VICP Registry Case Source Bundle
Canonical URL: https://vicp-registry.org/case/USCOURTS-cofc-1_17-vv-01109
Package ID: USCOURTS-cofc-1_17-vv-01109
Petitioner: E.M.
Filed: 2017-08-16
Decided: 2025-03-05
Vaccine: HPV/Gardasil; influenza
Vaccination date: 2015-07-20
Condition: optic neuritis and Rasmussen's encephalitis with seizures and severe neurologic sequelae
Outcome: entitlement_granted_pending_damages
Award amount USD: 

AI-assisted case summary:
On August 16, 2017, Leah and Jeremy Marsh filed a petition under the National Childhood Vaccine Injury Act on behalf of their minor daughter, E.M. They alleged that the Human Papillomavirus (HPV) vaccine administered on July 20, 2015, caused optic neuritis and Rasmussen's encephalitis. They later amended the petition to include the allegation that E.M.'s influenza (flu) vaccine, received on November 10, 2015, also contributed to the Rasmussen's encephalitis. The respondent opposed entitlement. Special Master Daniel T. Horner found that the HPV vaccine caused E.M.'s optic neuritis and that this vaccine-induced optic neuritis was a substantial contributing factor in the development of her Rasmussen's encephalitis.

E.M., born May 1, 2003, had no significant medical issues before 2015. She received her first HPV vaccine on February 17, 2015, and her second on July 20, 2015. By mid-August 2015, approximately one month after her second HPV vaccine, E.M. began experiencing visual disturbances. An optometrist noted papilledema, and an ophthalmologist diagnosed optic nerve edema. A neuro-ophthalmologist observed left-sided optic neuritis with atypical disk swelling and suggested a possible demyelinating disorder. An MRI showed an enlarged left optic nerve with increased T2 signal and scattered white-matter foci. E.M. was treated with IV Solu-Medrol and underwent a lumbar puncture, which revealed elevated white blood cells and a single oligoclonal band, consistent with a systemic immune reaction.

E.M. reported improvement in her vision by November 10, 2015, though she still experienced intermittent headaches. On that date, she received her seasonal flu vaccine. Dr. Lloyd continued to diagnose left-sided optic neuritis and planned monitoring. On December 9, 2015, E.M. experienced her first seizure. Conflicting reports existed regarding any preceding illness, but an EEG showed left-hemisphere abnormalities consistent with an acute left-hemisphere process. HSV testing was negative in the cerebrospinal fluid (CSF).

E.M.'s condition rapidly escalated. A subsequent MRI showed persistent white-matter abnormalities and a new lesion in the left periatrial region. She developed right-hand numbness and language deficits. Neurologists suspected autoimmune encephalitis. E.M. experienced further seizures and was admitted to the hospital with frequent seizures, fever, and increasing neurologic deficits. She received extensive treatments, including anticonvulsants, steroids, plasmapheresis, and IVIG. Imaging showed progressive left-hemisphere abnormalities. A left frontal lobe biopsy revealed chronic active encephalitis, most consistent with a T-cell mediated immune-mediated or infectious encephalitis. Later MRI evidence of left-hemisphere volume loss supported a diagnosis of Rasmussen's encephalitis.

Petitioners' expert, neuroimmunologist Dr. Lawrence Steinman, proposed a "two-hit" model, suggesting the HPV vaccine caused optic neuritis and associated left-sided brain pathology, which then predisposed E.M. to Rasmussen's encephalitis, potentially with the flu vaccine acting as a second hit. Respondent's experts, Dr. Christine McCusker and Dr. Jenny Linnoila, disputed the vaccine connection, arguing that optic neuritis and Rasmussen's encephalitis were distinct and that E.M.'s condition was likely triggered by an infection like HSV.

Special Master Horner found that E.M.'s optic neuritis began within a medically acceptable interval after the HPV vaccine and met the Althen prongs for vaccine causation. He further concluded that the vaccine-induced optic neuritis, including left-sided brain pathology, was a but-for cause and substantial contributing factor to E.M.'s Rasmussen's encephalitis. The Special Master found that respondent did not prove that HSV or any other factor unrelated to vaccination was the sole cause. Entitlement was granted, with damages to be determined in a separate proceeding.

Theory of causation field:
Second HPV/Gardasil vaccine on July 20, 2015, age about 12.2, followed about one month later by optic neuritis; later influenza vaccine on November 10, 2015, alleged as part of a two-hit pathway to Rasmussen's encephalitis, seizures, and severe neurologic sequelae. ENTITLEMENT GRANTED; damages pending in staged public text. Petitioners Leah and Jeremy Marsh relied on Dr. Lawrence Steinman. Respondent's experts Dr. Christine McCusker and Dr. Jenny Linnoila disputed vaccine causation and suggested infection such as HSV. Special Master Horner found the HPV vaccine caused optic neuritis and that the vaccine-induced optic neuritis substantially contributed to Rasmussen's encephalitis.

Public staged source text:

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DOCUMENT 1: USCOURTS-cofc-1_17-vv-01109-0
Date issued/filed: 2025-04-04
Pages: 62
Docket text: PUBLIC ORDER/RULING (Originally filed: 3/5/2025) regarding 130 Ruling on Entitlement. Signed by Special Master Daniel T. Horner. (ksb) Service on parties made.
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Case 1:17-vv-01109-UNJ Document 132 Filed 04/04/25 Page 1 of 62
In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 17-1109V
Filed: March 5, 2025
Special Master Horner
LEAH MARSH, as mother and natural
guardian of E.M., and JEREMY
MARSH, as father and natural
guardian of E.M.,
Petitioner,
v.
SECRETARY OF HEALTH AND
HUMAN SERVICES,
Respondent.
Jeffrey S. Pop, Jeffrey S. Pop & Associates, Beverly Hills, CA, for petitioner.
Neil Bhargava, U.S. Department of Justice, Washington, DC, for respondent.
RULING ON ENTITLEMENT1
On August 16, 2017, petitioners filed a petition on behalf of their minor child,
E.M., under the National Childhood Vaccine Injury Act, 42 U.S.C. § 300aa-10, et seq.
(2012).2 (ECF No. 1.) Petitioners allege that the Human Papillomavirus (“HPV”)
vaccine E.M. received on July 20, 2015, caused her to suffer optic neuritis, as well as a
particular form of encephalitis known as Rasmussen’s encephalitis. (Id. at 1.) They
further allege that her November 10, 2015 influenza (“flu”) vaccination additionally
contributed to the development of her Rasmussen’s encephalitis. (ECF No. 59, pp. 1,
15.) For the reasons set forth below, I conclude that petitioners are entitled to
compensation for E.M.’s injuries.
1 Because this document contains a reasoned explanation for the action taken in this case, it must be
made publicly accessible and will be posted on the United States Court of Federal Claims' website, and/or
at https://www.govinfo.gov/app/collection/uscourts/national/cofc, in accordance with the E-Government
Act of 2002. 44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of Electronic
Government Services). This means the document will be available to anyone with access to the
internet. In accordance with Vaccine Rule 18(b), Petitioner has 14 days to identify and move to redact
medical or other information, the disclosure of which would constitute an unwarranted invasion of privacy.
If, upon review, I agree that the identified material fits within this definition, I will redact such material from
public access.
2 Within this decision, all citation to § 300aa will be the relevant sections of the Vaccine Act at 42 U.S.C.
§ 300aa-10-34.
1

Case 1:17-vv-01109-UNJ Document 132 Filed 04/04/25 Page 2 of 62
I. Applicable Statutory Scheme
Under the National Vaccine Injury Compensation Program, compensation
awards are made to individuals who have suffered injuries after receiving vaccines. In
general, to gain an award, a petitioner must make a number of factual demonstrations,
including showing that an individual received a vaccination covered by the statute;
received it in the United States; suffered a serious, long-standing injury; and has
received no previous award or settlement on account of the injury. Finally – and the key
question in most cases under the Program – the petitioner must also establish a causal
link between the vaccination and the injury.
In some cases, the petitioner may simply demonstrate the occurrence of what
has been called a “Table Injury.” That is, it may be shown that the vaccine recipient
suffered an injury of the type enumerated in the “Vaccine Injury Table,” corresponding to
the vaccination in question, within an applicable time period following the vaccination
also specified in the Table. If so, the Table Injury is presumed to have been caused by
the vaccination unless it is affirmatively shown that the injury was caused by some
factor other than the vaccination. § 300aa-13(a)(1)(A); § 300aa-11(c)(1)(C)(i);
§ 300aa-14(a); § 300aa-13(a)(1)(B). In many cases, however, the vaccine recipient
may have suffered an injury not of the type covered in the Vaccine Injury Table. In such
instances, an alternative means exists to demonstrate entitlement to a Program award.
That is, the petitioner may gain an award by showing that the recipient’s injury was
“caused-in-fact” by the vaccination in question. § 300aa-13(a)(1)(B);
§ 300aa-11(c)(1)(C)(ii). In that context, the presumptions available under the Vaccine
Injury Table are inoperative. The burden is on the petitioner to introduce evidence
demonstrating that the vaccination actually caused the injury in question. Althen v.
Sec’y of Health & Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005); Hines ex rel.
Sevier v. Sec’y of Health & Human Servs., 940 F.2d 1518, 1525 (Fed. Cir. 1991).
In this case, petitioners allege that E.M.’s vaccinations caused her optic neuritis
and Rasmussen’s encephalitis. Because these injuries are not Table Injuries,
petitioners must establish causation-in-fact.3
The showing of “causation-in-fact” must satisfy the “preponderance of the
evidence” standard, the same standard ordinarily used in tort litigation.
§ 300aa-13(a)(1)(A); see also Althen, 418 F.3d at 1279; Hines, 940 F.2d at 1525.
Under that standard, the petitioner must show that it is “more probable than not” that the
vaccination was the cause of the injury. Althen, 418 F.3d at 1279. The petitioner need
not show that the vaccination was the sole cause but must demonstrate that the
vaccination was at least a “substantial factor” in causing the condition, and was a “but
for” cause. Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352 (Fed. Cir.
1999). Thus, the petitioner must supply “proof of a logical sequence of cause and effect
showing that the vaccination was the reason for the injury[,]” with the logical sequence
3 Encephalitis is a Table Injury relative to some vaccinations, but not either of the vaccinations at issue in
this case. 42 C.F.R. § 100.3(a) (as effective March 21, 2017 to January 2, 2022).
2

Case 1:17-vv-01109-UNJ Document 132 Filed 04/04/25 Page 3 of 62
being supported by “reputable medical or scientific explanation.” Althen, 418 F.3d at
1278; Grant v. Sec’y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992).
Ultimately, petitioner must satisfy what has come to be known as the Althen test, which
requires: (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 proximate temporal relationship between vaccination
and injury.4 Id.
A petitioner may not receive a Vaccine Program award based solely on his or her
assertions, but may support the petition with either medical records or by the opinion of
a competent physician. § 300aa-13(a)(1). 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). 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.
§ 300aa-13(b)(1). A petitioner may also rely upon circumstantial evidence. Althen, 418
F.3d at 1280. In that regard, the Althen court noted that a petitioner need not
necessarily supply evidence from medical literature supporting petitioner’s causation
contention, so long as the petitioner supplies the medical opinion of an expert. Id. at
1279-80. While scientific certainty is not required, that expert’s opinion must be based
on “sound and reliable” medical or scientific explanation. Boatmon v. Sec’y of Health &
Human Servs., 941 F.3d 1351, 1359 (Fed. Cir. 2019).
Cases in the Vaccine Program are assigned to special masters who are
responsible for “conducting all proceedings, including taking such evidence as may be
appropriate, making the requisite findings of fact and conclusions of law, preparing a
decision, and determining the amount of compensation, if any, to be awarded.” Vaccine
Rule 3. Special masters must ensure each party has had a “full and fair opportunity” to
develop the record but are empowered to determine the format for taking evidence
based on the circumstances of each case. Vaccine Rule 3(b)(2); Vaccine Rule 8(a);
Vaccine Rule (d). Special masters are not bound by common law or statutory rules of
evidence but must consider all relevant and reliable evidence in keeping with
fundamental fairness to both parties. Vaccine Rule 8(b)(1). 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
4 Additionally, petitioners allege that E.M.’s later flu vaccine significantly aggravated her pre-existing
condition. However, for the reasons discussed below, it is not necessary to reach that question. Where a
petitioner in an off-Table case is seeking to prove that a vaccination aggravated a preexisting injury, the
petitioner must establish the three Althen prongs along with three additional factors described in the prior
Loving case. See Loving ex rel. Loving v. Sec’y of Health & Human Servs., 86 Fed. Cl. 135, 144 (2009)
(combining the first three Whitecotton factors for claims regarding aggravation of a Table injury with the
three Althen factors for off table injury claims to create a six-part test for off-Table aggravation claims);
see also W.C. v. Sec’y of Health & Human Servs., 704 F.3d 1352, 1357 (Fed. Cir. 2013) (applying the six-
part Loving test). The additional Loving factors require petitioners to demonstrate aggravation by
showing: (1) the vaccinee’s condition prior to the administration of the vaccine, (2) the vaccinee’s current
condition, and (3) whether the vaccinee’s current condition constitutes a “significant aggravation” of the
condition prior to the vaccination. Loving, 86 Fed. Cl. at 144.
3

Case 1:17-vv-01109-UNJ Document 132 Filed 04/04/25 Page 4 of 62
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.” § 300aa-13(b)(1)(A). The special master is required to consider the
entirety of record, draw plausible inferences, and articulate a rational basis for the
decision. Winkler v. Sec’y of Health & Human Servs., 88 F.4th 958, 963 (Fed. Cir.
2023) (citing Hines, 940 F.2d at 1528).
II. Procedural History
Petitioners filed their petition on August 16, 2017, alleging that the HPV vaccine
E.M. received on July 20, 2015, caused her to develop both optic neuritis and an
autoimmune encephalitis consistent with Rasmussen’s encephalitis, and filed medical
records to support their claim. (ECF Nos. 1, 7, 10, 15; Exs. 1-22.) Respondent filed his
Rule 4(c) report, recommending against compensation, in March of 2018. (ECF No.
16.) Petitioners then filed an expert report with supporting medical literature from
neuroimmunologist Dr. Lawrence Steinman. (ECF Nos. 21-24; Exs. 23-58.)
Respondent filed responsive expert reports with supporting medical literature from Drs.
Christine McCusker (immunology) and Jenny Linnoila (neurology). (ECF Nos. 29-31;
Exs. A-C.) The case was then reassigned to the undersigned’s docket in June of 2019.
(ECF No. 32.)
Petitioners filed a supplemental report and supporting medical literature from Dr.
Steinman in November of 2019, and respondent filed additional reports by Drs.
McCusker and Linnoila in February of 2020. (ECF Nos. 36, 38-40; Exs. 59-62; Exs. E-
F.) Thereafter, petitioners filed updated medical records (ECF No. 43; Ex. 63) and
advised that no additional expert reports were needed (ECF No. 41). Therefore, a two-
day entitlement hearing was set to commence on March 3, 2022. (ECF No. 44.)
However, the hearing was cancelled in February 2022 when petitioners requested an
opportunity to pursue the additional theory that E.M.’s subsequent flu vaccine also
played a role in the development of her Rasmussen’s encephalitis. (ECF No. 48.) The
two-day entitlement hearing was rescheduled to commence on December 12, 2022.
(ECF No. 51.)
In April of 2022, petitioners filed additional medical records, an expert report from
radiologist Dr. Jeffrey Silverman, and a supplemental report from Dr. Steinman. (ECF
Nos. 52-54; Exs. 64-88.) Petitioners then filed an amended petition on July 6, 2022,
alleging that the HPV vaccination E.M. received on July 20, 2015, caused her to suffer
injuries including both optic neuritis and Rasmussen’s encephalitis and that her
November 10, 2015 flu vaccine, either alone or in conjunction with the prior HPV
vaccine, caused Rasmussen’s encephalitis. (ECF No. 59, p. 15.) Respondent filed
supplemental reports by his experts in August of 2022. (ECF Nos. 61-62; Exs. G-H.)
On September 26, 2022, the parties confirmed that the case was ripe for the entitlement
hearing. (ECF No. 63.)
4

Case 1:17-vv-01109-UNJ Document 132 Filed 04/04/25 Page 5 of 62
The entitlement hearing commenced on December 12-13, 2022; however, it
failed to conclude within the allotted time. (ECF No. 97; see Transcript of Proceedings
(“Tr.”), at ECF Nos. 102-03.) The hearing continued on March 28, 2023, and April 17,
2023. (ECF Nos. 100, 105, 108; see Transcript of Proceedings (“Tr.”), at ECF No. 114;
Transcript of Proceedings (“Tr.”), at ECF No. 118.) Following the hearing, both parties
filed motions for leave to file additional evidence. (ECF Nos. 120-23.) Both motions
were granted in part and denied in part. (ECF No. 124.) However, the parties
subsequently advised in a joint status report that they did not intend to file additional
evidence and that they agreed the record was closed. (ECF No. 125.)
Petitioners filed their post-hearing brief on September 15, 2023; respondent filed
his responsive post hearing brief on October 16, 2023; and petitioners filed their reply
on November 16, 2023. This case is now ripe for a ruling on entitlement.
III. Medical Conditions Discussed Throughout This Ruling
Demyelination: Demyelination is the loss or destruction of the myelin sheath that covers
the axons of the nerves. Demyelination is a manifestation of several conditions that are
believed to result from autoinflammatory attacks on the myelin. For example, Guillain-
Barre syndrome (“GBS”) is a syndrome of ascending polyneuropathy with multiple
variants that is believed to be autoimmune. In one form known as Acute Inflammatory
Demyelinating Polyneuropathy (“AIDP”), it results in demyelination of the peripheral
nerves. Several other conditions, such as optic neuritis and ADEM, as discussed
below, cause various patterns of demyelination within the central nervous system.5
Optic Neuritis: Optic neuritis is inflammation of the optic nerve. This can be intraocular,
affecting the optic disk, or retrobulbar, affecting the portion of the optic nerve behind the
eyeball. Optic neuritis can occur in several contexts; however, acute optic neuritis is
generally associated with vision loss due to demyelination. Optic neuritis may occur as
an isolated, monosymptomatic event, or it may occur as part of a broader primary
demyelinating condition affecting the central nervous system, such as neuromyelitis
optica (“NMO”), multiple sclerosis (“MS”), or ADEM. Optic neuritis is rarer in children
than in adults. Pediatric optic neuritis affects 0.2 per 100,000 children.6
5 Demyelination, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=13092 (last visited Jan. 7, 2025); Demyelination,
STEDMAN’S MEDICAL DICTIONARY (28th ed. 2006); Guillain-Barré Syndrome, DORLAND’S MEDICAL
DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=110689 (last visited Jan. 7,
2025); Acute inflammatory demyelinating polyradiculoneuropathy, DORLAND’S MEDICAL DICTIONARY
ONLINE, https://www.dorlandsonline.com/dorland/definition?id=99421 (last visited Jan. 7, 2025);
Polyradiculoneuropathy, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=40276 (last visited Jan. 7, 2025); Melinda Y. Chang
& Stacy L. Pineles, Pediatric Optic Neuritis, 24 SEMINARS PEDIATRIC NEUROLOGY 122 (2017) (Ex. C, Tab 8,
pp. 2-3).
6 Optic neuritis, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=92519 (last visited Jan. 7, 2025); Discus nervi
optici, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=70033 (last visited Jan. 7, 2025); Roger Baxter et
5

Case 1:17-vv-01109-UNJ Document 132 Filed 04/04/25 Page 6 of 62
ADEM: One of the conditions that may include optic neuritis is “ADEM” or acute
disseminated encephalomyelitis. ADEM is an acute syndrome that includes an
encephalopathy (i.e., degeneration of the brain) and multifocal demyelinating lesions
disseminated throughout the brain. ADEM can have a similar presentation to multiple
sclerosis, but is distinguished by being a monophasic condition. ADEM can also
resemble autoimmune encephalitis clinically.7
Encephalitis: Encephalitis is a debilitating form of progressive encephalopathy that
results specifically from inflammation. Typically, it presents clinically with progressive
disorientation, confusion, and other cognitive changes. A specific etiology is often
unknown. Infection accounts for about half of all identifiable causes of encephalitis.8
Autoimmune Encephalitis: Historically, diagnostic criteria for encephalitis assumed an
infectious origin. However, beginning in the 2000’s, “autoimmune encephalitis” has
increasingly been recognized as a category of encephalitides that resemble infectious
encephalitis while being non-infectious. Autoimmune encephalitis is a form of immune-
mediated disorder and may be idiopathic or paraneoplastic. It represents a “spectrum”
of conditions with differing pathophysiology. It can be associated with a number of
different, novel neural autoantibodies. However, the absence of autoantibodies does
not preclude an immune-mediated encephalitis.9
Rasmussen’s Encephalitis: Rasmussen’s encephalitis is a syndrome “at the frontier of
autoimmune encephalitis.” It is a chronic inflammatory disease characterized by
intractable focal onset seizures, deterioration of neurologic function, and a characteristic
progressive atrophy of one side of the brain. The pathogenesis of Rasmussen’s
encephalitis is not definitively established, but the prevailing understanding is that it
involves a cytotoxic T-cell autoimmune response. The extent to which Rasmussen’s
encephalitis is distinct from “autoimmune encephalitis” and the question of whether it
involves an autoantibody response in addition to being T-cell mediated are points of
al., Case-Centered Analysis of Optic Neuritis After Vaccines, 63 CLINICAL INFECTIOUS DISEASES 79 (2016)
(Ex. A, Tab 1, p. 1); Raed Behbehani, Clinical Approach to Optic Neuropathies, 1 CLINICAL
OPHTHALMOLOGY 233 (2007) (Ex. C, Tab 1, pp. 1, 4-5); L.A. Rolak et al., Cerebrospinal Fluid in Acute
Optic Neuritis: Experience of the Optic Neuritis Treatment Trial, 46 NEUROLOGY 368 (1996) (Ex. C, Tab 2,
p. 1); Chang & Pineles, supra, at Ex. C, Tab 8, p. 1.
7 Acute disseminated encephalomyelitis, Dorland’s Medical Dictionary Online,
https://www.dorlandsonline.com/dorland/definition?id=73033 (last visited Jan. 7, 2025); Encephalopathy,
DORLAND’S MEDICAL DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=16202
(last visited Jan. 7, 2025); Chang & Pineles, supra, at Ex. C, Tab 8, pp. 2-3; Francesc Graus et al., A
Clinical Approach to Diagnosis of Autoimmune Encephalitis, 15 LANCET NEUROLOGY 391 (2016) (Ex. 153,
p. 4).
8 Encephalitis, Dorland’s Medical Dictionary Online,
https://www.dorlandsonline.com/dorland/definition?id=16168 (last visited Jan. 7, 2025); Graus et al.,
supra, at Ex. 153, p. 3; Michael J. Bradshaw & Jenny J. Linnoila, An Overview of Autoimmune and
Paraneoplastic Encephalitides, 38 Seminars Neurology 330 (2018) (Ex. C, Tab 5, p. 4).
9 Graus et al., supra, at Ex. 153, p. 3; Bradshaw & Linnoila, supra, at Ex. C, Tab 5, pp. 1, 11.
6

Case 1:17-vv-01109-UNJ Document 132 Filed 04/04/25 Page 7 of 62
disagreement in this case. Rasmussen’s encephalitis presents primarily in children and
is extremely rare, affecting 1-2 per 10,000,000 people.10
IV. Factual History
a. Medical Records
E.M. was born on May 1, 2003, and had no significant medical issues prior to
onset of her optic neuritis and seizure disorder in 2015. (See Ex. 3, p. 1.) She received
her first HPV vaccination on February 17, 2015. (Ex. 4, pp. 8-10.) She had a basic eye
exam on May 9, 2015, with unremarkable findings. (Ex. 5, p. 2.) E.M. received her
second HPV vaccination, one of the vaccinations at issue, on July 20, 2015. (Ex. 2; Ex.
4, pp. 6-7.)
Nearly two months after her second HPV vaccination, E.M. was seen by
optometrist Dr. Shawn Beagley on September 15, 2015, for complaints of one month of
seeing spots with blurred vision. (Ex. 5, p. 3.) Dr. Beagley assessed E.M. with a
papilledema11 and referred her to ophthalmology. (Id.) E.M. then saw ophthalmologist
Dr. William Barlow on September 17, 2015. (Ex. 6, p. 1.) Dr. Barlow assessed E.M.
with optic nerve edema, noting that the etiology was unclear, and referred E.M. to
neuro-ophthalmology. (Id.)
E.M. visited neurologic ophthalmologist Dr. Kathleen Digre on September 24,
2015. (Ex. 6, p. 5.) Dr. Digre recorded a medical history of dark spots and tunnel vision
since July, originally occurring in both eyes but progressing to only her left eye. (Id.)
E.M. reported that her vision problems initially occurred almost daily and primarily in the
morning; however, her symptoms progressed to affecting her during the day. (Id.) E.M.
also reported some pain with eye movements, but no headaches or light flashes. (Id.)
The ocular exam noted a “4+ swelling” in the disk of E.M.’s left eye. (Id. at 7-8.) Dr.
Digre’s impression was that E.M. had a swollen optic nerve on the left with an optic
neuropathy, noting that “[t]his could be papilledema from raised intracranial pressure or
an optic neuritis.” (Id. at 9.) Dr. Digre recommended E.M. receive a head/brain MRI,
lumbar puncture, CBC and chemical labs, and, if necessary, follow up with pediatric
neurology. (Id.) E.M. received orbital face/neck and brain MRIs on September 25,
2015. (Ex. 7, pp. 158-60; Ex. 8, pp. 740-43.) The results of E.M.’s orbital face/neck
MRI showed an “abnormally enlarged” left optic nerve “with mild protrusion of the optic
nerve head and increased T2 signal intensity.” (Ex. 8, p. 740.) E.M.’s brain MRI
10 Graus et al., supra, at Ex. 153, p. 31; Lawrence Steinman, Blocking Immune Intrusion into the Brain
Suppresses Epilepsy in Rasmussen’s Encephalitis Model, 128 J. CLINICAL INVESTIGATION 1724 (2018) (Ex.
31, p. 1).
11 Papilledema is edema, or the presence of an abnormally large amount of fluid, in the intracellular
spaces of the optic disk. Papilledema, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=36673 (last visited Jan. 7, 2025); Edema,
DORLAND’S MEDICAL DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=15589
(last visited Jan. 7, 2025).
7

Case 1:17-vv-01109-UNJ Document 132 Filed 04/04/25 Page 8 of 62
revealed “numerous scattered small foci of T2 hyperintensity in the subcortical white
matter,” with “no abnormal enhancement following contrast administration to suggest an
active demyelinating lesion.”12 (Id. at 742.)
E.M. returned to Dr. Digre on October 1, 2015. (Ex. 6, p. 14.) Although E.M.
reported that her vision had improved (“[g]ood vision both eyes”), E.M.’s physical and
ocular exams were consistent with her previous visit. (Id. at 14-16.) At this encounter,
Dr. Digre diagnosed left-side optic neuritis with atypical disk swelling, further noting that
“this could be more likely a demyelinating disorder such as Acute disseminated
encephalomyelitis [“ADEM”] vs multiple sclerosis [“MS”] or other.” (Id. at 17.)
Additionally, Dr. Digre preliminarily concluded E.M.’s condition was related to her prior
immunizations, diagnosing (“Post vaccination opti”). (Id.; see also id. at 14 (“this
summer had shots done HPV, ? DPT -- could this be related?”); id. at 17 (“will try to get
her immunization records to review too”).) E.M. was referred to pediatric neurologist
Michael Lloyd, M.D., at the Primary Children’s Hospital. (Id. at 17.)
E.M. presented to Dr. Lloyd on October 8, 2015. (Ex. 8, p. 668.) E.M.’s
neurologic exam was normal apart from confirming the presence of optic neuritis. (Id. at
669.) Noting that E.M.’s prior MRI showed increased T2 signal in addition to optic
neuritis, Dr. Lloyd performed a lumbar puncture to further investigate whether a broader
demyelinating disorder was present. (Id. at 668-69.) E.M. began a three-day course of
Solu-Medrol13 infusions.14 (Id. at 598, 622, 662, 669, 697.) The lumbar puncture
12 As discussed further below, petitioner’s radiology expert interpreted the September 25, 2015 MRI as
additionally showing a left temporal lobe lesion that may or may not have been included in the reference
to “numerous scattered small foci.” (Tr. 305.) The parties’ experts agree that this lesion would have been
part of E.M.’s optic neuritis. (Tr. 423, 425-26 (Dr. Linnoila); Ex. 68, p. 2 (Dr. Silverman).)
13 Solu-medrol is an intramuscularly or intravenously infused synthetic glucocorticoid that is used as an
anti-inflammatory and immunosuppressant in a wide variety of disorders. Solu-medrol, DORLAND’S
MEDICAL DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=46174 (last visited
Jan. 8, 2025); Methylprednisolone sodium succinate, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=89219 (last visited Jan. 8, 2025);
Methylprednisolone, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=31014 (last visited Jan 8, 2025).
14 Petitioners contend that E.M. also received a 21-day steroid taper in treatment of her optic neuritis
following her infusion treatment. (ECF No. 127, p. 63.) However, in support of this assertion they cite a
later history from a medical record dated April 22, 2016. (Id. (citing Ex. 134, p. 245).) It is difficult to tell
from the contemporaneous medical records whether E.M. actually received a steroid taper in October and
November of 2015. E.M.’s hospitalization records confirm that she did begin a prednisone taper at a later
time, on January 4, 2016 (E.g., Ex. 8, p. 1221 (noting as of January 5, 2016 that a taper was started
“yesterday”)), but her earlier treatment records with Dr. Lloyd indicate only that petitioner was prescribed
a 3-day course of IV infusions, as well as a course of Vitamin D, when she was being treated for her optic
neuritis (Ex. 115, p. 245). Dr. Lloyd’s November 10, 2015 consultation report in particular indicates that
E.M. was “doing well” after IV Solu-Medrol treatment with no reference to a steroid taper. (Id.) However,
when E.M. presented for a neurology consult on December 12, 2015, her parents specifically reported a
“steroid taper over one month through mid-November, 2015.” (Ex. 8, p. 477.) Though a somewhat later
record, this is still a treatment record in which E.M.’s parents would have had a motivation to provide an
accurate history and is not so far removed from the time the steroid taper would have been administered
that it can be completely disregarded. And, because the reports of the prior steroid taper pre-date the
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showed low vitamin D, elevated white blood cells, slightly elevated IgM, and “a single
[oligoclonal] band in the CSF as well as identical bands present in both the CSF and the
serum.” (Ex. 134, pp. 721-25.) It was noted that “some individuals with a single band
subsequently develop oligoclonal bands several months later,” and that “[t]he presence
of matching bands is consistent with a systemic immune reaction.” (Id. at 721.)
E.M. had an outpatient follow up with Dr. Lloyd on November 10, 2015. (Ex. 115,
pp. 243-46.) She had tolerated treatment well and reported that she felt her vision was
back to normal. (Id. at 244.) However, she was still reportedly experiencing intermittent
headaches affecting her frontal temporal area, including pain affecting her eyes. (Id.)
On exam, Dr. Lloyd noted the “[f]undi overall appear clear,” but did not specifically
indicate whether the previously observed optic disk swelling had resolved. (Id. at 245.)
Dr. Lloyd interpreted the lumbar puncture results as normal and, after noting that her
brain lesions were not in a typical pattern for multiple sclerosis, diagnosed left-sided
optic neuritis. (Id.) The plan was to monitor and follow up in 3 months unless additional
problems arose sooner. (Id.) E.M. received her seasonal flu vaccination that day – the
second vaccination at issue in this case. (Ex. 8, p. 591; Ex. 2, p. 1.)
E.M. next presented for medical attention on December 9, 2015. At that time,
she was brought to the emergency department via ambulance after experiencing an
apparent seizure. (Ex. 14, pp. 1-5; Ex. 8, pp. 540-43.) There are conflicting reports as
to whether E.M. was suffering an illness in the days prior to her seizure. The EMG
records indicate that E.M. “was ill for past 2 days, taking ibuprofen for fever.” (Ex. 14, p.
1.) However, a history provided at the hospital indicated that “[m]om said she seemed
to be fine in recent days with no recent illness. No fever, no cough, no runny nose, no
respiratory symptoms . . . Of note, she had not had any recent illness with any fever.”
(Ex. 8, p. 578.) A further history indicated she “had no fever or chills. No diarrhea. She
does endorse sore throat 2 days prior, headaches day before, but today has been
feeling well with no complaints.” (Ex. 134, p. 540.) When EMS arrived, they initially
recorded that E.M. had an elevated temperature of 100.1⁰F. (Ex. 14, p. 1.) However,
both parties’ experts agree that seizures can elevate body temperature. (Tr. 526-27,
533 (Dr. Linnoila); Tr. 802-03 (Dr. Steinman).) E.M. had a normal body temperature of
37⁰C (98.6ºF) by the time she was initially examined in the emergency department. (Ex.
134, p. 541.)
The neurology team recommended another lumbar puncture, a herpes simplex
virus (“HSV”) test, and prescribed the anticonvulsant Keppra. (Ex. 134, pp. 541, 578-
80.) Petitioner’s repeat lumbar puncture showed improved, but still elevated, white
blood cell count of 24, but no organisms were detected. (Id. at 579-80.) Pertinent to the
discussion below, testing was also negative for HSV 1 and 2. (Id. at 582.) E.M.
underwent an EEG, which was interpreted by Dr. Francis Filloux on December 10,
2015, as revealing an abnormal wake and sleep results “due to left hemisphere
January 4, 2016 taper otherwise confirmed in the records, it is not possible that E.M.’s parents were
simply mis-remembering the timing of the later January steroid taper. Respondent’s neurology expert, Dr.
Linnoila, did base her opinion on the understanding that E.M. was treated with a steroid taper in addition
to her infusion. (Tr. 423-24.)
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abnormalities consisting of nearly continuous left posterior epileptiform discharges as
well as clusters of left hemisphere polymorphic slow waves intermixed with posterior
spikes as well as brief periods of nearly 3 per second sharp and slow wave or spike and
wave like discharges.” (Id. at 533.) Dr. Filloux felt that the findings were “consistent
with some sort of relatively acute left hemisphere process . . . [and] could be consistent
with some form of an epileptic condition.” (Id.) An additional HSV PCR test was
ordered; however, the neurology team felt it was safe to send E.M. home based on the
CSF results, given that the pleocytosis had improved since October. (Id. at 580.)
Discharge diagnoses were new onset of generalized seizure, CSF pleocytosis, and
history of optic neuritis. (Id.)
E.M. underwent a follow up MRI of the brain on December 12, 2015. (Ex. 8, p.
498.) The impression included focal areas of increased T2 signal in the white matter of
both cerebral hemispheres as seen in the prior September MRI and one new lesion in
the left periatrial region. (Id. at 498-99.) The impression further indicated: “Some of the
smaller lesions are no longer detected. None of the lesions show[] enhancement or
diffusion restriction. Significance of these lesions is uncertain. They are not typical of
the demyelinating lesions of MS, but in the presence of optic neuritis, could represent
MS.” (Id. at 499.) However, the report indicated that “the orbital structures are not
specifically studied, as they had been in the past.” (Id.) Shortly after her MRI, E.M.
developed a number of concerning symptoms, including right hand numbness and
language deficits, which quickly resolved. (Id. at 474.) Accordingly, she was seen in
the emergency department by neurologist Dr. Carey Wilson. (Id. at 477.) Dr. Wilson
reviewed E.M.’s medical history, including her more recent labs and imaging,
concluding that her suspicion was “autoimmune encephalitis process as [a] unifying
diagnosis,” given the continued pleocytosis and progression of symptoms without
evidence of an infection. (Id. at 478.) She planned to send E.M.’s lab results to Mayo
clinic for an autoimmune panel and prescribed an additional course of Keppra. (Id.)
E.M. reportedly had two additional seizures lasting two minutes each on
December 20, 2015, but she recovered easily. (Ex. 8, p. 467.) She had a further follow
up for her seizures with her primary care provider, Dr. Garcia, on December 23, 2015.
(Ex. 4, p. 2.) Dr. Garcia reviewed E.M.’s medical history, including her lab results and
imaging reports, and noted that E.M. began to experience fever and sore throat three
days prior. (Id.) It was observed that E.M.’s seizures appeared to coincide with her
fevers and that febrile illnesses can lower the seizure threshold. (Id. at 2, 4.) It was
reported that, on December 22, 2015, E.M. experienced four seizures, each lasting
approximately two minutes or less. (Id. at 2.) Several different seizures were described
as including confusion, twitching, and stiffness. (Id.) E.M. had experienced another 30-
second seizure on the morning of December 23, 2015. (Id.) It was also noted that E.M.
was constipated and appeared to be more easily confused. (Id. at 2-3.) Dr. Garcia
diagnosed petitioner with acute pharyngitis, slow transit constipation, and seizure
disorder. (Id. at 3.) She recommended that E.M. undergo a neurology evaluation and,
in the interim, aggressive treatment of her fevers with over-the-counter medicines. (Id.)
A strep culture was later reported as negative. (Id. at 4.)
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E.M. was subsequently admitted to the Riverton Hospital emergency department
on December 24, 2015, after experiencing four more seizures over the course of 15
hours. (Ex. 16, p. 33.) E.M.’s mother reported that she was having seizures almost
daily since her diagnosis of epileptic seizures earlier that month. (Id.) E.M. was postical
for several minutes but returned to baseline between the seizures. (Id.) E.M.
experienced one seizure at the hospital before being treated with Ativan and IV Keppra.
(Id. at 34.) After E.M. had gone several hours without a seizure, she was discharged
home and ordered to follow up with Dr. Lloyd in the following week. (Id.) However,
E.M.’s mother called Dr. Lloyd’s office several times on December 25, 2015, to report
that E.M. had experienced four seizures over a “few hour period, each lasting one
minute apiece.” (Ex. 8, p. 465.) The care provider noted that E.M.’s seizures were
escalating and that she had prescribed oxcarbazepine as a new course of treatment.
(Id.)
On December 28, 2015, E.M. was admitted to the Primary Children’s Hospital
neurology department with a history of epilepsy and possible autoimmune encephalitis,
as well as increased seizure frequency over the past nine days. (Ex. 8, p. 1306.) E.M.
presented with a fever and was administered Ativan. (Id.) E.M. had reportedly suffered
approximately eight or nine seizures earlier in the day, as well as two seizures within 15
minutes of each other prior to her admission. (Id.) It was reported that E.M.’s seizures
typically last 20-30 seconds and are characterized by right facial twitching. (Id.)
Although E.M. was usually still responsive during her seizures, she was sometimes
unresponsive while seizing with her body falling to the right side. (Id.) Her seizures
were also occasionally accompanied by fever. (Id.) It was noted that the prescribed
Ativan initially alleviated her seizures entirely. (Id.) However, E.M.’s mother reported
that, since December 20, 2015, E.M. had begun acting “more child like.” (Id.) E.M. had
also been experiencing constipation for several days. (Id.) E.M.’s physical exam was
unremarkable, while her neurological exam revealed dysarthric speech with intermittent
response and normal motor function but with decreased reflexes in her bilateral biceps,
knees, and ankles. (Id. at 1307.) E.M. was admitted for a continuous video EEG to
observe further seizure characterization and localization, as well as for medication
management of her seizures. (Id. at 1309.) During her admission, E.M. underwent
near daily sessions of speech and language, physical, and occupational therapies.
(See id. at 1217-2116.) She was treated with various anticonvulsants, including Ativan,
Keppra, oxcarbazepine, clonazepam, lacosamide, phenytoin, and IV fosphenytoin, as
well as steroids, including IV Solu-Medrol and prednisone, and plasmapheresis. (See
id. at 1238-41, 1264-70, 1285-89, 1681-709, 1946-50, 2017-20, 2059-61, 2112-14,
2480-87; Ex. 115, pp. 209-13.) Despite her treatments and therapy, E.M. continued to
experience seizures and struggled with fevers, ataxia, aphasia, and dysarthria. (See
Ex. 8, pp. 1249-52, 1262, 1847, 1946-50, 1955, 2010, 2017-20, 2059-60, 2068, 2076-
77, 2095-96, 2103, 2466; Ex. 115, pp. 198-200.)
As of December 29, 2015, the pediatric neurology department had yet to reach a
unifying diagnosis and scheduled an additional brain MRI. (Ex. 8, p. 1294.) E.M.’s
brain MRI from December 29, 2015, showed increasing T2 signal abnormality
compared to her previous imaging. (Id. at 1290-91.) The radiologist believed that these
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results could show either a transient parenchymal signal change related to the seizures
if E.M. was seizing during the MRI, but otherwise, the worsening signal “could represent
a glial neoplasm.” (Id. at 1291.) The absence of diffusion restriction was found to be
inconsistent with an ischemic or cerebritis condition, and “[t]he lack of volume loss (and
in fact mild thickening of the cortex) argues against Rasmussen encephalitis.” (Id.)
However, the radiologist noted that these findings would require correlation with clinical
information and short-term imaging follow ups to track E.M.’s course. (Id.)
On December 30, 2015, the pediatric neurology team reviewed E.M.’s brain MRI,
noting concerns that she was “becoming progressively encephalopathic with unrelenting
seizures from an autoimmune process.” (Ex. 8, pp. 1285-88.) The team prescribed
continued IV Solu-Medrol for further evaluation of seizures and encephalopathy. (Id. at
1286.) E.M.’s autoantibody Ma1 and Ma2 testing from this date revealed no abnormal
levels of autoantibodies. (Id. at 1754-55.) On December 31, 2015, E.M. received a
nephrology consultation in consideration of therapeutic plasma exchanges (“TPE”) to
treat E.M.’s progressive encephalitis. (Id. at 1268.) Dr. Meredith Seamon concluded
that E.M. would benefit from TPE and scheduled the various procedures necessary to
prepare E.M. for the therapy. (Id. at 1270.) Due to E.M.’s troubles with her oral motor
skills, beginning on December 31, 2015, she received periodic clinical feeding
evaluations during her admission. (Id. at 1274-75.) It was noted December 31, 2015
that E.M.’s seizure frequency and mental status improved following her early inpatient
treatment with IV Solu-Medrol; however, her treaters planned to initiate plasmapheresis
if E.M.’s condition plateaued. (Id. at 1278-80.) Plasmapheresis was initiated on
January 1, 2016, after E.M.’s condition did not sufficiently improve with the IV Solu-
Medrol. (Id. at 1264-66.) E.M. received plasmapheresis treatment every other day
between January 1, 2016, and January 9, 2016, for a total of five treatments. (Id. at
1234, 1253-54, 2117, 2050, 2091.)
A January 2, 2016 neurology note indicates that E.M. was having persistent
difficulty with both receptive and expressive components of speech, and that she was
likely exhibiting “2/2 L temporal lobe involvement,” which was expected to improve with
the planned treatment regimen. (Ex. 8, pp. 1249-51.) The note further indicated that, if
E.M. did not improve as planned, then she would need additional imaging to evaluate
the progression of her condition and for alternative etiologies. (Id.) A January 3, 2016
neurology note explains that E.M. experienced a seizure the previous day, after which
she experienced Todd’s paralysis of her right upper and lower extremities. (Id. at 1238-
41.) The neurologists believed that this was further evidence of her left temporal lobe
involvement. (Id. at 1240.) E.M.’s treaters observed that, despite escalating
treatments, her seizures persisted. (Id.) E.M. was taking Keppra, oxcarbazepine, and
phenytoin, but her treating physicians believed that clonazepam could be beneficial
without worsening her encephalopathy. (Id.) Following her last treatment with IV Solu-
Medrol on January 3, 2016, E.M. was started on a prednisone taper on January 4,
2016. (Id. at 1222, 1240.)
By January 4, 2016, E.M. was noted to be “doing much better” with her seizures
and aphasia. (Ex. 8, p. 1231.) The physician was unsure whether E.M.’s improvement
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was due to the IV Solu-Medrol, plasmapheresis, or clonazepam, but chose to continue
the existing course of treatment. (Id.) A January 6, 2016 neurology note indicated that
E.M. was again experiencing facial twitching. (Id. at 2113.) An EEG was scheduled to
determine whether the conditions were due to her seizures. (Id.) E.M. underwent an
EEG on January 7, 2016, which showed “very abnormal” results, including the presence
of a “marked hemispheric asymmetry with abundant left hemispheric epileptiform
discharges.” (Id. at 2099-100.) There were also “numerous predominantly subclinical
seizures arising posteriorly on the left.” (Id. at 2100.) The frequency, duration, and
electrographic severity of E.M.’s seizures lessened as the EEG progressed, and the
impression was an epileptic encephalopathy with greater involvement of the left
hemisphere. (Id.) A January 8, 2016 neurology note indicates that E.M. continued to
experience subclinical seizures as observed during the January 7, 2016 EEG, despite
having completed a five-day course of IV Solu-Medrol and four plasmapheresis
sessions, as well as taking multiple anti-epileptic drugs. (Id. at 2077.) E.M.’s clinical
seizures had become “infrequent,” and she continued to suffer “persistent but
improving” expressive and receptive aphasia. (Id.) Although E.M. denied sensation to
light touch, the reason for her sensory symptoms was unclear. (Id.) E.M.’s CSF and
MRI findings were noted to be consistent with a possible autoimmune
encephalopathy/encephalitis. (Id.) E.M. was still scheduled for a final plasmapheresis
treatment, at which point the neurology team intended to conduct CT scans to evaluate
for possible tumors. (Id.) E.M. underwent CT scans of her abdomen, chest, and pelvis
that same day. (Id. at 2064-67.) Her results were normal with the exception of a large
stool burden in her abdomen. (Id. at 2047, 2064-67.)
E.M. underwent another EEG on January 9, 2016, which showed some
improvement; however, she continued to have seizure activity, aphasia, and difficulty
with her gait. (Ex. 8, pp. 2047-48.) On January 10, 2016, it was noted E.M.’s progress
had effectively plateaued. (Id. at 2047.) The neurology team planned to conduct further
imaging to evaluate the progress of her inflammation and, if not improved, to proceed
with IVIG or rituximab. (Id. at 2048.)
E.M. was referred to the infectious disease team on January 11, 2016. (Ex. 8,
pp. 2023-27.) The team considered infectious, post-infectious, and autoimmune
etiologies, but felt that an autoimmune cause was most likely, given “the length of
symptoms and relapsing remitting episodes.” (Id. at 2026.) After excluding several
causes including fungal etiologies and rabies, the team also noted that:
There is also the potential that her symptoms may be due to a rare ADEM
reaction to the HPV vaccine series. Her symptoms of optic neuritis and
subsequent development of seizures occurred within weeks after her
second HPV vaccine . . . . Though this temporal relationship does not
necessitate causality, there are a few case reports of a similar nature . . . .
This could potentially explain the MRI findings, negative infectious CSF
work up to date, and symptom progression. A VAERS report should be
completed.
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(Id.) Petitioner was also seen by rheumatology on January 11, 2016. (Id. at 2030-33.)
The rheumatology team agreed that E.M. was suffering from an autoimmune or
autoinflammatory central nervous system disease. (Id. at 2033.) An infectious process
was deemed unlikely due to the lack of progression during the first two months of E.M.’s
course; however, it was noted that E.M.’s initial treatment with steroids could have
masked inflammation associated with an indolent infection. (Id.) Additionally, although
a malignancy was suggested, this too seemed unlikely based on her imaging results.
(Id.) The team noted that E.M.’s lack of response to corticosteroids and plasmapheresis
was troublesome, and they raised some suspicion for neurosarcoidosis or neuro-
bechet’s. (Id.) Other considerations were interferonopathy, Aicardi-goutierre’s
syndrome, adenosine deaminase type 2 deficiency, lymphomatoid granulomatosis, and
lupus, all of which were deemed much less probable. (Id.)
E.M. also underwent a further brain MRI on January 11, 2016, which revealed
“[i]ncreasing extent and conspicuity of multiple areas of cortical thickening and T2 signal
abnormality within the left cerebral hemisphere also involving the adjacent white matter”
in the left cerebral hemisphere. (Ex. 8, pp. 2037-38.) Due to the rapid progression of
E.M.’s brain lesions over a short period of time, neoplastic process was less likely,
though not excluded, and inflammatory process of autoimmune or vasculitic etiology
remained a primary differential consideration. (Id.) Additional considerations based on
E.M.’s early optic neuritis and rapid progression included Bechet’s disease, sarcoidosis,
or ADEM, although the radiologist noted that E.M.’s CT scans made sarcoidosis less
likely. (Id.) A January 11, 2016 neurology note recounted E.M.’s treatment course and
repeated the group’s earlier recommendation for IVIG or rituximab therapy. (Id. at
2040.) Differential diagnoses at that time included malignancy; infectious etiology due
to consistent pleocytosis; autoimmune encephalitis, despite a negative encephalopathy
autoimmune panel; and Rasmussen’s encephalitis based on the isolated involvement of
E.M.’s left hemisphere and poor response to immunosuppression. (Id.) The same day,
E.M. had a neurosurgery consult and was scheduled for a brain biopsy to occur on
January 14, 2016. (Id. at 2043-45.)
E.M. presented to Dr. Carol Bruggers for an oncology consultation on January
12, 2016. (Ex. 8, pp. 2000-03.) After reviewing E.M.’s medical history, treatment
course, and imaging results, Dr. Bruggers assessed E.M. with epilepsy and worsening
encephalitis with persistent pleocytosis on CSF and abnormal MRI. (Id.) Dr. Bruggers
indicated that there was concern for malignancy, given E.M.’s MRI findings, and
recommended a brain biopsy for tissue diagnosis in order to further distinguish the
nature of E.M.’s encephalitis. (Id.) Further lab results showed no malignant cells in the
CSF. (Ex. 134, p. 2004-05.) A January 12, 2016 flow cytometry report was negative for
non-Hodgkin lymphoma. (Id. at 2021-22.)
During an infectious disease consultation on January 12, 2016, it was noted that
E.M. was not improving, and further testing for less common entities, including for HIV,
HSV, CMV, and EBV, was recommended. (Ex. 134, pp. 2009-11.) E.M. underwent
extensive testing that same day. (Id. at 1339-48.) In pertinent part, E.M. tested positive
for HSV Type 1/2 Combined Antibodies, IgM and HSV Type 1 Antibodies, IgG on serum
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testing; however, she tested negative for HSV Type 2 Antibodies, IgG on serum testing.
(Id. at 1341, 1343-44.) She also tested negative for HSV on PCR, as well as negative
for both HSV Type 1/2 Combined Antibodies, IgG and HSV Type 1/2 Combined
Antibodies, IgM on CSF. (Id. at 1343-46.) E.M. also tested negative for both HSV Type
1/2 Combined Antibodies, IgG and HSV Type 1/2 Combined Antibodies, IgM on CSF.
(Id. at 1344-45.) A progress note from January 12, 2016, lists differential diagnoses
including malignancy, infectious etiology, autoimmune encephalitis, demyelinating
process in the central nervous system, Rasmussen’s encephalitis, and Gardasil-related
ADEM. (Id. at 2018.) The physician noted that the mayo clinic returned a negative
autoimmune panel and that prior testing were negative for a demyelinating process.
(Id.)
E.M. underwent another brain MRI on January 13, 2016, which revealed no
changes from her previous January 11, 2016 MRI. (Ex. 8, pp. 1986-87.) A January 13,
2016 infectious disease report noted that E.M. continued to be afebrile and suffer
multiple seizures throughout the day. (Id. at 1988.) It was noted that some case
studies have associated adverse immune reactions, including ADEM, with the HPV
vaccine, and that such a reaction was being considered in E.M.’s case based on the
temporal relationship between her optic neuritis and HPV vaccination. (Id. at 1990.)
The team noted, however, that this was “a diagnosis of exclusion” and that
“autoimmune vs infection etiologies seem the most likely working differential at this
point.” (Id.) E.M. was scheduled for an additional MRI and a brain biopsy. (Id.)
The same day, Dr. Thorell, E.M.’s infectious disease specialist, submitted a
report to the Vaccine Adverse Event Reporting System (“VAERS”). (Ex. 139, pp. 3-4.)
The vaccine reportedly at issue was E.M.’s July 20, 2015 HPV vaccine and the date of
the adverse event was noted as September 1, 2015. (Id.) The reported adverse event
was: “Optic neuritis bilaterally developed 6-7 weeks after her 2nd vaccine. She then
developed weakness, behavioral change, dysarthria, facial tics, sensory losses, and
difficult-to-manage seizures, w/ multifocal encephalitis, CSF pleocytosis.” (Id.) It was
further explained that a “[b]road workup of autoimmune, infectious, oncologic etiologies
over the past month unrevealing so far.” (Id.) Dr. Thorell explained that
An inflammatory process of autoimmune or vasculitis etiology remains a
primary differential consideration. The absence of true diffusion restriction
argues against vasculitis however. Absence of meningeal enhancement
and diffusion restriction also argue against infectious cerebritis or meningitis
(bacterial or fungal). . . . [A]dditional differential considerations could include
Bechet’s disease, sarcoidosis, or atypical demyelinating (ADEM) process
as unifying diagnoses to explain brain and orbital involvement.
(Id. at 2-3)
E.M. then underwent a left frontal lobe biopsy on January 14, 2016, which
revealed chronic active encephalitis. (Ex. 19.) E.M. was subsequently transferred to
the pediatric intensive care unit (“PICU”) for post-operative monitoring following her
biopsy. (Ex. 8, pp. 1946-47, 1955.) The PICU admission note indicates that E.M. had
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“acute worsening” since January 12, 2016, “with slurred speech and increased seizure
frequency (5x/day) and on 1/13 had new onset right sided arm and leg weakness after
seizure and also new onset vomiting.” (Id. at 1955.) She was intubated and provided
IV nutrition. (Id.) E.M. was also started on IV acyclovir15 due to the positive serum
studies for HSV. (Id. at 1908, 1959.) On January 15, 2016, serum samples again were
positive for HSV IgG and IgM, and E.M.’s prescribed dose of acyclovir was corrected.
(Ex. 134, p. 1334; Ex. 8, pp. 1900, 1936.) There was no evidence of new neurological
deficits, and the neurology team planned to taper her steroid treatment post-biopsy. (Id.
at 1935.) A January 16, 2016 infectious disease report recommended additional CSF
and blood labs, indicated that the neurology department planned to administer an
additional course of IVIG therapy, and confirmed that a VAERS report was filed. (Ex. 8,
pp. 1915-16.) E.M. underwent an MRI spectroscopy on January 17, 2016, which
revealed “mild NAA diminution and choline peak elevation compatible with neuronal
dysfunction or dropout and membrane turnover.” (Id. at 1893.) The spectroscopy also
showed that E.M.’s myoinositol was mildly elevated, and it was suggested that this
finding was “probably related to membrane turnover.” (Id.)
A January 17, 2016, neurology note indicates that E.M. had a fever, elevated
inflammatory markers, a rash, and eosinophilia. (Ex. 8, p. 1898-99.) It was thought that
her condition could either be serum sickness related to IVIG therapy or from an infection
following her biopsy. (Id.) Later, however, Dr. Dodson from the neurology team
examined E.M. and found her to be doing “somewhat better,” but exhibiting mild
extremity weakness with rare clonic movements of the right hand and forearm, which
were believed to be simple partial seizures. (Id. at 1900-01.) Due to her lack of
improvement on acyclovir, E.M. was also started on vancomycin.16 (Id. at 1900.) The
following day, on January 18, 2016, the neurology team noted that E.M.’s rash was
worsening and that she showed elevated liver enzymes and eosinophils, which was
likely indicative of a drug reaction with eosinophilia and systemic symptoms (“DRESS”)
caused by her anti-epileptic drugs. (Id. at 1885.) The team decided to discontinue IVIG
therapy and oxcarbazepine, but prescribed topical steroids to treat E.M.’s rash. (Id.)
Vancomycin and acyclovir were also discontinued due to negative culture and no repeat
fevers. (Id.) The team prescribed a reduced form of ubiquinol, riboflavin, vitamin C, and
carnitine on the off chance that she was suffering from a mitochondrial disease. (Id. at
1886.) On January 19, 2016, E.M. was noted to be experiencing increased seizures
after discontinuing oxcarbazepine and phenytoin. (Id. at 1878.) She was continued on
Keppra and prednisone and started on a new anti-convulsant (lacosamide); however,
clonazepam was discontinued. (Id.)
15 Acyclovir is a “synthetic acyclic purine nucleoside with selective antiviral activity” that is used in the
treatment of HSV. Acyclovir, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=833 (last visited Jan. 15, 2025).
16 Vancomycin is an antibiotic that is used to treat cocci (and other gram-positive bacteria), severe
staphylococcal infection, staphylococcal enterocolitis, and antibiotic-associated pseudomembranous
enterocolitis. Vancomycin, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=52529 (last visited Jan. 15, 2025).
16

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E.M.’s brain biopsy results were received by the neurology team on January 21,
2016, and showed extensive inflammatory response with peri-neuronal inflammatory
cells, perivascular cuffing, extensive gray and white matter edema, no viral particles, no
neoplastic cells, and no features consistent with Creutzfeldt-Jakob Disease. (Ex. 8, p.
1854.) The findings were “most consistent with a ‘T-Cell mediated’ extensive immune
mediated or infectious encephalitis.” (Id.) The infectious disease team additionally
observed that “since serum HSV titers had evolved from IgM to IgG response it is not
possible to exclude the possibility that HSV could have triggered an immune response
in part responsible for this disease (even if there is no evidence of HSV in the brain).”
(Id.) Although it was noted that Rasmussen’s encephalitis is a T-cell mediated
autoimmune process and that E.M.’s symptom presentation was consistent with that
diagnosis, there remained concern that the MRI imaging was not indicative of
Rasmussen’s encephalitis and the preceding optic neuritis was atypical. (Id. at 1816,
1826, 1835; see also id. at 1816 (noting that E.M.’s T-cell mediated encephalitis was
“similar to” Rasmussen’s encephalitis, but her presentation “does not fit the complete
picture” of Rasmussen’s).) However, it was felt that immune modulating treatment for
an autoimmune process was appropriate. (Id.) The neurology team determined that
they would begin to treat E.M. with an immune modulator due to increasing suspicion of
an autoimmune process at work, as well as acyclovir due to concern for latent HSV
infection. (Id. at 1816, 1826.) Because E.M. was experiencing several seizures per
day, the team decided to increase her prescriptions of lacosamide and clonazepam and
continue treatment with Keppra and prednisone. (Id. at 1816, 1835.) After consultation
between the neurology, neuroimmunology, and rheumatology teams, it was decided
that E.M. would be treated with IV rituximab, as well as IV pulse steroids, IVIG, and anti-
epileptic drugs. (Id. at 1761-67, 1774, 1787, 1789, 1794, 1805.)
Extensive additional medical records are in evidence. E.M. continued to undergo
both evaluation and management of her condition and her treating physicians continued
to struggle with any definitive diagnosis. However, it is not necessary to discuss the
later medical records. Even as the treating physicians remained concerned about the
atypical presentation, both parties’ experts agree that E.M.’s biopsy and subsequent
MRIs demonstrating left hemisphere volume loss are sufficient to confirm her condition
as Rasmussen’s encephalitis. (Ex. C, pp. 9-11; Tr. 179, 293-94, 396-98, 452-58; Ex. 9,
pp. 164-65; Ex. 115, p. 9; Ex. 17, p. 15.) Subsequent to Dr. Thorell’s January 13, 2016
VAERS submission, the treating physicians do not appear to have meaningfully
discussed likely underlying triggers of E.M.’s condition.
b. Testimony
i. E.M.
During the hearing, E.M. testified briefly and in a limited capacity. (Tr. 9-10.)
She confirmed her name and age and that she does not have the use of her right arm
and leg. (Id.) E.M.’s presence during the hearing demonstrated that she has profound
deficits as a result of her injury.
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ii. Jeremy Marsh
Petitioner and E.M.’s father, Jeremy Marsh, testified during the entitlement
hearing. (Tr. 10-24.) He testified that, in the summer of 2015, he took a trip with his
family, during which E.M. was not experiencing any health issues. (Id. at 12.) After this
trip, E.M. took another trip to see family. (Id. at 13.) When E.M. returned home in the
beginning of July, she received her second HPV vaccination. (Id.) He testified that,
after this vaccination, she began reporting some issues with her eyes in the middle of
August. (Id.) Thereafter, he testified that E.M. had a seizure on December 9, 2015, and
was subsequently scheduled for an MRI on December 12, 2015. (Id. at 16.) While at
the hospital following E.M.’s MRI, petitioner testified that he realized something was
wrong when E.M. “looked like she was thinking about what she wanted to say and
couldn’t remember the words.” (Id. at 16.) He described how E.M. “couldn’t say any
words. She couldn’t get anything out. She started pulling at her eye and shaking her
head, and just couldn’t move one of her hands.” (Id. at 17.)
Mr. Marsh testified that, thereafter, E.M.’s condition progressed, and she was
hospitalized from December 28, 2015, until the end of January 2016. (Tr. 18.) He
explained that E.M.’s neurologist, Dr. Filloux, found E.M.’s course to resemble atypical
Rasmussen’s encephalitis. (Id. at 19, 21-22.) He testified that, during this time, he was
frustrated by the lack of answers as to what caused his daughter’s encephalitis. (Id. at
18-19.)
Mr. Marsh testified that, before the summer of 2015, E.M. was an excellent
student who excelled in math, played the piano, and loved to read and ride her horse.
(Tr. 14-15.) Now, E.M. cannot use her right hand and arm. (Id. at 19.) She cannot
walk without the assistance of a cane and someone standing next to her to help with
balance. (Id.) He explained that she now has limited cognitive abilities; she can answer
simple questions but is easily confused if the questions become too complex. (Id. at
20.) She also has a limited vocabulary of less than 10 words. (Id.) Petitioner described
E.M. as happy and playful, noting that she likes to joke with her siblings. (Id.)
iii. Leah Marsh
Petitioner and E.M.’s mother, Leah Marsh, filed an affidavit and provided
testimony during the entitlement hearing in this case. (Ex. 1; Tr. 25-65.) Mrs. Marsh
testified that E.M. was born on May 1, 2003, with “no significant prenatal problems.”
(Ex. 1, ¶¶ 2, 4 (citing Ex. 3; Ex. 11, pp. 477, 668).) She testified that, before July 20,
2015, E.M. had no preexisting conditions, was an honor student, and enjoyed playing
piano and online games, reading, and horseback riding. (Ex. 1, ¶ 5 (citing Ex. 4, p. 8;
Ex. 8, pp. 477, 668, 2001; Ex. 12; Ex. 13).) Specifically, before the summer of 2015,
E.M. was in good health and only wore glasses for slight nearsightedness. (Tr. 25-28.)
Mrs. Marsh testified that, in June of 2015, E.M. went on a few trips with family
before returning home in July of 2015. (Tr. 28.) During this time, E.M. was completely
healthy and active. (Id. at 28-29.) She explained that E.M. received her first HPV
18

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vaccination on February 17, 2015, and her second HPV vaccination on July 20, 2015.
(Ex. 1, ¶ 6 (citing Ex. 2, pp. 1-2; Ex. 4, pp. 6-9); Tr. 29.) She described how, about a
month later, E.M. reported “visual disturbances” and was eventually diagnosed with
optic neuritis. (Tr. 31-32; Ex. 1, ¶ 7.) She stated that, in early September 2015, she
noticed that E.M. had begun to struggle in school, which was unusual. (Ex. 1, ¶ 8; Tr.
43-44.) Mrs. Marsh went on to summarize E.M.’s medical course prior to her November
10, 2015 flu vaccination. (Ex. 1, ¶¶ 9-14; Tr. 31-48.) She explained that, in October
2015, E.M.’s vision had begun to improve. (Tr. 43-44.) Although E.M. began
experiencing headaches, petitioner explained that this symptom was not particularly
concerning at that time. (Id. at 45-46.) She testified that, in November 2015, E.M.’s
doctors recommended against the third dose of the HPV vaccine. (Id. at 47.) On
November 10, 2015, E.M. was administered the flu vaccine. (Id. at 47-48.) E.M.
continued to struggle with her schoolwork, but she was no longer complaining of vision
issues. (Id. at 48; Ex. 1, ¶ 14.) Then, on December 9, 2015, petitioner found E.M.
having a seizure and called an ambulance. (Tr. 48-49; Ex. 1, ¶ 15.) Mrs. Marsh went
on to summarize E.M.’s medical course including her emergency room visits and
subsequent Rasmussen’s encephalitis diagnosis. (Tr. 49-55; Ex. 1, ¶¶ 16-27.) She
explained her understanding of the atypical diagnosis as stemming from how quickly
E.M.’s condition progressed and the fact that Rasmussen’s encephalitis usually occurs
in much younger patients. (Tr. 64.) She testified that, throughout December 2015 and
January 2016, E.M.’s condition continued to progress with an increase in seizure
frequency. (Id. at 51-52.) She stated that, eventually, Dr. Filloux filed a VAERS report
because, after ruling out other possible causes, E.M.’s treaters had not found any other
cause for her condition. (Id. at 54.)
Petitioner averred that, “E.M. continues to experience severe sequelae of
encephalitis, including but not limited to progressive left side cerebral atrophy.” (Ex. 1,
¶ 29.) E.M.’s condition has left her unable to use her right arm and leg, and she
“endures constant facial twitching.” (Id.) “[E.M.] is severely limited in nearly every
activity in her daily life,” and “these diminishments are permanent.” (Id.)
V. Expert Opinions
a. Petitioners’ Experts
i. Lawrence Steinman, M.D.
In support of their claim, petitioners presented an expert opinion by
neuroimmunologist Lawrence Steinman, M.D. Dr. Steinman submitted three expert
reports and provide testimony during the entitlement hearing. He was offered without
objection as an expert in neurology, immunology, and neuroimmunology.17 (Exs. 23,
17 Dr. Steinman received his medical degree from Harvard University in 1973. (Ex. 24, p. 1; Tr. 67..) He
is board-certified in neurology and practices at Stanford University, where he also serves as a Professor
of Neurology. (Ex. 24, pp. 1-2; Ex. 23, p. 1; Tr. 66-69.) Dr. Steinman has treated patients, both adults
and children, who suffered from various forms of inflammatory neuropathy, including optic neuritis,
transverse myelitis, ADEM, neuromyelitis optica, multiple sclerosis, and others. (Ex. 23, p. 1; Tr. 70-71.)
Dr. Steinman’s research focuses on how the immune system attacks the nervous system, and he has
19

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59, 69; Tr. 77.) Dr. Steinman opined that E.M. suffered from optic neuritis,
characterized by inflammation of the optic nerve, as well as “an autoimmune seizure
disorder with epilepsia partialis continua (EPC) affecting one hemisphere greater than
the other, likely Rasmussen’s encephalitis.” (Ex. 23, p. 15 (citing Rasmussen’s
Encephalitis Information Page, NAT’L INSTS. OF HEALTH: NAT’L INST. OF NEUROLOGICAL
DISORDERS & STROKE (June 6, 2015) (Ex. 30), Steinman, supra, at Ex. 31); Tr. 77-80.)
Dr. Steinman testified that his assessment of the case can be boiled down to three
medically reasonable possibilities: (1) the HPV vaccine caused both E.M.’s optic neuritis
and Rasmussen’s encephalitis18; (2) the HPV vaccine and flu vaccine acted
synergistically to cause E.M.’s overall condition; or (3) the HPV vaccine caused E.M.’s
optic neuritis and, separately, the flu vaccine caused her Rasmussen’s encephalitis.
(Tr. 214, 229.) Pertinent to the analysis that follows, Dr. Steinman explained that, in a
“two-hit” model of Rasmussen’s encephalitis, E.M.’s optic neuritis lesions could have
“exploded into what we call Rasmussen’s” encephalitis with the flu vaccine acting as a
second necessary “hit,” stressing that both conditions are autoinflammatory. (Id. at 200-
04, 214, 233-34, 248, 776-77.) This is his preferred explanation for E.M.’s condition (Id.
at 220, 229), and he asserted that it withstands respondent’s contention that optic
neuritis and Rasmussen’s encephalitis involve distinct pathologies. (Id. at 212-14.)
Dr. Steinman explained that “Rasmussen’s encephalitis is a rare, chronic
inflammatory neurological disease that usually affects only one hemisphere of the
brain.” (Ex. 23, p. 15 (quoting Rasmussen’s Encephalitis Information Page, supra, at
Ex. 30); Tr. 83-84.) It typically occurs in children under the age of ten and results in
“frequent and severe seizures, loss of motor skills and speech, paralysis on one side of
the body (hemiparesis), inflammation of the brain (encephalitis), and mental
deterioration.” (Ex. 23, p. 15 (quoting Rasmussen’s Encephalitis Information Page,
supra, at Ex. 30).) He noted that the typical disease course is characterized by eight to
twelve months of progressive brain damage followed by permanent neurological
deficits. (Id. (citing Rasmussen’s Encephalitis Information Page, supra, at Ex. 30).) Dr.
Steinman explained that E.M.’s Rasmussen’s encephalitis has led to continuous
seizures, or epilepsia partialis continua. (Tr. 86-87.) He noted that, like ADEM,
Rasmussen’s encephalitis can have an autoimmune pathophysiology that, specifically,
involves cytotoxic T cells. (Tr. 180-81, 778-79 (citing Graus et al., supra, at Ex. 153, p.
31), 781-82 (citing A. Orsini et al., Rasmussen’s Encephalitis: From Immune
Pathogenesis Towards Targeted-Therapy, 81 SEIZURE: EUR. J. EPILEPSY 76 (2020) (Ex.
G, Tab 2)).)
published on various topics involving vaccines and neurological disorders, including molecular mimicry.
(Ex. 23, p. 3; Tr. 70.) He holds numerous American and European patents, including several U.S.
patents relating to vaccines. (Ex. 23, p. 4.) Dr. Steinman is a listed author on over 550 publications,
including one on Rasmussen’s encephalitis and several on optic neuritis and molecular mimicry. (Ex. 24,
pp. 5-46; Tr. 71-73, 76.)
18 In support of this theory, Dr. Steinman included a discussion of cross-reactive potential between
components of the HPV vaccine and glutamate receptors that have separately been implicated in the
pathophysiology of Rasmussen’s encephalitis. However, in light of the analysis that follows, it is not
ultimately necessary to fully address that aspect of Dr. Steinman’s opinion. The fact of this aspect of Dr.
Steinman’s theory is briefly discussed in note 39, infra, but is noted to be beyond what petitioners
ultimately need to demonstrate.
20

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Although two distinct conditions, Dr. Steinman opines that E.M.’s optic neuritis
and Rasmussen’s encephalitis can be causally related. (Ex. 23, p. 15 (citing
Rasmussen’s Encephalitis Information Page, supra, at Ex. 30; Steinman, supra, at Ex.
31).) He acknowledged that the scientific literature does not specifically report cases of
optic neuritis associated with Rasmussen’s encephalitis, but referenced case reports of
ocular inflammation, namely uveitis, preceding Rasmussen’s encephalitis. (Id. (citing A.
Simon Harvey et al., Chronic Encephalitis (Rasmussen’s Syndrome) and Ipsilateral
Uveitis, 32 ANNALS NEUROLOGY 826 (1992) (Ex. 33); Tokiko Fukuda et al., Chronic
Localized Encephalitis (Rasmussen’s Syndrome) Preceded by Ipsilateral Uveitis: A
Case Report, 35 EPILEPSIA 1328 (1994) (Ex. 34)).) While only optic neuritis is a
demyelinating condition, both conditions are inflammatory in nature. (Tr. 183, 204-05,
233.) In particular, Dr. Steinman noted that E.M.’s MRI after her optic neuritis diagnosis
showed “some evidence of a pathological process going on outside the optic nerve,” in
her left temporal lobe, which he concluded meant that “the process was more
widespread than just the optic nerve.” (Id. at 157-58.) Even after E.M. had a good
clinical recovery from her optic neuritis, E.M. still had ongoing optic neuritis
radiologically which, according to Dr. Steinman, indicates ongoing inflammation at the
time of her subsequent flu vaccine and development of Rasmussen’s encephalitis. (Id.
at 158-59.) In particular, while E.M.’s December 12, 2015 MRI did not specifically
examine her orbits, Dr. Steinman noted that her subsequent December 29, 2015 MRI
confirmed continued enhancement of the optic nerve, consistent with ongoing optic
neuritis.19 (Id. at 766-67.)
Dr. Steinman opined that the HPV vaccine has components that “are
immunologically cross-reactive with components on neurons and myelin.” (Ex. 23, p. 17
(citing Gardasil [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine,
Recombinant] Package Insert (2011) (Ex. 35) [hereinafter Gardasil Package Insert];
Lawrence Steinman, Autoimmune Disease: Misguided Assaults on the Self Produce
Multiple Sclerosis, Juvenile Diabetes and Other Chronic Illnesses. Promising Therapies
Are Emerging, 269 SCI. AM. (SPECIAL ISSUE) 106 (1993) (Ex. 36)).) He explained that the
Gardasil vaccine “is a non-infectious recombinant quadrivalent vaccine prepared from
the purified virus-like particles (VLPs) of the major capsid (L1) protein of HPV Types 6,
11, 16, and 18.” (Id. (citing Gardasil Package Insert, supra, at Ex. 35); Tr. 88-89.) In
particular, he noted that the L1 protein is an external protein of the virus that the vaccine
makes accessible to the immune system. (Tr. 89.) Moreover, Dr. Steinman explained
that Gardasil “elicits a stronger immune response than the natural viral infection,”
meaning vaccination induces more antibodies than infection. (Ex. 23, p. 19 (citing Nizar
Souayah et al., Guillain-Barré Syndrome After Gardasil Vaccination: Data from Vaccine
Adverse Event Reporting System 2006-2009, 29 VACCINE 886 (2011) (Ex. 39)); Tr. 90-
19 Dr. Steinman opined further on E.M.’s MRIs from September 2015 to December 2015. (Tr. 157-61.) I
have reviewed Dr. Steinman’s testimony in its entirety; however, because he ultimately agrees with Dr.
Silverman (Id. at 161), it is not necessary to separately summarize Dr. Steinman’s opinion regarding the
MRIs.
21

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91.) Dr. Steinman opined that this is significant because it generally shows a stronger
response to vaccination than to a natural infection. (Tr. 91-93.)
Dr. Steinman noted that “[o]ne of the main antigens that drives optic neuritis is an
immune response to a myelin protein known as MOG” (Myelin oligodendrocyte
glycoprotein). (Ex. 23, p. 20 (citing Estelle Bettelli et al., Myelin Oligodendrocyte
Glycoprotein-Specific T Cell Receptor Transgenic Mice Develop Spontaneous
Autoimmune Optic Neuritis, 197 J. EXPERIMENTAL MED. 1073 (2003) (Ex. 43); Lawrence
Steinman, Optic Neuritis, A New Variant of Experimental Encephalomyelitis, A Durable
Model for All Seasons, Now in its Seventieth Year, 197 J. EXPERIMENTAL MED. 1065
(2003) (Ex. 44); Kimihiko Kaneko et al., CSF Cytokine Profile in MOG-IgG+
Neurological Disease is Similar to AQP4-IgG+ NMOSD but Distinct from MS: A Cross-
Sectional Study and Potential Therapeutic Implications, 89 J. NEUROLOGY
NEUROSURGERY & PSYCHIATRY 927 (2018) (Ex. 45); Yael Hacohen et al., Myelin
Oligodendrocyte Glycoprotein Antibodies are Associated with a Non-MS Course in
Children, 2 NEUROLOGY NEUROIMMUNOLOGY & NEUROINFLAMMATION 1 (2015) (Ex. 46)); Tr.
96, 132.)20 Dr. Steinman performed BLAST21 searches for MOG and components of
the Gardasil vaccine (specifically, the HPV 16 and HPV 18 viral proteins) and identified
sequences of identical amino acids that he opined were sufficient to trigger
neuroinflammation as demonstrated experimentally by animal models. (Ex. 23, pp. 24-
29 (citing Anand M. Gautam et al., A Viral Peptide with Limited Homology to a Self
Peptide Can Induce Clinical Signs of Experimental Autoimmune Encephalomyelitis, 161
J. IMMUNOLOGY 60 (1998) (Ex. 51); Anand M. Gautam et al., Minimum Structural
Requirements for Peptide Presentation by Major Histocompatibility Complex Class II
Molecules: Implications in Induction of Autoimmunity, 91 PROC. NAT’L ACAD. SCIS. USA
767 (1994) (Ex. 52); Anand M. Gautam et al., A Polyalanine Peptide with Only Five
Native Myelin Basic Protein Residues Induces Autoimmune Encephalomyelitis, 176 J.
EXPERIMENTAL MED. 605 (1992) (Ex. 53)); Tr. 129-32, 134-35.) Further to these animal
models, Dr. Steinman presented a study by Lanz et al., in which this degree of
homology was confirmed as a molecular mimic between the Epstein-Barr virus and
glialCAM within human subjects in the context of multiple sclerosis. (Tr. 150-54; Tobias
V. Lanz et al., Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and
GlialCAM, 603 NATURE 321 (2022) (Ex. 71).)22 Dr. Steinman acknowledged that
20 The article by Kaneko et al. that was filed into evidence is noted to be an “Epub ahead of print”;
however, the article has since been published and is herein cited in accordance with the publication
information that is available on PubMed at https://pubmed.ncbi.nlm.nih.gov/29875186/.
21 Basic Local Alignment Search Tool or “BLAST” is a program that “compares nucleotide or protein
sequences to sequence databases and calculates the statistical significance of matches.” Basic Local
Alignment Search Tool, NAT’L LIBR. MED., https://blast.ncbi.nlm.nih.gov/Blast.cgi (last visited Jan. 21,
2025). BLAST searches “can be used to infer functional and evolutionary relationships between
sequences as well as help identify members of gene families.” Id.
22 The article by Lanz et al. that was filed into evidence is noted to be an “Accelerated Article Preview”
and is without publication details beyond the date of online publication. The Lanz article is herein cited in
accordance with the publication information that is available on Nature at
https://www.nature.com/articles/s41586-022-04432-7.
22

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molecular mimicry is widespread; however, he asserted that he “increase[s] the
relevance of the molecular mimics” by using the Immune Epitope Data Base to filter and
ensure the mimics match his criteria. (Ex. 59, pp. 3-7.)
Dr. Steinman acknowledged that a study by Baxter et al. found no statistically
significant epidemiologic relationship between the HPV vaccine and optic neuritis. (Ex.
59, pp. 1-2 (citing Baxter et al., supra, at Ex. A, Tab 1).) However, he explained that the
study listed several limitations and noted that “safe by epidemiological standards” does
not mean that the vaccination did not cause petitioner’s condition in this specific case.
(Id.) Dr. Steinman cited a different study that identified an increased risk of optic
neuritis following the second dose of the HPV vaccine. (Ex. 23, p. 20 (citing Gayathri
Sridhar et al., Evaluation of Optic Neuritis Following Human Papillomavirus Vaccination,
13 HUM. VACCINES & IMMUNOTHERAPEUTICS 1705 (2017) (Ex. 40; Ex. A, Tab 4)); Tr. 135-
36.)
Dr. Steinman also offered molecular mimicry as the theory by which
Rasmussen’s encephalitis can develop. (Ex. 23, p. 17 (citing Steinman, supra, at Ex.
36); Tr. 101-02 (citing Yukitoshi Takahashi, Infections as Causative Factors of Epilepsy,
1 FUTURE NEUROLOGY 291 (2006) (Ex. 85)); Ex. 69.) Following a subacute or prodromal
phase, T cells cross-react with glutamate receptors in the central nervous system
leading to autoantibodies and Rasmussen’s encephalitis.23 (Ex. 23, p. 17; Tr. 101-05
(citing Takahashi, supra, at Ex. 85, p. 3, figs.1 & 6); see also Anjan Nibber et al.,
Antibodies to AMPA Receptors in Rasmussen’s Encephalitis, 20 EUR. J. PAEDIATRIC
NEUROLOGY 222 (2016) (Ex. 48); Sophia Varadkar et al., Rasmussen’s Encephalitis:
Clinical Features, Pathobiology, and Treatment Advances, 13 LANCET NEUROLOGY 195
(2014) (Ex. 49); Yukitoshi Takahashi et al., Autoantibodies and Cell-Mediated
Autoimmunity to NMDA-Type GluRε2 in Patients with Rasmussen’s Encephalitis and
Chronic Progressive Epilepsia Partialis Continua, 46 EPILEPSIA 152 (2005) (Ex. 50).)
23 In light of the analysis that follows, it is not necessary to address the specific link that Dr. Steinman
seeks to draw between the flu vaccine and the glutamate receptors. Briefly, Dr. Steinman performed a
BLAST search and identified a peptide sequence from the influenza A hemagglutinin protein, which was a
component in the 2015-2016 flu vaccine, with 7 out of 12 homology with the NMDA-R-glutamate receptor
epsilon 2. (Ex. 69, p. 5; Tr. 94 (citing Influenza Virus Vaccine for the 2015-2016 Season: Cumulative
2015/2016 Season Lot Release Status, FED. DRUG ADMIN. (last updated Dec. 16, 2015) (Ex. 73)), 144-
49.) Dr. Steinman explained that the hemagglutinin protein serves a similar purpose as the L1 protein in
the HPV vaccine. (Tr. 89.) Additionally, hemagglutinin has been identified as a potential cross-reactive
molecule with glutamate receptors associated with Rasmussen’s encephalitis. (Id. at 105-06 (citing
Yukitoshi Takahashi, supra, at Ex. 85, p. 3, fig.4).) Dr. Steinman also explained that T cell cross reactions
between components of the flu vaccine and glutamate receptors have been identified by lymphocyte
stimulation tests, which measure “how T cells are responding to an antigen.” (Tr. 108-11 (citing Yukitoshi
Takahaski et al., Vaccination and Infection as Causative Factors in Japanese Patients with Rasmussen
Syndrome: Molecular Mimicry and HLA Class I, 13 CLINICAL & DEVELOPMENTAL IMMUNOLOGY 381 (2006)
(Ex. 86)).) The identified sequence is part of a twenty-five amino acid protein segment of hemagglutinin
shown to induce antibodies following a flu infection. (Ex. 69, pp. 5-6 (citing Niloufar Kavian et al.,
Vaccination with ADCC Activating HA Peptide Epitopes Provides Partial Protection from Influenza
Infection, 38 VACCINE 5885 (2020) (Ex. 75)).) Dr. Steinman therefore concluded that the flu vaccine can
“trigger an immune reaction to the Glutamate receptor, targeted in Rasmussen’s [encephalitis].” (Id. at 7.)
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Although Rasmussen’s encephalitis is considered an ultra-rare orphan condition
(Tr. 84), Dr. Steinman identified several case reports associating vaccinations with
Rasmussen’s encephalitis (Id. at 97). One such case report identified two patients who
reported that they developed Rasmussen’s encephalitis after vaccination. (Id. at 99-101
(citing Yukitoshi Takahashi et al., Vaccination and Infection as Causative Factors in
Japanese Patients with Rasmussen Syndrome: Molecular Mimicry and HLA Class I, 13
CLINICAL & DEVELOPMENTAL IMMUNOLOGY 381 (2006) (Ex. 86)).) One patient developed
seizures two months after vaccination, had MRI lesions on his frontal lobe, and “had
autoimmune antibodies against glutamate receptor epsilon 2.” (Id. at 100 (citing
Takahashi et al., supra, at Ex. 86).) The second patient developed aseptic meningitis
three weeks after receiving the MMR vaccine, and then developed seizures. (Id. at 100-
01 (citing Takahashi et al., supra, at Ex. 86).)
Dr. Steinman acknowledged that the studies he identified linking the flu vaccine
to Rasmussen’s encephalitis also identify infection as a cause. (Tr. 112 (citing
Takahashi, supra, at Ex. 85, p. 5, fig.5).) However, he asserted that E.M.’s physicians
ruled out infection as a possible cause. (Id. at 112-13 (discussing Ex. 152), 122-25
(citing Ex. 139), 170-71 (citing Ex. 134, p. 1926).) He noted that E.M. did have a
positive HSV IgM test; however, he explained that this test does not differentiate
between HSV type 1 or type 2 and, when tested again for HSV using IgG, she was
positive for HSV type 1, which is very common and is not necessarily evidence of an
acute infection. (Id. at 114-16.) Instead, Dr. Steinman suggested that the positive HSV
IgM results were possibly due to E.M’s treatment with plasmapheresis. (Id. at 119.)
Additionally, E.M.’s brain biopsy, which did find T cells, did not show any evidence of
HSV. (Id. at 116-18 (discussing Ex. 152), 125-26 (discussing Ex. 139).) Nor did her
CSF results. These results, according to Dr. Steinman, suggest that there is an
inflammatory response in the brain; however, it is unlikely a result of an HSV infection.
(Id. at 118.) Ultimately, Dr. Steinman opined that, based on her lab results, E.M. was
infected with HSV at some point in her life, “but certainly not in her brain or in her CSF.”
(Id. at 120-21.)
With respect to timing, Dr. Steinman opined that between one to two days and
eight weeks is “an acceptable time frame between vaccinations and onset of
neuroinflammatory condition.” (Tr. 162-63 (citing Lawrence B. Schonberger et al.,
Guillain-Barre Syndrome Following Vaccination in the National Influenza Immunization
Program, United States, 1976-1977, 110 AM. J. EPIDEMIOLOGY 105 (1979) (Ex. 96)).) Dr.
Steinman cited a review article that analyzed cases of inflammatory central nervous
system conditions, including encephalitis, optic neuritis, and myelitis, following
administration of various vaccines, including both the flu and HPV vaccine, and
determined that onset occurred within days to around five months. (Tr. 164-65 (citing
Dimitrios Karussis & Panayiota Petrou, The Spectrum of Post-Vaccination Inflammatory
CNS Demyelinating Syndromes, 13 AUTOIMMUNITY REVS. 215, 218-19 (2014) (Ex. 42,
pp. 4-5)).) He noted that E.M. received the HPV vaccine on July 20, 2015, and started
experiencing visual disturbances approximately one month later, on August 15, 2015.
(Ex. 23, p. 40; Tr. 79, 121-22, 185-88.) He further noted that petitioner began
experiencing papilledema around September 15, 2015. (Ex. 23, p. 40.) According to
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Dr. Steinman, this timeline “is consistent with the onset of neuroinflammation following
vaccination.” (Ex. 23, p. 40 (citing Til Menge et al., Neuromyelitis Optica Following
Human Papillomavirus Vaccination, 79 NEUROLOGY 285 (2012) (Ex. 47); L. Bennetto &
N. Scolding, Inflammatory/Post-Infectious Encephalomyelitis, 75 J. NEUROLOGY
NEUROSURGERY & PSYCHIATRY (SUPP. 1) i22 (2004) (Ex. 58)); Tr. 169.)
Dr. Steinman further explained that E.M. received her flu vaccination on
November 10, 2015. (Tr. 78.) He acknowledged that petitioner did not begin having
seizures until December 9, 2015; however, he maintained that, “[i]n some patients, a
prodromal period of mild hemiparesis or infrequent seizures might precede the onset of
the acute stage by up to several years.” (Ex. 23, p. 40 (quoting Varadkar et al., supra,
at Ex. 49); Tr. 215-16.) He explained further that the lesions on E.M.’s MRI in
September may have been evidence that something was “brewing” or “preclinical
manifestations” of what would eventually become (but was not yet) Rasmussen’s
encephalitis. (Tr. 211, 216-18.) Nonetheless, Dr. Steinman opined that, in his opinion,
the flu vaccine was a contributing factor in E.M.’s development of Rasmussen’s
encephalitis. (Id. at 218-19.) Dr. Steinman opined that onset of seizures beginning
December 9, 2015, following a flu vaccination administered on November 10, 2015,
constitutes an appropriate timeframe from which to infer causation. (Tr. 165-69 (citing
Karussis & Petrou, supra, at Ex. 42; William Huynah et al., Post-Vaccination
Encephalomyelitis: Literature Review and Illustrative Case, 15 J. CLINICAL NEUROSCI.
1315 (2008) (Ex. 98) (patient with bilateral optic neuropathies who developed ADEM
three months after receipt of a flu vaccine); S. Vilain et al., Encephalomyelitis and
Bilateral Optic Perineuritis After Influenza Vaccination, 277 BULLETIN SOCIETE BELGE
D’OPHTALMOLOGIE 71 (2000) (Ex. 106) (patient who developed presumptive
encephalomyelitis diagnosis, with symptoms that included headaches, urinary retention,
bilateral optic disk swelling, and mild bilateral visual defect, five days after receiving a flu
vaccination); Sabrina Ravaglia et al., Post-Infectious and Post-Vaccinal Acute
Disseminated Encephalomyelitis Occurring in the Same Patients, 251 J. NEUROLOGY
1147 (2004) (Ex. 112) (two patients who suffered a relapse of post-infectious
encephalomyelitis and myelitis roughly two weeks after receiving a flu vaccine); Paolo
Pellegrino et al., Acute Disseminated Encephalomyelitis Onset: Evaluation Based on
Vaccine Adverse Events Reporting Systems, 8 PLOS ONE e77766 (2013) (Ex. 93)
(VAERS and EudraVigilance post-authorisation module data reveals that most patients
developed ADEM between 2 and 30 days following flu or HPV vaccination, with some
patients reporting even longer after vaccination)).)
ii. Jeffrey M. Silverman, M.D.
Petitioners also presented the opinion of Dr. Jeffrey M. Silverman. Dr. Silverman
submitted one expert report and testified during the entitlement hearing. He was offered
without objection as an expert in radiology.24 (Ex. 68; Tr. 267.) Dr. Silverman reviewed
24 Dr. Silverman is a board-certified radiologist. (Ex. 68, p. 1; Ex. 137, p. 3.) He received his medical
degree from University of California San Diego School of Medicine, completed an internship in internal
medicine at Cedars-Sinai Medical Center, and completed a residency in diagnostic radiology at Cedars-
Sinai Medical Center. (Ex. 68, p. 1; Ex. 137, p. 2; Tr. 261.) He also completed a fellowship in
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E.M.’s various brain MR scans, as well as her orbit MR scan, cervical spine MR scan,
and head PET-CT. (Ex. 68, p. 2; Tr. 267.) In his report, Dr. Silverman offered three
observations:
• E.M.’s September 25, 2015 MRI study “showed not only evidence of left optic
neuritis and a few bilateral hyperintense nonspecific nonenhancing findings in the
subcortical white matter” but also “a small volume of left temporal lobe abnormal
signal on the T2 weighted and T2 weighted FLAIR sequences that does not have
evidence of enhancement or restricted diffusion.” (Ex. 68, p. 3.)
• E.M.’s December 29, 2015 MRI study showed “new abnormal signal and other
areas of worsening abnormal signal in the brain.” (Id.)
• “The abnormal findings have progressed (with areas of atrophy and gliosis) as
reflected in the November 15, 2019 MR scan.” (Id.)
During the hearing, Dr. Silverman expanded on these observations, presenting
several images from the MRI studies and also addressing the significance of certain
findings from an MRI conducted in the interim, on December 12, 2015. Pertinent to the
analysis below, Dr. Silverman acknowledged that the left temporal lobe abnormality
seen on the September 25, 2015 MRI was not visible on the December 12, 2015 MRI.
(Tr. 282, 309.) However, he explained that inflammatory lesions can wax and wane
over time, whereas an MRI is only a snapshot; that intervening treatment can be
confounding; and that the technology used between the two scans differed significantly.
(Id. at 282-83, 314-15, 572-91.) In effect, the September 25, 2015 MRI was more
sensitive than the December 12, 2015 MRI. (Id. at 572-91.) In particular, the scanner
used in September was 3 tesla with an echo train length of 1, whereas the scanner
used on December 12 was 1.5 telsa with an echo train length of 14. (Id. at 578-79.)
According to Dr. Silverman, these are meaningful differences that have “significant
effects of image quality.” The higher tesla improves the contrast between “signal” and
“noise,” and the shorter echo train reduces spatial blurring. (Id.) These differences will
affect how conspicuous a lesion appears on the resulting imaging, meaning that the two
scans are not an “apples to apples” comparison. (Id. at 580-81.) Thus, Dr. Silverman
opines that the seeming disappearance of some of E.M.’s September lesions is actually
due, at least in part, to the difference in MRI technology. (Id. at 581.) Additionally, he
opines that E.M.’s MRIs, beginning with her September 25, 2015 MRI, showed a
progression of inflammatory abnormalities predominantly on the left side. (Id. at 296.)
According to Dr. Silverman, this opinion “mostly” agrees with the radiology reports within
the medical records, except that the September 25, 2015 radiology report did not
CT/Ultrasound/MRI Body Imaging with Special Emphasis in Cardiothoracic imaging at Cedars-Sinai
Medical Center. (Ex. 68, p. 1; Tr. 262.) He has practiced as an attending physician since 1991. (Ex. 68,
p. 1.) From 1995 to 2001, he served as the Director of Magnetic Resonance Imaging at Cedars-Sinai
Medical Center. (Ex. 68, p. 1; Ex. 137, p. 11; Tr. 263.) He currently works as a Clinical Associate
Professor of Radiology at the University of Southern California Keck School of Medicine. (Ex. 68, p. 1;
Ex. 137, p. 10; Tr. 260.) Throughout his career, he has reviewed over 10,000 brain and spine MR scans.
(Ex. 68, p. 1.) Additionally, he has authored multiple peer-reviewed articles and lectured on the specialty
of MR imaging. (Id.; Ex. 137, pp. 12-28.)
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separately identify the left temporal lobe abnormality identified by Dr. Silverman, though
he suggests that it may have been implicitly included in the finding of “numerous
scattered small foci of T2 hyperintensity.” (Id. at 304-05 (discussing Ex. 8).) Dr.
Silverman explained that, from a radiology perspective, the lesions are most likely
inflammatory; however, determining whether they are demyelinating is a matter of
clinical correlation. (Id. at 286-87, 300.)
b. Respondent’s Experts
i. Jenny Linnoila, M.D., Ph.D.
Respondent offered an expert neurology opinion from Dr. Jenny Linnoila. Dr.
Linnoila submitted three expert reports and testified at the entitlement hearing. She was
offered without objection as an expert in neurology, neuroimmunology, and autoimmune
neurology.25 (Exs. C, F, H; Tr. 331.)
Dr. Linnoila opined that E.M. developed optic neuritis in the autumn of 2015.
During the hearing, she noted that the timing of onset is unclear from the medical
records, but ultimately placed onset in late August or early September. (Tr. 347-48,
463-64.) Because the specific findings of afferent papillary defect (“ADP”) and red
desaturation were not observed until her September 24, 2015 encounter, Dr. Linnoila
opined that E.M.’s optic neuritis was initially “fairly mild” and reached its maximum
severity after weeks, and around the time of her September 24, 2015 encounter. (Ex.
C, pp. 6-7.) She opined that E.M. had a good clinical recovery following her steroid
treatment. (Id. at 7-8.) She stressed that the optic neuritis had resolved clinically,
according to patient report, by early November. (Id. at 7; Tr. 348-50.) During the
hearing, she also testified that, based on E.M.’s December 12, 2015 MRI, the optic
neuritis also resolved radiologically by that time. (Tr. 362-63.) In her initial report,
however, she had opined that E.M.’s December 10, 2015 lumbar puncture, which
showed improved but still elevated white blood cell count in her CSF, was consistent
with still “resolving” optic neuritis. (Ex. C, p. 8 (citing Ex. 8, p. 542).)
Dr. Linnoila disagreed that the scattered lesions noted on E.M.’s September 25,
2015 MRI report were related to her optic neuritis, as they were appropriately
characterized as non-specific. (Ex. C, p. 7 (citing Ex. 8, p. 742).) However, during the
hearing, she agreed that a left temporal lobe lesion identified by Dr. Silverman, but not
explicitly referenced in the radiology report, was associated with the optic neuritis. (Tr.
25 Dr. Linnoila is a board-certified neurologist. (Ex. C, p. 2; Ex. D, p. 5; Tr. 321.) She received her
medical degree and her Ph.D. in basic neuroscience and molecular pharmacology from the University of
Pittsburgh in 2009 and 2007, respectively. (Ex. C, p. 1; Ex. D, p. 1; Tr. 318.) She completed a joint
Harvard Neurology Residency Training Program at Massachusetts General Hospital and Brigham and
Women’s Hospital. (Ex. C, p. 1; Ex. D, p. 1.) Dr. Linnoila then completed a clinical fellowship in
Autoimmune Neurology at the Mayo Clinic in Rochester, Minnesota. (Ex. C, p. 1; Ex. D, p. 1; Tr. 320.)
After completing the fellowship, she returned to Massachusetts General Hospital to start a clinical practice
in paraneoplastic and autoimmune neurology, as well as a research program focused on creating a
rodent model of autoimmune encephalitis. (Ex. C, p. 1.) She has written several review articles and book
chapters on autoimmune encephalitis, as well as peer-reviewed basic science and clinical research
articles. (Id. at 2; Ex. D, pp. 6-8.)
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426-27.) Thus, Dr. Linnoila agreed that E.M.’s optic neuritis constituted a broader
demyelinating syndrome. (Id. at 567-68.) She stressed, however, that the left temporal
lobe lesion was not evidenced on E.M.’s December 12, 2015 MRI, meaning that, in her
opinion, it had resolved prior to that point, consistent with recovery due to E.M.’s steroid
treatment for the optic neuritis.26 (Tr. 420-27.)
Dr. Linnoila explained that, in a patient of E.M.’s age, inflammation and resulting
demyelination is the most likely cause of optic neuritis. (Ex. C, p. 7.) She also agreed
that MOG-related syndrome, a demyelinating syndrome, is among the causes of optic
neuritis, as indicated by Dr. Steinman. (Id. at 10 (citing Chang & Pineles, supra, at Ex.
C, Tab 8); Tr. 351.) In E.M.’s case, Dr. Linnoila opined that the optic neuritis is
consistent with a demyelinating cause and, further, that “it is possible that her optic
neuritis, in particular, could have been secondary to MOG-antibody-related disease.”
(Ex. C, pp. 10, 17 (citing Yael Hacohen & Brenda Banwell, Treatment Approaches for
MOG-Ab-Associated Demyelination in Children, 21 CURRENT TREATMENT OPTIONS
NEUROLOGY 1 (2019) (Ex. C, Tab 16)).) However, Dr. Linnoila does not agree that
E.M.’s HPV vaccine caused her optic neuritis, stressing that linear sequence homology
is insufficient to demonstrate molecular mimicry. (Id. at 11; Tr. 351.)
Dr. Linnoila further opined that E.M.’s condition from December of 2015 onward
is best characterized as Rasmussen’s encephalitis. Dr. Linnoila emphasized that
Rasmussen’s encephalitis is distinct from “autoimmune encephalitis,” stressing that, in
E.M.’s case, “testing for antibodies that are known to be associated with autoimmune
encephalitis was negative.” (Ex. C, p. 8 (citing Ex. 8, p. 1359).) Dr. Linnoila described
Rasmussen’s encephalitis as a “chronic, progressive condition of one-half of the brain,”
in which that half of the brain atrophies, causing seizures and neurological deficits. (Tr.
396-97.) On the other hand, autoimmune encephalitis causes alteration of mental
status and seizures, focal findings on an MRI, or abnormalities in the spinal fluid. (Id. at
400-02 (citing Graus et al., supra, at Ex. 153).) Additionally, Dr. Linnoila explained that
ADEM, which was also in E.M.’s differential diagnosis, causes large disseminated
demyelinating lesions throughout the brain and spinal cord. (Id. at 403-04.) Dr. Linnoila
concluded that E.M.’s subsequent neurological disorder “is most consistent with
Rasmussen’s encephalitis,” not ADEM. (Ex C, p. 10; Tr. 352, 405.)
Dr. Linnoila confirmed that scientific literature does not document an association
between optic neuritis and Rasmussen’s encephalitis and noted that, although Dr.
Steinman offered literature showing a link between uveitis and Rasmussen’s
encephalitis, uveitis is distinct from inflammation of the optic nerve. (Ex. C, p. 11; Tr.
381-83.) Specifically, a review published by Fauser et al. “concluded that patients who
develop [Rasmussen’s encephalitis] were not more likely to have a history of
autoimmune disease than control patient.” (Ex. H, p. 3 (citing Susanne Fauser et al.,
Rasmussen Encephalitis: Predisposing Factors and Their Potential Role in Unilaterality,
26 During the hearing, petitioner’s counsel questioned Dr. Linnoila’s qualifications to opine on E.M.’s
MRIs, given that she is not board eligible in diagnostic radiology nor had she completed any diagnostic
radiology training. (Tr. 488-502.) Dr. Linnoila explained that she reads MRIs on a daily basis to treat her
patients. (Id. at 551-53.)
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63 EPILEPSIA 108 (2022) (Ex. H, Tab 4)).) During the hearing, Dr. Linnoila
acknowledged that patients with Rasmussen’s encephalitis often have “unilateral early
acquired structural brain lesions” or facial autoimmune diseases that affect the skin or
eye; however, she pointed out that E.M. did not track the course of the patients with
early structural lesions, nor was optic neuritis one of the associated autoimmune
diseases. (Tr. 529-31 (quoting Fauser et al., supra, at Ex. H, Tab 4, p. 10).) Thus, she
disagreed that optic neuritis can lead to Rasmussen’s encephalitis. (Id. at 352.)
Dr. Linnoila acknowledged that both conditions involve neuroinflammation;
however, “neuroinflammation is found in many disorders of the brain that do not
represent the same disease process.” (Ex. H, p. 2 (citing Eduardo Candelario-Jalil et
al., Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging
Modalities, 53 STROKE 1473 (2022) (Ex. H, Tab 3); Mahmoud S. Alghamri et al.,
Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms,
Pharmacological Targets, and Neuropharmaceutical Developments, 12 FRONTERS
PHARMACOLOGY 1 (2021) (Ex. H, Tab 1)).) She stressed that these two conditions are
distinct in that optic neuritis is an autoimmune demyelinating condition that is responsive
to treatment and Rasmussen’s encephalitis is not.27 (Id.; Ex. C, p. 11; Tr. 345.)
However, during the hearing, while she again reiterated that Rasmussen’s encephalitis
was distinct from autoimmune encephalitis, she also acknowledged that Rasmussen’s
encephalitis can involve an autoimmune process and can be considered an immune
mediated disease. (Tr. 343-45, 512-13.) Specifically, T cells in the brain evidence that
such an autoimmune process is taking place. (Id. at 343-45.) She also acknowledged
that a patient can have both a demyelinating condition and an autoimmune encephalitis
at the same time. (Id. at 511-12.)
Dr. Linnoila explained that infections, and particularly the fevers associated with
infections, can trigger Rasmussen’s encephalitis. (Tr. 357 (citing Fauser et al., supra, at
Ex. H, Tab 4).) She indicated that “autoimmune processes are often secondary or . . .
triggered by some infectious process happening first, and then” the immune system
warps and manifests as an autoimmune reaction. (Id. at 358-59.) Further, she
described the infection as usually being the first event, followed by inflammation, and
then leading to Rasmussen’s encephalitis. (Id. at 360.) Dr. Linnoila opined that E.M.’s
27 Dr. Linnoila explained Dr. Steinman’s theory as being based on the presumption that Rasmussen’s
encephalitis and the associated epilepsy “are manifestations of an autoimmune disease.” (Ex. C, p. 13
(quoting Ex. 23, p. 17).) However, Dr. Linnoila noted that the National Institute of Neurological Disorders
and Stroke (“NINDS”) definition of Rasmussen’s encephalitis states that the condition “has features of an
autoimmune disease,” not that it is one. (Ex. C, p. 13.) Instead, she explained that “Rasmussen’s
encephalitis has been associated with T cell infiltration in the brains of patients”; however, it is “also
associated with severe seizures, which themselves have been shown to cause immune cells to enter the
brain,” resulting in inflammation. (Id.) This inflammation then leads to more seizures, creating an
inflammation-seizure cycle, which she explains is why these seizure disorders can be treated with anti-
inflammatory medications, even though they are not autoimmune disorders. (Ex. C, p. 13.) She opined
that because “it is difficult to separate the effect of seizures from the Rasmussen’s encephalitis itself and
Rasmussen’s encephalitis is notoriously refractory to treatment,” it is not solely an autoimmune
neurogenic process. (Ex. C, p. 14 (citing Jenny Linnoila & Sean J. Pittock, Autoantibody-Associated
Central Nervous System Neurologic Disorders, 36 SEMINARS NEUROLOGY 382 (2016) (Ex. C, Tab 14)).)
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Rasmussen’s encephalitis was most likely the results of a viral illness and fevers, not
the flu vaccine. (Ex. H, p. 5.) She noted that, according to the EMTs, E.M. had a fever
of 101.1 when she was evaluated in the ambulance. (Tr. 486. But see id. at 537-47
(cross-examination regarding the presence of fever).) Moreover, “E.M. initially tested
positive for IgM antibodies for herpes simplex virus (HSV), which implies early
infection.” (Ex. H, p. 5 (citing Ex. 8, p. 1854); Tr. 506.) Dr. Linnoila acknowledged that
even a positive IgM test could be positive for as many as 12 months and that E.M.’s
biopsy showed no evidence of HSV; however, she noted that infections outside of the
brain can have neurological consequences. (Tr. 510 (citing Ex. 134, p. 1341), 519-20,
553.) She further explained that, even if HSV was not the culprit, E.M. had reported a
sore throat and some chills for two days before her seizure. (Id. at 559-61 (citing Exs.
14, 115).)
Dr. Linnoila explained that, apart from case reports, she was unable to find any
literature that linked any vaccine to Rasmussen’s encephalitis. (Tr. 340-41.)
Additionally, she explained that the studies cited by petitioner do not conclusively link
vaccinations and Rasmussen’s encephalitis, and instead call for immunogenic studies
to investigate the possible link. (Id. at 477-78 (citing Takahashi, supra, at Ex. 85, p. 3).)
These studies, however, also report infection as a possible theoretical cause. (Id.
(citing Takahashi, supra, at Ex. 85, p. 3).) Therefore, she opined that Rasmussen’s
encephalitis “developed after what was most likely a viral illness and low grade fevers,
which preceded the development of seizures that were difficult to control and
progressed overtime,” which then led “to a cycle of inflammation, which can exacerbate
circumstances by leading to a cycle of further seizures and inflammation.” (Ex. C, p. 18;
Ex. H, p. 5.) Dr. Linnoila later acknowledged that only about 15% of Rasmussen’s
encephalitis patients have a proceeding fever. (Tr. 529 (citing Fauser et al., supra, at
Ex. H, Tab 4).)
Dr. Linnoila also concluded that E.M.’s Rasmussen’s encephalitis occurred after
her optic neuritis had resolved in October of 2015, and five months after the
administration of the second HPV vaccine. Thus, she does not believe “that the timing
for Rasmussen’s encephalitis fits with an adverse event from E.M.’s second HPV shot.”
(Ex. C, pp. 16-17; Ex. F, p. 2.) When asked about a prodromal phase for Rasmussen’s
encephalitis, Dr. Linnoila explained that this is a general term that only means there is
an initial symptom that may then develop into a syndrome. (Tr. 373-74.) She opined
that a prodromal phase lasting three to four months would be extremely unlikely. (Id. at
468-69.) She explained that, if there was a prodrome in this case, it would encompass
the fact that E.M. was not feeling well and had a fever before her seizure; it would not
extend back to her optic neuritis. (Id. at 470-72.) Dr. Linnoila also acknowledged E.M.’s
problems in math in the months prior to her seizures, but explained that, in her opinion,
this is not evidence of her Rasmussen’s encephalitis developing and, instead, may be a
symptom of the steroids she was on for her optic neuritis. (Id. at 473.) Additionally, she
noted that there is no MRI evidence in this case of Rasmussen’s encephalitis beginning
before E.M.’s December MRI. (Id. at 376-77.) Therefore, Dr. Linnoila explained that the
first clinical event of petitioner’s Rasmussen’s encephalitis was her seizure. (Id. at 469-
70.) She concludes that “[b]ased on the lack of a demonstrated link between optic
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neuritis and Rasmussen’s encephalitis . . . . as well as the timing of the initial seizures, it
cannot be logically concluded that the vaccine more likely than not caused E.M.’s
Rasmussen’s encephalitis.” (Ex. C, p. 17.) Dr. Linnoila acknowledged the case reports
by Takahaski et al., which reported one patient developing Rasmussen’s encephalitis
two months after the Japanese encephalitis vaccine and another patient developing
Rasmussen’s encephalitis a year after the MMR vaccine, but explained that she “would
not draw any conclusions from that data.” (Tr. 480.)
ii. Dr. Christine McCusker, M.Sc., M.D.
Respondent’s immunology expert, Dr. McCusker, submitted three expert reports
and testified during the entitlement hearing. She was proffered, without objection, as an
expert in pediatric immunology.28 (Exs. A, E, G; Tr. 610.)
Dr. McCusker explained that “optic neuritis is characterized by sudden onset
vision loss, usually unilateral, and associated with demyelination of the optic nerve.”
(Ex. A, p. 3.) She stated that the cause is unknown but noted that there is often “a
history of an acute viral illness in the month preceding onset of symptoms leading to the
suggestion that there may be an infectious trigger in this disease.” (Id.) She
acknowledged that vaccination “has also been temporally linked to onset of [optic
neuritis].” (Id.) She further explained that Rasmussen’s encephalitis “is a rare
progressive disease, usually with childhood onset, characterized by hemispheric brain
inflammation leading to, often unilateral, brain atrophy.” (Id. at 4 (citing Tiziana Granata
& Frederick Andermann, Rasmussen Encephalitis, 111 HANDBOOK CLINICAL NEUROLOGY
511 (2013) (Ex. A, Tab 7)).) Like optic neuritis, the cause of the disease is unknown,
but Dr. McCusker noted that viral infection has been proposed as a trigger, especially
because triggering of CD8+ve T cells that target astrocytes and neurons, which has
been associated with Rasmussen’s, is a sign of viral infection. (Id. (citing Granata &
Andermann, supra, at Ex. A, Tab 7); Ex. E, p. 3 (citing Granata & Andermann, supra, at
Ex. A, Tab 7); Ex. G, p. 4 (citing Granata & Andermann, supra, at Ex. A, Tab 7).) Dr.
McCusker opined that optic neuritis and Rasmussen’s encephalitis are immunologically
different diseases that would require different immune responses. (Tr. 703-04.)
Specifically, optic neuritis is caused by Th17 T cell inflammation, whereas the formation
of cytotoxic T cells causes Rasmussen’s encephalitis. (Id. at 704.) Usually, if a patient
has two autoimmune conditions, Dr. McCusker testified that they “follow the same path.”
(Id. at 709.)
28 Dr. Christine McCusker holds a Master of Science degree in molecular biology and a medical degree,
both received from McMaster University in Ontario, Canada. (Ex. A, p. 1; Ex. B, p. 1; Tr. 601.) She is
certified by the American Board of Pediatrics and by the Royal College of Physicians and Surgeons of
Canada and by the College des Medecins du Quebec in both allergy and clinical immunology and
pediatrics. (Ex. A, p. 1; Ex. B, p. 2; Tr. 605.) She currently serves as an associate professor of pediatric
allergy and immunology at McGill University and as Division Director of Pediatric Allergy, Immunology,
and Dermatology at the Montreal Children's Hospital. (Ex. A, p. 1; Ex. B, p. 3; Tr. 600, 603-04.) In her
clinical capacity, Dr. McCusker sees an average of 50 to 120 children per week in allergy and clinical
immunology and urgent care. (Ex. A, p. 2.) In her research capacity, she has submitted roughly 100
publications, primarily focused on immune response regulation. (Ex. B, pp. 20, 25-36; Ex. A, p. 1.)
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Dr. McCusker stressed that there is no evidence that the HPV vaccine causes
optic neuritis or encephalitis. She cited a study by Baxter et al., which found no
increased frequency of optic neuritis within four to six weeks following vaccination. (Ex.
A, p. 3 (citing Baxter et al., supra, at Ex. A, Tab 1); Ex. E, pp. 2-3; Ex. G, p. 5; Tr. 612-
14, 618.) During the hearing, Dr. McCusker acknowledged that the Baxter et al. study
reported that, while there were no statistically significant associations found between
vaccines and optic neuritis, larger studies were needed to completely rule out
associations. (Tr. 726 (citing Baxter et al., supra, at Ex. A, Tab 1, p. 3).) She also
discussed a study by Liu et al., which examined the risk of autoimmune disorders,
including optic neuritis, following the HPV vaccine. (Ex. A, p. 3 (citing Erin Y. Liu et al.,
Quadrivalent Human Papillomavirus Vaccination in Girls and the Risk of Autoimmune
Disorders: The Ontario Grade 8 HPV Vaccine Cohort Study, 190 CANADIAN MED. ASS’N
J. E648 (2018) (Ex. A, Tab 2)); Ex. G, p. 5.) Among almost 300,000 girls, the Liu et al.
study found no increased frequency of demyelinating disease of the central nervous
system following the HPV vaccination. (Ex. A, p. 3; Tr. 620-22.) Additionally, another
study that “examined all codes for [optic neuritis] and compared the frequency of onset
with HPV vaccination using data from 4.6 million individuals” found “no difference in
frequency of [optic neuritis] following HPV vaccination.” (Ex. A, p. 4 (citing Sridhar et
al., supra, at Ex. A, Tab 4)); Tr. 624-25.) However, again, Dr. McCusker later
acknowledged that the study called for additional larger studies to confirm their result.
(Tr. 726-27 (citing Sridhar et al., supra, at Ex. A, Tab 4, p. 7).) Another study by
Mouchet et al. found no significant association between the HPV vaccine and
demyelinating diseases, including optic neuritis. (Ex. A, p. 4 (citing Julie Mouchet et al.,
Human Papillomavirus Vaccine and Demyelinating Diseases—A Systematic Review
and Meta-Analysis, 132 PHARMACOLOGICAL RSCH. 108 (2018) (Ex. A, Tab 5)); Tr. 626-
28.) Dr. McCusker also discussed a study by Miranda et al. which analyzed over two
million girls who had received the HPV vaccine to see if there was any causal
relationship between the HPV vaccine and autoimmune diseases. (Tr. 622-23 (citing
Sara Miranda et al., Human Papillomavirus Vaccination and Risk of Autoimmune
Diseases: A Large Cohort Study of Over 2 Million Young Girls in France, 35 VACCINE
4761 (2017) (Ex. A, Tab 3)); Ex. A, p. 3.) The study did not find an increased risk of
optic neuritis, but did find an increased incidence of GBS. (Tr. 623 (citing Miranda et al.,
supra, at Ex. A, Tab 3).) While Dr. McCusker acknowledged that there have been
cases demonstrating a temporal association between the HPV vaccine and optic
neuritis, she stressed that no evidence supports a causal relationship. (Ex. A, p. 4; Tr.
614-19, 629.)
Regarding Dr. Steinman’s theory that the HPV vaccine can cause Rasmussen’s
encephalitis via molecular mimicry, Dr. McCusker emphasized that, in the earliest stage
of inflammation in patients with the condition, “there is the formation of microglial
nodules with increase in expression of the innate immunity.” (Ex. A, p. 5 (citing Anna R.
Trӧscher et al., Microglial Nodules Provide the Environment for Pathogenic T Cells in
Human Encephalitis, 137 ACTA NEUROLPATHOLOGICA 619 (2019) (Ex. A, Tab 8)); Tr. 673-
74.) However, “there is no evidence of T cells in the areas of these nodules although
expression of chemokines involved in attracting [CD8+ve CTL] cells are increased.”
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(Ex. A, p. 5 (citing Trӧscher et al., supra, at Ex. A, Tab 8).) During the intermediate
stage of inflammation, Dr. McCusker explained that T cells infiltrate the area of the
micronodules and form secondary nodules. (Ex. A, p. 5 (citing Trӧscher et al., supra, at
Ex. A, Tab 8); Tr. 674.) However, she noted, that the T cells do not just appear in the
brain, and instead, must be called there. (Tr. 679-80.) At this stage, Dr. McCusker
explained that cytokines are expressed, and initial neurodegeneration occurs. (Ex. A, p.
5.) In the acute stage, “there is extensive [CD8+ve CTL] cell infiltration with significant
microglial cell activation and neurodegeneration.” (Ex. A, p. 5 (citing Trӧscher et al.,
supra, at Ex. A, Tab 8).) Dr. McCusker opined that Rasmussen’s encephalitis “is
initiated by increased expression of TLR3 and 7, usually increased in response to viral
RNA, followed by T cell infiltration and cell death.” (Ex. A, p. 5.) As support for her
hypothesis, Dr. McCusker explains that viruses such as HPV, EBV, CMV, and HSV
have been detected in the brain tissues of Rasmussen’s encephalitis patients. (Ex. A,
p. 5 (citing Shuai Chen et al., Elevated Expression of Human Papillomavirus Antigen in
Brain Tissue of Patients with Rasmussen’s Encephalitis, 126 EPILEPSY RSCH. 119
(2016) (Ex. 41)); Tr. 676 (citing Yao Zhang et al., Expression of Human
Cytomegalovirus Components in the Brain Tissues of Patients with Rasmussen’s
Encephalitis, 32 VIROLOGICA SINICA 115 (2017) (Ex. G, Tab 9)).) Dr. McCusker
theorized that, for the Rasmussen’s encephalitis to be limited to one area of the brain,
there must be an anatomical reason or the Rasmussen’s encephalitis must be the result
of a viral infection in that part of the brain. (Tr. 675.) Dr. McCusker noted that E.M. had
evidence of an acute viral (HSV) infection at the time of her hospitalization. (Ex. A, p. 6
(citing Ex. 8, p. 1854).) Additionally, E.M. “had uni-hemisphere disease and showed no
evidence of autoantibody formation and viral particles were not detected in the CNS.”
(Id.) Thus, Dr. McCusker opined that E.M. “first developed micronodules followed by T
cell infiltration and onset of symptoms.” (Id.) Had petitioner first developed T cell
autoimmunity after the HPV vaccination as Dr. Steinman suggested, Dr. McCusker
opined that petitioner would have bilateral disease. (Id. (citing Hania Kebir et al.,
Humanized Mouse Model of Rasmussen’s Encephalitis Supports the Immune-Mediated
Hypothesis, 128 J. CLINICAL INVESTIGATION 2000 (2018) (Ex. A, Tab 10)).)
Dr. McCusker noted that there are limitations with Dr. Steinman’s use of BLAST
searches to identify sequence homologies. (Ex. A, p. 6 (citing Christophe Benoist &
Diane Mathis, Autoimmunity Provoked by Infection: How Good Is the Case for T Cell
Epitope Mimicry?, 2 NATURE IMMUNOLOGY 797 (2001) (Ex. A, Tab 11)).) She noted that
“Dr. Steinman failed to provide any control analysis showing no other sequence
homology existed between the virus and other human proteins,” nor did he analyze any
other virus that may have infected” E.M. (Id.; Tr. 683-84.) Additionally, she explained
that Dr. Steinman “is postulating antigenic mimicry for activation of CD8+ve T cells”
without analyzing “the sequences for binding into class I major histocompatibility
antigens (MHC),” which “is required . . . to determine if any of the homologous
sequences are presentable to T cells via MHC.” (Ex. A, p. 6.) Finally, she explained
that Dr. Steinman would also need to analyze the MHC phenotype of E.M. “to determine
if she bears the appropriate MHCs for binding and presenting the relevant peptides to T
cells.” (Id.) Dr. McCusker also noted that the criteria Dr. Steinman used to identify
mimics is developed from studies performed on animals that do not “examine[]
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sequences from human papilloma virus.” (Ex. E, pp. 3-4 (citing Gautam et al., supra, at
Ex. 51; Gautam et al., supra, at Ex. 52; Gautam et al., supra, at Ex. 53).) Additionally,
Dr. McCusker noted that not all mimics are clinically relevant. (Tr. 669-70.)
Dr. McCusker performed her own BLAST search and highlighted that there is a
high frequency of matches that fit Dr. Steinman’s criteria, suggesting that “match
frequencies occur as a product of chance and do not represent a biologically meaningful
association.” (Ex. A, p. 7 (citing Andre Silvanovich et al., The Value of Short Amino
Acid Sequence Matches for Prediction of Protein Allergenicity, 90 TOXICOLOGICAL SCIS.
252 (2006) (Ex. 54)); Ex. G, p. 3).) She also performed a BLAST search for HSV,
specifically due to E.M.’s IgM positivity and the fact that viruses have been proposed as
a trigger for Rasmussen’s encephalitis, and identified some homology. (Tr. 690-91.)
Further, Dr. McCusker explained that T cells autoreactive to myelin basic protein have
been found in patients with and without MS, suggesting “the presence of these
autoreactive T cells are part of normal immunoregulation and do not necessarily
participate in the development of disease.” (Ex. A, p. 7 (citing Kohei Ota et al., T-Cell
Recognition of an Immuno-Dominant Myelin Basic Protein Epitope in Multiple Sclerosis,
346 NATURE 183 (1990) (Ex. 56); M. Pette et al., Myelin Basic Protein-Specific T
Lymphocyte Lines from MS Patients and Healthy Individuals, 40 NEUROLOGY 1770
(1990) (Ex. 57)).) Additionally, Dr. McCusker explained that the T cells identified by Dr.
Steinman as responsible for E.M.’s condition, CD8+ve T cells “do not recognize proteins
alone but rather they only identify proteins that have been picked up by MHC
molecules,” which “are used by the immune system to identify ‘self.’” (Id.) Therefore,
the identified protein sequences must be those that are identified by MHC molecules,
which, as Dr. McCusker explained, is unaddressed by Dr. Steinman’s BLAST searches.
(Ex. A, p. 7; Ex. E, p. 5.)
In addressing Dr. Steinman’s use of the Immune Epitope Data Base, Dr.
McCusker explained that Dr. Steinman’s criteria still do not identify any association
between the molecular mimics he singles out and autoimmunity. (Ex. E, p. 4.) Dr.
McCusker performed a similar analysis on six sequences from HSV and found that all of
these sequences met Dr. Steinman’s criteria. (Id. at 5.) However, there were also
“multiple references for these sequences being implicated in autoimmune diseases for
[three] of these sequences,” unlike the sequences identified by Dr. Steinman. (Id. at 4-
5.)
Dr. McCusker additionally challenged Dr. Steinman’s theory that the flu vaccine
can cause Rasmussen’s encephalitis. (Ex. G.) Dr. McCusker questioned the relevance
of a study by Kavian et al., noting that no patients suffered seizures caused by the
influenza-specific antibodies and that no study shows the presence of NMDA-R
antibodies in sera following the flu vaccine. (Ex. G, pp. 2-3 (citing Kavian et al., supra,
at Ex. 75).) She emphasized that E.M. received five flu vaccines prior to the one at
issue and “thus would have broad cross protective immunity to influenza.” (Id. at 3
(citing Ex. 8, p. 1752).) She further stressed that E.M. “did not have any pathologically
associated autoantibodies including NMDA-R despite extensive screening.” (Id.
(emphasis omitted).) While Dr. McCusker noted that several autoantibodies have been
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identified in patients with Rasmussen’s, she stressed that for “each autoantibody
specificity is not consistently found.” (Id.) She further noted that Rasmussen’s
encephalitis usually affects one hemisphere of the brain while proteins of identified
autoantibodies are expressed bilaterally. (Id. at 3-4.) She concluded that this
“suggest[s] that these autoantibodies are an epiphenomenon rather than a real
pathological mechanism” in Rasmussen’s encephalitis. (Id. at 4.) Finally, Dr. McCusker
also noted that a study performed by Kawai et al. reported “no increased risk of
encephalitis following influenza vaccine.”29 (Id. (citing Alison Tse Kawai et al., Absence
of Associations Between Influenza Vaccines and Increased Risks of Seizures, Guillain-
Barré Syndrome, Encephalitis, or Anaphylaxis in the 2012-2013 Season, 23
PHARMACOEPIDEMIOLOGY & DRUG SAFETY 548 (2014) (Ex. G, Tab 12)).) Dr. McCusker
also cited a study by Britton et al., where the “finding of infrequent varicella related
encephalitis” suggested “that vaccination reduces the incidence of encephalitis in
general.” (Ex. G, p. 5 (citing Philip N. Britton et al., Causes and Clinical Features of
Childhood Encephalitis: A Multicenter, Prospective Cohort Study, 70 CLINICAL
INFECTIOUS DISEASES 2517 (2020) (Ex. G, Tab 4)).) During the hearing, Dr. McCusker
discussed the Takahashi et al. article cited by Dr. Steinman and noted that the
lymphocyte stimulation was an expected immune response to a flu vaccine. Without a
control incorporating the flu vaccine and not the glutamate receptors, it is not possible to
isolate the significance of the glutamate receptors. (Tr. 696-700.)
Dr. McCusker explained that if petitioner’s HPV vaccine did cause her optic
neuritis, which then resolved, it is unlikely that the immune system would then trigger
the cytotoxic T cell response that occurs in Rasmussen’s encephalitis. (Tr. 704-06.) Dr.
McCusker noted that the HPV and flu vaccines were not live viruses and produced
antibodies, not the cytotoxic T cells that lead to Rasmussen’s encephalitis. (Id. at 676-
78.) Instead, Dr. McCusker pointed out that viral infections are a known cause of
Rasmussen’s encephalitis and can elicit that needed T cell response. (Id. at 691-92.)
In this case, Dr. McCusker interpreted E.M.’s IgG and IgM tests to indicate a primary
infection that could have caused her Rasmussen’s encephalitis. (Id. at 691, 739-40.)
Additionally, she performed a BLAST search because HSV is occasionally found in
biopsies of patients with Rasmussen’s encephalitis. (Id. at 690.) Additionally, HSV can
infect neurons. (Id. at 690-91.) During the hearing, Dr. McCusker acknowledged that
E.M.’s CSF PCR test, her January 12, 2016 IgG and IgM tests, and biopsy were
negative for HSV and confirmed that no viruses were found in E.M.’s central nervous
system. (Id. at 721-23, 744, 755.)
Regarding timing, Dr. McCusker noted that E.M. had her first seizure 4.5 months
after vaccination, when the HPV vaccination would have been cleared from her system.
(Ex. A, p. 6; Tr. 676.) She also noted that E.M.’s first seizure occurred within 30 days of
her flu vaccination. (Tr. 724.) Dr. McCusker cited an animal study that found seizure
activity began within three weeks of infusion with cells from Rasmussen’s encephalitis
donors. (Ex. A, p. 6 (citing Kebir et al., supra, at Ex. A, Tab 10); Ex. G, p. 5.) Dr.
McCusker did acknowledge that influenza infection has been linked to an increase in
29 At the hearing, Dr. McCusker acknowledged that this study only analyzed individuals 21 days post-
vaccination. (Tr. 729-30 (citing Kawai et al., supra, at Ex. G, Tab 12).)
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the risk of encephalitis; however, there was no increased risk up to 180 days after flu
vaccination. (Ex. G, p. 4 (citing Sara Ghaderi et al., Encephalitis After Influenza and
Vaccination: A Nationwide Population-Based Registry Study from Norway, 2017 INT’L J.
EPIDEMIOLOGY 1618 (2017) (Ex. G, Tab 11)).) Thus, Dr. McCusker concluded that the
onset of petitioner’s Rasmussen’s encephalitis was not temporally associated with her
HPV vaccination. (Ex. A, p. 6.)
VI. Analysis
This case presents an unusual and striking circumstance. E.M., by all measures,
was an active and healthy twelve-year-old child in the summer of 2015, received her
HPV vaccination in July, and subsequently suffered an uncommon syndrome of central
nervous system demyelination inclusive of left-side optic neuritis and at least some
degree of demyelination of the left side of the brain. The parties dispute whether that
condition fully resolved, but she had a seemingly good clinical recovery. After
completion of a steroid treatment, E.M. was doing well and was administered a flu
vaccine in November, just three or so months after her HPV vaccination. Less than a
month later, E.M. began experiencing seizures and successive MRIs showed a
progressive condition on the left side of her brain. A brain biopsy confirmed a T-cell
mediated encephalitis, consistent with Rasmussen’s encephalitis, an ultra-rare
neurologic condition distinct from her prior demyelinating condition. Although E.M.’s
condition eventually plateaued, she cannot walk independently and will continue to have
limited cognitive abilities, including a vocabulary of less than ten simple words and an
inability to answer even somewhat complex questions. (Tr. 19-20.) E.M.’s mother
testified that, around the time of her December hospitalization, E.M’s final words before
her cognitive ability declined were “Mama, I’m scared.” (Id. at 52.)
Petitioners offer three potential explanations: E.M.’s entire presentation was
caused by the HPV vaccine; E.M.’s HPV vaccine caused optic neuritis and her flu
vaccine separately caused Rasmussen’s encephalitis; or E.M. suffered optic neuritis
caused by her HPV vaccine that acted as a first hit in the development of Rasmussen’s
encephalitis, with the flu vaccine additionally acting as a second hit, resulting in a
significant aggravation. In all events, petitioners ultimately contend that, given the
sequence of events, it is “inconceivable” that her vaccines were not factors in bringing
about her condition. Petitioners’ expert, Dr. Steinman, prefers the two-hit model of
Rasmussen’s encephalitis that supports a synergistic relationship between the two
vaccinations. Respondent, by contrast, suggests that E.M.’s Rasmussen’s encephalitis
was caused solely by an HSV infection. Respondent does not suggest any alternative
cause of E.M.’s optic neuritis. However, he stresses that optic neuritis and
Rasmussen’s encephalitis are too distinct to be causally related to one another. His
experts, particularly Dr. McCusker, are content with the notion of lightning striking twice.
(Tr. 706-08.)
To resolve the issues raised by the parties, the analysis that follows is divided
into two parts. First, petitioners have preponderantly demonstrated that E.M.’s July
2015 HPV vaccine can and did cause her optic neuritis. Second, the evidence
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preponderates in favor of a finding that E.M.’s optic neuritis was itself a cause of the
later development of her Rasmussen’s encephalitis, even though it would not have been
the sole cause. This is a threshold finding with regard to petitioners’ theory of causation
vis-à-vis the flu vaccine; however, it also means that E.M.’s vaccine-caused optic
neuritis was a proximate cause of her later Rasmussen’s encephalitis. Thus, these
findings are sufficient to entitle petitioners to compensation for E.M.’s complete post-
vaccination clinical presentation regardless of whether her subsequent November 2015
flu vaccination is additionally implicated. Therefore, it is not necessary to reach
petitioners’ separate significant aggravation contention.
a. There is Preponderant Evidence that E.M. Suffered Optic Neuritis
Caused-in-Fact by her HPV Vaccine (Althen Analysis with Respect to
Optic Neuritis)
i. A medical theory of general causation is preponderantly supported
(Althen prong one)
Under Althen prong one, petitioners must provide a “reputable medical theory,”
demonstrating that the vaccine received can cause the type of injury alleged. Pafford v.
Sec’y of Health & Human Servs., 451 F.3d 1352, 1355-56 (Fed. Cir. 2006) (citation
omitted). To satisfy this prong, 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. However, 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 v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1325-26 (Fed. Cir.
2006)).
Dr. Steinman’s theory as to how the HPV vaccine can cause optic neuritis is
based on molecular mimicry30 between a myelin protein, i.e., MOG, and elements of the
30 Molecular mimicry “is a generally accepted scientific principle, [but] mere invocation of the scientific
term does not carry a petitioner’s burden in a Program case.” Deshler v. Sec’y of Health & Human
Servs., No. 16-1070V, 2020 WL 4593162, at *20 (Fed. Cl. Spec. Mstr. July 1, 2020) (citing Forrest v.
Sec’y of Health & Human Servs., No. 14-1046V, 2019 WL 925495, at *3 (Fed. Cl. Spec. Mstr. Jan. 18,
2019)). This is because “the finding of sequence homology does not necessarily mean the similarity has
significance to the immune system.” Tullio v. Sec’y of Health & Human Servs., No. 15-51V, 2019 WL
7580149, at *15 (Fed. Cl. Spec. Mstr. Dec. 19, 2019), mot. rev. denied, 149 Fed. Cl. 448 (2020); see also
Caredio v. Sec’y of Health & Human Servs., No. 17-0079V, 2021 WL 4100294, at *31 (Fed. Cl. Spec.
Mstr. July 30, 2021) (noting that “demonstration of homology alone is not enough to establish a
preponderant causation theory” (emphases omitted)), mot. for rev. denied, No. 17-79V, 2021 WL
6058835 (Fed. Cl. Dec. 3, 2021). However, as noted above, petitioners in this program are not required
to establish scientific certainty. Therefore, prior cases have expressed, with regard to the application of
molecular mimicry, that “[t]he line must be drawn somewhere between speculation and certainty.”
Brayboy v. Sec’y of Health & Human Servs., No. 15-183V, 2021 WL 4453146, at *19 (Fed. Cl. Spec.
Mstr. Aug. 30, 2021). Thus, for example, in Brayboy, an omnibus proceeding addressing autoimmune
premature ovarian insufficiency, the special master found it sufficient that the petitioners “identified cross-
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HPV vaccine. (Ex. 23, pp. 20-29; Tr. 96-97.) Dr. Steinman explained that an
autoimmune response to MOG is one of the main causes of optic neuritis (Ex. 23, p. 20
(citing Bettelli et al., supra, at Ex. 43; Steinman, supra, at Ex. 44; Kaneko et al., supra,
at Ex. 45; Hacohen et al., supra, at Ex. 46), and respondent’s neurology expert, Dr.
Linnoila, agreed on respondent’s behalf that MOG can be implicated as among the
causal pathways to optic neuritis within related demyelinating disorders (Tr. 351). In
fact, Dr. Linnoila agreed that it was possible that E.M.’s optic neuritis in particular was
secondary to a MOG-antibody related disease. (Ex. C, p. 17 (citing Hacohen &
Banwell, supra, at Ex. C, Tab 16)).)
From an immunologic perspective, Dr. McCusker cautioned on respondent’s
behalf that the pathophysiology of optic neuritis is not fully understood, but did agree
that it is autoimmune and inflammatory. (Tr. 673, 704.) She further agreed that
molecular mimicry is valid as a concept in general. (Id. at 717-18.) However, a
significant issue for Dr. McCusker is “how does the vaccine in the arm get to the [central
nervous system,] get to the pathology in the central nervous system, this is where I
have trouble connecting the dots in this case.” (Id. at 683.) Yet, Dr. Linnoila testified on
respondent’s behalf that “it’s actually very common that there are autoimmune disorders
that are triggered against the nervous system that didn’t – that started or were triggered
by a preceding infection that was somewhere else in the body.” (Id. at 357.) Moreover,
in discussing optic neuritis in her initial report, Dr. Linnoila cited approvingly to literature
that accepts vaccination as a cause of optic neuritis, albeit without implicating the HPV
vaccine specifically. (Ex. C, pp. 10, 17 (citing Chang & Pineles, supra, at Ex. C, Tab 8);
see also Chang & Pineles, supra, at Ex. C, Tab 8, p. 2 (stating that “[o]ptic neuritis in
children may be an idiopathic, isolated event; an autoimmune response to infection or
immunization; or a manifestation of a systemic demyelinating disorder. In younger
children, optic neuritis is more likely to occur following infection or vaccination, or as part
of acute disseminated encephalomyelitis (ADEM).”).) To that point, Dr. Steinman
explained that, due to being adjuvanted, the Gardasil HPV vaccine produces a 40-fold
more potent immune response than a natural viral HPV infection. (Ex. 23, pp. 19-20.
(citing Souayah et al., supra, at Ex. 39).) For the specific HPV 16 and 18 components
implicated by Dr. Steinman’s theory, the immune response was 11-times higher than
infection. (Id. (citing Souayah et al., supra, at Ex. 39).)
To demonstrate molecular mimicry between MOG proteins and the HPV vaccine,
Dr. Steinman used a program called BLAST that allows for comparison of different
peptide sequences. (Ex. 23, pp. 19-36.) Dr. Steinman has employed this type of
search in many prior cases. It has been previously criticized. E.g., Forrest v. Sec’y of
Health & Human Servs., No. 14-1046V, 2019 WL 925495, at *4-5 (Fed. Cl. Spec. Mstr.
Jan. 28, 2019); A.T. v. Sec’y of Health & Human Servs., No. 16-393V, 2021 WL
6495241, at *24-25 (Fed. Cl. Spec. Mstr. Dec. 17, 2021). However, it has also been
credited in some cases as contributing to the overall conclusion that petitioners have
reaction between components of the vaccine and proteins in the body that are directly responsible for the
health and productivity of the organ at issue” and further expressed that requiring further steps, or
“insisting on direct, testable evidence,” would impermissibly heighten the petitioners’ burden of proof. Id.
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met their burden of proof under Althen. E.M. v. Sec’y of Health & Human Servs., No.
14-753V, 2021 WL 3477837, at *36-39 (Fed. Cl. Spec. Mstr. July 9, 2021); White v.
Sec’y of Health & Human Servs., No. 15-1521V, 2019 WL 7563239, at *24 (Fed. Cl.
Spec. Mstr. Dec. 19, 2019). A significant limitation of Dr. Steinman’s BLAST searches
is that the results showing homology are not in themselves predictive of meaningful
molecular mimics, having a high likelihood of showing matches that result merely from
chance. J.C. v. Sec’y of Health & Human Servs., No. 17-69V, 2024 WL 3412625, at
*18-19 (Fed. Cl. Spec. Mstr. May 16, 2024). Therefore, I have previously concluded
that “the evidentiary value of these search results is limited and turns on whether the
other evidence of record likewise supports a causal relationship between the
vaccination and the type of injury at issue . . . . Without more, BLAST search results do
not meet petitioner’s preponderant burden of proof under Althen prong one.” Id. at 19.
The testimony elicited from respondent’s immunology expert in this case is consistent
with this conclusion. Dr. McCusker testified that, using BLAST, “I can find sequence
homology to anything,” but nonetheless also acknowledged that the tool could
reasonably be used for “reverse engineering” a potentially significant match. (Tr. 687-
88.)
Dr. Steinman compared MOG against the L1 protein from HPV 18 and HPV 16.
(Ex. 23, pp. 24, 26.) He explained that the L1 protein is an external part of the virus and
therefore is accessible to antibodies and T cells. (Tr. 88-89.) For HPV 18, he located a
sequence with six of eleven identical amino acids. (Ex. 23, p. 25-26.) For HPV 16, he
located a sequence with six of ten identical amino acids. (Id. at 27-28.) Dr. Steinman
asserted that this degree of homology has been shown in peer-reviewed animal model
studies as sufficient to trigger clinical neuroinflammation. (Id. at 36 (citing Gautam et
al., supra, at Ex. 51; Gautam et al., supra, at Ex. 52; Gautam et al., supra, at Ex. 53).)
Dr. McCusker disputed that short homologies of this type are predictive of any causally
significant molecular mimicry and stressed the limitations of these animal models. (Ex.
E, pp. 3-4; Ex. G, p. 3.) However, Dr. Steinman has also submitted a more recent
publication by his own research group as proof of concept that a five out of twelve
homology was sufficient to implicate the EBV virus as a cause of multiple sclerosis in
humans. (Tr. 149-54 (Lanz et al., supra, at Ex. 71).) Dr. McCusker did not seek to
rebut Dr. Steinman’s reliance on the Lanz paper. Dr. Steinman also presented a study
by Ufret-Vincenty et al. that specifically demonstrated in a mouse model of experimental
autoimmune encephalomyelitis (“EAE”), an established model for the study of central
nervous system demyelination, that peptides derived from the human papilloma virus
were recognized by myelin basic protein-specific T cell clones from a multiple sclerosis
patient, resulting in induction of autoimmune disease. (Ex. 23, pp 26-37; Rafael L.
Ufret-Vincenty et al., In Vitro Survival of Viral Antigen-Specific T Cells that Induce
Experimental Autoimmunity Encephalomyelitis, 188 J. EXPERIMENTAL MED. 1725 (1998)
(Ex. 55).)
Dr. Steinman further cited a study by Sridhar et al. that purported to show that a
second dose of Gardasil vaccine (as at issue in this case) carries an increased risk for
the development of optic neuritis. (Tr. 135 (Sridhar et al., supra, at Ex. 40); Ex. 23, p.
20.) On respondent’s behalf, Dr. McCusker opined that the Sridhar study overall does
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not support a causal relationship between the HPV vaccine and optic neuritis after
considering the secondary analysis, though she did acknowledge the study includes the
specific finding relied upon by Dr. Steinman. (Tr. 726-27.) She also acknowledged that
a separate study found an increased risk of GBS following HPV vaccination. (Id. at 727;
Miranda et al., supra, at Ex. A, Tab 3.) Although GBS is a different condition, it is
likewise viewed as a demyelinating condition in many cases.31
Thus, Dr. Steinman presented a sound and reliable opinion, based on the nature
of optic neuritis (which literature filed by respondent agrees can be vaccine-caused),
BLAST search results showing a proposed homology between HPV antigen and MOG,
a mouse model showing HPV peptides being recognized by myelin basic protein-
specific T cells, and other circumstantial evidence, supporting the theory that the HPV
vaccine can cause optic neuritis. Additionally, E.M.’s treating physicians likewise felt
that the HPV vaccine can cause optic neuritis. Specifically, both E.M.’s treating neuro-
ophthalmologist (Dr. Digre) and infectious disease specialist (Dr. Thorell) cited within
their assessments the fact that medical literature has reported demyelinating conditions,
including optic neuritis and ADEM, as adverse reactions to the HPV vaccine (Ex. 7, pp.
66-67 (neuro-opthalmologist Dr. Digre); Ex. 134, pp. 1915-16 (infectious disease
specialist Dr. Thorell)) before ultimately concluding that E.M. suffered vaccine-caused
optic neuritis (Ex. 6, p. 17 (Dr. Digre diagnosing “Post vaccination opti” as of October 1,
2015); Ex. 139, p. 1 (Dr. Thorell reporting to VAERS that E.M. suffered optic neuritis
following her second HPV vaccine). This further supports petitioners’ Althen prong one
showing. See Patton v. Sec’y of Health & Human Servs., 157 Fed. Cl. 159, 169 (2021)
(finding that the diagnoses of the treating physicians that the petitioner suffered vaccine-
caused brachial neuritis supported the reliability of petitioner’s expert’s theory of
causation); Capizzano, 440 F.3d at 1326 (explaining that evidence used to satisfy one
Althen prong can overlap to help satisfy another).
Additionally, though not controlling, it is worth noting that several special masters
have concluded that the HPV vaccine can cause demyelinating central nervous system
conditions, including optic neuritis. Girardi v. Sec’y of Health & Human Servs., No. 17-
181V, 2024 WL 4565887, at *27-30 (Fed. Cl. Spec. Mstr. Sept. 27, 2024) (finding the
Cervarix HPV vaccine can trigger optic neuritis via molecular mimicry); White v. Sec’y of
Health & Human Servs., No. 15-1521V, 2019 WL 7563239, at *21-24 (Fed. Cl. Spec.
Mstr. Dec. 19, 2019) (finding the Gardasil HPV vaccine can cause acute transverse
myelitis via molecular mimicry); B.A. v. Sec’y of Health & Human Servs., No. 11-51V,
2018 WL 6985218, at *31-32 (Fed. Cl. Spec. Mstr. Dec. 6, 2018) (finding preponderant
evidence supporting a medical theory linking the HPV vaccine and ADEM). But see
Maciel v. Sec’y of Health & Human Servs., No. 15-362V, 2018 WL 6259230, at *26-28
31 A potentially important distinction is that the demyelinating forms of GBS involve the peripheral nerves
whereas optic neuritis is a condition affecting the central nervous system. In this case, however,
respondent’s neurology expert, Dr. Linnoila, herself invoked GBS as a prime example of how neurologic
autoimmune conditions develop. (Tr. 357-58.) She invoked GBS in a discussion supporting her opinion
that E.M.’s Rasmussen’s encephalitis, also a central nervous system condition, could have been caused
by an HSV infection even without entry of the HSV infection into the central nervous system. (Id.)
Accordingly, both parties in this case present expert opinions that embrace GBS as usefully analogous
despite involving the peripheral nervous system.
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(Fed. Cl. Spec. Mstr. Oct. 12, 2018) (noting that, “[a]t a minimum, there is not enough
reliable and persuasive evidence offered herein for me to find it plausible that the HPV
vaccine could significantly aggravate the overall course of MS”); Heddens v. Sec’y of
Health & Human Servs., No. 15-734V, 2018 WL 5726991 (Fed. Cl. Spec. Mstr. Oct. 5,
2018) (concluding that petitioner has not preponderantly shown that the HPV vaccine
can cause or significantly aggravate multiple sclerosis), mot. for rev. denied, 143 Fed.
Cl. 193 (2019). And, notably, this includes cases accepting Dr. Steinman’s specific
contention in this case that peptide sequences from antigens in the HPV vaccine (as
contained in both Gardasil and Cervarix) can cross-react with MOG proteins within
myelin. Girardi, 2024 WL 4565887, at *28; White, 2019 WL 7563239, at *22.
A primary aspect of Dr. Linnoila’s and Dr. McCusker’s contrary view is that,
despite a number of large studies having been conducted, no epidemiologic link has
been uncovered between HPV vaccination and optic neuritis. The Federal Circuit has
previously stressed that a petitioner is not obligated to prove a case with epidemiology.
Capizzano, 440 F.3d at 1325. Yet, “[n]othing in Althen or Capizzano requires the
Special Master to ignore probative epidemiological evidence that undermines
petitioner’s theory.” D’Tiole v. Sec’y of Health & Human Servs., 726 F. App’x 809, 811
(Fed. Cir. 2018). Accordingly, it is necessary to examine the epidemiology cited by
respondent. In this case, the epidemiologic evidence, though entitled to some weight,
does not significantly undermine Dr. Steinman’s theory of causation.
Dr. McCusker cited Baxter et al., a case centered analysis that found no
association between optic neuritis and any vaccine. (Baxter et al., supra, at Ex. A, Tab
1, p. 1.) The Baxter study began with the premise that “[t]he institute of Medicine
observed that there was not sufficient evidence to either accept or reject the notion that
vaccines are causally related to [optic neuritis].” (Id. (emphasis added).) Thus, the
authors set out to examine numerous vaccinations administered in the Kaiser
Permanente system for northern California, a population of 3.5 million members. (Id.)
Focusing on this overall population figure, Dr. McCusker stressed the study as
representing “a very big number when it comes to studies.” (Tr. 617.) Importantly,
however, the study only included 566,643 doses of HPV vaccine administered, which
accounted for less than 3% of the vaccinations captured by the study. (Baxter et al.,
supra, at Ex. A, Tab 1, p. 2, tbl.1.) Thus, Dr. McCusker admitted upon cross-
examination that the study authors had explicitly concluded that they could not rule out
an increased risk of post-HPV vaccine optic neuritis without a larger study. (Tr. 726;
Baxter et al., supra, at Ex. A, Tab 1, p. 3.) Dr. McCusker added, “that’s why more
studies have been done and published.” (Tr. 726.) However, among the studies she
additionally cited, Liu et al. did not match the Baxter study for size. Liu et al. was a
cohort study of 290,939 HPV vaccine-eligible girls, of which 180,819 girls received at
least one vaccine dose and 681 incident cases of autoimmune disorders were
diagnosed. (Liu et al., supra, at Ex. A, Tab 2, p. 3.) This was as self-controlled series,
meaning each subject was their own control. (Id. at 2.) Sixty-seven cases of optic
neuritis were examined. (Id. at 5, tbl.1.)
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Miranda et al. did exceed the size of the Baxter study, having examined 842,120
HPV-vaccinated girls. (Miranda et al., supra, at Ex. A, Tab 3, p. 3.) However, this study
did not address optic neuritis separately (assessing central nervous system
demyelinating conditions collectively)32 and did not completely exonerate the HPV
vaccine as a cause of autoimmune demyelination, given that it did detect an increased
risk of post-HPV vaccination GBS, as noted above. (Id.) Dr. McCusker also cited a
meta-analysis by Mouchet et al., which she characterized as applying a “rigorous”
literature review. (Tr. 626; Mouchet et al., supra, at Ex. A, Tab 5.) She stated that
Mouchet stands for the proposition that, “not just statistically speaking, but massively
statistically speaking,” there is no evidence that the HPV vaccine causes optic neuritis.
(Tr. 628.) Looking at the study’s specific discussion of optic neuritis, the authors identify
six studies with risk estimates for optic neuritis. (Mouchet et al., supra, Ex. A, Tab 5, p.
7.) However, among those six studies are Baxter et al., in which the authors confirmed
they could not rule out all increased risk of post-HPV vaccination optic neuritis, and
Sridhar et al., which, as discussed above, included one specific finding of increased risk
of optic neuritis after a second dose of HPV vaccine, i.e., the dose at issue in this case.
(Id. at 4, 7.) For a third study, the authors explicitly note that, due to study flaws, “it
should be interpreted with caution.” (Id. at 3.) Thus, Miranda et al. and Mouchet et al.
are not strong evidence.
In light of all of the above, and considering the record as a whole, there is
preponderant evidence on this record that the HPV vaccine can cause optic neuritis.
ii. A logical sequence of cause and effect and an appropriate temporal
relationship preponderantly support specific causation (Althen
prongs two and three)
Having shown that the HPV vaccine can cause optic neuritis, petitioners must
also establish that it did cause optic neuritis in this specific case. Pafford, 451 F.3d at
1356. This aspect of petitioners’ prima facie showing is generally broken down into two
further questions pursuant to Althen prongs two and three. The second Althen prong
requires proof of a logical sequence of cause and effect usually supported by facts
derived from a vaccinee’s medical records. Althen, 418 F.3d at 1278; Andreu, 569 F.3d
at 1375-77; Capizzano, 440 F.3d at 1326; Grant, 956 F.2d at 1148. The third Althen
prong requires establishing a “proximate temporal relationship” between the vaccination
and the injury alleged. Althen, 418 F.3d at 1278. That term has been equated to the
phrase “medically-acceptable temporal relationship.” Id. at 1281. A petitioner must
offer “preponderant proof that the onset of symptoms occurred within a timeframe
which, given the medical understanding of the disorder’s etiology, it is medically
acceptable to infer causation.” de Bazan v. Sec’y of Health & Human Servs., 539 F.3d
1347, 1352 (Fed. Cir. 2008).
32 This is a potential issue because central nervous system demyelinating disorders have differing
presentations and/or prevalence. See, e.g. Doles v. Sec’y of Health & Human Servs., No. 17-642V, 2022
WL 3229286, at *26-27 (Fed. Cl. Spec. Mstr. June 24, 2022) (quoting a review article by Mailand and
Frederiksen explaining that a limitation in epidemiologic study of multiple sclerosis includes delay in
diagnosis and significant variation in symptom presentation), vacated on other grounds, 163 Fed. Cl. 726
(2022).
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E.M. received the second dose of her HPV vaccine on July 20, 2015 and
subsequently developed optic neuritis in mid-August, roughly or close to a month after
vaccination. A mid-August onset of optic neuritis is preponderantly supported based on
review of the complete medical records. (Ex. 5, p. 2 (routine eye exam with optometrist
of May 9, 2015 negative for any pathology and finding only myopia); Ex. 4, pp. 6-7 (no
complaints recorded at July 20, 2015 encounter for second HPV vaccination); Ex. 5, p.
3 (return encounter with optometrist noting as of September 15, 2015, “one month” of
symptoms later diagnosed as optic neuritis, placing onset in mid-August); Ex. 6, p. 1
(ophthalmology encounter noting onset of symptoms “[t]owards the end of summer,”
consistent with a mid-August onset); Ex. 8, p. 668 (neurology consultation recording as
of October 8, 2015, a history of symptoms beginning “a couple months ago,” potentially
consistent with an August onset, and noting the normal eye exam in May).) The
Federal Circuit has held that contemporaneous medical records are to be given
significant weight because “the records contain information supplied to or by health
professionals to facilitate diagnosis and treatment of medical conditions. With proper
treatment hanging in the balance, accuracy has an extra premium. These records are
also generally contemporaneous to the medical events.” Cucuras, 993 F.2d at 1528.
Petitioners’ testimony further supports a mid-August onset of optic neuritis. Mr. Marsh
testified that E.M. began showing discomfort with her eye around mid-August of 2015.
(Tr. 13.) Mrs. Marsh testified that E.M.’s eye problems began one month before her
appointment with Dr. Beagley, likewise placing onset around mid-August. (Id. at 31.)
Nonetheless, respondent argues that several records place the onset of E.M.’s
optic neuritis before she received the second dose of her HPV vaccine. (ECF No. 128,
pp. 26-27.) In particular, on September 24, 2015, E.M.’s neuro-ophthalmologist, Dr.
Digre, recorded that the duration of E.M.’s symptoms of optic neuritis was “3 months,”
which would place onset in June. (Ex. 6, p. 5.) However, the same record indicates in
the history of present illness that the symptoms began “in July.” (Id.) Thus, the history
provided within this encounter reccord is internally inconsistent and in referencing a July
onset does not clearly place onset prior to the July 20, 2015 vaccination.33 Moreover,
this history is in contrast to the earlier treatment records and stands alone in placing
onset in June or July. Additionally, on December 12, 2015, E.M. underwent a neurology
consultation during which it was noted that E.M. developed black spots with progressive
tunnel vision in Spring of 2015. (Ex. 8, p. 477.) However, this consult took place six
months after E.M.’s vaccination, and, as explained above, more contemporaneous
records support a mid-August onset. Moreover, E.M.’s essentially normal eye exam
from May of 2015 is in tension with onset occurring in the Spring of 2015. Ultimately,
both of respondent’s experts agreed that E.M.’s symptoms began after her vaccination.
(Tr. 347-48, 361 (Dr. Linnoila indicating onset is unclear but agreeing it occurred after
33 The two notations can potentially be harmonized if one were to conclude that the reference to “3
months” merely means that E.M.’s optic neuritis had to that point spanned three calendar months, i.e.
beginning in July and continuing throughout August and into September. It should be noted that Dr. Digre
did at a later encounter opine that E.M. was suffering post-vaccination optic neuritis (Ex. 6, p. 17) without
specifically revisiting the timing of onset (Id. at 14). Accordingly, it would be illogical to interpret Dr.
Digre’s records as indicating she was under the impression that onset of the optic neuritis occurred prior
to the vaccination.
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the July 20, 2015 vaccination); Tr. 724-25 (Dr. McCusker acknowledged that there is
some equivocation within the record with regards to timing, but placed onset of E.M.’s
optic neuritis between one to two months after vaccination).)
There is preponderant evidence on this record that onset of a central nervous
system demyelinating condition, such as optic neuritis, occurring approximately one-
month post vaccination constitutes a medically acceptable temporal relationship. (Tr.
162-65; Ex. 23, p. 40; Karussis & Petrou, supra, at Ex. 42, p. 5, tbl.2 (identifying optic
neuritis occurring 10 days to five months post-HPV vaccination); Pellegrino et al., supra,
at Ex. 93, p. 3, tbl.1 (finding a majority of post-vaccination ADEM cases arose between
2-30 days post-vaccination); Huynah et al., supra, at Ex. 98, pp. 7-8 (patient presenting
with bilateral optic neuropathies three weeks after flu vaccination developed ADEM
three months after vaccination); Vilain et al., supra, at Ex. 106, p. 2 (patient with
presumptive diagnosis of encephalomyelitis with bilateral optic perineuritis caused by
influenza vaccination who developed symptoms five days after receiving his vaccine);
Schonberger et al., supra, at Ex. 96, p. 1 (finding elevated risk of post-vaccination GBS
“primarily” within five weeks). Prior program cases have often concluded that 2-42 days
is an appropriate interval for post-vaccination onset of demyelinating conditions. See
e.g., Girardi, 2024 WL 4565887, at *32-33 (noting that a timeframe of 3-42 days has
been accepted in cases involving peripheral and central nervous system diseases and
finding as medically acceptable a 38-day onset of post-HPV vaccination optic neuritis);
Day v. Sec’y of Health & Human Servs., No. 12-630V, 2015 WL 8028393, at *21-23
(Fed. Cl. Spec. Mstr. Nov. 13, 2015) (finding a primary risk interval of 5-28 days and a
secondary risk interval of 2-42 days persuasive with regards to post-vaccinal
neurological disorders in a case involving post-HPV vaccination neuromyelitis optica);
Koller v. Sec’y of Health & Human Servs., No. 16-439V, 2021 WL 5027947, at *22-23
(Fed. Cl. Spec. Mstr. Oct. 8, 2021) (accepting a timeframe of 2-34 days for onset of
GBS following Prevnar 13 vaccination); Giannetta v. Sec’y of Health & Human Servs.,
No. 13-215V, 2017 WL 4249946, at *24-25 (Fed. Cl. Spec. Mstr. Sept. 1, 2017) (finding
an onset with 42-47 days is an acceptable timeframe for onset of multiple sclerosis
following Menactra vaccination); Brancheau v. Sec’y of Health & Human Servs., No. 21-
1209V, 2024 WL 1619606, at *23-26 (Fed. Cl. Spec. Mstr. Mar. 21, 2024) (noting the
onset period for a Table Injury of GBS following flu vaccination is 3-42 days). Thus, a
causal inference supporting vaccine causation is medically reasonable in this case
based on the preponderantly established date of onset.
Following his review of E.M.’s medical history, Dr. Steinman has opined on
petitioners’ behalf that E.M.’s optic neuritis was caused by her July 20, 2015 HPV
vaccination. (Ex. 23, p. 41.) As a neuroimmunologist, he is qualified to render that
opinion. (Id. at 1 (noting that Dr. Steinman has cared for “hundreds of adults and
children with various forms of inflammatory neuropathy,” including optic neuritis).)
Although respondent’s neurology expert, Dr. Linnoila, reached the opposite conclusion,
it is difficult to separate that opinion from her opinion regarding petitioner’s theory of
general causation with respect to optic neuritis. Dr. Linnoila did not raise any specific
aspect of E.M.’s own clinical history as being incompatible with petitioner’s proffered
theory, which has been accepted as preponderantly demonstrated. Apart from
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opposition under Althen prong one, the only issue respondent raises with respect to
whether E.M.’s own clinical presentation of optic neuritis could have been vaccine
caused is his assertion that onset of the condition pre-dated her July 20, 2015 HPV
vaccination, which is unpersuasive for the reasons discussed above.34 (ECF No. 128,
pp. 26-28.) Respondent has not argued that E.M.’s optic neuritis was due to any factor
unrelated to her vaccination. (Id. at 28-30.)
Indeed, E.M. was evaluated by a neuro-opthalmologist and an infectious disease
specialist, both of whom felt E.M.’s history was potentially indicative of HPV-vaccine
caused optic neuritis. (Ex. 6, p. 17 (neuro-opthalmologist Dr. Digre diagnosing “Post
vaccination opti” as of October 1, 2015); Ex. 7, p. 66-67 (Dr. Digre writing that post-
vaccination optic neuritis is to be considered as a diagnosis of exclusion, given that
“[t]here have been reports of post HPV vaccination causing optic neuritis”); Ex. 134, p.
1915-16 (Dr. Thorell signing off as of January 16, 2016, on a consultation explaining
that “[a] very rare ADEM/adverse immunization reaction to HPV has been reported in a
few case studies and is also being entertained in light of the temporal relationship of her
acquiring [optic] neuritis a few weeks after her second HPV vaccine,” further noting that
“autoimmune vis infection etiologies seem the most likely working differential at this
point” and that a VAERS report was filed); Ex. 139, p. 3 (Dr. Thorell reporting to VAERS
that E.M. suffered optic neuritis following her second HPV vaccine). Respondent
challenges the validity of Dr. Thorell’s VAERS report as it pertains to E.M.’s broader,
longer-term condition, mainly because Dr. Thorell still suspected ADEM, but does not
directly address Dr. Thorell’s separate identification of a vaccine-related optic neuritis.35
(ECF No. 128, pp. 21-25.)
Accordingly, petitioners have preponderantly demonstrated that onset of E.M.’s
optic neuritis occurred during a post-vaccination timeframe from which vaccine
causation can be inferred and also that a logical sequence of cause and effect,
supported by both expert and treater medical opinion, supports the conclusion that
E.M.’s HPV vaccine did cause of her optic neuritis.
34 Though respondent argues onset pre-dated the vaccination, respondent does also seek to further cloud
the question of onset by raising the fact that Dr. Thorell’s VAERS submission indicated that E.M.’s optic
neuritis occurred 6-7 weeks following her vaccination. (ECF No. 128, pp. 22, 24.) Dr. Thorell’s VAERS
report does not outweigh the contemporaneous treatment records. But in any event, a six-week onset
would not be incompatible with a causal inference as explained above.
35 Respondent contends that “[t]he Court of Federal Claims has repeatedly upheld special masters’
decisions to give little weight to VAERS reports as evidence of causation.” (ECF No. 128, n. 7.)
However, this is misleading. What respondent cites are examples wherein special masters have rejected
attempts to cull data from the VAERS database regarding other purportedly vaccine-injured individuals to
support their claim. This is generally viewed as an unreliable approach because VAERS is a passive
surveillance system and anyone can file a VAERS report. However, these concerns are irrelevant here.
Dr. Thorell’s VAERS submission is a detailed first-hand accounting of her reasoning, as E.M.’s treating
physician, as to why a vaccine adverse event may be implicated in this very case.
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b. There is Preponderant Evidence that E.M.’s Optic Neuritis was a But
For Cause and Substantial Contributing Factor in the Development of
her Subsequent Rasmussen’s Encephalitis
Having established that E.M.’s optic neuritis was vaccine-caused, a key
additional question necessary to a full resolution of this case is what – if any –
relationship exists between E.M.’s optic neuritis and her subsequently occurring
Rasmussen’s encephalitis. Petitioners contend that they “have established that more
likely than not the HPV vaccine caused [E.M.]’s Optic Neuritis. At the time [E.M.]
received the influenza vaccine on November 10, 2015, she was suffering from Optic
Neuritis. Thereafter, within thirty (30) days, her seizures began, which eventually were
diagnosed as Rasmussen’s Encephalitis. This supports the two-hit theory of
Rasmussen’s Encephalitis.” (ECF No. 129, p. 32.) Thus, they suggest that “[i]t is
inconceivable that [E.M.], thirty (30) days after the HPV vaccination, had an onset of
Optic Neuritis and then thirty (30) days after her influenza vaccination had an onset of
her seizures without the vaccine(s) being a substantial factor in her illness.” (Id. at 32-
33.)
Respondent likewise stresses that “[i]n an attempt to connect all the vaccine and
all the theories, Dr. Steinman postulates that E.M.’s optic neuritis never resolved, and in
fact led to the Rasmussen’s Encephalitis.” (ECF No. 128, p. 26.) Yet, respondent
maintains that “E.M. suffered from two different entities – optic neuritis and
Rasmussen’s Encephalitis.” (Id. at. 22.) And, moreover, “optic neuritis is not a feature
of Rasmussen’s Encephalitis.” (Id.) Petitioners explain, however, that they “have never
contended that optic neuritis itself caused or led to [E.M.]’s Rasmussen’s Encephalitis.”
(ECF No. 129, p. 19.) Instead, they assert that the “HPV vaccine caused [E.M.]’s optic
neuritis and brain inflammation. The autoimmune condition was present at the time of
[E.M.]’s flu vaccination. The flu vaccination was the second hit which caused [E.M.]’s
seizures.” (Id. at 22.) In other words, the parties agree that E.M.’s Rasmussen’s
encephalitis is not merely an extension of her optic neuritis, given that they are distinct
conditions; however, petitioners nonetheless argue that E.M.’s preexisting brain
inflammation and autoimmunity due to her optic neuritis were causal factors
contributing, with the addition of a second hit, to the development of her Rasmussen’s
encephalitis.
The two-hit model of Rasmussen’s encephalitis proffered by petitioners, and
preferred by their expert, Dr. Steinman, is distinct from the separately advanced
alternative hypothesis that E.M.’s two vaccines each acted separately to cause two
separate injuries. It seeks to place E.M.’s initial autoimmune injury as a first-hit,
meaning that, despite not being the sole cause of her Rasmussen’s encephalitis, the
optic neuritis was a but for cause and substantial contributing factor in the development
of the condition. Accordingly, any finding in petitioners’ favor vis-à-vis the flu
vaccination based on the two-hit model of Rasmussen’s encephalitis would necessarily
encompass a threshold finding that the Rasmussen’s encephalitis was caused, at least
in part, by the optic neuritis. Yet, because petitioners have demonstrated that the optic
neuritis was vaccine caused, this same finding is sufficient to bring E.M.’s Rasmussen’s
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encephalitis under the umbrella of her compensable HPV vaccine-related optic neuritis
claim, mooting any need to actually determine what constituted the second hit leading to
her Rasmussen’s encephalitis. In that regard, petitioners’ amended petition, while
additionally alleging a causal role for E.M.’s flu vaccination, explicitly preserved the
allegation that the HPV vaccine causally contributed to the development of E.M.’s
Rasmussen’s encephalitis.36 (ECF No. 59, p. 15.)
This is consistent with the standard adopted by the Federal Circuit in Shyface vs.
Secretary of Health & Human Services, 165 F.3d 1344 (Fed. Cir. 1999). In Shyface, a
child had died from respiratory failure brought about by a high fever along with
dehydration and an infection. Id. at 1345. The petitioners argued that a prior
vaccination was a proximate cause of the death because it had caused the fever that in
turn contributed to the death. Respondent countered, however, that the infection was
the principal cause of the death. Id. at 1345-46. The Federal Circuit held that the
vaccine was a proximate cause of the death, explaining that, under the tort principles of
proximate causation applicable to the Vaccine Act, petitioners are only obligated to
demonstrate that the vaccine is both a “but for” cause and a “substantial contributing
factor” in any alleged injury, rather than the sole cause. Id. at 1352. The Circuit further
explained that, when concurrent causes are at issue, a petitioner may demonstrate the
vaccine to have been a substantial contributing factor when it can be demonstrated that
there is a causal theory connecting the vaccine and the injury, as well as a logical
sequence of cause and effect showing that the vaccine was the reason for the injury,
i.e., a showing consistent with the Althen test. Id. at 1352-53. Whereas the Shyface
petitioners alleged that vaccination caused a fever that in turn contributed to a
subsequent death due to multiple causes, here petitioners allege the vaccine at issue
caused optic neuritis that in turn contributed to development of Rasmussen’s
encephalitis, which they contend resulted from multiple causes.
Moreover, compensable injuries within this program encompass complications
and residual effects of an initially vaccine-caused injury. § 300aa-11(c)(1)(D)(i). A
complication is a disease or morbid process that co-occurs in the same patient as a
result of another disease, without being an essential part of that disease. Wright v.
Sec’y of Health & Human Servs., 22 F.4th 999, 1006 (Fed. Cir. 2022). In determining
whether a complication is the result of an initially vaccine-caused condition, the same
tort principles as adopted by the Shyface court are used. Id. at 1005. Thus, it is
sufficient that a vaccine injury be both a but for cause and substantial contributing factor
in bringing about a complication, even without necessarily being a predominant factor.
36 As discussed below, the expert testimony in this case was clear in debating the potential
interrelationship between Rasmussen’s encephalitis and preceding optic neuritis; however, the parties’
post hearing briefs were less helpful on this point in that they tended to gloss over this threshold question
in favor of jumping straight to their respective arguments regarding the viability of the flu vaccine as the
proposed second-hit within the multi-hit model of Rasmussen’s encephalitis. (ECF Nos. 127-29.) See
Sword v. U.S., 44 Fed. Cl. 183, 187 (1999) (explaining that “[n]o judge or jury can be forced to accept or
reject an expert’s opinion or a party’s theory at face value. To require such a choice in this context is to
neglect the Special Master’s duty to ‘vigorously and diligently investigate the factual elements’ underlying
the petition.”).
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Id. (citing Shyface, 165 F.3d at 1352). Under this standard, E.M.’s Rasmussen’s
encephalitis can be conceived of as a complication or sequela of her optic neuritis, i.e.,
a co-occuring, but causally related, disease that cannot be said to be a part of the optic
neuritis itself.
Accordingly, consistent with Shyface, the three-part Althen test will be applied to
determine whether E.M.’s Rasmussen’s encephalitis is causally related to her optic
neuritis. As a result of that analysis, there is preponderant evidence that (1) optic
neuritis can be a promoting factor in the development of Rasmussen’s encephalitis
(Althen prong one), (2) the timing of the course of events supports a causal inference
that the optic neuritis contributed to the Rasmussen’s encephalitis in E.M.’s case
(Althen prong three), and (3) there is a logical sequence of cause and effect implicating
E.M.’s optic neuritis in the development of her Rasmussen’s encephalitis (Althen prong
two). The last of these points encompasses a finding that respondent is unpersuasive
in contending that an HSV infection, if implicated, would constitute the sole cause of the
Rasmussen’s encephalitis to the exclusion of the optic neuritis. Accordingly, there is
preponderant evidence that E.M.’s Rasmussen’s encephalitis is causally related to her
prior optic neuritis and that her entire post-HPV vaccine presentation therefore
constitutes a compensable injury.
i. There is preponderant evidence that optic neuritis can causally
contribute to Rasmussen’s encephalitis as a predisposing or
promoting factor (Althen prong one)
Respondent’s experts stress that optic neuritis and Rasmussen’s encephalitis
represent two distinct disease processes and therefore cannot reasonably be viewed as
a single entity stemming from a single cause. (Tr. 352, 472, 704-08; Ex. C, pp. 11-12.)
Dr. Steinman explained during the hearing, however, that it is nonetheless scientifically
or medically reasonable to consider E.M.’s optic neuritis as a contributor to the
development of the autoimmune process that led to her later Rasmussen’s encephalitis,
suggesting that two-hits involved “two anatomic levels.” (Tr. 211-14.) Thus, he opined
that, while it is also potentially reasonable to suggest that E.M.’s HPV and flu vaccines
caused two separate injuries, the most likely scenario is that, as a result of a second hit,
such as the later flu vaccine, the optic neuritis lesions “exploded into what we call
Rasmussen’s [encephalitis].” (Id. at 214.) Thus, he opined that both the HPV vaccine-
caused optic neuritis lesions and the subsequent “hit” together culminated in the
Rasmussen’s encephalitis. (Id.) This explanation is persuasive as a theory, especially
(but not only) in light of the literature filed by respondent. As explained above,
petitioners must present a legally probable, but not necessarily scientifically certain,
theory of causation based on a “sound and reliable medical or scientific explanation.”
Knudsen, 35 F.3d at 548-49.
Dr. Linnoila introduced into the record of this case a paper by Fauser et al.
(Susanne Fauser et al., Rasmussen Encephalitis: Predisposing Factors and Their
Potential Role in Unilaterality, 63 EPILEPSIA 108 (2022) (Ex. H, Tab. 4).) Dr. Linnoila
endorsed this paper as the work of a research group headed by Christian Bien, who she
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identifies as “a world’s expert” in Rasmussen’s encephalitis. (Ex. H, p. 3.) Dr. Linnoila
cited the Fauser paper for the proposition that there is no “general, nonspecific
autoimmune predisposition” for Rasmussen’s encephalitis. (Id. (quoting Fauser et al.,
supra, at Ex. H, Tab 4).) Consistent with Dr. Steinman’s opinion, however, Fauser et al.
indicate that pre-existing ipsilateral brain pathology37 is compatible with a multi-hit
pathogenesis for Rasmussen’s encephalitis. (Fauser et al., supra, at Ex. H, Tab 4, p.
10.) While this pathology is often noted in the context of pre- or perinatal structural
abnormalities, the authors observed broadly that Rasmussen’s encephalitis may
constitute a form of secondary autoimmune encephalitis that requires acquired
comorbidities to disrupt the blood brain barrier and even suggested that incidental
ipsilateral pathology findings have been tentatively interpreted as part of the multistage
pathogenesis of Rasmussen’s encephalitis. (Id. at 10-11.) Thus, they characterize pre-
existing ipsilateral lesions as “promotive” of a “multiple hit” cascade that could also
include subsequent febrile infection.38 (Id. at 6.)
Furthermore, Dr. McCusker likewise explained on respondent’s behalf that the T
cells implicated in the development of Rasmussen’s encephalitis must somehow be
“invited” into the central nervous system. (Tr. 679-80.) Citing Trӧscher et al., she
opined that the T cells in Rasmussen’s encephalitis act as responders, rather than
initiators of disease. (Id. at 673-75 (citing Anna R. Trӧscher et al., Microglial Nodules
Provide the Environment for Pathogenic T Cells in Human Encephalitis, 137 ACTA
NEUROPATHOLOGICA 619 (2019) (Ex. G, Tab 7)).) Thus, in order for the T cells that
cause Rasmussen’s encephalitis to attack the brain in the characteristic uni-hemisphere
pattern, some form of anatomic change or infectious nidus must already be at work in
the affected portion of the brain. (Id. at 675; Trӧscher et al., supra, at Ex. G, Tab 7; see
also Fauser et al., supra, at Ex. H, Tab 4, p. 10 (explaining that a subset of
Rasmussen’s encephalitis patients had one-sided early brain lesions or facial
autoimmune lesions prior to onset of Rasmussen’s encephalitis); Orsini et al., supra, at
Ex. G, Tab 7, p. 4 (explaining that “studies performed on brain tissue, cerebrospinal fluid
and blood from patients with [Rasmussen’s encephalitis] demonstrated that the T-cells
infiltrating the brain tissue expand from discrete precursor T-cells, supporting the theory
of immune activation against a single, unidentified, antigen”).)39 Therefore, regardless
37 Ipsilateral means “situated on, pertaining to, or affecting the same side.” Ipsilateral, DORLAND’S
MEDICAL DICTIONARY ONLINe, https://www.dorlandsonline.com/dorland/definition?id=26077 (last visited
Feb. 10, 2025). As discussed further below, Dr. Linnoila agreed during the hearing that E.M.’s own optic
neuritis constituted a broader syndrome of demyelination inclusive of a left hemisphere temporal lobe
lesion (Tr. 567), the same hemisphere implicated as affected by the Rasmussen’s encephalitis.
38 Although much of petitioners’ briefing focuses on the separate question of whether the flu vaccine can
be implicated as the second hit, petitioners do specifically argue in their post-hearing submissions that
respondent’s filing of the Fauser paper supports Dr. Steinman’s two-hit theory for the development of
Rasmussen’s encephalitis. (ECF No. 129, p. 12.)
39 Both Dr. McCusker’s testimony and the medical literature of record are broadly enough stated that
petitioners cannot reasonably be tasked with demonstrating the actual antigen-presenting characteristics
of a preexisting lesion. “Despite the identification of different pathogens in the brain tissue of patients with
[Rasmussen’s encephalitis], an association between the disease and a specific pathogen has not yet
been identified.” (A. Orsini et al., Rasmussen’s Encephalitis: From Immune Pathogenesis Towards
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of the fact that optic neuritis and Rasmussen’s encephalitis involve distinct autoimmune
pathways, Dr. McCusker’s testimony, as well as the Fauser and Trӧscher articles,
support a causal role for a pre-existing brain abnormality or lesion in the development of
Rasmussen’s encephalitis. And, despite Dr. McCusker’s overall conclusion against a
causal relationship, this also substantiates Dr. Steinman’s multi-hit explanation for
Rasmussen’s encephalitis. (E.g., Fauser et al., supra, at Ex H, Tab 4, p. 10 (“We
suggest a multihit model for the development of [Rasmussen’s encephalitis], with early
lesions, facial autoimmunity, or febrile onset being predisposing factors.”); Tr. 213-14
(Dr. Steinman confirming during the hearing that his two-hit conceptualization
withstands the assumption that the optic neuritis and Rasmussen’s encephalitis are two
separate disease processes).)
Dr. Steinman further explained that Rasmussen’s encephalitis also involves an
autoimmune process in which an initial T-cell driven response ultimately leads to the
development of autoantibodies against glutamate receptors, either GLuR3 or GluRε2,40
rendering it a form of autoimmune encephalitis.41 (Tr. 137, 777-78; Ex. 50.) In that
Targeted-Therapy, 81 SEIZURE: EUR. J. EPILEPSY 76 (2020) (Ex. G, Tab 2, p. 4).) However, to the extent
Dr. McCusker hypothesizes a role for an antigen-presenting nidus in particular, petitioner has filed
literature demonstrating that elevated expression of HPV antigen has been found in the brain tissue of
Rasmussen’s encephalitis patients. (Chen et al., supra, at Ex. 41.) Petitioners’ theory of vaccine-
causation for E.M.’s optic neuritis, as discussed above, would not suggest that HPV antigen was itself
present in E.M.’s brain tissue; however, the literature filed by both parties suggests that “the main
infiltrating T-lymphocyte population in [Rasmussen’s encephalitis] was likely explained from a few
precursor T-cells that responded to discrete antigenic epitopes.“ (Id. at 1 (emphasis added); see also
Orsini et al., supra, at Ex. G, Tab 2, p. 4 (“T-cells infiltrating the brain tissue expand from discrete
precursor T-cells . . . .” (emphasis added)). In that regard, Dr. Steinman has purported to show molecular
mimicry both between HPV antigen and MOG, as implicated in optic neuritis, as well as between HPV
antigen and the glutamate receptor antibodies implicated in Rasmussen’s encephalitis, at the T cell level.
(Tr. 131-36.) Accordingly, while it is not necessary to reach this question, Dr. Steinman has at least
raised the prospect that the T cells that are implicated in the development of E.M.’s optic neuritis, as a
result of being implicated as responsive to molecular mimics of HPV antigen, could likewise be causally
significant to the Rasmussen’s encephalitis.
40 Dr. Steinman suggests that GluRε2, which forms the basis of his theory implicating the flu vaccine, is
better supported by the literature, though he notes that both types of receptor have been described in the
literature. (Ex. 23, pp. 21, 28-36; Tr. 96, 137.)
41 Respondent strenuously argues that Rasmussen’s encephalitis cannot be equated to autoimmune
encephalitis. (ECF No. 128, pp. 6-8.) Despite acknowledging that Rasmussen’s encephalitis does result
from T-cell autoimmunity (Tr 338, 343-44, 512), Dr. Linnoila opined that Rasmussen’s encephalitis is not
equivalent to “autoimmune encephalitis,” which she explained is a distinct clinical entity with its own
diagnostic criteria. (Ex. C, p. 10; Tr. 343-45, 354-56, 405, 512-13.) However, Dr. Steinman was
persuasive in explaining that the literature cited by Dr. Linnoila, mainly Graus et al., identifies
Rasmussen’s encephalitis as a subset of autoimmune encephalitis. (Tr. 777-78 (citing Graus et al.,
supra, at Ex. 153, pp. 17-18, 31).) Graus et al. explain that the diagnostic criteria for autoimmune
encephalitis is merely a “syndrome-based diagnostic approach” to a category of non-infectious
encephalatides, rather than constituting definitive evidence of a distinct pathophysiology. (Graus et al.,
supra, at Ex. 153, pp. 1-2.) Thus, the authors note that, while Rasmussen’s encephalitis has a different
clinical presentation, the underlying autoimmune basis overlaps with autoimmune encephalitis. (Id. at 4.)
Therefore, the distinction between autoimmune encephalitis and Rasmussen’s encephalitis diagnostic
criteria, as drawn by respondent, is primarily relevant to diagnosis, treatment, and prognosis (Tr. 513),
and is less useful as a means of otherwise separating out the relative import of specific etiologies.
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regard, respondent has filed literature explaining that at least one type of autoimmune
encephalitis, namely NMDA receptor encephalitis,42 is known to present as an “overlap
syndrome” with demyelinating syndromes such as optic neuritis. (Bradshaw & Linnoila,
supra, at Ex. C, Tab 5, p. 10.) The Graus et al. article, first cited by Dr. Linnoila during
the hearing and later filed into evidence by petitioner, explains:
About 4% of patients with anti-NMDA receptor encephalitis develop two
different syndromes that can occur separately or simultaneously. Each
syndrome is related to a distinct pathogenic mechanism, such as anti-
NMDA receptor encephalitis along with MOG-related or aquaporin 4
(AQP4)-related syndromes . . . . In practice, physicians should be aware
that a demyelinating disorder can present as an autoimmune encephalitis
disorder, and that overlapping syndromes can occur. Patients with a
demyelinating disorder and atypical features (eg, dyskinesias or prominent
psychiatric manifestations) or patients with anti-NMDA receptor encephalitis
with atypical features (eg, optic neuritis or demyelination on MRI) should be
comprehensively studied for coexisting disorders, rather than being
classified as having an expansion of the spectrum of a single disease.
(Graus et al., supra, at Ex. 153, pp. 14-15 (internal footnote omitted).) Consistent with
the above explanation by Graus et al., Dr. Linnoila cautions that it is still unknown
Moreover, Dr. Linnoila’s opinion distinguishing the two conditions is based in part on the fact that she
does not necessarily accept as established the specific theory, as cited by Dr. Steinman, that glutamate
receptors act as targets of autoantibody attack in Rasmussen’s encephalitis. (Ex. C, p. 12.) However,
this amounts to a search for scientific certainty. Dr. Steinman’s invocation of this theory is supported by
medical literature establishing that it is considered among the viable theories of causation for
Rasmussen’s encephalitis. For example, literature filed by Dr. McCusker explains that “experimental
studies underlined that also both humeral and innate immunity plays a role in the pathogenesis of
[Rasmussen’s encephalitis], even if their mechanism has yet to be fully elucidated.” (Orsini et al., supra,
at Ex. G, Tab 2, p. 4.) Thus, Graus et al. address Rasmussen’s encephalitis under the heading of
conditions “at the frontier of autoimmune encephalitis.” (Graus et al., supra, at Ex. 153, p. 31.) The
parties argue extensively in their post-hearing briefs about whether the treating physicians’ focus on
autoimmune encephalitis constituted a critical misdiagnosis in E.M.’s case. (See ECF No. 127, pp. 6-8;
ECF No. 128, p. 8 & n.3; ECF No. 129, pp. 12-14.) However, while the treating physicians often listed
autoimmune encephalitis and Rasmussen’s encephalitis separately among their differential diagnoses,
there are notations in the medical records confirming that the treating neurology team approached
autoimmune encephalitis as a broader diagnosis, potentially encompassing of Rasmussen’s encephalitis,
rather than a mutually exclusive diagnosis. (E.g., Ex. 8, p. 1965 (Dr. Sweeney, an autoimmune neurology
fellow, discussing “autoimmune encephalitis with a similar phenotype . . . sometimes termed
Rasmussen’s encephalitis” and noting that antibodies including GLuR3 and NMDA and others have been
identified in some patients, though are negative in E.M.’s case); Ex. 8, p. 1825 (diagnosing “[p]robable
autoimmune encephalopathy/encephalitis, features suggestive of Rasmussen’s encephalitis, with prior
optic neuritis”).)
42 GluRε2 and GluR3 are part of a family of central nervous system receptors that also includes N-methyl-
D-aspartate (NMDA) receptors. (Takahashi et al., supra, at Ex. 50, p. 2.) According to Dr. Steinman,
GluRε2 is an “NMDA-type” receptor. (Tr. 137-38.) As Dr. Linnoila explains, NMDA receptor antibodies
are the most common antibody identified in patients with autoimmune encephalitis. (Id. at 401.)
However, the NMDA antibodies in NMDA receptor encephalitis target different NMDA subunits as
compared to the GluRε2 antibodies. (Ex. C, p. 12-13.)
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whether the demyelinating conditions involved in overlap syndromes have any causal
connection to the co-occurring encephalitis. (Tr. 378-81.) However, the fact that the
medical community recognizes “overlap syndrome” as an identifiable entity at a
minimum counsels against treating the presence of the two conditions at issue as mere
coincidence even as they remain different disease processes. In that regard, Fauser et
al., citing GluR3 antibodies, does specifically posit that the glutamate receptor antibody
theory of Rasmussen’s encephalitis autoimmunity, as discussed by Dr. Steinman, is
considered compatible with the multi-hit model of Rasmussen’s encephalitis. (Fauser et
al., supra, at Ex. H, Tab 4, p. 10.)
Furthermore, Fauser et al., though cautioning against a “general, nonspecific
autoimmune predisposition” to Rasmussen’s encephalitis, explain that certain prior
autoimmune conditions affecting one side of the face, including scleroderma en coup de
sabre,43 uveitis,44 or chorioretinitis,45 have been identified as predisposing factors in the
development of Rasmussen’s encephalitis. (Id. at 6-7, 10.) Petitioners have likewise
filed case reports of uveitis preceding Rasmussen’s encephalitis. (Harvey et al., supra,
at Ex. 33; Fukuda et al., supra, at Ex. 34.) Although optic neuritis is not specifically
identified by Fauser et al., it is likewise an inflammatory autoimmune condition that can
present unilaterally, albeit affecting the optic nerve, rather than the iris or retina as in
uveitis or chorioretinitis, respectively.46 (Baxter et al., supra, at Ex. A, Tab 1, p. 1; see
43 Patients with scleroderma en coup de sabre experience a linear lesion of hardening and thickening skin
affecting the frontal or frontoparietal area of the forehead and scalp. Scleroderma, DORLAND’S MEDICAL
DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=45002 (last visited Feb. 12,
2025); Coup de sabre, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=67318 (last visited Feb. 12, 2025).
44 Uveitis is an inflammation of part or all of the uvea, which commonly involves the other tunics of the eye
(i.e., sclera, cornea, and retina). Uveitis, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=52355 (last visited Feb. 12, 2025). The uvea is the
vascular coat of the eye that is comprised of the choroid, the ciliary body, and the iris. Uvea, DORLAND’S
MEDICAL DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=52354 (last visited
Feb. 12, 2025); Tunica vasculosa bulbi, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=115933 (last visited Feb. 12, 2025).
45 Chorioretinitis involves inflammation of choroid and retina. Chorioretinitis, DORLAND’S MEDICAL
DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=9589 (last visited Feb. 12,
2025).
46 It should be noted, however, that the retina is continuous with the optic nerve and does contain
neurons. Retina, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=43499 (last visited Feb. 12, 2025). The choroid, in
particular, as affected in chorioretinitis, is a thin, vascular coating of the eyeball that permits nerve
conduction from the optic nerve to the anterior structures of the eye. Choroid, DORLAND’S MEDICAL
DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=9593 (last visited Feb. 12,
2025). In E.M.’s case, she had confirmed optic disk swelling and papilledema (Ex. 5, p. 3; Ex. 6, p. 9),
suggesting that her optic neuritis had an intraocular component, rather than merely being retrobulbar (i.e.,
affecting the nerve behind the eye). Intraocular neuritis, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=92511 (last visited Feb. 12, 2025); Papilitis,
DORLAND’S MEDICAL DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=36676
(last visited Feb. 12, 2025); Retrobulbar neuritis, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=92527 (last visited Feb. 12, 2025).
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also Granata & Andermann, supra, at Ex. A, Tab 7, p. 6 (hypothesizing more broadly
that “[t]he possibility that a peripheral noxious agent may enter the brain and induce
chronic inflammatory damage is raised by the few reports of [Rasmussen’s encephalitis]
associated with unilateral uveitis and choriorenretinitis”).) And, interestingly, Fauser et
al. suggest that facial autoimmunity may be of particular significance in cases of
teenage onset of Rasmussen’s encephalitis as compared to the more typical earlier
childhood onset.47 (Fauser et al., supra, at Ex. H, Tab 4, p. 10.)
Dr. Linnoila stressed that optic neuritis is distinct from the types of autoimmunity
otherwise implicated as predisposing to Rasmussen’s encephalitis in that it is
demyelinating; however, it is inflammatory like the other conditions identified by Fauser
et al. and, when asked to explain the relationship between inflammation and
demyelination, Dr. Linnoila testified that the demyelination in optic neuritis is simply one
consequence of inflammation. (Tr. 378-83.) Accordingly, this difference does not
readily distinguish optic neuritis from the other forms of unilateral facial
autoinflammation that have been shown to predispose patients to Rasmussen’s
encephalitis, especially given that demyelinating conditions are otherwise known to
“overlap” with autoimmune encephalitis. Nothing in the Fauser et al. paper suggests
optic neuritis is incompatible with the authors’ observations. Fauser et al. observed
broadly that “11 patients with facial autoimmune diseases also had their skin or eye
affected on the side later intracranially affected by [Rasmussen’s encephalitis],”
phrasing that is broad enough to encompass intraocular optic neuritis. (Fauser et al.,
supra, at Ex. H, Tab 4, p. 10.) And, in fact, Fauser et al. do separately purport to refute
the notion that several other autoimmune conditions – not including any demyelinating
conditions – are predisposing to Rasmussen’s encephalitis. (Id.)
Ultimately, Dr. McCusker testified that, because the two conditions at issue in this
case require two different types of immune response, it is more reasonable based on
what we know about these conditions to conclude that “[l]ightning struck twice” than to
conclude that two pathophysiologically different conditions could be interrelated. (Tr.
703-08.)48 However, this is not persuasive in light of the above. Fauser et al.
specifically suggest, consistent with Dr. Steinman’s opinion, that their findings are
compatible with the idea that Rasmussen’s encephalitis requires an “interaction of
different pathogenic mechanism[s] as a prerequisite for a subsequent
immunopathological reaction.” (Fauser et al., supra, at Ex. H, Tab 4, p. 10.) In
particular, they suggest that preceding ipsilateral pathology may act as the “lateralizing
element” that explains the uni-hemispheric presentation of Rasmussen’s encephalitis.
47 At twelve years of age, E.M. was beyond the typical childhood onset age of six to ten years on average.
(Orsini et al., supra, at Ex. G, Tab 2, p. 1 (noting the mean age at presentation of Rasmussen’s
encephalitis is between six and eight years); Fauser et al., supra, at Ex. H, Tab 4, p. 4 (recording an
average age at onset, based on the 244 Rasmussen’s encephalitis patients studied, was ten years).)
48 In addition to what is discussed throughout this section, it should also be noted that this reasoning was
based in part on Dr. McCusker’s assumption that E.M.’s optic neuritis had entirely resolved prior to the
development of her Rasmussen’s encephalitis. (Tr. 705-06.) However, this is not preponderantly
supported for the reasons discussed in the next section.
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(Id.) And, although Dr. Linnoila maintained that there is no basis for extending the
Fauser group’s research to include optic neuritis specifically, she indicated that she
otherwise had no dispute with the multi-hit model of Rasmussen’s encephalitis as
explained by Fauser, et al. (Tr. 530-31.)
Moreover, all of the opining experts in this case have stressed that Rasmussen’s
encephalitis is an ultra-rare or “extremely rare” condition. (Tr. 83-84, 249-51, 336-39,
556, 732; Ex. A, p. 4.) Dr. Steinman characterized it as an “ultra orphan” disease,
meaning that it is far less studied than other more common conditions. (Tr. 83-84.) In
that context, it would impermissibly heighten petitioners’ burden of proof to require direct
evidence from literature of this unique combination of conditions – a somewhat rare
neurologic condition (affecting 1 per 500,000 children) followed by an ultra-rare
neurologic condition (affecting 1-2 per 10,000,000 children) – when the available
literature otherwise (1) correlates demyelinating conditions with autoimmune
encephalitis, (2) also separately correlates pre-existing ipsilateral facial
autoinflammation affecting the eye with Rasmussen’s encephalitis in particular, and (3)
proposes a multi-hit model of Rasmussen’s encephalitis that attributes a causal role to
both pre-existing brain lesion(s) and autoimmunity affecting the face and eyes. Given
the rarity of the condition, these three points represent clear circumstantial evidence
supportive of a legally probable theory of causation. Petitioners are obligated only to
present a sound and reliable, legally probable, causal explanation and are not required
to present directly supporting medical literature. Andreu, 569 F.3d at 1378-79 (finding
the special master erred in requiring conclusive evidence in the medical literature and
citing Daubert v. Merrell Dow Pharms., Inc., 509 U.S. 579, 593 (1993), as explaining
that “[s]ome propositions, moreover, are too particular, too new, or of too limited interest
to be published”); Althen, 418 F.3d at 1280 (observing that requiring medical literature
prevents the use of circumstantial evidence and contravenes “the purpose of the
Vaccine Act’s preponderance standard[, which] is to allow the finding of causation in a
field bereft of complete and direct proof of how vaccines affect the human body”); but
see also Caves v. Sec’y of Health & Human Servs., 100 Fed. Cl. 119, 143 (2011)
(noting that [t]he standard of proof does not operate as a sliding scale that varies
depending upon the quantity and quality of the scientific evidence that is available”),
aff’d, 463 F. App’x 932 (Fed. Cir. 2012).
Accordingly, there is preponderant evidence on this record that optic neuritis,
especially when associated with additional brain lesion(s), can be a substantial
contributing factor in, and but for cause of, the later development of ipsilateral
Rasmussen’s encephalitis.
ii. There is preponderant evidence that the latency between E.M.’s
optic neuritis and Rasmussen’s encephalitis is compatible with a
causal inference (Althen prong three)
Under Althen prong three, petitioners must demonstrate a “medically-acceptable
temporal relationship.” Althen, 418 F.3d at 1281. This showing is informed by the
theory presented under Althen prong one. Accordingly, the question to be addressed
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under Althen prong three is whether the time between the development of E.M.’s optic
neuritis and the later development of her Rasmussen’s encephalitis accords with what
would be expected if the former were to be considered among the causes of the latter,
consistent with the above-discussed multi-hit understanding of Rasmussen’s
encephalitis.
Pertinent among the hypotheses for the cause(s) of Rasmussen’s encephalitis is
the theory that Rasmussen’s encephalitis is a para-infectious autoimmune process
wherein a T-cell mediated immune response evolves into antibody-driven autoimmunity,
most likely to glutamate receptors. (Takahashi et al., supra, at Ex. 86, p. 3.) As
explained above, Fauser et al. felt the multi-hit model of Rasmussen’s encephalitis is
consistent with this understanding. (Fauser et al., supra, at Ex. H, Tab 4, p. 10.) In that
regard, a review of Japanese patients found that 38.2% of patients had a preceding
infection. (Takahashi et al., supra, at Ex. 86, p. 4, tbl.1.) One third of patients had an
infection within one month of onset. (Id. at p. 1.) Dr. McCusker further stressed that it is
theorized that Rasmussen’s encephalitis develops in three stages (identified as stages
0-2), with the inflammatory T-cell response beginning at stage one, after microglia in the
brain have already become antigen-presenting in the context of pathologic changes that
begin in “stage zero.” (Tr. 673-74; Trӧscher, supra, at Ex. G, Tab 7, p. 2.) Stage one
constitutes a prodromal period of disease progression and stage two represents the
acute phase of the condition. (Trӧscher, supra, at Ex. G, Tab 7, p. 2.) The prodromal
phase, which sees intermittent symptoms, can last for months. (Orsini et al., supra, at
Ex. G, Tab 2, p. 1.)49 Takahashi further examined Rasmussen’s encephalitis by
analyzing glutamate (GluRε2) autoantibodies from 46 patients with acute encephalitis or
encephalopathy. (Takahashi, supra, Ex. 85, p. 6.) He categorized the patients as
having either “localized” or “widespread” encephalitis based on the initial clinical
symptoms. (Id.) Patients with localized encephalitis had psychiatric symptoms, solitary
seizures, and/or mildly impaired consciousness, and then later developed more severe
conditions with a convulsive status. (Id.) According to Takahashi, the presence of
autoantibodies against GluRε2 in the cerebral spinal fluid is significantly correlated to
the onset of epilepsy in cases of widespread encephalitis. (Id.) Among those initially
presenting with localized encephalitis, antibodies tended to appear between 0-60 days
after the first onset of neurologic symptoms. (Id. at 7.) All of this together indicates that
it can take up to about 30-60 days for the expected immune response to culminate in
the acute phase of Rasmussen’s encephalitis.
In this case, the parties’ experts agree that E.M.’s first seizure on December 9,
2015, heralded the acute phase of her Rasmussen’s encephalitis. (Tr. 216, 377.)
Accordingly, if E.M.’s optic neuritis is to be considered causally relevant as the source of
the initiating precursor T cells (at stage zero), then this autoinflammation should have
been ongoing until at least sometime between mid-October to mid-November, about 30-
60 days prior to onset of the acute phase of E.M.’s Rasmussen’s encephalitis, occurring
49 The articles by Orsini et al. and Trӧscher et al. discuss the same underlying disease process but use
different labels when discussing its stages, with Orsini et al. identifying stages based on clinical
presentation and Troscher, et al. focusing on pathogenesis.
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on about December 9.50 Dr. McCusker, in particular, viewed it as problematic that there
would be any gap in time between the ongoing immune response underlying E.M.’s
optic neuritis and the subsequent development of her Rasmussen’s encephalitis. (Tr.
681-83.) In that regard, respondent contends that E.M.’s optic neuritis had fully
resolved both clinically and radiologically by the time she began experiencing seizures
on December 9, 2015. (ECF No. 128, p. 11.) More specifically, respondent argues that
E.M.’s optic neuritis appears to have resolved by October 1, 2015. (Id. at 3 (citing Ex. 6,
pp. 5-11, 14-20; Ex. 7, p. 157).) However, this is not credible.
While E.M. had a good clinical recovery and her vision did return to normal early-
on, petitioners are persuasive in contending that E.M.’s good clinical recovery is not
evidence of a complete recovery. The October 1, 2015 encounter with Dr. Digre cited
by respondent indicates that E.M.’s vision had stabilized, but also confirms by physical
exam that E.M. was still experiencing left-sided optic disk swelling. (Ex. 6, pp. 14-20.)
E.M. was diagnosed with optic neuritis at that encounter and was only subsequently
treated with steroids for the condition. (Id. at 16-17.) No repeat MRI was conducted
until after the relevant period, after onset of what was later diagnosed as Rasmussen’s
encephalitis. Respondent and Dr. Linnoila additionally stress the November 10, 2015
notation by Dr. Lloyd that E.M. was “back to normal.” (ECF No. 128, p. 10; Ex. 115, p.
244; Tr. 350.) However, this notation is in specific reference to E.M.’s vision. As
previously noted, Dr. Digre had likewise recorded as of October 1, 2015, that E.M. was
“fine” and with “good vision” while still also finding the continued presence of a swollen
optic nerve upon physical exam. (Ex. 6, pp. 14, 16-17.) Although the November 10,
2015 encounter observed the fundi were clear “overall,” resolution of the optic disk
swelling was not specifically confirmed, the impression remained left-sided optic
neuritis, and continued monitoring was planned. (Ex. 115, pp. 244-45.) Accordingly,
the November 10, 2015 encounter is not dispositive of whether there was a complete
resolution of E.M.’s optic neuritis. E.M. was not seen again until after she experienced
the clinical onset of her Rasmussen’s encephalitis.
Additionally, while optic neuritis was not specifically observed in E.M.’s
subsequent December 12, 2015 MRI, that MRI study noted that the eye orbits were “not
specifically studied.”51 (Ex. 134, pp. 498-99.) Thus, Dr. Steinman persuasively
50 Respondent argues in his post-hearing brief that “E.M.’s optic neuritis could not have caused her
December 9, 2015 seizures, and accordingly, could not have caused her Rasmussen’s encephalitis.”
(ECF No. 128, p. 11 (emphasis omitted).) However, contrary to this framing, the question at issue is not
whether E.M.’s optic neuritis directly caused her seizures. The seizures were a result of the Rasmussen’s
encephalitis under either party’s understanding of the issue. (ECF No. 127, p. 21; ECF No. 128, p. 6;
ECF No. 129, p. 32.) Rather, the question is whether, consistent with Dr. McCusker’s explanation of the
disease process, the inflammation due to optic neuritis was present at stage zero of the development of
Rasmussen’s encephalitis, such that it could have been attractant to the commencing Rasmussen’s-
related T cell responders in stage one that ultimately propagated the proposed autoantibody response
that then culminated in the acute phase of Rasmussen’s encephalitis at stage two, which began clinically
on or about December 9, 2015.
51 During the hearing, Dr. Linnoila did present images from the December 12 scan that she indicated
show a lack of enhancement of the left optic nerve; however, she acknowledged that the optic nerve is
“pretty hard to see” in the image. (Tr. 413-14.)
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explained that the later December 29, 2015 MRI, which did examine the eye orbits, did
confirm enhancement of the left optic nerve, consistent with ongoing optic neuritis. (Tr.
767-68; see also Ex. 8, pp. 1290-91.) Therefore, regardless of clinical history, there is
objective evidence demonstrating that E.M.’s optic neuritis had not resolved at any point
prior to the clinical onset of her Rasmussen’s encephalitis. With regard to the additional
left temporal lobe lesion identified from the September 2015 scan, the fact that it was
not visible on the December 12, 2015 scan is not necessarily dispositive, given the
limitations of the December 12, 2015 scan as explained by Dr. Silverman. (Tr. 282-83,
314-15, 572-91.) But, in any event, as explained above, petitioners need not
specifically prove that this lesion persisted up until seizure onset in order to be casually
relevant. Even assuming arguendo that Dr. Linnoila is more persuasive than Dr.
Silverman in concluding the less sensitive MRI would still have detected the left
temporal lobe lesion if it remained present during the December 12 scan, it would still
be speculative giving the timing of the two MRI studies to attempt to pinpoint the date of
its resolution as occurring prior to the mid-October to Mid-November period discussed
above. Although Dr. Linnoila sought during the hearing to bolster her radiographic
interpretation with clinical correlation (Tr. 413-15), she had initially opined that E.M.’s
December 10, 2015 lumbar puncture results, which showed improved but ongoing
pleocytosis, was consistent with a still resolving optic neuritis (Ex. C, p. 8).
Based on all of the above, there is preponderant evidence that E.M.’s optic
neuritis occurred (and was ongoing) during a timeframe from which it is medically and
scientifically reasonable to draw a causal inference implicating her optic neuritis as a
cause of her later manifesting Rasmussen’s encephalitis.
iii. There is preponderant evidence of a logical sequence of cause and
effect causally connecting E.M.’s optic neuritis and Rasmussen’s
encephalitis (Althen prong two)
Even having established that optic neuritis can contribute to the development of
Rasmussen’s encephalitis, and even having established that the temporal association is
present, petitioners must also demonstrate a logical sequence of cause and effect that
implicates the optic neuritis as a factor in the development of E.M.’s own condition.
Althen, 418 F.3d at 1278; Wright, 22 F.4th at 1004-06 (citing Shyface, 165 F.3d at
1352). Based on the parties’ presentations, three considerations warrant discussion.
First, was E.M.’s own condition consistent with the above-discussed theory? Second,
how did E.M.’s treating physicians approach the relationship, if any, between the two
conditions at issue? And, third, is respondent in any event persuasive in contending
that a proposed HSV infection is sufficient explanation in itself for the development of
E.M.’s Rasmussen’s encephalitis?
E.M. was first seen for what was later diagnosed as optic neuritis on September
15, 2015, with a one-month history of vision disturbance in her left eye.52 (Ex. 5, p. 3;
52 When E.M. later presented to neuro-ophthalmologist Dr. Digre, it was indicated that E.M. did initially
have symptoms in both eyes, but as the symptoms worsened, the condition progressed to affecting only
the left eye. (Ex. 6, p. 5.) Upon examination, only left-side optic nerve swelling was ever observed. (Id.
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see also Ex. 6, pp. 1-4.) She was referred to neuro-ophthalmology where she was
assessed with a swollen left optic nerve and optic neuropathy, suspected of being
papilledema due to optic neuritis. (Ex. 6, p. 9.) Follow-up MRIs were completed on
September 25, 2015, showing abnormal enlargement and enhancement of the left (but
not right) optic nerve, as well as multiple small nonspecific foci of subcortical white
matter. (Ex. 8, pp. 740, 743.) E.M. was subsequently diagnosed with left optic neuritis
and, though the radiology report indicated the relationship between the white matter foci
and optic neuritis is unclear and with no indication of active demyelination (Id. at 742-
43), a broader demyelinating disorder such as ADEM was also suspected as a matter of
clinical correlation (Ex. 6, p. 17).
Both Drs. Steinman and Linnoila agree with the optic neuritis diagnosis. (Ex. 23,
p. 40; Ex. C, p. 6.) However, while Dr. Steinman was more willing to at least entertain
the ADEM diagnosis suggested by the treating physicians (Ex. 23, p. 40; Tr. 175.), Drs.
Silverman and Linnoila both observed that E.M.’s scattered brain lesions were not
disseminated and were non-specific (Tr. 311-13, 435-36, 446-49, 592), counseling
against an ADEM diagnosis. Nonetheless, Dr. Silverman presented imaging during the
hearing showing that E.M.’s September 25, 2015 MRI evidenced a left temporal lobe
lesion that was not specifically identified in the radiology report. (Id. at 304-05.)
Ultimately, while Dr. Linnoila maintained that the scattered nonspecific foci observed in
the radiology report were not necessarily related to E.M.’s optic neuritis, she did agree
that the lesion identified by Dr. Silverman was likely a part of E.M.’s optic neuritis.53
(Compare id. at 496-97 (noting the radiologist’s notation that the relationship between
the September 25, 2015 MRI findings and optic neuritis was “unclear”), with id. at 420-
27 (agreeing that the lesion identified by Dr. Silverman “is part of the process of the
optic neuritis”).) Accordingly, there is preponderant evidence that E.M. suffered left-side
optic neuritis, inclusive of left-side brain pathology, which is therefore ipsilateral to her
subsequent primarily left-side Rasmussen’s encephalitis.
Additionally, E.M.’s subsequently occurring encephalitis was confirmed as a T-
cell mediated form of encephalitis by brain biopsy. (Ex. 19; Ex. 8, p. 1854; Tr. 126, 206.)
This demonstrates that E.M.’s own encephalitis is consistent with the pathophysiologic
explanation of Rasmussen’s encephalitis discussed in section (VI)(b)(i), supra.
Although the Mayo Clinic autoimmune panel does include some NMDA receptors, it
does not include the specific glutamate receptors implicated by Dr. Steinman’s theory.
(Ex. C, p. 12.) Accordingly, Dr. Linnoila acknowledged that further confirmation in the
at 8-9.) Dr. Thorell’s subsequent VAERS report also indicated that the initial optic neuritis was bilateral
(Ex. 139, p. 3); however, Dr. Thorell was not involved in the diagnosis and treatment of E.M.’s initial optic
neuritis. E.M. was never diagnosed as having bilateral optic neuritis.
53 Dr. Linnoila initially felt that the left temporal lobe lesion was an old, chronic abnormality, but eventually
agreed that it was related to E.M.’s optic neuritis. (Tr. 421-26, 438-41, 501-02, 567-68.) Lesions typically
only enhance for about two weeks. Greenslade v. Sec’y of Health & Human Servs., No. 14-1140V, 2024
WL 3527665, at *28 (Fed. Cl. Spec. Mstr. June 28, 2024). While Dr. Linnoila noted that the lesion cannot
be dated due to the lack of enhancement, E.M.’s first MRI was on September 25, 2015, over a month
post-vaccination, meaning it cannot be identified as pre-dating the vaccination.
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form of antibody testing for the type of glutamate receptors implicated by Dr. Steinman’s
theory would be beyond the scope of what is available in an ordinary clinical setting
using commercial labs. (Id. at 13.) To the extent there has been some indication that
E.M. had predominantly, rather than exclusively, left-sided brain lesions, Fauser et al.
preclude only exclusively contralateral lesions from their hypothesis. (Fauser et al.,
supra, at Ex. H, Tab 4, pp. 10-11.) But in any event, the treating physicians doubted
whether any of the MRI findings relative to E.M.’s right hemisphere, which were stable,
were relevant to the progressive findings affecting her left hemisphere. (Ex. 8, p. 1909
(explaining that “[s]mall focus of T2 hyperintensity in the right periventricular white
matter is unchanged over all 4 imaging examinations dating to 9/25/2015, and may be
chronic and unrelated to the findings of concern in the left cerebral hemisphere”); Ex. 8,
p. 1853 (noting “isolated involvement of left hemisphere” supports Rasmussen’s
encephalitis).) And, as discussed in section (VI)(b)(ii), supra, there is preponderant
evidence that E.M.’s optic neuritis persisted up-to and after the onset of her seizure
disorder, meaning that the timing of the clinical onset of the encephalitis is appropriate
for a causal inference for the reasons discussed above. Apart from the preponderantly
supported presence of optic neuritis, respondent has not identified any other brain
pathology that could otherwise explain the uni-hemisphere presentation of E.M.’s
Rasmussen’s encephalitis.
Thus, there is clinical evidence in this case sufficient to support a logical
sequence of cause-and-effect implicating E.M.’s optic neuritis as a cause of her later
developing Rasmussen’s encephalitis.
Nonetheless, respondent’s experts suggest that E.M. suffered optic neuritis and
then – lightning striking twice – suffered an entirely unrelated Rasmussen’s encephalitis
a short time later. However, this conclusion is in tension with the clinical judgment of
the treating physicians who were charged in the first instance with making sense of this
highly unusual disease pattern. In fact, both parties’ positions are in some tension with
the treating physicians. The probative value of the treating physician opinions is
reduced on the whole due to the lack of a clear diagnosis throughout much of E.M.’s
early treatment. However, there is a clear pattern wherein the treating physicians
repeatedly incorporated E.M.’s earlier optic neuritis into their evaluation of her clinical
picture, which actually contributed to their hesitancy in diagnosing Rasmussen’s
encephalitis.
Yet, as previously addressed, Dr. Thorell, an infectious disease specialist,
submitted a VAERS report as of January 13, 2016, in which she reported both E.M.’s
optic neuritis and her subsequent epileptic presentation as an adverse event following
her July 2015 HPV vaccination. (Ex. 139, p. 3.) Respondent focuses on that part of the
submission that indicates that ADEM remained within the differential diagnosis (ECF
No. 128, p. 24); however, Dr. Thorell described E.M.’s adverse event as optic neuritis
with later developing syndrome inclusive of “difficult-to-manage seizures” and “multifocal
encephalitis” (Ex. 139, p. 3). Dr. Thorell explained that, at that point, a “[b]road workup
of autoimmune infectious, [and] oncologic etiologies” was unrevealing, but that “[a]n
inflammatory process of autoimmune or vasculitic etiology remains a primary differential
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consideration.” (Id.) Accordingly, Dr. Thorell’s opinion cannot be reduced to one of
narrowly proposing post-vaccinal ADEM even as ADEM was proposed as a potential
unifying diagnosis. Indeed, the reason ADEM remained a part of E.M.’s differential
diagnosis for so long is precisely because the treating physicians felt that E.M.’s earlier
optic neuritis needed to be accounted for resolving the correct diagnosis. (Ex. 8, p.
1816 (noting that E.M. “has a diagnosis of T-cell mediated encephalitis similar to
Rasmussen[’]s encephalitis but does not fit the complete picture of Rasmussen[’]s (optic
neuritis preceding current issues)”); id. at 2026 (offering ADEM as a possible unifying
diagnosis for both optic neuritis and subsequent seizure disorder); id. at 2038 (“Given
the previous eye findings in conjunction with rapid progression of brain parenchymal
lesions, additional differential considerations could include . . . atypical demyelinating
(ADEM) process . . . .”).) Although a clear diagnosis did not emerge immediately, the
treating physicians, best positioned to assess a logical sequence of cause and effect,
were hesitant or unwilling to conclude based on the pattern of E.M.’s own clinical
presentation that her earlier optic neuritis was entirely unrelated to her subsequent
condition. Despite continued uncertainty, they did identify a diagnostic framing that
accords with what petitioners have proposed. As of January 24, 2015, E.M.’s neurology
team diagnosed “[p]robable autoimmune encephalopathy/encephalitis, features
suggestive of [R]asmussen’s encephalitis, with prior optic neuritis.” (Ex. 8, p. 1825.)
Though neither binding nor sacrosanct, treating physician opinions are probative and
are often afforded considerable weight in themselves. Andreu, 569 F.3d at 1375-76;
Capizzano, 440 F.3d at 1326.
Finally, respondent’s experts both opine that E.M.’s Rasmussen’s encephalitis
was more likely caused by an HSV infection. (Tr. 502-07, 690-91.) Respondent’s
contention is primarily based on two observations. First, E.M. tested positive for HSV
IgM and later IgG. (Id. at 506, 691, 739-40.) Second, E.M. experienced fevers prior to
onset of her seizures on December 9, 2015, and the records contain at least some
reports of an illness (sore throat) in the days prior to seizure onset. (Id. at 521-22, 689-
90, 740.) Petitioners dispute both points.
According to Dr. Steinman, E.M.’s reported fevers are likely a consequence of
the Rasmussen’s encephalitis prodrome itself, especially given that seizures
themselves can increase body temperature. (Tr. 802-03.) To that point, there are
conflicting notations with respect to whether E.M. was suffering any other potential
symptoms of infection. Although one record documents a reported sore throat, another
contemporaneous record explicitly denies any preceding illness. (Compare Ex. 134, p.
540 (December 9, 2015 notation of 2-day history of sore throat), with Ex. 8, p. 578
(December 9, 2015 notion of “no recent illness”).) Further to this, Dr. Steinman stresses
that E.M. underwent extensive workup for an infectious cause of her condition and none
was identified. (Tr. 112.) And, notably, while an infectious cause was included in E.M.’s
differential diagnosis, none of E.M.’s medical records actually conclude that her
condition was caused by an infection. (See, e.g., Ex. 8, p. 2033 (January 13, 2016
rheumatology note that “infectious process seems unlikely”); id. at 1761-62 (January 28,
2016 discharge summary noting that “patient was afebrile and no infections were
identified”).) At best, the treating physicians felt based on the HSV serology that an
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HSV infection could not be definitively excluded as a possible trigger for E.M.’s
condition. (Id. at 1854.)
But in any event, respondent’s experts are unpersuasive to the extent they opine
that an HSV infection, if it occurred, would constitute the sole cause of E.M.’s
Rasmussen’s encephalitis. As explained above, Dr. McCusker opined that the
development of Rasmussen’s encephalitis requires some kind of antigen-presenting
lesion within the brain that would attract T-cells in a uni-hemisphere pattern. (Tr. 673-
78.) Thus, especially because infection has otherwise been associated with
Rasmussen’s encephalitis, Dr. McCusker opined that HSV within E.M.’s brain would
have acted as that attractant. (Id. at 691-93.) However, while this is consistent with one
theory of causation for Rasmussen’s encephalitis, Dr. Steinman stressed that E.M. was
specifically tested for HSV in her cerebral spinal fluid and biopsy tissue and it was not
present.54 (Id. at 112-18.) Thus, he opined that E.M.’s condition was autoinflammatory,
but with no HSV (or any) infection within the central nervous system. (Id. at 118-21,
776-77, 800.) This is consistent with how the treating infectious disease specialist
viewed the issue. (Ex. 8, p. 1854 (noting that “it is not possible to exclude the possibility
that HSV could have triggered an immune response in part responsible for this disease
(even if there is no evidence of HSV in the brain” (emphasis added)).) Therefore, Dr.
McCusker’s causal opinion relative to HSV infection in the central nervous system is
unpersuasive as applied to the facts of this case based on objective evidence in E.M.’s
own clinical history.
Consistent with the treating physicians, Dr. Linnoila nonetheless opines that it is
not unusual for an infection in the periphery to commence an autoimmune process in
the central nervous system, carefully distinguishing E.M.’s condition from a herpes
encephalitis that would involve a direct viral infection within the central nervous system.
(Tr. 356-60, 505-07; see also Ex. 8, p. 1835 (noting viruses can cause autoimmune
encephalitis); id. at 1854 (noting HSV need not be evident in the brain to trigger an
immune response leading to E.M.’s condition).) Notably, however, Dr. Linnoila’s
explanation, though it accounts for the lack of HSV in E.M.’s cerebral spinal fluid and
biopsy, lacks any identification of a predisposing factor, such as the direct central
nervous system infection otherwise posited by Dr. McCusker, and therefore fails to
distinguish E.M.’s presentation from Dr. Steinman’s two-hit explanation for the
development of Rasmussen’s encephalitis. In effect, she merely posits that an HSV
infection outside the central nervous system, rather than the flu vaccine, would be the
source of inflammation that acted as the second hit. (Tr. 357-59.) Yet, Dr. McCusker
was clear in opining on respondent’s behalf that, immunologically, some kind of
predisposing abnormality within the left-hemisphere was necessary to explain how an
autoimmune attack could occur in a uni-hemisphere pattern. (Id. at 675.) Neither Dr.
Linnoila nor Dr. McCusker has explained how, absent such a predisposing abnormality,
Rasmussen’s encephalitis would take hold predominantly in E.M.’s left hemisphere
following a peripheral HSV infection. Therefore, because E.M.’s left-side optic neuritis
54 Some of E.M.’s medical records incorrectly indicate that her brain biopsy was positive for herpes. (E.g.,
Ex. 8, pp. 1842-43.) However, the biopsy report confirms that immunostaining of the biopsy sample did
not reveal the presence of either HSV 1 or 2. (Ex. 18, p. 2; Tr. 520.)
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with brain lesion is preponderantly established, but an HSV infection within the central
nervous system is not, Dr. Linnoila’s opinion implicating a peripheral HSV infection does
not readily call into question the additional causal role the optic neuritis in the
development of E.M.’s Rasmussen’s encephalitis.
Although the preceding optic neuritis alone would not explain E.M.’s development
of Rasmussen’s encephalitis, petitioners need not prove her vaccination to be the sole
cause of her injury. Shyface, 165 F.3d at 1352-53; see also Wright, 22 F.4th at 1005
(explaining that a vaccine injury need only be a but for cause and substantial
contributing factor of any complication or residual effect, rather than a predominant
factor). Petitioners have established a logical sequence of cause and effect whereby
E.M.’s vaccine-caused optic neuritis substantially contributed to, and was a but for
cause of, her Rasmussen’s encephalitis. This remains true regardless of whether the
final trigger leading to Rasmussen’s encephalitis was E.M.’s flu vaccination as
petitioners contend, a peripheral HSV infection as respondent contends, or a combined
effect of both.55
VII. Conclusion
After weighing the evidence of record within the context of the program, I find by
preponderant evidence that E.M.’s optic neuritis was caused-in-fact by her HPV
vaccination. I further find by preponderant evidence that E.M.’s HPV vaccination was a
but for cause and substantial contributing factor in the development of her subsequent
Rasmussen’s encephalitis, given that the vaccine-caused optic neuritis was a cause of
the Rasmussen’s encephalitis. Petitioners are therefore entitled to compensation for
these injuries. A separate damages order will issue.
IT IS SO ORDERED.
s/Daniel T. Horner
Daniel T. Horner
Special Master
55 This analysis also suffices to explain why respondent likewise has not met his own shifted burden of
proof to demonstrate that E.M.’s injury was due to any factor unrelated to her vaccination. § 300aa-
13(a)(1)(B); Deribeaux v. Sec’y of Health & Human Servs., 717 F.3d 1363, 1367 (Fed. Cir. 2013). In
order to meet his burden, respondent must demonstrate by preponderant evidence “that a particular
agent or condition (or multiple agents/conditions) unrelated to the vaccine was in fact the sole cause (thus
excluding the vaccine as a substantial factor).” de Bazan, 539 F.3d at 1354 (emphasis omitted). As with
petitioner’s burden under Althen, respondent must show a logical sequence of cause and effect linking
the injury to the proposed factor unrelated. Deribeaux, 717 F.3d at 1368-69. It need not be scientifically
certain but must be legally probable. Id. Significantly, the Federal Circuit has rejected the contention that
the presence of a viral infection can per se be considered a factor unrelated to vaccination. Knudsen, 35
F.3d at 548-50. Rather, respondent bears a burden of proving not only that there was a viral infection,
but also that the infection was principally responsible for causing petitioner’s injury. Id. (citing §300aa-
13(a)(2)). Here, for the reasons discussed above, respondent has not substantiated that the infection, if it
occurred, would have been the sole cause of the Rasmussen’s encephalitis to the exclusion of the
vaccine-caused optic neuritis. Although respondent also disputes that E.M.’s optic neuritis was vaccine
caused, he has not proposed any factor unrelated to vaccination as a cause of that condition. (ECF No.
128, pp. 28-30.)
62