  United States Court of Appeals
      for the Federal Circuit
                ______________________

                          W.C.,
                  Petitioner-Appellant,
                           v.
      SECRETARY OF HEALTH AND HUMAN
                 SERVICES,
             Respondent-Appellee.
                ______________________

                      2012-5058
                ______________________

    Appeal from the United States Court of Federal
Claims in case no. 07-VV-456, Judge Charles F. Lettow.
                 ______________________

              Decided: January 15, 2013
               ______________________

    SYLVIA CHIN-CAPLAN, Conway, Homer & Chin-
Caplan, P.C., of Boston, Massachusetts, argued for peti-
tioner-appellant. Of counsel on the brief was RONALD C.
HOMER.

    DEBRA A. FILTEAU BEGLEY, Trial Attorney, Torts,
Branch, Civil Division, United States Department of
Justice, of Washington, DC, argued for respondent-
appellee. With her on the brief were STUART F. DELERY,
Acting     Assistant    Attorney     General,    RUPA
2                                                W.C.   v. HHS

BHATTACHARYYA, Director, MARK W. ROGERS, Deputy
Director, and VINCENT J. MATANOSKI, Assistant Director.

                 ______________________



Before RADER, Chief Judge, PROST and Reyna, Circuit
Judges.
RADER, Chief Judge.
    The United States Court of Federal Claims affirmed
the special master’s decision denying W.C. (Petitioner)
compensation under the National Childhood Vaccine
Injury Act of 1986, 42 U.S.C. §§ 300aa-1 to -34 (Vaccine
Act). W.C. v. Sec’y of Health & Human Servs. (Trial Court
Decision), 100 Fed. Cl. 440 (2011). Because the special
master’s factual determinations were not arbitrary or
capricious and the decision was in accordance with law,
this court affirms.
                         I.
    Petitioner alleges that an influenza vaccination he re-
ceived at the age of thirty-four resulted in the onset of
multiple sclerosis or significantly aggravated his preexist-
ing, but asymptomatic, multiple sclerosis. Trial Court
Decision, 100 Fed. Cl. at 443. Multiple sclerosis is a
disorder of the central nervous system that causes clinical
symptoms including weakness, loss of coordination,
speech disturbances, and visual complaints. Id. at 443
n.2. The cause of multiple sclerosis is unknown. W.C. v.
Sec’y of Health & Human Servs. (Special Master Deci-
sion), No. 07–456V, 2011 WL 4537877, at *3 (Fed. Cl. Feb.
22, 2011). For many years, researchers have considered
multiple sclerosis to be an autoimmune disease. Id. The
disease may begin with a breach in the blood-brain barri-
er that allows cells from the immune system to cross into
the brain. Id. These immune cells may mistakenly
 W.C.   v. HHS                                          3
attack the myelin sheath that coats nerve cells. Id. This
attack would cause inflammation and subsequent scar-
ring of the brain, called lesions. Id.
    Petitioner suffers from the most common type of mul-
tiple sclerosis, known as relapsing remitting multiple
sclerosis. Id. at *4. Patients with this type of multiple
sclerosis usually have about one relapse of clinical symp-
toms per year. Id. “Much of the disease process is clini-
cally silent,” meaning that a person can have active brain
inflammation and develop new lesions without experienc-
ing relapse (i.e., clinical symptoms). Bruce D. Trapp and
Klaus-Armin Nave, Multiple Sclerosis: An Immune or
Neuodegenerative Disorder?, 31 Annu. Rev. Neurosci. 247,
249 (2008). Brain imaging studies in patients with multi-
ple sclerosis “indicate that inflammatory brain lesions can
outnumber relapses by as much as 10 to 1.” Id. In this
context, the term “clinical symptoms” refers to the out-
wardly-visible symptoms associated with a relapse (e.g.,
numbness and loss of motor function), as distinguished
from clinically-silent brain lesions, which are also a
symptom of multiple sclerosis.
    Medical professionals use magnetic resonance imag-
ing (MRI) to observe lesions in the brain of a patient
diagnosed with or suspected to have multiple sclerosis.
Id. at *6. By administering a contrast agent called gado-
linium before an MRI, medical professionals can locate
active inflammation at the site of a brain lesion. Id. In
active brain inflammation, a breakdown in the blood-
brain barrier permits gadolinium to enter the brain. Id.
When gadolinium enters the brain, active lesions appear
on an MRI as “enhanced.” Id. After inflammation sub-
sides, the body repairs the blood-brain barrier and lesions
no longer appear enhanced. Id. Most new lesions (ap-
proximately 90%) first appear as enhanced on MRI for a
period of time, while older lesions do not enhance. Id.
The trial court dedicated considerable time to considering
4                                                W.C.   v. HHS

the length of time that new lesions appear enhanced on
MRI. See Part III. B. below.
    Petitioner received the influenza vaccine on December
13, 2004. Special Master Decision, 2011 WL 4537877, at
*1. Before then, Petitioner had no clinical symptoms of
multiple sclerosis or other neurological problems. Id. On
December 24, 2004, Petitioner experienced numbness in
his left hand, arm, and the left side of his head and face.
Id. An MRI performed on December 30, 2004 identified
six scattered lesions in Petitioner’s brain, none of which
were enhanced on the gadolinium MRI. Id. at *7. The
interpreting physician noted the “MRI in conjunction with
the patient’s clinical history suggest multiple sclerosis as
a possible etiology.” Id. at *1.
     Petitioner experienced another episode of numbness
and loss of motor function in his left hand and arm in
January 2005. Id. at *2. Petitioner then saw a neurolo-
gist, Dr. John Hannam, who suggested that Petitioner
might have multiple sclerosis. Dr. Hannam noted that “if
[Petitioner] had [multiple sclerosis], I can’t blame it on
the flu shot.” Id. Dr. Hannam recommended a second
opinion from Dr. Rifaat Bashir, who specializes in multi-
ple sclerosis. Id. Dr. Bashir noted that Petitioner’s MRI
“is certainly consistent with a demyelinating disease. He
could have had a single isolated event possibly related to
his vaccination which he did receive two weeks before the
event.” Id. After two additional MRIs, the latter of which
showed a new, enhanced lesion, Dr. Bashir diagnosed
Petitioner with multiple sclerosis. Id. at *3.
    Petitioner filed a claim for compensation under the
Vaccine Act in June 2007, alleging the influenza vaccine
caused his multiple sclerosis or significantly aggravated
his pre-existing, subclinical multiple sclerosis. In support
of his claim, Petitioner presented an expert report and
testimony by Dr. Carlo Tornatore, the director of the
Multiple Sclerosis Center at Georgetown University
 W.C.   v. HHS                                           5
Hospital. Id. at *4. Dr. Tornatore opined that the influ-
enza vaccine caused Petitioner’s multiple sclerosis
through a process called “molecular mimicry.” Id. In this
process, the immune system attacks normal proteins in
the body because they are structurally similar to foreign
substances, such as viral or bacterial peptides. Id. at *11.
Specifically, Dr. Tornatore opined that portions of the
influenza vaccine mimic myelin basic protein, a compo-
nent of the central nervous system that is implicated in
multiple sclerosis. Id. According to Dr. Tornatore’s
theory, the influenza vaccine could trigger production of
immune cells (called T-cells) that are “cross-reactive” with
myelin and therefore attack the person’s own nerve cells.
Id.
    On February 22, 2011, the special master denied Peti-
tioner compensation under the Vaccine Act. Id. at *1.
The special master found Petitioner had multiple sclerosis
before receiving the influenza vaccine and therefore the
vaccine could not have caused Petitioner’s disease. Id.
Further, the special master found Petitioner did not
establish a plausible medical theory that the influenza
vaccine causes significant aggravation of multiple sclero-
sis. Id. The Court of Federal Claims affirmed. Trial
Court Decision, 100 Fed. Cl. at 456. Petitioner appeals,
and this court has jurisdiction under 42 U.S.C. § 300aa-
12(f).
                            II.
    When reviewing decisions under the Vaccine Act, this
court “performs the same task as the Court of Federal
Claims and determines anew whether the special master’s
findings were arbitrary or capricious.” Lampe v. Sec’y of
Health & Human Servs., 219 F.3d 1357, 1360 (Fed. Cir.
2000). This court reviews the special master’s legal
determinations under a “not in accordance with law”
standard. Pafford v. Sec’y of Health & Human Servs., 451
F.3d 1352, 1355 (Fed. Cir. 2006).
6                                                  W.C.   v. HHS

    The Vaccine Act created the National Vaccine Injury
Compensation Program, which allows certain petitioners
to be compensated upon showing, among other things,
that a person “sustained, or had significantly aggravated”
a vaccine-related “illness, disability, injury, or condition.”
42 U.S.C. § 300aa-11(c)(1)(C). The Vaccine Act provides
two avenues to compensation: “table” claims and “off-
table” claims. Althen v. Sec’y of Health & Human Servs.,
418 F.3d 1274, 1278 (Fed. Cir. 2005). In a table claim, the
petitioner benefits from a statutory presumption of causa-
tion upon showing that the injury is listed in the Vaccine
Injury Table for the vaccine received and occurred within
the time period in the table. 42 U.S.C. § 300aa-14(a); see
Althen, 418 F.3d at 1278. If the injury is not listed in the
table, the petitioner must prove actual causation by a
preponderance of the evidence. 42 U.S.C. §§ 300aa-
11(c)(1)(C)(ii), 300aa-13(a)(1); Moberly v. Sec’y of Health &
Human Servs., 592 F.3d 1315, 1321 (Fed. Cir. 2010).
Multiple sclerosis is not on the Vaccine Injury Table. See
42 C.F.R. § 100.3 (2012).
    In this off-table case, the petitioner must show that it
is “more probable than not” that the vaccine caused the
injury. Althen, 418 F.3d at 1279–80. This level of proof
does not require scientific certainty, nor epidemiologic
studies such as might be needed for a theory to achieve
“general acceptance in the scientific or medical communi-
ties.” Andreau v. Sec’y of Health & Human Servs., 569
F.3d 1367, 1378 (Fed. Cir. 2009) (internal quotations
omitted). Indeed, “the purpose of the Vaccine Act’s pre-
ponderance standard is to allow the finding of causation
in a field bereft of complete and direct proof of how vac-
cines affect the human body.” Althen, 418 F.3d at 1280.
    Nonetheless, the petitioner must do more than
demonstrate a “plausible” or “possible” causal link be-
tween the vaccination and the injury; he must prove his
case by a preponderance of the evidence. Moberly, 592
 W.C.   v. HHS                                           7
F.3d at 1322. Specifically, a petitioner seeking to prove
causation in an off-table case must provide: “(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 show-
ing of a proximate temporal relationship between vaccina-
tion and injury.” Althen, 418 F.3d at 1278. “[N]either a
mere showing of a proximate temporal relationship be-
tween vaccination and injury, nor a simplistic elimination
of other potential causes of the injury suffices, without
more, to meet the burden of showing actual causation.”
Id. (citing Grant v. Sec’y of Health & Human Servs., 956
F.2d 1144, 1149 (Fed. Cir. 1992)).
     In this case, Petitioner argues in the alternative that
if the influenza vaccine did not cause his multiple sclero-
sis, then it significantly aggravated his preexisting condi-
tion. This court has not previously addressed the proof
required to establish a prima facie case of significant
aggravation for an off-table claim.
    In Whitecotton v. Sec’y of Health & Human Servs., 81
F.3d 1009, 1107 (Fed. Cir. 1996), this court articulated a
four-prong test to evaluate an on-table significant aggra-
vation claim. Whitecotton requires the special master to
compare the injured person’s condition prior to vaccina-
tion with his or her current condition to determine wheth-
er a significant aggravation occurred, and then determine
whether the first symptom of aggravation occurred within
the time period in the Table. Id. If so, the petitioner
receives the statutory presumption that the vaccine
caused the aggravation.
    Here, Petitioner asserts that the Vaccine Act “does
not make a distinction between on-Table and off-Table
claims of significant aggravation.” Pet’r’s Br. 10–11. He
therefore suggests that under Whitecotton, he need only
show that his condition worsened after administration of
8                                                  W.C.   v. HHS

the vaccine, and that the aggravation occurred within a
medically appropriate time frame. Id.
     This argument runs counter to the language of the
statute. The statute distinguishes table claims from off-
table claims for both initial onset and significant aggrava-
tion cases. See 42 U.S.C. § 300aa-11(c)(1)(C)(i) (table
claims) and § 300aa-11(c)(1)(C)(ii) (off-table claims). For
off-table claims that an injury was either “sustained, or [ ]
significantly aggravated,” a petitioner must show the
vaccine “caused” the injury or aggravation. § 300aa-
11(c)(1)(C)(ii). As this court previously observed in the
context of on-table claims, “[t]he statutory requirements
to make out a prima facie significant aggravation claim
are analogous to those required to make out a prima facie
initial onset claim.” Whitecotton, 81 F.3d at 1103. Thus,
a petitioner in an off-table case must show the vaccine
actually caused the significant aggravation—not just that,
accepting petitioner’s medical theory as sound, the per-
son’s condition worsened within a medically-acceptable
time frame.
    In Loving v. Sec’y of Health & Human Servs., 86 Fed.
Cl. 135, 144 (2009), the Court of Federal Claims articulat-
ed a six-factor test for proof of off-table significant aggra-
vation claims. The Loving test combines the first three
Whitecotton factors, which establish significant aggrava-
tion, with the Althen factors, which establish causation.
We hold that the Loving case provides the correct frame-
work for evaluating off-table significant aggravation
claims. A petitioner must prove by preponderant evi-
dence that the vaccination caused significant aggravation
by showing:
       (1) the person’s condition prior to admin-
      istration of the vaccine, (2) the person's cur-
      rent condition (or the condition following the
      vaccination if that is also pertinent), (3)
      whether the person’s current condition con-
 W.C.   v. HHS                                            9
        stitutes a “significant aggravation” of the
        person's condition prior to vaccination, (4) a
        medical theory causally connecting such a
        significantly worsened condition to the vac-
        cination, (5) a logical sequence of cause and
        effect showing that the vaccination was the
        reason for the significant aggravation, and
        (6) . . . a proximate temporal relationship be-
        tween the vaccination and the significant ag-
        gravation.
Id. at 144.
                             III.
                              A.
    In analyzing Petitioner’s claim that the influenza vac-
cine caused his multiple sclerosis, the special master
identified a “preliminary question” of whether Petitioner
had subclinical multiple sclerosis before the vaccination.
Special Master Decision, 2011 WL 4537877, at *5. Be-
cause the special master found it was more likely than not
that Petitioner had multiple sclerosis before receiving the
vaccine, he recognized the vaccine could not have caused
the disease. Id. at *5–8. The special master therefore
denied compensation without applying the three-factor
causation test set forth in Althen. Id. at *8; cf. Althen,
418 F.3d at 1278.
    The special master cited Broekelschen v. Secretary of
Health & Human Services, 618 F.3d 1339 (Fed. Cir. 2010)
as support for resolving a preliminary issue before con-
ducting an Althen analysis. In Broekelschen, this court
held the special master did not err by preliminarily de-
termining which of two possible diagnoses was correct
before determining whether the vaccine caused the condi-
tion. Id. at 1350. Unlike in Broekelschen, the parties in
this case agree on Petitioner’s diagnosis. Because the
issue is whether the vaccine caused Petitioner’s multiple
10                                                 W.C.   v. HHS

sclerosis, the special master should have expressly ap-
plied the analysis set forth in Althen.
    While this court disagrees with the special master’s
suggestion that Althen could be bypassed in this case, the
Court of Federal Claims correctly determined the error
was harmless. See Trial Court Decision, 100 Fed. Cl. at
451. The special master’s finding that Petitioner had
multiple sclerosis before receiving the vaccine means that
Petitioner did not establish a “logical sequence of cause
and effect showing that the vaccination was the reason for
[his] injury” as required by prong two of Althen. 418 F.3d
at 1278. If a petitioner has a disorder before being vac-
cinated, the vaccine logically cannot have caused the
disorder.
     Additionally, prong three of Althen requires a “medi-
cally-acceptable temporal relationship” between vaccina-
tion and onset of symptoms. Id. at 1281; De Bazaan v.
Sec’y of Health & Human Servs., 539 F.3d 1347, 1353
(Fed. Cir. 2008) (holding a petitioner’s causation claim
may fail because disease onset occurs “too early to be
attributable to the vaccine”). In this case, Petitioner’s
first episode of numbness occurred eleven days after the
vaccination—a time period which the government’s expert
agreed would be consistent with Petitioner’s medical
theory that the influenza vaccine triggered an immune-
mediated disorder. However, the special master found
Petitioner’s first symptom of multiple sclerosis—telltale
lesions in the brain—appeared before the vaccination.
Special Master Decision, 2011 WL 4537877, at *8. This
finding implies that the disease onset did not occur “with-
in a time frame for which . . . it is medically acceptable to
infer causation-in-fact,” such that Petitioner’s claim did
not meet Althen prong three. De Bazaan, 539 F.3d at
1352.
    Because a petitioner must establish “all three prongs
of the Althen test,” id., it was not necessary for the special
 W.C.   v. HHS                                          11
master to evaluate whether Petitioner established a
medical theory as required by Althen prong one. The lack
of a logical sequence of cause and effect, and the lack of a
“medically-acceptable temporal relationship” between the
vaccination and disease onset, prevented Petitioner from
establishing his claim. In sum, the special master’s
finding that Petitioner had multiple sclerosis before he
was vaccinated necessarily implies that Petitioner could
not demonstrate causation under Althen.
                            B.
    The special master’s underlying factual findings that
Petitioner had multiple sclerosis before receiving the
influenza vaccine were not arbitrary or capricious. The
special master carefully evaluated the clinical record,
expert testimony, and medical literature in finding it is
“more probable than not that at least some, if not all, of
the six lesions detected on [Petitioner’s] December 30,
2004 MRI existed before the December 13, 2004 flu vac-
cination.” Special Master Decision, 2011 WL 4537877, at
*8.
    The parties dispute the implications of the December
30, 2004 MRI that the trial court used to gauge when
Petitioner developed multiple sclerosis. See id. at *6. The
December 30, 2004 MRI showed six lesions in Petitioner’s
brain, none of which were enhanced by gadolinium. Id. at
*7. The government’s expert, Dr. Arun Venkatesan, an
assistant professor in the Department of Neurology at
John Hopkins University, testified that “if the vaccination
caused the lesions, at least one of them should have been
enhanced when the MRI was done 17 days after vaccina-
tion.” Id. Petitioner’s expert, Dr. Tornatore, responded
that the December 30, 2004 MRI was “not useful in de-
termining whether the lesions were present before the
vaccination.” Id. at *6.
12                                              W.C.   v. HHS

    Dr. Venkatesan supported his opinion with a pub-
lished article studying the duration of gadolinium en-
hancement of lesions identified in weekly MRIs performed
on multiple sclerosis patients. Francois Cotton et al.,
MRI Contrast Uptake in New Lesions in Relapsing-
Remitting MS followed at Weekly Intervals, 60 Neurology
640–646 (2003) (Cotton Study). The Cotton Study deter-
mined the average duration of enhancement was “3.07
weeks,” while the median duration was “2 weeks.” Id. at
642. Importantly, because MRIs were performed only
once per week, a lesion that appeared enhancing for “1
week” may have been enhancing for anywhere from one to
thirteen days. Id. at 641. For example, a lesion that
appeared enhanced on only the second weekly scan could
have appeared the day after the first weekly scan and
enhanced until the day before the third weekly scan (13
days), or it could have enhanced only on the day of the
MRI in which it appeared (1 day). Similarly, a “2 week”
enhancement means the lesion was enhancing for 8–20
days, and “3 weeks” means the lesion appeared enhanced
for 15–27 days. See Special Master Decision, 2011 WL
4537877, at *7. The Cotton Study’s finding that the
median enhancement was “two weeks” indicates that one-
half of the observed lesions lasted “two weeks” (i.e., 8–20
days) or less, while one-half lasted “two weeks” or more.
Id.
    Dr. Venkatesan explained that, under the medical
theory proposed by Dr. Tornatore, lesions “would take at
least a few days and potentially even a week or two” after
the vaccination to develop. Id. (quoting Hearing Tr. 302).
Thus, if Petitioner’s vaccination on December 13, 2004
had caused him to develop multiple sclerosis, lesions
could have developed as early as December 16, 2004 or as
late as December 27, 2004. Id. Adding the median dura-
tion of enhancement from the Cotton Study of 8–20 days,
a lesion that developed on the earliest possible date
 W.C.   v. HHS                                          13
(December 16, 2004) would have appeared enhanced on
MRI until between December 24, 2004 and January 5,
2005. Alternatively, adding the average enhancement
duration of 15–27 days, the earliest possible lesion would
have enhanced until at least December 31, 2004.
     The special master acknowledged that the “timeline
can be compressed” so that a lesion could have developed
and become non-enhancing within the seventeen day
window between Petitioner’s vaccination and his MRI. Id.
at *8. Nonetheless, he found it improbable that all six
lesions identified in Petitioner’s December 30, 2004 MRI
would have developed and become non-enhancing in less
than the average amount of time reported by the Cotton
Study. Id. The Cotton Study supports the trial court’s
finding because “[d]ifferent lesions in a same patient
appeared to develop largely independent of each other and
demonstrated large variation in the duration of enhance-
ment . . .” Cotton Study, supra, at 640. In other words,
the Cotton Study indicates it is unlikely that Petitioner
regularly exhibits lesions with a short duration of en-
hancement.
    Ultimately, it is Petitioner’s burden to prove causa-
tion by preponderant evidence.         42 U.S.C. § 300aa-
13(a)(1)(A); Althen, 418 F.3d at 1278. The special master
carefully considered the evidence in the record, drew
plausible inferences, and articulated a rational basis for
his determination that, more likely than not, Petitioner’s
lesions existed before he received the influenza vaccina-
tion on December 13, 2004. Special Master Decision, 2011
WL 4537877, at *8; see Lampe, 219 F.3d at 1360 (discuss-
ing arbitrary and capricious standard of review). This
court does not find the special master’s determination
arbitrary or capricious. Consequently, because Petitioner
did not show a logical sequence of cause and effect or a
medically-acceptable time period between the vaccination
and disease onset, this court affirms the denial of benefits
14                                              W.C.   v. HHS

on Petitioner’s claim that the influenza vaccine caused his
multiple sclerosis.
                           IV.
    Petitioner claims that, if he had preexisting multiple
sclerosis when he received the influenza vaccine, the
vaccination significantly aggravated his condition. The
special master applied the correct law in evaluating this
claim under Loving. 86 Fed. Cl. at 144. The special
master found dispositive the fourth item of the Loving
test, which requires petitioner to present a medical theory
connecting his significantly worsened condition to the
vaccination. Special Master Decision, 2011 WL 4537877,
at *9.
    As noted above, Petitioner’s medical theory is that,
through the process of molecular mimicry, the influenza
vaccine triggered an immune response which released T-
cells that were cross-reactive with myelin. Trial Court
Decision, 100 Fed. Cl. at 454. Some of those T-cells
crossed into Petitioner’s brain, where they attacked the
myelin coating on his nerve cells. This induced an im-
mune cascade resulting in inflammation, demyelination,
and nerve damage characteristic of multiple sclerosis.
    The government’s expert, Dr. Venkatesan, agreed that
molecular mimicry is accepted as playing a role in the
autoimmune disease Sydenham’s chorea. Id. Medical
science generally accepts that Sydenham’s chorea devel-
ops as a result of immune response cross-reactivity follow-
ing infection with streptococcus bacteria. Id. The special
master found that “[m]olecular mimicry is a well-regarded
theory in some contexts,” Special Master Decision, 2011
WL 4537877, at *11, but correctly required additional
evidence showing that molecular mimicry can cause the
influenza vaccine to significantly aggravate multiple
sclerosis, see Broekelschen, 617 F.3d at 1345 (holding “a
petitioner must provide a reputable medical or scientific
 W.C.   v. HHS                                         15
explanation that pertains specifically to the petitioner’s
case”).
    In support of his theory that molecular mimicry be-
tween the influenza virus and myelin caused Petitioner’s
multiple sclerosis, Dr. Tornatore relied primarily on an
article by Wucherpfennig and Strominger at Harvard
University’s Department of Molecular and Cellular Biolo-
gy. Kai Wucherpfennig & Jack L. Strominger, Molecular
Mimicry in T Cell-Mediated Autoimmunity: Viral Peptides
Activate Human T Cell Clones Specific for Myelin Basic
Protein, 80 Cell 695 (1995). The Wucherpfennig article
showed that human myelin basic protein-specific T-cell
clones derived from the blood of multiple sclerosis pa-
tients were “cross-reactive” with one peptide from a wild
influenza Type A strain. Id. at 697. Dr. Tornatore testi-
fied that this evidence, demonstrating that influenza
proteins can stimulate T-cells specific to myelin basic
protein, makes it “beyond plausible” that the influenza
vaccine could stimulate the immune response that led
Petitioner to develop multiple sclerosis. J.A. 170.
    The special master noted, however, that the Wu-
cherpfennig article showed three other peptides derived
from the wild influenza virus were not cross reactive with
the myelin basic protein-specific T-cells. Wucherpfennig
& Strominger, supra, at 698 (Table 1); Special Master
Decision, 2011 WL 4537877, at *12. In other words, only
certain portions of the influenza virus generated a cross-
reactive immune response.
    Petitioner provided no evidence that the portions of
the influenza virus shown by Wucherpfennig to mimic
myelin basic protein were present in the influenza vaccine
Petitioner received. Special Master Decision, 2011 WL
4537877, at *12. Petitioner also did not provide evidence
that any peptide from the influenza vaccine he received
was cross-reactive with myelin basic protein-specific T-
cells. Id. The special master reasonably considered the
16                                               W.C.   v. HHS

lack of evidence connecting the cross-reactivity observed
by Wucherpfennig to the facts of Petitioner’s case to weigh
“against finding that Dr. Tornatore’s opinion is persua-
sive.” Id.; see Moberly, 592 F.3d at 1324 (holding special
master did not err in rejecting a theory of causation where
“there was no evidence in the record suggesting that the
proposed mechanism was at work in [the petitioner’s]
case”).
     Moreover, the special master credited several pub-
lished studies of multiple sclerosis patients who received
the influenza vaccine showed no aggravation of symptoms
following vaccination. Special Master Decision, 2011 WL
4537877, at *14–15. The Confavreaux study, involving
643 patients with multiple sclerosis, found that “common-
ly administered vaccinations (specifically, against teta-
nus, hepatitis B and influenza) do not increase the risk of
relapse in patients with multiple sclerosis.” Christian
Confavreaux et al., Vaccinations and the Risk of Relapse
in Multiple Sclerosis, 344 New England J. of Med. 319
(2001). Confavreaux found the “odds ratio” of a relapse in
the two months following the flu shot was 1.08, meaning
there was a slightly higher rate of relapse in patients who
had the vaccine, but the difference was not statistically
significant. Id. at 324.
    Similarly, the Miller article reported a randomized,
double-blind trial of influenza immunization in 104 mul-
tiple sclerosis patients. A.E. Miller et al., A Multicenter,
Randomized, Double-Blind, Placebo-Controlled Trial of
Influenza Immunization in Multiple Sclerosis, 48 Neurol-
ogy 312 (1997). The patients were divided into two
groups, one of which received the influenza vaccine while
the other received placebo. The patients were monitored
for relapses in the six months following vaccination. The
authors found “[i]nfluenza immunization in [multiple
sclerosis] patients is neither associated with an increased
exacerbation rate in the post-vaccination period nor a
 W.C.   v. HHS                                          17
change in disease course over the subsequent 6 months.”
Id. at 312. Petitioner emphasizes that the vaccinated
group had nearly twice as many patients experience
relapse during the six months following vaccine admin-
istration than the placebo group (eleven vs. six). This
difference was not statistically significant. Id. at 313.
Moreover, the authors noted that the average time be-
tween vaccination and relapse was higher in the vaccine
group than the placebo group, indicating the difference in
relapse rate between the two groups was due to random
variation rather than a causal connection to the vaccine.
Id.
    The special master evaluated all of the evidence of
record, and found that the large studies of multiple scle-
rosis patients “reinforce Dr. Venkatesan’s opinion that the
theory offered by Dr. Tornatore is ‘extremely unlikely.’”
Special Master Decision, 2011 WL 4537877, at *15 (quot-
ing Tr. 149–50). The special master correctly applied the
law in requiring Petitioner to demonstrate by preponder-
ant evidence that the influenza vaccine caused significant
aggravation of Petitioner’s multiple sclerosis. This court
cannot say that the special master’s evaluation of the
expert testimony or weighing of the scientific evidence
was arbitrary or capricious.
                            V.
     Therefore, for the reasons discussed above, this court
affirms the judgment of the Court of Federal Claims
upholding the special master’s decision denying Petitioner
compensation under the Vaccine Act.
                      AFFIRMED
