Zuzow v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 14-920V

(to be published)

************************* Special Master Corcoran

*

L.Z., *

* Filed: August 24, 2018

Petitioner, *

* Decision; Denial of Entitlement;

v. * Multiple Sclerosis (“MS”); Influenza

* (“flu”) Vaccine; Significant

SECRETARY OF HEALTH AND * Aggravation.

HUMAN SERVICES, *

*

Respondent. *

*

*************************

Ronald Craig Homer, Conway, Homer, P.C., Boston, MA, for Petitioner.

Adriana R. Teitel, U.S. Dep’t of Justice, Washington, DC, for Respondent.

DECISION DENYING ENTITLEMENT1

On September 29, 2014, L.Z. filed a Petition under the National Vaccine Injury

Compensation Program (the “Vaccine Program”2), alleging that the influenza (“flu”) vaccine she

received on October 16, 2011, caused her to suffer an unspecified “neurological demyelinating

injury.” Pet. at 1, ECF No. 1. She later amended her claim, alleging that the flu vaccine either

caused transverse myelitis (“TM”), optic neuritis (“ON”), and/or multiple sclerosis (“MS”), or

1

This Decision will be posted on the United States Court of Federal Claims’ website in accordance with the E-

Government Act of 2002, 44 U.S.C. § 3501 (2012). This means the Decision will be available to anyone with access

to the internet. As provided by 42 U.S.C. § 300aa-12(d)(4)(B), however, the parties may object to the published

Decision’s inclusion of certain kinds of confidential information. Specifically, under Vaccine Rule 18(b), each party

has fourteen (14) days within which to request redaction “of any information furnished by that party: (1) that is a trade

secret or commercial or financial in substance and is privileged or confidential; or (2) that includes medical files or

similar files, the disclosure of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b).

Otherwise, the entire Decision will be available in its current form. Id.

2

The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660,

100 Stat. 3755 (codified as amended at 42 U.S.C. §§ 300aa-10–34 (2012)) (hereinafter “Vaccine Act” or “the Act”).

All subsequent references to sections of the Vaccine Act shall be to the pertinent subparagraph of 42 U.S.C. § 300aa.

significantly aggravated an underlying neurologic condition. Am. Pet. at 2, Nov. 5, 2015, ECF No.

26.

A hearing in this matter was held on November 13, 2017. After consideration of the record

and testimony provided at hearing, I find that Petitioner is not entitled to a compensation award.

The record best supports the conclusion that Petitioner suffered from MS predating her

vaccination, leaving only the claim that the flu vaccine significantly aggravated that illness. But

Petitioner has not established a plausible causation theory that the flu vaccine could cause an MS

relapse/exacerbation, nor has she offered sufficient preponderant evidence that in her specific case

the flu vaccine was the cause of any subsequent symptoms she experienced or that it likely

worsened her overall expected course.

I. Factual Background

Pre-Vaccination History

L.Z.’s pre-vaccination history strongly suggests that she was already experiencing some

kind of neurologic injury at the time she received the flu vaccine in 2011.

For example, on March 5, 2009—over two years prior to the vaccination at issue—

Petitioner was seen at the Nicklas Chiropractic practice in Paso Robles, California, for a visual

change involving her right eye that she said had begun the previous day. Ex. 4 at 1–3. A week

later, on March 11, 2009, she reported persistent visual change affecting distance vision, as well

as neck pain. Id. at 5–6. The following year, on September 22, 2010, she returned to Nicklas

Chiropractic with complaints of left-sided neck stiffness of one-week duration. Id. at 12. Two days

later, on September 24, 2010, L.Z. underwent a new patient visit with Klyda White, D.O. Ex. 25

at 1. At this time, she complained of bilateral hearing loss, tinnitus, and pain for several days. Id.

Medical history was positive for neck and back pain, although she was treated only for cerumen

impaction. Id.

A few months later, in late December 2010, L.Z. returned to Nicklas Chiropractic

complaining of tingling at the tip of her right thumb which she reported had been ongoing for the

past month. Ex. 4 at 14. She sought additional treatment at Nicklas Chiropractic on January 21,

2011, stating that she had awoken with a stiff neck (which she attributed to lifting a heavy item

after moving the prior weekend). Id. at 15. She also reported having a resolving headache and

numbness of her left thumb pad. Id.

The following summer, Petitioner saw her primary care physician, Dr. Donella Jenkins, on

August 27, 2011, complaining of right eye redness, photophobia, and decreased vision for one

2

week. Ex. 18 at 1. Her conjunctiva appeared inflamed and a pterygium3 was noted laterally. Id.

Dr. Jenkins’s impression was that Petitioner had conjunctivitis, and antibiotic eye drops were

prescribed. Id. Approximately a month later, on September 28, 2011, L.Z. returned to Nicklas

Chiropractic, and was again treated with manual therapy and traction for recurrent neck pain and

stiffness. Ex. 4 at 18.

Receipt of Flu Vaccine and Purported Reaction

On October 16, 2011, L.Z. received a flu vaccine in her left deltoid. Ex. 1 at 1–2; Ex. 24 at

3. There is no contemporary record evidence suggesting she experienced any immediate reaction

to the vaccination. However, a little over three weeks later, on November 7, 2011, Petitioner was

examined by Rex Stevens, D.C. (a chiropractor), at SLO Wellness Center in San Luis Obispo,

California, after complaining of chronic lower back pain and random pain mid-back and in her

neck. Ex. 17 at 1. She specifically described having experienced bilateral lower extremity

numbness with associated weakness, plus right foot tingling and the feeling that her left leg would

give out after prolonged standing and walking, reporting that all of the above had lasted a week

since receipt of the flu vaccine. Id. L.Z. also provided written statements in this case alleging that

she began experiencing adverse symptoms approximately two weeks post-vaccination. See Aff.

filed as Ex. 29 at 3, Mar. 31, 2015, ECF No. 17-1.

Dr. Stevens’s exam of Petitioner revealed positive straight leg raising on the right with

inability to walk on right heel, 2/5 strength for dorsiflexion, decreased sensation to pinprick along

L4-5 and L5-S1 dermatomes, and reduced range of motion of lumbar spine. Ex. 17 at 1–2. Based

upon the history Petitioner provided (which included her pre-vaccination experiences), Dr. Stevens

noted in the medical history portion of the relevant record that “[p]ast MD suggests patient may

have MS.” Id.

The following week, L.Z. went to see Dr. Jenkins on November 12, 2011, complaining of

symptoms comparable to what she had described to Dr. Stevens (e.g., right foot numbness, left

foot dragging, and loss of coordination). Ex. 18 at 2. As the visit notes indicate, Petitioner reported

at this time that ten years earlier she had experienced vertigo and vision problems, and that in the

past she had thrown her back out, suffered urinary incontinence, and had fallen at work resulting

in hand numbness. Id. She also informed Dr. Jenkins that her current symptoms worsened the

longer she was on her feet, but improved with sitting. Id. An examination revealed ankle weakness,

and based upon Dr. Jenkin’s recommendation, L.Z. was referred for a magnetic resonance imaging

(“MRI”) and consultation with a neurologist, Dr. Mary Amir. Id.

3

A pterygium is an abnormal triangular fold of membrane in the interpalpebral fissure of the eye that extends from

the conjunctiva to the cornea. Dorland’s Illustrated Medical Dictionary 1551 (32nd ed. 2012) (hereinafter

“Dorland’s”).

3

Petitioner’s Neurology Work-up

L.Z. was examined by Dr. Amir on November 14, 2011. Ex. 16 at 33. Petitioner reported

to Dr. Amir the same general history that she had provided treaters over the prior week, suggesting

again that her numbness and leg movement problems began in October. Id. However, she also

informed Dr. Amir of symptoms predating vaccination. For example, she reported that five weeks

before (or immediately prior to her receipt of the flu vaccine), she had experienced the sensation

of having a “ball” in the center of her right foot that was accompanied by numbness. Id. She also

indicated that the frequency and intensity of her recent urinary incontinence had increased over

the past three weeks, although it had begun after her children were born. And she complained of

exercise intolerance, as well as back and neck sensations that Dr. Amir identified as Lhermitte’s

sign.4 Id. at 34.

Dr. Amir’s exam of L.Z. revealed a normal gait, mild weakness in her right hamstring,

mildly increased muscle tone in her left lower extremity, abnormal bilateral Babinski5 signs, and

a bilateral upper extremity tremor (although worse on the left side). Ex. 16 at 34. Based upon the

above, Dr. Amir assessed Petitioner’s symptoms as evidencing MS. Id. She recommended a Solu-

Medrol infusion,6 requested an ophthalmology evaluation, and advised Petitioner to undergo a

lumbar puncture. Id.

At the same time as her visit to Dr. Amir, Petitioner also had several MRIs performed. The

brain MRI revealed white matter changes in her brainstem consistent with MS. Ex. 10 at 1. The

treating radiologist did not test for lesion enhancement, however.7 The lumbar spine MRI showed

a disc protrusion at L5-S1 that impinged on the right S1 nerve root. Id. at 2. Petitioner’s thoracic

and cervical spine MRIs showed scattered areas of T2 hyperintensity, most consistent with MS.

Id. at 3–4.

4

Lhermitte’s sign refers to “electriclike shocks spreading down the body” occurring when a patient “flexes the head

forward.” Dorland’s at 1713. It is seen mainly in MS. Id.

5

Babinksi reflexes or signs are produced by stimulation of the sole of the foot; in adults, the upward flexing of the big

toe can be a sign of neurologic dysfunction. Dorland’s at 1611.

6

A Solu-Mendrol infusion (or “methylprednisolone injection”) is a corticoid steroid used to treat MS flares. See

Methylprednisolone (Injection Route), Mayo Clinic (Mar. 1, 2017), https://www mayoclinic.org/drugs-

supplements/methylprednisolone-injection-route/description/drg-20075216 (last accessed on July 25, 2018).

7

Lesion enhancement on MRI occurs after the uptake in the lesion of a gadolinium-based contrast agent injected into

a subject’s blood. See W.C. v. Sec’y of Health & Human Servs., 100 Fed. Cl. 440, 444 (2011). Enhancement reveals a

breakdown of the blood-brain barrier (since the contrast agent is able to go into the brain). Id. Such a breakdown can

trigger neurological injury, by allowing infectious or inflammatory agents into the brain and central nervous system,

causing damage. Id. In an MS patient, enhancement typically reveals the presence of new lesions (as opposed to old

lesions which are considered “non-enhancing”). See Taylor v. Sec’y of Health & Human Servs., No. 13-700V, 2018

WL 2050857, at * 21 & n. 4 (Fed. Cl. Spec. Mstr. Mar. 9, 2018). MRI Enhancement can assist treaters in distinguishing

between MS and other neurological diseases such as acute disseminated encephalomyelitis (“ADEM”).

4

The following month, L.Z. was evaluated by an ophthalmologist, Dr. Ahmad Amir,8 on

December 6, 2011, for “possible MS, visual disturbance [right eye].” Ex. 12 at 6. At this time,

Petitioner recalled an episode of visual disturbance two weeks earlier that she associated with

numbness and an inability to pick up her right foot, although she also repeated earlier statements

that most of her symptoms had begun six to eight weeks before (which would be around the same

time as, or prior to, her flu vaccine receipt). Id. Dr. Amir’s exam revealed mild pallor of the optic

disc, mild color distortion, and a large afferent pupillary defect involving the right eye. Id. Dr.

Amir’s impression was that Petitioner suffered from ON, and he discussed initiating oral steroids

but proposed deferring treatment decisions to a neurologist. Id.

Based on the above exams, diagnostic testing, and the MRIs, Dr. Mary Amir prepared a

letter to Petitioner’s primary care provider, Dr. Jenkins, on December 8, 2011. Ex. 2 at 2. In it, Dr.

Amir opined that L.Z. suffered from relapsing/remitting multiple sclerosis. Id. at 1. The letter also

noted a concern for an elevated Lyme’s disease titer. Id. According to Dr. Amir, L.Z. was

counseled with respect to the MS diagnosis and encouraged to keep records to track her symptoms,

and to begin adhering to a strict medical regiment. The letter did not propose any date of onset of

L.Z.’s symptoms, however, nor did it mention the flu vaccine. See id. By 2012, Petitioner

demonstrated overall improvement, although she continued to experience some numbness and

other sequelae that suggested ongoing neurologic deficits. Ex. 12 at 1; Ex. 17 at 11.

Subsequent Treatment for MS and Related Symptoms

In the ensuing years since being diagnosed with MS, L.Z. has continued to receive

treatment for her condition. She visited an orthopedic surgeon, Dr. James Carr, in 2013, in the

hope of confirming whether certain symptoms she continued to experience were connected to her

prior MS diagnosis or instead reflected separate back and spine issues. Ex. 5 at 1; Aff. filed as Ex.

29 at 6 (confirming visit). At this time, she informed Dr. Carr of the various neurologic symptoms

she had experienced in the past (i.e., gait abnormalities, incontinence, numbness in the right leg,

bilateral lower extremity weakness, and sexual dysfunction). Ex. 5 at 1. Dr. Carr’s physical

examination revealed normal results, however. Id. at 2–3. He referred L.Z. for additional brain and

cervical spine MRIs (which were reviewed by Dr. Nelson Yamagata, a neurologist, the following

April 2014) and prescribed six weeks of physical therapy for mild disc herniation. Id. at 4, 12.

Approximately a year later, on March 3, 2014, L.Z. had a follow-up appointment with Dr.

Carr, at which time she stated that she had not experienced any “bad” episodes of weakness for

about two and one-half years. Ex. 5 at 5. Dr. Carr assessed her with lower back pain, lumbar

degenerative disc disease, herniated disc, and radiculopathy, and proposed no surgical

8

Petitioner’s neurologist, Dr. Mary Amir referred her to Dr. Ahmad Amir for an eye exam. See Ex. 12 at 2. Treatment

notes do not indicate if the two Dr. Amirs were related.

5

intervention, but also referred her to a neurologist, Dr. Yamagata, for further evaluation. Id. at 8,

11.

Petitioner saw Dr. Yamagata on April 16, 2014. Ex. 7 at 3–5. She described her prior

history with neurologic problems, noting that although over time the weakness in her feet had

improved, she still felt that she had not returned to her baseline level, and stated that she continued

to experience exercise intolerance and a sense of bladder urgency. Id. at 3. Dr. Yamagata’s initial

assessment was that L.Z. had likely not experienced “further exacerbations since her initial spells

[of TM and ON],” but proposed a follow-up MRI to assess where she was from a neurological

standpoint. Id. at 4.

Petitioner’s May 2, 2014 MRI revealed new, non-enhancing foci of high signal in the

bilateral frontal gyri, but no lesions in the brainstem compared to her November 2011 study. Ex.

5 at 16; Ex. 7 at 6. Around this time, L.Z. also experienced “sudden increased weakness and

stiffness in her legs and difficulty walking.” Ex. 5 at 16. Dr. Yamagata concluded that petitioner

had “probable transverse myelitis with an episode of visual change in the past,” though “the cause

for her initial symptoms [was] not clear.” Id. MS, neuromyelitis optica, and Lyme disease were

included in the differential diagnosis. Id. A second opinion obtained from an infectious disease

specialist was consistent with Dr. Yamagata’s assessment. Ex. 9 at 3.

Since the spring of 2014, L.Z. has continued to monitor her MS with treatment and

additional imaging studies. She has experienced what may be additional MS-related episodes that

have been responsive to proper treatment. See, e.g., Ex. 23 at 1–2; Ex. 27 at 3; Ex. 35 at 21, 33;

Ex. 38 at 1, 3. MRI studies performed in March 2016 and May 2017 revealed further radiologic

evidence of lesions and white matter damage that confirms the accuracy of her 2011 initial MS

diagnosis. See, e.g., Ex. 35 at 5; Ex. 36 at 1; Ex. 39.

II. Expert Opinions

A. Dr. Salvatore Napoli

Dr. Napoli authored two reports and testified at the entitlement hearing on Petitioner’s

behalf. See Expert Report filed as Ex. 31, Oct. 15, 2015, ECF No. 25 (“First Napoli Rep.”); Expert

Report filed as Ex. 33, July 15, 2016, ECF No. 32 (“Second Napoli Rep.”). Dr. Napoli opined that

L.Z. suffers from a relapsing/remitting form of MS that was subclinical at the time of vaccination

but exacerbated by the flu vaccine. Tr. at 39, 69.

Dr. Napoli obtained his medical degree from Albany Medical College in Albany, New

York, where he also completed his residency in neurology. See CV filed as Ex. 32, Oct. 8, 2015,

ECF No. 24-2 (“Napoli CV”). After medical school, Dr. Napoli went on to complete two

6

fellowships, one in EMG/neurophysiology/spasticity training at Tufts University St. Elizabeth’s

Hospital, and one in MS at Harvard Medical School. Tr. at 5; Napoli CV at 2. Following his clinical

fellowship years, he served as an associate neurologist at Brigham and Women’s Hospital Partners

Multiple Sclerosis Center in Boston. Napoli CV at 2. Thereafter, he served as the Medical Director

for the Steward Spasticity Service Center at Steward Foxboro and Norwood Hospital in

Massachusetts. Id. He then joined the Neuro Institute of New England’s Multiple Sclerosis Center,

where he presently serves as the President and Medical Director. Tr. at 6; Napoli CV at 2. He also

continues to serve as the Medical Director for the Steward Multiple Sclerosis Institute at Steward

Foxboro and Norwood Hospital. Napoli CV at 2.

Dr. Napoli has ample clinical expertise treating neurologic illnesses like MS—and in

particular deep knowledge on the use of imaging technologies and interpretation of their results.

Tr. at 5–6, 29. He estimated that he has treated or overseen 1,500 patients with MS (or similar

diseases) during his tenure. Tr. at 6. Dr. Napoli acknowledged, however, that he has far less

experience with research. Id. at 30. He has also had little exposure to immunologic matters beyond

a fellowship in which he participated from 2003–05. Id. at 5; Napoli CV at 2. Dr. Napoli has

published two professional articles and one case study. Napoli CV at 6.

Dr. Napoli’s opinion relied on his reading of Petitioner’s medical history. He noted that

indicia of pre-vaccination symptoms from the medical records were somewhat vague (making it

difficult for him to be certain that her MS predated receipt of the flu vaccine), and that it was

indisputable that L.Z. was “functioning” in an overall healthy manner before vaccination. Tr. at 9,

12, 18, 19, 39. Dr. Napoli nevertheless acknowledged that Petitioner’s illness likely existed (albeit

in an arguably subclinical form) prior to receiving the flu vaccine. E.g., id. at 19 (“she had it to

begin with”), 42 (“I think she definitely had some kind of subclinical stuff going on to begin with”),

44, 67. In particular, he agreed that Petitioner’s pre-vaccination bilateral thumb numbness, along

with her previously-reported bladder problems, could constitute initial presenting symptoms of

MS. Id. at 39–40.9

Dr. Napoli next identified record evidence of MS-related symptoms after vaccination that

he deemed significant under Petitioner’s causation theory. He characterized her post-vaccination

course of symptoms as “fulminant,”10 beginning with myelitis/spinal cord myelopathy and

followed by ON. Tr. at 9, 18, 28. Her initial fall 2011 MRI revealed a thoracic lesion that he opined

likely would have shown enhancement had contrast been employed in the imaging process. Tr. at

11, 66–67. She also displayed bilateral, lower-extremity weakness—a symptom distinguishable

from what Petitioner had previously experienced before vaccination. Id. at 68. And Dr. Napoli

9

Dr. Napoli did not, however, deem the evidence of a possible pre-vaccination ophthalmologic problem as a likely

pre-vaccination MS symptom, arguing that it did not appear to have had a neurologic origin. Id. at 42–43, 59, 60–61.

10

Dr. Napoli defined fulminant to mean “severe and quick or sudden.” Tr. at 144.

7

characterized her ON diagnosis in December 2011 as an unusual occurrence that suggested a

susceptibility to autoimmune injury or an environmental cause underlying all of her post-

vaccination symptoms. Id. at 15–17.

Based upon the above, Dr. Napoli opined that L.Z. “took a hit” after receipt of the flu

vaccine, causing “disability” and “residual issues downstream,” confirming that she was suffering

from MS11 (whether or not her illness predated vaccination). Tr. at 10, 19, 20. To explain

biologically how this occurred, he proposed molecular mimicry between components of the flu

vaccine12 and self protein sequences resulting in autoimmune cross-reactivity, whereby the

immune system would mistakenly attack self structures, confusing them with presenting antigens

in the vaccine. First Napoli Rep. at 5. He noted that this mechanism had been confirmed as reliable

by literature discussing animal models and the wild flu virus (although not the vaccine). Tr. at 22–

23, 25, 48–49, 61–62; First Napoli Rep. at 5; Second Napoli Rep. at 4. He admitted that most flu

virus peptides had not been shown to have a cross-reaction potential with the myelin basic protein

(“MBP”) components of nerve cells (found in the central nervous system (“CNS”), where MS

would be expected to begin), but stressed that the rarity of a vaccine-caused injury meant that the

biologic process he proposed could not be ruled out as implausible (and that in fact there was

evidence that flu virus components could instigate an MBP reaction). Tr. at 51–52, 61–62.

Because of his acknowledgement of the strong likelihood that L.Z.’s MS predated

vaccination, Dr. Napoli spent some time at hearing testifying about the nature of MS’s course. In

his experience, MS-associated lesions can be subclinical for a long time while other unaffected

parts of brain “pick[] up the slack,” with the result that patients do not manifest symptoms. Tr. at

38. Thus (and in keeping with his earlier admissions about Petitioner’s pre-vaccination history),

Dr. Napoli seemed to accept that the Petitioner’s claim actually turned on whether the flu vaccine

could have aggravated her underlying disease—and he answered that question in the affirmative.

To do so, Dr. Napoli discussed how MS “flares,” or exacerbations (a term which he deemed

congruent with an MS relapse), occur. Tr. at 37. Different environmental factors can trigger an MS

exacerbation—stress, weather changes, or an infection. Id. at 21, 47–48, 70. But such triggers

would generally not cause a significant worsening of the patient’s condition (nor would they

establish a new event akin to the formation of new lesions). Id. at 21–22, 70. Because vaccines are

intended to elicit an adaptive immune response (so that the body will in the future recognize and

fight off wild infections comparable to the vaccine administered), they “create potentially a remote

11

Dr. Napoli spent some time in his testimony addressing the propriety of MS as a diagnosis applicable to L.Z.’s

symptoms—although it is not really a contested issue in light of Dr. Venkatesan’s agreement that Petitioner had MS.

Tr. at 26–27, 35–36.

12

Even though the flu vaccine’s formula changes year to year, Dr. Napoli proposed that “antigenic similarity” between

yearly variations would still be able to spark an autoimmune cross-reaction, and thus an individual previously

vaccinated might nevertheless respond to the newer version of the vaccine. Tr. at 62–63.

8

chance of a cascade” that could have a more significant and dramatic effect on susceptible

individuals.13 Id. at 48, 73. Here, there was no evidence of other environmental triggers, like

stress—but there was evidence of vaccination before L.Z.’s symptomatic flare in November 2011.

Id. at 74, 146.

Dr. Napoli offered some scientific and medical evidence to support his assertions that

vaccines could trigger a worsening of an individual’s preexisting MS. First Napoli Rep. at 5;

Second Napoli Rep. at 2–4. However, certain of these articles were less supportive of his opinion

than they seemed at first glance. For example, at hearing Dr. Napoli referenced a 1967 article that

reviewed nine case reports in which vaccines are alleged to have caused MS exacerbations or

relapses—none of which involved the flu vaccine. Tr. at 57–58; see H. Miller, et al., Multiple

Sclerosis and Vaccination, 2 Brit. Med. J. 210, 210–13 (1967), filed as Ex. 31, Tab F, ECF No.

45-6 (“Miller”). Dr. Napoli also acknowledged that case reports generally were not particularly

probative of causation, although he stressed that the rarity of a vaccine-induced MS exacerbation

had to be taken into account. Id. at 48. Overall, Dr. Napoli could not point to any studies

demonstrating an association between the flu vaccine and MS exacerbation—and even accepted

the legitimacy of articles offered by Respondent establishing the contrary (as discussed below)—

but again maintained that the rare character of the injury at issue had to be taken into account when

weighing such evidence. Id. at 57–58 (admitting Respondent’s studies show “there’s no link”

between the flu vaccine and an increased risk of MS exacerbation).

In addition to the above, Dr. Napoli opined that the timing of onset of L.Z.’s alleged

exacerbation—two to three weeks post-vaccination—was medically acceptable based on reliable

medical literature. Tr. at 26; First Napoli Rep. at 5; Second Napoli Rep. at 3; see L. Schoenberger,

et al., Guillain-Barré Syndrome Following Vaccination in the National Influenza Immunization

Program, United States, 1976–1977, 110 Am. J. Epid. 105, 105 (1976), filed as Ex. 31, Tab G,

ECF No. 45-7; K. Stratton, et al., Adverse Events Associated with Childhood Vaccines: Evidence

on Causality, Institute Med. 47 (1994), filed as Ex. 31, Tab H, ECF No. 45-8. He acknowledged,

however, that some of that literature was distinguishable—for example, because it involved a

slightly different mechanism inapplicable to the theory proposed. Tr. at 49–50 (discussing K.

Wucherpfennig, et al., Molecular Mimicry in T Cell-Mediated Autoimmunity: Viral Peptides

Activate Human T Cell Clones Specific for Myelin Basic Protein, 80 Cell 695, 695, 698 (1995),

filed as Ex. 31, Tab C, ECF No. 45-3 (“Wucherpfennig”)). Dr. Napoli also noted that evidence

from the medical record of possible neurologic symptoms (for example, a foot dropping) within

days or a week of vaccination might present an unreasonable onset timeframe, given the period he

felt the biologic mechanism of molecular mimicry would take to unfold. Id. at 32–33. On the other

13

Dr. Napoli proposed (in somewhat conclusory fashion) that L.Z. likely had some genetic predisposition to suffer

from an autoimmune response induced by vaccination. A person’s genetics, he opined, can render them susceptible to

demyelination caused by an autoimmune process. Tr. at 10, 20–21. He acknowledged, however, that such assertions

were suppositions based principally on the fact that Petitioner’s MS was diagnosed after receiving the flu vaccine, and

not upon actual evidence of L.Z.’s genetic susceptibility. Id. at 66.

9

side of the spectrum, Dr. Napoli proposed that, based on his reading of the relevant literature, a

timeframe exceeding two to three months was likely too long—although a vaccine might still be

causal even if exacerbation was evident up to nine to twelve weeks later. Id. at 34. At all times,

Dr. Napoli stressed the relatively brief temporal relationship between vaccination and L.Z.’s initial

symptoms as particularly persuasive evidence to him of an association. Id. at 11.

Finally, Dr. Napoli’s testimony addressed whether any alleged vaccine-caused MS

exacerbation could be deemed to have worsened the overall expected course of L.Z.’s MS. He

opined that this had occurred—but did so based on the circular logic that because Petitioner

experienced an MS relapse post-vaccination, her illness had by definition “worsened.” Tr. at 69.

He admitted, however, that he could not opine whether she would have experienced a similar “hit”

at some time in the future regardless of whether she had received a vaccine. Id. At bottom, he

placed great weight on the fact that there was nothing else in the record other than the flu vaccine’s

administration that might explain her exacerbation. Id. at 27.

B. Dr. Arun Venkatesan

Dr. Venkatesan filed a single report and testified on Respondent’s behalf at hearing. See

Expert Report filed as Ex. A, Mar. 8, 2016, ECF. No. 28-1 (“Venkatesan Rep.”). Dr. Venkatesan

received his medical degree and a Ph.D. in microbiology and immunology from the University of

California, Los Angeles. CV filed as Ex. B, Mar. 8, 2016, ECF No. 28-2 (“Venkatesan CV”).

Following medical school, he completed a neurology residency at Johns Hopkins University in

Baltimore, Maryland. Id. at 1. He also completed a second fellowship in neuroimmunology and

neuroinfectious diseases at Johns Hopkins, and later joined the faculty in 2007 as an assistant

professor in the neurology department. Id.

Since 2009, Dr. Venkatesan has served as the director of the encephalitis center at Johns

Hopkins, and frequently sees both adult and pediatric patients with MS and other autoimmune

CNS disorders. Tr. at 77. According to Dr. Venkatesan, thirty percent of his time involves a clinical

practice seeing patients, with the remainder involving research, teaching, and overseeing

neurology residents. Id. at 79, 81. Dr. Venkatesan estimates that in his career he has seen more

than 1,000 MS patients. Id. at 78. He has also published numerous articles related to

neuroinflammatory and neuroinfectious diseases. Venkatesan CV at 1–2.

Dr. Venkatesan agreed with Dr. Napoli that L.Z. was properly diagnosed with MS,

although he more affirmatively placed its onset as predating her vaccination. Tr. at 114. He also

disputed Petitioner’s contention that the flu vaccine can (and in this case did) cause exacerbation

of MS. Id. at 82.

10

Dr. Venkatesan began his testimony by discussing MS and its relationship to other

neuroinflammatory conditions. He defined MS as a chronic demyelinating disease of the CNS,

resulting in progressive neurologic dysfunction. Tr. at 83. It often features relapses after an initial

event, and thus its course can be characterized by plateaus (with limited or controlled symptoms)

and flares. Id. Other identified CNS inflammatory conditions, such as TM (inflammation of the

spinal cord) or ON (inflammation of the optic nerve) can be symptomatic of MS (and can even

constitute an initial presenting symptom), but can also stand on their own as separate illnesses

(especially if other indicia for MS have not been established). Id. at 78, 83, 88. Dr. Venkatesan

characterized such kinds of CNS inflammation as more “eloquent,” or indicative of MS, than

others. Id. at 86–87.

When generally diagnosing MS, Dr. Venkatesan stressed the importance of reviewing

radiologic evidence in conjunction with a patient’s clinical symptoms. He referred to instances in

which a patient’s MRI reveals the presence of CNS lesions but where no clinical symptoms are

present as “radiologically isolated syndrome” (“RIS”), while he defined evidence of symptoms

suggestive of CNS demyelination or inflammation without corroborative MRI evidence as

“clinically isolated syndrome” (“CIS”). Tr. at 84–85. Ultimately, an MS diagnosis depends on a

finding of dissemination of lesions and symptoms both in time (meaning that they are not seen on

only a single occasion) and space (i.e. across multiple locations in the CNS). Id. at 85, 88. In Dr.

Venkatesan’s view, a lack of radiologic evidence of lesions makes it difficult to confirm an MS

diagnosis. Id. at 85–86. Symptom relapses could occur in a timeframe of once a year to once every

few years, and an individual relapse could last a few weeks or longer. Id. at 89–90.

Dr. Venkatesan disputed the sufficiency of Petitioner’s evidence supporting her contention

that the flu vaccine could cause or exacerbate MS, given its chronic nature. Tr. at 113. He

acknowledged the reliability of scientific evidence establishing that direct infection can cause MS

and/or contribute to an autoimmune process. Id. at 122, 130–31. He also did not contest that other

illnesses involving demyelination (for example, the peripheral neuropathy Guillain Barré

syndrome (“GBS”)) could be vaccine-induced. Id. at 124. But in his view, vaccines could not

produce an MS relapse. Rather, a vaccine could at most (and indirectly—by, for example, causing

a fever leading to an increase in body temperature) only induce transient changes in an individual

already suffering from MS—not alter an existing course of MS for the worse. Id. at 114.

To support his opinion, Dr. Venkatesan (in his report and direct testimony) offered the

views of trustworthy members of the relevant scientific community, as well as reliable scientific

and medical literature, that he proposed contradicted Petitioner’s theory. He noted that the

American Academy of Neurology has stated that there is “level A” evidence establishing no risk

of post-vaccination MS exacerbation. Tr. at 99–100; Venkatesan Rep. at 3. One article offered by

Respondent directly studied the effect of the flu vaccine on MS but found no post-vaccination

relapse. Tr. at 91–92; see C. Confavreux, et al., Vaccinations and the Risk of Relapse in Multiple

11

Sclerosis, 344 New Engl. J. Med. 319, 319 (2001), filed as Ex. C, ECF No. 49-1 (“Confavreux”).

The Confavreux study examined 643 MS patients (fifteen percent of whom reported having been

vaccinated during the preceding twelve months) to evaluate the relative risk of a vaccine-related

relapse. But Confavreaux determined that a vaccinated individual had a reduced chance of

relapse—and its authors expressed high confidence in the statistical accuracy of their findings in

concluding that vaccinations did not appear to increase the risk of relapse in MS patients. Tr. at

93–94; Confavreaux at 324–25. Dr. Venkatesan admitted, however, that the sample size of the

Confavreaux study was relatively small—a factor that suggests its findings should have less

probative weight than Respondent urged. Tr. at 125.

In another article filed by Respondent, a number of vaccines were evaluated to determine

if they were associated with demyelinating events like MS or ON, but its authors did not find such

an association. Tr. at 94–95; see F. DeStefano, et al., Vaccinations and the Risk of Central Nervous

System Demyelinating Diseases in Adults, 60 Arch. Neuro. 504 (2003), filed as Ex. D, ECF No.

49-2 (“DeStefano”). Although the DeStefano study did not specifically include TM as a separate

category, Dr. Venkatesan still maintained that the study would have included persons similarly

situated to L.Z., whose MS presented initially as spinal cord inflammation that might first appear

to be TM to treaters. Id. at 95. DeStafano did, however, include the flu vaccine among the studied

vaccines, and found with high statistical confidence that the vaccine was not associated with MS.

Id. at 96.

Dr. Venkatesan also discussed a third article involving a randomized trial of flu vaccine

administration intended to determine whether MS exacerbations occurred at an increased rate. Tr.

at 96–97; see A. Miller, et al., A Multicenter, Randomized, Double-Blind, Placebo-Controlled

Trial of Influenza Immunization in Multiple Sclerosis, 48 Neuro. 312 (1997), filed as Ex. E, ECF

No. 49-3 (“Miller 2”). Although Dr. Napoli proposed in his second report that Miller 2 revealed a

risk of exacerbation double those in the non-vaccinated cohort, Second Napoli Rep. at 3, Dr.

Venkatesan argued that this finding was not statistically significant (a point supported also by the

authors of the study)—and more importantly, that Miller 2 included individuals who had

experienced exacerbation or MS flares up to 175 days after vaccine administration, and thus (under

Petitioner’s own theory) were highly unlikely to have experienced a vaccine-induced exacerbation

within a medically acceptable timeframe. Tr. at 97, 126–28. 14

Besides highlighting literature and other evidence tending to rebut any association between

the flu vaccine and MS exacerbation, Dr. Venkatesan reviewed the specific elements of

14

In addressing the Miller 2 MS flare/exacerbation timeframes, Dr. Venkatesan also briefly touched on the scientific

reliability of Petitioner’s broader argument that her alleged flu vaccine-induced exacerbation occurred in a medically

acceptable timeframe. He noted that timeframes of 42 days, or even three months, post-vaccination for flares observed

in some of Petitioner’s literature applied to non-vaccinated individuals as well, and thus it could not be concluded that

these periods were reasonable from a medical standpoint. Tr. at 98–99.

12

Petitioner’s causation theory. He admitted that molecular mimicry as a general matter is a

scientifically plausible biologic mechanism to explain how an autoimmune process might unfold.

Tr. at 131. However, he questioned its relevance to the pathologic processes of chronic diseases

involving a “sustained immune response,” such as MS, as opposed to acute diseases that progress

rapidly like GBS. Id. at 139–40. He noted that certain literature confirmed the fact that MS

progresses as a result of an overall failure in the immune system response, and is therefore less

likely to be driven simply by cross-reactivity attributable to homology between antigens in a

vaccine and self protein sequences. Id. at 140–41.

Another article offered by Respondent to establish the lack of association between the flu

vaccine and MS exacerbation considered the larger question of whether the flu vaccine could

encourage a nonspecific T cell autoreactive response in patients with MS—finding that it did not.

See N. Moriabadi, et al., Influenza Vaccination in MS: Absence of T-Cell Response Against White

Matter Proteins, 69 Neuro. 938, 942–43 (2001), filed as Ex. G, ECF No. 49-5 (“Moriabadi”). In

Dr. Venkatesan’s reading, Moriabadi reduced the likelihood that the flu vaccine would produce

any auto-immune cross-reaction against MBP in the first place. Tr. at 108–09. He later

acknowledged, however, that the extremely small sample size of tested individuals greatly reduced

Moriabadi’s overall probative value. Id. at 109, 129.

Dr. Venkatesan otherwise denied knowledge of reliable scientific evidence establishing

that MS would occur via molecular mimicry, and endeavored to rebut those items Petitioner

offered to link the flu vaccine to MS. Id. at 111. Certain items of literature purporting to make such

a connection involved TM rather than MS, or involved acute cases of TM rather than MS

presenting with TM-like symptoms, and were therefore distinguishable on those grounds, he

reasoned. Tr. at 110; see, e.g., F. Pidcock, et al., Acute Transverse Myelitis in Childhood: Center-

Based Analysis of 47 Cases, 68 Neuro. 1474 (2008), filed as Ex. 31, Tab E, ECF No. 45-5; N.

Agmon-Levin, et al., Transverse Myelitis and Vaccines: A Multi-Analysis, 18 Lupus 1198 (2009),

filed as Ex. 31, Tab D, ECF No. 45-4 (“Agmon-Levin”). Agmon-Levin also was completely based

on case reports, reducing its overall scientific reliability. Tr. at 130; Agmon-Levin at 1199. And

an article offered by Petitioner to establish molecular mimicry, Wucherpfennig, involved flu virus

strains different from the formula relevant to this case, and/or established that an absence of precise

homology could result in no cross-reactive potential at all. Tr. at 100-07; Wucherpfennig at 698–

99.

Besides questioning the science supporting Petitioner’s theory, Dr. Venkatesan looked

carefully at L.Z.’s medical history and concluded that Petitioner’s MS likely predated her

vaccination. In so opining, he acknowledged that the evidence was not iron-clad, but that he found

significant certain symptoms she had displayed prior to October 2011, such as incontinence as well

as her bilateral thumb numbness, reasonably suggestive of MS (if not fully supportive of the

diagnosis). Tr. at 111, 116–17, 133, 136. Based on his own experience, he also proposed that a

13

pre-vaccination MRI might have produced radiologic findings consistent with MS, although he

noted that this was ultimately only informed speculation. Id. at 112, 132. Dr. Venkatesan took

issue with Dr. Napoli’s proposal that Petitioner’s MS (to the extent it predated vaccination) may

have existed at a “subclinical” level, arguing that the concept had no scientific meaning. Tr. at 86.

By contrast, although Dr. Venkatesan did not dispute that Petitioner displayed significant

and concerning MS symptoms post-vaccination, he questioned whether her post-vaccination

course reflected an alarming worsening of existing MS. Tr. at 117–18. In so maintaining, Dr.

Venkatesan took issue with Petitioner’s assertion that her post-vaccination symptoms were

“fulminant.” Id. at 113, 116. In his professional view, “fulminant” would only describe an

exacerbation that was characterized by both greater symptomatic severity and evidence of

extensive and expanding lesions—not what was reflected in Petitioner’s medical history. Id. at

119–20, 137. In Dr. Venkatesan’s view, Petitioner’s course was consistent with what a typical MS

patient would likely experience in a relapse, and thus did not reveal anything out of the ordinary.

Id. at 90–91, 112, 120.

III. Procedural History

As noted above, this case was initiated in September 2014. Petitioner subsequently filed

relevant medical records, concluding the process at the end of December 2014 with the Statement

of Completion. ECF No. 13. Respondent’s Rule 4(c) Report was thereafter filed on February 27,

2015, ECF No. 15, in which Respondent challenged the appropriateness of an entitlement award.

Petitioner’s first expert report from Dr. Napoli was filed later that fall, on October 8, 2015.

Based upon representations contained therein that seemed to allow for the possibility that L.Z.’s

MS predated her October 2011 vaccination, but that the vaccine was nevertheless responsible for

her subsequent symptoms, I ordered Petitioner to amend her claim to include significant

aggravation as a claim, Min. Order, Oct. 19, 2015, and she did so in early November. Am. Pet. at

2, Nov. 5, 2015, ECF No. 26.

The following spring of 2016, Respondent filed an expert report from Dr. Venkatesan, and

Petitioner responded in July 2016 with Dr. Napoli’s second expert report. The parties next agreed

that the matter was ready for hearing, and I set it down to be tried on November 13, 2017. Prehr’g

Order, Aug. 22, 2016, ECF No. 35. The hearing went forward as scheduled, and the parties filed

post-hearing briefs in the first quarter of 2018. The matter is now ripe for decision.

14

IV. Applicable Law

A. Petitioner’s Overall Burden in Vaccine Program Cases

To receive compensation in the Vaccine Program, a petitioner must prove either: (1) that

he suffered a “Table Injury”—i.e., an injury falling within the Vaccine Injury Table—

corresponding to one of the vaccinations in question within a statutorily prescribed period of time

or, in the alternative, (2) that his illnesses were actually caused by a vaccine (a “Non-Table

Injury”). See Sections 11(c)(1), 13(a)(1)(A), 14(a); see also Moberly v. Sec’y of Health & Human

Servs., 592 F.3d 1315, 1321 (Fed. Cir. 2010); Capizzano v. Sec’y of Health & Human Servs., 440

F.3d 1317, 1320 (Fed. Cir. 2006).15 In this case, Petitioner does not assert a Table claim.

For both Table and Non-Table claims, Vaccine Program petitioners bear a “preponderance

of the evidence” burden of proof. Section 13(a)(1)(a). That is, a petitioner must offer evidence that

leads the “trier of fact to believe that the existence of a fact is more probable than its nonexistence

before [he] may find in favor of the party who has the burden to persuade the judge of the fact’s

existence.” Moberly, 592 F.3d at 1322 n.2; see also Snowbank Enters. v. United States, 6 Cl. Ct.

476, 486 (1984) (mere conjecture or speculation is insufficient under a preponderance standard).

Proof of medical certainty is not required. Bunting v. Sec’y of Health & Human Servs., 931 F.2d

867, 873 (Fed. Cir. 1991). In particular, a petitioner must demonstrate that the vaccine was “not

only [the] but-for cause of the injury but also a substantial factor in bringing about the injury.”

Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344,

1352–53 (Fed. Cir. 1999)); Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355 (Fed.

Cir. 2006). A petitioner may not receive a Vaccine Program award based solely on his assertions;

rather, the petition must be supported by either medical records or by the opinion of a competent

physician. Section 13(a)(1).

In attempting to establish entitlement to a Vaccine Program award of compensation for a

Non-Table claim, a petitioner must satisfy all three of the elements established by the Federal

Circuit in Althen v. Secretary of Health & Human Services, 418 F.3d 1274, 1278 (Fed. Cir. 2005):

“(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.” Althen, 418 F.3d at 1278.

Each of the Althen prongs requires a different showing. Under Althen prong one, petitioners

must provide a “reputable medical theory,” demonstrating that the vaccine received can cause the

15

Decisions of special masters (some of which I reference in this ruling) constitute persuasive but not binding

authority. Hanlon v. Sec’y of Health & Human Servs., 40 Fed. Cl. 625, 630 (1998). By contrast, Federal Circuit rulings

concerning legal issues are binding on special masters. Guillory v. Sec’y of Health & Human Servs., 59 Fed. Cl. 121,

124 (2003), aff’d 104 F. App’x 712 (Fed. Cir. 2004); see also Spooner v. Sec’y of Health & Human Servs., No. 13-

159V, 2014 WL 504728, at *7 n.12 (Fed. Cl. Spec. Mstr. Jan. 16, 2014).

15

type of injury alleged. Pafford, 451 F.3d at 1355–56 (citations omitted). To satisfy this prong, a

petitioner’s theory must be based on a “sound and reliable medical or scientific explanation.”

Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). Such a theory

must only be “legally probable, not medically or scientifically certain.” Id. at 549.

Petitioners may satisfy the first Althen prong without resort to medical literature,

epidemiological studies, demonstration of a specific mechanism, or a generally accepted medical

theory. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1378–79 (Fed. Cir. 2009)

(citing Capizzano, 440 F.3d at 1325–26). Special masters, despite their expertise, are not

empowered by statute to conclusively resolve what are essentially thorny scientific and medical

questions, and thus scientific evidence offered to establish Althen prong one is viewed “not through

the lens of the laboratorian, but instead from the vantage point of the Vaccine Act’s preponderant

evidence standard.” Id. at 1380. Accordingly, special masters must take care not to increase the

burden placed on petitioners in offering a scientific theory linking vaccine to injury. Contreras v.

Sec’y of Health & Human Servs., 121 Fed. Cl. 230, 245 (2015), vacated on other grounds, 844

F.3d 1363 (Fed. Cir. 2017).

In discussing the evidentiary standard applicable to the first Althen prong, many decisions

of the Court of Federal Claims and Federal Circuit have emphasized that petitioners need only

establish a causation theory’s biological plausibility (and thus need not do so with preponderant

proof). Tarsell v. United States, 133 Fed. Cl. 782, 792–93 (2017) (special master committed legal

error by requiring petitioner to establish first Althen prong by preponderance; that standard applied

only to second prong and petitioner’s overall burden); Contreras, 121 Fed. Cl. at 245

(“[p]lausibility . . . in many cases may be enough to satisfy Althen prong one” (emphasis in

original)); see also Andreu, 569 F.3d at 1375. At the same time, there is contrary authority from

the Federal Circuit suggesting that the same preponderance standard used overall in evaluating a

claimant’s success in a Vaccine Act claim is also applied specifically to the first Althen prong. See,

e.g., Broekelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1350 (Fed. Cir. 2010)

(affirming special master’s determination that expert “had not provided a ‘reliable medical or

scientific explanation’ sufficient to prove by a preponderance of the evidence a medical theory

linking the [relevant vaccine to relevant injury]”) (emphasis added). Regardless, one thing

remains: petitioners always have the ultimate burden of establishing their Vaccine Act claim

overall with preponderant evidence. W.C. v. Sec’y of Health & Human Servs., 704 F.3d 1352, 1356

(Fed. Cir. 2013) (citations omitted); Tarsell, 133 Fed. Cl. at 793 (noting that Moberly “addresses

the petitioner’s overall burden of proving causation-in-fact under the Vaccine Act” by a

preponderance standard).

The second Althen prong requires proof of a logical sequence of cause and effect, usually

supported by facts derived from a petitioner’s medical records. Althen, 418 F.3d at 1278; Andreu,

569 F.3d at 1375–77; Capizzano, 440 F.3d at 1326; Grant v. Sec’y of Health & Human Servs., 956

16

F.2d 1144, 1148 (Fed. Cir. 1992). In establishing that a vaccine “did cause” injury, the opinions

and views of the injured party’s treating physicians are entitled to some weight. Andreu, 569 F.3d

at 1367; Capizzano, 440 F.3d at 1326 (“medical records and medical opinion testimony are favored

in vaccine cases, as treating physicians are likely to be in the best position to determine whether a

‘logical sequence of cause and effect show[s] that the vaccination was the reason for the injury’”)

(quoting Althen, 418 F.3d at 1280). Medical records are generally viewed as particularly

trustworthy evidence, since they are created contemporaneously with the treatment of the patient.

Cucuras v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).

However, medical records and/or statements of a treating physician’s views do not per se

bind the special master to adopt the conclusions of such an individual, even if they must be

considered and carefully evaluated. Section 13(b)(1) (providing that “[a]ny such diagnosis,

conclusion, judgment, test result, report, or summary shall not be binding on the special master or

court”); Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 746 n.67 (2009) (“there is

nothing . . . that mandates that the testimony of a treating physician is sacrosanct—that it must be

accepted in its entirety and cannot be rebutted”). As with expert testimony offered to establish a

theory of causation, the opinions or diagnoses of treating physicians are only as trustworthy as the

reasonableness of their suppositions or bases. The views of treating physicians should also be

weighed against other, contrary evidence present in the record—including conflicting opinions

among such individuals. Hibbard v. Sec’y of Health & Human Servs., 100 Fed. Cl. 742, 749 (2011)

(not arbitrary or capricious for special master to weigh competing treating physicians’ conclusions

against each other), aff’d, 698 F.3d 1355 (Fed. Cir. 2012); Caves v. Sec’y of Dept. of Health &

Human Servs., No. 06-522V, 2011 WL 1935813, at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011), mot.

for review denied, 100 Fed. Cl. 344, 356 (2011), aff’d without op., 475 Fed. App’x 765 (Fed. Cir.

2012).

The third Althen prong requires establishing a “proximate temporal relationship” between

the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been equated to the

phrase “medically-acceptable temporal relationship.” Id. A petitioner must offer “preponderant

proof that the onset of symptoms occurred within a timeframe which, given the medical

understanding of the disorder’s etiology, it is medically acceptable to infer causation.” de Bazan

v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for

what is a medically acceptable timeframe must also coincide with the theory of how the relevant

vaccine can cause an injury (Althen prong one’s requirement). Id. at 1352; Shapiro v. Sec’y of

Health & Human Servs., 101 Fed. Cl. 532, 542 (2011), recons. denied after remand, 105 Fed. Cl.

353 (2012), aff’d mem., 2013 WL 1896173 (Fed. Cir. 2013); Koehn v. Sec’y of Health & Human

Servs., No. 11-355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review

denied (Fed. Cl. Dec. 3, 2013), aff’d, 773 F.3d 1239 (Fed. Cir. 2014).

17

B. Standards Applicable to Significant Aggravation Claim

In this matter, besides arguing that the flu vaccine caused her MS, Petitioner also offers a

parallel theory that the vaccine significantly aggravated her neurologic illness by causing an MS

relapse or flare. Where a petitioner so alleges, the Althen test is expanded, and the petitioner has

additional evidentiary burdens to satisfy. See generally Loving v. Sec’y of Health & Human Servs.,

86 Fed. Cl. 135, 144 (2009). In Loving, the Court of Federal Claims combined the Althen test with

the test from Whitecotton v. Secretary of Health & Human Services, 81 F.3d 1099, 1107 (Fed. Cir.

1996), which related to on-Table significant aggravation cases. The resultant “significant

aggravation” test has six components, which require establishing:

(1) the person’s condition prior to administration of the vaccine, (2) the person’s current

condition (or the condition following the vaccination if that is also pertinent), (3) whether

the person’s current condition constitutes a “significant aggravation” of the person’s

condition prior to vaccination, (4) a medical theory causally connecting such a

significantly worsened condition to the vaccination, (5) a logical sequence of cause and

effect showing that the vaccination was the reason for the significant aggravation, and (6)

a showing of a proximate temporal relationship between the vaccination and the

significant aggravation.

Loving, 86 Fed. Cl. at 144; see also W.C., 704 F.3d at 1357 (holding that “the Loving case provides

the correct framework for evaluating off-table significant aggravation claims”). In effect, the last

three prongs of the Loving test correspond to the three Althen prongs.

Subsumed within the Loving analysis is the requirement to evaluate the likely natural

course of an injured party’s preexisting disease, in order to determine whether the vaccine made

the petitioner worse than he would have been but for the vaccination. Locane v. Sec’y of Health &

Human Servs., 685 F.3d 1375, 1381–82 (Fed. Cir. 2012) (upholding special master’s determination

that petitioner had failed to carry her burden of proof in establishing that her preexisting injury

was worsened by the relevant vaccine); Hennessey v. Sec’y of Health & Human Servs., No. 01-

190V, 2009 WL 1709053, at *41–42 (Fed. Cl. Spec. Mstr. May 29, 2009), mot. for review denied,

91 Fed. Cl 126 (2010). The critical point of examination is thus “whether the change for the worse

in [petitioner’s] clinical presentation was aggravation or a natural progression” of the underlying

condition. Hennessey, 2009 WL 1709053, at *42.16 The Federal Circuit has upheld the

16

The legislative history of the Vaccine Act strongly supports interpreting “significant aggravation” as requiring a

claimant to establish that a vaccine rendered a preexisting condition qualitatively worse than it would have been

otherwise—not simply that the affected individual experienced a post-vaccination symptom that contrasts with the

individual’s comparatively better pre-vaccination health. See H.R. Rep. No. 99-908, at 15 (1986) (“This [significant

aggravation] provision does not include compensation for conditions which might legitimately be described as pre-

existing (e.g., a child with monthly seizures who, after vaccination, has seizures every three and a half weeks), but is

meant to encompass serious deterioration (e.g., a child with monthly seizures who, after vaccination, has seizures on

a daily basis” (emphasis added)).

18

determinations of special masters that worsening was not demonstrated in connection with

establishing a petitioner’s overall preponderant burden of proof for a non-Table causation-in-fact

claim. See, e.g., Snyder/Harris v. Sec’y of Health & Human Servs., 553 F. App’x 994, 999–1000

(Fed. Cir. 2014); Locane, 685 F.3d at 1381–82.17

The mere fact a vaccine might “trigger” a transient negative response in an individual with

an underlying condition is not proof of worsening if that individual would be expected to

experience a similar overall course regardless. Faoro v. Sec’y of Health &Human Servs., No. 10-

704V, 2016 WL 675491, at *27 (Fed. Cl. Spec. Mstr. Jan. 29, 2016), mot. for review denied, 128

Fed. Cl. 61 (Fed. Cl. Apr. 11, 2016) (finding that “the vaccinations would not have changed her

clinical course and thus, the vaccinations did not significantly aggravate her preexisting

condition”). This point has been emphasized in a subcategory of Program cases involving the claim

that a child’s Dravet syndrome (a rare seizure disorder now understood to be caused by the SCN1A

gene mutation) was significantly aggravated by vaccination. Faoro, 2016 WL 675491, at *1. In

such cases, special masters have repeatedly determined that petitioners failed to show that a child’s

expected outcome would have been different but for the vaccination—even though it was not

disputed that the child’s first major seizure had been triggered by vaccination. Id. at *2 (“[a]lthough

H.E.F.’s vaccinations may have caused a low-grade fever or otherwise triggered her first seizure,

neither the initial seizure nor her vaccinations caused or significantly aggravated her Dravet

syndrome and resulting neurological complications”); see also Snyder/Harris, 553 F. App’x at

1003 (special master was not arbitrary in finding that petitioners’ expert failed to show that the

child’s outcome would have been different had he not received the vaccinations at issue).

C. Law Governing Analysis of Fact Evidence

The process for making determinations in Vaccine Program cases regarding factual issues

begins with consideration of the medical records. Section 11(c)(2). The special master is required

to consider “all [] relevant medical and scientific evidence contained in the record,” including “any

diagnosis, conclusion, medical judgment, or autopsy or coroner’s report which is contained in the

record regarding the nature, causation, and aggravation of the petitioner’s illness, disability, injury,

condition, or death,” as well as the “results of any diagnostic or evaluative test which are contained

in the record and the summaries and conclusions.” Section 13(b)(1)(A). The special master is then

required to weigh the evidence presented, including contemporaneous medical records and

testimony. See Burns v. Sec’y of Health & Human Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (it is

17

This is consistent with the fact (well recognized by controlling precedent) that evidence of “worsening” relevant to

Respondent’s alternative cause burden may reasonably by evaluated by a special master in determining the success of

a petitioner’s prima facie showing. Snyder/Harris, 553 F. App’x at 1000, quoting Stone, 676 F.3d at 1380 (“no

evidence should be embargoed from the special master’s consideration simply because it is also relevant to another

inquiry under the statute”); see also de Bazan v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1353 (Fed. Cir.

2008) (“[t]he government, like any defendant, is permitted to offer evidence to demonstrate the inadequacy of the

petitioner’s evidence on a requisite element of the petitioner’s case-in-chief”).

19

within the special master’s discretion to determine whether to afford greater weight to

contemporaneous medical records than to other evidence, such as oral testimony surrounding the

events in question that was given at a later date, provided that such determination is evidenced by

a rational determination).

Medical records that are created contemporaneously with the events they describe are

presumed to be accurate and “complete” (i.e., presenting all relevant information on a patient’s

health problems). Cucuras, 993 F.2d at 1528; Doe/70 v. Sec’y of Health & Human Servs., 95 Fed.

Cl. 598, 608 (2010) (“[g]iven the inconsistencies between petitioner’s testimony and his

contemporaneous medical records, the special master’s decision to rely on petitioner’s medical

records was rational and consistent with applicable law”); Rickett v. Sec’y of Health & Human

Servs., 468 F. App’x 952 (Fed. Cir. 2011) (non-precedential opinion). This presumption is based

on the linked propositions that (i) sick people visit medical professionals; (ii) sick people honestly

report their health problems to those professionals; and (iii) medical professionals record what they

are told or observe when examining their patients in as accurate a manner as possible, so that they

are aware of enough relevant facts to make appropriate treatment decisions. Sanchez v. Sec’y of

Health & Human Servs., No. 11-685V, 2013 WL 1880825, at *2 (Fed. Cl. Spec. Mstr. Apr. 10,

2013); Cucuras v. Sec’y of Health & Human Servs., 26 Cl. Ct. 537, 543 (1992), aff’d, 993 F.2d at

1525 (Fed. Cir. 1993) (“[i]t strains reason to conclude that petitioners would fail to accurately

report the onset of their daughter’s symptoms”).

Accordingly, if the medical records are clear, consistent, and complete, then they should

be afforded substantial weight. Lowrie v. Sec’y of Health & Human Servs., No. 03-1585V, 2005

WL 6117475, at *20 (Fed. Cl. Spec. Mstr. Dec. 12, 2005). Indeed, contemporaneous medical

records are generally found to be deserving of greater evidentiary weight than oral testimony—

especially where such testimony conflicts with the record evidence. Cucuras, 993 F.2d at 1528;

see also Murphy v. Sec’y of Health & Human Servs., 23 Cl. Ct. 726, 733 (1991), aff’d per curiam,

968 F.2d 1226 (Fed. Cir. 1992), cert. denied sub. nom. Murphy v. Sullivan, 506 U.S. 974 (1992)

(citing United States v. United States Gypsum Co., 333 U.S. 364, 396 (1947) (“[i]t has generally

been held that oral testimony which is in conflict with contemporaneous documents is entitled to

little evidentiary weight”)).

However, there are situations in which compelling oral testimony may be more persuasive

than written records, such as where records are deemed to be incomplete or inaccurate. Campbell

v. Sec’y of Health & Human Servs., 69 Fed. Cl. 775, 779 (2006) (“like any norm based upon

common sense and experience, this rule should not be treated as an absolute and must yield where

the factual predicates for its application are weak or lacking”); Lowrie, 2005 WL 6117475, at *19

(“[w]ritten records which are, themselves, inconsistent, should be accorded less deference than

those which are internally consistent”) (quoting Murphy, 23 Cl. Ct. at 733)). Ultimately, a

determination regarding a witness’s credibility is needed when determining the weight that such

20

testimony should be afforded. Andreu, 569 F.3d at 1379; Bradley v. Sec’y of Health & Human

Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

When witness testimony is offered to overcome the presumption of accuracy afforded to

contemporaneous medical records, such testimony must be “consistent, clear, cogent, and

compelling.” Sanchez, 2013 WL 1880825, at *3 (citing Blutstein v. Sec’y of Health & Human

Servs., No. 90-2808V, 1998 WL 408611, at *5 (Fed. Cl. Spec. Mstr. June 30, 1998)). In

determining the accuracy and completeness of medical records, the Court of Federal Claims has

listed four possible explanations for inconsistencies between contemporaneously created medical

records and later testimony: (1) a person’s failure to recount to the medical professional everything

that happened during the relevant time period; (2) the medical professional’s failure to document

everything reported to her or him; (3) a person’s faulty recollection of the events when presenting

testimony; or (4) a person’s purposeful recounting of symptoms that did not exist. La Londe v.

Sec’y of Health & Human Servs., 110 Fed. Cl. 184, 203–04 (2013), aff’d, 746 F.3d 1334 (Fed. Cir.

2014). In making a determination regarding whether to afford greater weight to contemporaneous

medical records or other evidence, such as testimony at hearing, there must be evidence that this

decision was the result of a rational determination. Burns, 3 F.3d at 417.

D. Analysis of Expert Testimony

Establishing a sound and reliable medical theory often requires a petitioner to present

expert testimony in support of his claim. Lampe v. Sec’y of Health & Human Servs., 219 F.3d

1357, 1361 (Fed. Cir. 2000). Vaccine Program expert testimony is usually evaluated according to

the factors for analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharm., Inc., 509

U.S. 579, 594–96 (1993). See Cedillo v. Sec’y of Health & Human Servs., 617 F.3d 1328, 1339

(Fed. Cir. 2010) (citing Terran v. Sec’y of Health & Human Servs., 195 F.3d 1302, 1316 (Fed. Cir.

1999)). “The Daubert factors for analyzing the reliability of testimony are: (1) whether a theory or

technique can be (and has been) tested; (2) whether the theory or technique has been subjected to

peer review and publication; (3) whether there is a known or potential rate of error and whether

there are standards for controlling the error; and (4) whether the theory or technique enjoys general

acceptance within a relevant scientific community.” Terran, 195 F.3d at 1316 n.2 (citing Daubert,

509 U.S. at 592–95).

The Daubert factors play a slightly different role in Vaccine Program cases than they do

when applied in other federal judicial fora (such as the district courts). Daubert factors are usually

employed by judges (in the performance of their evidentiary gatekeeper roles) to exclude evidence

that is unreliable and/or could confuse a jury. In Vaccine Program cases, by contrast, these factors

are used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec’y of Health

& Human Servs., 94 Fed. Cl. 53, 66–67 (2010) (“uniquely in this Circuit, the Daubert factors have

been employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness of

21

expert testimony already admitted”). The flexible use of the Daubert factors to evaluate the

persuasiveness and reliability of expert testimony has routinely been upheld. See, e.g., Snyder, 88

Fed. Cl. at 742–45. In this matter (as in numerous other Vaccine Program cases), Daubert has not

been employed at the threshold, to determine what evidence should be admitted, but instead to

determine whether expert testimony offered is reliable and/or persuasive.

Respondent frequently offers one or more experts of his own in order to rebut a petitioner’s

case. Where both sides offer expert testimony, a special master’s decision may be “based on the

credibility of the experts and the relative persuasiveness of their competing theories.”

Broekelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing

Lampe, 219 F.3d at 1362). However, nothing requires the acceptance of an expert’s conclusion

“connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too

great an analytical gap between the data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743

(quoting Gen. Elec. Co. v. Joiner, 522 U.S. 146 (1997)); see also Isaac v. Sec’y of Health & Human

Servs., No. 08-601V, 2012 WL 3609993, at *17 (Fed. Cl. Spec. Mstr. July 30, 2012), mot. for

review denied, 108 Fed. Cl. 743 (2013), aff’d, 540 Fed. App’x 999 (Fed. Cir. 2013) (citing Cedillo,

617 F.3d at 1339). Weighing the relative persuasiveness of competing expert testimony, based on

a particular expert’s credibility, is part of the overall reliability analysis to which special masters

must subject expert testimony in Vaccine Program cases. Moberly, 592 F.3d at 1325–26

(“[a]ssessments as to the reliability of expert testimony often turn on credibility determinations”);

see also Porter v. Sec’y of Health & Human Servs., 663 F.3d 1242, 1250 (Fed. Cir. 2011) (“this

court has unambiguously explained that special masters are expected to consider the credibility of

expert witnesses in evaluating petitions for compensation under the Vaccine Act”).

E. Consideration of Medical Literature

Both parties filed medical and scientific literature in this case, but not every filed item

factors into the outcome of this decision. While I have reviewed all of the medical literature

submitted in this case, I discuss only those articles that are most relevant to my determination

and/or are central to Petitioner’s case—just as I have not exhaustively discussed every individual

medical record filed. Moriarty v. Sec’y of Health & Human Servs., No. 2015-5072, 2016 WL

1358616, at *5 (Fed. Cir. Apr. 6, 2016) (“[w]e generally presume that a special master considered

the relevant record evidence even though he does not explicitly reference such evidence in his

decision”) (citation omitted); see also Paterek v. Sec’y of Health & Human Servs., 527 F. App’x

875, 884 (Fed. Cir. 2013) (“[f]inding certain information not relevant does not lead to—and likely

undermines—the conclusion that it was not considered”).

22

ANALYSIS

I. Overview of Medical Terms and Relevant Prior Decisions

The parties’ experts agreed largely on the proper definition of MS and what kind of clinical

or radiologic evidence establishes its existence. As Program case law recognizes, MS is

categorized as a demyelinating central nervous system disease. See Taylor v. Sec’y of Health &

Human Servs., No. 13-700V, 2018 WL 2050857, at *21 (Fed. Cl. Spec. Mstr. Mar. 9, 2018).

Patients diagnosed with MS typically experience multiple episodes of CNS demyelination

separated in time and space, evidencing a more progressive decline in their overall health course.

Id. An MRI can be used to corroborate the dissemination in space and time requirement, and often

reveals old lesions as well as enhancing/new lesions. Id. Evidence of oligoclonal bands in

cerebrospinal fluid testing, which reveal brain inflammation, is also frequently seen in patients

with MS. Id. Symptoms can include numbness or weakness in the body, loss of vision, tremors,

unsteady gait, slurred speech, and dizziness. Id.

Other Program claimants have attempted to argue that a vaccine (including the flu vaccine)

significantly aggravated a person’s preexisting MS, to varying degrees of success. See, e.g.,

Quackenbush-Baker v. Sec’y of Health & Human Servs., No. 14-1000V, 2018 WL 1704523 (Fed.

Cl. Spec. Mstr. Mar. 14, 2018) (flu vaccine significantly aggravated the petitioner’s preexisting

MS); W.C. v. Sec’y of Health & Human Servs., 100 Fed. Cl. 440 (2011) (upholding special master’s

determination that flu vaccine did not significantly aggravate preexisting MS); Bubb v. Sec’y of

Health & Human Servs., No. 01-721V, 2005 WL 1025707 (Fed. Cl. Spec. Mstr. Apr. 29, 2005)

(tetanus toxoid vaccine did not significantly aggravate preexisting MS). None of these decisions

are completely on point (and some are actually distinguishable), but they nevertheless provide

guidance in addressing the claim at hand.

In W.C., the claimant (as here) alleged that the flu vaccine aggravated his previously-

asymptomatic MS (with onset about 12 days after vaccination), but the special master responsible

for the case denied entitlement. Upon review, in discussing the fourth Loving prong (the “can

cause” element under the direct Althen test), the Court of Federal Claims noted that Respondent

had offered much of the same medical literature used in this case to attack the association between

the flu vaccine and exacerbation of MS—Moriabadi, Confavreaux, DeStefano, and Miller 2. W.C.,

100 Fed. Cl. at 455–56. The Court upheld the special master’s determination, but in doing so was

careful to note that factually and scientifically, the case presented some close calls that could have

been decided by a different special master with the opposite result, and thus the underlying decision

was upheld mainly as a function of the proper application of the review standards. Id. at 456 (noting

that although that the evidence was “so closely balanced that the decision could have gone either

way,” nevertheless “the court cannot say that the special master’s findings were arbitrary”).

23

Bubb does not involve the flu vaccine, but is a stronger endorsement of the case against an

association between vaccines and MS exacerbation than W.C. There, it was undisputed that the

petitioner suffered from MS before vaccination. Bubb, 2005 WL 1025707, at *2. In addition, the

record supported the conclusion that not only had the petitioner experienced a relapse post-

vaccination, but that the relapse overall resulted in a sufficiently severe worsening of her condition

to constitute a “significant aggravation” under the Act. Id. at *22. Nevertheless, the special master

decided the claim against the petitioner, largely due to her inability to connect the tetanus

vaccination to her MS worsening. Id. at *24. Like the present case and W.C., the respondent offered

Confavreaux and DeStefano to rebut any purported association between vaccination and MS

exacerbation, id. at *20–21—evidence the special master found persuasive in “significantly

undercut[ting]” the case study evidence offered by the petitioner. Id. at *24. This in addition to the

lack of other probative evidence relating exacerbation to the vaccine (such as the views of

contemporaneous treaters) resulted in the denial of entitlement.

In Quackenbush-Baker, by contrast, a petitioner succeeded in establishing that the flu

vaccine significantly aggravated her MS. However, the petitioner’s MS was wholly asymptomatic

prior to vaccination, and thus deemed to have preexisted solely on the basis of MRI evidence

(unlike the present case). Quackenbush-Baker, 2018 WL 1704523, at *8. The asymptomatic, RIS

nature of petitioner’s MS seems to have factored heavily in the special master’s finding in

petitioner’s favor. Id. at *14–15. It also appears that the scientific evidence deemed so persuasive

in W.C. or Bubb on the question of a vaccine’s capacity to exacerbate MS was not offered by the

experts in Quackenbush-Baker either. Id. at *15–17.

II. Petitioner Has Not Established Her Significant Aggravation Claim with Sufficient

Preponderant Evidence

Although Dr. Napoli made some attempt to hedge his opinion, he ultimately acknowledged

several times that it was reasonable to conclude from the medical record that L.Z.’s MS predated

her receipt of the flu vaccine. See, e.g., Tr. at 19, 39–40, 42, 44, 67; First Napoli Rep. at 4. Dr.

Venkatesan was not so equivocal on this point. Tr. at 111, 116–17, 133, 136. Both views were

based on record evidence of pre-vaccination neurologic symptoms.

After consideration of the same evidence plus expert testimony, I find as well that it is more

likely than not the case that Petitioner’s MS began before vaccination. The radiologic evidence

bulwarks this conclusion. Although the MRIs performed on L.Z. were not “enhanced,” and

therefore could not help treaters determine whether any lesions viewed were old or more recent,

they were performed within a month of vaccination, and revealed sufficient amounts of lesions to

corroborate (with Petitioner’s clinical presentation) an MS diagnosis. As has been recognized in

other Program cases, lesions can preexist an MRI by weeks or even months. See, e.g., Borrero v.

Sec’y of Health & Human Servs., No. 01-417V, 2008 WL 4527837, at *21 (Fed. Cl. Spec. Mstr.

Sept. 24, 2008); Stevens v. Sec’y of Health & Human Servs., No. 99-594V, 2006 WL 659525, at

24

*23 (Fed. Cl. Spec. Mstr. Feb. 24, 2006). Accordingly, it is more likely that these lesions predated

vaccination (especially when considered in the context of the medical record evidence suggesting

L.Z. had been experiencing neurologic symptoms for some time before vaccination).

Based on this initial determination, Petitioner’s direct causation claim cannot succeed, as

she cannot demonstrate a vaccine “caused” an illness predating vaccination. See, e.g., Locane v.

Sec’y of Health & Human Servs., 99 Fed. Cl. 715 (2011) (petitioner’s alleged vaccine-induced

injury began prior to her vaccinations and therefore vaccine causation could not be established),

aff’d, 685 F.3d 1375 (Fed. Cir. 2012); W.C., 100 Fed. Cl. at 453 (upholding special master’s denial

of direct causation claim where petitioner’s medical records suggested lesions developed pre-

vaccination). I therefore will not engage in an Althen review of her direct causation claim. Instead,

I turn to Petitioner’s alternative claim: that the flu vaccine significantly aggravated her MS. I

address the most relevant Loving factors in order of their importance to my overall determination.18

A. Petitioner Has Not Established a Plausible Causation Theory

Having heard the experts and reviewed each side’s medical literature, I find that Petitioner

has not presented a plausible theory, supported by sufficient reliable evidence, that the flu vaccine

could exacerbate an existing course of MS. At best, Dr. Napoli offered persuasive evidence that

the flu virus or vaccine could initiate MS. He certainly proposed a mechanism, molecular mimicry,

that has been deemed reliable in this context in past Program cases, and I do not consider the

argument to lack a scientific foundation. See, e.g., Quackenbush-Baker, 2018 WL 1704523, at

*16–17.

But, as noted above, Petitioner’s claim required establishing that the flu vaccine could be

associated with flares/exacerbations of an existing case of MS, and that those vaccine-induced

flares could produce a worsened overall course. As Respondent and Dr. Venkatesan established,

the evidence offered herein preponderates against this conclusion. The literature filed by

Respondent on this point—e.g., Confavreux and DeStefano—is particularly reliable and

persuasive, as other decisions have recognized. See W.C., 100 Fed. Cl. at 455–56; Bubb, 2005 WL

1025707, at *20–21. Petitioner’s arguments that I should not give such evidence much weight

because it cannot conclusively disprove a connection between the vaccine and MS

flare/exacerbation miss the mark, and reflect an attempt to evade evidence that undercuts

18

I do not address all of the Loving prongs, however, for the simple reason that Petitioner’s failure to establish linchpin

elements of her claim (in particular, that the vaccine could, or did, exacerbate her MS) renders a rote determination of

Petitioner’s success in establishing each individualized prong unnecessary. See, e.g., Bigbee v. Sec’y of Health &

Human Servs., No. 06-663V, 2012 WL 1237759, at *36 (Fed. Cl. Spec. Mstr. Mar. 22, 2012) (citing Althen, 418 F.3d

at 1278). I do note, however, that Petitioner’s evidentiary showing regarding the timing prong is similarly deficient

based on the scientific literature submitted (which involves diseases distinguishable from MS). See First Napoli Rep.

at 5 (relying on the Schonberger study relating to GBS).

25

Petitioner’s case without addressing its substantive merits.19 Indeed, as noted above, Dr. Napoli

effectively conceded that this literature was reliable. See Tr. at 57–58.

In response, Petitioner relied heavily on case reports or articles involving different

demyelinating conditions like GBS (a peripheral neuropathy) that are distinguishable from CNS

conditions. Dr. Napoli otherwise could not imbue Petitioner’s theory with reliability that the

literature did not support; although I found him to be a competent, credible expert with more than

sufficient expertise on the topic of MS and interpretation of the radiologic evidence relevant to it,

he lacked the immunologic expertise needed to fill in evidentiary holes in Petitioner’s case not

otherwise adequately served by the written scientific evidence filed in the case.

Most significantly, there is an absence of reliable scientific proof in this case establishing

a central component of Petitioner’s significant aggravation claim: that the flu vaccine can cause a

preexisting case of MS to worsen beyond what would be expected based on its expected normal

course. Petitioner offered no literature discussing this particular concept directly, Tr. at 57, and Dr.

Napoli did not relate in his testimony particularized observations from his own medical experience

that would render this contention plausible. Respondent, by contrast, offered reliable scientific

evidence suggesting that the flu vaccine does not worsen MS (and indeed that the vaccine should

be administered to MS patients given the greater risks that intervening wild virus infections pose

such individuals). See, e.g., Moriabadi at 943. Respondent also offered credible and reliable

literature suggesting that the flu vaccine might not be able to encourage the chronic

autoinflammatory process that characterizes MS. Id. at 942–43.

B. Petitioner Has Not Established Her MS Course Was Worsened by Vaccination

As noted above, I am cognizant of the fact that in a few situations claimants have

successfully established the “can cause” fourth Loving prong with respect to the flu vaccine (e.g.,

Quackenbush-Baker, 2018 WL 1704523)—and that resolution of the issue can turn on the quality

19

While I also take note of Petitioner’s argument that epidemiologic evidence cannot conclusively refute a causation

theory that is otherwise reliable and/or scientifically plausible, this argument does not diminish the value such evidence

can have in appropriate cases. See Harris v. Sec’y of Health & Human Servs., No. 10–322V, 2014 WL 3159377, at

*11 (Fed. Cl. Spec. Mstr. June 10, 2014) (epidemiologic studies cannot absolutely refute causal connections, because

it is possible that a larger study could always detect an increased risk); Crutchfield v. Sec’y of Health & Human Servs.,

No. 09-0039V, 2014 WL 1665227, at *15 (Fed. Cl. Spec. Mstr. Apr. 7, 2014) (“[i]t is, in fact, always true that

epidemiologic studies can never prove definitively that Factor A never causes Condition B . . . [b]ut it is not the

Respondent’s burden in this case to prove that it is impossible that [the relevant vaccine] can cause [the alleged

injury]”). However, that does not mean such evidence has no value at all. See, e.g., Johnson v. Sec’y of Health &

Human Servs., No. 14-113V, 2017 WL 772534, at *19 (Fed. Cl. Spec. Mstr. Jan. 6, 2017) (“I generally find that such

[epidemiologic] evidence can be relevant in rebutting a petitioner’s arguments about the causal natures of different

vaccines”).

26

of expert opinions offered in a specific case, or extent of scientific and medical proof bulwarking

the theory. W.C., 100 Fed. Cl. at 455–56.20 As a result, I allow that a different outcome would be

reasonable, if different facts (bulwarked by a stronger causation theory) were offered to establish

that a claimant’s MS was greatly worsened by receipt of a flu vaccine.

However, even if I deem plausible, for sake of argument, the theory that the flu vaccine

could worsen a person’s MS course, I do not find on this record that Petitioner’s MS was worsened

by the vaccine.

Contrary to Dr. Napoli’s argument, the medical record does not suggest that L.Z.’s MS was

sufficiently worse post-vaccination to be deemed “fulminant.” Rather, it appears that although

after receiving the flu vaccine she did experience a transient MS relapse sufficiently debilitating

to seek medical intervention, her symptoms were echoes of the milder symptoms she had

experienced pre-vaccination over a lengthy period of time. They did not dramatically spike, and

therefore did not appear to Dr. Venkatesan, an expert with substantial experience in MS, to reflect

an alarming course distinguishable in severity from what other MS patients he has treated would

experience. Indeed, after the neurologic consult that Petitioner received in the fall of 2011 resulted

in her formal MS diagnosis, it does not appear she had any related medical issues at all for an

entire year, and did not even have another formally-diagnosed flare until the spring of 2014. See

Ex. 5 at 16; Ex. 7 at 6. This clinical record does not reflect an individual whose MS was set onto

a more destructive and debilitating course than would have been anticipated but for vaccination.

Beyond the above, there is no contemporaneous treater support for the contention that

L.Z.’s post-vaccination symptoms were vaccine-caused, or for the larger proposition that the

vaccine made her MS worse than it would have been. There is also no medical record evidence

suggesting an immediate reaction to vaccination, independent of the symptoms she unquestionably

experienced. I cannot conclude from this record that the flu vaccine had anything more than a

temporal relationship to Petitioner’s MS flare—and such a relationship is well understood in the

Program to have little evidentiary bearing when determining entitlement. See, e.g., LaLonde v.

Sec’y of Health & Human Servs., 746 F.3d 1334, 1341 (Fed. Cir. 2014) (“[a] temporal correlation

alone is not enough to demonstrate causation”).

CONCLUSION

Based upon the aforementioned analysis, I conclude that L.Z. has not carried her burden of

proof, and therefore I must DENY entitlement in this case.

20

The literature filed in the present matter does provide reliable support for the contention that a flu vaccine (or wild

virus exposure) could cause MS directly, as opposed to significantly aggravate a preexisting MS condition. See, e.g.,

Wucherpfennig at 702; First Napoli Rep. at 5.

27

In the absence of a timely-filed motion for review (see Appendix B to the Rules of the

Court), the Clerk shall enter judgment in accord with this decision.21

IT IS SO ORDERED.

/s/ Brian H. Corcoran

Brian H. Corcoran

Special Master

21

Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment by filing a joint notice renouncing their

right to seek review.

28