Doles v. Secretary of Health and Human Services

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 17-642V
Filed: June 24, 2022
PUBLISHED
Special Master Horner
ELIZABETH DOLES,
Decision on Remand; Multiple
Petitioner, Sclerosis (“MS”); Significant
v. Aggravation; Tetanus
Diphtheria acellular Pertussis
SECRETARY OF HEALTH AND (“Tdap”) Vaccine; Polio Vaccine
HUMAN SERVICES,
Respondent.
Joseph Alexander Vuckovich, Maglio Christopher & Toale, PA, Washington, DC, for
petitioner.
Catherine Elizabeth Stolar, U.S. Department of Justice, Washington, DC, for
respondent.
DECISION ON REMAND 1
On May 16, 2017, petitioner filed a petition under the National Childhood Vaccine
Injury Act, 42 U.S.C. § 300aa-10-34 (2012)2, alleging that she suffered acute
disseminated encephalomyelitis (“ADEM”) as a result of her receipt of the polio
vaccination on April 4, 2016, and/or a tetanus, diphtheria, and pertussis (“Tdap”)
vaccination on April 22, 2016. (ECF No. 1.) On July 5, 2019, petitioner amended her
petition, now alleging that the vaccinations she received in April of 2016 caused her
central nervous system (“CNS”) demyelination best categorized as multiple sclerosis
(“MS”). (ECF No. 44.) Petitioner alleged that her condition was caused, or alternatively
significantly aggravated, by her vaccinations. (Id. at 2-3.)
1 Because this decision contains a reasoned explanation for the special master’s action in this case, it will
be posted on the United States Court of Federal Claims’ website in accordance with the E-Government
Act of 2002. See 44 U.S.C. § 3501 note (2012) (Federal Management and Promotion of Electronic
Government Services). This means the decision will be available to anyone with access to the
Internet. In accordance with Vaccine Rule 18(b), 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 the special master, upon review, agrees that the identified material fits within this definition, it will be
redacted from public access.
2All references to “§ 300aa” below refer to the relevant section of the Vaccine Act at 42 U.S.C. § 300aa-
10-34.
1
Initially, I issued a ruling on entitlement finding petitioner entitled to compensation
for a significant aggravation of her pre-existing MS. Respondent moved for review of
that determination and the Court of Federal Claims subsequently granted the motion,
finding error both with respect to procedure and consideration of the record evidence.
The Court remanded the case for further proceedings and for a determination of
entitlement under the correct legal and scientific standards. The instant decision results
from that remand. For the reasons set forth below I find that petitioner is entitled to
compensation.
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, and the petitioner is
automatically entitled to compensation, unless it is affirmatively shown that the injury
was caused by some factor other than the vaccination. § 300aa-13(a)(1)(A); § 300 aa-
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 vaccine recipient’s injury was “caused-in-fact” by the
vaccination in question. § 300aa-13(a)(1)(B); § 300aa-11(c)(1)(C)(ii). In such a
situation, of course, 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 v. Sec’y of Health &
Human Servs., 940 F.2d 1518, 1525 (Fed. Cir. 1991).
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 of the injury or condition 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
2
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;” the logical sequence must be supported by “reputable medical or scientific
explanation, i.e., evidence in the form of scientific studies or expert medical testimony.”
Althen, 418 F.3d at 1278; Grant v. Sec’y of Health & Human Servs., 956 F.2d 1144,
1148 (Fed. Cir. 1992). A petitioner may not receive a Vaccine Program award based
solely on his or her assertions; rather, the petition must be supported by either medical
records or by the opinion of a competent physician. § 300aa-13(a)(1).
In what has become the predominant framing of this burden of proof, the Althen
court described the “causation-in-fact” standard, as follows:
Concisely stated, Althen’s burden is to show by preponderant evidence that
the vaccination brought about her injury by providing: (1) a medical theory
causally connecting the vaccination and the injury; (2) a logical sequence
of cause and effect showing that the vaccination was the reason for the
injury; and (3) a showing of proximate temporal relationship between
vaccination and injury. If Althen satisfies this burden, she is “entitled to
recover unless the [government] shows, also by a preponderance of the
evidence, that the injury was in fact caused by factors unrelated to the
vaccine.”
Althen, 418 F.3d at 1278 (citations omitted). 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. The court also indicated that, in finding causation, a Program
fact-finder may rely upon “circumstantial evidence,” which the court found to be
consistent with the “system created by Congress, in which close calls regarding
causation are resolved in favor of injured claimants.” Id. at 1280.
Generally, respondent bears the burden of demonstrating the presence of any
alternative cause by preponderant evidence only if petitioner satisfies her prima facie
burden. § 300aa-13(a)(1)(B); Walther v. Sec’y of Health & Human Servs., 485 F.3d
1146, 1150 (Fed. Cir. 2007). However, respondent may also present evidence relating
to an alternative cause to demonstrate the inadequacy of petitioner’s evidence
supporting her case in chief, but petitioner does not bear the burden of eliminating
alternative causes where the other evidence on causation is sufficient to establish a
prima facie case under Althen. de Bazan v. Sec’y of Health & Human Servs., 539 F.3d
1347, 1352-53 (Fed. Cir. 2008); Walther, 485 F.3d at 1150.
In this case, petitioner has alleged that her Tdap and/or polio vaccines caused or
significantly aggravated ADEM, MS, or, more generally, CNS demyelination. Because
these conditions are not listed on the Vaccine Injury Table relative to either the Tdap or
polio vaccines, petitioner would need to satisfy the above-described Althen test for
establishing causation-in-fact to prevail on the basis that her vaccinations initially
caused her condition. At first, petitioner did focus on causation-in-fact based on the
3
Althen test, asserting her vaccine(s) caused an attack of acute partial transverse
myelitis (“APTM”). (ECF No. 68.) However, respondent argued that petitioner suffered
underlying, pre-existing MS that prevented her from demonstrating that her vaccinations
initially caused her CNS demyelination. (ECF No. 70, p. 23.) This raises an additional
question of whether petitioner experienced a significant aggravation of that condition
consistent with her alternative pleading of the claim. (ECF No. 44, pp. 2-3.) In
supplemental briefing on remand, petitioner clarifies that she contends that the attack of
APTM she alleges to have been caused by her vaccines was a part of her MS disease
process and constituted a significant aggravation of her MS. (ECF No. 97.)
The Vaccine Act defines a significant aggravation as any change for the worse in
a pre-existing condition which results in markedly greater disability, pain, or illness
accompanied by substantial deterioration of health. § 300aa-33(4). Where a petitioner
in an off-Table case is seeking to prove that a vaccination aggravated a pre-existing
injury, the petitioner must establish the three Althen prongs along with three additional
factors described in the prior Loving case. See Loving v. Sec’y of Health & Human
Servs., 86 Fed. Cl. 135, 144 (Fed. Cl. 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. Id.II. Procedural History
This case was originally assigned to Special Master Millman. (ECF No. 4.) Upon
review of the records filed initially (Exs. 1-11), Special Master Millman raised the issue
of a conflict in diagnosis. (ECF No. 9.) Special Master Millman suggested that the
medical records favored the diagnosis of MS rather than ADEM. (Id. at 1.) Additionally,
Special Master Millman noted that upon her review of the records, it appears that
petitioner’s onset of symptoms was June 4, 2016. (Id.)
Subsequently, petitioner filed additional records and a Statement of Completion.
(ECF Nos. 14-16.) On April 24, 2018, respondent filed his Rule 4(c) report,
recommending against compensation. (ECF No. 21.) Respondent indicated that the
medical records presented an unclear diagnosis, and even assuming petitioner can
establish that she suffered ADEM, petitioner failed to meet her burden in proving
causation. (Id. at 16-17.)
On May 30, 2018, petitioner filed a letter from her treating physician, Dr.
Slavenka Kam-Hansen to support her claim. (ECF No. 23; Ex. 17.) Dr. Kam-Hansen
opined that petitioner suffered ADEM. (Id.) Respondent indicated that he intended to
continue defending the claim. (ECF Nos. 24, 25.) However, petitioner advised that an
4
additional report from a different expert would be filed and, on May 24, 2019, petitioner
filed a report from Dr. John G. Steel. (ECF No. 34; Ex. 20.) Dr. Steel did not support
Dr. Kam-Hansen’s ADEM opinion, opining instead that petitioner’s correct diagnosis is
MS.
This case was reassigned to my docket on June 6, 2019, upon Special Master
Millman’s retirement. (ECF No. 41.) Respondent requested that petitioner file an
amended petition and updated medical records clarifying the nature of the injury in light
of Dr. Steel’s report opining that petitioner has MS rather than ADEM. (ECF No. 42.)
On July 5, 2019, petitioner filed an amended petition alleging that her vaccinations
caused her to suffer from “residual effects and complications of CNS demyelination,
including but not limited to: fatigue, significantly heightened temperature sensitivity, pain
and neuropathy in her right upper extremity, and the severe emotional and
psychological effects of these and other chronic symptoms,” noting that Dr. Steel felt the
condition was best categorized as MS. (ECF No. 44, p. 2.)
In response, respondent filed a report from neurologist, Dr. Subramaniam Sriram.
(ECF No. 52, Ex. A.) On January 31, 2020, petitioner filed Dr. Steel’s supplemental
expert report. (ECF No. 57, Ex. 54.) Thereafter, respondent filed his supplemental
expert report from Dr. Sriram on May 14, 2020. (ECF No. 62, Ex. O.) Petitioner then
requested that this case be resolved based on the written record. (ECF No. 63.)
On July 29, 2020, petitioner filed a motion for findings of facts and conclusions of
law accompanied by a supporting memorandum. (ECF Nos. 67, 68.) In her motion,
petitioner argued that the polio and Tdap vaccinations administered on April 4 and 22,
2016, triggered an attack of APTM that revealed her MS. (ECF No. 68.) Although
petitioner acknowledged her expert had opined she had pre-existing subclinical MS and
she had pleaded significant aggravation, significant aggravation was not raised in her
motion for a ruling on the written record. (Id.) Instead, petitioner argued that she met
the Althen test based on the post-vaccination APTM alone. (ECF No. 68.) On October
27, 2020, respondent filed a response contending that petitioner had not met her burden
of proof and that the case should be dismissed. (ECF No. 70.) Respondent followed
petitioner’s framing of the case and also did not directly address the significant
aggravation aspect of the pleading. (Id.) Petitioner filed a reply on December 4, 2020.
(ECF No. 72.)
On February 1, 2021, I issued a ruling on entitlement finding petitioner entitled to
compensation for a significant aggravation of pre-existing MS. (ECF No. 73; 2021 WL
750416.) Based on my review of the record as a whole, I concluded that the record did
not preponderate in favor of a finding that petitioner suffered an injury of APTM separate
from her MS, but nonetheless concluded that there was preponderant evidence that
petitioner’s post-vaccination demyelination constituted a vaccine-caused significant
aggravation of her MS. (Id.) The parties subsequently resolved damages informally
and I issued a decision awarding damages based on respondent’s proffer on October
15, 2021. (ECF No. 84; 2021 WL 5055851.) Thereafter, respondent moved for review
of the ruling on entitlement. (ECF No. 86.)
5
On April 1, 2022, the Court of Federal Claims issued an Opinion and Order
granting respondent’s motion, vacating the decision awarding damages, and remanding
the case for further proceedings. (ECF No. 90; 159 Fed. Cl. 241.) Explaining that the
parties had not had a full and fair opportunity to brief the issue of significant aggravation
and assigning error to the ruling’s treatment of a specific study by Langer-Gould, et al.,
the Court of Federal Claims concluded that the initial ruling on entitlement “adopted a
theory of injury and causation that Petitioner never advanced and that does not appear
to have been obvious from the evidence submitted.” (ECF No. 90, p. 6.) The Court
remanded the case “for the Special Master to consider the parties’ arguments on
aggravation of MS and to re-evaluate the medical evidence under the correct legal and
scientific standards.” (Id. at 10.) The Court also instructed that “[o]n remand, the
Special Master should give the parties the opportunity for briefing – and, if appropriate,
new written or live evidence – on whether Petitioner’s vaccinations aggravated her MS.”
(Id. at 9-10.) The Court ordered that “[t]he special master shall issue a new entitlement
decision within ninety days of this decision.” (Id. at 10 (emphasis omitted).)
On April 15, 2022, a status conference was held to discuss the remand
instructions. (ECF No. 94.) In discussing the Court of Federal Claims’ Opinion and
Order, the parties agreed to sequential briefing on the issue of significant aggravation in
accordance with a mutually agreeable schedule. (Id.) The parties also decided to forgo
supplementing the record with additional expert evidence. 3 (Id.) Petitioner filed her
remand brief on May 10, 2022. (ECF No. 97.) Respondent filed his response on May
27, 2022. (ECF No. 98.) Petitioner’s reply was filed June 3, 2022. (ECF No. 99.)
Additionally, on June 16, 2022, the parties confirmed in a joint status report that in the
event petitioner is found entitled to compensation on remand, damages should again be
awarded based on the previously filed proffer at ECF No. 82. (ECF No. 101.)
III. Prefatory Explanation of Expert Reports and the Parties’ Briefs
Regarding Significant Aggravation
As noted in the procedural history above, three experts opined in this case, Drs.
Kam-Hansen and Steel for petitioner and Dr. Sriram for respondent. Dr. Kam-Hansen
discussed petitioner’s condition as ADEM. 4 Drs. Steel and Sriram discussed petitioner’s
condition as MS, with Dr. Steel additionally asserting that TM has further relevance.
Each expert’s qualifications and opinion are summarized in the initial ruling on
entitlement and no additional expert evidence was subsequently filed. Accordingly,
3In his supplemental brief, respondent confirms only that “[p]etitioner elected not to present any additional
evidence.” (ECF No. 98, p. 4, n. 2.) During the status conference, however, respondent’s counsel
additionally confirmed that respondent also did not wish to file additional evidence on remand so long as
petitioner was not filing additional evidence. (See ECF No. 94 (confirming both parties agreed not to
supplement the record with additional expert evidence).)
4 The initial ruling on entitlement previously resolved the question of whether petitioner’s diagnosis may
have been ADEM as Dr. Kam-Hansen had opined, finding Dr. Kam-Hansen less persuasive and agreeing
with Drs. Steel and Sriram that petitioner was properly diagnosed with MS. (ECF No. 73, p. 18.) Nothing
in the subsequent history requires that analysis to be revisited. Accordingly, that finding with respect to
diagnosis is incorporated by reference and the accompanying analysis is not repeated.
6
familiarity with the prior ruling is assumed and these summaries will not be repeated
herein. However, due to the issues discussed by the Opinion and Order remanding this
case and the parties’ subsequent briefing regarding significant aggravation of
petitioner’s MS, additional discussion confirming the undersigned’s understanding of Dr.
Steel’s opinion is warranted. In particular, respondent continues to contend on remand
that Dr. Steel did not articulate a significant aggravation theory.
As observed by the reviewing Court, the phrasing of Dr. Steel’s reports has led to
some confusion that has been compounded by petitioner’s initial approach to her own
expert’s reports. (ECF No. 90, p. 4.) Specifically, the Court observed that some of the
language in Dr. Steel’s report is consistent with a significant aggravation claim as the
prior ruling on entitlement had initially concluded, but that “it is difficult to understand in
the context of Dr. Steel’s other opinions.” (Id. at n. 3.) This confusion may be
attributable in part to the fact that Dr. Steel did not specifically address the legal
requirements of the Program. Often experts in this Program will provide a discussion
addressing how their medical analysis relates to the relevant legal test (e.g., discuss
each Althen or Loving prong). Dr. Steel did not do this, leaving some room for
subsequent interpretation. Additionally, three specific aspects of Dr. Steel’s opinion,
discussed below, potentially hinder the clarity of his reports: he refers to MS as a “red
herring;” he characterizes petitioner’s pre-existing MS merely as a “susceptibility” to a
vaccine injury; and he references petitioner as having APTM. However, although some
of this specific language seems as though it is in tension, Dr. Steel’s medical opinion
has been consistent in identifying a significant aggravation of petitioner’s MS,
notwithstanding his further references to transverse myelitis (“TM”).
“Transverse myelitis is a common manifestation or presenting feature of acquired
demyelinating diseases of the central nervous system.” (Elliot M. Frohman & Dean M.
Wingerchuk, Transverse Myelitis, 363 N. ENGL. J. MED. 564, 567 (2010) (Ex. 39).) Thus,
when Dr. Steel wrote his first report in this case, he opined that:
It is my opinion that [petitioner] experienced an attack of focal myelitis
(inflammation of the spinal cord), caused by neuroimmune activation from
receiving two vaccinations in close proximity. Focal myelitis can be
associated with several different diagnoses, including Multiple Sclerosis . .
. Following the attack of myelitis, [petitioner] meets current diagnostic
criteria for Multiple Sclerosis. She experienced a clinically symptomatic
event in a limited time window following vaccinations. This event, called a
Clinically Isolated Event, was her first episode of neurological symptoms
typical of an MS relapse in a person not known to have MS.
(Ex. 20, p. 3 (emphasis original).)
The literature filed in this case explains that “[a]ttack, relapse, exacerbation, and
(when it is the first episode) clinically isolated syndrome are synonymous.” 5 (Alan J.
5 In her supplemental reply on remand, petitioner distinguishes her theory of a significant aggravation
leading to clinically isolated syndrome as being distinct from a “relapse.” (ECF No. 99, pp. 6-7.)
Petitioner is correct insofar as clinically isolated syndrome refers uniquely to a first onset of neurologic
symptoms.
7
Thompson, et al., Diagnosis of multiple sclerosis: 2017 revisions of the McDonald
criteria, 17 LANCET NEUROL. 162, 163 (2018) (Ex. C).) Dr. Steel explained that the spinal
lesion at issue “is typical for an episode of focal spinal myelitis, as opposed to
Transverse Myelitis (where the lesion would cross the spinal cord) or Neuromyelitis
Optica. The lesion is radiographically typical for an MS plaque in the spinal cord.” (Ex.
20, p. 3.) In his second report, Dr. Steel further refined his opinion to specify that the
focal myelitis constituting petitioner’s Clinically Isolated Syndrome (“CIS”) is best
characterized as APTM. (Ex. 54, pp. 3, 7.) However, he further indicated that “[a]cute
partial myelitis is strongly associated with multiple sclerosis, either as an initial
presenting disease or as part of the ongoing relapsing-remitting course of MS.” (Id. at
3.)
Dr. Steel further explained that prior to vaccination petitioner’s condition
constituted what is called Radiographically Isolated Syndrome (“RIS”), which means MS
was present, but evidenced only by lesions that could have been detected by MRI while
the disease remained clinically silent by neurologic exam. (Id.) According to Dr. Steel, a
person with RIS (or clinically silent MS) is already suffering autoimmune disease
process even though their condition is subclinical. (Ex. 20, p. 5.) Thus, he clarified that
in this case “[t]he vaccinations likely did not cause the MS but rather unmasked it, i.e.
caused it to become clinically significant during her medical evaluation.” (Ex. 20, p. 3.)
However, because he acknowledged that epidemiologic evidence specifically
linking vaccination and MS relapse is lacking, Dr. Steel’s initial report discussed the
causes of immune-related demyelination in the broader context of other CNS
demyelinating conditions, such as TM, based on the premise that petitioner’s clinically
isolated event (synonymous with a relapse or attack of MS) manifested as a focal
myelitis of the spine. (Ex. 20, p. 4.) Dr. Steel characterized both MS and TM as
existing within a category of immune-mediated CNS demyelinating disorders that differ
epidemiologically but nonetheless have pathophysiologic commonalities. (Id. at 3-4.)
He further asserted in his initial report that “there is epidemiological evidence and
clinical experience that vaccinations, along with other non-specific immunogenic
stresses, such as insect bites, minor trauma, surgery, infectious illness and
environmental or psychological stress, may trigger an immune-mediated attack of
demyelination in persons who are susceptible for genetic or other reasons.” (Ex. 20, p.
4 (emphasis added).) By Dr. Steel’s terms of reference, clinically silent MS is such a
susceptibility due to the presence of ongoing autoimmunity. (Ex. 20, p. 5; Ex. 54, p. 7.)
More specifically, Dr. Steel suggested that MS tilts the CNS toward a pro-
inflammatory state and that vaccines may further activate subclinical autoimmunity in
the CNS as an unintended consequence of stimulating a heightened immune response.
(Ex. 20, pp. 4-5.) In that regard he cited literature discussing a “fertile field” theory of
autoimmunity specifically explaining why multiple immune stimuli may lead to clinically
overt MS. (Ex 20, pp. 4-5 (citing Robert S. Fujinami et al., Molecular Mimicry,
Bystander Activation, or Viral Persistence: Infections and Autoimmune Disease, 19(1)
CLIN. MICROBIOL. REV. 80 (2006) (Ex. 24).) Thus, Dr. Steel stressed language from his
supporting literature indicating that while TM may occur in isolation, “infection or
immunization may also trigger attacks of myelitis in the context of underlying disease,
8
especially multiple sclerosis or neuromyelitis optica.” (Ex. 20, pp. 4-5 (quoting Frohman
& Wingerchuk, supra, at Ex. 39, p. 567).)
However, in responding to Dr. Steel’s first report, Dr. Sriram focused on
associational data specifically examining relapses in MS and dismissed any evidence
regarding myelitis that was not strictly limited to the context of MS. (Ex. A, pp. 9-10.)
Thus, when Dr. Steel wrote his second report responding to Dr. Sriram, he explained:
[Petitioner] had clinically silent MS that came to light after her attack of TM
but her MS is a red herring and has served to confuse the issue. In my
report of 21 May 2019 I made no assertion of a causal relationship between
the vaccines and MS. I gave a limited and carefully worded opinion
regarding the myelitis only. Dr. Sriram’s rebuttal of 22 November 2019
focused on MS but did not address the actual causal relationship that I have
asserted, between [petitioner’s] April 2016 vaccinations and her subsequent
attack of spinal myelitis. By discussing MS only, he failed to address our
central point.
(Ex. 54, p. 2 (emphasis added).)
Based at least in part on this passage, the parties originally briefed this case
under the Althen test for causation-in-fact on the premise that petitioner suffered an
acute TM injury that was distinct or separate from her more chronic course of MS. (ECF
Nos. 68, 70, 72.) However, while some of Dr. Steel’s language (such as the above “red
herring” statement) may be viewed as lending support to this approach, it does not fully
or accurately capture Dr. Steel’s opinion. Dr. Steel was very clear in his first report in
opining that petitioner’s post-vaccination focal myelitis constituted CIS (i.e., a first attack
of MS) and continued to confirm in his second report that he understood the attack of
myelitis to be a part of her ongoing MS, which was clinically silent prior to vaccination
and became clinically overt after vaccination. (Ex. 54, pp. 3, 7.)
Additionally, Dr. Steel’s causal theory was specifically premised on the presence
of ongoing autoimmunity in the form of pre-existing subclinical MS, including citation to
literature explaining why subclinical MS in particular may respond to a second immune
insult. Dr. Steel opines that “[a]lthough there is little evidence that vaccinations cause
multiple sclerosis in healthy patients, there is convincing evidence that vaccinations
occasionally trigger single attacks of TM, ADEM, optic neuritis, and isolated spinal
myelitis, and there is good reason to think that such an event is more likely in patients
with subclinical MS.” (Ex. 20, p. 5.) Ultimately, Dr. Steel concluded his final report by
explaining that “Dr. Sriram’s extensive discussion of the epidemiology of vaccinations
and MS does not address my claim that the vaccine triggered an episode of spinal
myelitis in the context of the patient’s pre-existing clinically silent MS.” (Id. at 7
(emphasis added)).
Importantly, notwithstanding how the parties initially postured the case in their
briefs, respondent’s expert, Dr. Sriram, fully understood Dr. Steel’s opinion, albeit while
strongly disagreeing. In response to Dr. Steel’s first report, Dr. Sriram responded
directly to Dr. Steel’s line of reasoning. He offered the competing opinion that “[t]he
prevailing opinion does not support the view that vaccines, even when given ‘in close
9
temporal proximity,’ in anyway way ‘trigger’ onset or relapses in patients with MS,
including individuals with previously clinically silent MS.” (Ex. A, p. 15.) In response to
Dr. Steel’s second report, Dr. Sriram correctly paraphrased Dr. Steel as opining that
“what Dr. Steel is attempting to state is that while [petitioner] has MS and myelitis is part
of the MS syndrome, her myelitis was caused by the vaccine.” (Ex. O, p. 2 (emphasis
added).) He countered that opinion by indicating that “Dr. Steel goes on to provide
literature to support his position of a putative relationship between vaccines and
transverse myelitis, fully aware that the literature does not provide any relationship,
causal or otherwise, between transverse myelitis seen in patients with MS and receipt of
vaccines.” (Ex. O, p. 2.)
Dr. Sriram contended that “Dr. Steel’s argument that ‘very likely, the immune
stimulation from multiple vaccinations altered her biological equilibrium,’ resulting in an
‘unmasking’ of [petitioner’s] MS, lacks any scientific foundation and contravenes what
we know about MS as a disease process.” (Ex. O, p. 6.) Thus, Dr. Sriram understood
that Dr. Steel had offered an opinion that petitioner’s vaccines had acted upon her MS
disease process. However, because he opines that petitioner’s MS is itself the sole
explanation for petitioner’s myelitis, Dr. Sriram characterized Dr. Steel’s attempt to find
causal factor for petitioner’s disease-associated TM beyond the MS itself as “a mistake
in clinical diagnosis.” (Ex. O, p. 6.) Dr. Sriram contended that “[t]here is no confusion
here about [petitioner’s] MS diagnosis. The confusion is in trying to invoke an alternative
etiology for transverse myelitis, when none is evident.” (Id. at 2.)
Petitioner previously acknowledged in response to respondent’s motion for
review that in her initial motion for a ruling on the record she elided the significant
aggravation opinion inherent to her expert’s opinion. (ECF No. 89, p. 5 (expressing
surprise the case was decided based on significant aggravation).) In supplemental
briefing on remand, however, petitioner indicates that her original argument was made
in light of the fact that Dr. Steel’s reports “conceptualized her APTM as a discrete
medical event caused by the vaccines.” (ECF No. 97, p. 9 (emphasis added).)
Petitioner now also confirms that the medical “event” in question – her alleged APTM –
was, as Dr. Steel had opined, “radiographically typical for an MS plaque in the spinal
cord.” (Id. (quoting Ex. 20, p. 3).) Petitioner further contends that based on Dr. Steel’s
reports “[p]etitioner’s attack of APTM can only be understood as the first clinical event in
the progression of her MS which pre-existed her vaccinations.” (Id.) Thus, petitioner
argues that “her development of APTM secondary to vaccination did in fact constitute
significant aggravation of her pre-existing MS per the Loving test.” (Id. at 10.)
Petitioner maintains that her prior discussion of the Althen test relative to APTM
otherwise remains operative with respect to vaccine causation. After explaining that
vaccine causation under Loving is decided under the same three prong test as Althen,
petitioner incorporated by reference her prior argument as to why petitioner’s APTM
was caused by her vaccines. (Id. at 9-10 (citing ECF No. 68, pp. 15-25).)
In his supplemental brief on remand respondent likewise agrees that petitioner
did suffer a significant aggravation of her MS within the legal framework of this Program.
(ECF No. 98, p. 7, n. 3.) Respondent confirmed that for that reason he would not brief
the first three Loving prongs on remand. (Id.) Rather, respondent contends that
petitioner’s claim should fail with respect to the fourth Loving / first Althen prong. (Id. at
10
6-7.) Respondent argues that Dr. Steel did not actually articulate a significant
aggravation theory and that, even addressing such a theory arguendo, it is not reliably
supported. (Id. at 7-13.) Because respondent asserts petitioner did not satisfy the
fourth Loving prong regarding a theory of general causation, he concluded that
petitioner therefore necessarily also could not satisfy Loving prongs five and six and
opted not to provide any additional substantive argument regarding specific causation.
(Id. at 13-14.)
However, like petitioner, respondent also incorporated by reference his
arguments made in connection with petitioner’s initial motion for a ruling on the written
record. (ECF No. 70, p. 1, n. 1.) Although respondent has disputed that petitioner’s
expert articulated a theory of significant aggravation, respondent nonetheless
responded to petitioner’s initial motion with an Althen analysis that was responsive to
such a theory, contending that “[p]etitioner has not demonstrated with preponderant
evidence that the polio and Tdap vaccines can cause ‘focal myelitis’ or APTM in
someone with MS, i.e., a relapse” and “[p]etitioner has also failed to prove by a
preponderance of the evidence that, in this case, the vaccinations, rather than her
underlying MS, caused her to experience a relapse.” (ECF No. 70, p. 16.)
In light of all of the above, and having completed the remand instruction for
additional briefing, I conclude that the parties have had a full and fair opportunity to
develop the record of this case with regard to significant aggravation and that the case
is ripe for resolution on the existing record. 6 I have considered the parties’ additional
arguments on remand and now reexamine petitioner’s claim that her vaccinations
significantly aggravated her pre-existing MS pursuant to the six-part Loving test and in
light of the Court’s guidance. Respondent’s contention that Dr. Steel did not articulate a
theory of significant aggravation of MS is not persuasive given the above.
Respondent relies heavily on the idea that Dr. Steel’s reference to MS as a
“susceptibility” necessarily indicates that his opinion was limited to an assertion that
petitioner’s pre-existing MS left her at heightened risk of TM as a separate condition.
(ECF No. 98, pp. 7-8.) However, the term “susceptibility” is not in itself informative. A
person can be said to be susceptible to a further harm just as a person can be said to
be susceptible to a new harm. In this case, respondent’s interpretation is incompatible
with Dr. Steel’s explicit assertion that petitioner’s focal myelitis constituted CIS leading
to a diagnosis of MS. While there is no doubt Dr. Steel finds acute TM and its causes to
be relevant to his opinion, he specifically explained that TM does also occur as part of
the MS disease process.
6 As noted above, the parties have provided supplemental briefing on the question of significant
aggravation, but otherwise confirmed during a status conference regarding the parameters of the remand
that they did not wish to pursue further expert evidence. (ECF No. 94.) Special masters “must determine
that the record is comprehensive and fully developed before ruling on the record.” Kreizenbeck v. Sec’y
of Health & Human Servs., 945 F.3d 1362, 1366 (Fed. Cir. 2020) (citing Simanski v. Sec’y of Health &
Human Servs., 671 F.3d 1368, 1385 (Fed. Cir. 2012); Jay v. Sec’y of Health & Human Servs., 998 F.2d
979, 983 (Fed. Cir. 1993.)); see also Vaccine Rule 8(d); Vaccine Rule 3(b)(2). The parties must have a
full and fair opportunity to present their case and develop a record sufficient for review. Id.11
Respondent also argues: “[p]etitioner further conceded that ‘Dr. Steel’s report
and Petitioner’s Memorandum conceptualized her APTM as a discrete medical event
caused by the vaccines.’ In other words, petitioner herself admits that Dr. Steel did not
provide an opinion that her TM constituted a significant aggravation of her MS.” (ECF
No. 98, p. 8 (internal citation omitted).) Respondent’s reinterpretation of petitioner’s
brief does not track. Petitioner specified in that same brief that “[p]etitioner’s attack of
APTM can only be understood as the first clinical event in the progression of her MS
which pre-existed her vaccinations.” (ECF No. 97, p. 9.) Moreover, a relapsing,
remitting disease such as MS will necessarily comprise discrete events. Respondent’s
own expert, who clearly opines that MS is the only relevant condition, also characterizes
the myelitis at issue in this case as a discrete medical event. He explains that in MS
“[t]he first neurological event . . . is referred to as clinically isolated syndrome. In a
patient later diagnosed with MS, the clinically isolated syndrome constitutes the first
attack of the disease.” (Ex. A, p. 7.) With regard to petitioner’s own condition, he cites
petitioner’s MRIs to note that “[t]he enhancing lesions suggested a recent acute event.”
(Ex. O, p. 1.) Petitioner’s reference to APTM as a “discrete medical event” is not
contrary to a significant aggravation claim.
The remainder of the parties’ arguments are addressed within the Loving
analysis below.
IV. Medical History 7
a. Pre-Vaccination
Petitioner, 67 at the time of the vaccinations at issue, has a history of Graves’
disease. (Ex. 2, p. 51-54.) Petitioner sought treatment at Cambridge Health Alliance for
her hypothyroid condition. (Ex. 3.) Her primary care records from 2010 to 2012
indicated she also had a bladder hernia, degenerative joint disease, and underwent a
hysterectomy. (Id.) She is allergic to penicillin. (Id. at 7.) Petitioner has received
several vaccinations in the past. (Id.) In 2011, petitioner received a physical exam in
order to travel to Sri Lanka for work. (Id. at 28.) Her exam was normal and she
requested several immunizations, denying any allergies to flu vaccine and history of
Guillain-Barré syndrome. (Id. at 29-30, 33.) In 2015, petitioner had a physical therapy
evaluation for ongoing knee and hip pain that worsened over 10 years. (Ex. 4, p. 141-
43; Ex. 14, p. 44.)
b. Vaccination and Initial Treatment
Petitioner received a polio vaccination on April 4, 2016, and a Tdap vaccination
more than two weeks after on April 22, 2016. (Ex. 1.) Petitioner had a mammogram
and pap smear on April 4, 2016 (Ex. 5) and an evaluation for colonoscopy on April 8,
2016 (Ex. 7.) Petitioner had a colonoscopy on April 13, 2016. (Ex. 4, p. 116; Ex. 7, p.
6; Ex. 14, p. 28.) On April 21, 2016, petitioner visited Capital Cardiology Associate PA
for an evaluation of an abnormal EKG. (Ex. 14, p. 24.) Dr. Bipinpreet Nagra
7This medical history is copied verbatim from the prior February 1, 2021, ruling on entitlement. No further
medical records were filed subsequent to issuance of that ruling.
12
recommended an echocardiogram and stress test due to petitioner’s family history. (Id.)
On April 22, 2016, petitioner visited Lotus Medical Care for “PPD reading, 8 Tetanus
shot, forms to be signed.” (Ex. 19, p. 3.) Dr. Arkadiy Shraytman noted the visit was for
screening of tuberculosis, follow up exam, and immunization. (Id. at 5.) Petitioner
returned to Lotus Medical Center on May 27, 2016 for “Polio titer” and low back pain
and primary generalized osteoarthritis were also noted as problems. (Id. at 7.) On June
1, 2016, petitioner visited Lotus Medical again to review her results and occipital
neuralgia and iodine-deficiency were noted. (Id. at 10-12.)
On June 5, 2016, petitioner sought treatment at Capital Health Regional Medical
Center emergency room for right side weakness and numbness, which began two
nights prior. (Ex. 2, p. 50-51.) Two hours prior to arriving at the emergency room,
petitioner reported experiencing itchiness and redness from scratching along AC joint
and right shoulder. (Ex. 8, p. 39.) Petitioner had a consultation for a transient ischemic
attack (TIA). (Ex. 8, p. 2.) Petitioner presented with achy pain in her right upper
extremity, including her shoulder, neck stiffness, and mild weakness in her right grip.
(Id.) Petitioner’s head CT did not show any acute changes, only chronic lacunar
infarctions. (Id.) Dr. Rajat Kumar examined petitioner and assessed that she presented
with transient right upper extremity achiness and grip weakness. Dr. Kumar indicated
that petitioner’s CAT scan found lacunar infarcts and therefore, recommended
additional imaging. (Ex. 2, pp. 60-61.) Petitioner underwent several imaging studies on
June 5, 2016. Her angiography of the neck and head without contrast found no
evidence of aneurysmal dilation or significant stenosis. (Id. at 36-37, 42-43.)
Petitioner’s brain MRI without contrast found no acute infarction, intracranial mass or
hemorrhage, but did find multiple nonspecific foci of white matter hyperintensity that
suggest a clinical diagnosis of a demyelinating disease. (Id. at 40.) Petitioner’s head
CT without contrast also found no signs for acute intracranial hemorrhage but revealed
patchy regions of white matter hypoattenuation that may reflect microvascular ischemic
changes, age indeterminate infarcts, and/or demyelinating disease. (Id. at 47-48.)
Additionally, right maxillary sinus disease was noted. (Id. at 48.) Petitioner received
steroids and her symptoms improved. (Ex. 8, p. 54.) Petitioner was discharged to
rehab and was found to have an acute demyelinating disease with TM. 9 (Ex. 8, p. 33.
54.)
The next day, petitioner returned to Capital Health and was admitted. (Ex. 4, p.
43.) Petitioner also saw Dr. Kumar again for a neurology consult for weakness. Dr.
Kumar noted white matter lesions in the periventricular region and subcortically that do
not demonstrate enhancement but observed active demyelinating disease in the right
lateral cervical area at C3-C4 that did enhance. (Ex. 8, p. 74.) Dr. Kumar assessed
petitioner with acute demyelinating CNS disease, noting her presentation was
“suggestive of multiple sclerosis.” (Ex. 8, pp. 71-76.) Petitioner received a consultation
8
PPD refers to a tuberculin skin test.
9In fact, the discharge diagnosis was “acute demyelinating CNS disease/multiple sclerosis.” (Ex. 8, p.
54.) Only the “hospital course” notation references “acute demyelinating disease with transverse
myelitis.” (Id.)
13
from Dr. Michael S. Beede on June 11, 2016, for “positive ANA, in the context of
previous Graves’ disease, and with new multiple sclerosis.” (Ex. 8, p. 64.) Petitioner’s
brain and cervical MRI were compatible with the diagnosis of MS. (Id. at 64, 152.) Dr.
Beede indicated that the positive ANA may be either from petitioner’s thyroid disease or
MS. (Id. at 65.)
Petitioner underwent various MR imaging on June 6, 2016. (Ex. 2, pp. 16-28.)
An MRI of the thoracic spine with and without contrast revealed overall no abnormal
signal or enhancement within the thoracic spinal cord. (Id. at 16.) However, certain
regions demonstrated enhancement that were indeterminate and there were mild
degenerative changes in the thoracic spine. (Id. at 16-17.) Additionally, there was a
small disc protrusion that caused mild right subarticular zone stenosis. Follow up was
recommended. (Id. at 17.) The MRI of the lumbar spine with and without contrast
showed degenerative changes in the lumbar spine and a possible impingement upon
certain nerve roots. Additionally, the MRI findings also suggested an atypical
hemangioma and follow up was recommended. (Id. at 20-21.) The MRI of the cervical
spine with and without contrast found an abnormal signal within the spinal cord involving
the right lateral column. (Id. at 23-24.) The brain MRI with and without contrast taken
on June 6, 2016, was compared with the MRI without contrast taken on the day before.
The more recent MRI still showed multiple regions of white matter hyperintensity mostly
in the periventricular and subcortical area running perpendicular to the ependymal
surface regions; however, the white matter lesions did not demonstrate enhancement.
(Ex. 2, pp. 27-28.) She had a chest x-ray that showed bibasilar subsegmental
atelectasis and cardiomegaly. (Id. at 31.) And petitioner’s head CT did not reveal any
acute intracranial findings. However, “scattered areas of white matter hypoattenuation
are unchanged with corresponding signal abnormality on the preceding brain MRI, most
compatible with a demyelinating process. There is no mass effect.” (Id. at 34.)
Petitioner was discharged to rehab from Capital Health on June 14, 2016, with
multiple diagnoses including acute demyelinating CNS disease / MS, acute weakness of
the right side. (Id. at 50.) During her stay, petitioner was found to have an acute
demyelinating disease with TM and was treated with high dosage of steroids. Petitioner
showed drastic improvements but was still weak and therefore needs rehab and a
neurological follow up. (Id. at 51.)
Petitioner was admitted into St. Lawrence Rehabilitation Center for general
debility upon discharge from Capital Health. (Ex. 4, p. 10.) Dr. Madhu Jain, upon
review of systems, noted that petitioner reported double vision in the right eye
(premorbid). (Id.) Upon examination, petitioner was noted with decreased grip strength
and overall strength, decreased fine motor control, and decreased balance. Dr. Jain’s
impression was mild right-side weakness with new onset diagnosis of MS post steroid
therapy with continued weakness in right upper and lower extremity. Petitioner was
recommended both physical and occupational therapy to address transfers, ambulation,
and self-care. (Id. at 11.)
14
On June 23, 2016, petitioner visited Dr. Shukia for a follow up evaluation of her
right-sided weakness. (Ex. 2, p. 2.) Petitioner reported that while she was at Capital
Health System, she had a brain MRI that showed some white matter changes, but a
couple of days after being discharged, she experienced right leg weakness and
returned for a C-spine MRI, which showed an enhancing area of abnormal signal. (Id.
at 3.) Petitioner sought treatment at St. Lawrence Rehab and reported that her strength
significantly improved. Dr. Shukia reported that other than a mild limping feeling in the
right leg, petitioner seemed to have returned to baseline. Dr. Shukia suggested a full
work up including a spinal tap. However, he noted that petitioner did not have any
episode of blindness and that “this lesion in the C-spine is also not more than 2
segments of the cervical column.” Petitioner also visited Dr. Shukia on July 14, 2016,
for a follow up evaluation for history of possibility of demyelinating disease. (Ex. 2, p.
1.) Dr. Shukia noted that petitioner had a “somewhat bloody” spinal tap that tested
positive for oligoclonal bands. (Id.) Upon physical examination, petitioner presented
normal upper and lower extremity strength. Dr. Shukia’s impression was that petitioner
presented with a demyelinating disease, most likely MS and discussed petitioner’s
options regarding treatment and medicine during this visit. (Id.)
Petitioner had an occupational therapy evaluation and treatment on June 27,
2016, for MS exacerbation. (Ex. 4, p. 43.) Petitioner showed improvements after one
month in rehabilitation in upper extremity strength, coordination, and endurance, but
had mild deficits in right shoulder strength and fine motor coordination. (Ex. 4, p. 46.)
c. Subsequent Post-Vaccination History
On July 6, 2016, petitioner received an initial consultation from Dr. Chitharanjan
Rao at the Lawrenceville Neurology Center. (Ex. 4, p. 8.) Dr. Rao’s assessment was
that petitioner has a history of acute/subacute onset right sided weakness since June 5,
2016 “in the setting of TDP vaccination in early April 2016.” (Id.) However, the
symptoms have nearly resolved and no further episodes, and therefore petitioner is
normal from a neurological standpoint notwithstanding the mild sensory loss in her left
hand and diffuse hyperreflexia. Dr. Rao diagnosed petitioner with likely ADEM,
probably related to her vaccination, but MS is a possibility. (Id.) Dr. Rao recommended
continuing physical and occupational therapy and avoiding receiving vaccinations for
the season. (Id. at 9.)
Petitioner returned to Lotus Medical on July 12, 2016, for a follow up appointment
post hospitalization for possible MS. (Ex. 19, p. 12.) Dr. Shraytman ruled out ADEM
but noted MS and low back pain among petitioner’s list of problems. (Id. at 13-14.)
Aside from seeking treatment from Dr. Rao, petitioner continued visiting Dr.
Shukia for her demyelinating disease. (Ex. 4, p. 104; Ex. 14, p. 18.) Dr. Shukia
continued to believe that petitioner most likely has MS. (Id.) Petitioner had a broken
pinky toe and was treated at Champion Orthopedics on August 1, 2016. (Ex. 4, pp. 95-
97.) Petitioner underwent physical therapy at St. Lawrence Rehabilitation Center from
June 27, 2016 and was discharged on August 10, 2016. (Ex. 6.) Petitioner “progressed
15
very well with therapy [and met] all goals therefore has been discharged with [home
exercise program].” (Id. at 5.)
A cervical spine MRI performed on August 17, 2016, again showed lesions and
enhancement compatible with a demyelinating process related to petitioner’s history of
MS. (Ex. 4, p. 49-51.) Petitioner received a follow up evaluation for her MS from Dr.
Rao on August 19, 2016. 10 (Ex. 4, p. 1; Ex. 14, p. 1.) According to Dr. Rao, petitioner’s
VEP tests indicated a mild conduction delay involving the right optic nerve but her spinal
tap was traumatic and negative for oligoclonal bands. 11 (Ex. 4, p. 1, 33-35, 52.)
Petitioner reported paresthesia in her right and left upper extremity, numbness in her left
hand, hyperpathia to touch, but believed she was much better with nearly normal gait.
(Id. at 1.) Upon review of petitioner’s MRI imaging, Dr. Rao indicated that the results
were consistent with a history of MS and that no new abnormal findings were detected.
(Id. at 2.)
Petitioner began receiving primary care at Beth Israel Deaconess Medical Center
after moving back to Boston from New Jersey in September 2016. (Ex. 11, p. 2.)
Petitioner reported that three neurologists had diagnosed her with MS; however, she
“saw a neurologist in whom she now has a lot of confidence who diagnosed her as
having [ADEM].” (Id.) Petitioner reported experiencing continuing weakness and
dysesthesias and acute cramping in right upper extremity. (Id.) Dr. Harvey Bidwell
noted ADEM after polio vaccine and Tdap injection as part of petitioner’s history of
present illness. (Id. at 12.) Dr. Bidwell accepted petitioner’s diagnosis of ADEM and
referred petitioner for physical and occupational therapy. (Id. at 25.) In addition,
petitioner saw Simone D. Martell, LCSW, for emotional support in coping with a
neurological disease diagnosis. (Id. at 10-12, 17-21.)
On September 20, 2016, petitioner was admitted to the emergency department at
Beth Israel Deaconess Medical Central for seizures. (Ex. 10, p. 3.) Petitioner reported
a recent diagnosis of ADEM 12 and symptoms of aura and weakness to extremities
(right 13 leg arm and leg numbness). (Id. at 6, 8.) Petitioner had a neurology consult for
right hand and leg spasms. (Id. at 27.) Upon examination Dr. Fay Gao found that
petitioner had subjective positive sensory symptoms but no objective deficits to all
sensory modalities tested. (Id. at 30.) Dr. Gao noted that “[w]hile tonic spasm can
occur in the setting of recent demyelination, [petitioner] does not have any other
10Petitioner additionally had follow-up visits with Dr. Rao on July 28, 2016, August 18, 2016. The exams
were similar and Dr. Rao had the same observations/conclusions.
11 As Special Master Millman previously observed, Dr. Rao incorrectly stated that petitioner did not have
oligoclonal bands and seemed unaware that petitioner had abnormal VEP on the right. (ECF No. 9, p. 1.)
Dr. Rao concluded that the lesions of her spinal cord were consistent with petitioner’s history of MS, yet
Dr. Rao concluded that petitioner did not have MS but ADEM. (Id.)
12 Petitioner reported a possible diagnosis of ADEM or MS. (Ex. 10, p. 22.)
13In another part of the emergency room records, it was noted that petitioner had left lower extremity
numbness. (Ex. 10, p. 11.)
16
significant signs of myelopathy such as weakness, loss of sensation, though her
reflexes are somewhat brisk. A superimposed peripheral sensory neuropathy is possible
as well.” (Id. at 30-31.) In addition, since the symptoms were brief and resolved, Dr.
Gao noted that petitioner should follow up with her neurologist and thus, no additional
head imaging was ordered; however, Dr. Gao recommended blood work up and routine
EEG. (Id. at 13, 31.) Petitioner was discharged on the same day. (Id. at 20, 26.)
On September 27, 2016, petitioner had a neurological consultation with Dr.
Slavenka Kam-Hansen for complaints of development of left lower leg burning following
vaccinations. (Ex. 15, p. 5.) Toward the end of October in 2016, petitioner returned to
the Japanese Acupuncture Center of Independent Practitioners for acupuncture
treatment. (Ex. 9, p. 2.) Petitioner experienced “hot spots” in legs, fatigue, and
symptoms in her right and left arm. (Id. at 3-6.) Petitioner continued seeking weekly
treatment throughout 2016 and into January 2017 but remained symptomatic. (Id. at 6-
7.)
Petitioner returned to Dr. Kam-Hansen seven weeks after her initial consultation
on November 14, 2016. (Ex. 15, p. 15.) Dr. Kam-Hansen listed petitioner’s neurological
problems as presumed ADEM following two vaccinations in April, where the onset of
lower leg burning sensation and pressure in right shoulder began in May. (Id.) Dr.
Kam-Hansen noted that petitioner was initially diagnosed with MS until Dr. Rao
diagnosed ADEM instead. Petitioner reported continued burning sensation in her left
shin, foot, and hip as well as throbbing, achy, and pins and needles sensation in her
right shoulder running down to her fingertips. (Id.) Additionally, petitioner reported
experiencing focal seizures again. (Id.) Dr. Kam-Hansen concluded that petitioner has
ADEM rather than MS, but time will give a clearer diagnosis since recovery after ADEM
can take months. (Id. at 16.) Subsequent imaging was ordered and petitioner returned
to see Dr. Kam-Hansen to discuss the results. (Id. at 18.) Petitioner’s imaging did not
show any new lesions and the cervical cord lesion decreased. (Id. at 18, 51-54)
On March 23, 2017, petitioner received another physical therapy evaluation for
her diffuse body aches, balance issues, and weakness. (Ex. 15, p. 21.) Petitioner
reported sensitivity to cold in her right arm and hot spots and weakness in her legs.
(Id.) The evaluation resulted in physical therapy diagnoses including impaired muscle
performance and “impaired motor function and sensory integrity associated with non-
progressive disorders of the CNS acquired in adolescent or adulthood.” (Id.) It was
noted that petitioner’s presentation seems to be a combination of ADEM related
impairments combined with deconditioning; however, petitioner had a good prognosis in
light of high functionality and general improvement since onset of symptoms. (Id. at 25-
26.) She continued with therapy.
On August 3, 2017, petitioner visited Dr. Bidwell for a follow up visit. Petitioner
reported fatigue, incontinence, and remaining symptoms of burning sensation in her left
shin and foot, throbbing, achy, and pins and needle sensation in her right shoulder to
her fingertips. (Ex. 50, p. 4.) Dr. Bidwell assessed that petitioner has a history of
ADEM following vaccination in April 2016 and still has fatigue, sensory and pain
17
symptoms, and incontinence. (Id. at 6.) He added that petitioner’s November 2016
imaging did not show any new lesions and the lesions in her spinal cord decreased.
(Id.) Additionally, petitioner saw Dr. Bidwell for urinary and fecal incontinence worsened
by petitioner’s ADEM in August 17, 2017. (Ex. 15, p. 48; Ex. 50, p. 8-9.) Thereafter,
petitioner had a urogynecology evaluation at Beth Israel Deaconess Medical Center in
October 2017. (Ex. 16, p. 9; Ex. 50, p. 12.) Petitioner was diagnosed with Stage II
cystocele and urogenital atrophy. (Ex. 50, p. 16.) Dr. Roger Lefevre indicated that
“[a]lthough her documented ADEM lesions occur in the C3-C4 distribution, her urinary
and fecal incontinence may be due in part to autonomic/neurogenic dysfunction in the
setting of ADEM.” (Ex. 16, p. 13.)
Petitioner visited the emergency department in late October 2017 due to
swelling, pain, and tenderness in her right toes, which was caused by stubbing them
against a chair. (Ex. 51, p. 37.) Petitioner had a closed displaced fracture, but
otherwise stable and released home. (Id. at 39.) Additionally, on November 15, 2017,
petitioner presented to Dr. Adam Landsman as a new patient with complaint of pain in
her right foot. (Id. at 41.) Dr. Landsman did not recommend surgery, but instead for
follow up evaluations and repeat radiographs. (Id. at 42.) Thereafter, also in November
2017, petitioner returned to Dr. Bidwell reporting that she had a fracture in her toe. (Ex.
50, p. 25.) Otherwise, this visit was similar to petitioner’s visit in August with no
particular changes to petitioner’s neurological symptoms. (Id. at 25-28.)
In early 2018, petitioner sought treatment again from Dr. David Baron, whom she
last saw in 2012. (Ex. 51, p. 43.) Petitioner reported developing ADEM following polio
and Tdap vaccinations and experiencing mild spasms in her left arm. (Id.) On March
22, 2018, petitioner went to the emergency department following a mechanical fall and
complained of left wrist pain. (Id. at 46.) She was diagnosed with a closed
nondisplaced fracture in her left hand. (Id. at 49.)
During an encounter on August 13, 2018, with Dr. Baron, petitioner reported that
her right arm numbness/encephalopathy “has not been as bad recently.” (Ex. 51, p.
57.) Dr. Baron accepted ADEM as the primary encounter diagnosis and noted that it
was “thought due to vaccine.” (Id. at 58.) Two months later, during another encounter,
petitioner was minimally symptomatic and stopped taking gabapentin. (Id. at 61.) At
this visit in October 2018, Dr. Baron assessed petitioner with neuropathic pain generally
as the primary encounter diagnosis. (Id.)
In March 2019, petitioner returned to Dr. Bidwell for a referral for physical therapy
to improve balance and leg strength. (Ex. 50, p. 30.) Additionally, petitioner requested
a form to that would allow her to avoid vaccinations. (Id.) Aside from Dr. Bidwell,
petitioner also sought care at Cambridge Health Alliance. During a visit on March 27,
2019, petitioner indicated that she hasn’t had symptoms for the past two years but
started having right arm paresthesia and right shoulder pain over the past few days.
(Ex. 51, p. 2; Ex. 53, p. 2.) After consulting with the on-call neurologist and Dr. Kam-
Hansen, Dr. Jaeyoung Yang reported that petitioner’s neurological exam was normal.
(Ex. 51, p. 67.)
18
In April 2019, petitioner continued seeking urology treatment from Dr. Heidi
Rayala. (Ex. 51, p. 7.) Dr. Rayala described petitioner as having a history of ADEM
following vaccination in 2016, “which is when her urination problems started.” (Id.) In
October 2019, petitioner visited Cambridge Health Alliance to visit Dr. Baron, her PCP.
(Ex. 53, p. 2.) Dr. Baron noted that petitioner was doing well and the plan was to follow
up with Dr. Kam-Hansen regarding her neurological symptoms. (Id. at 9.)
V. Analysis Regarding Petitioner’s Multiple Sclerosis
For the reasons discussed above, the relevant framework for determining
whether petitioner’s injury was caused-in-fact by her vaccination(s) is the six-part Loving
test for significant aggravation claims. Loving prongs one through three are addressed
first. These prongs examine petitioner’s condition before and after vaccination,
ultimately asking whether petitioner suffered a worsening of her pre-existing condition
subsequent to vaccination. Finding that petitioner did experience a worsening of her
pre-existing MS, the analysis turns to whether that significant aggravation was caused
by her vaccine(s).
The remaining three Loving prongs match the three-part Althen test for
determining causation-in-fact. For the reasons discussed below, I find that petitioner
has preponderantly established all three of these prongs. The fourth Loving prong
speaks to general causation, addressing whether petitioner has presented a medical
theory establishing that her vaccines can cause her alleged injury. This is the most
extensively discussed point of analysis below. Loving prongs five and six address
specific causation, asking whether there is a logical sequence of cause and effect to
establish vaccine causation in this specific instance (Loving prong five) and whether the
timing of the injury is medically appropriate to infer vaccine causation (Loving prong six).
These two prongs are discussed together, starting out of typical order with Loving prong
six. Lastly, respondent’s potential demonstration of a causal factor unrelated to
vaccination is briefly addressed.
a. Loving Prongs One Through Three
i. Loving prong one
Petitioner’s pre-vaccination medical records contain no significant evidence of
any outward clinical signs or symptoms of MS or any other CNS demyelinating condition
prior to her vaccination. However, both Dr. Steel and Dr. Sriram agree that petitioner’s
post-vaccination MRI study of June 5, 2016, revealed non-enhancing lesions that
suggest she had pre-existing, subclinical MS prior to her vaccination. (Ex. 20, pp. 3-4;
Ex. A, pp. 7-8.) Specifically, Dr. Steel characterized petitioner’s MRI as revealing
“lesions in the brain consistent with MS, likely preexistent, likely old, and clinically silent”
and opined that this pre-existing MS represented an underlying susceptibility. (Ex. 54,
p. 6.) He explained that petitioner’s pre-vaccination status constituted RIS, which
means petitioner had lesions visible to MRI, but no clinical neurologic symptoms. (Ex.
20, p. 3.)
19
Thus, petitioner argues in her supplemental brief that “[i]n sum, the parties’
experts agree that [petitioner’s] June 5, 2016, brain MRI provides objective evidence
that she was already undergoing a clinically silent MS disease process prior to her April
2016 vaccinations.” (ECF No. 97, p. 11.) Respondent opted not to provide
supplemental briefing with respect to Loving prong one. (ECF No. 98, p. 7, n. 3.)
The weight of evidence preponderantly establishes that petitioner had pre-
existing clinically silent MS prior to the receipt of her polio and Tdap vaccinations in April
2016.
ii. Loving prong two
It is undisputed that petitioner experienced an attack of CNS demyelination by
early June of 2016. (Ex. 2, p. 51.) This is evidenced both by petitioner’s first outward
clinical manifestation of symptoms and also by objective imaging. (Id.) Petitioner first
sought treatment on June 5, 2016, for right side weakness and numbness, which began
two nights prior, i.e., June 3, 2016. (Id. at 51, 59.) On June 6, 2016, a subsequent MRI
showed white matter lesions in the periventricular region and subcortically that do not
demonstrate enhancement, but also active demyelinating disease in the right lateral
cervical area at C3-C4 that did enhance. (Ex. 8, p. 74.) Both parties present experts
(Drs. Steel and Sriram) who agree that ultimately MS is petitioner’s correct diagnosis
following this attack. (Ex. 20, p. 3; Ex. A, p. 7.) It is also undisputed that petitioner was
ultimately diagnosed with MS (correctly according to Drs. Steel and Sriram) by at least
some of her physicians following this initial attack of CNS demyelination. (Ex. 2, pp. 2,
50; Ex. 14, p. 18; Ex. 20, p. 3; Ex. 54, p. 3; Ex. A, p. 8; Ex. O, p. 6; ECF No. 70, p. 12.)
More specifically, Dr. Steel has opined that this post-vaccination presentation
constituted an attack of focal myelitis of the spine. He also explained that “[s]he
experienced a clinically symptomatic event in a limited time window following
vaccinations. This event, called a Clinically Isolated Event, was her first episode of
neurological symptoms typical of an MS relapse in a person not known to have MS.”
(Ex. 20, p. 3.) Dr. Sriram likewise agrees that when petitioner sought treatment on June
5, 2016, she had an enhancing spinal lesion evidenced on MRI and that this spinal cord
demyelination led to her symptoms of arm and leg weakness. (Ex. A, pp. 8-9.) He
further agreed that this was petitioner’s first clinical attack of her MS. (Id. at 8.)
In her supplemental brief, petitioner contends that “[t]here is no dispute that she
experienced a clinically acute episode of CNS demyelination following her
vaccinations.” (ECF No. 97, p. 12.) Respondent opted not to provide supplemental
briefing with respect to Loving prong two. (ECF No. 98, p. 7, n. 3.)
The weight of evidence preponderantly establishes that petitioner suffered spinal
myelitis constituting her first clinical attack of her pre-existing MS by no later than June
3, 2016. To the extent Dr. Steel additionally characterized petitioner’s spinal myelitis as
APTM (Ex. 54, p. 7), this is addressed under Loving prong three.
iii. Loving prong three
There has been some suggestion, most notably from petitioner herself in her
original motion for a ruling on the record, that the post-vaccination myelitis forming the
20
basis for this claim should be considered as APTM separately from petitioner’s MS. For
his part, Dr. Steel indicated that petitioner suffered an attack of APTM, but also stressed
that APTM is associated with MS and that petitioner’s focal myelitis constituted CIS.
(Ex. 20, p. 3; Ex. 54, pp. 3, 7.) Petitioner now acknowledges in her supplemental brief
that her APTM was a part of her MS, though she still maintains that the APTM
nonetheless constituted a discrete medical “event.” (ECF No. 97, p. 9.) The record
preponderates in favor of a finding that petitioner’s APTM is a manifestation of her pre-
existing MS.
Petitioner has filed literature broadly cautioning that idiopathic or primary TM
should be distinguished from disease-associated TM, suggesting that “[i]dentification of
etiologies may suggest medical treatment, whereas no clearly established medical
treatment currently exists for idiopathic ATM.” (Transverse Myelitis Consortium Working
Group, Proposed Diagnostic Criteria and Nosology of Acute Transverse Myelitis, 59
NEUROLOGY 499, 499 (2002) (Ex. 68).) Moreover, Dr. Sriram stressed that MS is an
exclusionary factor in the diagnosis of TM under the prevailing diagnostic criteria. (Ex.
O, pp. 2-3.) Dr. Steel further suggested that subsequent literature distinguishes
between idiopathic TM, APTM, and acute complete TM (“ACTM”). (Thomas F. Scott,
Nosology of Idiopathic Transverse Myelitis Syndromes, 115 ACTA NEUROL. SCAND. 371,
373 (2007) (Ex. 65) (Table 1)).) Dr. Steel contends that petitioner’s case is consistent
with the latter APTM. (Id.)
Critically, however, Dr. Steel acknowledges that APTM, in contrast to ACTM, “is
strongly associated with multiple sclerosis, either as an initial presenting disease or as
part of the ongoing relapsing-remitting course of MS.” (Id.) Dr. Scott explains that,
while not all cases of APTM will ultimately constitute clinically definite MS (“CDMS”),
“[w]hen patients present with APTM and cerebral MRI showing lesions typical of MS,
the transition rate to CDMS is known to be quite high, in the range of 80-90% within a
few years.” (Scott, supra, at Ex. 65, p. 375.) While patients with MS often initially
present with APTM, it is not accurate to say that patients with MS also carry a diagnosis
of APTM. Rather, as Dr. Sriram explains, once the MS diagnosis is made, the prior TM
“becomes a feature” of the MS. (Ex. O, p. 3.)
The literature that Dr. Steel cited for the specific proposition that immunization
may trigger attacks of myelitis in the context of underlying disease (Frohman and
Wingerchuk), also specifically indicates partial TM is associated with a high risk of MS.
(Frohman & Wingerchuk, supra, at Ex. 39, p. 566 (chart)).) That literature includes a
diagnostic flow chart that indicates that findings of demyelination on brain MRI,
oligoclonal bands, and an abnormal visual evoked response should lead to the
conclusion of a high risk of MS rather than a diagnosis of TM. (Id.) Under this
framework, only the absence of all of these findings would allow for a reconsideration of
the clinical history that could potentially lead to a diagnosis of idiopathic, postinfectious,
or post-vaccination TM. (Id.) Thus, respondent argued that “if Dr. Steel had employed
the methodology outlined by Frohman and Wingerchuk, he would have concluded that
21
petitioner’s ‘focal myelitis’ or APTM was caused by her underlying MS, not her
preceding vaccinations.” 14 (ECF No. 70, p. 23.)
In that regard, Dr. Steel also acknowledged that petitioner’s overall presentation
around the time her symptoms first manifested is more consistent with MS than with an
isolated attack of TM. (Ex. 20, p. 3.) Dr. Steel opined that petitioner’s spinal lesion is
distinct from complete TM, because it did not cross the midline of the spinal cord. (Id.)
He also opined that the presence of oligoclonal bands and optic neuropathy distinguish
petitioner’s condition from TM generally. (Id.) Further, there is agreement that
petitioner’s presentation at the time of her clinical attack evidenced dissemination in
time and space, a key diagnostic consideration for MS that is not consistent with an
isolated attack. (Ex. 20, p. 3; Ex. A, pp. 7-8; see also Thompson et al., supra, at Ex. C.)
Dr. Steel explained that petitioner’s spinal lesion, though typical of MS, is not itself
diagnostic. (Ex. 20, p. 3.) However, he agreed that the presence of oligoclonal bands
in petitioner’s cerebral spinal fluid suggested dissemination in time. (Id.) Dr. Steel
further indicated that petitioner’s abnormal visual evoked responses in the right optic
nerve evidenced dissemination in space. (Id.) Additionally, although he stressed that
petitioner’s outward clinical symptoms began post-vaccination, her MRI “revealed
lesions in the brain consistent with MS, likely preexistent, likely old, and clinically silent.”
(Ex. 54, p. 6.) These factors support the understanding that petitioner’s APTM would be
considered a part of her MS by Frohman & Wingerchuk.
However, although Frohman and Wingerchuk diagnostically distinguish between
post-vaccination TM and disease-associated TM, Dr. Steel also quotes language that
demonstrates the authors believe disease-associated TM can still be vaccine triggered.
Specifically, Dr. Steel notes that the authors state: “[t]he occurrence of transverse
myelitis after infection or vaccination does not preclude the need for further evaluation,
since infection or immunization may also trigger attacks of myelitis in the context of
underlying disease (especially multiple sclerosis or neuromyelitis optica).” (Frohman &
Wingerchuk, supra, at Ex. 39, p. 567.) This language underscores Dr. Steel’s premise
that vaccine-related TM is possible “in the context of the patient’s pre-existing clinically
silent MS.” (Ex. 54, p. 7.)
Based on this statement, Dr. Sriram contends that Frohman and Wingerchuk
take inherently contradictory positions. (Ex. O, pp. 4-5.) He states that the quoted
language is incompatible with a further discussion by the authors distinguishing post-
vaccination TM from TM in patients with MS. Specifically, he quotes the following
language:
identifying the cause of transverse myelitis facilitates the prediction of the
future clinical course and informs the decision about whether to provide
prophylaxis against future neurologic events. The postinfectious,
postvaccination, and idiopathic forms of transverse myelitis are usually
14 Respondent is correct that Frohman and Wingerchuk’s diagnostic method would lead to a diagnosis of
MS rather than post-vaccination APTM; however, as discussed further below, respondent misstates the
Frohman and Wingerchuk article to the extent he presents the authors as opining that the MS diagnosis is
mutually exclusive of vaccine causation.
22
monophasic syndromes, whereas multiple sclerosis and neuromyelitis
optica – spectrum disorders are relapsing diseases that are associated with
high risk of future attacks of transverse myelitis and other neurologic events.
(Ex. O, p. 5 (quoting Frohman & Wingerchuk, supra, at Ex. 39, p. 567).)
Dr. Sriram opines that “Frohman and Wingerchuk cannot simultaneously claim
that vaccines cause transverse myelitis in patients with underlying MS and at the same
time draw a line between postvaccination transverse myelitis and MS-associated
transverse myelitis.” (Ex. O, p. 5.) However, the contradiction Dr. Sriram posits only
exists if one assumes the authors share Dr. Sriram’s overall point of view regarding
clinical parsimony rather than agreeing with Dr. Steel’s opinion that MS is multifactorial
and that neurologic events in MS respond to external triggers, including vaccines. 15
This difference of opinion is explored further with respect to Loving prong four, below.
For purposes of Loving prong three, however, petitioner’s supplemental brief
cites approvingly to respondent’s expert’s statement that “TM becomes a feature of MS
once the MS diagnosis is made[.]” (ECF No. 97, p. 13 (quoting Ex. O, p. 3).) Thus,
petitioner contends that “both experts are clear that petitioner is best thought of as
having experienced an attack of spinal myelitis as the first clinical manifestation of her
MS, and as part of the progress of the disease.” (ECF No. 97, p. 12.) Because Dr.
Steel opined that petitioner’s condition went from “clinically silent” to “clinically
significant,” petitioner contends that “[i]f a patient’s underlying disease process goes
from clinical silence to extreme clinical salience, it is inarguable that that patient’s
condition has undergone a ‘significant aggravation.’” (Id. at 12-13.) Respondent opted
not to provide supplemental briefing with respect to Loving prong three, agreeing that
petitioner did suffer a significant aggravation of her MS. (ECF No. 98, p. 7, n. 3.)
In light of the above, the evidence preponderates in favor of a finding that
diagnostically speaking petitioner’s post-vaccination demyelination is better understood
as a part of the course of her pre-existing MS rather than as a separate idiopathic
APTM. Additionally, combined with the findings pursuant to Loving prongs one and two,
there is preponderant evidence on this record that due to this attack of myelitis
petitioner suffered a change for the worse in her pre-existing MS, resulting in markedly
greater disability, pain, or illness accompanied by substantial deterioration of health. §
300aa-33(4). As explained above, Dr. Steel opines that petitioner suffered RIS pre-
vaccination and experienced a post-vaccination “unmasking” of her MS in the form of a
spinal myelitis constituting CIS. Although Dr. Sriram ultimately disputes vaccine-
causation, he likewise agrees that the spinal myelitis at issue was a part of the course of
15Per the diagnostic flow chart created by Frohman and Wingerchuk, only if the patient is at “low risk” for
MS is it advisable to conclude that the patient’s TM is likely to be monophasic as a post-vaccination
phenomenon. This is not an opinion that vaccinations are irrelevant in the MS context. In the language
quoted by Dr. Steel the authors simply amplify that this “low risk” is not “no risk,” because they opine that
vaccination can have an effect in either context. In other words, in their view the fact that a clinician
concludes that an episode of TM was vaccine-caused should not in itself provide complete comfort that it
will not ultimately also be the first presentation of MS. Pertinent to this point, Dr. Sriram himself indicates
that the precipitating factors for MS relapse are not fully known. (Ex. O, p. 6.)
23
petitioner’s MS and that it constituted the first clinical attack of her condition.
Accordingly, petitioner has satisfied Loving prong three by preponderant evidence,
leaving the question of whether her vaccination(s) played a causal role in that significant
aggravation.
b. Loving Prong Four
Petitioner’s burden under the first Althen prong / fourth Loving prong is to
provide, by preponderant evidence, “a medical theory causally connecting the
vaccination and the injury.” Althen, 418 F.3d at 1278. Such a theory must only be
“legally probable, not medically or scientifically certain.” Knudsen v. Sec’y of Human &
Health Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994). Moreover, scientific evidence
offered to establish Althen prong one / Loving prong four is viewed “not through the lens
of the laboratorian, but instead from the vantage point of the Vaccine Act's preponderant
evidence standard.” Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1380
(Fed. Cir. 2009). The Federal Circuit instructs that “a paucity of medical literature
supporting a particular theory of causation cannot serve as a bar to recovery.” Id. at
1379. However, to satisfy this prong, petitioner’s theory must be based on a “sound and
reliable medical or scientific explanation.” Knudsen, 35 F.3d at 548; Boatmon v. Sec’y
of Health & Human Servs., 941 F.3d 1351, 1359 (Fed. Cir. 2019).
The initial ruling on entitlement in this case held that petitioner had
preponderantly satisfied Loving prong four and discussed three factors in a more
abbreviated fashion: Dr. Steel’s scientific explanation of the underlying disease
process; the limitations of the relevant epidemiology; and a single study by Langer-
Gould, et al., that nonetheless detected at least some signal of temporary post-
vaccination CNS demyelination inclusive of one of the vaccines at issue. The initial
ruling characterized the Langer-Gould study as “especially relevant and persuasive.”
(ECF No. 73, p. 23.) On remand, however, this decision does not consider the Langer-
Gould study as evidence of causation for the reasons discussed in the Court of Federal
Claims’ Opinion and Order. Accordingly, this decision on remand amplifies several
points of analysis to explain why removing the Langer-Gould study from consideration
based on the Court of Federal Claims’ guidance does not ultimately change the
outcome of this case upon further consideration of the record as a whole. 16
In this case, there is no doubt that what Dr. Steel proposes as a medical theory
supporting his opinion constitutes only a circumstantial case. As Dr. Sriram stresses
and Dr. Steel acknowledges, no epidemiologic signal has specifically proven that
vaccines can cause or significantly aggravate MS. However, it is important to note that,
while Dr. Sriram notes MS patients to be a “highly studied population” (Ex. A, p. 10), the
record of this case also indicates that central nervous demyelinating conditions as a
16Dr. Steel suggested that both vaccines – polio and Tdap – could have contributed to petitioner’s
condition. (Ex. 20, p. 5.) However, in his second report he focused more heavily on evidence relating
specifically to the Tdap vaccine. (Ex. 54.) Thus, there is more evidence of record implicating the Tdap
vaccine in autoimmune demyelination than there is for the polio vaccine. Moreover, as discussed below
with regard to Loving prong six, the temporal relationship at issue is clearer with respect to the later Tdap
vaccine than for the earlier polio vaccine. Accordingly, this decision will focus primarily on the Tdap
vaccine. Having concluded petitioner has met her burden of proof with respect to that vaccine, it is not
necessary to definitively resolve whether her polio vaccine may have additionally contributed to her injury.
24
whole are not considered to be well understood. 17 In fact, Dr. Sriram acknowledges on
respondent’s behalf that the ultimate cause of MS, as well as the precipitating factors for
MS relapse, are considered unknown. (Ex. A, p. 8; Ex. O, pp. 6-7.) In that context, Dr.
Steel’s opinion constitutes the type of sound and reliable scientific explanation that can
carry a case where there is a paucity of medical literature. Dr. Sriram’s rebuttal offers
little to no direct substantive response to the particulars of Dr. Steel’s opinion. Instead,
the thrust of Dr. Sriram’s opinion is to assert that much of what Dr. Steel discusses is
irrelevant based primarily on two points – epidemiology and “clinical prudence and
parsimony” (explained further below). On this record neither of these points is
persuasive as rebuttal.
i. Dr. Steel’s explanation of MS autoimmunity is sound and reliable
Dr. Steel explains that MS is the most common inflammatory immune-mediated
CNS demyelinating disease. (Ex. 20, p. 3.) He notes that others include TM, focal
myelitis, ADEM, and neuromyelitis optica. (Id.) These disorders represent a “family” of
conditions for which “[c]ausation is likely multifactorial, with contributing factors including
genetic predisposition, environment, nutritional status, comorbidities, and exposure to
various triggers.” (Ex. 54, p. 2.) In that context, he proposes that MS patients are
predisposed to CNS inflammation. (Ex. 20, p. 4.) He further explains that:
Vaccines, as well as other immunogenic stressors, stimulate a heightened
immune reaction in response to the antigens in the vaccines. However, this
desirable response may have unintended effects by activating the immune
system in the CNS, particularly in susceptible individuals such as patients
with clinically asymptomatic MS, who are already undergoing an
autoimmune process. Possible mechanisms include molecular mimicry,
epitope spreading, bystander activation, T-helper cell activation, and
cytokine induction. In a given instance, one or more of these mechanisms
may be operative. Molecular mimicry is often posited as a plausible process
by which vaccination could induce autoimmunity. The theory is that
antibodies formed in response to the vaccine may attack myelin related
epitopes if these epitopes are like the antigens in their chemical and
physical structure. Although there is little evidence that vaccinations cause
17 For example, an article filed in this case regarding the immunopathogenesis of acute TM explains in
introduction that:
Acute transverse myelitis (ATM) is a group of poorly understood inflammatory disorders
resulting in neuronal injury to the spinal cord. It is unclear what are the triggers and effector
mechanisms resulting in neural injury, although tantalizing clues have emerged. ATM
exists on a continuum of neuroinflammatory disorders that also includes Guillain-Barre
syndrome (GBS), multiple sclerosis (MS), acute disseminated encephalomyelitis and
neuromyelitis optica (NMO). Each of these disorders differs in the spatial and temporal
restriction of inflammation within the nervous system. However, clinical and pathological
studies support the notion that there are many common features of the inflammation and
neuronal injury.
(Douglas A. Kerr, Harold Ayetey, Immunopathogenesis of acute transverse myelitis, CURR. OP.
NEUROL. 339 (2002) (Ex. 40).)
25
multiple sclerosis in healthy patients, there is convincing evidence that
vaccinations occasionally trigger single attacks of TM, ADEM, optic neuritis,
and isolated spinal myelitis, and there is good reason to think that such an
event is more likely in patients with subclinical MS.
(Ex. 20, p. 5.)
At the broadest level, the reliability of this explanation is borne out in large portion
by respondent’s expert’s own discussion of MS. Dr. Sriram likewise explains that MS is
a chronic demyelinating disorder of the CNS that results in neurologic deficits resulting
from lesions affecting the optic nerves, brainstem, and spinal cord. (Ex. A, p. 7.) He
also agrees that MS is generally believed to be autoimmune and that it also has an
inflammatory component leading to myelitis and demyelination. He explains that
[t]he prevailing opinion on MS is that it is mediated by T lymphocytes, which
target the white matter of the central nervous system. The ongoing
inflammatory response in the central nervous system results in the
development of lesions in the white matter and in particular the myelin
membranes of the central nervous system. Myelin is in the membranes
which insulate the axons and optimize nerve conduction from one neuron
to another. Loss of myelin membrane leads to impaired conduction which
often results in clinical disability.
(Ex. A, p. 8.)
Further to this explanation, Dr. Steel highlights literature by Fujinami, et al.,
explaining what is known as the “fertile field” understanding of autoimmunity in MS.
(Fujinami et al., supra, at Ex. 24, p. 83.) It explains why an individual already
experiencing autoimmunity in the form of clinically silent MS may nonetheless be
susceptible to later insults that bring about clinically apparent disease. The authors
state: “[f]or example, an infection with a virus having molecular mimicry to self CNS
proteins can potentially prime autoreactive T cells but not to the point where they can
initiate autoimmune inflammatory CNS disease; later events may trigger these cells to
cause disease.” (Fujinami et al., supra, at Ex. 24, p. 83.) The Institute of Medicine
(“IOM”) has identified Fujinami’s work as providing experimental evidence supporting
molecular mimicry as a mechanism of autoimmunity for MS. 18 (Institute of Medicine,
18 The Institute of Medicine (known as the National Academy of Medicine since 2015) is the medical arm
of the National Academy of Sciences. The National Academy of Sciences (“NAS”) was created by
Congress in 1863 to be an advisor to the federal government on scientific and technical matters (see An
Act to Incorporate the National Academy of Sciences, ch. 111, 12 Stat. 806 (1863)), and the Institute of
Medicine is an offshoot of the NAS established in 1970 to provide advice concerning medical issues.
When it enacted the Vaccine Act in 1986, Congress directed that the IOM conduct studies concerning
potential causal relationships between vaccines and illnesses. See § 300aa–1 note. However, the IOM
employs a standard for finding causation that is higher than what is required by petitioner’s burden of
proof. E.g. Raymo v. Sec’y of Health & Human Servs., No. 11-654V, 2014 WL 1092274, at *21, n.39
(Fed. Cl. Spec. Mstr. Feb. 24, 2014). Accordingly, IOM reports and findings should be approached with
caution. Special Masters may rely on IOM reports as evidence, but they are not dispositive. See, e.g.,
Crutchfield v. Sec’y Health & Human Servs., 125 Fed. Cl. 251, 262 (2014) (noting that “it was appropriate
for the special master to consider the medical literature presented, including the IOM report” and that “the
court often has relied on the findings of the Institute of Medicine.”); See also, Isaac v. Sec’y Health &
26
Adverse Effects of Vaccines: Evidence and Causality, NAT’L ACAD. SCI. 1, 71 (2012) (Ex.
66).) The “fertile field” is also considered compatible with the bystander activation
mechanism additionally cited by Dr. Steel. (Fujinami et al., supra, at Ex. 24, p. 83.)
The Fujinami authors explain that myelin basic protein has been shown to react
to a variety of viral and bacterial proteins. (Fujinami et al., supra, at Ex. 24, p. 81.)
Based on experiments using their murine model of experimental autoimmune
encephalomyelitis (EAE) (a commonly used model in the study of MS and other
demyelinating conditions (see Neeta Garg & Thomas W. Smith, An update on
immunopathogenesis, diagnosis, and treatment of multiple sclerosis, 5(9) BRAIN AND
BEHAVIOR 1, 2 (2015) (Ex. 45); Byron Waksman & Raymond Adams, Studies of the
Effect of the Generalized Shwartzman Reaction on the Lesions of Experimental Allergic
Encephalomyelitis, 33(1) AM. J. PATHOL. 131 (1957) (Ex. 30)), Fujinami demonstrated
that after a mouse clears an initial infection, even without initially producing
inflammatory lesions, it is primed to produce such lesions later in life upon insult with
either an adjuvant 19 or certain wild virus. (Fujinami et al., supra, at Ex. 24, p. 84-85.)
Respondent challenges the relevance of this paper based on the premise that it
addresses only how viruses rather than vaccines can cause autoimmunity. (ECF No.
70, p. 17.) However, pertinent to Dr. Steel’s reliance on this concept vis-à-vis
vaccination, the Fujinami authors’ findings were not limited to viral infection as they also
produced results with an adjuvant. (Fujinami et al., supra, at Ex. 24, p. 84.) They also
explained that their model predicts that the priming effect can occur following an
infection occurring only in the periphery (i.e., not itself reaching the CNS) and can
trigger CNS disease without a second infection targeting the organ in question. (Id. at
85.) Respondent’s expert opted not to specifically address the Fujinami paper. 20 (Exs.
A, O.)
Human Servs., 108 Fed. Cl. 743, 755 (2013), aff'd, 540 Fed. Appx. 999 (Mem.) (Fed. Cir. 2013) (affirming
the special master's reliance on findings of the IOM); Porter v. Sec’y Health & Human Servs., 663 F.3d
1242, 1252 (Fed.Cir.2011) (noting the special master's comment that “IOM reports are favored, although
not dispositive, in the Vaccine Act Program,” then affirming the special master's decision).
19 The authors explain that “[i]n most if not all the models where molecular mimicry has been used to
induce an autoimmune disease, an adjuvant such as [complete Freund’s adjuvant] or an actual infection
is required. This suggests that, in addition to having a cross-reacting disease, inducing epitope-sufficient
activation of [antigen presenting cells] is required.” (Fujinami et al., supra, at Ex. 24, p. 81.) An
“adjuvant” is “a nonspecific stimulator of the immune system.” Adjuvant, DORLAND’S MEDICAL DICTIONARY
ONLINE, https://www.dorlandsonline.com/dorland/definition?id=1074 (last accessed June 6, 2022).
Adjuvants are also added to some vaccines in order to increase the immune response to the vaccine.
(Institute of Medicine, supra, at Ex. 66, p. 59.) Interestingly, the record evidence shows that the specific
Tdap vaccine petitioner received was adjuvanted. (Ex. 1, p. 2 (identifying manufacturer as GSK); Ex. 58
p. 16 (package insert for GSK Boostrix describing vaccine as adjuvanted with aluminum hydroxide).)
However, Dr. Steel did not specifically rely on this fact and the mechanism by which adjuvants support
vaccine efficacy is not known. (Institute of Medicine, supra, at Ex. 66, p. 59.)
20 Dr. Sriram’s discussion of the Fujinami paper was limited to including a footnote confirming that the
paper does, in fact, concern molecular mimicry, but dismissing its relevance because Dr. Steel did not in
his view sufficiently address “how the molecular mimicry theory applies specifically to [petitioner’s] case.”
(Ex. A, p. 14, n. 4.) However, this paper was cited as support for specific statements by Dr. Steel in his
report indicating that non-specific immunogenic stresses, including vaccines, can trigger demyelinating
27
Based on their specific findings, the Fujinami authors proposed two different
mechanisms of injury. (Fujinami et al., supra, at Ex. 24, p. 85.) First, molecular mimicry
during a priming infection initially generates autoreactive T cells to a subclinical degree.
Bystander activation resulting from a secondary event can then cause the autoreactive
T cells to proliferate to sufficient numbers to cause disease. 21 Second, the priming
infection could generate memory T cells with unrecognized cross-reactive potential. A
second infection involving an antigen sharing a common epitope can expand that
response and proliferate autoreactive T cells to a disease-causing level. 22 (Id.)
To further evidence the ability of components of the Tdap and polio vaccines to
cause autoimmune injury to myelin basic protein in humans Dr. Steel relies on other
vaccine-caused CNS demyelinating conditions, such as TM. 23 Specifically, Dr. Steel
opined that while vaccines have not been shown epidemiologically to be an initiating
cause of MS itself, “there is sufficient evidence in the medical literature to link
vaccination to TM to make a biologically plausible argument for causation” (Ex. 54, p. 1)
and ultimately that “the vaccine triggered an episode of spinal myelitis in the context of
the patient’s pre-existing clinically silent MS” (Id. at 7). 24 Thus, Dr. Steel relied on
attacks in individuals suffering subclinical autoimmunity in MS. Additionally, petitioner’s filing of the
Fujinami paper included marking by Dr. Steel highlighting specific passages relating to the “fertile field”
theory, the specific findings of the above-discussed murine study, and portions of the authors’ explanation
of the study’s findings. (See ECF No. 36-4; Fujinami et al., supra, at Ex. 24.)
21 Bystander activation involves “a robust or exaggerated immune response to an exogenous agent that
induces local tissue inflammation and stimulation of otherwise normal unaffected cells.” (Institute of
Medicine, supra, at Ex. 66, p. 75.) This inflammation “can result in the release of normally sequestered
self-antigens. The inflammation can result in nonspecific activation of previously dormant autoreactive
Th1 cells that then react against newly released self-antigens.” (Id.)
22 Langer-Gould, et al., previously considered significant as part of the prior ruling on entitlement, similarly
hypothesized based on their findings in humans that vaccinations may act in the same manner as
infection to “enhance autoimmunity through expansion of autoreactive T-cell clones by molecular mimicry,
later stimulation of autoreactive T-cell clones, or enhancement of antigen presentation by bystander
activation . . . .” (Annette Langer-Gould et al., Vaccines and the Risk of Multiple Sclerosis and Other
Central Nervous System Demyelinating Diseases, 71(12) JAMA NEUROL. 1506, 1511-12 (2014) (Ex. 63).)
23 It should be noted that while petitioners do not prevail by “merely chanting the magic words ‘molecular
mimicry,’” McKown v. Sec’y of Health & Human Servs., No. 15-1541V, 2019 WL 4072113, at *50 (Fed. Cl.
Spec. Mstr. July 15, 2019), it is also not the case that every petitioner citing molecular mimicry must prove
the precise molecular mimic to prevail. For example, GBS caused by the flu vaccine is so widely
compensated in this Program that it has been designated as a table injury, and yet, although it is
assumed to occur due to molecular mimicry, the molecular mimic has not yet been identified. See
Pierson v. Sec’y of Health & Human Servs., No. 17-1136V, 2022 WL 322836, at *23-26 (Fed. Cl. Spec.
Mstr. Jan. 19, 2022) (providing extended discussion of molecular mimicry in the context of GBS). In the
Vaccine Program, it is well understood that petitioners are not obligated to prove the precise mechanism
of injury as a component of their causation theory. Knudsen, 35 F.3d at 548.
24 A clarification regarding use of the word “plausible” may be useful. Petitioner argues that her burden
under Loving prong four is to provide both a “biologically plausible” and “reliable” theory of causation.
(ECF No. 97, p. 6.) However, the Federal Circuit has been clear in stating that “[w]e have consistently
rejected theories that the vaccine only ‘likely caused’ the injury and reiterated that a ‘plausible’ or
‘possible’ causal theory does not satisfy the standard.” Boatmon, 941 F.3d at 1360. Respondent likewise
alludes to this point. (ECF No. 98, p. 9, n. 6.) This is not to be confused with Dr. Steel’s reference to
28
collected case reports from review literature identifying various CNS demyelinating
conditions as following certain vaccinations, specifically including both tetanus-
containing and polio vaccines. 25 (Dimitrios Karussis, Panayiota Petrou, The spectrum
of post-vaccination inflammatory CNS demyelinating syndromes, 13 AUTOIMMUNITY
REVIEWS 215 (2014) (Ex. 36); N. Agmon-Levin et al., Transverse myelitis and vaccines:
a multi-analysis, 18 LUPUS 1198 (2009) (Ex. 42); Xuan-Hung Nguyen, Abdelhadi Saoudi,
Roland Liblau, Vaccine-associated inflammatory diseases of the central nervous
system: from signals to causation, 29 CURR. OPIN NEUROL. 362 (2016) (Ex. 63).) Dr.
Steel also separately cited a case report of two pregnant women who suffered optic
neuritis following the Tdap vaccine. (Jose Cabrera-Maqueda et al., Optic neuritis in
pregnancy after Tdap vaccination: Report of two cases, 160 CLIN. NEUROL. NEUROSURG.
116 (Ex. 35).) There is also some evidence of record to support a suspicion that the
tetanus vaccine is implicated in autoimmune demyelination in the context of Guillain-
Barré Syndrome (“GBS”), a peripheral but also demyelinating disorder. (Ex. 59, p. 3;
Ex. 64, p. 4 (vaccine package inserts warning against Tdap vaccine for those who
experienced GBS following prior tetanus vaccination).)
In her original motion for a ruling on the record (incorporated by reference in her
supplemental brief), petitioner argued:
Dr. Sriram attempts to dismiss these reviews and case reports with the
comment that ‘anecdotal accounts do not constitute evidence.’ With all due
respect to Dr. Sriram, this statement is incorrect. It is appropriate for this
Court to take judicial notice of the fact that case reports are an accepted
and longstanding feature of medical research and are routinely published in
peer-reviewed medical and scientific journals. This state of affairs
presumably reflects the medical community’s belief that case reports
provide useful information to clinicians and researchers, i.e., that case
reports constitute evidence.
what is “biologically plausible,” which simply expresses that the point being made is consistent with
existing medical knowledge. E.g. Doe93 v. Sec’y of Health and Human Servs., 98 Fed Cl. 553, 567
(2011) (collecting citations to cases where petitioners have been required to present a “biologically
plausible” theory as that term is understood in the scientific community).); accord Kottenstette v. Sec’y of
Health & Human Servs., 861 Fed. Appx. 433, 440-41 (Fed. Cir. 2021) (assigning error where the Court of
Federal Claims interpreted the special master’s refence to “biologic credibility” as equivalent to the type of
merely “plausible” theory presented in Boatmon.) A proposed theory must necessarily be biologically
plausible (i.e., consistent with existing medical knowledge) in order to be sound and reliable; however,
biologic plausibility is not itself the legal standard. Thus, petitioner’s acknowledgement that her expert’s
theory must be “reliable” as well as “biologically plausible” is important. According to the Federal Circuit,
petitioner’s expert must present an explanation in support of Althen prong one / Loving prong four that is
“sound and reliable.” Boatmon, 941 F.3d at 1359-60.
25 While there is literature filed in this case that broadly states that vaccines in general may be a trigger of
TM, there is also literature filed explaining that certain specific vaccines not at issue in this case are more
strongly evidenced as causes of demyelination than others. (E.g., Karussis & Petrou, supra, at Ex. 36;
see also Loebermann, et al, infra, at Ex. 38, p. 7 (distinguishing inactivated and live attenuated
vaccines).) Accordingly, general references to vaccinations as a trigger of TM must be approached with
caution and the availability of evidence specifically implicating the particular vaccine(s) at issue is an
important consideration.
29
(ECF No. 68, pp. 15-16 (quoting Ex. O, p. 4 (internal citation omitted)).)
Petitioner is correct that case reports constitute evidence and cannot be
summarily rejected. “[C]ase reports ‘do not purport to establish causation definitively,
and this deficiency does indeed reduce their evidentiary value’…. [but] ‘the fact that
case reports can by their nature only present indicia of causation does not deprive them
of all evidentiary weight.’” See Paluck v. Sec'y of Health & Human Servs., 104 Fed. Cl.
457, 475 (2012) (quoting Campbell v. Sec'y of Health & Human Servs., 97 Fed. Cl. 650,
668 (2011), aff’d 786 F.3d 1373 (Fed. Cir. 2015)). Thus, for example, in a prior case
involving TM caused by the Tdap vaccine, a prior chief special master concluded that
the rarity of TM (citing approximately 1,400 new cases diagnosed annually in the U.S.)
coupled with the rarity of adult administration of the Tdap vaccine (boosters
recommended only every ten years) counseled in favor of allowing greater weight to
case reports involving that combination of vaccine and injury. Raymo v. Sec’y of Health
& Human Servs., No. 11-654V, 2014 WL 1092274, at *21 (Fed. Cl. Spec. Mstr. Feb. 24,
2014). 26
In addition, as discussed by both the initial ruling and the Court of Federal
Claims’ Opinion and Order, Dr. Steel relied in his second report on a case-controlled
study by Langer-Gould, et al., that found a statistically significant 30-day risk period for
onset of acquired demyelinating syndromes of the CNS following various vaccinations,
including Tdap. (Ex. 54, pp. 5-6 (citing Langer-Gould et al., supra, at Ex. 63).) Dr. Steel
cited this study for the specific proposition that “within a narrow time frame after
vaccination, there is an increased risk of CNS Acute Demyelinating Syndromes,
including TM.”27 (Ex. 54, p. 6.) Under “conclusions and relevance” the authors stated:
26 There is some prior track record of petitioners being awarded compensation for Tdap-caused TM;
however, it has not been universally embraced. Compare Raymo, 2014 WL 1092274 (petitioner
established entitlement to compensation for a claim alleging TM following receipt of the HPV, Hepatitis A,
meningococcal, and Tdap vaccines); Roberts v. Sec’y of Health & Human Servs., 09-427V, 2013 WL
5314698 (Fed. Cl. Spec. Mstr. Aug. 29, 2013) (petitioner was entitled to compensation for a claim alleging
TM following receipt of the Tdap vaccine); Helman v. Sec'y of Health & Human Servs., No. 10-813V, 2012
WL 1607142 (Fed. Cl. Spec. Mstr. Apr. 5, 2012) (petitioner was entitled to compensation for a claim
alleging TM and NMO following receipt of the Tdap vaccine) and, I.J. v. Sec’y of Health & Human Servs.,
No. 16-846, 2021 WL 1232733, at *29 (Fed. Cl. Spec. Mstr. Jan. 4, 2021) (noting that most Tdap/TM
cases have resolved via stipulation and proffer, but distinguishing Raymo, Roberts, and Hellman, and
denying entitlement), rev’d 155 Fed. Cl. 20 (2021).
27 The study examined 780 cases of various newly diagnosed CNS demyelination syndromes, including
MS (54.7% of cases), optic neuritis (22.7%), TM (15.6%), CIS (4.2%), and ADEM (2.7%). (Langer-Gould
et al., supra, at Ex. 63, p. 1508.) They reviewed patient records for reports of any vaccine within three
years prior and indicated that the most commonly reported in adults were Hepatitis B, HPV, influenza,
Tdap, and varicella vaccines. (Id. at 1507.) The study identified 24 individuals (younger than 50) who
suffered some form of a CNS demyelinating condition within 30 days of vaccination, eleven had MS, nine
had optic neuritis, three had TM, and 1 had ADEM. (Id. at 1509.) Among those 24, eight had received
the Tdap vaccine, though the study’s ultimate finding was not vaccine specific. (Id.) As Dr. Steel
explained, although different breakdowns of data by different conditions did not show any statistically
significant signal, when considering all of these demyelinating conditions collectively (including MS), they
observed a 30-day increased risk window among the under 50 population as compared to the controls.
30
We found no longer-term association of vaccines with MS or any other
[acquired central nervous system demyelinating syndromes], which argues
against a causal association. The short-term increase in risk suggests that
vaccines may accelerate the transition from subclinical to overt
autoimmunity in patients with existing disease. Our findings support clinical
anecdotes of [acquired central nervous system demyelinating syndromes]
symptom onset shortly after vaccination but do not suggest a need for a
change in vaccine policy.
(Langer-Gould et al., supra, at Ex. 63, p. 1506.) Thus, petitioner contends in effect that,
by the study authors’ own conclusion, the Langer-Gould study bolsters the validity of
prior case reports of post-vaccination CNS demyelination, such as those cited by Dr.
Steel, and suggests that epidemiology examining an overall causal relationship between
MS and vaccines is not dispositive regarding the question of significant aggravation.
The initial ruling on entitlement characterized the Langer-Gould study as “especially
relevant and persuasive” as a crystallization of Dr. Steel’s theory because it included a
statistically significant finding of post-vaccination acquired CNS demyelinating
syndromes in humans that implicated the Tdap vaccine and included an explanation of
its findings by the study authors mirroring the “fertile field” understanding of
autoimmunity underlying Dr. Steel’s own opinion in this case. (ECF No. 73, pp. 23-25.)
On review, however, the Court of Federal Claims assigned error in the initial
ruling’s consideration of the Langer-Gould study. The Court looked at the fact that no
association was found when MS was viewed in isolation, the fact that no association
was found for the over 50 group, and the fact that onset of petitioner’s own condition
was outside the 30-day risk window identified by the study. Accordingly, the Court
indicated that “there is no way to look at the data and find an association between
vaccinations and Petitioner’s own condition.” (ECF No. 90, p. 8.) The Court further
indicated that “[a]lthough there can be association without causation, there cannot be
causation without association.” (Id.)
Nonetheless, petitioner continues to argue in her supplemental brief on remand
that the Langer-Gould study should carry some evidentiary weight. Specifically,
petitioner contends that “the authors of the study themselves appear to believe that their
findings are of general applicability when it comes to vaccinations and CNS disease,
including MS. Dr. Steel is simply re-iterating their conclusion and applying it to the
instant case – an application that their wording plainly allows.” (ECF No. 97, p. 16.)
The Court remanded the case with the instruction “to re-evaluate the medical
evidence under the correct legal and scientific standards.” (ECF No. 90, p. 10.)
However, the Court also made explicit findings regarding the Langer-Gould study itself
that preclude it from further consideration. The Court highlighted language from
Broekelschen v. Secretary of Health and Human Services, instructing that a petitioner
must provide “a reputable medical or scientific explanation that pertains specifically to
the petitioner’s case[.]” (ECF No. 90, pp. 3, 9 (quoting 618 F.3d 1339, 1345 (Fed. Cir.
(Id. at 6 (Figure 2).) The authors indicated that a limitation of the study was that “the number of older
individuals was relatively small.” (Id. at 7.)
31
2010).) The Court concluded that “[t]he fact that the Langer-Gould study shows no
association relevant to Plaintiff means that it does not evidence causation: A finding of
causation would have to be despite the Langer-Gould study, not because of it.” (Id.
(emphasis original).) Thus, although this decision on remand otherwise re-evaluates
the medical evidence as a whole in accordance with the Court’s remand instruction, it
adopts the Court’s specific finding that the Langer-Gould study does not evidence
causation as the law of the case. 28
Given that the Langer-Gould study – at least by petitioner’s and Dr. Steel’s
account – bolstered the value of prior case reports regarding post-vaccination CNS
demyelination, removing the study from consideration does leave this a closer case.
However, Langer-Gould was never the sole support for Dr. Steel’s theory. In fact, it was
not even cited until he submitted his second report. In any event, “[t]he Vaccine Act
does not contemplate full blown tort litigation in the Court of Federal Claims. The
Vaccine Act established a federal ‘compensation program’ under which awards are to
be ‘made to vaccine-injured persons quickly, easily, and with certainty and generosity.’”
Knudsen, 35 F.3d at 549 (quoting H.R.Rep. No. 99–908, 99th Cong., 2d Sess. 18,
reprinted in 1986 U.S.C.C.A.N. 6344.) Accordingly, the Federal Circuit has suggested
that this program represents a “system created by Congress, in which close calls
regarding causation are resolved in favor of injured claimants.” Althen, 418 F.3d at
1280.
Even without the Langer-Gould study, Dr. Steel’s explanation of the underlying
immunology remains sound and reliable and preponderantly establishes that vaccines,
including Tdap, can significantly aggravate subclinical MS to produce demyelinating
lesions. Important to this point, Dr. Sriram likewise acknowledges that MS relapses are
known to respond to immune precipitating factors such as intercurrent infections and
abrupt withdrawal of immune modulating therapies. (Ex. O, pp. 6-7.) Although Dr.
Sriram does not extend this conclusion beyond these two established triggers, he
acknowledges that ultimately the cause(s) or precipitating factors of MS relapses
otherwise remain unknown. (Id.) In that regard, Dr. Steel’s filing of a meta-analysis by
Mohr, et al., provides evidence going beyond what Dr. Sriram readily accepts and
further suggests, as Dr. Steel contends, that the stimuli at issue with specific regard to
MS relapse can be non-specific immunogenic stresses beyond active infection. 29 (Ex.
28 Law of the case is a judicially created doctrine, the purpose of which is to prevent relitigation of issues
that have been decided. See Gould, Inc. v. United States, 67 F.3d 925, 927–28 (Fed.Cir.1995). The
Federal Circuit has confirmed that the law of the case doctrine applies in Vaccine Act cases. Suel v.
Sec'y of Health & Human Servs., 192 F.3d 981 (Fed. Cir. 1999). Respondent also argued substantively
that the decision on remand cannot rely upon the Langer-Gould study but did not specifically cite the law
of the case doctrine. (ECF No. 98, pp. 8-9.) Because I am following the law of the case, I do not reach
respondent’s substantive arguments on remand regarding Langer-Gould. I do note, however, that
respondent’s argument generally repeats the analysis contained in the Court’s Opinion and Order.
29 The Mohr authors hypothesize that reducing stress in people with MS can reduce T cell production,
suggesting based on prior animal studies that increases in stress-related cortisol may enhance sensitivity
to proinflammatory T cells. (Mohr et al., supra, at Ex. 44, p. 3.) Even setting aside that specific
hypothesis, this meta-analysis provides some indication in humans that the course of MS attacks respond
to stimuli as Dr. Steel explains, though the authors caution that “the occurrence of any specific
exacerbation cannot yet be linked to any specific stressor.” (Id. at 4.)
32
20, p. 4; see also David C. Mohr et al., Association between stressful life events and
exacerbation in multiple sclerosis: a meta-analysis, BMJ 1 (2004) (Ex. 44).) Further, Dr.
Steel cites to researchers who have included statements in their papers expressing
views consistent with the theory offered by Dr. Steel in this case. (Frohman &
Wingerchuk, supra, at Ex. 39, p. 567 (“The occurrence of transverse myelitis after
infection or vaccination does not preclude the need for further evaluation, since infection
or immunization may also trigger attacks of myelitis in the context of an underlying
disease (especially multiple sclerosis or neuromyelitis optica).”); Langer-Gould, supra,
at Ex. 63, p. 1512 (“our findings are consistent with vaccines acting as a
proinflammatory cofactor in individuals with subclinical autoimmunity because this
mechanism would be expected to hasten symptom onset but not change the long-term
risk of developing MS or CIS.” 30); Kerr and Ayetey, supra, at Ex. 61, p. 344 (“emerging
evidence suggests that a variety of immune stimuli, through such processes as
molecular mimicry or superantigen-mediated immune activation, may trigger the
immune system to injure the nervous system. The activation of previously quiescent
autoreactive T lymphocytes or the generation of humoral derangements may be effector
mechanisms in this process.” (emphasis added)).)
ii. Dr. Sriram is unpersuasive in rebuttal
As noted above, the affirmative case presented by petitioner in support of her
prima facie burden under Loving prong four is a close call. Accordingly, the lack of
persuasiveness in Dr. Sriram’s response is a significant factor further contributing to the
outcome in this case. Dr. Sriram’s rebuttal to Dr. Steel’s theory is primarily grounded in
two points – the lack of epidemiologic support and “clinical prudence and parsimony.”
Neither is persuasive on this record. I address each in turn.
1. Epidemiology
Dr. Sriram agrees that the underlying premise of Dr. Steel’s theory has been a
relevant concern in the medical community and that a causal role for vaccinations has
been suspected in the worsening of MS. Specifically, he explains that “[s]ince vaccines
are proteins and are given to induce an immune response to deter bacterial and viral
infections, there was concern that introducing antigens into the body could worsen
autoimmune diseases, including multiple sclerosis.” (Ex. A, p. 9.) However, based on
his review of relevant epidemiology, Dr. Sriram takes the view that this concern was not
ultimately borne out. (Id. at 9-10.)
The Federal Circuit has previously stressed that a petitioner is not obligated to
present an epidemiological case supporting her claim. Capizzano v. Sec’y of Health &
Human Servs., 440 F.3d 1317, 1325 (Fed. Cir. 2006). Nonetheless, “[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) (citing Andreu, 569 F.3d at 1379 (“Although Althen and
Capizzano make clear that a claimant need not produce medical literature or
30Though noting the expressed views of the authors, this study itself does not support causation for the
reasons discussed above.
33
epidemiological evidence to establish causation under the Vaccine Act, where such
evidence is submitted, the Special Master can consider it in reaching an informed
judgment as to whether a particular vaccination likely caused a particular injury.”).
Here, however, the epidemiology at issue has significant limitations, which Dr. Steel has
addressed, and does not ultimately undermine petitioner’s theory.
Dr. Steel agrees that the epidemiological evidence indicates that “MS, a chronic,
recurrent and progressive disorder, is not likely caused by any single immune insult
event.” (Ex. 20, p. 4.) However, Dr. Steel also cautioned that “since all vaccine injuries
are quite rare relative to the total number of vaccinations administered . . . [i]t is possible
for a given adverse event to occur, but not to occur with sufficient frequency to produce
an epidemiological signal.” (Ex. 54, p. 7.) He also opined that “[t]he dissemination of
MS clinical events in time means that relating onset of symptoms to specific immune
challenges is difficult, and it is likely that triggering of clinically significant MS by vaccine
is underreported for this reason.” (Ex. 20, p. 4.) Mailand and Fredericksen, a literature
review on vaccines and MS that is often cited as authoritative and was relied upon by
Dr. Sriram in this case, agrees, noting that:
Another problem of studying MS risk factors is the lag between onsets of
the initial symptoms and final diagnosis. Time between symptoms and
diagnosis varies considerably depending on several factors, including
individual health-seeking behaviour, health care systems, diagnostic
techniques, etc. As a result, studies with short follow-up have a risk of
disregarding potential association. However, studies with a too long follow-
up risk diluting a potential association or to find false positive association
due to subsequent triggers. Finally, manifestations of MS vary significantly
between patients, making it difficult to compare the course of the disease.
(Mia T. Mailand & Jette L. Frederiksen, Vaccines and multiple sclerosis: a systematic
review, 264 J. NEUROL. 1035, 1048 (2017) (Ex. E).)
Mailand and Fredericksen note in their conclusion that accumulated evidence so
far does not find an association between a number of vaccines, including tetanus-
containing vaccines, and MS relapses, but ultimately indicate that an association cannot
be fully excluded without further research. (Id.) Dr. Sriram cited one study that post-
dated the Mailand and Frederickson review; however, that study was not able to reach
any conclusion with respect to tetanus-containing vaccines specifically. 31 (Alexander
Hapfelmeier et al., A large case-control study on vaccination as risk factor for multiple
sclerosis, 93(9) NEUROLOGY e908 (2019) (Ex. J).) Many of the earlier epidemiologic
studies were previously addressed by the IOM in its 2012 report. As of 2012, the
Institute of Medicine concluded that epidemiologic evidence is “insufficient or absent” to
assess whether there is an association between diphtheria toxoid or acellular pertussis
31 When discussing the effects of specific vaccinations, the authors explained that “[s]ufficient numbers for
meaningful analysis were available for vaccinations against TBE virus, HPV, pneumococci,
meningococci, influenza, hepatitis A and B, meningococci [sic], MMR, and varicella viruses[,]” i.e. not
tetanus-containing vaccines. (Hapfelmeier et al., supra, at Ex. J, p. e912.)
34
vaccine and either onset or relapse of MS in adults. (Institute of Medicine, supra, at Ex.
66, p. 583.)
In his response to petitioner’s original motion for a ruling on the written record
(incorporated by reference in his supplemental brief), respondent contended: “[f]or
example, in Exhibit 28, Loebermann et al. affirm that ‘a recent extensive review from the
US Institute of Medicine’ debunked ‘[c]oncerns . . . that . . . vaccination might [] trigger
the onset of MS in susceptible individuals.’” (ECF No. 70, p. 20 (emphasis added)
(quoting Ex. 28, p. 1).) However, respondent’s incomplete quotation from Loebermann
misstates the IOM’s conclusion. The Loebermann article itself accurately states that
“[t]he US Institute of Medicine did not find sufficient evidence to accept or reject a
causal relationship between onset of MS and vaccination against [various
vaccinations].” (Micha Loebermann et al., Vaccination against infection in patients with
multiple sclerosis, NATURE REVIEWS NEUROL. 143 (2012) (Ex. 28) (emphasis added).)
The finding by the IOM that the available evidence is insufficient to reject a causal
relationship explicitly contradicts respondent’s framing of the report as “debunking”
petitioner’s theory. With specific regard to tetanus-containing vaccinations, two of the
four studies cited by Loebermann, et al. – DeStefano (Loebermann ref. 15) and
Confraveux (Loebermann ref. 16), both discussed below – have been separately filed in
this case and contributed to the 2012 IOM review that concluded a causal relationship
could not be rejected.
In particular, respondent urged that “original research by DeStefano et al. refuted
the theory that ‘exposures that occur shortly before initial clinical symptoms,’ e.g.,
vaccinations, ‘would be most likely acting as triggers of clinical disease expression in
individuals who already have an underlying disease process,’ e.g., MS.” (ECF No. 70,
p. 20 (quoting Ex. 34, p.4) (emphasis original).) However, the IOM concluded that this
DeStefano study “lacked validity and precision” and noted that it had specific limitations
in how it addressed timing and failed to include a short-term assessment in its primary
analysis. The IOM indicated it had “limited confidence in the epidemiologic evidence”
addressing onset or relapse of MS in adults following tetanus containing vaccines.
(Institute of Medicine, supra, at Ex. 66, p. 549-51.) This conclusion also included review
of the additional Confavreux, et al, study cited by Loebermann and stressed by Dr.
Sriram in his second report. 32 (Institute of Medicine, supra, at Ex. 66, p. 549-51); see
also Ex. O, p. 7 (citing Christian Confavreux et al., Vaccinations and the Risk of Relapse
in Multiple Sclerosis, 344(5) N.E. J. MED. 319 (Ex. P)).)
Dr. Sriram goes still further, stressing that certain of the prior epidemiologic
studies suggest not only the lack of any association but instead that tetanus vaccine has
32 In his supplemental brief, respondent stresses that the initial ruling on entitlement characterized the
Confavreaux study as having been cited by Dr. Sriram. (ECF No. 98, p. 10, n. 8.) Respondent notes
instead that Dr. Steel cited the study first. (Id.) However, Dr. Sriram did not merely respond to Dr. Steel’s
initial citation, he affirmatively cited it as rebuttal to Dr. Steel’s separate reliance on the above-discussed
Frohman and Wingerchuk paper. (Ex. O, p. 4.) In any event, there can be absolutely no question that it
is ultimately respondent rather than petitioner relying on the body of epidemiology regarding vaccines and
MS. Thus, any short-comings apparent in the study necessarily have more impact on respondent’s
arguments.
35
a protective effect against MS. 33 (Ex. A, pp. 9-10.) He similarly stresses that “[a]s
clinicians we don’t withhold immunizations on the belief that [vaccinations] may ‘trigger’
relapses in MS patients.” (Ex. A, p. 15.) This is confounded by the possibility of
infection being the more significant risk as compared to vaccination. (See, e.g.,
Loebermann et al., supra, at Ex. 28, p. 149 (explaining that “[a]voidance of infection in
patients with MS generally reduces the risk of relapse and deterioration of health status
. . .”).) That vaccines protect against the still greater risk of infection does not mean that
they are themselves entirely risk free. Thus, for example, Mailand and Fredericksen
explain that “[i]n general, it seems that more benefits than costs are associated with
vaccination of MS patients. First and foremost to evade potential life-threatening
diseases, but also to avoid infections that might accelerate progression of the disease.”
(Mailand & Frederiksen, supra, at Ex. E, p. 1048.) They identify the potential protective
effect of tetanus vaccination but explain that many of the relevant studies lack statistical
power or contain confounding factors. (Id. at 1046.) They conclude that the protective
effect “might exist” but that further study is necessary. (Id.)
Thus, despite the lack of any clear epidemiologic signal, and contrary to Dr.
Sriram’s suggestion that concern regarding vaccine-related worsening of MS is only a
past tense concern, the medical literature filed in this case shows that researchers in
the relevant field continue to consider this an open question unresolved by
epidemiology. While some of the literature filed does include stronger language
purporting to rule out vaccines as causally important (e.g., Loebermann et al., supra, at
Ex. 28, p. 149), when considering the record as a whole Dr. Sriram is unpersuasive in
his suggestion that there is a “prevailing view” in the relevant medical community that
epidemiology precludes petitioner’s claim. (Ex. A, p. 9.)
2. Clinical prudence and parsimony
Apart from epidemiology, the crux of Dr. Sriram’s critique of Dr. Steel’s opinion is
the assertion that Dr. Steel’s reliance on evidence relating to acute TM in the context of
MS is unreasonable “conflation.” (Ex. O, p. 3.) Dr. Sriram opines that “[w]hen a
neurological syndrome like spinal myelitis is a well-defined part of the clinical picture of
a given disease, e.g., MS, it is clinical prudence and parsimony (Occam’s Razor)[34] to
recognize that the clinical picture is more than likely to be due to the underlying disease
process, i.e., MS, than some other cause.” (Id. at 1-2.) He also asserts that Dr. Steel
33Dr. Sriram has previously presented this logic and it has been rejected. Jane Doe/74 v. Sec'y of Health
& Human Servs., No. [Redacted], 2010 WL 2788239, at *9 (Fed. Cl. Spec. Mstr. June 28, 2010)
(explaining that “[Dr. Sriram] noted that Hernán and his co-authors in respondent's Exhibit C–5 did a
meta-analysis of studies showing a decreased risk of MS among those who received tetanus vaccine but
were unable to explain why [sic.] the reasons for this. If this result is accurate, it does not mean that no
one who receives tetanus vaccine can get MS. It just means the risk is less.”)
34“Occam’s razor is “[t]he principle of parsimony. William of Occam (14th century) stated it thus: ‘The
assumptions introduced to explain a thing must not be multiplied beyond necessity.” Fisher v. Sec’y of
Health & Human Servs., 99-432V, 2009 WL 2365459, at n. 6 (Fed. Cl. Spec. Mstr. July 13, 2009) (quoting
Stedman’s Medical Dictionary 27th ed. (2000) at 1250.)
36
“seeks to collapse the well-accepted distinction between idiopathic transverse myelitis
and disease-associated transverse myelitis . . . .” (Id. at 6.) However, in the context of
this case, this critique is unpersuasive without more and inconsistent with petitioner’s
burden of proof. 35
Dr. Steel observes that among all CNS demyelinating conditions “[t]he disorders
differ in epidemiology (i.e., age and sex predilection), and clinical factors such as speed
of onset, diversity of symptoms, severity of attacks, outcome, and prognosis.” (Ex. 20,
p. 4.) However, he explains that “[t]hese disorders are all acquired diseases of the
white matter of the central nervous system caused by self-directed attack by both
humoral and cellular immune elements.” (Id.) He further indicates that CNS
demyelinating disorders “share common histopathological findings on microscopic study
of damaged tissue including perivenular extravasation of inflammatory cells
(lymphocytes, monocytes), destruction of astrocytes and myelin sheaths, proliferation of
microglia, and accumulation of antibodies and mediator of inflammation in a spotty or
sometimes diffuse fashion in the CNS white matter.” (Id. at 3-4.)
That is, according to Dr. Steel, relapsing MS, though having distinct features of
its own, still includes discrete episodes of immune-related, inflammatory demyelination
likely occurring as the result of the same immune process as other CNS demyelinating
conditions and causing the same type of damage as seen in those other conditions.
Thus, for example, the TM Consortium Working Group, discussed with respect to
Loving prong three above, stressed the importance of distinguishing idiopathic ATM
from disease-associated ATM for purposes of medical treatment and improved care,
but, consistent with Dr. Steel’s opinion, also nonetheless observed that “the
inflammatory pathologies of MS, ADEM, and NMO may exist on a continuum with ATM.”
(TM Consortium Working Group, supra, at Ex. 68, p. 501.) Indeed, the gravamen of
much of the literature addressing diagnosis is that a first attack of MS cannot always be
clinically distinguished from TM upon initial presentation. In fact, Dr. Sriram himself
35
It must be stressed here that Dr. Sriram’s specific statement favoring clinical parsimony is part of an
overarching opinion that charges Dr. Steel with a “mistake in clinical diagnosis” regarding the invocation
of TM in a patient with MS. (Ex. O, p. 6.) In some contexts, clinical parsimony or Occam’s razor can be
invoked with specific regard to choosing among diagnoses. E.g. Fisher, 2009 WL 2365459, at *15
(explaining Dr. Sriram’s use of clinical parsimony with specific respect to identifying a unifying diagnosis
to explain all symptoms). And, as discussed regarding Loving prong three above, it is clear that Dr.
Sriram is correct to the extent that petitioner cannot be diagnosed with a separate APTM. However, the
specific question of diagnosis is not the limit of what Dr. Sriram contends in this case. Dr. Sriram also
explained that “Dr. Steel’s statement, ‘[a]cute partial transverse myelitis is strongly associated with
Multiple Sclerosis either as an initial presenting disease or as part of the ongoing relapsing-remitting
course of MS’ is in agreement with my position that [petitioner] in fact presented with a myelitic picture
compatible with her MS diagnosis . . . the initial presentation of an inflammatory demyelinating condition
like TM becomes a feature of MS once the MS diagnosis is made; it does not remain a separate disease
for which there is no clear etiology.” (Ex. O, p. 3 (emphasis added).) Later in the same report Dr. Sriram
states that “Dr. Steel’s argument that ‘very likely, the immune stimulation from multiple vaccinations
altered her biologic equilibrium,’ resulting in an ‘unmasking’ of [petitioner’s] MS, lacks any scientific
foundation and contravenes what we know about MS as a disease process.” (Id. at 6.) Thus, it is clear
that Dr. Sriram’s point is not only that the APTM diagnosis should not be separately applied. He also
contends that the MS disease process provides a “clear etiology” and should itself be considered
explanation enough for the myelitic event at issue. This section discusses why this further assertion is
unpersuasive.
37
quotes literature characterizing MS as “often ‘indistinguishable [from transient
demyelinating syndromes] at the time of initial presentation.’” (Ex. O, p. 3 (quoting
Lauren B. Krupp, Brenda Banwell, Silvia Tenembaum, Consensus definitions proposed
for pediatric multiple sclerosis and related disorders, 68 NEUROL. 1, 1-3 (2007) (Ex. L).)
Although Dr. Sriram provides a competing view that scientific evidence regarding
the causes of acute TM is not at all relevant in the context of MS, his written opinion
offers little to substantiate that view. In fact, he otherwise acknowledges on
respondent’s behalf that MS is an inflammatory and autoimmune demyelinating
condition for which “ultimately the cause of the disease remains unknown.” (Ex. A, p.
8.) RIS quite often leads to an eventual clinical manifestation of MS, but it is not
inevitable. One study filed in this case found that 84% of patients with RIS findings in
the spinal cord progressed to CIS. (See D.T. Okuda et al., Asymptomatic spinal cord
lesions predict disease progression in radiologically isolated syndrome, 76 NEUROL. 686
(2011) (Ex. 46).) However, that same study indicated that only 7% of patients with RIS
without cervical spinal involvement, like petitioner prior to vaccination, progressed to
CIS. (Id. at 690.) The literature filed in this case also explains that “[t]he absence of a
relation between relapses and irreversible disability suggests that there is a dissociation
at the biologic level between recurrent acute focal inflammation and progressive
degeneration of the central nervous system.” (Christian Confavreux et al., Relapses
and Progression of disability in Multiple Sclerosis, 343(20) N.E. J. MED. 1430, 1437
(2000) (Ex. 29).) Thus, Dr. Sriram offers only that “[r]elapses are a central feature of
MS and their occurrence &/or factors precipitating it are not known.” (Ex. O, p. 6.)
Dr. Sriram’s written opinion also lacks any specific challenge to Dr. Steel’s
broader assertion that MS attacks are affected by external factors and immune stimuli.
In fact, he acknowledges that intercurrent infections and abrupt withdrawal of
immunomodulatory medication are examples of immune-related triggers that do cause
relapses. (Id. at 6-7; see also Nathan Young, Brian G. Weinshenker, Claudia F.
Lucchinetti, Acute Disseminated Encephalomyelitis: Current Understanding and
Controversies, 28(1) SEMIN. NEUROL. 84, 86-87 (2008) (Ex. M) (noting patients with a
first presentation of MS as having increased frequency of antecedent infections)).
Additionally, as explained above, Mohr, et al., provides at least some support for the
proposition that the course of MS exacerbations responds to stimuli beyond those
acknowledged by Dr. Sriram. (Mohr et al., supra, at Ex. 44.)
Dr. Sriram stresses that Dr. Steel’s own citations support the distinction between
disease-caused and idiopathic TM. (Ex. O, p. 6.) Respondent likewise stresses that
demyelinating diseases are not interchangeable. (ECF No. 98, p. 13, n. 15 (citing Chen
v. Sec’y of Health & Human Servs., No. 16-634V, 2019 WL 2121208).) This is
undoubtedly true, as is made is clear by the above discussion relative to Loving prong
three. The distinction clearly has meaning in terms of prognosis and treatment, but
these conditions are not entirely unrelated for the reasons discussed by Dr. Steel. The
necessary further question is what, if any, significance the distinction between idiopathic
and disease-associated TM ultimately has regarding the underlying pathophysiology
and potential cause(s) and/or trigger(s). To be persuasive, respondent and his expert
would need to substantiate the implicit assertion that the differences among related
38
demyelinating conditions are more important to the analysis of petitioner’s causal theory
than the commonalities. That has not been done here. 36
Dr. Sriram contends of Dr. Steel’s supporting citations that “one of the papers
which he presents (Exhibit 54, reference 3, Exhibit 61) clearly distinguishes between
disease-associated TM and putative ‘postvaccination’ TM, which is categorized as a
type of idiopathic TM.” (Ex. O, p. 4.) Dr. Sriram explains that this paper describes the
immunopathogenesis of TM as “varied” and further explains that TM associated with MS
includes “perivascular lymphocytic cuffing and mononuclear cell infiltration
immunopathogenically and with variable complement and antibody deposition.” (Id.
(quoting Douglas A. Kerr, Harold Ayetey, Immunopathogenesis of acute transverse
myelitis, CURR. OP. NEUROL. 339, 340 (2002) (Ex. 61).) Significantly, however, the
purpose of that quoted language is to distinguish MS-related TM from other disease-
associated TM related to lupus, thrombotic infarction, and neurosarcoid-associated non-
caseating granulomas. (Id. at 340.) The article goes on to explain that all are “poorly
understood” and that the article will simply focus on idiopathic acute TM. (Id.) This is
the only attempt Dr. Sriram offers to physiologically distinguish MS-associated TM from
idiopathic TM. Yet nowhere in Dr. Sriram’s report does he explain why the features
identified (i.e. lymphocytic cuffing and mononuclear cell infiltration, as well as
complement and antibody deposition) should be viewed as incompatible with a vaccine-
triggered immune response leading to disease-associated TM. Rather, Dr. Sriram
points again to the fact that this paper notes there is no associational evidence linking
36 It is important to note that while the relevance of each article is not a given, special masters are
obligated to consider the record as a whole and petitioners must be permitted to prove their cases
circumstantially. Althen, 418 F.3d at 1280 (citing Knudsen, 35 F.3d at 549). It is not necessarily unusual
for experts to rely in part on evidence pertaining to separate, but related, conditions. E.g. Patton v. Sec’y
of Health & Human Servs., No. 15-1553, 157 Fed. Cl. 159 (2021) (reversing the special master where the
special master rejected petitioner’s expert’s reliance on evidence relating to GBS to show that the flu
vaccine can cause brachial neuritis.); Koller v. Sec’y of Health & Human Servs., No. 16-439, 2021 WL
5027947 (Fed. Cl. Spec. Mstr. Oct. 8, 2021) (special master finding petitioner established Prevnar
vaccine can cause GBS where a key piece of evidence was a study about MS). Thus, given Dr. Steel’s
explanation (supported by record evidence) that demyelinating diseases, including MS, idiopathic TM,
and disease-associated TM, represent a family of pathophysiologically related conditions, respondent
does not defeat petitioner’s claim merely by declaring that the conditions are not “interchangeable” and
therefore contending that only literature strictly addressing MS may be considered. In fact, although CNS
demyelinating conditions are not all the same, in some prior instances the precise diagnosis has not been
treated as dispositive of the causation analysis. E.g., Hitt v. Sec’y of Health & Human Servs., No. 15-
1283V, 2020 WL 831822, at n.8 (Fed. Cl. Spec. Mstr. Jan. 24, 2020) (finding preponderant evidence of
an initial diagnosis of TM followed by a subsequent diagnosis of multiple sclerosis, but noting that “the
importance of the diagnosis is diminished” by respondent’s expert’s agreement that either condition can
be caused by the flu vaccine.); Jane Doe/74, 2010 WL 2788239, at *10 (finding that “[p]etitioner has
fulfilled the first Althen prong by proving through Dr. Smith’s testimony that an antigen in
diphtheria/tetanus or MMR can cause demyelinating disease, such as TM/MS, through an autoimmune
process . . .”). The Althen petitioner herself suffered optic neuritis that was part of a broader a CNS
demyelinating disorder without a clear diagnosis. Id. at 1276-77. The Federal Circuit upheld the Court of
Federal Claims’ conclusion that the petitioner had met her burden where, inter alia, her expert opined that
“in his judgment, whether petitioner’s condition is diagnosed as relapsing ADEM, MS, or CNS vasculitis ‘is
not a big issue’ as ‘the underlying inflammatory process is undoubtedly the same in each instance.’”
Althen v. Sec’y of Health & Human Servs., 58 Fed. Cl. 270, 276-77 (2003).
39
vaccinations and increased incidences of neurological complications, a point which is
addressed separately above. 37 (Ex. O, p. 4.)
It is conceivable that Dr. Sriram could have persuasively developed these points
given that prior MS cases in this program have been presented to mixed results. 38 On
this record, however, Dr. Steel is persuasive in suggesting that the causes of MS
relapses are multifactorial. (Ex. 54, p. 2.) Accordingly, without more, labeling
petitioner’s attack of myelitis as an MS relapse is not an answer that precludes vaccine
causation as Dr. Sriram proposes. That is, it does not preclude other contributing
causal factors apart from the MS itself and does not in itself persuasively suggest that
Dr. Steel is engaged in unreasonable conflation when he considers the causes of acute
TM as evidence supportive of what may likewise trigger comparable demyelination in
the context of a relapse in MS.
37 The Kerr article is not itself informative of whether these distinctions are ultimately significant for
purposes of causation, and it should be further noted that the article stresses in the introduction that TM
and MS exist on a continuum of neuroinflammatory disorders and that “clinical and pathological studies
support the notion that there are many common features of the inflammation and neuronal injury” among
these conditions. (Kerr and Ayetey, supra, at Ex. 61, p. 339.) The authors specifically note that for all of
these conditions there are outstanding “critical questions that must be answered before we truly
understand acute transverse myelitis.” (Id.) Among these questions, the authors highlight “What are the
various triggers for the inflammatory process that induces neuronal injury in the spinal cord?” (Id.)
However, in their conclusion the authors posit without respect to any specific diagnosis that: “emerging
evidence suggests that a variety of immune stimuli, through such processes as molecular mimicry or
superantigen-mediated immune activation, may trigger the immune system to injure the nervous system.
The activation of previously quiescent autoreactive T lymphocytes or the generation of humoral
derangements may be effector mechanisms in this process.” (Id. at 344 (emphasis added).) This
hypothesis is consistent with Dr. Steel’s reliance on the fertile field theory for this case, as cited
separately above.
38 See Robinson v. Sec'y of Health & Human Sers., No. 14-952V, 2021 WL 2371721 (Fed. Cl. Spec. Mstr.
Apr. 12, 2021) (finding flu vaccine caused MS); Hitt v. Sec’y of Health & Human Servs., No. 15-1283V,
2020 WL 831822 (Fed. Cl. Spec. Mstr. Jan. 24, 2020) (finding that the flu vaccine caused petitioner “to
develop transverse myelitis and, ultimately, multiple sclerosis”); Quackenbush-Baker v. Sec’y of Health &
Human Servs., No. 14-1000V, 2018 WL 1704523, at *17-19 (Fed. Cl. Spec. Mstr. Mar. 14, 2018) (finding
flu vaccine significantly aggravated MS); Smith v. Sec'y of Health & Human Servs., No. 08–864V, 2016
WL 2772194 (Fed. Cl. Spec. Mstr. Apr. 18, 2016) (awarding compensation for MS linked to a hepatitis B
vaccine); Fisher v. Sec'y of Health & Human Servs., No. 99-432V, 2009 WL 2365459 (Fed. Cl. Spec.
Mstr. July 13, 2009) (same); Werderitsh v. Sec'y of Health & Human Servs., No. 99–310V, 2006 WL
1672884 (Fed. Cl. Spec. Mstr. May 26, 2006) (same); but see W.C., 704 F.3d 1352 (affirming special
master’s decision denying entitlement for MS significantly aggravated by flu vaccine). Tetanus has also
been implicated as causally contributing to MS injury in connection with other vaccines, but not in
isolation. Giannetta v. Sec'y of Health & Human Servs., No. 13-215V, 2017 WL 4249946 (Fed. Cl. Spec.
Mstr. Sept. 1, 2017) (MS found to be caused by meningococcal vaccine based on tetanus toxoid
component of the vaccine); Jane Doe/74 v. Sec'y of Health & Human Servs., No. [Redacted], 2010 WL
2788239 (Fed. Cl. Spec. Mstr. June 28, 2010) (awarding compensation for TM and MS linked to tetanus-
diphtheria and measles-mumps-rubella (“MMR”), hepatitis B, and meningococcal vaccines); but see Pek
v. Sec’y of Health & Human Servs., No. 16-736V, 2020 WL 1062959 (Fed. Cl. Spec. Mstr. Jan. 31, 2020)
(denying entitlement where petitioner alleged flu and Tdap vaccines caused MS); Bubb v. Sec’y of Health
& Human Servs., No. 01-721V, 2005 WL 1025707 (Fed. Cl. Spec. Mstr. Apr. 29, 2005).
40
In the context of a significant aggravation claim, petitioner is obligated to
demonstrate as a matter of specific causation that her vaccination(s) affected her
condition rather than having initially caused it and will not have any burden to prove that
her ultimate condition is worse than her expected outcome. Sharpe v. Sec’y of Health &
Human Servs., 964 F.3d 1072, 1081 (Fed. Cir. 2020). Thus, in terms of presenting a
medical theory of general causation, the Federal Circuit has explained that “[u]nder
Loving prong 4, a petitioner need only provide ‘a medical theory causally connecting
[petitioner]’s significantly worsened condition to the vaccination.’ In other words,
Petitioner was required to present a medically plausible theory demonstrating that a
vaccine ‘can’ cause a significant worsening of [petitioner’s injury].” Sharpe, 964 F.3d at
1083 (citing quoting Loving, 86 Fed. Cl. at 144 (internal citation omitted).) Thus, the
Circuit emphasized that “a petitioner may be able to make out a prima facie case under
Loving prong 4 without eliminating a preexisting condition as the cause of her
significantly aggravated injury.” 39 Id. at 1083.
In the context of this case, the Sharpe holding suggests that while it could be
potentially relevant that the demyelinating episode at issue is ultimately attributable to
petitioner’s ongoing MS, that fact is not necessarily dispositive, as Dr. Sriram urges. In
light of all of the above, Dr. Sriram is not persuasive in asserting that clinical parsimony
dictates that a patient’s MS is itself the only relevant causal factor in any given instance
of MS-related CNS demyelination or that the causes of other CNS demyelinating
conditions are wholly irrelevant to determining the triggers of MS attacks. In that
context, adopting Dr. Sriram’s tact of clinical parsimony would impermissibly heighten
petitioner’s burden of proof. According to Sharpe, petitioner is not obligated to provide a
theory under Loving prong four that entirely rules out her MS as causally relevant. Even
if petitioner’s ongoing MS is a significant part of the explanation for her post-vaccination
myelitis, petitioner need not demonstrate her vaccine to have been the sole or
predominant cause of her injury. Shyface, 165 F.3d at 1344.
c. Loving Prongs Five and Six
Whereas the fourth Loving prong addresses general causation (i.e., can the
vaccine in general significantly aggravate a given condition), Loving prongs five and six
address specific causation (i.e., did the vaccine significantly aggravate this petitioner’s
39 In Sharpe, the petitioners argued that their minor child suffered a seizure disorder that was significantly
aggravated by vaccination. However, the special master concluded that the seizure disorder was solely
caused by a genetic mutation. Sharpe, 964 F.3d at 1080. The Federal Circuit assigned several errors
which were ultimately interrelated. With respect to Loving prong three, the Circuit concluded that it was
error for the special master to require petitioners to demonstrate the expected outcome of the genetic
seizure disorder at issue and then prove that the child’s condition was worse than that expected outcome.
Id. at 1082. The Circuit suggested there is “a fine line between a court properly considering evidence of
record and improperly placing the burden on the petitioner to prove that her significantly aggravated
condition was not caused by her gene mutation.” Id. (discussing Stone ex rel. Stone v. Sec’y of Health &
Human Servs., 676 F.3d 1373 (Fed. Cir. 2012) (internal citation omitted).) The Circuit distinguished a
prior case, Locane v. Secretary of Health and Human Services, on the basis that the special master in
that case had considered whether the vaccine affected the petitioner’s condition rather than requiring the
petitioner to prove that her significantly aggravated condition was not caused by her pre-existing
condition. Id. (citing 685 F.3d 1375 (Fed. Cir. 2012)). That analysis, in turn, informed the Circuit’s
treatment of Loving prong four.
41
condition). Specific causation is necessarily predicated on general causation and the
attendant analysis is premised on the nature of the theory of general causation. The
“did it” analysis is split between two prongs. Loving prong five requires a logical
sequence of cause and effect and Loving prong six relatedly, but separately, requires a
proximate temporal relationship. I start by taking timing under Loving prong six out of
order.
i. Loving prong six
The sixth Loving prong requires establishing a “proximate temporal relationship”
between the vaccination and the injury alleged. Loving, 86 Fed. Cl. at 144; Althen, 418
F.3d at 1281. That term has been equated to the phrase “medically-acceptable
temporal relationship.” Althen, 418 F.3d 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, 539 F.3d at 1352. The explanation for what is a medically acceptable
timeframe must also coincide with the theory of how the relevant vaccine can cause an
injury (Althen prong one's requirement). Id.; Shapiro v. Sec'y of Health & Human
Servs., 101 Fed. Cl. 532, 542 (2011), recons. den'd after remand, 105 Fed. Cl. 353(2012), aff'd mem., 503 Fed. Appx. 952 (Fed. Cir. 2013); Koehn v. Sec'y of Health &
Human Servs., No. 11–355V, 2013 WL 3214877, at *26 (Fed. Cl. Spec. Mstr. May 30,
2013), mot. for review den'd (Fed. Cl. Dec. 3, 2013), aff'd, 773 F.3d 1239 (Fed. Cir.
2014).
Here, petitioner first sought treatment on June 5, 2016, for right side weakness
and numbness, which began two nights prior, i.e., June 3, 2016. (Ex. 2, pp. 51, 59.)
Although the initial suspicion was transient ischemic attack, after extensive further follow
up, MS was eventually diagnosed. Dr. Steel opined that prior to vaccination petitioner’s
condition was best characterized as RIS, but that she “experienced a clinically
symptomatic event in a limited time window following vaccinations.” (Ex. 20, p. 3.) He
indicated that following this post-vaccination myelitis, petitioner met the diagnostic
criteria for MS based on this clinically isolated event. (Id.) Although Dr. Sriram did not
agree petitioner’s vaccinations were a relevant trigger, he similarly opined more
generally that petitioner’s “enhancing lesions suggested a recent acute [neurologic]
event.” (Ex. O, p. 1.) In addition to clinical symptoms, this is based on the fact that
petitioner’s spinal lesion grew in size from when it was first observed on June 6, 2016,
to when petitioner had a second MRI on August 17, 2016. (Ex. A, p. 8.) Dr. Sriram
agreed that MS-related spinal demyelination was the cause of petitioner’s weakness of
the arms and legs. (Id. at 9.) Dr. Sriram also opines that petitioner had never had a
clinical attack of MS prior to her June 5, 2016, presentation. (Id. at 8.)
In sum, Drs. Steel and Sriram agree that prior to vaccination petitioner’s MS was
clinically silent and that after vaccination she suffered a clinical attack of spinal
demyelination in the context of her MS that caused her to seek treatment on June 5,
2016. (Ex. 20, pp. 3, 5; Ex. 54, pp. 1, 6-7; Ex. A, pp. 7-8, 13.) Thus, the fact that
petitioner suffered onset of spinal demyelination occurring on or about June 3, 2016, is
essentially undisputed. (Ex. A, pp. 8-9.) June 3, 2016, was approximately 42 days
42
following her April 22, 2016, Tdap vaccination. 40 (Ex. 1.) Dr. Steel further opines that
this constitutes a medically appropriate onset for the type of autoimmune demyelination
at issue. (Ex. 20, p. 3 (opining based on petitioner’s CIS occurring “in a limited time
window following vaccinations”).) Additionally, some of petitioner’s treating physicians
implicitly agreed that the timing is appropriate to implicate petitioner’s prior vaccination
in autoimmune demyelination, albeit in the context of suspecting a different, though
somewhat related, demyelinating condition (ADEM). (Ex. 4, p. 8 (Dr. Rao); Ex. 50, p. 4
(Dr. Bidwell); Ex. 5, p. 58 (Dr. Baron), Ex. 17 (Dr. Kam-Hansen).)
Petitioner has filed literature explaining that a six-week latency is generally
accepted as appropriate for autoimmunity leading to demyelination. This is based on a
seminal study of GBS following 1976 and 2009 flu pandemics, but also extended to
CNS demyelination and MS within the literature based on case report. (Yahel Segal,
Yehuda Shoenfeld, Vaccine-induced autoimmunity: the role of molecular mimicry and
immune crossreaction, 15 CELLULAR & MOLECULAR IMMUNOL. 586, 588-89 (2018) (Ex.
25).) Some additional literature suggests other periods of onset extending for two or
more months post-vaccination may be reasonable. One piece of literature filed in the
case indicates that post-vaccination TM, which again Dr. Steel considers relevant,
occurs up to three months following vaccination. (Agmon-Levin et al., supra, at Ex. 42.)
Interestingly, an epidemiologic study that examined the risk of post-vaccination relapse
in MS (and found none) indicated that they restricted the study to relapses occurring
within two months of vaccination, explaining that “[t]he choice of a two-month risk period
in which vaccination might be considered to trigger a relapse was based on data from
the literature and on expert opinion.” (Confavreux et al., supra, at Ex. P, p. 325.) A
literature review filed by petitioner indicated that, while CNS demyelination often occurs
within three to four weeks of vaccination, it can also occur up to six months following
vaccination. (Karussis & Petrou, supra, at Ex. 60, p. 7.) The latter timeframe of six
months is much less persuasive given the other literature of record; however, it does
underscore that the three-to-four week period cannot be taken as a hard and fast
deadline. Special masters are discouraged from setting hard and fast deadlines for
onset based on specific studies that do not purport to set such definitive timelines.
Paluck v. Sec’y of Health & Human Servs., 786 F.3d 1373, 1383-84 (Fed. Cir. 2015)
(stating that “[t]he special master further erred in setting a hard and fast deadline” for
onset and noting that the medical literature filed in the case “do not purport to establish
any definitive timeframe for onset of clinical symptoms.”).
Prior cases in this Program have likewise identified the relevant temporal period
for vaccine-related CNS demyelination, including MS and ADEM, as being up to about
42 days, comparing that period to the timing of adaptive immune response otherwise
commonly accepted for peripheral demyelinating conditions such as GBS. See Smith,
2016 WL 2772194, at *18; Quackenbush, 2018 WL 1704523, at *20; Robinson, 2021
40 In point of fact, Dr. Sriram states in his second report that onset was about 45 days following the Tdap
vaccine. (Ex. O, p. 5.) However, this would refer to the date petitioner presented to the hospital rather
than the date of onset of her symptoms. Dr. Sriram clearly indicated in his first report that it was the
condition that led to her June 5, 20216 admission that constituted onset of her attack. (Ex. A, p. 8.) At
her initial medical encounter, petitioner indicated she had been suffering her symptoms for two nights,
placing onset on June 3. (Ex. 2, p. 51, 59.)
43
WL 2371721, at *22 (applying Langmuir’s six-week (42-day) onset interval to MS and
finding 13 days post influenza vaccination is a medically acceptable timeframe to infer
causation given the mechanism of molecular mimicry). In fact, an onset period of up to
42 days has also been widely acknowledged in other Vaccine Program cases in a
variety of other contexts in which molecular mimicry has been proffered as the causal
mechanism. See e.g., Ferguson v. Sec'y of Health & Human Servs., No. 17-1737V,
2021 WL 6276204 (Fed. Cl. Spec. Mstr. Dec. 10, 2021) (finding ITP onset within 30
days post Tdap vaccination is a medically acceptable timeframe to infer causation given
the mechanism of molecular mimicry and O’Leary et al.’s timeframe of 1 to 42 days as
the period of exposure); Randolph v. Sec'y of Health & Human Servs., No. 15-146V,
2021 WL 5816271 (Fed. Cl. Spec. Mstr. Nov. 12, 2021) (finding that petitioner’s
Bickerstaff Brainstem Encephalitis symptoms manifested in 43 days, one day over the
appropriate six-week (42-day) medically acceptable timeframe post influenza
vaccination); Koller v. Sec'y of Health & Human Servs., No. 16-439V, 2021 WL
5027947, at *23 (Fed. Cl. Spec. Mstr. Oct. 8, 2021) (citing “42-day timeframe” and
finding GBS onset of 12 days after Prevnar 13 vaccination to be “within the medically
accepted timeframe consistent with petitioner’s theory of molecular mimicry [and] that
has been accepted in other Vaccine Program cases.”); Barone v. Sec'y of Health &
Human Servs., No. 11-707V, 2014 WL 6834557, at *13 (Fed. Cl. Nov. 12, 2014)
(“[S]pecial masters have never gone beyond a two-month (meaning eight week) interval
in holding that a vaccination caused a demyelinating illness).
Dr. Sriram, for his part, opined that the vaccinations at issue were entirely
irrelevant. Accordingly, he did not specifically opine as to any temporal relationship.
Notably, however, he did not otherwise raise any additional reasons why petitioner’s
assertion of a temporal relationship should be viewed as incorrect. To the extent he
agreed that infections and withdrawing of immune modulating therapy can precipitate
MS relapse, he did not identify any other relevant temporal relationship between those
triggers and MS relapse. (Ex. O, pp. 6-7.) To the extent Dr. Sriram agreed that MS is
likely autoimmune generally and Dr. Steel further explicitly invoked molecular mimicry,
Dr. Sriram did not suggest that molecular mimicry and/or autoimmunity occur on any
time course incompatible with the facts of this case. That is, Dr. Sriram did not
challenge the notion that there is an apparent temporality as Dr. Steel opined. 41
41 For example, in his first report Dr. Sriram specifically responded to Dr. Steel’s statement that the
vaccines were in “close temporal proximity” to onset of petitioner’s MS. He responded only that “[t]he
prevailing opinion does not support the view that vaccines, even when given in ‘close temporal proximity,’
in any way ‘trigger’ onset or relapses in patients with MS, including individuals with previously clinically
silent MS.” (Ex. A, p. 15.) He concluded that report by indicating that “[o]ther than offering a temporal
relationship between [petitioner’s] receipt of the Tdap and polio vaccines and the development of clinical
and new MRI lesions, Dr. Steel does not provide a biological basis on which vaccines can cause
worsening of MS.” (Id. at 16.) Thus, Dr. Sriram appears to accept Dr. Steel’s assertion of temporal
proximity at face value. However, contrary to Dr. Sriram’s quoted statement, Dr. Steel did cite a biological
basis for causation – citing well established theories of autoimmunity, including molecular mimicry – in his
first report. (Ex. 20, p. 5.)
44
Based on all of the above, petitioner has preponderantly shown that onset of her
MS attack occurred within a timeframe during which a causal relationship to her Tdap
vaccination can be inferred. 42
ii. Loving prong five
The fifth Loving prong requires proof of a logical sequence of cause and effect
connecting petitioner’s vaccination(s) and injury, usually supported by facts derived from
a petitioner's medical records. Loving, 86 Fed. Cl. at 144; 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.
However, medical records and/or statements of a treating physician 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. See 42 U.S.C. §300aa-13(b)(1) (providing that
“[a]ny such diagnosis, conclusion, judgment, test result, report, or summary shall not be
binding on the special master or court”); Snyder v. Sec'y of Health & Human Servs., 88
Fed. Cl. 706, 746 n.67 (2009) (“there is nothing ... that mandates that the testimony of a
treating physician is sacrosanct—that it must be accepted in its entirety and cannot be
rebutted”).
Many of the factors underlying the logical sequence of cause and effect at issue
have been discussed in the preceding analyses. As explained relative to Loving prongs
one through three, there is preponderant evidence that petitioner suffered an attack of
spinal demyelination as the first clinical attack of her MS within 42 days of her Tdap
vaccine. As further noted in discussion of Loving prong six, this much is effectively
undisputed by respondent’s expert in that Dr. Sriram’s review of petitioner’s history
confirms petitioner presented for treatment on June 5, 2016, suffering a recent acute
neurologic event. (Ex. O, p. 1.) I have additionally concluded pursuant to Loving prong
three that this constituted a significant aggravation of her pre-existing MS and pursuant
to Loving prong six that the timing is medically appropriate to infer vaccine causation.
However, two issues hinder strict reliance on petitioner’s medical records for any further
assessment of whether a logical sequence of cause-and-effect supports vaccine-
causation.
First, uncertainty regarding petitioner’s correct diagnosis has obscured any direct
causal opinion. Some of petitioner’s treating physicians were willing to causally link her
initial presentation to her prior vaccination(s); however, those physicians had diagnosed
42Some cases involving GBS have noted a period of up to about two months to be medically reasonable
for autoimmune demyelination. Barone, 2014 WL 6834557, at *13. This is also consistent with at least
some of the literature discussed above and would further bring petitioner’s earlier polio vaccine into
medically appropriating temporal proximity. However, Dr. Steel discussed the combined effects of the two
vaccines. (Ex. 20, p. 5; 54, p. 7.) Thus, it is ultimately the timing of the second vaccine, the Tdap
vaccine, that is most relevant. It is less obvious that petitioner would be able to prevail if her claim was
based on the earlier polio vaccine alone. E.g., Archer v. Sec’y of Health & Human Servs., No. 15-656V,
2021 WL 2666692 (Fed. Cl. Spec. Mstr. May 27, 2021) (noting that petitioner’s expert indicated
appropriate timing for post-Tdap TM to be up to six weeks and finding petitioner unpersuasive in
suggesting 54-day onset is medical appropriate).
45
ADEM rather than MS. (Ex. 4, p. 8 (Dr. Rao); Ex. 50, p. 4 (Dr. Bidwell); Ex. 5, p. 58 (Dr.
Baron), Ex. 17 (Dr. Kam-Hansen).) This difference in diagnosis makes it impossible to
credit those causal opinions beyond a general recognition that onset of what they
recognized as immune-mediated demyelination occurred within the timeframe for which
vaccine causation of such demyelination could be inferred. 43 Those treating physicians
who diagnosed MS were simply silent as to any underlying cause or trigger for
petitioner’s attack, providing no evidence either supporting or contradicting her claim.
Second, Dr. Steel and Dr. Sriram generally agree on petitioner’s clinical history
and both experts are fundamentally speaking to the same disease process. That is,
regardless of whether I accept Dr. Steel’s or Dr. Sriram’s opinion, there is still
agreement that petitioner was suffering a first clinical attack of MS and that this attack of
MS constitutes inflammatory and autoimmune demyelination. This fact alone will
explain virtually all of petitioner’s relevant clinical findings and test results. For example,
while the presence of oligoclonal bands may be important evidence of CNS
inflammation in a more broadly contested case, both Drs. Steel and Sriram can claim
that finding as consistent with their opinion. Neither expert discusses any test or factor,
apart from personal clinical history, that can distinguish MS relapses by trigger. 44
Important then is the fact that the record of this case does not identify any other
suspected cause for petitioner’s clinically isolated event based on her own clinical
history. For example, although Dr. Sriram indicates that the precipitating factors for MS
relapses remain unknown, he also specifically opines that infections and immune
modulating therapy withdrawal can bring about a relapse. (Ex. O, pp. 6-7.) In that
regard, he has not suggested that either of these factors were present in this case. Nor
does my review of the medical records suggest that petitioner had any relevant prior
infection or immune modulating treatment. Dr. Steel separately filed literature indicating
that stressful life events can exacerbate MS (Mohr et al., supra, at Ex. 44); however,
43 As respondent notes, CNS demyelinating conditions are not interchangeable. (ECF No. 98, p. 13, n.
15.) They are, however, closely related. As discussed in the prior ruling on entitlement in addressing Dr.
Kam-Hansen’s causal opinion, although petitioner’s correct diagnosis is MS, ADEM and MS can be
difficult to distinguish upon initial presentation. (ECF No. 73, p. 18; 2021 WL 750416, at *13.) In that
regard the medical records suggest that the perceived temporality to vaccination partly informed the
ADEM diagnosis in this case. (Ex. 17, p. 1 (Dr. Kam-Hansen stating “[t]hese neurological findings are not
unique for ADEM or MS, but the fact that there was a temporal relationship between her symptom start
and the preceding vaccination, as well as the lack of any prior neurological symptoms which would
suggest the presence of MS before June of 2016, means that ADEM was more likely to cause her
symptoms.”)
44 For example, one paper filed by petitioner regarding MS explains that:
There is no single diagnostic test for MS and the diagnosis is usually based on the clinical
presentation, supported by neuroimaging and in some cases by CSF analysis (to look for
inflammatory markers oligoclonal bands and/or elevated IgG index) and evoked potential
studies (to look for clinically silent lesion in visual, brainstem, or spinal cord pathways).
(Garg & Smith, supra, at Ex. 45, p. 4.) CSF inflammatory markers are present in up to 85% [of] patients
with MS; IgG index is less sensitive and specific than oligoclonal bands. (Id. (internal citations omitted).)
46
nothing in the record suggests that petitioner was experiencing any such event at or
prior to onset of her MS. Although petitioner did have some chronic complaints
unrelated to her MS, neither Dr. Sriram nor Dr. Steel has suggested that they were
contributory to the specific MS attack at issue. 45
In Capizzano v. Secretary of Health and Human Services, the Federal Circuit
explained that:
“A logical sequence of cause and effect” means what it sounds like—the
claimant's theory of cause and effect must be logical . . . We see no reason
why evidence used to satisfy one of the Althen III prongs cannot overlap to
satisfy another prong. In other words, if close temporal proximity, combined
with the finding that hepatitis B vaccine can cause RA, demonstrates that it
is logical to conclude that the vaccine was the cause of the RA (the effect),
then medical opinions to this effect are quite probative . . . We recognize,
as the Court of Federal Claims observed, that the immense number of
people receiving the hepatitis B vaccine statistically results in instances
where individuals suffer an initial onset of rheumatoid arthritis shortly after
receiving the vaccine, but not as the result of the vaccine. However, the
statute requires only that the claimant show that it is more likely than not
that this claimant's RA was caused by the vaccine.
440 F.3d 1317, 1326 (Fed. Cir. 2006) (emphasis original, internal citations omitted). 46
The Capizzano Court reached its conclusion in light of the strength of treating
physician opinions available in the case. In later cases, however, the Federal Circuit
further indicated that “a petitioner is certainly permitted to use evidence eliminating
other potential causes to help carry the burden on causation and may find it necessary
to do so when the other evidence on causation is insufficient to make out a prima facie
case.” Walther, 485 F.3d at 1151; see also Pafford v. Sec’y of Health & Human Servs.,
451 F.3d 1352 (Fed. Cir. 2006). The Walther court also explained that:
45Dr. Steel did suggest that the fact that petitioner had pre-existing autoimmune disease in the form of
unrelated Graves’ Disease could be an additional predisposing factor, though there has been no
suggestion the condition played any specific role in the onset of her clinically overt MS. (Ex. 54, p. 7.)
46 On the other hand, the Capizzano Court also stated that:
[t]he second prong of the Althen III test is not without meaning. There may well be a
circumstance where it is found that a vaccine can cause the injury at issue and where the
injury was temporally proximate to the vaccination, but it is illogical to conclude that the
injury was actually caused by the vaccine. A claimant could satisfy the first and third prongs
without satisfying the second prong when medical records and medical opinions do not
suggest that the vaccine caused the injury, or where the probability of coincidence or
another cause prevents the claimant from proving that the vaccine caused the injury by
preponderant evidence.
440 F.3d at 1327 (emphasis original).
47
[w]hen a case involves multiple causes acting in concert (not the situation
involved here), we recognized in Shyface that a petitioner need not show
the asserted vaccine was the predominant cause but must show that it
was substantial. Where multiple causes act in concert to cause the injury,
proof that the particular vaccine was a substantial cause may require the
petitioner to establish that the other causes did not overwhelm the
causative effect of the vaccine.
485 F.3d 1146, at n. 4 (internal citation omitted) (citing Shyface, 165 F.3d at 1352-53).
In this case, petitioner’s satisfaction of Loving prongs three, four, and six, Dr.
Steel’s further diagnostic and causal opinion and explanation, the lack of any
contradictory treating physician opinion, and the absence of any known alternative
trigger, all support a logical sequence of cause and effect pursuant to Loving prong five.
Also notable to this point is the fact that the medical event at issue was CIS, the first
onset of petitioner’s clinically overt MS, rather than just one relapse indistinguishable
from an established pattern of relapses experienced by the petitioner. This is consistent
with Dr. Steel’s reliance on the “fertile field” concept of MS autoimmunity and has
previously been considered a relevant factor favoring a prior petitioner’s demonstration
of a logical sequence of cause and effect supporting significant aggravation of MS.
Quackenbush-Baker, 2018 WL 1704523, at *17-19. The literature filed in this case
shows that most, but certainly not all, patients with RIS will go on to develop CIS and/or
ultimately be diagnosed with clinically definite MS. (Okuda et al., supra, at Ex. 46, p.
686 (noting up to 84% of patients with RIS progressing to CIS); and Scott, supra, at Ex.
65, p. 375 (explaining 80-90% of patients with APTM will transition to clinically definite
MS).) In that regard, the literature indicates that RIS is not destiny. Thus, when
considering all of this, the sequence of cause and effect between vaccination and injury
is “logical” just as the Federal Circuit noted in Capizzano.
To the extent Dr. Sriram opined that petitioner’s MS should be viewed as the sole
cause of the relapse at issue, this is not persuasive for the reasons discussed above
with respect to Loving prong four. Dr. Steel is persuasive in presenting MS as
multifactorial and MS relapses as responsive to immune stimuli. Moreover, Dr. Sriram
offered no explanation of the relapsing nature of MS that could otherwise explain why
petitioner’s own relapse was necessarily solely attributable to the MS itself. Rather, he
acknowledged that the reason for that pattern of disease is not known. Moreover, the
literature filed in this case indicates that relapses are biologically “disassociated” from
the neurological progression of the disease. In any event, Dr. Sriram acknowledges
that at least some immune triggers do cause MS relapses, which is in tension with his
underlying premise that MS alone must necessarily be viewed as the sole causal factor.
d. Factor unrelated
Based on the analysis above, petitioner has demonstrated that her MS was, in
fact, significantly aggravated by vaccination by satisfying each of the six Loving prongs
by preponderant evidence. Once petitioner has satisfied her own burden pursuant to
the Loving test, the burden shifts to respondent to demonstrate that the injury was
caused by factors unrelated to vaccination. § 300aa-13(a)(1)(B); Deribeaux v. Sec’y of
Health & Human Servs., 717 F.3d 1363, 1367 (Fed. Cir. 2013).
48
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. 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 1369. It need not be scientifically
certain but must be legally probable. Id. Conditions or other factors that are “idiopathic,
unexplained, unknown, hypothetical, or undocumentable” cannot defeat a petitioner’s
claim. § 300aa-13(a)(2); Knudsen, 35 F.3d at 548.
As discussed in the preceding section, Dr. Sriram has not identified any relevant
alternative trigger to the specific MS relapse at issue. He urges “clinical prudence and
parsimony,” however, and opines that petitioner’s MS itself should be viewed as the
sole cause of her demyelinating attack that happened to occur post-vaccination.
Specifically, he opined that “[w]hen a neurological syndrome like spinal myelitis is a
well-defined part of the clinical picture of a given disease, e.g., MS, it is clinical
prudence and parsimony (Occam’s Razor) to recognize that the clinical picture is more
than likely to be due to the underlying disease process, i.e., MS, than some other
cause.” (Ex. O, p. 2.) However, for all the reasons discussed within the Loving analysis
above, Dr. Steel is persuasive in opining that the underlying etiology of MS and MS
relapses are multifactorial and Dr. Sriram has not persuasively substantiated his
contrary view. Additionally, as noted in the preceding section, Dr. Sriram acknowledges
that at least some immune triggers do cause MS relapses, which is in tension with his
premise pursuant to Occam’s razor that petitioner’s underlying MS necessarily
constitutes the sole explanation of petitioner’s post-vaccination condition. Thus,
respondent does not meet his burden of preponderantly establishing that petitioner’s
pre-existing MS is a factor unrelated to her vaccination that solely explains her condition
such that vaccination would be precluded as a substantial contributing factor.
VI. Conclusion
This case was remanded “for the Special Master to consider the parties’
arguments on aggravation of MS and to re-evaluate the medical evidence under the
correct legal and scientific standards.” (ECF No. 90, p. 10.) The Opinion and Order
remanding this case instructed that “[t]he Special Master shall issue a new entitlement
decision within ninety days of this decision.” 47 (Id.)
For all the reasons discussed above, I have completed this remand instruction
and issue the instant decision on remand. On remand, I find that petitioner is entitled to
compensation for a significant aggravation of her MS caused-in-fact by her April 22,
2016, Tdap vaccination. Additionally, based on the record as a whole I find that
47 Pursuant to Vaccine Rule 28.1(a) “[i]f the assigned judge remands the case to the special master, the
special master, after completing the remand assignment, must file a decision on remand resolving the
case, unless the remand order directs otherwise.” Pursuant to Vaccine Rule 28.1(b) “[u]nless otherwise
specified in the remand order, the decision on remand constitutes a separate decision for purposes of
Vaccine Rules 11, 18, and 23, i.e., judgment automatically will be entered in conformance with the special
master’s decision on remand unless a new motion for review is filed pursuant to Vaccine Rule 23.”
49
petitioner is entitled to an award as stated in respondent’s October 4, 2021 proffer on
award of damages at ECF No. 82.
Accordingly, I award petitioner a lump sum payment of $137,400.00,
representing $135,000.00 in compensation for pain and suffering and $2,400.00 in
compensation for past unreimbursable expenses, in the form of a check payable
to Petitioner. This amount represents compensation for all damages that would be
available under § 15(a).
In the absence of any motion for review, the clerk of the court is directed to enter
judgment in accordance with this decision. 48 Pursuant to Vaccine Rule 28.1(a), the
clerk of court is directed to notify the assigned judge of the filing of this decision on
remand.
IT IS SO ORDERED.
s/Daniel T. Horner
Daniel T. Horner
Special Master
48Pursuant to Vaccine Rule 11(a), entry of judgment can be expedited by the parties’ joint filing of notice
renouncing the right to seek review.
50