provide a
definition)). In her view, the black-and-white QAI definition is nonsensical, because under it “[n]o
petitioner can demonstrate that her pre-vaccination illness, injury or condition ‘manifests’ ‘within
the applicable period’ after vaccination specified in the Vaccine Injury table.” Memo. at 2.

        In support of this argument, Petitioner relies on a decision written by former Chief Special
Master Golkiewicz, DeRoche v. Sec’y of Health & Human Servs., No. 97-643V, 2002 WL 603097
(Fed. Cl. Spec, Mstr. Mar. 28, 2002). In it, the special master found that it was “infeasible” to
apply the existing Table definition of “encephalopathy” to a Table significant aggravation claim,
because the language in the definition dealing with post-vaccination onset rendered devoid a claim
based on aggravation of a preexisting encephalopathy. Id. at *27. Thus, although a Table
encephalopathy claim based on receipt of the DTaP vaccine required proof that the encephalopathy
had acutely manifested within seventy-two hours of vaccination, the very fact that the claim was
one for significant aggravation presupposed that the encephalopathy already existed.

      However, although DeRoche proposed a reading of “encephalopathy” that (as discussed
below) simply excised the portions incompatible with a significant aggravation claim while

                                                46
retaining the majority of the remaining parts of the definition (DeRoche, 2002 WL 603097, at *29),
Petitioner asks me to totally disregard its proposed reading (despite the embrace of DeRoche’s
reasoning in subsequent decisions like Wiechart v. Secretary of Health & Human Services, No.
07-283V, 2007 WL 4285328, at *3 (Fed. Cl. Spec. Mstr. Nov. 21, 2007) (utilizing revised
definition of encephalopathy first enunciated in DeRoche)). Memo. at 8. That reading, in
Petitioner’s estimation, still relies on an understanding of encephalopathy that pertains only to
cases in which identifying onset is the critical issue. I should instead utilize the “common, ordinary,
and accepted” meaning of “encephalopathy” when determining whether L.M. suffered a pre-
vaccination encephalopathy, referencing Waddell to support her contention that undefined terms
in the Table should be given their ordinarily-understood meaning. Memo. at 6 (citing Waddell,
2012 WL 4829291, at *9; Nuttall v. Sec’y of Health & Human Servs., No. 07-810, 2015 WL
691272, at *10 (Fed. Cl. Spec. Mstr. Jan. 20, 2015)).

        Respondent disputes Petitioner’s arguments about the proper construction of a significant
aggravation Table claim involving a pre-vaccination encephalopathy. See Respondent’s Response
to Petitioner’s Motion for a Determination of Law Governing Petitioner’s Table Significant
Aggravation Claim, April 25, 2016, ECF No. 44 (“Opp.”). In so arguing, Respondent mostly
maintains that the evidence in this case does not establish an “acute” encephalopathy, relying on
the QAI definition over Petitioner’s objection. Opp. at 7–9. Respondent otherwise maintains that
neither DeRoche nor Wiechart are binding and thus should not determine the definition of
encephalopathy in this matter. Id. at 9–10 n. 7.45

        Because Petitioner’s argument centers on DeRoche, it is worth examining that decision
more carefully. There, former Chief Special Master Golkiewicz expressly recognized the extent to
which the Table definition of encephalopathy was in tension with a Table significant aggravation
claim based on an alleged pre-vaccination encephalopathy. DeRoche, 2002 WL 603087, at *29
(“[t]he literal application of [Section] 100.3(b)(2) to presumptive significant aggravation claims,
as required by [Section] 11(c)(1)(C)(i), leads to absurd results and thwarts [C]ongressional intent
to provide petitioners a Table significant aggravation theory of recovery and a corresponding
definition for encephalopathy-based cases”). But in so ruling, he did not jettison completely the
Table definition, as Petitioner contends. Instead, the special master removed the phrases “within
the applicable period” and “and then a chronic encephalopathy persists in such persons for more
than 6 months beyond the date of vaccination” from 42 CFR § 100.3(b)(2), relying on what

45
  Petitioner filed a reply that refined somewhat the argument she originally made with respect to the proper definition
of encephalopathy within a Table significant aggravation claim. Reply, May 13, 2016, ECF No. 47. She now maintains
that I should merely determine if L.M.’s post-vaccination status was evidence of worsening of her alleged pre-
vaccination encephalopathy, and not require that this evidence itself establish encephalopathy as defined by the QAIs.
Id. at 2, 4–6. Because, as noted in Whitecotton, special masters are free to consider evidence from outside the table
time period in determining whether an individual suffered the first symptom or manifestation of a significant
aggravation of an injury within the table time period, I should “consider all the available evidence and keep in mind
that symptoms first documented on February 15, 2011 may have begun on February 10, 2011.” Id. at 6.

                                                         47
remained of the Table definition (including the QAIs pertaining to “acute” encephalopathy) to
decide the petitioner’s claim. Id. at *27. This modified reading was subsequently embraced by a
different special master. Wiechart, 2007 WL 4285328, at *3.

        Petitioner’s argument—which simultaneously asks me to follow and reject DeRoche—is
unpersuasive. DeRoche reasonably interpreted the definition of encephalopathy so as to permit
Table claims for significant aggravation of a preexisting encephalopathy by judiciously limiting
what it excised from the definition (in particular, language requiring proof of a preexisting chronic
encephalopathy). But it does not constitute a total abandonment of the Table definition, as
Petitioner urges. DeRoche is consistent with the federally-recognized guidelines of statutory
construction that favor narrow excisions of inconsistent language over wholesale rejection of an
entire provision. See Green v. Bock Laundry Machine Co., 490 U.S. 504, 511–27 (1989) (finding
that, as written, Federal Rule of Evidence 609(a)(1) “can’t mean what it says,” but choosing to
read the rule narrowly rather than throw out the rule altogether); see also Mountain States Tel. &
Tel. co. v. Pueblo of Santa Ana, 472 U.S. 237 (1985) (narrowly modifying the reading of a statute
“so as not to render one part inoperative”) (citations omitted); Hellebrand v. Sec’y of Health &
Human Servs., 999 F.2d 1565, 1570–71 (Fed. Cir. 1993).

        Successful Table claims require petitioners to make a precise factual showing, meeting
definitions that are often more narrow than what a claimant would have to establish for a non-
Table claim (as observed above in comparing the Table and non-Table treatment of
“encephalopathy”). DeRoche reasonably accounted for the contradiction in the Table definition of
encephalopathy by excising only the portion of the definition that negated a significant aggravation
claim. It did not hold that the Table definition was entirely void for this reason, and its logic for so
determining is consistent with the federal common law approaches to statutory construction.

        Based on the foregoing, I find that to establish a Table claim of significant aggravation of
an alleged preexisting encephalopathy, Petitioner must meet DeRoche’s harmonized definition of
“encephalopathy,” relying on most of how that is defined in the Table, and therefore proving at a
minimum that L.M. experienced a pre-vaccination “acute” encephalopathy as set forth in the QAIs.

       B.      Petitioner Has Not Demonstrated that L.M. Experienced a Pre-Vaccination
               Acute Encephalopathy as Defined by the Table
        Applying the above, the facts in this case do not support the conclusion that L.M.’s brain
structural irregularities, or pre-vaccination symptoms, rose to the level of an “acute
encephalopathy.” The Table definition of acute encephalopathy does not encompass the kind of
structural brain malformation observed by Dr. Shuman. Dr. Shuman’s diagnosis of PNTLE was
also not persuasive, as it lacked sufficient scientific foundation (and appears largely to rely on
white matter deficiency conditions like PVL most commonly associated with prematurity—
something that does not characterize L.M.’s birth). His assessment that L.M. had a preexisting

                                                  48
brain malformation was otherwise rebutted by analysis of L.M.’s treating physicians—in
particular, the radiologists who reviewed the same initial MRIs but deemed them largely normal.
And although it is not disputed by either party that L.M.’s DYNC mutation preceded vaccination,
an underlying genetic disorder does not, by itself, constitute encephalopathy given the term’s
definition in the QAIs.

        The record also does not provide support for the conclusion that L.M. experienced a
“decreased level of consciousness” prior to receiving the DTaP vaccine. And there is nothing about
her pre-vaccination status, as reflected in the medical records or the statements of Petitioner and
Mr. Moore, that smacks of an acute condition significant enough to warrant hospitalization. At
best (although it is not a fact accepted by Petitioner), in the month before vaccination, L.M.
experienced some initial seizure activity likely related to her post-vaccination infantile spasm
disorder—but the Table explicitly excludes seizure as sufficient evidence for a finding of acute
encephalopathy. 42 C.F.R. § 100.3(b)(2)(i)(3)(D). Thus, because the evidence in this case does not
meet the QAI definition of encephalopathy, Petitioner’s Table claim cannot succeed.

III.   Petitioner’s Causation-in-Fact Significant Aggravation Claim Fails

        Ms. Sharpe’s non-Table claim focuses on both L.M.’s DYNC mutation and “subtle cortical
malformations” alleged to exist by Dr. Shuman, maintaining that the vaccines she received (not
limited to the DTaP) in February 2011 constituted an “epileptogenic stimulus” sufficient to
produce “profound neurologic injury” given L.M.’s preexisting conditions (which placed her at an
increased risk of injury). Pet. Brief at 27–28. Below, I address the Loving factors in order of their
significance to my decision, rather than in their ordinal sequence.

       A.      Loving Prong Three: the Petitioner did not Successfully Establish that L.M.’s
               Post-Vaccination Condition was Sufficiently Worse to Constitute a “Significant
               Aggravation” of her DYNC Mutation

        The lynchpin of a non-Table significant aggravation claim is the demonstration of
“significant aggravation.” As noted above, it is not enough for a claimant to establish that (in
contrast to his pre-existing health) he was “worse” after the vaccine in comparison to his health
immediately before, and that this initial worsening is plausibly attributable to the vaccine
negatively interacting with a preexisting condition. Rather, the claimant must demonstrate that his
or her post-vaccination condition is overall qualitatively worse than what would be expected given
what is known about the preexisting condition (which might otherwise have deleterious effects on
its own). Locane, 685 F.3d at 1381–82; Hennessey, 2009 WL 1709053, at *42.

                                                 49
        Petitioner was unsuccessful in meeting this Loving prong. There is no question that she
possesses the DYNC mutation,46 and both experts agreed that the mutation is associated with poor
outcomes overall consistent with L.M.’s course (although, as discussed below, Dr. Boles
unsuccessfully attempted to establish that the location of L.M.’s mutation predicted a less severe
outcome). Moreover, the medical record does not allow the conclusion that L.M.’s trajectory was
appreciably worse after receiving vaccines in February 2011. At best, the record establishes that
L.M. experienced some infantile spasms after vaccination (and likely had already experienced
some even if her parents did not recognize them as such), and then over time experienced more
severe developmental problems, consistent (as Dr. Zempel persuasively testified) with what a child
possessing a genetic variant known to be associated with such an outcome would experience.
Beyond the manifestation of L.M.’s West syndrome itself, the record does not support the
conclusion of a dramatic worsening (for example, the February and April MRIs are largely
consistent) post-vaccination.

        Certainly Petitioner made several sound arguments regarding L.M.’s course consistent with
her overall claim. The record does supports the conclusion that L.M.’s condition was worse
immediately post-vaccination (if compared only to her immediate pre-vaccination condition). In
addition, Petitioner has pointed to evidence from the medical record that L.M. displayed some
motor control issues and diminished responsiveness on February 15, 2011, after the seizure that
resulted in her being taken to the hospital—although such evidence must be balanced against the
fact that by the time of her discharge from St. Vincent Hospital two days later, she had returned to
baseline (and indeed the fact that she was discharged cuts against the conclusion that she had
dramatically worsened on the 15th, as treaters were comfortable letting her go home).

        But to argue that this meets the legal standard of significant aggravation is to misapprehend
that standard, at least as applied in cases involving genetic variants like the DYNC mutation known
to be associated with outcomes largely consistent with what L.M. experienced. See, e.g., Faoro,
2016 WL 675491, at *25. That legal standard requires an evaluation of what is known about the
preexisting mutation and its likely impact on an affected individual’s life. Here, preponderant
evidence (while not as conclusive as that pertaining to the SCN1A mutation) still favors the
determination that L.M.’s outcome would most likely be as it was regardless of vaccination.47

46
  Petitioner also maintained (via Dr. Shuman’s testimony) that L.M.’s brain structural malformation could have been
aggravated, but the underlying assumption for that position—that she did possess such a malformation (and/or white
matter abnormality)—was not persuasively established on this record by Dr. Shuman, as discussed below.
Accordingly, I primarily consider the genetic variant that L.M. definitively possesses—and, as both Drs. Boles and
Descartes agreed, unquestionably was pathogenic in some respect in this case.
47
   As discussed above, the court in Barclay noted that genetic mutation cases might be better analyzed under the
“factor unrelated” analysis rather than requiring such petitioners to satisfy the Loving significant aggravation standards
by proposing an expected prognosis. Barclay, 122 Fed. Cl. at 193 (citing Knudsen, 35 F.3d at 547). Although in this
case I do not find that Petitioner carried her initial burden, even if I had I would find that Respondent did establish a
“factor unrelated,” in the form of the relationship between the DYNC mutation and L.M.’s illness. Once a petitioner
makes a prima facie showing of causation, “the burden shifts to respondent to demonstrate by a preponderance of the

                                                           50
L.M.’s overall course is consistent with what is known about the effects of a DYNC mutation. The
evidence therefore does not preponderate in favor of the conclusion that L.M.’s spasm disorder
otherwise attributable to her DYNC mutation was worsened by vaccination.

         B.       Loving Prong Four: Petitioner’s Causation Theory was Unreliable

       Loving prong four, which echoes Althen prong one, requires a petitioner to put forth a
plausible and scientifically reliable theory of causation. The Petitioner in this case has failed to do
so.

         Dr. Shuman’s opinion was overall the weaker of the two, especially in light of the fact that
his first two reports were filed prior to the determination that L.M. possessed the DYNC mutation,
and thus proposed a theory that did not take into account a significant fact. Even at hearing,
however, Dr. Shuman did not abandon his initial theory. His proposal that L.M. had a pathogenic
brain malformation was not corroborated by the medical record (and specifically by the MRIs upon
which that opinion relied). His assertion that she alternatively had some kind of white matter
deficiency relied upon a diagnosis that not only L.M. never received but which elevated a
diagnostic concept (PNTLE) into something that it does not appear medical science recognizes
with any degree of trustworthy sufficiency. And his arguments about the capacity of pertussis
toxin-containing vaccines to promote seizure activity relied heavily on somewhat outdated medical
literature like the UK Study and/or involved conflation of the DPT vaccine with the DTaP version
L.M. actually received.

        This leaves only Dr. Boles’s opinion, which forthrightly acknowledged the existence of
L.M.’s DYNC mutation and its pathogenic character, but argued that the precise location of the
mutation on the gene predicted an otherwise more favorable prognosis that was made worse by
vaccination. This theory certainly raised interesting and valid scientific points regarding the
significance of the mutation’s location, and was based on the undisputed fact that L.M.’s mutation
was located in the stem/tail gene location rather than the more critical motor function location. It

evidence that a ‘factor unrelated’ to the vaccine ‘was the sole substantial factor in bringing about the injury.’” Hammitt
v. Sec’y of Health & Human Servs., 98 Fed. Cl. 719, 726 (2011), aff’d sub nom. Stone v. Sec’y of Health & Human
Servs., 676 F.3d 1373 (Fed. Cir. 2012) (citing Bazan, 539 F.3d at 1352). In this case, preponderant evidence was
offered by Respondent not only that the DYNC mutation is generally associated with outcomes similar to what L.M.
experienced, but also that an individual with the same mutation and location as L.M. experienced a parallel course.
Tr. at 270; Helbig at 11. I also give some weight to evidence offered relating to the SCN1A mutation. Unquestionably
this mutation is not identical to the DYNC mutation, and there is far more robust proof (especially in the form of
studies considering the impact of vaccination on such affected individuals) that the SCN1A variant’s course is only
transiently impacted by the immunologic stress of a vaccination. Nevertheless, the science and literature regarding
this mutation (as reflected in the numerous decisions—repeatedly upheld on appeal—denying causation) is persuasive
support for the conclusion that genetic mutations understood to have poor phenotypic presentations consistent with an
injury alleged to be vaccine-caused are a more reliable explanation for that presentation than the vaccine. And Dr.
Descartes’s testimony on this point was more reliable than Dr. Boles’s, who admitted that the mutation itself is
generally pathogenic, but who did not persuasively establish that location was determinative of likely outcome.

                                                           51
also was based in part on reliable scientific literature discussing the significance of mutation
location. See, e.g., Strickland at 8. Nevertheless, the theory was flawed in two critical respects.

        First, Dr. Boles did not establish with reliable proof Petitioner’s contention that location
was as outcome-determinative as he maintained in his testimony. At most, he offered literature
supporting the conclusion that all things being equal, a stem or tail mutation would be less severe
in comparison located in the motor/stalk location. He did not provide support for the contention
that any DYNC mutation did not have some capacity to produce a severe phenotype—or one
consistent with what L.M. experienced—despite being located in the stem/tail region.

        Consideration of two ostensibly dueling pieces of literature in this case—Strickland and
Hoang—demonstrates the insufficiencies in Petitioner’s argument. Based on a very small sample
size, Strickland does observe some differences in the phenotypic outcomes for DYNC mutations
based on where the mutation occurs on the gene, and its conclusions are scientifically reliable as
far as they go (although, as noted by Respondent, Strickland did observe at least one individual
who experienced significant intellectual disability for a mutation in the stem/tail region). However,
Hoang, published two years after Strickland, simultaneously expands upon scientific knowledge
of the nature of DYNC mutations and calls into question the idea that mutation location is strongly
outcome-determinative. Indeed, Hoang specifically observes another instance of a tail mutation
with an outcome congruent with the kind Petitioner argues are only found when the mutation
occurs in the motor region. Hoang at 8–9, Table S1.

        Besides Hoang, Respondent offered other compelling evidence demonstrating that the
location of a genetic mutation is not alone predictive of mutation outcome. Tr. at 268–70 (Dr.
Descartes describing the individual in the Helbig article index with DYNC mutation in stem/tail
also suffered from infantile spasms and epileptic encephalopathy). Such literature acknowledges
the comparative difference in location and outcome, but concludes that it is the mutation itself that
is pathogenic overall (and not that a more benign location will inherently mean a more favorable
outcome).

       Scoto, for example, provides a gene structure map identifying the location on the DYNC
gene of the position of different mutations either studied specifically in the article or previously
reported in other literature. Scoto at 673 fig. 1. As it indicates, “the mutations identified in this
study to cause both [spinal muscular atrophy with lower extremity predominance] and
[malformations of cortical development]48 can be seen to span the entire length of the protein,”
and thus phenotypes associated with more severe cognitive impairment could also be seen derived
from mutations not solely in the motor domain. Id.; see also id. at 677 (“[o]ur findings confirm

48
   Dr. Boles’s report acknowledged that “spinal muscular atrophy with lower extremity predominance,” or SMA-LED,
is the kind of phenotypic outcome more commonly observed in association with tail-located mutations and is not
deemed as severe. Boles Rep. at 9–10.

                                                      52
that heterozygous missense [DYNC] mutations can lead to a wide range of neuronal migration
defects in association with a variable degree of cognitive/behavioral impairment”). Other literature
reaches the same conclusion. See, e.g., Willemsen at 4 (comparing two individuals—one with a
DYNC mutation in the stem domain, the other in the motor region—but finding that both displayed
severe intellectual disability, and (even allowing for the difference in outcome as possibly relating
to mutation location) concluding that “de novo missense mutations in [DYNC] are a novel cause
of severe [intellectual disability] associated with variable neuronal migration defects”).

        More persuasively, there is the Ambry Genetics report, which similarly acknowledges
differences comparatively in mutation location and outcome, but does not bulwark the importance
of location for purposes of predicting likely outcome. In fact, the report’s allusion to a child with
a DYNC mutation having a phenotype qualitatively comparable to what L.M. experienced was
particularly telling in revealing the deficiency of Dr. Boles’s argument. Consistent with the Ambry
Genetics report, Dr. Descartes’s report noted that the relevant variant involved an alteration in a
specific amino acid (p.F1093S) located in the stem domain of the gene. Descartes Rep. at 3; Ex.
42 at 41. Helbig, which provides somewhat more detail about the comparable patient alluded to in
the Ambry Genetics report, confirmed that this same individual possessed the precise same amino
acid alteration location as L.M., and an outcome comparable to that experienced by L.M.. Helbig
at 11. While such evidence does not rebut Dr. Boles’s overall point that location of the mutation
affects phenotype, it does rebut his point that location alone suggests a “more likely than not”
phenotypic outcome.49

        All in all, Petitioner’s argument advanced about the significance of mutation location as
bearing on severity of outcome had some reliable scientific support. But it did not go far enough
to establish a fully reliable theory—not only because not enough is yet known about the interplay
between mutation location and outcome for DYNC mutations to conclude as Petitioner urges, but
(more compellingly) because the similarly-situated patient identified in Helbig and the Ambry
Genetics test results report experienced almost the same outcome as L.M.—belying Petitioner’s
argument about the conclusions that can be drawn about DYNC mutation location. No doubt future
research may better demonstrate the significance of location and its determination of phenotype,
and may in a different Vaccine Program case make it easier to conclude that a tail-located DYNC
mutation is unlikely to be pathogenic in the manner relevant herein. But such research does not
yet exist, and on the present record I do not find that Petitioner’s showing established the first “can
cause” Althen prong.

49
  The fact that the female patient referenced in Helbig and the Ambry Genetics test results report might not have
received any vaccines—a point raised by Dr. Boles in his argument that the environmental factors affecting the
unnamed individual were unknown, thus reducing the comparability of her circumstances—actually only strengthens
the relevance of this data point. For if the unnamed patient experienced the same outcome as L.M. without vaccination,
the conclusion that the vaccines had no impact on L.M.’s outcome is strengthened.

                                                         53
        Dr. Boles could not invoke or rely upon his own individual experience to counter the above.
His demonstrated expertise on genetic matters was not paired with comparable experience
studying the DYNC mutation, the genetic sources of West syndrome, or the consistent treatment
of such patients over his career, rendering his opinion on mutation location significance with
respect to phenotypic outcome less compelling. I thus cannot conclude on such a showing that a
stem/tail DYNC mutation would inherently not present as it did in L.M.’s case.

        The second deficiency in Petitioner’s theory is more fatal to the claim. Even if I were to
assume for sake of argument that Petitioner’s tail-located DYNC mutation meant a less severe
outcome than she in fact experienced, Dr. Boles did not persuasively explain how the vaccines
interacted with the mutation to worsen than anticipated phenotype—or even that they could do so.
He is not an immunologist, could not refer to specific expertise in studying the impact of
vaccination on mutations, and offered no literature speaking to the connection between vaccination
and genetic outcome (where a specific mutation is known to have a negative phenotypic
presentation) that could fill such experiential gaps. Instead, Dr. Boles relied on personal
supposition, or the general proposition that vaccination constitutes an environmental factor that
can interact with genetic expression, basing such contentions on his own generalized observations
from the treatment of unspecified twins. See, e.g., Tr. at 185; Boles Rep. at 11. Such argument was
effectively rebutted by Respondent’s comparison of the DYNC mutation to the extensive literature
regarding the SCN1A mutation, and the fact that in the latter case the environmental impact of
vaccination was not deemed significant enough to alter the course otherwise plotted by the
preexisting mutation.50

        Absent support in Dr. Boles’s testimony for the connection between vaccines and a
mutation-driven pathologic disease, Petitioner was left with Dr. Shuman’s points about the seizure-
inducing potential of the DPT vaccine - which is not interchangeable with the acellular version
administered in this case. She also did not offer persuasive reliable evidence establishing that the
pneumococcal vaccine could negatively interact with any mutation let alone the DYNC variant.
At most, such evidence establishes that a vaccine might (especially if causing fever) spark a
transient seizure—not that it would worsen a spasm disorder otherwise understood to be genetic
in origin.

        C.       Loving Prong Five: the Vaccines at Issue did not Worsen L.M.’s Seizure Disorder

        Upon review of the record as a whole, I cannot conclude that it is more likely than not that
the vaccines L.M. received on February 10, 2011, “did cause” a worsening of the course of her
seizure disorder.

50
  Petitioner perhaps could have rebutted evidence offered about SCN1A mutations by showing that the phenotype for
this mutation is (as argued with the DYNC mutation) also gene location-dependent, but no such argument or evidence
was offered.

                                                       54
        The record does support the conclusion that L.M. experienced a post-vaccination fever and
some reaction the evening of February 10, 2011, after she received the vaccinations at issue. But
it is more difficult to determine the degree to which this reaction persisted over the next several
days. Although Ms. Sharpe was credible in explaining her observations of L.M.’s state between
February 10th and 15th, contemporaneous records from L.M.’s initial presentation at the
Lewistown ER suggest that any vaccine-related fever or reaction had subsided by the time of the
seizure that led Ms. Sharpe to seek medical intervention (thus underscoring that the initial vaccine
reaction was likely transient). Ex. 3 at 13. L.M.’s overall presentation subsequently—both at
Lewistown as well as St. Vincent hospital thereafter—reveals evidence of the obvious
manifestation of the seizure disorder but does not suggest an acute worsening that could be
vaccine-related. Accordingly, the record best supports the conclusion that L.M. had some reaction
to vaccination, and that this reaction was closely followed by seizure activity—not that the overall
seizure disorder was made worse by vaccination.

        The record discussed above also reveals the likelihood that L.M. had already experienced
seizures before the February 15th ER visit. Ex. 3 at 13 (reporting “unexplained episode of sudden
flaccidity and unresponsiveness for 30 sec” a month prior). Such pre-vaccination seizure activity
was similarly reported at St. Vincent later that same day. Ex. 4 at 3. This evidence is also consistent
with Dr. Zempel’s testimony (confirmed in filed medical literature) that parents often do not
recognize initial seizure activity as part of a greater disorder before a more alarming seizure
incident. Tr. at 301–02; Arzimanoglou at 3 (“the spasms often go unnoticed”). Thus, if L.M.’s
seizure activity (like her underlying genetic DYNC mutation) predated vaccination, it becomes
more difficult to conclude that the February 10th vaccinations worsened it.

        The testimony of Petitioner’s experts could not rebut the above. Both admitted that they
found particularly compelling the fact that L.M.’s West syndrome became most obvious after
vaccination – in other words, that the latter preceded the former. Tr. at 133, 185. But it is axiomatic
in the Vaccine Program that a mere temporal relationship between vaccination and illness does not
establish causation. McCarren v. Sec’y of Health & Human Servs., 40 Fed. Cl. 142, 147 (1997).

        This leaves L.M.’s DYNC mutation as the most compelling explanation for her
predisposition to develop a seizure disorder. At most, the vaccines she received in February 2011
(due to the fever they caused) may have resulted in a transient seizure four days later. However, it
is quite likely that L.M.’s seizures in fact began prior to vaccination, and the evidence does not
support the contention that her vaccinations thereafter precipitated a substantial worsening of her
expected course given her underlying genetic mutation. There is nothing else in this record that
suggests that post-vaccination, L.M. experienced an immunologic reaction sufficient to
appreciably aggravate her genetic propensity to develop a seizure disorder.

                                                  55
       D.      Other Loving Prongs

         Turning to Loving Prongs One and Two, it cannot be disputed that L.M.’s underlying
DYNC mutation predated the vaccination, but that (although she more likely than not exhibited
some symptoms pre-vaccination), she was in better health before February 10th. In addition, her
symptoms were undoubtedly more severe and pronounced post-vaccination, and therefore she was
literally “worse” thereafter—although as discussed above, L.M.’s deterioration does not ultimately
correspond with Loving prong three’s worsening requirement.

        I do find that the onset of L.M.’s seizures after vaccination occurred in a medically-
acceptable timeframe (Loving prong six) based upon Petitioner’s theory. The record establishes
that she experienced a seizure within four days of receipt of vaccines on February 11, 2011. This
timeframe is medically reasonable under Petitioner’s causation theory, and is also consistent with
other cases that have found seizures to be vaccine-caused. See, e.g., Simon, 2007 WL 1772062.
Because, however, I have not also found that the theory that vaccines in question could worsen the
expected outcome of a DYNC mutation-associated seizure disorder was plausible and/or reliable,
and because the record does not support the conclusion that the vaccines were more likely than not
the cause of L.M.’s overall condition (even if I allow that the vaccines triggered the February 15th
seizure), the fact that the timing is acceptable does not result in a different overall outcome.

                                         CONCLUSION

        The record does not support Petitioner’s contention that the vaccines L.M. received could,
or did, injure her as alleged. Nor did she establish a fundamental aspect of any significant
aggravation claim: that L.M.’s overall state, given her preexisting DYNC mutation, was rendered
worse by the vaccines she received. And her Table claim was rooted in a legally untenable reading
of the claim. Thus, although I have tremendous respect for the loving struggles of Ms. Moore and
Mr. Hanson to care for their daughter (and also to identify an explanation for her developmental
problems), I am required to evaluate their claim on the basis of its success in meeting the legal
evidentiary burdens set by the Vaccine Act and controlling Federal Circuit precedent, rather than
on sympathies they deservedly elicit.

       Petitioners have not established entitlement to a damages award, and therefore I must
DISMISS their claim. In the absence of a timely-filed motion for review (see Appendix B to the
Rules of the Court), the Clerk shall enter judgment in accordance with this decision.

       IT IS SO ORDERED.
                                                             /s/ Brian H. Corcoran

                                                56
     Brian H. Corcoran
     Special Master

57