     In the United States Court of Federal Claims
                               OFFICE OF SPECIAL MASTERS
                                    Filed: March 18, 2019

* * * * * * * * * * * * *                     *   *
KENNETH BARON AND                                 *
JAYME BARON, on behalf of S.B.,                   *       No. 14-341V
a minor,                                          *       Special Master Sanders
                                                  *
                Petitioners,                      *
                                                  *
v.                                                *
                                                  *       Hepatitis A (“HAV”) Vaccine; Influenza
SECRETARY OF HEALTH                               *       (“Flu”) Vaccine; Althen; anti-NMDAR
AND HUMAN SERVICES,                               *       Encephalitis
                                                  *
          Respondent.                             *
* * * * * * * * * * * * * *                       *

Ronald Craig Homer, Conway, Homer, P.C., Boston, MA, for Petitioners.
Claudia Barnes Gangi, United States Department of Justice, Washington, DC, for Respondent.

                                               DECISION1

        On April 23, 2014, Kenneth and Jayme Baron (“Petitioners”) filed a petition on behalf of
S.B., pursuant to the National Vaccine Injury Compensation Program.2 Petitioners allege that the
Hepatitis A (“HAV”) and influenza (“flu”) vaccines S.B. received on November 11, 2011, caused
her to develop anti-N-methyl D-aspartate receptor (“anti-NMDAR”) encephalitis.

        After carefully analyzing and weighing all the evidence and testimony presented in this
case in accordance with the applicable legal standards, the undersigned finds that Petitioners have
not met their legal burden. Petitioners have failed to provide preponderant evidence that the HAV
and flu vaccinations S.B. received on November 11, 2011 caused her to develop anti-NMDAR
encephalitis. Accordingly, Petitioners are not entitled to compensation.


1
  This decision shall be posted on the United States Court of Federal Claims’ website, in accordance with
the E-Government Act of 2002, 44 U.S.C. § 3501 note (2012) (Federal Management and Promotion of
Electronic Government Services). This means the Decision will be available to anyone with access to
the Internet. In accordance with Vaccine Rule 18(b), a party has 14 days to identify and move to delete
medical or other information that satisfies the criteria in § 300aa-12(d)(4)(B). Further, consistent with the
rule requirement, a motion for redaction must include a proposed redacted decision. If, upon review, the
undersigned agrees that the identified material fits within the requirements of that provision, such material
will be deleted from public access.
2
  The Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, 42 U.S.C. §§ 300aa-
10 et seq. (hereinafter “Vaccine Act,” “the Act,” or “the Program”).
    I.      Procedural History

        Petitioners filed twenty-one medical records on May 15, 2014, and a compact disk
containing two additional medical records on May 27, 2014. See Pet’rs’ Exs. 1–21, ECF Nos. 9–
11; see Notice of Intent to File Pet’rs’ Exs. 22–23 on CD, ECF No. 12. On July 10, 2014,
Petitioners filed a statement of completion. ECF No. 15.

       Respondent filed his Rule 4(c) Report on September 22, 2014. ECF No. 20. In his report,
Respondent agreed with the diagnosis of anti-NMDAR encephalitis and agreed that S.B. had
suffered the residual effects or complications of this injury for more than six months. Id. at 8.
However, Respondent argued that compensation is not appropriate because Petitioners had “not
offered sufficient reliable evidence to establish a causal relationship between S.B.’s . . .
vaccinations and her anti-NMDAR encephalitis.” Id.

        Petitioners then filed two additional medical records on November 4, 2014. Pet’rs’ Exs.
24–25, ECF No. 22. On June 25, 2015, Petitioners filed an expert report from Dr. Murray Engel.
Pet’rs’ Exs. 26–27, ECF No. 34. Respondent filed his responsive expert report from Dr. Jessica
A. Panzer on November 23, 2015. Resp’t’s Exs. A–B, ECF No. 39. Respondent filed an additional
twelve pieces of medical literature on December 12, 2015. Resp’t’s Exs. C–N, ECF No. 41.
Petitioners filed their first supplemental expert report on April 22, 2016, and their second
supplemental expert report on August 10, 2016. Pet’rs’ Exs. 28–29, ECF Nos. 44, 50. On May
15, 2017, Respondent filed an additional eight exhibits, including a new expert report and
supporting medical literature from Dr. Eric Lancaster.3 Resp’t’s Exs. BB–II, ECF No. 57.

        An entitlement hearing occurred on August 28, 2018. See Hearing Order, ECF No. 63.
Petitioners filed four additional medical records before the hearing. Pet’rs’ Exs. 32–35, ECF Nos.
72–75.

    II.     Factual Background

        S.B. was born healthy on February 10, 2010, at Next Generation Pediatrics. Pet’rs’ Ex. 6
at 2. On July 10, 2010, S.B. had her five-month well child visit, and doctors noted that she was a
“healthy female infant [with] improving [gastroesophageal reflux disease4].” Id. at 8. S.B. had
her ten-month well child visit on December 13, 2010, where she was diagnosed with right otitis
media,5 but was otherwise healthy and developing normally. Id. at 27. In addition, S.B. received
her first flu vaccination at that visit. Id.; Pet’rs’ Ex. 1 at 3. On December 15, 2010, S.B.’s


3
  For personal reasons, Dr. Panzer was unable to continue as an expert in this case. Therefore,
Respondent notified the court on February 2, 2017, that he would need to provide in a new expert. ECF
No. 54.
4
  Gastroesophageal reflux disease is “any condition noted clinically or histopathologically that results
from gastroesophageal reflux, ranging in seriousness from mild to life threatening; principal
characteristics are heartburn and regurgitation.” Dorland’s Illustrated Medical Dictionary 533 (32nd ed.
2012) [hereinafter “Dorland’s”].
5
  Otitis media is “inflammation of the middle ear.” Dorland’s at 1351.


                                                    2
pediatrician prescribed her a ten-day course of Cefzil6 to correct her right otitis media. Pet’rs’ Ex.
6 at 27.

       On December 16, 2010, S.B. suffered a seizure while on a flight from New York City to
Fort Lauderdale, Florida. Pet’rs’ Ex. 21 at 11. The seizure lasted for approximately thirty seconds,
and S.B. was given a crushed 500 mg adult Tylenol tablet dissolved in juice. Id. Upon landing,
S.B. had a temperature of 102.7 degrees and paramedics transported her to a local emergency
room. Id. Medical records reveal that S.B. suffered a febrile seizure, and she was discharged the
same day. Id. at 4.

        Over the next year, S.B. experienced common childhood illnesses but continued to develop
normally and receive recommended childhood vaccines. See generally Pet’rs’ Exs. 1, 6. On
October 19, 2011, Petitioners brought S.B. to her pediatrician for a rash. Pet’rs’ Ex. 6 at 36. S.B.’s
pediatrician diagnosed her with viral exanthem. Id. On November 6, 2011, Petitioners called
S.B.’s pediatrician to notify her that S.B. had been experiencing “profuse and frequent watery
diarrhea” for one day. Pet’rs’ Ex. 6 at 38. S.B.’s pediatrician diagnosed S.B. with acute
gastroenteritis and directed Petitioners to keep S.B. hydrated and take her to the emergency room
if symptoms worsened. Id. There is indication that follow-up treatment was pursued in the record.

         S.B. received the HAV and flu vaccinations at issue in this case on November 11, 2011.
Pet’rs’ Ex. 1 at 2–3. The records reveal no subsequent medical visits until December 22, 2011,
when Petitioners called S.B.’s pediatrician to complain that S.B. had been congested with a nightly
cough.7 Pet’rs’ Ex. 6 at 44. S.B.’s pediatrician prescribed a ten-day course of Augmentin.8 Id.
The next day, Petitioners brought S.B. to her pediatrician’s office, complaining that S.B. had been
having temper tantrums and was not holding her left arm as she normally did. Id. at 43. During
the appointment, S.B.’s pediatrician observed S.B. “periodically fling [her] lower arm [and] hold
it close to her body.” Id. She referred S.B. to a neurologist. Id.

      Petitioners brought S.B. to Dr. Greg Rosenn, a pediatric neurologist, on December 23,
2011. Id. at 125. Upon examination, Dr. Rosenn noted that S.B. had left hemiparesis with “a
hemiparetic gait with circumduction of the left leg and decreased arm swing on the left.” Id. Dr.
Rosenn referred S.B. to the emergency room for neuroimaging. Id.

        S.B. was admitted to Cohen’s Children Medical Center on December 23, 2011. Pet’rs’ Ex.
16 at 1. She underwent two CT scans—one of her head and one of her neck—both of which were
normal. Id. at 54–57. On December 24, 2011, S.B. had a magnetic resonance imaging (“MRI”)
and a magnetic resonance angiogram (“MRA”) of her brain, as well as an MRI of her cervical
spine, all of which were unremarkable. Id. at 50–53.


6
  Cefzil is “trademark for a preparation of cefprozil.” Dorland’s at 312. Cefprozil is “a semisynthetic,
broad-spectrum, second-generation cephalosporin effective against a wide range of gram-negative and
gram-positive organisms, used in the treatment of otitis media and infections of the respiratory and
oropharyngeal tracts, skin, and soft tissues; administered orally.” Id. at 312.
7
  The records do not reveal how long S.B. had been suffering from these symptoms. Pet’rs’ Ex. 6 at 44.
8
  Augmentin is the “trademark for combination preparations of amoxicillin and clavulanate.” Dorland’s
at 179.


                                                    3
       On December 26, 2011, doctors transferred S.B. to the Pediatric Intensive Care Unit
(“PICU”) for respiratory status monitoring after she displayed poor suck and swallow ability,
increased irritability, inconsolability, and weakness. Pet’rs’ Ex. 22 at 26–27. S.B. was diagnosed
with rhinovirus and enterovirus on December 28, 2011. Id. at 40. S.B. was discharged from
Cohen’s Children Medical Center on December 31, 2011. Pet’rs’ Ex. 16 at 1.

        Immediately after discharge, Petitioners took S.B. to Weill Cornell Medical Center’s
emergency room to get a second opinion regarding S.B.’s diagnosis. Pet’rs’ Ex. 23 at 12. Dr.
Murray Engel examined S.B. and noted that her symptoms were “suggestive [of a] post-infectious
disorder[] involving [the] brain [and] possibl[y] [the] spinal cord and peripheral nerve and
muscle.” Id. at 20–21. Even though he noted in the medical records that S.B.’s symptoms were
not “typical [of] Guillain[-]Barre [syndrome9 (“GBS”)], Dr. Engel nonetheless prescribed S.B. the
typical treatment for GBS—a five-day course of IV gamma globulin. Id.

         On January 2, 2012, Dr. Engel performed a video electroencephalogram (“EEG”) on S.B.
Id. at 59. The video EEG showed some “background slowing” and “some sharp waves and slowing
in the right centrotemporal region,” but “no clinical seizures.” Id. Dr. Engel noted in the records
that he needed “further data . . . lab testing[] and . . . imaging” to determine the etiology of the
illness. Id. Dr. Engel sent S.B.’s cerebrospinal fluid (“CSF”) to the Mayo Clinic for further testing
related to anti-NMDAR encephalitis, and S.B. was diagnosed with anti-NMDAR encephalitis on
January 11, 2012. Pet’rs’ Ex. 17 at 135.

       S.B. was transferred to Children’s Hospital of Philadelphia (“CHOP”) for further treatment
on January 12, 2012. Pet’rs’ Ex. 18-3 at 3; Pet’rs’ Ex. 23 at 206. On January 17, 2012, S.B.
began a course of Rituximab10 infusions and a prednisone11 taper. Pet’rs’ Ex. 18-3 at 614. S.B.
was transferred to CHOP’s inpatient rehabilitation department on January 20, 2012, where she
underwent comprehensive rehabilitation until February 8, 2012. See Pet’rs’ Ex. 18-1 at 154–286.

       On February 8, 2012, S.B. was transferred to Blythedale Children’s Hospital where she
underwent continued rehabilitation until March 9, 2012. Pet’rs’ Ex. 9-1 at 3, 11. On April 5, 2012,
S.B. was seen by Dr. Michael Fisher at CHOP. Pet’rs’ Ex. 6 at 67–68. Dr. Fisher noted that S.B.
was “continu[ing] to improve tremendously.” Id. at 67.

        On May 2, 2012, S.B. tested positive again for anti-NMDAR antibodies in both her CSF
and serum. Pet’rs’ Ex. 18-1 at 56. On June 4, 2012, S.B. finished her last round of immunotherapy
and was noted to have “developmentally returned to the level of a regular [two-]year-old.” Pet’rs’
Ex. 6 at 63.

    III.   Experts

9
  Guillain-Barré syndrome is defined as a “rapidly progressive ascending motor neuron paralysis of
unknown etiology, frequently seen after an enteric or respiratory infection.” Dorland’s at 1832.
10
   Rituximab is “a chimeric murine/human monoclonal antibody that binds the CD 20 antigen; used as an
antineoplastic treatment of CD20-positive, B-cell non-Hodgkin lymphoma; administered intravenously.”
Dorland’s at 1650.
11
   Prednisone is “a synthetic glucocorticoid derived from cortisone, administered orally as an anti-
inflammatory and immunosuppressant in a wide variety of disorders.” Dorland’s at 1509.


                                                  4
           A. Expert Backgrounds

                   a. Petitioner’s Expert, Dr. Murray Engel, M.D.

        Dr. Engel received his medical degree from the University of Chicago in 1972. Pet’rs’ Ex.
27 at 1, ECF No. 34-2. He is board certified in pediatrics, psychiatry, and neurology with a special
competence in child neurology and subspecialties in neurodevelopmental disabilities and clinical
neurophysiology. Id. at 4–5. Dr. Engel’s post-doctoral training includes one year spent as a
pediatric resident at Yale-New Haven Hospital in New Haven, Connecticut, and an additional year
spent as an adult neurology resident at the same hospital. Id. at 3. He also spent two years as a
child neurology fellow at Columbia-Presbyterian Medical Center in New York, New York. Id.

        Dr. Engel’s clinical experience includes over forty years as an attending physician at
multiple hospitals. See id. at 3–4. He is currently an attending physician at Yale-New Haven
Hospital, Norwalk Hospital, Greenwich Hospital, Stamford Hospital, Blythedale Children’s
Hospital, and New York Presbyterian Hospital. Id. Dr. Engel has also held numerous academic
positions teaching neurology, clinical neurology, pediatrics, and clinical pediatrics. Id. at 3. He
is currently a professor of clinical pediatrics and neurology at Cornell University, a position he has
held since 2008. Id. Dr. Engel was admitted to testify as an expert in the field of pediatric
neurology. Tr. at 12.

        Dr. Engel submitted one expert report and two supplemental reports in this case. See
Pet’rs’ Exs. 26, 28–29.

                   b. Respondent’s Expert, Dr. Eric Lancaster, M.D., Ph.D.

       Dr. Lancaster received his medical degree from the University of Maryland School of
Medicine in 2003. Resp’t’s Ex. BB at 1, ECF No. 57-1. He completed an internship and neurology
residency from 2003 to 2007, and then a neuromuscular fellowship in 2008, at the University of
Pennsylvania. Id. He is board certified in neurology and has completed subspecialty boards in
both neuromuscular medicine and neuromuscular electrodiagnostic testing. Id.

       Dr. Lancaster has published twenty-two peer-reviewed articles. Id. He states in his first
expert report that “many of these publications deal entirely or in large part with anti-NMDAR
encephalitis and related disorders.” Id. Dr. Lancaster worked as part of Dr. Dalmau’s research
team which made “many of the original discoveries in this field.” Id. Dr. Lancaster also lectures
“frequently” on anti-NMDAR encephalitis and other neurological disorders. Id. at 1–2.

        Dr. Lancaster’s clinical practice is “currently focused on autoimmune neurological
diseases, and most adult patients with anti-NMDAR encephalitis at the University of Pennsylvania
are followed in [his] clinic.” Id. at 2. Over the past two years, he has directed “a quality
improvement project to improve the diagnosis of anti-NMDAR encephalitis and related disorders
at the University of Pennsylvania.” Id. He notes that he “personally studied over 700 patient
samples for NMDAR antibodies by several methods and measured the sensitivity and specificity
of different testing methods.” Id. Dr. Lancaster was admitted to testify as an expert in neurology
and autoimmune neurological disorders and diseases. Tr. at 56.



                                                  5
       Dr. Lancaster submitted one expert report in this case. See Resp’t’s Ex. BB.

           B. Expert Reports

                   a. Dr. Engel’s First Report

       Dr. Engel submitted his first report on June 25, 2015. Pet’rs’ Ex. 26, ECF No. 34-1. After
reviewing S.B.’s pertinent medical history, Dr. Engel stated that “[m]y opinion, to a reasonable
degree of medical certainty, is that [S.B.] developed a complex neurologic syndrome, anti-NMDA
receptor encephalitis, as a direct consequence of having received [the HAV] and flu shot . . . on
11/11/11.” Id. at 6.

         Dr. Engel wrote that encephalitis generally is “inflammation of the nervous system that can
result in multiplicity of neurologic signs, symptoms and disabilities[,]” including “seizures, motor
deficits, coordination disorders, aphasia and other cognitive deficits.” Id. He stated that anti-
NMDAR encephalitis is “[t]he most common form of this autoimmune based encephalitis,” with
possibly four percent of all encephalitis patients having anti-NMDAR encephalitis. Id. (citing
Pet’rs’ Ex. 26, Tab F).

        Dr. Engel described anti-NMDAR encephalitis as “an autoimmune disorder characterized
by the aberrant production of IgG antibodies targeting the NMDA receptor.” Id. These antibodies
affect “synaptic function” in the brain and are “thought to be the pathogenesis of the clinical
syndrome.” Id. Additional signs of anti-NMDAR encephalitis can include “behavioral changes,
movement disorders, seizures, hemiparesis, and autonomic changes.” Id. at 6–7. In a majority of
adult patients with anti-NMDAR encephalitis, “ovarian teratomas have been associated with a
paraneoplastic” cause of the disorder. Id. However, Dr. Engel went on to explain that in
approximately forty percent of all anti-NMDAR encephalitis patients, “there is no clinically
detectable tumor” and thus “[t]he mechanisms triggering the disorder . . . are unknown.” Id. (citing
Pet’rs’ Ex. 26, Tab K).

        Dr. Engel noted there may be an infectious trigger for anti-NMDAR encephalitis in
children, because “there have been infectious links to Mycoplasma, H influenza, mumps, HHV-6
and enterovirus that may occur weeks before” onset. Id. at 7 (citing Pet’rs’ Ex. 26, Tab B). He
also opined that anti-NMDAR encephalitis can be caused by vaccination. Id. Dr. Engel wrote,
“[v]accination triggers an immune-mediated response, which impacts specific antibodies to
synaptic components in the brain, specifically NMDA reception.” Id. Dr. Engel then referenced
a case study in which a patient developed anti-NMDAR encephalitis after receiving tetanus-
diphtheria-acellular-pertussis (“TDaP”) and inactivated polio virus (“IPV”) vaccines and noted
that the authors of the report concluded that “vaccines should be considered as a possible trigger
of immune response in anti-NMDAR encephalitis.” Id. (citing Pet’rs’ Ex. 26, Tab C).

       Dr. Engel then discussed how anti-NMDAR encephalitis is clinically diagnosed. He
explained that symptoms commonly associated with anti-NMDAR encephalitis, such as “coma,
aphasis, seizures, choreoathetosis and dystonia,” are “associated with a variety of laboratory
abnormalities.” Id. Therefore, he explained, “[c]onfirmation of [anti-NMDAR encephalitis]



                                                 6
occurs by demonstrating NMDA receptor antibodies in the blood or spinal fluid.” Id. Dr. Engel
noted that doctors were able to diagnose S.B. with anti-NMDAR encephalitis after tests showed
that “her CFS was positive for anti-NMDAR antibodies.” Id.

         Dr. Engel concluded that “based on S.B.’s clinical presentation and course, as well as her
laboratory studies including MRI, EEG, CSF and anti-NMDA receptor antibodies, . . . she
experienced a post-vaccination anti-NMDA receptor encephalitis.” Id. Dr. Engel noted that he
was one of S.B.’s treating physicians and explained that he thought that S.B. had anti-NMDAR
encephalitis before it was confirmed by laboratory testing. Id. He wrote that he “treated [S.B.]
presumptively with gamma globulin [and] steroids and then transferred [her] . . . to CHOP for
further immunotherapy.” Id. Dr. Engel then stated that S.B.’s “response to immunotherapy is
demonstrative of an immune-mediated mechanism as a cause of her anti-NMDA[R] encephalitis.”
Id. (citing Pet’rs’ Ex. 26, Tab J).

        Dr. Engel noted that S.B.’s case was discussed in a peer-reviewed journal. Id. (citing
Pet’rs’ Ex. 26, Tab H). The case report by Goldberg et al.12 stated that S.B.’s onset of anti-
NMDAR encephalitis occurred “approximately 2 weeks” after receiving the H1N1 flu vaccine and
HAV vaccine. Pet’rs’ Ex. 26, Tab H, at 182. The report also stated that the presenting symptoms
in infants and toddlers with anti-NMDAR encephalitis are “most commonly . . . behavioral
abnormalities, movement disorders, and speech arrest, with seizures being less commonly
reported.” Id. at 183. Dr. Engel also referenced an article by Dalmau et al.13 in which the authors
note that three patients developed anti-NMDAR encephalitis after vaccination: two developed the
disorder after receiving the H1N1 flu vaccine and the third after receiving the DPT vaccine. Id.
(citing Pet’rs’ Ex.26, Tab F).

        Dr. Engel concluded his report by discussing the onset of S.B.’s anti-NMDAR encephalitis.
Pet’rs’ Ex. 26 at 8. He stated that S.B.’s “initial symptoms were approximately [five] weeks”14
after receiving her vaccinations. Id. Dr. Engel again cited to the article by Dalmau et al.15 to show
that most patients, “usually less than 2 weeks [after initial onset], . . . develop psychiatric symptoms
and many are seen initially by psychiatrists.” Id. (citing Pet’rs’ Ex. 26, Tab F). In toddlers,
however, Dr. Engel noted, “the behavioral change can be difficult to detect because they often
present with temper tantrums, hyperactivity, or irritability as opposed to frank psychosis.” Id. Dr.
Engel concluded that S.B.’s behavioral changes occurred weeks before she initially presented to
the emergency room. Id. Therefore, “[t]he onset of her symptoms is well within the time frame
for an immune[-]mediated response (5 to 42 days).” Id. (citing Pet’rs’ Ex. 26, Tab I).

                   b. Dr. Engel’s First Supplemental Expert Report


12
   Ethan M. Goldberg et al., Anti‐N‐methyl‐Daspartate Receptor Mediated Encephalitis in Infants and
Toddlers. Case Report and Review of the Literature, PEDIATRIC NEUROLOGY (2014) 50:181–84.
13
   Josep Dalmau et al., Clinical experience and laboratory investigations in patients with anti‐NMDAR
encephalitis, LANCET NEUROL. (2011) 10:63–74.
14
   It is unclear why the Goldberg et al. article placed onset of S.B.’s disease as “approximately two
weeks” post-vaccination while Dr. Engel wrote that it was “approximately [five] weeks” post-vaccination.
Compare Pet’rs Ex. 26 at 8 with Pet’rs Ex. 26, Tab H, at 182.
15
   Dalmau et al., supra note 13.


                                                   7
        Dr. Engel authored his first supplemental report on April 22, 2016, in response to
Respondent’s criticisms of his causation theory.16 Pet’rs’ Ex. 28, ECF No. 44-1. Specifically,
Respondent argued that Dr. Engel’s causation theory was improbable because “the NMDA
receptors are in an ‘immune privileged’ state, and . . . the blood brain barrier (“BBB”) would need
to be breached in order for [Dr. Engel’s causation theory] to work.” Id. at 1. Dr. Engel explained
that “[t]he [BBB] normally prevents antibodies from entering the nervous system in sufficient
concentrations to cause disease.” Id. at 2. He noted that while “the BBB has very low paracellular
permeability[,]” certain “inflammatory reactions” or “trauma” can make the BBB more permeable.
Id. Specifically, Dr. Engel cited to an article by Wong et al.17 which showed that “inflammatory
mediators such as cytokines produced at the inflammatory site are at least partly responsible for
changes in vascular permeability.” Id. The study demonstrated that “injections of [TNF-alpha]
and [IL-1 beta] increase BBB permeability in rats, while [IFN-gamma], TNF-alpha, and
lipopolysaccharide (LPS) can all increase the permeability of in vitro models of the BBB.” Id.

         Dr. Engel explained that “[i]t is well-accepted that proinflammatory cytokines instigate
BBB dysfunction during neurological diseases.” Id. at 3 (citing Pet’rs’ Ex. 28, Tab C, ECF No.
79-2). Specifically, Dr. Engel wrote “[m]edical literature has demonstrated that cytokines injected
intraperitoneally cross the BBB and end up in measurable quantities in various parts of the brain.”
Id. (citing Pet’rs’ Ex. 28, Tab D, ECF No. 79-2). Dr. Engel cited an article by Threlkeld et al.18 in
which the authors studied the effects of IL-1 [beta] and IL-6 cytokines injected into mice and
concluded that these cytokines “cross the mouse BBB by saturable transport.” Id.

       Dr. Engel then discussed the lack of epidemiological studies associating vaccination with
anti-NMDAR encephalitis. Id. Dr. Engel noted that “[a]ny relationship between vaccination and
anti-NMDA receptor encephalitis is incredibly rare, and epidemiologic[al] studies are not powered
to detect rare events.” Id. Dr. Engel also wrote that case reports “are certainly useful when
discuss[ing] rare events[]” and “serve a unique purpose in the scientific and medical community
by offering anecdotal evidence where experimental evidence is lacking.” Id.

       Dr. Engel concluded by addressing S.B.’s medical history, specifically some infectious
exposures, unrelated to vaccination, that could have initiated an autoimmune response. Id. Dr.
Engel noted that the Institute of Medicine (“IOM”) “has repeatedly stated that the expected
timeframe for an immune[-]mediated response is 5 to 42 days.” Id. Dr. Engel again cited the
Goldberg paper19 and noted the “onset of symptoms . . . two weeks post vaccination (on or around
November 25, 2011).” Id. Dr. Engel concluded that some of these exposures “occurred after
S.B.’s symptoms began.” Id. (emphasis in original). Specifically, “the ‘otitis media noted on
12/22/2011’ and the ‘acute rhino-enteroviral infection as documented from a positive respiratory




16
   These criticisms are discussed in Dr. Panzer’s expert report. See Resp’t’s Ex. A, ECF No. 39-1.
17
   Donald Wong et al., Cytokines, nitric oxide, and cGMP modulate the permeability of an in vitro model
of the human blood-brain barrier, EXPERIMENTAL NEUROLOGY (2004) 190:446–55.
18
   Steven W. Threlkeld et al., Ovine Proinflammatory Cytokines Cross the Murine Blood-Brain Barrier
by a Common Saturable Transport Mechanism, NEUROIMMUNOMODULATION (2010) 17:405–10.
19
   Goldberg et al., supra note 12.


                                                   8
sample obtained [on] 12/26/2011’ occurred after the onset of [S.B.’s] symptoms, and would be a
very unlikely cause or trigger” for S.B.’s anti-NMDAR encephalitis.20 Id.

        Dr. Engel also opined that the vaccinations are a more likely cause of S.B.’s anti-NMDAR
encephalitis because the onset of symptoms—approximately two weeks—is “closer in time and
well-within [sic] the peak of immune-mediated process.” Id. Dr. Engel concluded that “several
treating physicians, including [him]self, agreed that it was logical to conclude that her vaccinations
were implicated in the pathogenesis of her diagnosis.” Id.

                    c. Dr. Engel’s Second Supplemental Report

        Dr. Engel authored his second supplemental expert report on July 29, 2016, in response to
questions from the undersigned. Pet’rs’ Ex. 29, ECF No. 50-1. The undersigned asked Dr. Engel
to “discuss the post-vaccination seizure S.B. had in 2010 and her concurrent otitis media and how
[they] affect[ed] his opinion of the case.” Id. Dr. Engel explained that S.B. had her ten-month
well child visit on December 13, 2010, during which she received a flu shot. Id. At this visit, S.B.
was also diagnosed with right otitis media and was prescribed Augmentin. Id. However, Dr. Engel
noted that the records did not contain evidence that S.B. had a fever at that appointment. Id.

        Three days later, on December 16, 2010, S.B. suffered a febrile seizure. Id. Dr. Engel
wrote that he “briefly discussed this December 16, 2010 febrile seizure in [his] previous report to
demonstrate that this child may have a predisposition to neurologic involvement following
stimulation of her immune system by vaccination.” Id. However, Dr. Engel concluded that “[t]his
does not speak directly to the mechanism involved in the onset of her anti-NMDAR encephalitis,
but is a notable event in her past medical history.” Id.

        The undersigned also requested that Dr. Engel “discuss what role [S.B.’s severe diarrhea
on November 6, 2011, five days before she received the [HAV and flu vaccines] played, if any,
and how it affect[ed] his opinion of the case.” Id. Dr. Engel noted that the medical records
surrounding this phone visit show that S.B. had “watery diarrhea for [one] day” and was “active,
playful, drinking well and looked well.” Id. Dr. Engel opined that “[t]here are many causes of
watery stools, and in the absence of fever and vomiting, there is little evidence that it was caused
by an infection.” Id. at 4.

                    d. Dr. Lancaster’s Expert Report

        Dr. Lancaster submitted his expert report on May 15, 2017. Resp’t’s Ex. BB, ECF No. 57-
1. Dr. Lancaster began his report by summarizing the key events in S.B.’s medical history. See
id. at 2–5. This summary did not differ substantially from the summary provided in Dr. Engel’s
expert report.

       Dr. Lancaster then provided background on anti-NMDAR encephalitis. Id. at 5. He
described anti-NMDAR encephalitis as “a rare autoimmune brain disease in which the immune
system generates autoantibodies to the N-methyl-D-aspartate . . . receptor.” Id. He noted that the

 These potential infectious exposures were listed in Dr. Panzer’s first report. See Resp’t’s Ex. A at 7.
20

Dr. Engel submitted his first supplemental report as a rebuttal to Dr. Panzer’s expert report.


                                                     9
disorder “affects more men than women,” and the median age of patients developing the disorder
is twenty years old. Id. Dr. Lancaster explained that some patients “may have a flu-like prodrome
(a few days to [two] weeks) before the onset of symptoms.” Id. However, he noted that “[i]t is
not well understood what this prodrome is.” Id.

        Dr. Lancaster wrote that in adults with anti-NMDAR encephalitis, the first symptom is
usually “psychosis and hallucinations, delusions, and inappropriate or aggressive behaviors.” Id.
In children, Dr. Lancaster stated that “[a]bnormal limb postures, abnormal gait, and dragging of a
limb are particularly common symptoms.” Id. at 6. Although seizures may occur, Dr. Lancaster
stated that they “tend to remit with treatment.” Id. Dr. Lancaster explained that some patients
may enter a state of catatonia in which “they are awake but do not respond,” whereas others may
become “comatose, sometimes for prolonged periods [of time].” Id. If patients enter a comatose
or catatonic state, “they often have autonomic instability, with wild swings in blood pressure and
heart rate.” Id.

        In terms of recovery, Dr. Lancaster noted that “[w]ith appropriate immune therapy, most
patients slowly recover over weeks to months.” Id. He also explained that recovery is possible
for patients that have entered a comatose or catatonic state, as they “may still gradually return to a
normal (or almost normal) life[] with proper immune therapy.” Id. However, he wrote that
approximately six percent of anti-NMDAR patients die from the disorder. Id.

        Dr. Lancaster explained that “[t]here are two known triggers of anti-NMDAR
encephalitis.” Id. The first is ovarian teratoma. Id. Dr. Lancaster described this as a “complex
tumor” that “generally [has] neuronal tissue with NMDARs on it.” Id. Dr. Lancaster opined that
approximately fifty percent of anti-NMDAR encephalitis patients have an ovarian teratoma, and
it is mostly seen in women of reproductive age. Id. He noted the possibility of other types of
tumors associated with this disorder but stated that they are “much rarer and less consistent . . .
[and] may be coincidence.” Id.

        Dr. Lancaster wrote that “the other known cause [of anti-NMDAR encephalitis] is a very
severe preceding brain infection known as HSV encephalitis.” Id. Dr. Lancaster described this
infection as causing “severe inflammation of the brain” which requires “a massive immune
response . . . to survive.” Id. This immune response, he continued, causes that immune system to
“encounter[] neurons that have been affected by viruses and the normal immune response is lost.”
Id. Dr. Lancaster opines that “[t]he presentation of a normal antigen in this context may be the
trigger.” Id.

       Dr. Lancaster explained that the HSV encephalitis precedes the anti-NMDAR encephalitis
by approximately seven to fifty-one days. Id. He discussed three articles to support this
proposition. The first, by Pruss et al.,21 “reported a series of patients with NMDAR antibodies
evolving within several weeks of HSV encephalitis.” Id. (citing Resp’t’s Ex. BB, Tab 3). The
second, Armangue et al.,22 presented five patients who developed clinical signs of anti-NMDAR

21
   Harald Prüss et al., N-Methyl-D-Aspartate Receptor Antibodies in Herpes Simplex Encephalitis, ANN.
NEUROL. (2012) 72(6):902–11.
22
   Thaís Armangue et al., Herpes Simplex Virus Encephalitis is a Trigger of Brain Autoimmunity, ANN.
NEUROL. (2014) 75(2):317–23.


                                                 10
encephalitis seven to forty-one days after HSV encephalitis. Id. (citing Resp’t’s Ex. BB, Tab 4).
Dr. Lancaster noted that this study found that “a variety of other types of brain antibodies may be
triggered by HSV encephalitis.” Id. He used this finding to “argue[] against a specific molecular
mimicry by the virus.” Id. Rather, Dr. Lancaster argued that his theory—“exposure of brain
antigens to the immune system and loss of self-tolerance in the context of life-threatening viral
infection of the brain”—is a more likely explanation for how HSV encephalitis causes anti-
NMDAR encephalitis. Id. The final article, another by Armangue et al.,23 “reported [eight]
additional cases of anti-NMDAR encephalitis occurring with a latency of [twelve to fifty-one]
days.” Id. (citing Resp’t’s’ Ex. BB, Tab 5).

        Dr. Lancaster then discussed Dr. Engel’s expert report. Dr. Lancaster agreed that anti-
NMDAR encephalitis is the correct diagnosis in this case. Id. at 7. However, Dr. Lancaster
disagreed with Dr. Engel that anti-NMDAR encephalitis must have an identifiable cause. Dr.
Lancaster wrote, “in about half of [anti-NMDAR encephalitis] cases no particular cause is
identified.” Id. Dr. Lancaster noted that “Dr. Engel’s report ignores numerous preceding
infections in a reasonable time-frame of the onset of anti-NMDAR encephalitis, which provide
alternative causes.” Id. Dr. Lancaster argued that, because of the prodrome resembling an
infection seen in many anti-NMDAR encephalitis patients and a known infectious cause (HSV
encephalitis), “it is more logical for infections to be triggers of anti-NMDAR encephalitis rather
than vaccines.” Id.

         Dr. Lancaster further explained that molecular mimicry, proposed as a mechanism for
autoimmune CNS disorders in the supporting medical literature attached to Dr. Engel’s first expert
report from vaccination is “very unlikely” in anti-NMDAR encephalitis cases for two reasons. Id.
First, the autoantibodies which cause anti-NMDAR encephalitis “are highly specific for a
particular part of the three[-]dimensional structure of the receptor, the ‘dominant epitope’ which
is the same for most patients.” Id. Dr. Lancaster wrote that “[t]hese antibodies can only target the
receptor in its intact conformation in the membrane of cells.” Id. Second, Dr. Lancaster explained
that these antibodies “do not recognize other closely related proteins.” He continued, “[r]eceptors
that are denatured (lose their [three-]dimensional shape) cannot be recognized[]” by these
antibodies. Id.

       Dr. Lancaster also disagreed with Dr. Engel’s use of case reports of individuals with anti-
NMDAR encephalitis with a possible connection to other vaccinations such as TDaP and IPV. Id.
Dr. Lancaster wrote that any association between anti-NMDAR encephalitis and these vaccines is
“most likely coinci[dental].” Id.

           C. Expert Testimony

                   a. Dr. Engel’s Testimony

        Dr. Engel described anti-NMDAR encephalitis as “autoimmune,” which he explained
meant a “misdirected immune response where it targets parts of the body when it thinks it’s
targeting an external antigen or an internal stimulus.” Tr. at 16:7–13. He listed “environment

23
  Thaís Armangue et al., Autoimmune Post–Herpes Simplex Encephalitis of Adults and Teenagers,
NEUROLOGY (2015) 85:1736–43.


                                                11
[and] genetics” as factors that influence autoimmunity. Tr. at 16:14–16. Dr. Engel referenced the
Venkatesan et al.24 article when discussing the mechanisms associated with autoimmunity. Dr.
Engel stated that there are “multiple potential mechanisms . . . [such as] molecular imaging” but
noted that “it’s not absolutely clear which is operative.” Tr. at 16:24–17:3.

          Dr. Engel generally described the mechanism by which the HAV and flu vaccines can
cause anti-NMDAR encephalitis as one where “the antibodies form in response to the stimulus
and then the antibodies cross the blood-brain barrier to the brain.” Tr. at 17:20–22. He stated that
it is a “two-step process” where there “is a breach of the blood-brain barrier and then the antibodies
gain access to the CNS.” Tr. at 17:24–18:1. Dr. Engel testified that the “permeability [of] the
blood-brain barrier [is impacted by] . . . proinflammatory cytokines.” Tr. at 18:5–7. He stated,
“[s]o basically, [H]ep A, influenza [vaccines] promote proinflammatory cytokines and that impacts
the blood-brain barrier.” Tr. at 18:9–11. When asked about the process of proinflammatory
cytokines crossing the BBB, Dr. Engel stated, “[w]ell, we don’t really know the mechanism and
so . . . we’re really not sure of the mechanism so we really can’t explain it.” Tr. at 43:20–22. He
was also unable to state whether molecular mimicry played a role in S.B.’s case, stating, “[w]e
don’t know . . . the mechanism, so it would be speculation. I really don’t have an opinion.” Tr. at
43:23–44:3.

        Dr. Engel testified that vaccines have been associated with anti-NMDAR encephalitis in
medical literature. Tr. at 19:10–20. To support this proposition, Dr. Engel cited the case reports
referenced in his written reports. First, he cited a report by Hoffman et al.25 which discussed a
patient who developed anti-NMDAR encephalitis one day after receiving the TDaP and IPV
vaccines. Pet’rs’ Ex. 26, Tab C. The authors of the report concluded that “[t]he onset of prodromal
symptoms shortly after the immunization is intriguing and suggests the vaccination as a possible
trigger of anti-NMDA[R] encephalitis.” Id. Second, he cited Dalmau et al.26 in which the authors
discussed three patients who developed anti-NMDAR encephalitis after vaccination. Pet’rs’ Ex.
26, Tab F, at 66. Third, he discussed Goldberg et al.,27 which centered on S.B.’s case.

         Dr. Engel analogized the connection between vaccines and other neurological disorders of
the CNS, including “acute disseminated encephalomyelitis” (“ADEM”) and “transverse myelitis”
(“TM”). Tr. at 19:24–20:3. He cited to the Institute of Medicine’s seminal text28 in which the
authors state that “ADEM and GBS can occur after the administration of . . . live or attenuated or
killed vaccines.” Pet’rs’ Ex. 26, Tab I, at 47. The authors continue, “ADEM and GBS in humans
. . . generally occur after an interval of [five] days to [six] weeks following infection (not clinical
disease) or injection of [an] antigen.” Id.



24
   Arun Venkatesan and David R. Benavides, Autoimmune Encephalitis and Its Relation to Infection,
CURR. NEUROL. NEUROSCI. REP. (2015) 15(3):3.
25
   Caroline Hofmann et al., Anti‐NMDA Receptor Encephalitis After TdaP-IPV Booster Vaccination:
Cause or Coincidence, J. NEUROL. (2011) 258:500–01.
26
   Dalmau et al., supra note 13.
27
   Goldberg et al., supra note 12.
28
   Vaccine Safety Committee, ADVERSE EVENTS ASSOCIATED WITH CHILDHOOD VACCINES: EVIDENCE
ON CAUSALITY 47 (Kathleen R. Stratton et al. eds., 1994).



                                                  12
         Dr. Engel stated that there was a logical sequence of cause and effect between S.B.’s flu
and HAV vaccines and her anti-NMDAR encephalitis because “[s]he was healthy beforehand. She
received the vaccine[s] and then her onset of symptoms occurred within the time frame for vaccine-
related anti-NMDA[R] encephalitis and [then] she responded to immunomodulatory therapy.” Tr.
at 20:8–12. Dr. Engel testified that he wrote “two months after immunization” in S.B.’s medical
records because he “speculated that the immunizations may have been etiologic in the development
of her [anti-NMDAR encephalitis].” Tr. at 22:7–16. He explained that “it seemed to be a post-
infection or after-infection disorder of the nervous system,” and “since this syndrome had a very .
. . significant cost,” he “felt that the risk of a five-day course of gamma globulin . . . was clinically
warranted.” Tr. at 22:24–23:8.

       Dr. Engel described the onset of S.B.’s symptoms as occurring when she had “the
behavioral change, insomnia, and then developed the motor problems on the left.” Tr. at 24:1–9.
He noted that tantrums and behavioral changes would not be easy to identify in a 22-month-old
child. Tr. at 24:22–25. Dr. Engel testified that the acknowledged period of time during which
immune-mediated reactions can occur is either five to forty-two days according to the Institute of
Medicine or seven to fifty-one days according to Dr. Lancaster’s report. Tr. at 25:19–22. He
opined that, regardless of which measure is used, S.B. is “within the range.” Tr. at 25:22–23.

         Dr. Engel then examined potential alternative causes of S.B.’s anti-NMDAR encephalitis.
Dr. Engel first discussed the respiratory virus panel by Polymerase Chain Reaction (“PCR”) which
showed that S.B. had rhinovirus and enterovirus on December 26, 2011. Tr. at 27:3–12. Dr. Engel
testified that he did not think that either virus could be an alternative cause of S.B.’s anti-NMDAR
encephalitis because “[i]t’s such a common finding.” Tr. at 27:11–12. He also testified that he
did not think that the otitis media with which S.B. was diagnosed on December 22, 2011, could be
an alternative cause because it “is a very common disorder.” Tr. at 28:13–24. Dr. Engel also
opined that S.B.’s upper respiratory infection mentioned in medical records from December 29,
2018, as having occurred two weeks prior could not be an alternative cause because he “[did not]
think the time frame works.” Tr. at 29:19–30:1.

         Dr. Engel then discussed S.B.’s watery diarrhea on November 6, 2011, which resulted in a
telephone visit with her primary care physician. Tr. at 30:9–31:19. He testified that he did not
think an infection caused S.B.’s diarrhea because “she was active and playful and . . . drinking
well, [which] does not support that she had a systemic illness.” Tr. at 30:9–11. Dr. Engel also
discussed S.B.’s viral exanthem, diagnosed on October 19, 2011. Tr. at 32: 21–24. He opined that
this is unlikely to be an alternative cause because S.B. “had no fever, the rash was [only present]
for 24 hours, [and] no testing was done.” Tr. at 33:3–6.

        On cross-examination, Dr. Engel was unable to say which of the vaccines S.B. received—
the HAV or flu—caused her to develop anti-NMDAR encephalitis. Tr. at 42:23–43:1. Dr. Engel
also agreed that, aside from ovarian teratoma and HSV, anti-NMDAR can be caused by “infectious
causes.” Tr. at 41:2–4. However, Dr. Engel testified that he believed that vaccines were more
likely the cause of S.B.’s anti-NMDAR encephalitis than her preceding infections because of “the
timing.” Tr. at 43:2–4. Dr. Engel stated that the HAV vaccine causes anti-NMDAR encephalitis
because “[t]he hepatitis . . . causes the body to make this antibody that then is able to cross the




                                                   13
blood-brain barrier.” Tr. at 44:9–14. Dr. Engel also opined that the “mechanisms are the same”
for how the flu vaccine can cause anti-NMDAR encephalitis. Tr. at 44:16–18.

         Dr. Engel testified during questioning by the undersigned that the immune response
triggered by vaccinations in general is what caused S.B.’s anti-NMDAR encephalitis, and not
something specific about the HAV or flu vaccines. Tr. at 45:21–46:6. Dr. Engel was unable to
list any other possible mechanisms besides molecular mimicry that could cause antibodies to cross
the BBB but stated, “I think there are probably other causes.” Tr. at 4613–23. He stated that he
is “actually a believer [that] there probably is a genetic predisposition” to autoimmunity in order
for a vaccination to trigger BBB permeability. Tr. at 47:3–8. He also opined that S.B. would have
had the autoimmune response regardless of her history of infections. Tr. at 47:13–19. Dr. Engel
stated, “[i]t would have occurred. I don’t think she had a usual number of infections for a two-
year-old child.” Tr. at 47–19:20.

                   b. Dr. Lancaster’s Testimony

        Dr. Lancaster confirmed S.B.’s diagnosis of anti-NMDAR encephalitis. Tr. at 57:10–11.
He described anti-NMDAR encephalitis as “a rare autoimmune brain disease where patients make
a very specific antibody to one part of one subunit of the NMDA receptor.” Tr. at 57:21–24.

         Dr. Lancaster testified that “about half of [anti-NMDAR encephalitis cases are] caused by
. . . ovarian teratoma.” Tr. at 63:21:22. He described this tumor as “a benign tumor of the ovary.”
Tr. at 63:22–23. He stated that the tumor is “interesting because it has NMDA receptors” on it.
Tr. at 64:1–3. He explained that ovarian teratoma causes anti-NMDAR encephalitis by “triggering
the immune system [which] select[s] a clone, a group of immune cells, . . . to make . . . good
antibodies to the NMDA receptor.” Tr. at 111:7–12. He stated that those cells “proliferate and
then produce the antibodies[.]” Tr. at 111:12–13. Dr. Lancaster conceded that “[w]e don’t know
precisely” at “what point . . . the tumor become[s] sufficient enough to produce a response in the
body to create anti-NMDA receptor antibodies[.]” Tr. at 112:16–113:6. Dr. Lancaster stated that
the mechanism by which ovarian teratoma causes anti-NMDAR encephalitis does not require the
BBB to become more permeable or be breached. Tr. at 113:21–24. He explained that “many
patients, on their MRI, show no evidence of any [BBB] breakdown.” Tr. at 113:25–114:2.

        In the other half of patients with anti-NMDAR encephalitis, Dr. Lancaster testified that
“there is no tumor or there’s almost never any tumor.” Tr. at 16–17. He stated that in about “[two]
percent” of anti-NMDAR encephalitis patients, the disease is caused by “HSV encephalitis” which
is “a severe infection of the brain itself.” Tr. at 64:16–20. Dr. Lancaster explained that if patients
survive HSV encephalitis, then approximately “seven to seventy-four days later, anti-NMDA[R]
encephalitis can occur.” Tr. at 64:25–65:2. He testified that the mechanism by which HSV
encephalitis causes anti-NMDAR encephalitis “is not precisely known.” Tr. at 115:7–8. However,
he stated that he would not classify the mechanism as “nonspecific.” Id. at 116:3–6. He continued,
“I would say [that a patient] has to generate a specific NMDA antibody to get anti-NMDA[R]
encephalitis.” Tr. at 116:6–8.

        Dr. Lancaster testified that in approximately half of anti-NMDAR encephalitis patients
overall, “there is a preceding infection in the weeks before the illness.” Tr. at 656–10. He cited



                                                 14
to the Florance et al.29 paper in which thirty-two adolescent anti-NMDAR patients were studied.
This study found that “[p]rodromal symptoms such as fever, headache, upper respiratory
symptoms, vomiting, or diarrhea were noted in [forty-eight percent] of patients.” Id. (Pet’rs’ Ex.
26, Tab K, at 3). Dr. Lancaster noted that there was “no evidence” that S.B. had an ovarian
teratoma or HSV encephalitis. Tr. at 67:8–9. However, he testified that there was evidence that
S.B. “experienced . . . the symptoms identified in the Florance paper.” Tr. at 67:15–19. He stated
that S.B. had “a viral exanthem on 10/19/2011,” “gastroenteritis on 11/[7/]2011,” “otitis media . .
. diagnosed on 12/22/2011,” and an “acute rhino enteroviral infection on 12/26[/2011].” Tr. at
67:21–68:1.

         Dr. Lancaster disagreed that S.B.’s behavioral changes occurred before her movement
disorder. Tr. at 94:4–6. He stated that the “dystonia seems to have [occurred] . . . as an early
symptom[] of the illness . . . at about the same time [as] these nonspecific irritability behavioral
change symptoms and probably . . . a little bit before changes [occurred] in her speech or at about
the same time.” Tr. at 94:14–19. He opined that the onset of S.B.’s anti-NMDAR encephalitis
occurred sometime between December 7, 2011, and December 21, 2011. Tr. at 96:1–4. He
explained that he “would favor the earlier part of that time frame as being most convincing because
there [was] a clear history of symptoms of dystonia.” Tr. at 68:17–19. He noted that the “abnormal
posture of the limb” was diagnosed around December 7, 2011, which “would put the gastroenteritis
as occurring . . . approximately 31 days” prior. Tr. at 68:20–69:2. Dr. Lancaster explained that
the “clearest evidence we . . . have . . . that relates to the cases of post-HSV anti-NMDA[R]
encephalitis, . . . [is that the disease occurs] . . . 7 to approximately 70 days after[] [the HSV
encephalitis].” Tr. at 69:6–13. Therefore, Dr. Lancaster opined that the “gastroenteritis probably
fits the timing the best” because it “fall[s] into a reasonable time frame.” Id. at 68:7–9.

        Dr. Lancaster discussed the paper he co-authored with Dr. Dalmau30 which “attempted to
provide a broad and pretty comprehensive description of anti-NMDA[R] encephalitis, what’s
known about the clinical features[,] . . . what’s known about the treatments that have been used,
what’s known about causes, what’s known about mechanisms and what our recommendations
were for how patients should be evaluated and treated.” Tr. at 71:6–12. The paper also included
a description of two patients who developed anti-NMDAR encephalitis after vaccination against
H1N1 flu. Tr. at 71:13–17; see also Resp’t’s Ex. EE at 5. Dr. Lancaster explained that he “thought
we should include [the patients who developed the disease after vaccination] in case subsequently
other cases . . . [showed that vaccinations] actually conveyed a risk of anti-NMDA[R]
encephalitis.” Tr. at 72:8–12. However, Dr. Lancaster stated, “[w]e have not been seeing
associations with the vaccines [and anti-NMDAR encephalitis].” Tr. at 72:14–15. He opined that
he did “not think there is any evidence it’s more likely than not that the flu [or HAV] vaccine[s]
would cause anti-NMDA[R] encephalitis.” Tr. at 73:12–20.

         Dr. Lancaster disagreed with Dr. Engel’s causation theory because “the theory is lacking
in that it doesn’t explain the key feature of the disease, which is how were the specific antibodies
to the NMDA receptor generated.” Tr. at 74:5–8. He explained that “many things could disrupt


29
   Nicole R. Florance et al., Anti‐N‐Methyl‐D‐Aspartate Receptor (NMDAR) Encephalitis in Children and
Adolescents, ANN. NEUROL. (2009) 66(1):11–18.
30
   Dalmau et al., supra note 13.


                                                 15
the blood-brain barrier,” and even if vaccines could disrupt the BBB, “it doesn’t explain where . .
. the specific antibodies come from.” Tr. at 74:16–21.

          Dr. Lancaster also testified that “at some level, antibodies are naturally found in the brain.”
Tr. at 75:2–5. He explained that “there are pathways for a certain level of antibodies to be sort of
transported across the blood-brain barrier to enter the brain just from your circulation.” Tr. at
75:12–15. He stated that this is “a very normal process and . . . [it doesn’t mean that] the [BBB
is] disrupted because it’s letting certain cells that are supposed to get through at low levels get
through . . . and seals up immediately behind them without causing any damage to the brain or loss
of integrity” of the BBB. Tr. at 75:12–76:10. In anti-NMDAR encephalitis patients, “the response
. . . starts peripherally. It’s an important part of the disease for these immune cells often to move
into the brain and cause . . . intrathecal production, production of antibod[ies] inside the brain.”
Tr. at 76:15–22. Dr. Lancaster explained that “[t]he [BBB] is not broken down[,]” and in many
patients—including S.B.—the “brain MRI is normal.” Tr. at 76:23–25. He opined that “this idea
that the [BBB] itself breaking down is either an important part of [anti-NMDAR encephalitis] or
sufficient to cause the disease” is not correct. Tr. at 77:15–18.

        Dr. Lancaster testified that the IOM “has looked at several conditions, such as ADEM and
[GBS] that have been associated with certain vaccinations. They propose somewhat different time
windows . . . [but] have not . . . addressed . . . anti-NMDA[R] encephalitis at all.” Tr. at 102:13–
19. He agreed that there is a connection between vaccination and GBS and ADEM. Tr. at 104:23–
105:6. However, he noted that ADEM is “quite distinct from anti-NMDA[R] encephalitis because
it involves an immune response against the myelin . . . and doesn’t involve specific antibodies to
the NMDA receptor.” Tr. at 102:23–103:4.

        Dr. Lancaster agreed that both the HAV and flu vaccines have been shown to increase the
production of proinflammatory cytokines. Tr. at 122:9–13;103:15–18. However, he stated that
the increase in proinflammatory cytokines—even if it caused a change in the permeability of the
BBB or a breach in the BBB—“still doesn’t get us close to understanding how someone would
develop [the antibodies necessary to develop] anti-NMDA[R] encephalitis.” Tr. at 122:20–22. He
analogized it to injecting “an adjuvant, which is designed to stimulate the immune system[,] . . .
directly into someone’s temporal lobe, I might well be able to generate in a percentage of people
an autoimmune disease targeting multiple brain proteins.” Tr. at 116:13–16. However, he stated
that “there still has to be that specific NMDA antibody or they don’t get [anti-NMDAR
encephalitis.” Tr. at 116:16–18. Dr. Lancaster also stated that “[t]he only reason I’m discussing
the [BBB] issue at all is [it] was proposed as a mechanism by [Dr. Engel] and I felt compelled to
respon[d] . . . and say [that] I don’t think [it] is a very good mechanism.” Tr. at 141:22–142:1.

       Dr. Lancaster agreed that “viral infections are also . . . as ubiquitous as vaccinations with
children.” Tr. at 132:16–20. He stated that if “we had looked at all of these children with anti-
NMDA[R] encephalitis and we were seeing vaccinations as the common antecedent event several
weeks before the onset of the illness and we were rarely seeing infections, that would make
vaccinations the likely cause.” Tr. at 131:16–21. He continued, “[i]nstead . . . [there is] this strong
association with half of [the patients] having infections, [and] the vaccine causes being these
occasional case reports that are likely chance[.]” Tr. at 132:1–4. He explained that if there were
an association between vaccinations and anti-NMDAR encephalitis, it would have a stronger



                                                   16
degree of evidence because “[t]he children, at a young age, . . . have so many vaccinations that just
by pure coincidence” there could be onset of anti-NMDAR encephalitis within one or two months
of a child receiving a vaccination. Tr. at 132:8–13. Therefore, even though vaccinations and viral
infections are equally ubiquitous in children, infections are more likely the cause because “we have
the association [of preceding infections and] anti-NMDA[R] encephalitis with a much, much
stronger degree of evidence” than with anti-NMDAR encephalitis and vaccinations. Tr. at 132:18–
20.

   IV.     The Applicable Legal Standard

         To receive compensation under the Vaccine Act, Petitioners must demonstrate either that:
(1) S.B. suffered a “Table injury” by receiving a covered vaccine and subsequently developing a
listed injury within the time frame prescribed by the Vaccine Injury Table set forth at 42 U.S.C. §
300aa-14, as amended by 42 C.F.R. § 100.3, or (2) that she suffered an “off-Table injury,” one not
listed on the Table as a result of her receipt of a covered vaccine. See 42 U.S.C. §§ 300aa-
11(c)(1)(C); 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, 1319–20 (Fed. Cir. 2006).
Petitioners do not allege a Table injury in this case; thus, they must prove that S.B.’s injury was
caused-in-fact by a Table vaccine.

        To establish causation-in-fact, Petitioners must demonstrate by a preponderance of the
evidence that the vaccine was the cause of the injury. 42 U.S.C. § 300aa-13(a)(1)(A). Petitioners
are required to prove that the vaccine was “not only a but-for cause of the injury but also a
substantial factor in bringing about the injury.” Moberly, 592 F.3d at 1321–22 (quoting Shyface
v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352–53 (Fed. Cir. 1999)).

        In the seminal case of Althen v. Sec’y of Health and Human Servs., the Federal Circuit set
forth a three-pronged test used to determine whether a petitioner has established a causal link
between a vaccine and the claimed injury. See 418 F.3d 1274, 1278–79 (Fed. Cir. 2005). The
Althen test requires the petitioner to set forth: “(1) a medical theory causally connecting the
vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination
was the reason for the injury; and (3) a showing of a proximate temporal relationship between
vaccination and injury.” Id. at 1278. To establish entitlement to compensation under the Program,
Petitioners are required to establish each of the three prongs of Althen by a preponderance of the
evidence. See id.

        Specifically, under the first prong of Althen, a petitioner must offer a scientific or medical
theory that answers in the affirmative the question “can the vaccine(s) at issue cause the type of
injury alleged?” See Pafford v. Sec’y of Health & Human Servs., No. 01-0165V, 2004 WL
1717359, at *4 (Fed. Cl. Spec. Mstr. July 16, 2004), aff’d, 64 Fed. Cl. 19 (2005), aff’d, 451 F.3d
1352 (Fed. Cir. 2006). To satisfy this prong, a petitioner’s theory must be based on a “sound and
reliable medical or scientific explanation.” Knudsen v. Sec’y of Health & 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 548–49. This may be accomplished in a number of ways.




                                                 17
         “Reliability and plausibility of [ ] pathogenesis can be bolstered by providing evidence
that at least a sufficient minority in the medical community has accepted the theory as to render
it credible.” Pafford, 2004 WL 1717359, at *4. Additionally, “epidemiological studies and an
expert’s experience, while not dispositive, lend significant credence to the claim of plausibility.”
Id. “Articles published in respected medical journals, which have been subjected to peer review,
are also persuasive.”31 Id.

        In addition to showing that the vaccine at issue can cause a particular injury, a petitioner
must also, under Althen’s second prong, prove that the vaccine actually did cause the alleged injury
in a particular case. See Pafford, 2004 WL 1717359, at *4; Althen, 418 F.3d at 1279. 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 v. Sec’y of Health
& Human Servs. of Health & Human Servs., 569 F.3d 1367, 1380 (Fed. Cir. 2009); Capizzano,
440 F.3d at 1326; Grant v. Sec’y of Health & Health Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992).
Medical records are generally viewed as particularly trustworthy evidence, because 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). A petitioner does not meet this obligation by
showing only a temporal association between the vaccination and the injury; instead, the petitioner
“must explain how and why the injury occurred.” Pafford, 2004 WL 1717359, at *4 (emphasis in
original).

        Although a temporal association alone is insufficient to establish causation, under the third
prong of Althen, a petitioner must show that the timing of the injury fits with the causal theory.
See Althen, 418 F.3d at 1278. For example, if the petitioner’s theory involves a process that takes
several days to develop after vaccination, an injury that occurred within a day of vaccination would
not be temporally consistent with that theory. Conversely, if the theory is one that anticipates a
rapid development of a reaction post-vaccination, the development of the alleged injury weeks or
months post-vaccination would not be consistent with that theory. Causation-in-fact cannot be
inferred from temporal proximity alone. See Grant, 956 F.2d at 1148; Thibaudeau v. Sec’y of
Health & Human Servs., 24 Cl. Ct. 400, 403–04 (1991); see also Hasler v. United States, 718 F.2d
202, 205 (6th Cir. 1983) (“Without more, [a] proximate temporal relationship will not support a
finding of causation.”).

        A petitioner who demonstrates by a preponderance of the evidence that she suffered an
injury caused by vaccination is entitled to compensation, unless Respondent can demonstrate by a
preponderance of the evidence that the injury was caused by factors unrelated to the vaccination.
See Althen, 418 F.3d at 1278; Knudsen, 35 F.3d at 547.


31
   Both parties filed medical and scientific literature in this case, but not every filed item factors
into the outcome of this decision. While the undersigned has reviewed all of the information filed
in this case, only those articles and records that are most relevant to the decision will be discussed. Moriarty
v. Sec’y of Health & Human Servs., 844 F.3d 1322, 1328 (Fed. Cir. 2016) (“We generally presume that a
special master considered the relevant record evidence even though he does not explicitly reference such
evidence in his decision.”) (citation omitted); see also Paterek v. Sec’y of Health & Human Servs., 527 F.
App’x 875, 884 (Fed. Cir. 2013) (“Finding certain information not relevant does not lead to—and likely
undermines—the conclusion that it was not considered.”).


                                                      18
   V.      Discussion

           A. Experts

         In this case, the experts presented by Petitioners and Respondent agree on S.B.’s diagnosis
of anti-NMDAR encephalitis. Both Dr. Engel and Dr. Lancaster are board certified in neurology,
and Dr. Engel has a special competence in child neurology. Dr. Lancaster’s clinical practice
focuses on autoimmune neurological diseases, and his clinic regularly sees all of the adult anti-
NMDAR encephalitis patients at the University of Pennsylvania hospital. Dr. Lancaster has also
personally studied numerous samples of NMDAR antibodies. In addition, Dr. Lancaster has
published twenty-two peer-reviewed articles, most of which focus on anti-NMDAR encephalitis.
In fact, Dr. Lancaster is a co-author of one of the articles cited by both parties. See Pet’rs’ Ex. 26,
Tab F; see also Resp’t’s Ex. DD. Dr. Engel has treated only one or two patients with anti-NMDAR
encephalitis, one of whom is S.B.

        Dr. Engel also seemed less familiar with S.B.’s medical record during parts of his
testimony. For example, Respondent’s counsel asked Dr. Engel whether he “agree[d] that S.B.
was diagnosed with an upper respiratory infection on August 2nd, 2001[.]” Tr. at 37. Dr. Engel
directed his response to Petitioners’ counsel, asking, “[t]oo many dates here. Is that accurate?”
Tr. at 37. In addition, Petitioners’ counsel asked Dr. Engel if he “was able to locate any
contemporaneous medical records diagnosing S.B. with a[n upper respiratory infection (“URI”);]”
to which Dr. Engel replied, “I don’t recall, but if you could direct me to it, I might have.” Id. at
30. These examples suggest that Dr. Engel did not conduct as thorough a review of the medical
records prior to the hearing, when compared to Dr. Lancaster. For these reasons, Dr. Lancaster’s
testimony explaining S.B.’s medical history was more persuasive.

        The undersigned is aware that Dr. Engel is not only a testifying expert on behalf of
Petitioners but also one of S.B.’s treating physicians. Under the Vaccine Program, a treating
physician’s notes are usually considered more persuasive than an expert relying solely on the
written record. Capizzano, 440 F.3d at 1326 (noting that “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) (internal quotation
marks omitted)); but see Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 745 n.67
(2009) (noting “there is nothing in Andreu that mandates that the testimony of a treating physician
is sacrosanct—that it must be accepted in its entirety and cannot be rebutted.”). However, the
undersigned will not afford substantial deference to Dr. Engel because of his relative inexperience
treating anti-NMDAR encephalitis. Dr. Engel conceded during his testimony that he had seen
only two or three patients during his career with anti-NMDAR encephalitis, including S.B. He has
not published any articles on this disease, nor has he done any research on it. When compared
with Dr. Lancaster, the difference in experience with anti-NMDAR encephalitis is significant. Dr.
Lancaster has treated or diagnosed approximately forty patients with anti-NMDAR encephalitis
throughout his career. He has published twelve peer-reviewed articles discussing and analyzing
anti-NMDAR encephalitis. Dr. Lancaster also directed a “project to improve the diagnosis of anti-
NMDAR encephalitis,” where he “personally studied over 700 patient samples for NMDAR
antibodies [using] several methods and measured the sensitivity and specificity of different testing
methods.” Resp’t’s Ex. BB at 2. In light of these differences in experience level with anti-



                                                  19
NMDAR encephalitis, Dr. Engel’s opinion as it relates to the cause of S.B.’s injuries will not be
given the level of deference normally afforded to treating physicians with a relevant specialty.

              B. Althen Prong One

        Petitioners have failed to present by a preponderance of the evidence a medical theory
causally connecting the HAV and flu vaccines to S.B.’s anti-NMDAR encephalitis. It is unclear
exactly what theory Petitioner is advancing and the undersigned was forced to parse one together
from Dr. Engel’s reports and testimony. It seems that Dr. Engel is proposing that an increase in
proinflammatory cytokines caused by the vaccinations resulted in a breakdown of the S.B.’s BBB.
NMDA receptor antibodies, also created as a result of the vaccine-induced immune response, were
then able to enter S.B.’s brain and attach to the NMDA receptors, thus leading to anti-NMDAR
encephalitis.

        Petitioners fail on prong one because they have not articulated a theory by which the HAV
and flu vaccines create the specific antibody necessary for anti-NMDAR encephalitis to occur. In
their pre-hearing brief, Petitioners cite the Venkatesan and Benavides32 article to explain
mechanisms by which “infection can lead to [the] breaking of the CNS immune tolerance[.]”
Pet’rs’ Pre-Hr’g Br. at 33, ECF No. 70 (quoting Pet’rs’ Ex. 26, Tab B, at 2). Petitioners then list
the following mechanisms: “molecular mimicry, change in antigen expression, alternative
splicing, posttranslational modification, covalent modification, enzymatic processing, protein
misfolding, unmasking of cryptic neural epitopes, dysregulation of immune regulators, bystander
activation, and ‘epitope spreading’ in the infectious microenvironment.” Id. (quoting Pet’rs’ Ex.
26, Tab B, at 2). Ultimately, Dr. Engel testified that he did not have an opinion on whether
molecular mimicry has any role in his causation theory because “it would be speculation.” Tr. at
38.

        The Vaccine Act, pursuant to the preponderance standard, does not require identification
and proof of specific biological mechanisms. Althen, 418 F.3d at 1280 (quoting Knudsen, 35 F.3d
at 549). In fact, the very nature of the program anticipates that vaccine injury is a “field bereft of
complete and direct proof of how vaccines affect the human body.” Id. Although Petitioners are
correct that they do not need to provide the specific components of the mechanism by which the
vaccines at issue can cause anti-NMDAR encephalitis, they do need to propose something more
than taking a vague “kitchen sink” approach and listing eleven mechanisms that have been
previously submitted in the Program for claims of vaccine-caused injury with various degrees of
success. Petitioners have listed many possibilities but have not identified a sound and reliable
explanation that can be applied to the vaccines and injury in this case.

        Both experts agreed that anti-NMDAR encephalitis requires a very specific antibody to
manifest. Dr. Engel was unable, both in his reports and his testimony, to link either the HAV or
the flu vaccine—or a combination of both—to this antibody. As Dr. Lancaster explained, “[a]nti-
NMDAR encephalitis involves an extremely specific antibody response against a specific three-
dimensional epitope on the NMDAR. . . . These antibodies are the core element of the disease[.]”
Resp’t’s Ex. BB at 7. Dr. Lancaster further explained that “[d]enatured viral proteins in a vaccine
have no structural relationship to the NMDAR, and it would be very unlikely for these proteins to
32
     Venkatesan & Benavides, supra note 18.


                                                 20
induce the specific antibody response to the NMDAR that is necessary for anti-NMDAR
encephalitis.” Id. By comparison, Dr. Lancaster testified that ovarian teratomas “ha[ve] the fully
intact NMDA receptor on it. So . . . that makes a very good stimulus for developing the antibody.”
Tr. at 85. He also hypothesized that in HSV encephalitis patients, the “natural receptors in the
temporal lobe [are] . . . expressed in the setting of an overwhelming viral infection that stimulates
the immune system incredibly strongly. . . . And in that setting, there can be a loss of self-tolerance.
[A patient] can be exposed to an NMDA receptor and perhaps generate these pathogenic antibodies
to it.” Id. at 85. Dr. Engel provided no persuasive evidence that the HAV and flu vaccines can
stimulate the production of the necessary antibodies.

         The only medical literature provided by Dr. Engel to support the proposition that vaccines
can cause anti-NMDAR encephalitis is in the form of case reports. One such report, by Hofmann
et al.,33 discusses a patient who developed anti-NMDAR encephalitis one day after receiving the
TDaP and IPV vaccines. Petitioners are correct that the authors of the report conclude that “[t]he
onset of prodromal symptoms shortly after the immunization . . . suggests the vaccination as a
possible trigger of [anti-NMDAR encephalitis].” Pet’rs’ Ex. 26, Tab C, at 1. However, this case
report lacks in-depth analysis of the patient’s specific medical history and the authors do not go
further than a suggestion of possible causality. It does not provide sufficient support for a
conclusion that the vaccines did in fact cause this patient to develop anti-NMDAR encephalitis.

         Another case report that Dr. Engel discussed in his report and his testimony is the article
by Dalmau et al. Dr. Lancaster is a named co-author of this study. Dr. Engel noted in his testimony
that “Dr. Lancaster was involved with Dr. Dalmau in describing two patients who developed [anti-
NMDAR encephalitis] after vaccination against H1N1.” Tr. at 19. However, as Dr. Lancaster
explained during his testimony, he included these patients in this study “in case subsequently other
cases . . . [showed that vaccinations] actually conveyed a risk of anti-NMDA[R] encephalitis.” Tr.
at 72. This report is not persuasive evidence for Petitioners for two reasons. First, the authors do
not state a belief that vaccines can cause anti-NMDAR encephalitis. In fact, Dr. Lancaster testified
that “[w]e have not been seeing associations with the vaccines.” Tr. at 72. As he is a credited co-
author of this report, Dr. Lancaster’s statements regarding this article are most pertinent. His
statements that he and Dr. Dalmau included these cases only “in case subsequently other cases . .
. [showed that vaccinations] actually conveyed a risk of anti-NMDA[R] encephalitis,” weaken any
purported link between the vaccines and the disease. Second, the article notes that the information
regarding the vaccination of these patients was obtained by “personal observation.”

        Finally, Dr. Engel argued that S.B.’s case report was particularly probative evidence.34 The
authors of the paper wrote that S.B. “was a previously healthy, developmentally normal 21-month-
old girl.” Pet’rs’ Ex. 26, Tab H, at 2. As Dr. Lancaster discussed in his report, this statement
demonstrates that “the authors were either unaware of the infectious illnesses preceding the onset
of anti-NMDAR encephalitis or chose not to include this information in their case report.” Resp’t’s
Ex. BB at 11. The authors’ decision, whether knowing or not, to omit this key information renders
this case report less persuasive.



33
     Hofmann et al., supra note 24.
34
     Goldberg et al., supra note 12.


                                                  21
        While the Vaccine Act allows for circumstantial evidence to demonstrate causality, see
Althen, 418 F.3d 1280, case reports documenting only four cases of anti-NMDAR encephalitis
following vaccination is not enough to meet Petitioners’ burden. These case reports, while
submitted to indicate a possible association between vaccinations generally and anti-NMDAR
encephalitis are not, in and of themselves, enough to demonstrate causality. Dr. Lancaster’s own
stated belief that these cases are more than likely “coincidence” is more persuasive than Dr.
Engel’s interpretation of Dr. Lancaster’s research. Resp’t’s Ex. BB at 7.

        During his testimony and in his reports, Dr. Engel discussed pro-inflammatory cytokines
and the breakdown of the BBB at length. He testified that while the BBB “normally prevents
antibodies from entering the nervous system in sufficient concentrations to cause disease[,]”
certain “inflammatory reactions” or “trauma” can make the BBB more permeable and allow in
antibodies that can cause disease. Pet’rs’ Ex. 28 at 2. However, he could not describe the
mechanism by which the inflammatory cytokines break down the BBB. Rather, he stated that
“[w]ell, we don’t really know the mechanism and so . . . we’re really not sure of the mechanism
so we really can’t explain it.” Tr. at 43.

        Dr. Lancaster’s testimony on this subject, on the other hand, was highly persuasive. He
noted that Dr. Engel “d[id] not provide any citations that the relevant vaccines can actually cause
production of these cytokines in sufficient levels to actually change [BBB] permeability.” Resp’t’s
Ex. BB at 8. More importantly, Dr. Lancaster stated that the BBB issue was a red herring because,
even if pro-inflammatory cytokines break down the BBB as Dr. Engel proposed, “there still has to
be that specific NMDA antibody or [you] don’t get [anti-NMDAR encephalitis].” Tr. at 116. Dr.
Lancaster also testified that in many anti-NMDAR patients, “[t]he [BBB] is not broken down” and
the “brain MRI is normal.” Id. at 76. In fact, Dr. Lancaster stated that he only discussed the BBB
in his report and during his testimony because it “was proposed as a mechanism by [Dr. Engel]
and [he] felt compelled to respon[d] . . . and say [that he doesn’t] think [it] is a very good
mechanism.” Id. at 141–42.

       Petitioners have not presented “a medical theory causally connecting the [HAV and flu]
vaccinations and [anti-NMDAR encephalitis].” Althen, 418 F.3d at 1278. Therefore, Petitioners
have not met their burden under Althen prong one.

           C. Althen Prong Two

       Neither party disputes that S.B. developed anti-NMDAR encephalitis after she received the
HAV and flu vaccinations. However, that chronology of events alone is not sufficient under the
preponderant standard. Both experts agreed that there are two definitive causes of anti-NMDAR
encephalitis: ovarian teratoma and HSV encephalitis, neither of which was present in S.B.’s case.
Both experts also agree that prior infections have been linked in medical literature to anti-NMDAR
encephalitis in some fashion. They disagree, however, on whether vaccines can cause this disease.

       Dr. Engel provided no evidence that the vaccines at issue created the type of antibody
required for anti-NMDAR encephalitis. Dr. Engel did not explain what, aside from “timing” of
the onset, led him to conclude that the vaccinations caused S.B. to develop anti-NMDAR
encephalitis. Dr. Lancaster, on the other hand, testified that “none of the cytokines or cell signaling



                                                  22
molecules directly interact with the receptor. None of them are really a sufficient cause for
someone to develop [anti-NMDAR encephalitis].” Tr. at 82. He also explained that the vaccines
“are denatured viral proteins that have no structural relationship to the NMDA receptor at all and
they’re . . . broken apart, they don’t have that three-dimensional structure.” Id. at 84. Therefore,
the viral proteins in the vaccine are incapable of attaching to the receptor and cannot cause this
disease.

         Dr. Engel’s theory requires a breakdown of the BBB by pro-inflammatory cytokines.
However, Dr. Engel was unable to provide any evidence that S.B.’s BBB actually broke down,
and S.B.’s levels of pro-inflammatory cytokines were never measured. Furthermore, Dr. Lancaster
testified that S.B. did not exhibit the “sort of infectious or parainfectious symptoms” that result
from an increase in pro-inflammatory cytokines and a BBB breakdown. Tr. at 81. In fact, S.B.’s
brain MRI was normal. Without any evidence of a breakdown in S.B.’s BBB, Dr. Engel’s theory
cannot be applied to S.B.’s case.

        In sum, Dr. Engel failed to demonstrate “a logical sequence of cause and effect showing
that the vaccination was the reason for the inquiry.” Althen, 418 F.3d at 1278. He did not provide
evidence that the vaccines S.B. received can create the type of antibody necessary to cause anti-
NMDAR encephalitis, nor that S.B.’s BBB was compromised or had increased permeability. For
those reasons, Petitioners have failed at prong two.

            D. Althen Prong Three

       Dr. Engel’s proposed timeframe for disease onset was five to forty-two days post-
vaccination. Pet’rs’ Ex. 26 at 7. He proposed this time frame because it is the timeframe listed by
the IOM for post-vaccination development of ADEM and GBS.35 Dr. Lancaster proposed a nine
to seventy-four day latency period. Resp’t’s Ex. BB at 8. He explained that he chose this time
frame because it is the time frame for confirmed post-HSV encephalitis triggered anti-NMDAR
encephalitis. Tr. at 69.

        The undersigned does not need to make a determination regarding which proposed time
frame is correct. S.B. received the HAV and flu vaccines on November 11, 2011. Both experts
agree that onset occurred sometime before December 23, 2011, the date when S.B. presented to
Dr. Rosenn.36 This onset period falls squarely within the ranges provided by both Dr. Engel and
Dr. Lancaster. Although Petitioners have failed to meet Althen prongs one and two, Petitioners
have presented preponderant evidence that S.B. developed anti-NMDAR encephalitis within an
appropriate time frame. Therefore, the undersigned finds that Petitioners have met their burden
under Althen prong three.

     VI.    Conclusion



35
  Vaccine Safety Committee, supra note 28.
36
  Dr. Engel stated “[S.B.’s] initial symptoms were approximately five weeks after her vaccinations.”
Pet’rs Ex. 26 at 7. Dr. Lancaster places S.B.’s onset “most likely between [December 7, 2011] and
[December 21, 2011].” Resp’t’s Ex. BB at 8.


                                                   23
       Anti-NMDAR encephalitis is a rare and vicious disease that most people are not even
aware of. Compounding the frustration of dealing with such a condition is the lack of information
that medical professionals have to explain what is happening. Despite those difficulties, it is
heartening to hear that S.B. is now doing well.

        Irrespective of the diagnostic outcome for any individual petitioner, a decision on
entitlement to compensation in the Vaccine Program cannot be made based on the nature and
severity of the disease alone. It must reflect a thorough analysis of the evidence and a thoughtful
balance against the applicable legal standards based upon probative weight and persuasiveness.
Petitioners have not established that S.B.’s HAV and flu vaccines caused her to develop anti-
NMDAR encephalitis. Therefore, the undersigned must DENY entitlement in this case.

       In the absence of a timely filed motion for review filed pursuant to Vaccine Rule 23, the
Clerk of the Court is directed to ENTER JUDGMENT consistent with this decision.37


        IT IS SO ORDERED.

                                                          s/Herbrina D. Sanders
                                                          Herbrina D. Sanders
                                                          Special Master




37
  Pursuant to Vaccine Rule 11(a), entry of judgment is expedited by the parties’ joint filing of a notice
renouncing the right to seek review.


                                                     24
