# In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS No. 16-949V (to be published)

* * * * * * * * * * * * * * * * * * * * * * * * * P.M., *

* Special Master Corcoran Petitioner, *

* Dated: September 24, 2019

v. *

* Multiple Sclerosis; Influenza

* Vaccine; Relapse; Significant SECRETARY OF HEALTH AND * Aggravation; Althen Prong I; Loving HUMAN SERVICES, * Prong Four; Treating Expert * Respondent. * * * * * * * * * * * * * * * * * * * * * * * * * * *

Ronald C. Homer , Conway, Homer, P.C., Bo ston, MA, for Petitioner.

Mallori B. Openchowski , U.S. Dep’t of Justice, Was hington, DC, for Respondent.

DECISION 1

On August 5, 2016, P.M. filed a petition seek ing compensation under the National Vaccine Injury Compensation Program (“Vaccine Program”) 2 alleging that he experienced the significant aggravation of his underlying mult iple sclerosis (“MS”)—a diagnos is which predated vaccination by three years—as a result of receiving the influe nza (“flu”) vaccine on October 9, 2014. Petition (“Pet.”) (ECF No. 1) at 1. An entitlement hear ing was held on June 7, 2018, in Washington, D.C., and the parties subsequently fi led post-hearing briefs and suppl emental reports, completing that process in late-April of 2019.

1 This Decision shall be posted on the C ourt of Federal Claims’ website in acco rdance with the E-Government Act of 2002, 44 U.S.C. § 3501 (2012)). This means that 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 Decision’s inclusion of certain kinds of confidenti al information. Specifi cally, under Vaccine Rule 18(b), each party has fourteen days within which to request redaction “of any information furnishe d by that party: (1) that is a trade secret or commercial or financial in substance and is privile ged 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 whole Decision will be available to the public. Id

.

2 The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3758, codified as amended at 42 U.S.C. §§ 300aa-10 thr ough 34 (2012) [hereinafter “Vaccine Act” or “the Act”]. Individual section references hereafter will be to § 300aa of the Act (but will omit that statutory prefix).2 The matter is finally ripe for resolution, and after review of the record and all submissions, I deny an entitlement award in this case. As disc ussed in greater detail below, although Petitioner succeeded in demonstrating that his preexisting MS became dramatically worse in a purely clinical
sense in the immediate weeks af ter vaccination, and offered a credible opinion from a treating expert to support his claim, the record does not permit the co nclusion that the flu vaccine can cause MS exacerbations, or that it did so in this case.

I. Factual Background

Pre-Vaccination MS Diagnosis

More than three years prior to the vaccination at issue, in 2011, P.M. was diagnosed with MS. The nature and basis for this diagnosis, along with Petitioner’s subseque nt disease course, has great significance in resolving this case.

The medical record establishe s that Petitioner’s symptoms dated back to 2003, when he first noticed pain in the left side of his face, scalp itch ing, numbness and weakness of the extremities, and ataxia. Ex. 6 at 12, 58. Indeed, a subsequent pain physician noted in a record from January 2012 that P.M. had previously been di agnosed with “unusual, right-sided temporal headaches,” in his twenties, even before his MS diagnosis. Ex. 5 at 2. A June 24, 2011 brain MRI showed multiple brain lesions, and then a follow-up MRI of the cervical spine (the upper portion of the spine closest to the brain) performed on June 29, 2011 revealed a “l arge, expansile” lesion at the C2 level (in addition to wh at was previously detected in the brain). Ex. 6 at 2, 6, 11. On August 16, 2011, P.M. was first diagnosed with “relapsing/remittin g MS” (“RRMS”) and prescribed appropriate medication. Id. at 57–60.

The following year, on January 18, 2012, Petitioner was treated wi th a cervical nerve root block for radicular pain that petitioner related to MS. E x. 16 at 13–14, 27 (Petitioner noting an eight month history of pain “sin ce I discovered I have MS”). He s ubsequently continued to follow a neurologist for his MS symp toms between 2012 and 2014. Petiti oner’s pain physician noted in this time period that his symptoms were severe enough to interfere with his work. Ex. 5 at 2. In addition, in June 2013, P.M.’s urol ogist described his MS as “pre tty severe,” ch aracterized by a “sudden fairly severe neurological deficit” and weakness and numbne ss of the left arm, although medication helped to stabili ze his condition. Ex. 10 at 4.

On January 30, 2014, P.M. saw neurologist Donna Graves, M.D. at the University of Texas Southwestern Medical Center in Dallas, Texas. At this time he reported “constant” nerve pain in the left face, neck, and chest, w ith itching and intermittent shock- like sensations in the face and scalp, and that these symptoms di d not improve despite medicinal tr eatment. Pet. Ex. 2 at 10. Dr. Graves specifically noted that a brain MRI performed on October 16, 2012, showed one new,3 additional lesion compared with the June 2011 study. Id. at 11. Dr. Graves did not perform a physical examination of petitioner, but assessed RRMS and neuropathic pain. Id. at 12. She recommended that Petitioner change his medici nes a bit, and recomme nded a repeat MRI and follow-up in six months. Id. at 13.

Six months later, on July 25, 2014, Petitioner presented to a new neurologist, Darin Okuda, M.D., also at the UT Southwestern Medical Ce nter. Pet. Ex. 2 at 54–56. (As discussed in great detail below, Dr. Okuda was also Petitioner’s sole testifying expert in this case). P.M. reported facial pain and pains radiating to the shoulders . Dr. Okuda did not perform a physical exam, and largely recommended that Petitioner maintain his existing treatments. Id. at 57. The next month, on August 26, 2014, P.M. saw his primary care physician (“PCP”) J. Shaun Murphy, M.D., reporting a three-week hist ory of severe left groin/testicular pain that radiated to his stomach during an erection. Ex. 4 at 1–2. Dr. Murphy descri bed Petitioner’s “MS symp toms” as left-sided neck, face, and arm pain, and diagnosed epididymitis, prescribing an antibiotic.

On September 24, 2014, P.M. went to an orthopedist, Kenneth Dauber, M.D., for evaluation of two-year history of intermittent righ t hip pain that was occu rring more frequently and interfering with exercise. Ex. 9 at 1–2. Pet itioner denied numbness and tingling but did report fatigue, and his examination and x-ray were un remarkable. Dr. Dauber di agnosed trochanteric bursitis, and prescribed Mobic (non- steroida l anti-inflammatory drug) and physical therapy. Id. at
5.

Vaccination And Subsequent MS Course

P.M. was thirty-two years-old when he re ceived a seasonal flu vaccination on October 9, 2014. Ex. 1 at 1. Seven days later, on October 16, 2014, he contacte d Dr. Okuda’s office by email and telephone, reporting new onset of numbness in hi s legs, and feelings of weakness for the last two days (or beginning October 14 th —five days after vaccination). Ex. 19 at 226–27, 230. Although Petitioner had then been planning to leave for vacation on October 19, 2014, he was advised to monitor his symptoms and go to an urgent care center if he started to experience burning pain or gait
abnormalities. He denied fever, cough, or any signs of infect ion but agreed to undergo laboratory testing and an MRI. Id. An MRI of the thoracic 3 level of the spine was performed on October 16, 2014. It revealed an approximately 1.2cm lesion in the ventral cord aro und the T6 level, with subtle enhancement (which could support the conclusion that the lesion was new) 4

3 The term “thoracic” pertains to the thorax (chest). Dorland’s Illustrated Medical Dictionary 1920 (32 ed. 2012) (hereinafter “ Dorland’s ”). The thoracic spine is the middle portion of th e spinal column in th e thoracic/chest region. Id.

4 As the experts explained at hearing (and consistent with what has been established in prior decisions), contrast enhancement involves injection of gadolinium into a patient, a substance that is readily detected by an MRI, and which will reveal active/new MS lesions (s ince it can leak across blood-brain barrier breaches). Tr. at 141–42; see also4 “suggestive of a focus of transverse myelitis, consistent with history of multip le sclerosis.” Ex. 2 at 23. (The results of this MRI, a nd its significance in light of Petit ioner’s claim, is a hotly-disputed issue that is explored be low in greater detail).

The next week, on October 23, 2014, P.M. saw Dr. Okuda, informing hi m of his onset on October 15, 2014, describing numbness from his stomach to his feet bilaterally, with weakness in his legs that was greater on the left than ri ght side. Ex. 2 at 5–6, 32–33. He had been placed on steroids “Saturday” [October 18, 2014] and was now “80% ” back to baseline, although he still was experiencing numbness at the wais t and in the right arm, erecti le dysfunction, significant fatigue, cognitive difficulties, imbalance, and weakness that prevented him from running. He denied recent illness but reported his receipt of the flu shot in early October. Id.

On examination, P.M. showed muscle weakness of the legs, left greater than right, sensory deficits in both legs, mild difficulty walking on heels and toes, slow foot tapping but normal
coordination. His medication was increased and a dditional MRIs were planned. Dr. Okuda at this time expressed the view that there was “a clear association between hi s recent vaccination and
disease recrudescence.” Id. at 5–6.

Petitioner continued to treat with Dr . Okuda through 2015 and beyond. Dr. Okuda maintained that petitioner suffered from RRMS, with notations of an aberra nt reaction to antigens
in the flu vaccine. See, e.g.

, Id. at 1, 45, 52–53; Ex. 19 at 130. A Fe bruary 2015 MRI (Ex. 2 at 17– 18) revealed no further advancem ent of the October 2014 spinal co rd lesion, with brain lesions first seen in 2012 also stable (in terms of size and appearance), suggesti ng that Petitioner’s MS was not progressing. Ex. 2 at 17–18. By the sp ring of 2015, Dr. Okuda was firmly proposing (relying on his substantial experience treating MS ge nerally and Petitioner specifically) that P.M.’s
exacerbation was vaccine-caused. Id. at 52–53.

Since mid-2015, P.M.’s condition has fluc tuated. Although he experienced some worsening of symptoms in August 2015, MRIs did not reveal the development of any new lesions. Ex. 19 at 72, 169–73. His ambulatory and other residua l motor deficits pers isted into early 2016, but he otherwise appeared to be copi ng and keeping up with his treatments. Id. at 130. The same was the case six months later, wi th ongoing weakness, fatigue, a nd motor difficul ties, but no new acute neurological events. Ex. 20 at 36–37. By the winter of 2018, P.M. be gan experiencing a new symptom impacting his vision and involving eye pain, resulting in a diagnosis of optic neuritis.

Ex. 29 at 1–9.

Maciel v. Sec'y of Health & Human Servs ., No. 15-362V, 2018 WL 6259230, at *2 n.5 (Fed. Cl. Spec. Mstr. Oct. 12, 2018).5 II. Expert Testimony

A. Dr. Darin Okuda

Dr. Okuda testified at heari ng for Petitioner, and also pr epared three expert reports. See Report, dated April 6, 2017, filed as Ex. 23 (ECF No. 15-1) (“First Okuda Rep.); Report, dated December 18, 2017, filed as Ex. 26 (ECF No. 27-1) (“Second Okuda Rep.”); Report, dated November 28, 2018, filed as Ex. 37 (ECF No. 57- 1) (“Third Okuda Rep.”). Dr. Okuda was personally familiar with Petitioner’s case, having served as Petitioner’s pr imary neurologic treater even before the vaccination in question. Dr. Okud a opined that there was an association between P.M.’s receipt of the flu vaccine and his subsequent clinical experi ence, and that in fact Petitioner experienced a nerve-demyelinating event that wors ened his preexisting MS due to vaccination. Tr. at 29, 36, 58.

Dr. Okuda is a board-certified neurologist cu rrently employed at the Clinical Center for Multiple Sclerosis in Dallas, Texas. Curriculum V itae of Dr. Okuda, filed as Ex. 24 (ECF No. 15- 2) (“Okuda CV”). He is a fellow in the Americ an Neurological Association, and he considers himself a specialist in MS, seeing approximate ly 2000 patients per year across the Dallas metropolitan area. Tr

. at 5–6, 11–12. He received his bachelo r’s, master’s, and medical degrees from the University of Hawaii. Okuda CV at 1. He then complete d a fellowship in neuroimmunology at the University of California, San Francisco. Id.

At present, Dr. Okuda is a professor of neur ology and neurotherapeutics at University of Texas – Southwest in Dallas, where he serves as director of the MS/neuroimmunology imaging program. Tr. at 7. He is also director of the “neuroinnovation” program, which he described as seeking to leverage technology with neuroscience in order to develop ne w and more effective neurodiagnostic tools (such as better thr ee-dimensional imaging of MS lesions). Id. at 7–8. He has performed research into new technologies de signed to better predic t MS’s advancement, specifically looking at the impact of lesion shape and structure, or the construc tion of more technologically-advanced hardware and softwa re used for imaging and testing generally. Id. at 13–
14. Dr. Okuda also has been involved in research evaluating the effectiveness of FDA-approved therapies for individuals with “r adiologic isolated syndrome,” or RIS (a diagnosis applicable to
individuals whose central nervous system (“CNS”) lesions, which w ould be indicative of MS, are discovered inadvertently, without the patient experiencing outward, t ypical MS symptoms). 5 Id. at

5 Dr. Okuda contrasted RIS with “clinically isolated sy ndrome,” or CIS, which presents the opposite set of circumstances (a patient with outward, recognizable MS symptoms who otherwise displays no evidence of imaging of CNS lesions). Tr. at 9–10. Individuals can live long lives without awareness that they possess the kinds of lesions indicative of MS (which can continue to a dvance without outward clinical symptoms). Id. at 11, 25–26, 42. CIS can be identified before the presence of lesions. Id. at 68.6 10, 12–13. He has published articles on RIS plus hi s work on 3-D imaging, and has won awards for technologic innovations as well. Id. at 15–16.

In forming an opinion in this case, Dr. Okuda emphasized th at his thought pr ocess did not occur simply in preparing to s upport Petitioner’s claim, but rath er in “real ti me”—beginning in October 2014, when Dr. Okuda was treating Pet itioner and witnessed th e purported immediate
after-effects of the flu vaccine. Tr . at 79. That opinion was in turn based on clinical experience plus background knowledge of the me dical and scientific field, alt hough Dr. Okuda noted that he
did consider additional lite rature that he researched as part of the process for preparing an actual written report. Id. at 79–80.

Dr. Okuda began his hearing te stimony by defining some medical terms relevant to this
case. He characterized MS as an autoimmune condition in volving immune system-mediated
inflammation in the CNS. Tr. at 44. It is the primary cause of neurol ogic impairment in young people, although it is more common in the female population than male, and also more prevalent
with Caucasians. Id. at 18, 37. MS most often has a relaps ing/remitting course, with it less commonly resolving completely (albeit leaving the person with defi cits) or taking a more severe progressive and downward course. Id. at 101–02, 106.

Diagnosing MS requires evaluati on of a combination of clinical and radiologic signs or symptoms. Clinically, treaters look for symptoms that would suggest the presence of CNS demyelination. Tr. at 19. From an imaging standpoint, MS is esta blished by dissemination of CNS lesions in “space and time,” taking into account the loca tion of the lesions, their appearance, and their recurrent development, all of which point to immunologic involvement. Id. at 19–20. In addition, MS can be diagnosed via evaluation of the results of paraclinical testing, including lumbar punctures to analyze cerebrospinal flui d, blood tests, and elec trophysiologic testing. Id. at 20. Although MS was historically as sociated with fairly severe out comes (often characterized by motor impairment that necessitated lifelong use of a wheelchair or walk er), advancements in
treatment have rendered its course more beni gn (although Dr. Okuda said it was not wholly understood why this was the case, noting that changes in the enviro nmental factors that had caused MS in the past may also be playing a role in making the disease less progressive). Id. at 43.

Dr. Okuda deemed MS as “principally driv en” by environmental factors, something he maintained had been borne out by twin studies. Tr . at 44–45. In particular, exposure to a direct infection or some other foreign contaminant coul d instigate the autoimmune process resulting in

MS. Id. at 46–48. He also allowed, however, that preexisting genetic susceptibility to autoimmunity might also be a factor in who experiences MS. Id. at 45. Some of the mechanistic processes that might me diate MS immunologically include molecular mimicry (in which antigens presented to the immune system resemble self protein sequences, causi ng the antibodies produced in response to those antigens to also attack the self structures) or sec ondary immune responses (in7 which an ongoing immune reaction is worsened or made chronic) lik e bystander activation. Id.

Dr. Okuda also provided a brief overview of a typical course of MS. The most benign course possible would be RIS with no clinical/out ward symptoms at all. Tr. at 43. Probably more than half of all MS patients have some sympto ms, but usually their overall course is light. Id. However, MS is often associated with symptoms relapse, which can be precipitated by a large variety of factors. Things like the failure to maintain medicinal treatments, the changing of kinds of medicine, or social stresso rs can all trigger MS flares. Id. at 30–33. He admitted that a flare trigger could not always be identified, but prop osed that, based on his experience, an educated guess was possible 30 to 40 percent of the time given th e context in which the flare occurred. Id.

at 75.

Turning to the facts of this case, Dr. Okuda be gan with an overview of Petitioner’s history. He first started treating P.M. in July 2014. Tr. at 17–18. P.M. had previously been diagnosed in 2011 with RRMS, which Dr. Okuda admitted meant that the Petitioner would be expected to experience later symptoms relapses. Id. at 18, 102. Petitioner’s symptoms had begun in 2003. Initial MRIs from 2011 revealed “typical” MS lesi ons and locations, with a clinical presentation also consistent with MS (e.g., weakne ss in limbs, sensory disturbances). Id. at 21; Ex. 6 at 11. By June 2011, Petitioner developed a single lesion located in the upper cervical spinal cord, reflecting that Petitioner’s MS largely constituted a “mix ed brain and spinal cord disease.” Tr. at 60; see also
id. at 20.

Despite its preexistence and lik elihood of recurrence, Dr. O kuda expressed the view that
Petitioner’s overall MS course be fore his vaccination in 2014 was mild—and likely to remain so. Tr. at 33. From a radiologic/imag ing standpoint, Petitioner’s pr e-vaccination “overall lesion
burden or extent of involvement was generally stable and not subs tantial,” suggesting his future course was not likely to be severe. Id . at 21. Dr. Okuda did acknowledge the identific ation of the new brain lesion in 2012, but deemed it asymptomat ic, and possibly attribut able to a “technical issue” from the perform ance of the MRI. Id. at 24–25, discussing Ex. 2 at 258 (October 17, 2012 MRI). Clinically, before vaccination P.M. was (i n Dr. Okuda’s view) doing well, since he was fully active at work and ambulatory, with sympto ms that were (at that time) mostly sensory in nature and impact and which were responsive to medicinal treatment. Id. at 24, 26. Dr. Okuda deemed especially significant the fact that Petitioner’s “expanded disability status scale” (“EDSS”) 6 score was zero or close to it. Id. at 22–23.

After vaccination, however, Petitioner became mu ch worse in Dr. Okuda’s estimate. Tr. at

6 EDSS is a diagnostic score used in MS to “gauge the clinical well-being of a given individual. Tr. at 22–23. A zero means no impairment, while a seven reflects being confined 50 percent to a wheelchair. Tr. at 23; see also J. Kurtzke, Historical and Clinical Perspectives of the Expanded Disability Status Scale , 31 Neuroepidemiology 1, 6 (2008), filed as Ex. 26, Tab A (ECF No. 27-1).8 36. As noted above, P.M. had contacted Dr. O kuda’s office on Octobe r 16, 2014, indicating that he had begun to experience new symptoms two da ys earlier (and thus not even a week from the

date of vaccination on October 9 th ). Id. at 66. The imaging that was subsequently performed ( see Ex. 3 at 3) revealed a lesion at the T6 level of th e thoracic spine that Dr. Okuda felt was consistent with P.M.’s symptoms. Id. at 27, 67. The lesion was also enhanc ing, revealing its recent nature. Id. at 67. Dr. Okuda did not actually see Petitione r for examination until October 23, 2014, at which time he presented with things Dr. Okuda deemed “r eferable to the spinal cord”— weakness in both legs and sensory disturbances lik e numbing and tingling, plus pyram idal muscle weakness. Tr. at 26–28. Thereafter, P.M.’s recovery has been in complete, with physical symptoms including fatigue, discomfort, low energy leve ls, lack of bladder control, and other things (along with a corroborating EDSS score of 6, in co ntrast to his previous zero)—all of which Dr. Okuda attributed
to the T6 lesion discovered in October 2014. Tr. at 28–29.

Dr. Okuda also commented on P.M.’s subseque nt course into 2015 and beyond. A February 2015 MRI (Ex. 2 at 17–18) revealed no further a dvancement of the October 2014 spinal cord lesion, with brain lesions first seen in 2012 also st able (in terms of size and appearance), as well as no other new enhancing lesions. Tr. at 35. At least at this time as revealed by MRI, Petitioner’s MS was not progressing. Id. at 35–36. By 2018, Petitioner did suffer a new clinical attack, in the form of an episode of optic neuritis. Id. at 34. Dr. Okuda admitted, ho wever, that he could not directly link this later relaps e to the October 2014 vaccination, although he allowed for the possibility that once the flu vaccine had “let the horse ou t of the barn,” any fu rther relapses could
be connected. Id. at 64–65.

A significant dispute between the parties in th is case is the proper interpretation of the October 16, 2014 thoracic spine MRI, and in particular whether the fact that the ne w lesion seen at that time was enhancing suggests when that lesion first arose. Dr . Okuda admitted that an enhancing lesion is primarily evid ence of the existence of an ongoing acute process, the start of which is difficult to ascertain given existing scie nce. Tr. at 67 (“[A]n MS lesion could enhance for up to one year.”); see also id. at 187–88. The presence of enhancement would typically allow the
conclusion that a lesion had arisen w eeks to a month befo re its detection. Id. at 22. In addition, Dr. Okuda admitted that (consistent with the CIS/RIS division) “we are able to pick up disease well before a lesion enhances,” while at the same time lesions can ex ist or develop unaccompanied by
symptoms. Id. at 185–86. He, however, expressed the opinion that a lesion could arise (and hence be detectible on MRI) in as little as one day, and thus maintained the view that the lesion that was observed on October 16, 2014 more likel y than not arose post-vaccination. Id. at 67–69, 186–87,
189–90.

Dr. Okuda went on to provide his views on vaccine causation specifically. First, he maintained that vaccines can pr oduce MS relapses. He deemed it a rare occurrence generally, but said he had personally encountered a handful of instan ces in his medical car eer in which he had9 seen a vaccine associated with some kind of other neurologic injury, such as Guillain-Barré syndrome, with only one other instance he coul d recall involving MS. Tr . at 30, 76–77. To support his contentions, Dr. Okuda offered some items of litera ture that reveal th e relationship between infectious pathogens and MS, t hus allowing for the inference th at vaccination (which apes the infectious process, albeit on a fa r more limited scale) could propaga te disease in a similar fashion. See, e.g. , Tr. at 56 (discussing J. Libbey, et al., Role of Pathogens in Multiple Sclerosis , 33 Int’l. Rev. of Immunology 266–83 (2014)), Filed as Ex. 23 Ta b C (ECF No. 44-3)). He also referenced one article discussing the known relationshi p between other autoimmune conditions and vaccination (although it noted a proposed associati on between MS and the Hepatitis B vaccine had not been confirmed). Tr. at 56 (discussing S. Salemi, et al., Could Autoimmunity be Induced by

Vaccination? , 29 Int’l Rev. Immunology 247–69 (2010), file d as Ex. 23 Tab E (ECF No. 44-5)). Dr. Okuda acknowledged, however, that he offered no direct proof a ssociating the flu vaccine with MS, allowing that relapse could not always be attributed to a prior vaccination. Id. at 87, 92. Nevertheless, Dr. Okuda felt that a vaccine coul d be causal of a relapse at least on a “one-off” basis, and that at bottom he saw no other explan ation for P.M.’s relapse bu t his prior receipt of the
flu vaccine under the circumstances of this case. Id. at 29–30, 51–52, 58–59, 87.

As for potential biologic mechanisms explaini ng how the flu vaccine might produce an MS relapse, Dr. Okuda offered several alternativ es. He noted that molecular mimicry—a wellunderstood autoimmune mechanism often invoked in vaccine injury cases, in which foreign antigens (whether presented by inf ection or vaccine) resemble, or “ mimic,” self protein sequences, causing antibodies produced in resp onse to the antigen to also atta ck the self—was in his view generally helpful in explaining CNS demyelinating events. Tr. at 46, 49. In addition, secondary mechanisms like bystander activation, in which prim ed immune cells nonspecific to a particular antigen causing a primary immune response are ne vertheless stimulated, thereby exacerbating and encouraging the initial response, might also be the engine of a vaccine-caused MS relapse. Id. at
46. Dr. Okuda admitted he could not in this cas e identify the specific ta rget of the proposed autoimmune response, or that there was simila rity between flu vaccin e antigens and some CNS
structure sufficient for mo lecular mimicry to occur. Id. at 86–87. He nevertheless insisted that “some antigen” in the flu vaccine was responsibl e, and that an autoimm une process could unfold through a combination of mechanisms , which could in turn be the re sult of the vaccine’s specific formulation or design. Id. at 86; see also id. at 48.

To support the above, Dr. Okuda offered some li terature that he main tained demonstrated how these potential mechanisms might initiate an autoimmune process resulting in an MS relapse. Tr. at 56–57 (discussing R. Fujinami, et al., Molecular Mimicry, Bystander Activation, or Viral Persistence: Infections and Autoimmune Disease , 19 Clinical Microbiology Rev. 80 (Jan. 2006), filed as Ex. 23 Tab D (ECF No. 44-4); A. Bar-Or, et al., Abnormal B-Cell Cytokine Responses a Trigger of T-Cell-Mediated Disease in MS? 67 Annals Neurology 452 (20 10), filed as Ex. 23 Tab F (ECF No. 44-6) (excited chemokine res ponse can mediate bystander activation of10 proinflammatory T cells, leading to MS relaps e) (“Bar-Or”). Important ly, however, Dr. Okuda
also admitted that these articles did not link vaccination to the proposed biologic processes. See,

e.g. , Bar-Or, supra , at 458 (addressing only the propensity of wild infection to trigger new MS disease activity via the evalua ted process). Dr. Okuda acknowle dged that it remained unclear whether the same mechanisms for how MS might in itiate could equally be applied to exacerbation
cases. Tr. at 50. But he stressed hi s belief that, given th at the “underpinning” of MS’s pathogenesis is likely autoimmune, there is no reason not to exp ect that exacerbation of an existing case of MS would proceed in the sa me mechanistic manner. Id.

Second, Dr. Okuda emphasized his determination that the flu vaccine did in fact produce P.M.’s MS relapse, beginning within a week of vaccination. He deemed the onset of symptoms
close in time to vaccination a “c lear inflection point,” making it di fficult for him not to associate the two. Tr. at 54. There was no question that Petit ioner’s overall health, motor skills, and mood
took a turn for the worse after the vaccination. Id. at 34. He also noted there appeared to be no other explanations for the relapse, li ke some unexpected social stressors. Id. at 75.

In the course of discussing Pe titioner’s immediate post-vaccination change in health, Dr.
Okuda was asked about record ev idence suggesting the existence of related symptoms before vaccination (some of which Dr. Okuda might not ha ve factored into his opinion). For example, Respondent asked him about Petitio ner’s August 2014 claim of testic ular pain when visiting his PCP—something that was not referenced in the history Dr. Okuda prepar ed in October 2014. Tr.
at 83–84. Dr. Okuda allowed that th e event might have some signifi cance, although he also pointed out that the effects of a demyel inating lesion in the thoracic regi on of the spinal cord would not likely locate to the testes in terms of pain or other symptoms. Id. at 83. He also admitted that his
consideration of P.M.’s histor y as of October 2014 might (due to his own hospital’s electronic records gathering system) have not taken into account Petitioner’s visit to the orthopedist for treatment of hip pain, although he again distingu ished it from the kind of symptoms he would associate with a CNS injury to the brain or spine. Id. at 73, 81–82, 99–100. Although a sudden onset of hip pain might, in Dr. Okuda’s estimation, be attribut able to a CNS issu e, in this case Petitioner’s hip problems have reportedly existed for some time, reducing the likelihood that they were associated with his October symptoms. Id. at 101.

Dr. Okuda also addressed the timing of P.M.’s post-vaccination symp toms onset, which he agreed (based on Petitioner’s symptoms complaint a nd date of MRI detection of the T6 lesion) had occurred within five days of v accination. Tr. at 51. Dr . Okuda deemed anything within a month of a trigger as medically reasonable, especially sinc e (in his understanding) symptoms could take up
to several months to manifest. Id. He did, however, also maintain that where a vaccine was the trigger for an MS relapse, he would only be comfortable with a timeframe of no more than a month.
Id. at 84. He added that even a reaction within 24 hours was in his view medically acceptable, based on the innate immune response to vaccination (which could cause an11 increase in body temperature), but added that this sort of reaction was akin to an MS “pseudoexacerbation,” which can also occur after a common in fection, and is distinguishable from a true MS relapse of the kind Petitioner experienced. Id. at 84–86. He ultimately proposed that P.M.’s lesion most likely formed between one day to a week after vaccination. Id. at 86.

Dr. Okuda’s testimony next touched on the la rger question of whether Petitioner’s MS course had been worsened by vaccination, answering that question in the affirmative. Tr. at 99, 102. He began with a discussion of “Kurtzke’s Ru le of Five”—a scale employed in the treatment of MS that rests on the assumption that a patient’s first five years of clini cal status “may provide great insights” into what the patient will e xperience with the disease in later years. Id. at 37; J. Kurtzke, Historical and Clinical Perspectives of the Expanded Disability Status Scale , 31 Neuroepidemiology 1, 1, 7 (2008), filed as Ex. 26, Tab A (ECF No. 27-1). Thus, a patient who does not experience significant moto r or cerebellar involvement in his disease course is unlikely to experience symptoms related to either later on. Id. In this case, P.M. did have motor impairment as of 2011 (although he recovered), but did not have cereb ellar involvement. Id. at 38. Overall, Dr. Okuda deemed Petitioner’s pre-vaccination course milder than post. First Okuda Rep. at 2–4.

Dr. Okuda also talked about “l esion burden,” i.e. the number of lesions an MS patient has and what that predicts about hi s likely prognosis. In support, he c ited an item of literature. L. Fisniku, et al., Disability and T 2 MRI Lesions: a 20-Year Follow-Up of Patients with Relapse Onset of Multiple Sclerosis, 131 Brain 808 (2008), filed as Ex. 26, Tab B (ECF No. 27-1) (the “Queen Square” Study). The Queen Square Study, Dr. Okuda maintained, establishe d that the number of
MS lesions an individual had was associated with their long-term outcome—and in particular the
likelihood that their disease course w ould be progressive rather than of lesser risk of future attack and impairment. Tr. at 38–39. Here, he proposed th at the relatively small number of lesions P.M. had before vaccination did not predict a notably adverse outcome. Id. at 29, 36, 38. Dr. Okuda acknowledged that the Queen Square Study involved a relatively small patient sample, and also did not take into account the impact of spinal cord impairment (a fact or more directly linked to poor outcomes—especially in this case), but still d eemed it overall a reas onable study given the difficulties in obtaining good data relevant to the subject. Id. at 38–39.

Complementing the above, Dr. Okuda discussed a different item of literature he coauthored that suggested cervical lesions in an MS patient pred icted thoracic lesion involvement. Tr. at 39–42; L. Hua, et al., Thoracic Spinal Cord Lesions are Influ enced by the Degree of Cervical Spine Involvement in Multiple Sclerosis, 53 Spinal Cord 520 (2015), filed as Ex. 26, Tab C (ECF No. 45-6) (“Hua”). Hua evaluated 126 MS patients, most of whom suffered from RRMS, and all of whom had MRI scans performe d in the brain, cervi cal, and thoracic spin e regions (although the scan evidence reviewed came from a single scanning session rather than from scans performed over the course of the patient ’s illness history). Hua, supra , at 522. Hua’s authors specifically observed that thoracic lesions were more likely in patients with two or mo re cervical lesions, as12 opposed to brain-located lesions—a lthough they also concluded that the risk of a thoracic lesion existed simply with the presence of a single cervical lesion (which Petitioner unquestionably had).
Id. at 523–24. Dr. Okuda, however, interpreted Hua’s findings as suggesting that “the chance of [Petitioner] having further disease within the thoracic spinal co rd [was] low” based on the single cervical lesion (even though Hua does not expressl y make this associatio n). Second Okuda Rep.

at 2.

Dr. Okuda also commented on certain articles , some of which Respondent offered (like large-scale epidemiologic studies), that arguably underm ine Petitioner’s claim that the flu vaccine exacerbated his MS. In so doing, he agreed that av ailable epidemiologic evidence largely confirms the overall safety of va ccination for MS patients , as reflected in the recommendations of the National MS Society Tr. at 92, 104. Indeed, he allo wed not only that receiving the flu vaccine may be especially important for MS patients (whose treatment therapies might weaken their immune systems and thus make them suscep tible to certain infections that vaccination could help prevent),
but also that vaccin es might in fact protect against future symptom flares. Id. at 93, 105. He maintained, however, that these ki nds of studies were not sufficiently powered to detect the rare occurrence of a post-vaccina tion adverse event or possibility of aggravation, and also have their own biases. Tr. at 52–54, 57, 94–95.

One such article goes directly to Petitioner’s contention—that the flu vaccine caused his relapse—but concludes the opposite . C. Confavreux, et al., Vaccinations and the Risk of Relapse in Multiple Sclerosis , 344 New Eng. J. Med. 319, 319, 324 (2001) , filed as Ex. F (ECF No. 30-2) (“Confavreux”). Confavreux examined 643 MS patie nts (fifteen percent of whom reported having been vaccinated during the preceding twelve months ) to evaluate the relativ e risk of a vaccinerelated relapse, determining that a vaccinated in dividual had a reduced chance of relapse—and its authors expressed high confidence in the statistica l accuracy of their findings in concluding that vaccinations did not appear to increase the risk of relapse in MS patients. Id. at 324–25. Another article, published around the same time as Confavreux, pe rformed a general literature search of studies looking into the purported associati on between vaccination an d MS, finding “strong
evidence” that the flu vaccine did not result in MS exacerbation. O. Rutschmann, et al., Immunization and MS: A Summary of Publ ished Evidence and Recommendations, 59 Neurology 1837, 1837 (2002), filed as Ex. J (ECF No. 30-6) (“Rutschmann”).

Dr. Okuda, however, disputed the application of such literature in th is case, arguing that (despite Confavreux’s ov erall large cohort sample size) the ev aluated patient sample would likely not have included P.M., due to his purported genetic susceptibility (a lthough Dr. Okuda tacitly acknowledged that Petitioner’s ethn ic heritage and gender did not co mpletely set him aside as an outlier under the circumstances). Tr. at 89–91. He also later observed that only 135 patients of the
total cohort could be confirmed to have had a v accine in the 12 months prior to relapse— with only 15 patients receiving a vaccine within one to two months of relapse (precisely the13 relevant time period herein), ther eby greatly reducing the statistical strength of the study’s overall findings when applied to this case. Tr. at 94, citing Confavreux, supra , at 324 Table 2. Dr. Okuda later pointed out that Rutschmann specifically stated that it could not “definitely exclude a slight
risk of increase of exacerbati on after [flu vaccine] immunization” (although it also concludes in the next paragraph that “there is definitive evidence against a substantial increased risk of MS exacerbation after influenza vaccine”). Tr. at 96, citing Rutschmann, supra , at 1840 (emphasis added).

B. Dr. Timothy Vartanian

Dr. Vartanian filed three reports for Respondent and te stified at hearing. Report, dated June 9, 2017, filed as Ex. C (ECF No. 19-1) (“First Vartanian Rep.”); Report, dated April 20, 2018, filed as Ex. K (ECF No. 43-1) (“Second Vartania n Rep.”); Report, dated April 22, 2019, filed as Ex. L (ECF No. 70-1) (“Third Vartanian Rep.”). He opined that P.M.’s pre-vaccination MS was not exacerbated by the flu vaccine, and specifi cally that the newly-discovered October 2014 thoracic lesion most likely predated vaccination by weeks. Tr. at 115–16, 145.

Dr. Vartanian received his Ph.D. and medical degree from the University of Chicago after obtaining his bachelor’s degree from Oakland University. Curriculum Vitae of Dr. Vartanian, dated Oct. 16, 2013, filed as Ex. D (ECF No. 19) (“Vartanian CV”). He then completed an internship at Brigham and Women’s Hospital, a residency in neurology at Massachusetts General Hospital, and fellowships at Beth Israel Hospital and Harvard Me dical School. Vart anian CV at 2.
Dr. Vartanian is board certified in adult neurolo gy and is a member of the American Society of
Neuroscientists. Id. at 3. He has published numerous ar ticles on neurologic matters. Id. at 15–21.

Dr. Vartanian is a professor of neurology at Weill Cornell Medical College, and the director of the MS and demyelinating diseases unit at New York Presbyterian Hospital. Tr. at 109. Consistent with his certifications, he is a specia list in MS as well as other autoimmune diseases implicating or involving the CNS. Id. at 110. His practice includes a mi x of research, teaching, and clinical work, and he estimates he presently is overseeing the cases of 500 to 600 patients. Id. at 111–12. He has performed research aimed at unde rstanding CNS lesion fo rmation and myelin repair, and has been published often. Id. at 112–14.

Much like Dr. Okuda, Dr. Vartanian devoted some time at heari ng to defining medical terms and concepts relevant to Petitioner’s claim. He stated that the co mmon, relapsing/remitting form of MS that P.M. was diagnosed with is ch aracterized by unpredictable swings that can vary in severity and length. Tr. at 116–17, 157, 183. He also echoed Dr. Okuda’s statements about RIS versus CIS, agreeing that MRI evidence of a di sease process can advance without corresponding symptoms, and that lesion location was highl y relevant to symptoms presentation. Id. at 117 (explaining that “[n]ot all lesions are clinically apparent.”); see also id. at 142–43. He14 also noted, however, that in his experience newl y-formed lesions tended not to be immediately symptomatic. Id. at 143.

Dr. Vartanian agreed that environmental fa ctors can trigger MS relapses, although he stressed that medical science cannot identify th e precise “agent” for relapse, and disputed Dr. Okuda’s contention that a triggeri ng factor can be identified even a third of the time. Tr. at 121– 22, 130, 161. On the contrary, he stated th at medical science typically could not explain what caused a new lesion or symptoms flare (consistent with the fact that patients can have numerous new lesions with no symptoms at all). Id. at 147. He denied, however, that the medical community considers vaccines to be a plau sible causal factor, pointing out the consensus among medical professionals and MS-oriented professional societie s of the safety of va ccination for MS patients (although he agreed vaccination was stil l a relevant fact to take into account in assessing a patient’s medical history). Tr. at 121, 123. At best, he proposed that the only trustworthy identifiable explanations for relapses are the “rebound effect ” if a patient is taken off certain MS drug treatments, or the results of stress. Id. at 122. He also observed that, re gardless of a flare’s proposed etiology, it would be treated in the same manner. Id.

Dr. Vartanian discussed the general utility of MRIs, and he specifically explained the use of enhancement in identifying activ e brain or spinal lesions. Tr. at 141–42. He maintained that a lesion that enhances in imaging is evidence of “massive destruction” sufficient to breach the bloodbrain barrier, such as after a stroke or the effects of a brain tumor. Id. at 142, 180. But, because enhancement “marks the apex of lesion,” it is likel y that a lesion that is observed via enhancement has been forming for some time before its observation on MRI. Id. at 144. As a result, the medical community (in Dr. Vartanian’s es timation) deems lesions to have likely formed weeks to even months prior to the time they enhance. Id. at 142, 145. This is true rega rdless of whether the lesion is located on the spine or in the brain. Id. at 144.

Dr. Vartanian’s opinion accepted the accuracy of P.M.’s RRMS diagnosis (Tr. at 131– 32), but he considered certain evidence from Petitioner’s pre-vaccination medical history as consistent
with his later disease course. The initial brain MRI (perform ed on Petitioner on June 24, 2011—a few days after he reported symptoms) revealed br ain and medulla lesions that were not initially deemed enhancing (thus suggesting that they were fairly old). Tr. at 132; Ex. 6 at 11. 7 Stressing the importance of “neuroanatomical localization” in neurology (i.e., the concept that different areas of the CNS control or impact different nerve sy stems in various parts of the body), Dr. Vartanian found it unsurprising that these lesi ons were primarily affecting “s ensory pathways.” Tr. at 134.

7 Dr. Vartanian stressed at hearing that his MRI comments were based not on direct review of the images themselves but the medical record history notations of the radiologists and neurologists who performed or analyzed them. Tr. at 137. I later ordered both parties to have their experts review the original images and file pos t-trial supplemental reports. Those reports are discussed below.15 However, the second MRI, performed on J une 29, 2011 (which revealed a nonenhancing, “expansile” 8 cervical spinal cord lesion close to the brai n’s base), prompted the radiologist to look again at the earlier MRI, and in so doing noticed “some minimal patchy enhancement” for the previously-discovered brain lesions. Tr

. at 133–35; Ex. 6 at 7. Although the radiologist proposed
that the lack of enhancement seen in the second MR I could be “due to the limitations of the study,”
Dr. Vartanian found the enhanci ng now identified on a second re view “interesting,” because it suggested to him that th e observed lesions likely predated the symptoms that prompted Petitioner to seek medical intervention at this time (and which led to performance of the MRI in the first place). Tr. at 135. Dr. Vartanian based this asse rtion on the view that “most contrast-enhancing
lesions last for a few weeks.” Id. at 136–37.

Petitioner’s course in the subse quent three-plus year period pr ior to vaccination was, in Dr. Vartanian’s estimation, best charact erized as “active” rather than “c linically silent.” Tr. at 137. He
noted that an October 2012 MRI revealed a new non-enhancing brain lesion, for example. Id. at 138; Ex. 2 at 67. He admitted that Petitioner was as ymptomatic from a clini cal standpoint for much
of this time. Id. at 139, 153. Dr. Vartanian, however, deemed that not uncommon for someone with overall ongoing MS, especially given the ra diologic evidence of additional lesions. Id. at 139–40 (“[T]he disease is never gone.”).

In addition, and contrary to Dr. Okuda, Dr. Vartanian expressed the opinion that P.M. was experiencing “a fairly signifi cant lesion burden” before Oct ober 2014. Tr. at 137. He later acknowledged (as stated in one of his reports) that even a total number of 4-9 lesions was in fact not a significant sum (Tr. at 155–56 ; Second Vartanian Rep. at 2). Bu t, Dr. Vartanian stressed that
lesion burden should also be deem ed a function of volume and severi ty in addition to pure number, and when those factors were taken into account, the record allowed for the conclusion that
Petitioner’s burden was actua lly “moderate to heavy.” Id. at 155. To support this contention, Dr. Vartanian noted that pre-vaccinat ion records described several “hyperintense” lesions, which to him meant signifi cant axon damage. Id. ; Ex. 2 at 67. He also stressed the size of the cervical lesion observed in 2011 as establishing ev idence of a somewhat severe pre- vaccination course. Tr. at 136.

Moving on to the post-vaccination period, Dr. Vartanian consider ed what the October 2014 MRI established. He agreed it reve aled the existence of the T6 thoracic lesi on (which he proposed was located around the lower part of the sternum), but maintained that de spite enhancement, the
lesion’s date of formation c ould not be pinpointed. Tr. at 144–45. He suggested, however, that it most likely “formed weeks befo re” its discovery (and hen ce before the October 9, 2014 vaccination). Id. He based this opinion in part on research he claimed establishes that lesion genesis typically predates enhancement by weeks to months, as well as th e concept that enhancement does

8 Dr. Vartanian defined expansile to mean “it’s occupying sp ace.” Tr. at 136.16 not shed light on the date a lesion came into exis tence, although he admitte d he had not set forth this aspect of his opinion in his reports, nor c ould he offer literature subs tantiating this proposition.
Id. at 146, 173, 180. He also discounted the importance of the lesion’s location as suggestive of its etiology, noting that thoraci c spinal cord lesions were not unco mmon in MS, and th at the existence of a single spinal cord lesion (here, the cervical lesion observe d in June 2011) suggested more were possible—even in different parts of the spinal cord, as observed in Hua. Id. at 147–48. 9

Besides commenting on the medical record, Dr. Vartanian opined that the flu vaccine could not likely produce MS relapses or symptoms flares. Tr. at 168. A lthough he accepted that vaccines have been credibly associated with certain advers e events (for example, the rabies vaccine with acute demyelinating encephalomyelitis, or earlier versions of the flu va ccine and Guillain-Barré syndrome), he denied that there was sufficient reliable scientific or medical evidence to link the flu vaccine to CNS demyelin ating events common to MS. Id. at 167–68, 170. In so testifying, he
noted that even if certain bi ologic mechanisms proposed by Dr . Okuda, like molecular mimicry, were reasonably associated with autoimmune processes resulting in other neurologic diseases, there was inadequate medical or scientific eviden ce to link them to the process that resulted in CNS demyelination. Id. at 169–70, 174. He deemed other envir onmental factors (for example, genetic variants among different ethn ic or nationality group s) as more likely to contribute to the pathogenesis of MS. Id. at 162 (discussing MS epidemic in Faroe Islands after British began occupation, when merely by the presence of British individuals, native islanders were exposed to uncommon viral infections to which they were susceptible, having not been exposed before).

Dr. Vartanian rejected the proposition that vaccination and wild virus infection were analytically interchangeab le for purposes of establishing cau sation. Tr. at 130. In so opining, he allowed that some kinds of infections (mycoplas ma or pneumonia) might cr edibly be associated with MS exacerbation, but denied that the influenza virus could also be included in that group. Id.
at 129. He also noted that the manner in whic h infection propagates in the body, via “multiple epitopes” that elicit more immune responses than vaccination, and through di rect tissue damage as well, “sets up a nidus for colonization and infec tion” and “also provides a more robust environment for the immune response,” making it a “much more dramatic immune stimulator than a vaccine.”
Id. at 131, 163, 165–66 (direct infection can cause “multifoca l inflammatory demy elination”). He opined that unlike vaccination, inf ection can directly cause breach of the blood-brain barrier “in the absence of an immune response,” leading to a secondary inflammatory immune response (which he did allow could be autoimmune in nature). Tr. at 163, 166. The same is true, he maintained, for lesion formation it self, which can be associated with initial blood-brain barrier openings (although they may not be initi ally detectable via enhancement). Id. at 163–64 (MS may

9 Dr. Vartanian also disc ussed some of Petitioner’s more recent medical records. He noted that P.M. experienced an MS flare in his optic nerve in 2018, resulting in neuritis sy mptoms in the ocular region for the first time. Tr. at 149– 50. He characterized this location as no t uncommon for an MS flare, however, and denied that it was the natural result of, or otherwise associated with, the 2014 thoracic lesion. Id. at 150.17 directly begin with “some insu lt to the blood-brain barrier,” rather than through an immune response).

To support his contention that the flu vaccine could not likely produce MS relapses, Dr.
Vartanian offered several items of scientific a nd medical literature, like Confavreux. Confavreux was a 2001 clinical study aimed at evaluating whet her there was a link between vaccination of any kind and MS flares. Confavreux, supra , at 319. In Dr Vartanian’s view, the fact that it was a “crossover” study (in which patients served as their own control) 10 made it sufficiently powered to
be reliable even if the overall sa mple size pertinent to the present case was not particularly large. Id. at 319–20; Tr.at 123–24. Confavreux ev aluated over a year-long period the medical histories of MS patients with no rela pse who had one thereafter , evaluating their relapses in two-month periods from vaccination, in comparison with two-months periods w ithout prior vaccina tion, and found no higher incidence of relapse. Confavreux, supra , at 320, 324; Tr. at 124–25. Dr. Vartanian emphasized that the eight-week ri sk interval used in Confavre ux to look for pos t-vaccination relapse was particularly “liberal,” as it would have caught almost any ad verse event that could arguably be vaccine-caused. Tr. at 125.

In addition to Confavreux, Dr. Vartanian offered another clin ical study that sought to directly evaluate the relationshi p between vaccines and MS relapse. B. Michielsens, et al., Serial Magnetic Resonance Imaging Studies With Para magnetic Contrast Me dium: Assessment of Disease Activity in Patients with Multiple Scle rosis Before and After Influenza Vaccination , 30 Eur. Neurology 258 (1990), filed as Ex. H (ECF No. 30-4) (“Michielsens”). Michielsens looked at MRIs for 11 patients with relaps ing-remitting MS within three w eeks of vaccination both before and after (a period of time consiste nt with the alleged timeframe in th is case), to assess the presence of post-vaccination flares. Tr. at 126–27, Michielsens, supra , at 258. The study found no higher interval of new/contrast-enhancing lesions post-vaccination. Tr. at 127, Michielsens, supra , at 259. Dr. Vartanian accepted, however, that an 11-patient sample size was likely too small to deem the study’s conclusions statistica lly significant. Tr. at 172–73.

Dr. Vartanian also cited literature review articles summarizing the state of medical
literature on the association between vaccinati on and MS relapse, none of which supported
Petitioner’s claim. See generally Rutschmann, supra , 1837; M. Mail and, et al., Vaccines and Multiple Sclerosis: A Systematic Review , 264 J. Neurology 1035 (2017), filed as Ex. G (ECF No. 30-3) (“Mailand”). Mailand, published just ove r 15 years after Confavreux, confirmed that no studies since that time had demonstrated a pl ausible association between vaccination and MS flares. Tr. at 126; Mailand, supra , at 1036. Rutschmann was publishe d in 2002, but had the same
focus and reached the same conclu sions (albeit based on fewer item s of literature than Mailand).

10 A crossover, or cross-sectional, analysis is a statistical tool for understanding the relationship between two or more variables in which each data point is associated with a different unit of observation meas ured at a specific point in time. Reference Manual on Scientific Evidence 352, 354 (3d ed. 2011).18 Rutschmann, supra , at 1840. Dr. Vartanian deemed such review articles a persuasive response to criticism focused on the scope of reliability of indivi dual clinical studies, like Confavreux, given
that the review articles took into account so many individual pieces of literature (while noting the absence of subsequent studies that would negate earlier determinations about the absence of a vaccine-MS exacerbation relationship). Tr. at 128. He acknowledged, however, that some of these
articles referenced studies that were somewhat supportive of Petitioner’s position. See, e.g. , Tr. at 171 (citing Rutschmann, supra , at 1841, Table 2) (citing study finding that five percent of 80 MS patients who experienced relapse did so with in six weeks of receipt of flu vaccine)).

Finally, regarding Petitioner’s comparative state both pre- and pos t-vaccination, Dr.
Vartanian admitted that the October 2014 thoracic lesion was directly connected to Petitioner’s “permanent residual symptoms,” a nd had contributed to his disabl ed state and risk of future disability simply due to the a ssociated scarring. Tr. at 156–57. But he maintained that Petitioner’s
overall disease course was neve rtheless not outside what would be expected in many MS cases.

Tr. at 151. 11 He also did not give the same importance to the EDSS score Petitioner had received before vaccination (which Dr. Okuda felt predicted a mild overall disease course), deeming the scale not a “great tool” for meas uring the “functional cap abilities” of a patient, especially since it was weighted for assessing motor function/ambu lation. Tr. at 118–19, 149 (no ting that EDSS “fell
out of favor” because it did not ta ke into account the impact of cognitive dysfunction attributable to brain lesions); see also id. at 179. He similarly discounted the value of the Kurtzke “five year rule” for predicting MS course, terming it only a “partial indicator” that did not preclude relapse even for patients doing well. Id. at 148. Ultimately, the disease course that an MS patient would experience is primarily the product of where a new lesion “lands,” i.e. whether it locates in an important place neurologically. Id. at 149.

III. Post-Hearing Expert Reports

As noted above, neither expert had the opportu nity to review the actual MRI images in formulating their opinions, relying instead on contemporaneous medical record notations or observations (and thus secondary sources). I theref ore ordered the parties to have their experts directly evaluate the relevant MRI images (since bo th were competent to do so), and then comment on them in supplementa l post-trial reports.

Petitioner filed Dr. Okuda’s supplemen tal report in late November 2018. See generally Third Okuda Rep. He agreed with the 2011 MRI fi ndings, but maintained that when compared with the 2014 MRI, “a reduc tion in the size and conspicuity of previously observed lesions around the [brain] ventricles was present. ” Third Okuda Rep. at 2. He also op ined that the cervical lesion

11 Dr. Vartanian did, however, also acknowledge that certain of Petitione r’s literature, like Queen Square, credibly suggested that a large percentage of MS patients could e xpect an overall mild diseas e course. Tr. at 159–60 (citing Queen Square study, supra , at 814).19 observed in June 2011 had s hown improvement over time. Id. He thus believed that prevaccination, the “overall burden of disease” ba sed solely on the “number and volume of T2 lesions” in the brain and spinal cord, was modest and stable. Id.

Dr. Okuda also took the opportunity to comment agai n on the question of MRI enhancement and what it says about the lesion’ s likely age. He allowed that “enhancement may persist for up to a month”—a st atement that would support the conclusion that Petitioner’s enhancing thoracic lesion, first observed on October 16, 2014, began before vaccination. But he
also maintained that “new cont rast enhancing lesions may devel op or resolve over a short period of time,” offering a nonpublished case study example of a male pa tient at his own hospital who displayed enhancing lesions within ten days of repeat brain MR Is. Third Okuda Rep. at 5, Fig. 2. 12 He thus argued that “contrast enhancement in humans may occur at the time of lesion onset,” supporting the conclusion that P.M.’s 2014 lesion ar ose in the short timefr ame after vaccination.

Dr. Vartanian’s supplemental report was filed in April 2019. See generally Third Vartanian Rep. Focusing on the October 2014 MRIs (including a follow-up of the brai n and spine imagining done at the end of October 2014), Dr . Vartanian questioned whether the thoracic lesion was in fact enhancing as of October 16 th , despite what the radiologic reco rd seemed to indicate. Third Vartanian Rep. at 2. He also noted the presen ce of a cervical lesion on an October 31, 2014 MRI that was non-enhancing, along with multiple lesi ons on the brain MRI performed at that time. Id. Comparing the 2011 to 2014 findings , he characterized the 2011 cerv ical lesion as “large and expansile,” in comparison to the 2014 thoracic lesion. Id. He deemed contrast enhancement “not so informative,” however, noting that while the prior cervical lesion had unquestionably been enhancing, the 2014 thoracic lesion, in his opinion, showed only “leptomeningeal ” enhancement (meaning it revealed in flammation or blood-brain barrier breach of the CNS membranes covering the spinal cord) 13 as opposed to enha ncement in the lesion itself —thus diminishing the likelihood that the lesion had developed in the brief post-vaccination timeframe. Id. at 3.

If “the most conservative estimate” is that lesions enhance for at least one to two weeks after detection, then, Dr. Vartanian opined (based on his determination from review of the MRIs
that the thoracic lesion was actua lly non-enhancing), it was “extre mely unlikely” the October 2014 thoracic lesion came into being post-vaccination. Third Vartanian Rep. at 4. His other primary conclusion from review of the MRI images was that Petitioner had already experienced aggressive lesion formation in the three years prior to vaccin ation (as evidenced by the large cervical lesion

12 Although Dr. Okuda filed literature to support the contentions in this supplemental report, this part of his opinion was not attributed to some other publication. I will nevertheless consider it valid, albeit only worthy of the weight given any single-patient case study.

13 Dorland’s at 123, 1445.20 observed in 2011), thus undermining the contention th at the overall course of Petitioner’s MS was more severe post-vaccination (even if clinical symptoms did worsen due to the impact of the thoracic lesion). Id.

IV. Procedural History

After filing the Petition, Petitioner gathered and submitted medical records and final statement of completi on on October 18, 2016 (ECF No. 11). Re spondent’s Rule 4(c) Report was thereafter filed on December 19, 2016 (ECF No. 12). Additional medical r ecords were filed in June 2017 (ECF No. 17), and January thr ough April 2018 (ECF Nos. 31, 33, 38, and 40).

Petitioner thereafter filed an expert report on April 12, 2017, after obtaining one extension of time. Respondent filed Dr. Va rtanian’s report on June 22, 2017. Pe titioner then filed a rebuttal expert report from Dr. Okuda on December 20, 2017 (ECF No. 27), and Respondent filed his supplemental report from Dr. Vartanian on April 26, 2018. (ECF No. 43). In the interim, I set the matter for an entitlement hearing to be held on June 7–8, 2018 (ECF No. 23). The entitlement hearing was held on June 7, 2018, and a post-heari ng briefing schedule was also set (in which I included deadlines for filing supplemental expert reports and post-hear ing briefs addressing unresolved issues at hearing). The matter is now ripe for resolution.

V. 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 pres cribed 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). 14 In this case, Petitioner does not assert a Table claim.

For both Table and Non-Table claims, Vaccine Program pet itioners bear a “preponderance of the evidence” burden of proof. Section 13(a)(1)(a). That is, a petitioner mu st offer evidence that
leads the “trier of fact to believe that the existence of a fact is mo re probable than its nonexistence before [he] may find in favor of the party who has the burden to pe rsuade 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.

14 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).21 476, 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 petitione r must demonstrate that the vaccine was “not only [the] but-for cause of the inju ry 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 r eceive a Vaccine Program award ba sed solely on his assertions; rather, the petition must be suppor ted 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 vacc ination and the injury; (2) a logical sequence of cause and effect showing that th e vaccination was the re ason 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 diff erent showing. Under Althen prong one, petitioners must provide a “reputable medical theory,” demonstrating that the vaccine received can cause the type of injury alleged. Pafford , 451 F.3d at 1355–56 (citations om itted). To satisfy this prong, a petitioner’s theory must be base d on a “sound and reliable medica l 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 me dically or scientifically certain.” Id. at 549.

Petitioners may satisfy the first Althen prong without resort to medical literature, epidemiological studies, demonstration of a specif ic 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 conclusive ly 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 mu st take care not to increase the burden placed on petitioners in offering a scie ntific 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 st andard 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 plausibi lity (and thus need not do so with preponderant proof). Tarsell v. United States, 133 Fed. Cl. 782, 792–93 (2017) (special master committed legal22 error by requiring petitioner to establish first Althen prong by preponderance; th at standard applied only to second prong and peti tioner’s overall burden); Contreras, 121 Fed. Cl. at 245 (“Plausibility . . . in many cases may be enough to satisfy Althen prong one.” (emphasi s in original)); see also
Andreu , 569 F.3d at 1375. At the same time, there is contrary author ity from the Federal Circuit suggesting that the same preponde rance 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 sc ientific explanation’ sufficient to prove by a preponderan ce of the evidence a medical theory linking the [relevant vaccine to relevant injury].”) (emphasis added). Regardless, one thing rema ins: petitioners always
have the ultimate burden of esta blishing 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 se quence of cause and effect, usually supported by facts derived from a petitioner’s me dical records. Althen , 418 F.3d at 1278; see also
Andreu , 569 F.3d at 1375–77; Capizzano , 440 F.3d at 1326; Grant v. Sec’y of Health & Human

Servs. , 956 F.2d 1144, 1148 (Fed. Cir. 1992). In establishi ng that a vaccine “did cause” injury, the opinions and views of the injured party’s trea ting physicians are enti tled to some weight. Andreu

, 569 F.3d at 1367; Capizzano , 440 F.3d at 1326 (“[M]edical reco rds 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 th e 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).

Medical records and/or statements of a treating physician’s views, however, 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, re port, or summary shall not be binding on th e special master or court”); Snyder v. Sec’y of He alth & Human Servs ., 88 Fed. Cl. 706, 746 n.67 (2009) (“[T]here is nothing . . . that mandates that the testimony of a treating physician is sacr osanct—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 treati ng 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 pres ent in the record—including conflicting opinions among such individuals. Hibbard v. Sec’y of Health & Human Servs. , 100 Fed. Cl. 742, 749 (2011) (finding that it is not arbitrar y or capricious for sp ecial masters to weigh competing treating physicians’ conclusions against each other), aff’d , 698 F.3d 1355 (Fed. Cir. 2012); Caves v. Sec’y23 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 medi cally 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 time frame must also coincide with the theory of how the relevant vaccine can cause an injury ( Althen prong one’s requirement). Id. ; see also 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).

B. Standards Applicable to Signi ficant Aggravation Claim

In this matter, Petitioner maintains that the flu vaccine significantly aggravated his previously-diagnosed MS. Where a petitioner so alleges, the Althen test is expanded, and the petitioner has additional evidentiary burdens to satisfy. 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. Sec’y of Health & Human Servs. , 81 F.3d 1099, 1107 (Fed. Cir. 1996), which related to on-Table significant aggravatio n cases. The resultant “s ignificant aggravation” test has six components, wh ich require establishing:

(1) the person’s condition prio r to administration of th e vaccine, (2) the person’s current condition (or the condition following the vaccination if that is also pertinent), (3) whether the person’s cu rrent condition constitutes a “significant aggravation” of the person’s condition prio r to vaccination, (4) a medical theory causally connecting such a significantly wo rsened condition to the vaccination, (5) a logical sequence of cause and effect s howing 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 (hol ding that “the Loving case provides
the correct framework for evaluatin g off-table significant aggravation claims”). In effect, the last three prongs of the Loving test correspond to the three Althen prongs.24 Subsumed within the Loving analysis is the requirement to evaluate the likely natural course of an injured party’s pr eexisting disease, in order to de termine 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 ma ster’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 na tural progression” of the underlying

condition. Hennessey, 2009 WL 1709053, at *42. 15 The Federal Circuit has upheld the determinations of special masters that worsen ing was not demonstrated in connection with establishing a petitioner’s overall preponderant bu rden 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. 16

C. Law Governing Analysis of Fact Evidence

The process for making determin ations in Vaccine Program cases regarding factual issues begins with consideratio n of the medical records. Section 11(c)(2). The special master is required to consider “all [] relevant me dical and scientific evidence cont ained in the record,” including “any diagnosis, conclusion, medical judg ment, or autopsy or co roner’s report which is contained in the record regarding the nature , causation, and aggravati on of the petitione r’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 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

15 The legislative history of the Vaccine Act strongly supports inte rpreting “significant aggr avation” as requiring a claimant to establish that a vaccine rendered a preex isting condition qualitatively wors e than it would have been otherwise—not simply that the affected individual experienced a post-vaccina tion symptom that contrasts with the individual’s comparatively be tter 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 preexisting (e.g., a child with monthly seiz ures 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 wh o, after vaccination, has seizures on a daily basis” (emphasis added)).

16 This is consistent with the fact (well recognized by co ntrolling precedent) that evidence of “worsening” relevant to Respondent’s alternative cause burden may reasonably by evaluated by a sp ecial master in determining the success of a petitioner’s prima facie showing. Snyder/Harris , 553 F. App’x at 1000 (“’[N]o evidence should be embargoed from the special master’s consideration simp ly because it is also relevant to a nother inquiry under the statute.’” ( quoting Stone , 676 F.3d at 1380)); see also de Bazan v. Sec’y of Health & Human Servs. , 539 F.3d 1347, 1353 (Fed. Cir. 2008) (“The 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.”).25 events in question that was given at a later date, provided that su ch determination is evidenced by a rational determination).

Medical records that are created contemporane ously with the events they describe are presumed to be accurate and “complete” (i.e., pres enting all relevant information on a patient’s health problems). Cucuras , 993 F.2d at 1528; see also Doe/70 v. Sec’y of Health & Human Servs.

, 95 Fed. Cl. 598, 608 (2010) (“Given the inconsiste ncies 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-preced ential opinion). This presumption is based on the linked propositions that (i) sick people vis it medical professionals; (i i) 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 concl ude that petitioners would fail to accurately report the onset of their daughter’s symptoms.”).

Accordingly, if the medical r ecords 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 evidentia ry weight than oral testimony— especially where such testimony conf licts 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) (“It has generally been held that oral tes timony which is in conflict with contemporaneous
documents is entitled to little evidentiary weight.”) (citing United States v. United States Gypsum

Co. , 333 U.S. 364, 396 (1948)).

There are, however, situations in which compelling oral tes timony 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) (“[L]ike any norm based upon common sense and experience, this rule should not be treat ed as an absolute and must yield where the factual predicates for its appl ication are weak or lacking.”); Lowrie , 2005 WL 6117475, at *19 (“Written records which are, them selves, 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 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).26 When witness testimony is offe red to overcome the presumpti on of accuracy afforded to contemporaneous medical records, such testim ony 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 inconsiste ncies between contempora neously created medical records and later testimony: (1) a person’s failure to recount to th e medical professional everything that happened during the relevant time period; (2) the medical pr ofessional’s failure to document everything reported to her or him; (3) a person’s fa ulty recollection of the events when presenting testimony; or (4) a person’s purposeful rec ounting 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, th ere must be evidence that this
decision was the result of a rational determination. Burns , 3 F.3d at 417.

D. Analysis of Ex pert Testimony

Establishing a sound and reliab le medical theory often requ ires 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) te sted; (2) whether the theory or technique has been subjected to peer review and publication; (3) whether there is a known or potenti al rate of error and whether there are standards for controlling the error; and (4) whether the theo ry 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 evid entiary 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) (“[U]niquely in this Circuit, the Daubert factors have been employed also as an acceptable evidentia ry-gauging tool with resp ect to persuasiveness of expert testimony already admitte d.”). The flexible use of the Daubert factors to evaluate the persuasiveness and reliability of expert testimony has routinely been upheld. See, e.g.

, Snyder , 8827 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 ev idence should be admitted, but instead to determine whether expert testimony offe red is reliable a nd/or persuasive.

Respondent frequently offers one or more experts of his own in order to rebut a petitioner’s case. Where both sides offer expe rt 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). But nothing requires th e 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 th e 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 th e relative persuasiveness of compet ing expert testimony, based on a particular expert’s credibility, is part of the ov erall reliability analysis to which special masters must subject expert testimony in Vaccine Program cases. Moberly , 592 F.3d at 1325–26 (“Assessments as to the re liability 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) (“[T]his court has unambiguously e xplained that special ma sters are expected to consider the credibility of e xpert witnesses in evaluating pe titions for compensation under the Vaccine Act.”).

E. Consideration of Medical Literature

Both parties filed medical and scientific litera ture in this case, but not every filed item
factors into the outcome of this decision. While I have review ed all of the me dical 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. See Moriarty v. Sec’y of Health & Human Servs. , 844 F.3d 1322, 1328 (Fed. Cir. 2016) (“We generally presume that a special ma ster considered the relevant record evidence even though he does not explicitly reference such evidence in his decision.”) (citation omitted); see also Paterek v. Sec’y of Health & Human Servs. , 527 F. App’x 875, 884 (Fed. Cir. 2013) (“Finding certain information not relevant does not lead to—and likely undermines—the
conclusion that it wa s not considered”).28 ANALYSIS

I. Overview of Medical Terms and Relevant Prior Decisions

Although the parties’ experts agr eed on the proper definition of MS and the kind of clinical or radiologic evidence that establishes its existence, some additional comment is warranted. As Program case law recognizes, MS is a demyelinating CNS 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). It likely has an autoimmune pathogenesis. W.C. v. Sec’y of Health & Human Servs., No. 07-456V, 2011 WL 4537877, at *3 (Fed. Cl . Spec. Mstr. Feb. 22, 2011), mot. for review den’d , 100 Fed. Cl. 440 (2011), aff’d, 704 F.3d 1352 (Fed. Cir. 2013). Patients dia gnosed with MS typically experience multiple episodes of CNS demyelination separa ted in time and space (meaning throughout the CNS), concurrent with a progressi ve, if remitting and relapsing, de cline in their overall health

course. Taylor , 2018 WL 2050857, at *21

. An MRI can be used to corroborate the dissemination in space and time requirement, and often reveal s old lesions as well as enhancing/new lesions. 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 argued that a vaccine (including the flu vaccine) significantly aggravated a pe rson’s preexisting MS, to va rying 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 signif icantly aggravated the petitioner’s preexisting MS); but see W.C. v. Sec’y of Health & Human Servs. , 100 Fed. Cl. 440 (2011) (upholding special
master’s determination that flu vaccine did not significantl y aggravate preexisting MS), aff’d, 704 F.3d 1352 (Fed. Cir. 2013), and Bubb v. Sec’y of Health & Human Servs. , No. 01-721V, 2005 WL 1025707 (Fed. Cl. Spec. Mstr. Apr. 29, 2005) (tet anus toxoid vaccine did not significantly aggravate preexisting MS); see also Maciel v. Sec'y of Health & Human Servs ., No. 15-362V, 2018 WL 6259230 (Fed. Cl. Spec. Mstr. Oct. 12, 2018) (HPV vaccine did not significantly aggravate existing MS). None of these decisions are completely on point (and some are actually distinguishable), and they do not control the outcome herein, but they nevertheless provide guidance in addressing the claim at hand.

In W.C. , the petitioner 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. W.C., 100 Fed. Cl. at 446–47. Upon review, in discussing the fourth Loving prong (the “can cause” el ement 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 a nd exacerbation of MS, like Confavreux. Id. 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 cal ls that could have been decided by a different29 special master with the opposite result, and thus the underlying decision was upheld mainly as a function of the proper applicati on of the review standards. Id. at 456 (noting that although that the evidence was “so closely balanced that the decisi on could have gone either way,” nevertheless “the court cannot say that the special ma ster’s findings we re arbitrary”).

Bubb does not involve the flu vaccine, but is a stronger endorsement of the medical/scientific case against an association between any vaccines and MS exacerbation. There, as here, it was undisputed that the petiti oner suffered from MS prior to vaccination. Bubb, 2005 WL 1025707, at *2. In addition, the record supported the conclusion that not only had the petitioner experienced a relapse post-vaccinatio n, 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 de cided the claim against the petitione r, largely due to her inability to connect the tetanus vaccination to her MS worsening. Id. at *24. Like the present case and W.C.

, Respondent offered Confavreux and similar studie s to rebut any purported association between any vaccination and MS exacerbation. Id. at *20–21. The special master found this evidence persuasive in “significantly undercut[ting]” the case study evid ence offered by the petitioner. Id. at *24. This, in addition to the la ck of other probative evidence re lating exacerbation to the vaccine (such as the views of contempo raneous treaters), resulted in the denial of entitlement.

Quackenbush-Baker , by contrast, stands as an outlier . There, a petitioner succeeded in establishing that the flu vaccine significantly ag gravated her MS. However (and unlike the present case), the petitioner’s MS was wholly asymptomatic prior to vaccination, and thus deemed to have been preexisting solely on the basis of MRI evidence—essentially RIS. Quackenbush-Baker , 2018 WL 1704523, at *8. The asymptomatic, subclinical na ture of petitioner’s MS seems to have factored heavily in the special master’s finding in petitioner’s favor, when compared to the postvaccination record of medical decline. 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 (or given low weight based on the special master’s estimation that epidem iologic evidence could never comp letely eliminate the possibility of the rare occurrence of a vaccine injury). Id. at *15–17.

I have previously decided cases in which MS was alleged to have been exacerbated by a
vaccine. See, e.g.

, L.Z. v. Sec’y of Health & Human Servs., No. 14-920V, 2018 WL 5784525 (Fed. Cl. Spec. Mstr. Aug. 24, 2018). In L.Z., I rejected a claim that th e flu vaccine significantly aggravated a petitioner’s pre-vacci nation MS (pled in the alternativ e to a claim th at the vaccine caused it directly). Becaus e MRIs performed about a month after vaccination revealed evidence of lesions, it could not be concluded th at the lesions had not predated vaccination. This, plus the fact that the petitioner had displayed some pre-vacci nation neurologic symptoms, led me to determine that her MS more likely than no t predated vaccination. I also found that Pe titioner’s expert had failed to preponderantly establish that vaccination could aggravate MS, noting the existence of30 literature like Confavreux, in comparison to Pe titioner’s over-reliance on evidence suggesting vaccines could directly cause MS , but not offering anything relating to a vaccine’s capacity to promote MS flares. L.Z., 2018 WL 5784525, at *18–19.

II. Petitioner Has Not Established His Signif icant Aggravation Claim with Sufficient Preponderant Evidence 17

A. Petitioner Has Not Offered a Persuasive and Reliable Causation Theory ( Loving Prong Four )

As discussed above, there is am ple persuasive evidence filed in this action that the flu
vaccine is not likely to exacerbate an individual’s preexisting MS. See

, e.g. , Confavreux; Rutschmann; Mailand; Michielsen. This kind of ev idence has also repeatedly been deemed reliable and persuasive in other Program cases involv ing claims of vaccine- caused MS exacerbation. See W.C., 100 Fed. Cl. at 455–56; Bubb, 2005 WL 1025707, at *20–21, 24. While many of these articles are broad reviews of other published lit erature, all involve di rect studies or other epidemiologic analyses, and the re view articles written in the ten- plus years since Confavreux’s publication identify no subsequent studies suggesting the contrary.

This scientific/medical evidence was ineff ectively rebutted by Peti tioner. The general argument against it—that epidemiologic studies, no matter how individually trustworthy or scientifically reliable, can never preclude the possibility that a part icular individual was in fact harmed by a vaccine, given the overall rareness of such injuries—has been unpersuasively maintained in other Program cases. See, e.g., McCollum v. Sec’y of Health & Human Servs., No. 14-790V, 2017 WL 5386613, at *18 (Fed. Cl . Spec. Mstr. Sept. 15, 2017), mot. for review den’d, 135 Fed. Cl. 735 (2017), aff’d, 760 Fed. App’x 1003 (Fed. Cir. 2019) (discussing Crutchfield v. Sec'y of Health & Human Servs., No. 09-0039V, 2014 WL 1665227 (Fed. Cl. Spec. Mstr. Apr. 7, 2014), mot. for review den’d , 125 Fed. Cl. 251 (2014)). As form er Special Master Hastings
observed in Crutchfield, “it is not the Respondent's burden in [a] case to prove that it is impossible that [the relevant vaccine] can cause [the alleged injury]. It is, rather, the Petitioner’s burden to [show the vaccine can cause the injury].” Crutchfield, 2014 WL 1665227, at *15 (emphasis in original).

Nor is it convincing to propose th at because a claimant need not offer such direct epidemiologic evidence to preva il, such evidence should (or must) be disregarded entirely. D’Toile v. Sec'y of Health & Human Servs. , 726 Fed. App’x 809, 811 –12 (Fed. Cir. Apr. 12, 2018) (special master may consider negative ep idemiologic evidence, even though petitioners are not obligated in the first instance to offer positive epidemiolo gic studies to meet th eir preponderant burden);

17 I address the relevant Loving prongs in order of their importance to this Decision, and only those prongs upon which the Decision turns.31 Grant , 956 F.2d at 1144. Here, the evidence exists and directly undercuts Petitioner’s claim, making it appr opriate under Daubert to consider it in weighing the scientific reliability of Dr. Okuda’s contrary assertions.

Petitioner’s other efforts to pick apart the st udies filed in this cas e—either by trying to show that P.M. himself might not have been included in some of th e studies, the sample sizes were too small, the studies were overall “underpower ed,” or that alleged genetic variability and susceptibility possessed by Petitioner distinguished his reaction from what was measured in the studies referenced by Respondent—w ere unsuccessful. At most, argum ents about deficiencies in certain items of literature or medical studies migh t cause me to reduce the weight they should be afforded (and I do not disregard Pet itioner’s points out of ha nd; the literature filed in this case does

not establish with medical certainty that the flu vaccine could not exacerbate MS). 18 But the overall
thrust of all of these items remains—and Petitione r did not offer medical or scientific literature suggesting the propensity of vaccination to produce MS flares.

Petitioner did somewhat better in establishing a plausible biologic process by which the flu vaccine could theoretically produce an MS exac erbation. Program law firmly does not require proof of mechanism—but in a case like this, where direct pr oof supporting the claim is lacking, a petitioner can bulwark his case with a variety of circumstantial evidence including persuasive and reliable proof establishing how the vaccine in que stion might precipitate a reaction resulting in the relevant injury. P.M. certainly proposed a mechanism, molecular mimicry, that has been deemed reliable in this context in past Program cases involving other kinds of related CNS injuries, and it could explain how the flu vaccine biologically might initiate a demyelinating process. See, e.g.

, Quackenbush-Baker , 2018 WL 1704523, at *16–17. Similar mech anisms have also been found plausible in the context of the direct causation of CNS injuries like transverse myelitis (“TM”) or acute disseminated encephalomyelitis (“ADEM”). See, e.g.

, Taylor , 2018 WL 2050857, at *23 (discussing credibility of theories involving ADEM); Bender v. Sec’y of Health & Human Servs., No. 11-693V, 2018 WL 3679637, at *25 (Fed. Cl. Spec. Ms tr. July 2, 2018) (discussing theories involving TM), mot. for review den’d, 141 Fed. Cl. 262 (2019). It is hardly unreasonable for Petitioner to have maintained that the same pr ocesses might bear on new lesion formation in an existing case of MS as well (even if the cont extual differences are meaningful).

This, however, reveals a core deficiency of Petitioner’s causation theory. The alleged exacerbation in this case began with the new thoraci c lesion (rather than just an increase in brain lesions). It would have been gr eatly helpful to Petiti oner’s case to highlight evidence supporting an association between the flu vaccine (or flu w ild virus) and (for individuals already suffering from MS) the initiations of lesions in specific parts of the CNS—especially a location not

18 Of course, the preponderance evidentiary test (which petitioners must satisfy) means that no party to a Vaccine Act case is required to establish their points with that degree of cer tainty. Just as petitioners are not required to conclusively establish that a vaccine caused an injury, but rather that it is “more likely than no t” that it did, Respondent can offer evidence of varying weights and probative value to shift the preponderant balance in the other direction.32 previously featuring lesions. Th e science supporting existing Progr am decisions involving direct CNS injury (like TM) by the flu vaccine to pers ons not previously suffering from MS had some value in this effort. But (as pointed out by Dr. Vartanian ( see Second Vartania n Rep. at 5)),
Petitioner has not attempted to make such a showing.

In fact, the literature filed in this case does not elide a distinction be tween brain and spinal
lesions in terms of overall MS disease process (beyond immedi ate clinical expression of symptoms). Articles like Hua (upon which Petitioner relied) actua lly suggest that in a person already suffering from MS, develo pment of thoracic lesions is like ly a function of whether lesions already exist on the spine (albeit closer to the brain). Hua, supra , at 523. 19 And Dr. Okuda’s reading of Hua to mean that only an MS patient with several cervical lesions has th e chance of a thoracic lesion is undercut by Hua’s own language, which allows that ev en a single cervical lesion can be associated with the later development of thoracic lesions. Id. (“Our results suggest an increase in risk for the presence of t horacic spinal lesions when one or more lesions are present within the cervical spinal cord.”) (emphasis added).

The strength of Petitioner’s expert showi ng somewhat counterbalanced the above. Dr. Okuda was a well-qualified and competent neur ology expert, whose opinion was reasonable and worthy of weight. Although he doe s not have a demonstrated expe rtise in immunology (and hence could not establish, based on his own expertise, what it is about vaccination that would stimulate the immune system of a person su ffering from MS sufficient to deve lop a relapse), his opinion that a vaccine could produce a damaging relapse thro ugh some general, immune-stimulation process,
and/or via mechanisms associated with other ki nds of direct CNS injury, must still be taken seriously—and I do so. His pr imary role as a treating expert does not mean that I cannot consider his testimony in evaluating the strength of Petitioner’s causation theory under the first Althen

prong. Capizzano , 440 F.3d at 1326.

Nevertheless, Dr. Okuda’s testimony was far more probative of the “did cause” Althen prong, and was not enough to carry Petitioner across the preponderant line in resolving the “can cause” prong. His reports and testimony did not pre ponderantly establish that the flu vaccine would be expected to produce any MS relapse, let alone a focal thoracic lesion. His assertions about an
association between the flu vaccine and the biol ogic processes that might theoretically produce
new lesions were also too general, as they pertained more to instances of new CNS injury rather than exacerbation. And his challeng es to the studies that negate an association between vaccination and MS relapse were not persuasive. In a case in which there were few on- point studies or items of literature pertaining to the va ccine or claimed injury, Dr. Okuda ’s strong testimony might carry the day. Not here. Nothing in Program precedent says a special master must give more weight to

19 I am also aware of no prior decision involving the flu vaccine causing an isolated occurrence of TM or ADEM in an individual already diagnosed with MS. And such a theory, even if formally articulated, would run into the brick wall of evidence (discussed abov e) suggesting that vaccines do not exacerbate existing cases of MS.33 the testimony of a testifying treating expert over dire ctly relevant medical or scientific literature. As good and reliable as Dr. Okuda ’s individual testimony was, he did not overcome the literature.

Because of the foregoing, my weighing pro cess did not produce a finding in Petitioner’s
favor on the first Althen prong, despite the fact that the Petition er offered some reliable evidence. In another case, with more medi cal or scientific evidence of how the flu vaccine affects MS patients, or how the vaccine (or even wild flu virus) can impact specific parts of the CNS, the outcome could easily be favorable to a petitioner. As science advan ces, and/or the i ssue is subject to further (or updated) study, more evidence may be developed that supports the kind of claim
asserted herein. But it does not exist today. Under the legal standards I must apply, the evidence in this case does not support a finding that the flu vaccine can likely produce MS exacerbations.

B. Petitioner has Not Established that the Short Timeframe in Which His Thoracic Lesion Developed and Resulted in Symptoms was Medically
Reasonable ( Loving Prong Six)

There is no dispute that Pe titioner began experiencing clin ical symptoms reflecting his subsequently-diagnosed MS relapse on October 14, 2014—five days after vaccination. Ex. 19 at 226–27, 230. Just two days later (now a week from th e date of vaccination), an MRI revealed the presence of the thoracic lesion, and the fact of its enhancement established that the lesion was

“new.” But how new? And is this overall timeframe medically reasona ble for a vaccine-induced
MS flare?

Were I solely relying on the reas oning of prior decisi ons, I might conclude that a new lesion
would take several weeks to a month to form at the soonest—precluding a finding that the lesion in question in this case could have formed in so short a time, and/or that it more likely predated vaccination (even if it was onl y discovered after the fact). See, e.g.

, L.Z., 2018 WL 5784525, at *17–18. However, I am not bound in this case by such prior decisions (even my own), and both experts offered reliable opin ions on this topic, so furt her discussion is in order.

Dr. Okuda made a number of persuasive points in favor of the conclusion that the lesion could have arisen post-vaccination. His third report in particular offered some direct evidence of studies demonstrating the short timeframes in which contrast-enha ncing lesions can develop. Third Okuda Rep. at 4. He also reasonably relied on his extensive expertis e in radiologic matters to offer this opinion, and although the ev idence he cited specifi c to thoracic lesions (as discussed above) was less probative in Petitioner’s favor, his assert ions still deserved weight. Dr. Vartanian argued the contrary, but did not substantia te his position with reliable l iterature of his own. Tr. at 146, 173, 180. The evidence thus preponderate s, if barely, in favor of Petitioner’s contention that a new MS-associated lesion (without taking into account its location) could develop in a week’s
timeframe.34 But could a thoracic lesion both appear and cause the degree of symptoms Petitioner experienced in that same narro w timeframe? When the question is so expanded (as it should be - since the symptoms not only predated lesion disc overy, but are an element of Petitioner’s claim that his symptoms worsened after vaccination), the evidence is no longer preponderantly in
Petitioner’s favor.

Both experts concurred (particularly when di scussing the differences between RIS and CIS, but also in commenting on the import of radiologic evidence of MS progre ssion generally) that lesions are very frequently unaccompanied by symptoms and can predate symptoms by a lengthy time period as well. See, e.g. , Tr. at 22, 43, 67, 185–88 (Dr. O kuda) and 142, 144-46, 173 (Dr. Vartanian). The fact that an individual can have “subclinical MS” (in effect, RIS) for a long period thus suggests that lesions and clinical symptoms do not automatically go ha nd-in-hand. As a result, even if a lesion can develop in such an acute manner, as alleged herein (and as supported by some
reliable scientific evid ence), it has not been pr eponderantly established th at such a new lesion
would also more likely than not be immediately accompanied by obvious and severe symptoms. Rather, a lesion more likely might take a long er time to develop an d cause symptoms. This
weakens the conclusion that the lesion Petitioner experienced more likely than not post-dated vaccination, and reverses preponde rance in Respondent’s favor.

This is so even if it is correct that P.M.’s immediate post-vaccination symptomatic complications, and associated sequelae, were direc tly attributable to the new lesion’s location in the thoracic spinal region. The record in fact unquestionably s upports that conclusion, and both experts concurred Petitioner’s ne w symptoms arose from the location of the new lesion. But, given
what is known about th e relationship between lesion developm ent and clinical presentation of symptoms, it cannot be determined that the ve ry short timeframe in which P.M. experienced both still supports the conclu sion that the lesion more likely than not post-da ted vaccination. Rather, because the symptoms presented so rapidly, it becomes more likely than not that the lesion already existed, and may have even been enhancing, prior to vaccination. 20 The literature relied upon by Dr. Okuda to establish the speed at which lesions can develop not on ly says nothing specific about thoracic lesions, but also does not discuss the temporal relationshi p between lesion s and clinical
symptoms.

20 In other words, had an MRI been perf ormed on Petitioner’s thoracic spine a we ek to a month prior to vaccination, it likely would have shown enhancement, even in the absence of the symptoms he later manifested.35 C. Even If Petitioner Established That Hi s Symptoms Worsened After Vaccination,
He Could Not Show that the Flu Vaccine Caused that Worsening (Loving Prongs Three and Five)

Both sides accept that Petitione r’s MS course generally took a turn for the worse after his receipt of the flu vaccine, as he began experienci ng symptoms that were of a different nature and severity than before. Their expert s also allowed that not all of Pe titioner’s subsequent experiences (such as his recent optic neuritis) could be vacci ne-attributed, or even co nnected to the October 2014 events. The experts do not, however , concur that Petitioner’s overall course was worse, with Dr. Vartanian disputing the characterization of P.M.’s MS before v accination as mild, and proposing that his symptoms were not uncommon for what a person with relapsing/remitting MS would experience, whereas Dr. Okuda maintained that Petitioner was likely to experience a mild
outcome before vaccination.

The evidence regarding Petitioner’s likely di sease course, based on what was known before his October 2014 vaccination, is ulti mately inconclusive. I found cr edible Dr. Okuda’s arguments
about Petitioner’s overall mild lesion burden pre-vaccination, al ong with his observation that
certain common clinical rules-of-thumb used in MS (like the “five-year rule ,” or Petitioner’s EDSS score) suggested that Pe titioner’s MS would not li kely be severe. At the same time, Dr. Vartanian also established persuasively that individuals with RRMS are always susceptible to downward symptoms progression at any time. And while Pe titioner’s pre-vaccination status may not have featured significantly debilitating symptoms (esp ecially when compared to thereafter), it is not wholly accurate to conclude that his earlier c ondition was notably or uniquely free of burdensome
symptoms. See, e.g. , Ex. 5 at 2 (Petitioner diagnosed with “unusual” headaches in the years prior to his MS diagnosis), Ex. 10 at 5 (treater charac terization of Petitioner’s MS as “pretty severe”).

In addition, although P.M.’s post-vaccination course may have featured some symptoms that he had not previously experienced and whic h were of a more severe degree (in particular because of their impact on motor function), his overall clinical presentation, fr om the time he was diagnosed to the present date, does not appear un iquely devastating (as much as it unquestionably has negatively impacted his health and life). I al so find that the course of Petitioner’s postvaccination disease was not completely progressi ve, and both sides agreed that certain of Petitioner’s more recent relapses (s uch as the optic neuritis he experienced) cannot necessarily be
attributed to the new thoracic lesi on purportedly caused by vaccination.

Based on the above, the record and other evid ence is ultimately mo re supportive of the
conclusion that overall Petitioner’s course, even if imme diately worse than what he had experienced pre-vaccination, was not so much more distinctive in severity thereafter to conclude that it was truly “worse” for pur poses of the present analysis. Yet even if I focused solely on the impact of the thoracic le sion, allowing it to charact erize the totality of Pe titioner’s post-vaccination36 disease process, I would still be una ble to find that such worsening was due to vaccination. Rather, the record only supports the conclusion that the ch ange in quality of Petitioner’s symptoms (and in particular the impact they had on his motor function) was attributable specifically to the thoracic
lesion— not that the flu vaccine itself “more likely than not” caused that lesion to come about in the first place. This is partially due to the fact, as noted above, that there is thin evidence suggesting the flu vaccine can produce MS flares of any ki nd, let alone exacerbations specifically targeting a particular spinal region, and also that it is unlikely a new lesion developing w ithin the space of a week would also immediately be a ssociated with significant symptoms.

The weaknesses of Petiti oner’s showing on these related prongs of the Loving test are best exemplified by his overreliance on the temporal relationship between vaccination and Petitioner’s mid-October new symptoms onset. Although Dr. Okuda was a particularly effective treating expert, he ultimately depended too much on the fact that the Petitioner had just received the flu
vaccine—and hence relied on the tem poral association to the vaccine. See, e.g. , Tr. at 29–30, 51– 52, 58–59. While the causal propensity of a prior vaccination may be heightened by the views of a knowledgeable treating expert, and therefore wort hy of some deference, it remains a slim reed upon which to base a causation determinat ion if the temporal association is primarily what the expert finds compelling, as opposed to the propensity of the relevant vaccine to injure, or some other medical development post-vaccin ation that implicates the vaccine . Moberly , 592 F.3d at 1323–24. Not all adverse post-vaccination events are caused by vaccination (since, were that the case, all a claimant would need to do to prevail in any Vaccine Act case would be to show onset of injury afte r vaccination).

Accordingly, even if Petitioner had preponderant ly established that his overall MS course worsened post-vaccination (a conc lusion I lean strongly against, although it finds some support in the record), he has not also shown such worsening could be v accine-attributed. Petitioner relies too much on the obvious temporal relationship be tween vaccination and his subsequent symptoms plus discovery of new radiologic ev idence of disease process advancem ent. This is an insufficient
basis for the conclusion that the flu v accine caused Petitioner’s MS exacerbation.

Conclusion

This was a difficult case. I take P.M.’s injury seriously and the negative impact it has had on his life. His good faith argumen ts were backed by many soli d items of proof, along with a credible treating expert opinion. Bu t on a fundamental point (the capacity of the flu vaccine to theoretically cause an MS flare close-in-time to vaccination, in a particular location, sufficient to constitute a significant aggr avation of the underlying disease process) it was not a close case. The
evidence in the record did not ultimate ly preponderate in a favorable ruling.37 Accordingly, and for the afor ementioned reasons, I DENY entitlement in this case. In the absence of a motion for review filed pursuant to RCFC Appendix B, th e clerk of the court SHALL

ENTER JUDGMENT in accordance with the terms of 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 entr y of judgment if (jointly or separately) they file notices renouncing their right to seek review.