Songero v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 18-300V

Filed: October 3, 2025

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

DIANA SONGERO, *

*

Petitioner, *

v. *

*

SECRETARY OF HEALTH *

AND HUMAN SERVICES, *

*

Respondent. *

*

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

Ronald Craig Homer, Esq. Conway, Homer, P.C., Boston, MA, for petitioner.

Madylan Louise Yarc, Esq., U.S. Department of Justice, Washington, DC, for respondent.

RULING ON ENTITLEMENT 1

Roth, Special Master:

On February 28, 2018, Diana Songero (“Ms. Songero” or “petitioner”) filed a petition

under the National Vaccine Injury Compensation Program, 42 U.S.C. § 300aa-10 et seq. 2

(“Vaccine Act” or “the Program”). Petitioner alleged that the influenza (“flu”) vaccine she

received on September 24, 2016, caused her to suffer from transverse myelitis (“TM”). See

Petition, ECF No. 1 at 1.

After carefully analyzing and weighing the evidence presented in this case in accordance

with the applicable legal standards, I find that petitioner has provided preponderant evidence that

her flu vaccine caused her TM, satisfying petitioner’s burden of proof under Althen v. Sec’y of

Health & Hum. Servs., 418 F.3d 1274, 1280 (Fed. Cir. 2005). Accordingly, Petitioner is entitled

to compensation.

1

Because this Ruling contains a reasoned explanation for the action taken in this case, it must be made publicly

accessible and will be posted on the United States Court of Federal Claims' website, and/or at

https://www.govinfo.gov/app/collection/uscourts/national/cofc, in accordance with the E-Government Act of 2002.

44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of Electronic Government Services). This means

the Ruling will be available to anyone with access to the internet. In accordance with Vaccine Rule 18(b), Petitioner

has 14 days to identify and move to redact medical or other information, the disclosure of which would constitute an

unwarranted invasion of privacy. If, upon review, I agree that the identified material fits within this definition, I will

redact such material from public access.

2

National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755 (1986). Hereinafter, for ease of

citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa (2018).

I. Procedural History

The petition was filed on February 28, 2018, and assigned to me on the same date. ECF

Nos. 1, 4. Medical records and affidavits from petitioner were filed in support of the petition on

March 5, 2018. Petitioner’s Exhibits (“Pet. Ex.”) 1-10, ECF Nos. 6-7. Petitioner filed a statement

of completion on March 7, 2018. ECF No. 11.

Following his review of the medical records, respondent filed his Rule 4(c) Report on

March 14, 2019. ECF No. 19. 3

Petitioner filed an expert report from Carlo Tornatore, M.D. 4 along with his CV and

supporting literature on July 30, 2019. Pet. Ex. 11-26, ECF Nos. 24-25. Respondent filed an expert

report of Peter Donofrio, M.D. 5 along with his CV and medical literature on February 26, 2020.

Respondent’s Exhibits (“Resp. Ex.”) A-D, ECF No. 29. A supplemental report from Dr. Tornatore

with additional literature was filed on September 24, 2020. Pet. Ex. 27-29, ECF No. 33. On

November 4, 2020, respondent filed a status report advising that he did not intend to respond to

Dr. Tornatore’s supplemental report at that time and requested that the Court schedule an

entitlement hearing in the matter. ECF No. 35.

At a status conference held on January 7, 2021, the expert reports were discussed. Also

discussed was respondent’s decision to defend the case on the 63-day onset and on the ground that

an undiagnosed urinary tract infection (“UTI”) was responsible for her TM rather than her flu

vaccination. ECF No. 36 at 2. The Court also alerted respondent to a prior case in which his expert,

Dr. Donofrio, was referenced agreeing with Dr. Tornatore’s TM onset period of 63 days. See Hitt

v. Sec'y of Health & Hum. Servs., No. 15-1283V, 2020 WL 831822, at *11 (Fed. Cl. Spec. Mstr.

January 24, 2020) (“Dr. Donofrio seemed to generally accept Dr. Tornatore’s timeframe” of “1 to

63 days” in a case where the flu vaccine caused petitioner’s TM.). This case, and Dr. Donofrio’s

response to it, will be discussed further below. The parties were encouraged to discuss informal

resolution. ECF No. 36 at 2.

3

Each party requested and was granted several extensions of time in this matter. ECF Nos. 14-15, 18, 20, 22-23, 27-

28, 30-32, 39-40, 43, 45, 51.

4

Dr. Tornatore has an undergraduate degree in neurobiology from Cornell University, an M.S. from Georgetown

University, Department of Physiology, and an M.D. from Georgetown University School of Medicine. Pet. Ex. 12.

Dr. Tornatore is the Chairman and Neurologist-in-Chief, Department of Neurology, for Medstar Georgetown

University Hospital; Chairman, Department of Neurology for Georgetown University Medical Center; and Professor

of Neurology at Georgetown University Medical Center. Pet Ex. 11 at 1; Pet. Ex. 12 at 4. He is also the Director of

the Multiple Sclerosis Clinic at Georgetown University Hospital. Pet Ex. 12 at 4. He is board certified in neurology.

Id. at 2.

5

Dr. Donofrio received his medical degree from Ohio State University School of Medicine in 1975. Resp. Ex. B at 1.

He completed an internal medicine residency at Good Samaritan Hospital in Cincinnati, Ohio, in 1978; a neurology

residency at the University of Michigan Medical Center in Ann Arbor, Michigan, in 1981; and a neuromuscular

fellowship at the University of Michigan in Ann Arbor, Michigan, in 1982. Id. at 2. He then worked as a professor of

neurology. Id. at 2-3. His positions have included Professor of Neurology and Chief of the Neuromuscular Section

and Director of the MDA and ALS Clinics at Vanderbilt University Medical Center. Resp. Ex. A at 1. He is board

certified in neurology, internal medicine, electrodiagnostic medicine, and neuromuscular disorders. Resp. Ex. A at 1;

Resp. Ex. B at 2. He has authored over 100 journal articles, a textbook, and several book chapters and abstracts, among

other publications, that touch on GBS, CIDP, and other neuropathies. Resp. Ex. A at 1; Resp. Ex. B at 12-62.

2

Pursuant to discussions at the January 7, 2021, status conference, respondent filed a

supplemental report from Dr. Donofrio along with medical literature on April 7, 2021. Resp. Ex.

E-F, ECF No. 44. Petitioner filed a status report on May 19, 2021, confirming that a demand had

been submitted to respondent. ECF No. 46. In a June 18, 2021, status report, petitioner advised

that respondent was maintaining his position to defend this case and would proceed with litigation.

ECF No. 47. A conference was held on July 14, 2021, after which the parties were ordered to

advise within 30 days of mutually agreeable dates in January or February 2023 for a hearing. ECF

No. 48. A two-day entitlement hearing was scheduled for January 26-27, 2023. ECF Nos. 49-50.

A supplemental expert report of Dr. Tornatore and medical literature were filed on October

29, 2021. Pet. Ex. 32-33, ECF No. 52. Updated medical records were filed on October 13, 2022;

November 18, 2022; and November 29, 2022. ECF Nos. 54, 56, 58.

Just prior to hearing and due to Dr. Tornatore being ill, the parties agreed to proceed by

Ruling on the Record. ECF No. 66. A briefing schedule was ordered. Petitioner filed her Motion

for Ruling on the Record on March 30, 2023. ECF No. 68. Respondent filed his Response on April

14, 2023. ECF No. 69. Petitioner filed a Reply on April 21, 2023. ECF No. 70.

I have determined that the parties have had a full and fair opportunity to present their cases

and that it is appropriate to resolve entitlement on the existing record. See Vaccine Rule 8(d);

Vaccine Rule 3(b)(2); see also Kreizenbeck ex rel. C.J.K. v. Sec’y of Health & Hum. Servs., 945

F.3d 1362, 1366 (Fed. Cir. 2020) (noting that “special masters must determine that the record is

comprehensive and fully developed before ruling on the record”). Accordingly, this matter is now

ripe for resolution.

II. Relevant Medical Terminology

Transverse myelitis (“TM”) is an immune-mediated inflammatory process causing damage

to the spinal cord, and is often associated with infection, collogen vascular disease, multiple

sclerosis, and radiation. Vaccinations, including hepatitis B, rabies, smallpox, influenza, and

rubella, have been linked to TM. Pet. Ex. 13 at 1; 6 Pet. Ex. 14 at 1. 7 Up to 40% of TM cases are

preceded by infections, including but not limited to influenza, measles, mumps, rubella,

cytomegalovirus, and the Epstein-Barr virus. Pet. Ex. 14 at 2. 8 Most cases begin after the patient

has recovered from the infection. Thus, TM appears not to be the result of a direct infectious

process, but an autoimmune response triggered by the infectious process. Id.

The etiology of autoimmune responses is multifactorial, involving genetics, immunology,

and hormonal and environmental factors. Pet. Ex. 14 at 2. 9 MRI findings for various forms of TM

include spinal cord enlargement, intramedullary increased T2 signal lesions, and variable

enhancement. Pet. Ex. 13 at 1. 10 Findings after the flu vaccine have shown extensive, longitudinal

6

Rohit Bakshi & John C. Mazziotta, Acute Transverse Myelitis After Influenza Vaccination: Magnetic Resonance

Imaging Findings, 6 J. of Neuroimaging 248 (1996) filed as “Pet. Ex. 13.”

7

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

Ex. 14.”

8

Id.

9

Id.

10

Bakshi & Mazziotta, supra note 6.

3

myelitis and diffuse cord enlargement extending over several spinal levels. Id. The development

of neurological complications ranges from 1 to 63 days after influenza vaccination and occurs, on

average, 16.5 days post-vaccination. Id. However, Agmon-Levin, et al. studied 37 cases of GBS

associated with different vaccines given to infants, children, and adults and found the temporal

association to be between several days to three months. Pet. Ex. 14 at 5. 11 Schonberger, et al.

showed an increased risk of vaccine-related GBS to be concentrated within a five-week period

after vaccination, but lasting for approximately 9-10 weeks. Pet. Ex. 28 at 1. 12 The Langmuir, et

al. study, resulting from a court order, computerized summaries of 1,300 cases of GBS reported to

the CDC during the swine flu vaccination program of 1976-1977 and found that the effects

attributed to the vaccine lasted for at least six weeks and possibly eight weeks but not longer. Resp.

Ex. D at 1. 13 The rarity of TM makes it difficult to study. Id.; Pet. Ex. 16 at 2. 14

The pathogenesis of TM is believed to be autoimmune and involves a breakdown of the

blood-brain barrier (“BBB”) resulting in an inflamed spinal cord in a focal area, pleocytosis, 15 or

both. Pet. Ex. 14 at 1. 16 Several mechanisms by which infectious agents may induce autoimmunity

include molecular mimicry, epitope spreading, and/or polyclonal activation or bystander

activation. Id. at 4. The diagnostic criteria include bilateral sensory, motor, or autonomic

dysfunction attributable to the spinal cord and a clearly defined sensory level with symptoms

peaking within 4 hours to 21 days. Id. at 1.

III. Factual Background

A. Medical History

1. Petitioner’s Health Before Receiving the Flu Vaccine

Petitioner was born on August 30, 1948. Pet. Ex. 2 at 1. Her past medical history was not

contributory but included, in part, deep vein thrombosis, asthma, melanoma with skin resection,

eczema, dry skin, cystocele in need of surgical repair, vitamin D deficiency, and left kidney

removal. See generally, Pet. Ex. 2; Pet. Ex. 3; Pet. Ex. 4 at 34-35; Pet. Ex. 5 at 2, 11, 133, 144,

222; Pet. Ex. 8 at 122.

Petitioner received a flu vaccine on September 24, 2016, at Sam’s Club. Pet. Ex. 1 at 1.

She was 68 years old.

11

Agmon-Levin et al., supra note 7.

12

Lawrence B. Schonberger et al., Guillain-Barre Syndrome Following Vaccination in the National Influenza

Immunization Program, United States, 1976-77, 110 Am. J. of Epidemiology 105 (1979), filed as “Pet. Ex. 28.”

13

Alexander D. Langmuir et al., An Epidemiologic and Clinical Evaluation of Guillain-Barré Syndrome Reporting in

Association with the Administration of Swine Influenza Vaccines, 119 Am. J. of Epidemiology 841 (1984), filed as

“Resp. Ex. D.”

14

Isabelle Korn-Lubetzki et al., H1N1 Vaccine-Related Acute Transverse Myelitis, 13 IMAJ 249 (2011), filed as “Pet.

Ex. 16.”

15

Pleocytosis is the “presence of a greater than normal number of cells in the cerebrospinal fluid.” Pleocytosis,

Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=39556 (last visited

August 28, 2025).

16

Agmon-Levin et al., supra note 7.

4

2. Petitioner’s Health After Receiving the Flu Vaccine

Petitioner presented to her dermatologist on November 23, 2016, for a skin check, dry skin,

and eczema. She had no other complaints. Pet. Ex. 3 at 8.

On November 26, 2016, sixty-three days following receipt of the flu vaccine, petitioner

presented to the emergency room at Community Hospital for numbness in both arms which started

that morning around 8:45 while she was folding towels. Pet. Ex. 5 at 2. Her shoulders felt as though

“‘she had just worked out.’” Id. She then experienced weakness and numbness in both hands. She

reported being fine when she woke up in the morning and denied injury or other cause. Id.

Neurological examination was positive for bilateral hand weakness and upper body numbness. Id.

at 4. She had weak dorsiflexion in both wrists and an inability to maintain any degree of

dorsiflexion versus resistance. Id. at 5. She had weak to absent hand grasp, right worse than left,

and was unable to hold her arms in front of her versus resistance. Id. The remainder of the

examination was normal or negative. Id.

CT scan of the head and MRI of the brain were unremarkable. Pet. Ex. 5 at 6-7, 213, 216.

MRI of the cervical spine revealed an abnormal signal and enhancement within the C6 and C7

vertebral bodies suspicious for metastatic disease; degenerative changes at C5 and C6; bulging

discs at C4-T1 which narrowed the subarachnoid space ventrally but did not affect the cord; and

the neural foramina was patent. Pet. Ex. 5 at 38. The impression was possible metastatic lesions at

C6 -7 and T10 [sic] in the setting of prior melanoma. Id. at 39. A workup with a bone scan, tissue

biopsy, and PET scan were ordered. Id. Lumbar puncture was to be considered along with

neurology checks and evaluations for physical and occupational therapy. Id. at 39-40. MRI of the

thoracic spine revealed a 6mm enhancement seen within T10 which could represent metastatic

disease. Id. at 38.

Petitioner was examined by Dr. Gong of neurology; Dr. Shenoy for asthma; Dr. Shukairy

of neurosurgery; Dr. Atassi of hematology; and Dr. Slotar of infectious disease. Pet. Ex. 5 at 22.

Following discussions with the multiple specialists, petitioner was admitted. Id. at 9.

More specifically, Dr. Gong noted a past medical history of melanoma in remission, a

sudden onset of shoulder and arm paresthesia, and bilateral hand weakness. Pet. Ex. 5 at 52. Dr.

Gong wrote that, given the sudden onset of bilateral upper arm and hand paresthesia and weakness,

there was a need to rule out spinal cord stroke and inflammation. Id. A bone scan and consult with

Dr. Mbaoma was ordered. Id. at 52. Dr. Gong ordered a lumbar puncture, rheumatology and ID

workup, acyclovir, and IV solumedrol for five days with calcium and GI prophylaxis. MRI with

diffusion weighted imaging and apparent diffusion coefficient showed no ischemic lesion of the

cervical spinal cord. Id. at 53. Dr. Gong noted mild weakness and positive reflexes on neurological

examination. Id. at 58. He noted no potential causes in petitioner’s medical history, except that

petitioner had her flu shot about a month prior. 17

Petitioner was examined by Dr. Shenoy of neurosurgery. She was noted to be in her usual

state of health until that morning when she noticed shoulder soreness, then numbness in her

Petitioner’s vaccination records show that she received the flu shot 63 days before she presented to Community

17

Hospital. Pet. Ex. 1.

5

extremities. Pet. Ex. 5 at 40. She had gotten worse since presenting to the emergency room. Her

neurological examination was intact, upper extremity strength was 2/5 bilaterally, with a 3/5 grip

strength and normal sensation. Id. at 43. Lower extremities were normal. Id.

Dr. Shukairy of neurosurgery also noted that her weakness was particularly bad in her

wrists. Pet. Ex. 5 at 79. His impression was sudden onset of weakness in the upper extremities,

and he was concerned about some type of autoimmune onset versus paraneoplastic syndrome. Id.

at 80. He noted no cord compression on objective testing and no need for surgical intervention. Id.

Dr. Atassi of hematology could not rule out malignancy and ordered a bone scan, D dimer,

ESR, serum protein electrophoresis, and serum line chain. Pet. Ex. 5 at 44.

Another MRI of the cervical spine was performed on November 27, 2016, and revealed an

abnormal signal from C4 through C7 determined to be transverse myelitis with demyelinating and

spondylotic changes of the cervical spine. Pet. Ex. 5 at 219.

Dr. Slotar of infectious disease examined petitioner after the finding of TM or other

demyelinating disease on repeat MRI. Pet. Ex. 5 at 81. He ordered a lumbar puncture with full

serologic workup. Id. IV acyclovir was to continue until test results were in. Id. The lumbar

puncture was scheduled for that day. Id. at 95.

Bone scan revealed mild degenerative or traumatic joint changes with no definite evidence

of metastatic bone lesions. Pet. Ex. 5 at 222.

A follow up with Dr. Shukairy on November 28, 2016, confirmed that no surgical

intervention was needed. Pet. Ex. 5 at 101. Test results included TM with no expansion of the cord.

Id. At that time, petitioner reported being able to move her hands better but still had numbness. Id.

On November 29, 2016, petitioner was examined by Dr. Zabiega of neurology. Pet. Ex. 5

at 121. The lumbar puncture was negative for white blood cells but was sent for further testing. Id.

IV solumedrol was continued. Id. Petitioner still had significant numbness in her upper extremities

but there was some improvement. Id.

Dr. Slotar’s concern remained TM even though the lumbar puncture showed no

pleocytosis. Pet. Ex. 5 at 134. Infectious etiologies were unlikely. Id. Acyclovir was to continue

until PCR results were received and IV solumedrol continued. Id. Petitioner was afebrile with

paresthesia and distal weakness that was nominally improved. Id.

Dr. Mbaoma of oncology and hematology examined petitioner on November 30, 2016, and

noted the C6-7 lesion on MRI but a negative bone scan. Pet. Ex. 5 at 178. There was concern for

multiple myeloma due to a high association with TM, though Dr. Mbaoma added he did not see

any evidence to suggest it. Id. Petitioner had improved with steroids and was referred back to

neurology. Id. at 179.

Dr. Zabiega examined petitioner on December 1, 2016, for TM and noted that she was

doing better and could be discharged on a tapering dose of prednisone with neurological follow up

6

in a month. Pet. Ex. 5 at 164. She had a zinc deficiency but not enough to cause myelopathy. A

supplement was needed. Id. Physical therapy evaluation was done that day. Id. at 188-92.

Petitioner was discharged to her home on December 1, 2016, with improving symptoms.

Pet. Ex. 5 at 21-22. The final diagnosis included acute TM, a demyelinating disease of the central

nervous system; other cervical disc degeneration, unspecified; mild intermittent asthma; zinc

deficiency; and allergy to penicillin. Id. at 21.

At a follow up with Dr. Gong on January 30, 2017, her history included a flu shot about

one month prior to onset of symptoms, and no injuries, illness, fever, or tick bites. Pet. Ex. 2 at

114. Her labs largely came back within normal limits, and she tested negative for Lyme. Id. at 115.

Sensation was intact and reflexes were positive, but she still had mild weakness. Id. at 117.

Repeat MRI of the cervical spine performed on February 25, 2017, when compared to her

prior films, revealed persistent but improved signal abnormality in the cervical spinal cord

compatible with history of myelitis. Pet. Ex. 5 at 578. There was also multi-level spondylosis. Id.

Petitioner returned to Dr. Gong on March 20, 2017, with improved weakness. Pet. Ex. 2 at

106-111.

At her visit with pulmonologist Dr. Layous for asthma on May 4, 2017, petitioner was told

that the flu vaccine exacerbated her TM and she was not to receive further flu shots. Pet. Ex. 6 at

9-10. He was also considering what type of pneumonia vaccine she was to receive for her second

shot. Id. at 10.

Dr. Gong documented her TM at her September 18, 2017 visit, noting that her weakness

had improved, but she had continued fingertip weakness. Pet. Ex. 7 at 1. She had cervical

spondylosis with a questionable vertebral bone lesion of unknown etiology. Id. She needed zinc,

B12, and Vitamin D supplements. Id.

Cervical MRI from March 17, 2018, when compared to one from February 25, 2017,

revealed a residual T2 hyperintense signal from C4-C7 with no cord enhancement and no new

signal abnormality. Pet. Ex. 35 at 171. There was multilevel cervical spondylosis. Id. at 171.

Dr. Gong’s impression at petitioner’s March 26, 2018 visit remained TM with cervical

spondylosis. Pet. Ex. 24 at 36. She needed supplements for vitamin D, zinc, and B12. Id. Dr. Gong

documented the onset of TM, including petitioner’s flu vaccine one month before. Id. at 36-37. He

detailed petitioner’s treatment, continued numbness in both hands, arm weakness, and difficulty

with fine motor skills. Id. Petitioner also reported neck stiffness with difficulty turning her head to

the side. Id. at 36.

Petitioner visited neurologist Dr. Joseph on January 28, 2021, with continued complaints

of difficulty with hand coordination, making it difficult to type and do fine motor tasks, following

post-flu vaccine TM. Pet. Ex. 34 at 102-03. Repeat cervical MRIs were noted as stable. Id. at 105.

Petitioner’s relevant medical records end here.

7

B. Petitioner’s Affidavit

Petitioner affirmed that prior to the flu vaccine she was in good health. Pet. Ex. 9 at 1. She

saw a doctor occasionally for a bad cold, skin checks for moles, and asthma for which she used an

inhaler. Id. She was diligent in receiving her flu and other vaccinations. Id.

Petitioner affirmed receipt of a flu vaccine on September 24, 2016, at Sam’s Club. Pet. Ex.

9 at 1. On the morning of November 26, 2016, while folding laundry at about 9:30 am, she

suddenly felt a prickly feeling in her shoulders that spread to her arms and hands. Id. at 1-2. She

became anxious and walked to keep moving. Id. Thinking she was having a stroke or heart attack,

she tried to get ready to go to the hospital, but lost feeling in her hands and arms. Id. By the time

she got to the emergency room at Community Hospital she could not use her hands. Id.

Petitioner affirmed that she saw many doctors, had many tests, and was ultimately

diagnosed with TM. Pet. Ex. 9 at 2. Doing routine tasks was difficult and she was concerned about

losing her job. Id. She was discharged from the hospital on December 1, 2016, and was prescribed

prednisone, which allowed her to better control her arms and hands. Id. She returned to work the

next day. Id. Initially she was driven to work as she was still unable to use her hands to turn the

key or use the gear shift. Id.

Petitioner affirmed that her hands and arms are still weak. Pet. Ex. 9 at 3. Although she can

now perform some tasks, petitioner is aware of every movement and still has a lack of coordination.

Id. at 3-4. At work she performs a variety of clerical tasks, including switchboard, typing, taking

minutes, and stapling hundreds of labels to single sheets of paper. Id. Her typing is slower with

more mistakes. Id. She drops papers because she does not feel them in her hands. Id. When she

became a grandmother, she could not carry the baby while walking due to fear of dropping the

baby. Id. at 4. She has difficulty changing a diaper and her arms are sore and weak from holding

the baby. Id at 4-5. She cannot be relied upon to babysit. Id.

Petitioner affirmed that her doctors have advised against receiving further flu vaccines. Pet.

Ex. 9 at 5.

IV. The Experts

Dr. Tornatore authored three reports in this matter: Pet. Ex. 11; Pet. Ex. 27; and Pet. Ex. 32.

Dr. Donofrio issued two reports: Resp. Ex. A and Resp. Ex. E.

A. Dr. Tornatore’s First Report – Pet. Ex. 11

Following an in-depth recital of petitioner’s medical history, Dr. Tornatore summarized

that petitioner received a flu vaccine on September 24, 2016, at the age of 68, had an onset of

neurologic symptoms in the upper extremities on November 26, 2016, an MRI on November 27,

2016, consistent with transverse myelitis, and other than the vaccination, no other etiology for

transverse myelitis was found. Pet. Ex. 11 at 2-9.

8

Dr. Tornatore described transverse (meaning inflammation across the width of the spinal

cord) myelitis (meaning inflammation of the spinal cord) as a rare clinical syndrome in which an

immune-mediated process causes neural injury to the spine, resulting in varying degrees of

weakness, sensory alterations, and autonomic dysfunction. Pet. Ex. 11 at 9. The inflammation in

TM destroys or damages the myelin, the fatty substance that insulates and covers the nerve fibers,

causing scars that interrupt communications between the nerves and the rest of the body. Id. TM

is part of a continuum of neuroimmunologic disorders which include Guillain-Barré syndrome

(GBS), multiple sclerosis (MS), and acute disseminated encephalomyelitis (“ADEM”). Id.

However, TM and MS are central nervous system (“CNS”) disorders, while GBS and CIDP

(chronic inflammatory demyelinating polyneuropathy) are peripheral nervous system (“PNS”)

disorders. Id.

Dr. Tornatore explained that with TM there is a breakdown of the blood-brain barrier with

cerebral spinal fluid (CSF) pleocytosis within a focal area of the spinal cord. Pet. Ex. 11 at 11; Pet.

Ex. 14 at 2. 18 Vaccines, including the flu vaccine, and various infectious agents have been

implicated in the pathogenesis of TM, which appears to be an autoimmune response triggered by

foreign antigens rather than a direct infectious process. Pet. Ex 11 at 11. In ADEM, a related

condition, “the presumptive mechanism is immune-mediated demyelination although immune-

complex mediated vasculopathy has also been postulated.” Id.; Pet. Ex. 19 at 1-2. 19

Dr. Tornatore explained that the body’s immune system has the ability to distinguish self

from non-self, which is essential for self-defense and protection from autoimmune destruction.

Pet. Ex. 11 at 11. However, a breakdown of self-tolerance to autoantigens is necessary to the

development of autoimmunity. Id. Therefore, it is reasonable that if an infectious antigen can cause

autoimmunity so can recombinant or live attenuated antigens in a vaccine. Id.

Dr. Tornatore then proposed several mechanisms by which autoimmunity can occur. Pet.

Ex. 11 at 11-12. Molecular mimicry between infectious antigens and self-antigens is the most

common. Id. at 11. Epitope spreading involves invading antigens that accelerate an ongoing

autoimmune process by local activation of antigen presenting cells and over-processing of

antigens. Id. at 12. Polyclonal activation of B lymphocytes or bystander activation, which enhances

cytokine production, may further induce the expansion of auto-reactive cells in response to

infectious agents. Id. Bystander activation has been associated with TM due to elevated IL-6 levels

found in the CSF of TM patients. Id. at 12; Pet. Ex. 14 at 4. 20

Dr. Tornatore added that molecular mimicry has more than one biologic process. Pet. Ex.

11 at 12. Classically, antibodies cross-react directly with viral and cellular proteins. Id. However,

another well-established model shows T-cell activation cross-reacting against myelin basic

protein. Id. The process of T-cell activation against an antigen can damage nearby cells, leading

to collaterally damaging effects to cell structures from the release of cytokines and macrophage

activation. Id. “[I]nteractions of the immune cells and the potential for a negative cascade of auto-

immunity have led to postulation of what is termed the ‘fertile field’ model.” Id. This model

18

Agmon-Levin et al., supra note 7.

19

William Huynh et al., Post-Vaccination Encephalomyelitis: Literature Review and Illustrative Case, 15 J. of Clinical

Neuroscience 1315 (2008), filed as “Pet. Ex. 19.”

20

Agmon-Levin et al., supra note 7.

9

features the activation of an immune response by an immunogen with sequence homology to self-

proteins which may prime autoreactive T-cells in the host, but which lack the momentum to initiate

an adverse autoimmune reaction by themselves. Id. A later or coincidental immune stimulation

from a vaccine or other immunogen, even one without cross-reactive antigens or sequence

similarity, could initiate an autoimmune reaction in a susceptible host that could lead to

inflammatory demyelination. Id. at 12; see generally Pet. Ex. 19. 21 Receptors on B and T cells

once thought to have a high level of specificity for individual foreign antigens are now known to

recognize peptide sequences with no shared homology. Pet. Ex. 11 at 13. A single T-cell receptor

may recognize thousands of different peptide sequences. Id.; see generally Pet. Ex. 26.22

Therefore, microbiologic antigens from bacteria or viruses that bear no similarity to nervous

system antigens could activate a B- or T-cell receptor causing the B or T cell to mount an

autoimmune response in the nervous system. Pet. Ex. 11 at 13. The general principle of antigenic

stimulation or vaccination as a trigger for autoimmune nervous system disease is well accepted.

An example is allergic encephalitis. Id. at 13.

Dr. Tornatore submitted that the clinical presentation of TM includes bilateral sensory,

motor or autonomic dysfunction attributable to the spinal cord, a clearly defined sensory level, and

peaking symptoms within four hours and 21 days. Pet. Ex. 11 at 10; Pet. Ex. 14 at 1. 23 Evidence

of TM includes inflamed spinal cord manifesting as cerebrospinal fluid pleocytosis, elevated IgG

index, or gadolinium enhancement by MRI. Pet. Ex. 11 at 10. The exclusion of “extra-axial

compressive etiology by neuroimaging should be observed.” Id. MRI findings for TM are

nonspecific, and may include spinal cord enlargement, intramedullary increased T2 signal lesions,

and variable enhancement. Id.; Pet. Ex. 13 at 1; 24 see Pet. Ex. 15 at 2.25 Petitioner presented with

the typical presentation and progression for TM. Id. An inflammatory lesion was seen on MRI

extending across more than three vertebral segments longitudinally (C4/5 to C7). Id.

Dr. Tornatore referenced case studies associating TM with vaccination. Bakshi, et al.

reported on cases involving TM following vaccines, including the flu vaccine. Pet. Ex. 11 at 9;

Pet. Ex. 13 at 1.26 Korn-Lubetzki, et al. was a case study involving the H1N1 influenza vaccine,

where cervical MRI revealed a hyperintense lesion at C6 and C7 with mild expansion of the cord

and enhancement with gadolinium. Pet. Ex. 11 at 10; Pet. Ex. 16 at 1. 27 The data supported the

diagnosis of post-vaccinal TM “due to an immunological reaction to the vaccine” and negative

results for alternative causes. Pet. Ex. 11 at 10; Pet. Ex. 16 at 1-2. 28 Akkad was a case study of a

patient with longitudinally extensive TM following the H1N1 flu vaccine, who presented with a

two-week history of back and lower extremity pain, gradual weakness, paresthesia of the legs, and

urinary retention which progressed to all extremities, leaving the patient unable to stand. Pet. Ex.

21

Huynh et al., supra note 19.

22

Don Mason, A Very High Level of Crossreactivity is an Essential Feature of the T-Cell Receptor, 19 Immunology

Today 395 (1998), filed as “Pet. Ex. 26.”

23

Agmon-Levin et al., supra note 7.

24

Bakshi & Mazziotta, supra note 6.

25

Wafa Akkad et al., Longitudinally Extensive Transverse Myelitis Following Vaccination with Nasal Attenuated

Novel Influenza A(H1N1) Vaccine, 67 Archives of Neurology 1018 (2010), filed as “Pet. Ex. 15.”

26

Bakshi & Mazziotta, supra note 6.

27

Korn-Lubetzki et al., supra note 14.

28

Id.

10

11 at 10; Pet. Ex. 15 at 1. 29 Examination revealed proximal muscle weakness with sensory loss in

the lower extremities and diminished sensation in the trunk with a T4 sensory level. There was

diffuse hyperreflexia, silent plantar response, and no clonus. MRI revealed extensive non-

enhancing T2 hypersensitivity from the cervical medullary junction throughout the length of the

thoracic cord. A brain MRI was negative for demyelinating lesions. Nerve conduction studies were

normal. Pet. Ex. 11 at 10-11; Pet. Ex. 15 at 1-2. 30 The diagnosis was arrived at by CSF and blood

testing for infectious causes and by ruling out MS, ADEM, vascular lesions, and neuromyelitis

optica. Pet. Ex. 11 at 11. Akkad linked the patient’s TM to the recent H1N1 vaccination fewer than

30 days before neurologic onset. Id. at 11; see Pet. Ex. 15.31 Nakamura, et al. showed TM

following vaccination as just as plausible as GBS. Id.; see Pet. Ex. 18. 32

In Dr. Tornatore’s opinion, the foregoing supports a biologically plausible hypothesis, as

well as a reasonable sequence of cause and effect. Petitioner received the flu vaccine which has

been causally associated with TM. Her medical records show that extensive testing ruled out any

other potential alternative cause. Pet. Ex. 11 at 13.

Relying on Agmon-Levin, Dr. Tornatore argued that most cases of TM have an onset

between several days and 3 months. Pet. Ex. 11 at 13; Pet. Ex. 14 at 5. 33 Neurological onset of

symptoms can develop with a latency ranging from 1 to 63 days with a mean of 16.5 days. Pet.

Ex. 11 at 13. Petitioner’s onset was 63 days. Id. at 14. Therefore, petitioner’s flu vaccine played a

significant causal role in initiating or triggering her TM and onset was within an appropriate

timeframe. Id.

B. Dr. Donofrio’s First Report – Resp. Ex. A

Following a recital of petitioner’s medical history, Dr. Donofrio focused on the 63-day

onset being too long for an immune response following vaccination and that petitioner had an

undiagnosed and untreated UTI that was the cause of her TM. Resp. Ex. A at 5-6.

Dr. Donofrio submitted that no epidemiological studies exist that show that the flu vaccine

can cause TM. The best evidence that can be offered is data about GBS from the swine flu epidemic

of 1976-1977. Resp. Ex. A at 5; Resp. Ex. D. 34 Dr. Donofrio noted that when considering that the

first licensed flu vaccine in the US was in 1943 with billions of vaccines administered over the

past 80 years, the absence of an epidemiologic relationship between the flu vaccine and the

development of TM was notable: “[A]ny reports of TM following flu vaccination are best

explained by chance occurrence rather than causality.” Resp. Ex. A at 6. Further, the 2012 Institute

of Medicine report, Adverse Effects of Vaccines, concluded that the epidemiological evidence was

insufficient or absent to assess an association between the influenza vaccine and TM and that the

mechanistic evidence was weak based on the knowledge of natural infection. Resp. Ex. A at 6;

29

Akkad et al., supra note 25.

30

Id.

31

Id.

32

Naoko Nakamura et al., Neurologic Complications Associated with Influenza Vaccination: Two Adult Cases, 42

Internal Medicine 191 (2003), filed as “Pet. Ex. 18.”

33

Agmon-Levin et al., supra note 7.

34

Langmuir et al., supra note 13.

11

Resp. Ex. C. 35 Therefore, the evidence was inadequate to accept or reject a causal relationship

between the flu vaccine and TM. Resp. Ex. A at 6.

Dr. Donofrio argued that a 63-day onset was not medically appropriate. The latency or lag

phase between primary exposure and the development of the primary antibody response is seven

to ten days or shorter for subsequent exposure to the same antigen. Resp. Ex. A at 5; Resp. Ex.

C. 36 Langmuir, et al. showed an increase of GBS within six weeks of swine flu vaccination which

led to the Vaccine Injury Table timeline of 3-42 days for GBS associated with flu vaccination.

Resp. Ex. A at 5; Resp. Ex. D at 1. 37 Therefore, a cause-and-effect determination should be much

shorter than the 63 days in this case.

Additionally, Dr. Donofrio argued that petitioner had an undiagnosed UTI. Pet. Ex. A at 6.

He referenced Agmon-Levin as showing that 40% of the 37 cases of TM studied between 1970 and

2009 were associated with preceding infectious illness: “[Petitioner’s] urinalysis from [November

26, 2016] showed 11 white blood cells, 2 red blood cells, and an elevated white blood cell esterase

25 (reference negative).” Id. at 5.; see Pet. Ex. 5 at 37. The “lab results were highlighted as

abnormal (A).” Id. According to Dr. Donofrio, petitioner’s UTI was a sufficient inciting event for

TM and much more likely the precipitating event than the flu vaccine. Resp. Ex. A at 5.

Dr. Donofrio added that TM is a monophasic illness and, because petitioner “denied

weakness, tremor, paresthesia or numbness” at her January 5, 2017, visit, her complaints of

ongoing numbness in her fingertips and difficulty with activities of daily living worsening after

January 2017 must be indicative of another cause. Resp. Ex. A at 6; Pet. Ex. 6 at 4. He did not

however indicate what that other cause was.

In Dr. Donofrio’s opinion, petitioner’s onset of injury 63 days after receipt of the subject

flu vaccine was “well beyond any interval considered reasonable for an immune reaction to the flu

vaccine.” Additionally, petitioner had an undiagnosed urinary tract infection which was more

likely the cause of her TM because infection precedes TM in 40% of patients. Resp. Ex. A at 6.

C. Dr. Tornatore’s Second Report – Pet. Ex. 27

In his second report, Dr. Tornatore maintained that a 63-day onset was medically

appropriate for TM and supported by the literature. The latency period for the development of

neurologic symptoms typically ranges from 1 to 63 days with a mean of 16.5 days, though there

are cases stretching to three months as well. Pet. Ex. 27 at 2; Pet. Ex. 13 at 1. 38 Further,

Schonberger, et al. reported an increased risk period of autoimmune disorders concentrated within

the five-week period after vaccination but lasting for approximately nine to ten weeks.

Schonberger, et al. found that post vaccinal autoimmune disorders of the nervous system can occur

up to 70 days post-vaccination. Pet. Ex. 27 at 2; Pet. Ex. 28. 39 Dr. Tornatore added that in

35

Institute of Medicine of the National Academies, Adverse Effects of Vaccines: Evidence and Causality (Kathleen

Stratton et al. eds., 2012), filed as “Resp. Ex. C.”

36

Institute of Medicine of the National Academies, supra note 34.

37

Langmuir et al., supra note 13.

38

Bakshi & Mazziotta, supra note 6.

39

Schonberger et al., supra note 12.

12

discussing GBS, Dr. Donofrio conceded that vaccinations can result in an autoimmune disorder of

the nervous system. Pet. Ex. 27 at 2.

Dr. Tornatore disagreed that petitioner had a UTI that was more likely the cause of her TM.

Pet. Ex. 27 at 2. Dr. Tornatore pointed out that the urinalysis performed on November 26, 2016,

showed no bacteria or cause for repeat testing and petitioner had no complaints of any symptoms

related to a UTI. Id.; Pet. Ex. 5 at 218. He discussed a phenomenon called sterile pyuria, where

patients with systemic autoimmune processes have white blood cells found in the urine even in the

absence of infection. In this case, the presence of white blood cells in the absence of infection

could have been caused by post-vaccinal immune activation that spilled into the bladder. Pet. Ex.

27 at 2. In his over 40 years of practice, Dr. Tornatore has encountered this phenomenon many

times in the TM patients he has treated. Id.

Dr. Tornatore maintained that petitioner’s September 24, 2016, flu vaccine triggered her

TM with lingering neurologic symptoms and deficits. He relied on his first report as detailing the

biologically plausible theory and logical sequence of cause and effect between the flu vaccine and

petitioner’s TM with no evidence of alternative cause seen in the medical records. The onset of

symptoms was within an appropriate time. Pet. Ex. 27 at 2.

D. Dr. Donofrio’s Second Report – Resp. Ex. E

In his second report, Dr. Donofrio again discussed the 63-day onset of petitioner’s TM

following her flu vaccine. He referenced Langmuir, et al. as the best data available showing that

“[t]he effect attributed to the vaccine lasted for at least six weeks and possibly for eight weeks but

not longer. . . . 00The authors did not consider any patients who developed GBS after 8 weeks (56

days) to have developed GBS from the flu vaccine.” Resp. Ex. E at 1. He noted that the Langmuir

study was ordered by the court five years after the Schonberger study and was a more rigid study

than Schonberger. Langmuir looked at cases of extensive motor involvement or weakness due to

concerns that patients with milder disease may not have GBS. Id.

Dr. Donofrio repeated that there is no epidemiologic data relating TM and flu vaccination.

The best data regarding immunologic response to the vaccine relates specifically to GBS from

1976-77. Pet. Ex. E at 1.

Dr. Donofrio maintained that petitioner’s undiagnosed UTI was the cause of her TM. He

disagreed that she had sterile pyuria resulting from a systemic autoimmune process that spilled

into the bladder. Pet. Ex. E at 2. He added that Dr. Tornatore did not mention what systemic

autoimmune disease to which he referred, and that petitioner did not have a systemic disease. Id.

at 2. Dr. Donofrio relied on Stamm, a 1984 study which measured pyuria, or white blood cells in

urine, in female patients with acute simple cystitis, concluding that white blood cells in urine are

the best indicator of infection. Id. at 1; Resp. Ex. F. 40 “Ten or more WBCs per mm3 occur in less

than 1 percent of asymptomatic, non-bacteriuric patients but in greater than 96 percent of the

symptomatic men and women with significant bacteriuria.” Resp. Ex. E at 1. Petitioner’s urinalysis

40

Walter E. Stamm, Measurement of Pyuria and Its Relation to Bacteriuria, 75 Am. J. of Medicine 53 (1983), filed

as “Resp. Ex. F.”

13

revealed 11 white blood cells, 2 red blood cells, and white blood cell esterase elevated at 25

(reference negative). Id. at 2. Therefore, petitioner had an undiagnosed and untreated UTI. Id.

Dr. Donofrio denied that in Hitt, 2020 WL 831822, he agreed to a 63-day onset of TM

from flu vaccine. Resp. Ex. E at 1. He disagreed that Langmuir’s data showed a bell-shaped curve

with an increased relative risk of GBS after eight weeks. Though Langmuir, et al. might have noted

patients whose GBS onset was more remote than eight weeks, the study did not consider these

patients to have developed GBS from the flu vaccine. Resp. Ex. E at 2.

E. Dr. Tornatore’s Third Report – Pet. Ex. 32

In his third report Dr. Tornatore addressed Dr. Donofrio’s reliance on Langmuir, et al.

which stated that the risk interval for the development of GBS following flu vaccine was restricted

to eight weeks. Pet. Ex. 32 at 1. Dr. Tornatore argued that a 63-day onset was an acceptable

timeframe for TM. He provided a paper by Freedman and Stark entitled, “The swine flu vaccine

and Guillain-Barré syndrome. A case study in relative risk and specific causation.” Pet. Ex. 33.41

This paper detailed the history of the first recorded influenza pandemic in 1918 that killed 20

million people worldwide. This was followed by the 1976-77 influenza pandemic, a virus with a

similar antigenic type to the 1918 virus, which led the federal government to organize a massive

immunization campaign. 151 million people over the age of 18 were targeted, with 43 million

people ultimately vaccinated. Id. at 3-6. The CDC set up a nationwide surveillance system to

collect data on GBS from state health authorities and hired Langmuir and associates to analyze the

data. Id. at 4. Unvaccinated GBS rates were used for comparison. Id.; Pet. Ex. 32 at 1-2. Notably,

Langmuir distinguished cases with extensive paralysis from limited paralysis showing strong

association for the extensive cases. Pet. Ex. 33 at 7. 42 The federal government took responsibility

for the over 4,000 claims filed as a result of the swine flu vaccine when insurance companies

refused to cover the injuries and drug companies refused to produce the vaccine without protection.

Over four billion dollars was paid in damages. Id. at 8.

One of those claims was detailed in the case of Manko v. United States, 636 F. Supp. 1419

(W.D. Mo. 1986) aff’d in part, 830 F. 2d 831 (8th Cir. 1987). The defendant argued that there was

only a small excess risk for developing GBS after the eighth week following vaccination. Pet. Ex.

32 at 2-3; Pet. Ex. 33 at 8. 43 The defendant did not agree with the methods and data results relied

on by the plaintiff’s experts but conceded that the plaintiff’s presentation was very different than

the data set used in the Langmuir paper. They concluded that the mathematical models showed

how individual differences can be represented in a more general but abstract setting with results

confirming that epidemiological data cannot determine the probability of causation in a meaningful

way because of those differences. Pet. Ex. 32 at 3. Dr. Tornatore concluded this was a compelling

argument for a prolonged onset interval for GBS following flu vaccine depending on how complete

the data is, how it is analyzed, and individual differences. Pet. Ex. 32 at 3; Pet. Ex. 33 at 15-16. 44

He concluded that, where biological plausibility and logical sequence of cause and effect exist,

41

David A. Freedman & Philip B. Stark, The Swine Flu Vaccine and Guillain-Barré Syndrome: A Case Study in

Relative Risk and Specific Causation, 64 Law and Contemporary Problems 49 (1999), filed as “Pet. Ex. 33.”

42

Id.

43

Id.

44

Id.

14

they buttress the argument that the flu vaccine can result in the development of TM with an onset

of 63 days. Pet. Ex. 32 at 4.

Dr. Tornatore maintained that petitioner did not have a UTI and UTI was not the cause of

her TM; rather, the 11 white blood cells on urinalysis was sterile pyuria. Pet. Ex. 32 at 4. He argued

that the table in Stamm demonstrated that pyuria can be found in 1.6% of asymptomatic,

abacteriuric patients, not the less than 1% as opined by Dr. Donofrio. Dr. Tornatore showed that,

like the petitioner, up to 3.1% of asymptomatic abacteriuric patients have sterile pyuria. Id.

Therefore, Stamm supported rather than rebutted the argument that sterile pyuria can exist in a

patient with WBC >10wbc/mm. Id. at 4; Resp. Ex. F. 45 Further, the presence of “[l]eukocyte

esterase is evidence of leukocytes, not infection.” 46 Pet. Ex. 32 at 4.

Dr. Tornatore maintained his opinion that the flu vaccine received by petitioner on

September 24, 2016, triggered her TM with lingering neurologic symptoms and deficits

attributable to the initial inflammatory insult. Pet. Ex. 32 at 4.

V. Legal Framework

A. Legal Standard Regarding Causation

The Vaccine Act provides two avenues for petitioners to receive compensation. First, a

petitioner may demonstrate a “Table” injury—i.e., an injury listed on the Vaccine Injury Table

that occurred within the provided time period. § 11(c)(1)(C)(i). “In such a case, causation is

presumed.” Capizzano v. Sec’y of Health & Hum. Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006);

see § 13(a)(1)(B). Second, where the alleged injury is not listed on the Vaccine Injury Table, a

petitioner may demonstrate an “off-Table” injury, which requires that the petitioner “prove by a

preponderance of the evidence that the vaccine at issue caused the injury.” Capizzano, 440 F.3d at

1320; see § 11(c)(1)(C)(ii). Initially, a petitioner must provide evidence that he or she suffered, or

continues to suffer, from a definitive injury. Broekelschen v. Sec’y of Health & Hum. Servs., 618

F.3d 1339, 1346 (Fed. Cir. 2010). A petitioner need not show that the vaccination was the sole

cause, or even the predominant cause, of the alleged injury; showing that the vaccination was a

“substantial factor” and a “but for” cause of the injury is sufficient for recovery. See Pafford v.

Sec’y of Health & Hum. Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006); Shyface v. Sec’y of Health

& Hum. Servs., 165 F.3d 1344, 1352 (Fed. Cir. 1999). 47

To prove causation for an “off-Table” injury, petitioners must satisfy the three-pronged test

established in Althen v. Sec’y of Health & Hum. Servs., 418 F.3d 1274 (Fed. Cir. 2005). Althen

requires that petitioners show by preponderant evidence that a vaccination caused petitioner’s

injury “by providing: (1) a medical theory causally connecting the vaccination and the injury; (2)

45

Stamm, supra note 39.

46

“Leukocyte [] esterase is a screening test used to detect leukocytes in the urine.” Kathleen Deska Pagana & Timothy

J. Pagana, Mosby’s Manual of Diagnostic and Laboratory Tests 900 (6th ed. 2018). Leukocytes are “white blood cells

[] that fight infections.” Id. at 648.

47

The Vaccine Act also requires petitioners to show by preponderant evidence the vaccinee suffered from the “residual

effects or complications” of the alleged vaccine-related injury for more than six months, died from the alleged vaccine-

related injury, or required inpatient hospitalization and surgical intervention as a result of the alleged vaccine-related

injury. § 11(c)(1)(D). It is undisputed that this requirement is satisfied in this case.

15

a logical sequence of cause and effect showing that the vaccination was the reason for the injury;

and (3) a showing of a proximate temporal relationship between vaccination and injury.” Id. at

1278. Together, these prongs must show “‘that the vaccine was not only a but-for cause of the

injury but also a substantial factor in bringing about the injury.’” Id. at 1278 (quoting Shyface, 165

F.3d at 1352-53). Causation is determined on a case-by-case basis, with “no hard and fast per se

scientific or medical rules.” Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 548 (Fed.

Cir. 1994). Petitioners are not required to identify “specific biological mechanisms” to establish

causation, nor are they required to present “epidemiologic studies, rechallenge, the presence of

pathological markers or genetic disposition, or general acceptance in the scientific or medical

communities.” Capizzano, 440 F.3d at 1325 (quoting Althen, 418 F.3d at 1280). “[C]lose calls

regarding causation are resolved in favor of injured claimants.” Althen, 418 F.3d at 1280.

Each of the Althen prongs requires a different showing. The first Althen prong requires

petitioner to provide a “reputable medical theory” demonstrating that the vaccines received can

cause the type of injury alleged. Pafford, 451 F.3d at 1355-56 (citation omitted). To satisfy this

prong, petitioner’s “theory of causation must be supported by a ‘reputable medical or scientific

explanation.’” Andreu ex rel. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1379 (Fed.

Cir. 2009) (quoting Althen, 418 F.3d at 1278). This theory need only be “legally probable, not

medically or scientifically certain.” Id. at 1380 (emphasis omitted) (quoting Knudsen, 35 F.3d at

548-49). Nevertheless, “petitioners must proffer trustworthy testimony from experts who can find

support for their theories in medical literature.” LaLonde v. Sec’y of Health & Hum. Servs., 746

F.3d 1334, 1341 (Fed. Cir. 2014).

The second Althen prong requires proof of a “logical sequence of cause and effect.”

Capizzano, 440 F.3d at 1326 (quoting Althen, 418 F.3d at 1278). In other words, even if the

vaccinations can cause the injury, petitioner must show that it did so in this particular case. See

Hodges v. Sec’y of Health & Hum. Servs., 9 F.3d 958, 962 n.4 (Fed. Cir. 1993) (finding that even

though petitioner’s expert showed that a particular vaccine could cause death, the expert failed to

show that it caused the death of petitioner, specifically). “A reputable medical or scientific

explanation must support this logical sequence of cause and effect,” id. at 961 (citation omitted),

and “treating physicians are likely to be in the best position to determine whether a logical

sequence of cause and effect show[s] that the vaccination was the reason for the injury,” Paluck v.

Sec’y of Health & Hum. Servs., 786 F.3d 1373, 1385 (Fed. Cir. 2015) (quoting Andreu, 569 F.3d

at 1375). Petitioner is not, however, required “to eliminate alternative causes as part of establishing

[their] prima facie case.” Doe v. Sec’y of Health & Hum. Servs., 601 F.3d 1349, 1357-58 (Fed. Cir.

2010); see Walther v. Sec’y of Health & Hum. Servs., 485 F.3d 1146, 1152 (Fed. Cir. 2007)

(holding that a “petitioner does not bear the burden of eliminating alternative independent potential

causes”).

To satisfy the third Althen prong, petitioner must establish a “proximate temporal

relationship” between the vaccination and the alleged injury. Althen, 418 F.3d at 1278. This

“requires preponderant proof that the onset of symptoms occurred within a timeframe for which,

given the medical understanding of the disorder’s etiology, it is medically acceptable to infer

causation-in-fact.” de Bazan v. Sec’y of Health & Hum. Servs., 539 F.3d 1347, 1352 (Fed. Cir.

2008). Typically, “a petitioner’s failure to satisfy the proximate temporal relationship prong is due

to the fact that onset was too late after the administration of a vaccine for the vaccine to be the

16

cause.” Id. However, “cases in which onset is too soon” also fail this prong; “in either case, the

temporal relationship is not such that it is medically acceptable to conclude that the vaccination

and the injury are causally linked.” Id.; see also Locane v. Sec’y of Health & Hum. Servs., 685

F.3d 1375, 1381 (Fed. Cir. 2012) (“[If] the illness was present before the vaccine was administered,

logically, the vaccine could not have caused the illness.”).

B. Legal Standard Regarding Fact Finding

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

begins with analyzing the medical records, which are required to be filed with the petition. §

11(c)(2). Medical records created contemporaneously with the events they describe are generally

considered to be more trustworthy. Cucuras v. Sec’y of Health & Hum. Servs., 993 F.2d 1525,

1528 (Fed. Cir. 1993); but see Kirby v. Sec’y of Health & Hum. Servs., 993 F.3d 1378, 1382-83

(Fed. Cir. 2021) (clarifying that Cucuras does not stand for proposition that medical records are

presumptively accurate and complete). While not presumed to be complete and accurate, medical

records made while seeking treatment are generally afforded more weight than statements made

by petitioners after-the-fact. See Gerami v. Sec'y of Health & Hum. Servs., No. 12-442V, 2013 WL

5998109, at *4 (Fed. Cl. Spec. Mstr. Oct. 11, 2013) (finding that contemporaneously documented

medical evidence was more persuasive than a letter prepared for litigation purposes), mot. for rev.

denied, 127 Fed. Cl. 299 (2014). Indeed, “where later testimony conflicts with earlier

contemporaneous documents, courts generally give the contemporaneous documentation more

weight.” Campbell ex rel. Campbell v. Sec’y of Health & Hum. Servs., 69 Fed. Cl. 775, 779 (2006);

see United States v. U.S. Gypsum Co., 333 U.S. 364, 396 (1948).

Despite the weight afforded medical records, special masters are not bound rigidly by those

records in determining facts such as the onset of a petitioner’s symptoms. Vallenzuela v. Sec’y of

Health & Hum. Servs., No. 90-1002V, 1991 WL 182241, at *3 (Fed. Cl. Spec. Mstr. Aug. 30,

1991); see also Eng v. Sec’y of Health & Hum. Servs., No. 90-175V, 1994 WL 67704, at *3 (Fed.

Cl. Spec. Mstr. Feb 18, 1994) (explaining that § 13(b)(2) “must be construed so as to give effect

to § 13(b)(1) which directs the special master or court to consider the medical record . . . but does

not require the special master or court to be bound by them”); see also Burns v. Sec'y of Health &

Hum. Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (holding that it is within the special master's

discretion to determine whether to afford greater weight to medical records or to other evidence,

such as oral testimony surrounding the events in question that was given at a later date, provided

that such determination is rational).

In short, “the record as a whole” must be considered. § 13(a).

C. Evaluating Expert Testimony

Establishing a sound and reliable medical theory connecting the vaccine to the injury often

requires a petitioner to present expert testimony in support of his or her claim. Lampe v. Sec’y of

Health & Hum. Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). The Supreme Court’s opinion in

Daubert v. Merrell Dow Pharms., Inc., 509 U.S. 579 (1993), requires that courts determine the

reliability of an expert opinion before it may be considered as evidence. “In short, the requirement

that an expert’s testimony pertain to ‘scientific knowledge’ establishes a standard of evidentiary

17

reliability.” Id. at 590 (citation omitted). Thus, for Vaccine Act claims, a “special master is entitled

to require some indicia of reliability to support the assertion of the expert witness.” Moberly ex

rel. Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315, 1324 (Fed. Cir. 2010). The Daubert

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

of Health & Hum. Servs., 94 Fed. Cl. 53, 66 (2010) (“[U]niquely in this Circuit, the Daubert factors

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

of expert testimony already admitted.”). Where both sides offer expert testimony, a special

master’s decision may be “based on the credibility of the experts and the relative persuasiveness

of their competing theories.” Broekelschen, 618 F.3d at 1347 (citing Lampe, 219 F.3d at 1362).

And nothing requires the acceptance of an expert’s conclusion “connected to existing data only by

the ipse dixit of the expert,” especially if “there is simply too great an analytical gap between the

data and the opinion proffered.” Snyder ex rel. Snyder v. Sec’y of Health & Hum. Servs., 88 Fed.

Cl. 706, 743 (2009) (quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)).

D. Consideration of Medical Literature

Finally, although this decision discusses some but not all of the literature in detail, the

undersigned reviewed and considered all of the medical records and literature submitted in this

matter. See Moriarty ex rel. Moriarty v. Sec’y of Health & Hum. Servs., 844 F.3d 1322, 1328 (Fed.

Cir. 2016) (“We generally presume that a special master considered the relevant record evidence

even though [s]he does not explicitly reference such evidence in h[er] decision.”); Simanski v.

Sec’y of Health & Hum. Servs., 115 Fed. Cl. 407, 436 (2014) (“[A] Special Master is ‘not required

to discuss every piece of evidence or testimony in her decision.’”) (citation omitted), aff’d, 601 F.

App’x 982 (Fed. Cir. 2015).

VI. Discussion & Analysis

There is no dispute that petitioner had an onset of TM symptoms 63 days after receipt of

the subject flu vaccination. Dr. Donofrio does little to dispute Dr. Tornatore’s theory of causation

in this case. Rather, his focus is twofold: 1) the 63-day onset is too long for an immune response

to flu vaccination, and 2) petitioner had a urinary tract infection which was the cause of her TM.

Dr. Donofrio submitted three publications in support of his opinions – the section of the 2012 IOM

report for flu vaccination and TM, Langmuir, et al. for onset, and Stamm discussing urinary tract

infection. Resp. Ex. C; 48 Resp. Ex. D; 49 Resp. Ex. F. 50

A. Althen Prong One

For Althen prong one, petitioner must establish a “reputable” medical theory that the flu

vaccination can cause her injury by a preponderance of the evidence, but she does not need to

prove that theory to the level of scientific certainty. Althen, 418 F.3d at 1278 (“A persuasive

medical theory is . . . supported by reputable medical or scientific explanation.”) (internal citations

omitted). In a later case, the Federal Circuit required that the theory be “legally probable.” Moberly

48

Institute of Medicine of the National Academies, supra note 34.

49

Langmuir et al., supra note 13.

50

Stamm, supra note 39.

18

ex rel. Moberly v. Sec'y of Health & Hum. Servs., 592 F.3d 1315, 1322 (Fed. Cir. 2010) (citation

omitted).

Dr. Tornatore opined that the flu vaccine can cause TM via molecular mimicry. Pet. Ex.

11 at 11-12. He relied on Agmon-Levin, et al. which noted that “[t]he pathogenesis of [TM] is

mostly of an autoimmune nature, triggered by various environmental factors, including

vaccination.” Pet. Ex. 14 at 1. 51 Agmon-Levin, et al. was a systemic review of journals published

between 1970 and 2009 analyzing cases of TM following vaccination. Id. at 1. Their initial search

included 43 cases, but six were excluded due to insufficient data. Id. at 2. Of the remaining 37

cases, two were reported after influenza vaccine. Id. at 2, 3. “In most of these cases the temporal

association was between several days and 3 months.” Id. at 5. Twenty-seven of the 37 cases (73%)

developed symptoms of TM within the first month after vaccination, three developed symptoms

between one and two months after vaccination, and seven developed symptoms more than two

months after vaccination. Id. at 2, 3. Of the two cases of TM following influenza vaccine, onset

was seven and nine days. Id. at 3. The authors added that a “host’s response to a vaccine, originally

generated to produce protective immunity, is similar to its response to an infectious invasion.” Id.

at 4. They concluded that “the temporal association between [ ] vaccines and TM, and the possible

mechanism associating these phenomena cannot be ignored. The rarity of TM makes it a difficult

disease to study.” Id. at 5.

Dr. Tornatore detailed how structural similarities between an antigen and self-peptides can

cause them to cross-react, resulting in the development of autoreactive B and T cells which can

cause inflammation and can lead to demyelination. Pet. Ex. 11 at 12-13. He added that homology

in amino acid sequences between an antigen and self-peptides is not the only mechanism that can

cause an autoimmune response. Id. at 13. Receptors on the B and T cells initially thought to have

a high level of specificity for individual foreign antigens are now known to recognize peptide

sequences that share no homology, with one T cell able to recognize thousands of peptide

sequences. This is called “degeneracy.” Id. at 13; Pet. Ex. 26 at 2-3. 52 Further, the mechanism of

bystander activation is the process by which activated T cells react to an antigen damaging cells

nearby, both releasing cytokines and by macrophage activation. Pet. Ex. 11 at 12; Pet. Ex. 25 at

2. 53

Finally, Dr. Tornatore discussed the concept of the fertile field model which includes both

aspects of molecular mimicry and bystander activation. Here, an antigen with sequence homology

to self-proteins may prime autoreactive T cells but lacks sufficient “momentum” to trigger an

autoimmune response by itself. Instead, a later immune stimulation, whether by infection or

vaccination, even without cross-reactive antigens or sequence homology, initiates an autoimmune

reaction in a susceptible host leading to inflammatory demyelination. Pet. Ex. 11 at 12; Pet Ex. 25

at 4. 54 Dr. Tornatore added that it is accepted that flu vaccination can cause autoimmune

demyelinating disease resulting from these various mechanisms which may occur sequentially or

51

Agmon-Levin et al., supra note 7.

52

Mason, supra note 22.

53

Robert S. Fujinami et al., Molecular Mimicry, Bystander Activation, or Viral Persistence: Infections and

Autoimmune Disease, 19 Clinical Microbiology Reviews 80 (2006), filed as “Pet. Ex. 25.”

54

Id.

19

concurrently. Pet. Ex. 11 at 13. Dr. Tornatore states that the flu vaccine “has been causally

associated with [TM]” in the cited literature. Id.

Dr. Tornatore submitted case studies to support the association between the flu and/or

H1N1 influenza vaccine(s) and TM and ADEM. Pet. Ex. 13; 55 Pet. Ex. 14; 56 Pet. Ex. 15; 57 Pet.

Ex. 16; 58 Pet. Ex. 17; 59 Pet. Ex. 20. 60 Dr. Donofrio argued that case reports carry little weight.

Resp. Ex. A at 6. Case reports are generally not sufficient to prove causation; but in the context of

rare conditions, such as TM, where epidemiologic studies are unavailable, they provide some

evidence of causation. See, e.g., Irwin v. Sec’y of Health & Hum. Servs., No. 16-1454V, 2024 WL

863690, at *18 (Fed. Cl. Spec. Mstr. Jan. 23, 2024) (finding that case reports do not, by themselves,

establish causation, but that they do provide evidence in favor of causation). Here, where medical

literature has reported TM associated with flu vaccines, the evidence weighs in favor of causation.

Importantly, Dr. Donofrio offered little disagreement with Dr. Tornatore’s medical

theories. He provided only that the 2012 IOM report concluded that there was insufficient evidence

to accept or reject a causal relationship between flu vaccine and TM. Resp. Ex. A at 4; Resp. Ex.

C.

In 2009, the IOM committee reviewed Vellozzi, et al., a study in which the committee

found data was gathered from a passive surveillance system and lacked an unvaccinated

comparison group. Resp. Ex. C at 3. 61 It also identified six other publications, Bakshi, Buchner,

Larner, Nakamura, Sugimoto, and Wells, all of which addressed post-flu vaccine TM and

concluded that there was no supporting evidence beyond temporality, some being too short a

timeframe based on the mechanism involved. Id. However, the IOM noted that influenza infection

has been, rarely, associated with TM and it considered the effects of natural infection as one type

of mechanistic evidence. Id. Autoantibodies, T cells, and molecular mimicry may contribute to the

symptoms of TM, but the publications did not provide evidence linking the mechanisms to flu

vaccine. Id. Therefore, the IOM considered the mechanistic evidence weak between the vaccine

and TM, but not nonexistent, concluding that the evidence was inadequate to accept or reject a

causal relationship between flu vaccine and TM. Id. at 3-4.

Further, in a prior case, in which Dr. Tornatore and Dr. Donofrio were the experts, Hitt v.

Sec’y of Health & Hum. Servs., No. 15-1283V, 2020 WL 831822, at *10 (Fed. Cl. Jan. 24, 2020),

Dr. Donofrio conceded that the medical theories presented by Dr. Tornatore, which mirrored those

presented here, describing how a flu vaccine could cause TM, were valid. His position and lack of

criticism of Dr. Tornatore’s medical theories in this case preponderates in favor of petitioner.

55

Bakshi & Mazziotta, supra note 6.

56

Agmon-Levin et al., supra note 7.

57

Akkad et al., supra note 25.

58

Korn-Lubetzki et al., supra note 14.

59

Christopher S. Ambrose et al., A Case Report of Transverse Myelitis Following Influenza Vaccination, 68 Archives

of Neurology 1085 (2011), filed as “Pet. Ex. 17.”

60

Isabelle Van Ussel et al., Encephalitis Related to an H1N1 Vaccination: Case Report and Review of the Literature,

124 Clinical Neurology and Neurosurgery 8 (2014), filed as “Pet. Ex. 20.”

61

Institute of Medicine of the National Academies, supra note 34.

20

I am not bound by decisions of other special masters, but I do take guidance from my

colleagues and their opinions in similar cases. See Boatmon v. Sec'y of Health & Hum. Servs., 941

F.3d 1351, 1358 (Fed. Cir. 2019). Many petitioners have been found entitled to compensation for

vaccine-induced TM and other demyelinating diseases based on molecular mimicry, as provided

by Dr. Tornatore and detailed above. 62

Based on the foregoing, I agree with the reasoning of other special masters who have found

molecular mimicry to be a sound and reliable mechanism for explaining how the flu vaccine can

cause TM and find that petitioner has satisfied her burden under Althen prong one.

B. Althen Prong III

Althen prong three requires petitioner to establish a “proximate temporal relationship”

between the vaccination and the injury alleged. Althen, 418 F.3d at 1278. That term has been

defined as a “medically-acceptable temporal relationship.” Id. at 1281. Petitioner must offer

“preponderant proof that the onset of symptoms occurred within a timeframe for which, given the

medical understanding of the disorder’s etiology, it is medically acceptable to infer causation-in-

fact.” de Bazan, 539 F.3d at 1352. The explanation for what is a medically-acceptable timeframe

must also coincide with the theory of how the relevant vaccine can cause the injury alleged under

Althen prong one. Id.; Koehn v. Sec’y of Health & Hum. Servs., 773 F.3d 1239, 1243 (Fed. Cir.

2014); Shapiro v. Sec’y of Health & Hum. Servs., 101 Fed. Cl. 532, 542 (2011) (“The etiology of

the disorder determines the appropriate temporal relationship”) (cleaned up). See also Pafford, 451

F.3d at 1358.

The parties agree that petitioner’s onset of TM was 63 days following her receipt of the flu

vaccine. Dr. Tornatore proposed a medically-acceptable range of 1 to 63 days but noted that

62

See, e.g., J.G. v. Sec’y of Health & Hum. Servs., No. 20-664V, 2023 WL 2752634, at *30 (Fed. Cl. Spec. Mstr. Feb.

13, 2023) (observing that “[t]he experts do not dispute the theory of molecular mimicry, or that it is a sound and

reliable theory generally as it relates to GBS” and that “[m]olecular mimicry has been accepted as a sound and reliable

theory in many Vaccine Program cases dealing with demyelinating conditions”); Osso v. Sec’y of Health & Hum.

Servs., No. 18-575V, 2023 WL 5016473, at *21 (Fed. Cl. Spec. Mstr. July 13, 2023) (finding that molecular mimicry

is accepted as a “sound and reliable theory” in a case in which the hepatitis B vaccine was found to cause GBS);

Introini v. Sec’y of Health & Hum. Servs., No. 20-176V, 2022 WL 16915818, at *25 (Fed. Cl. Spec. Mstr. Oct. 19,

2022) (finding that the theory of molecular mimicry is sound and reliable for many demyelinating conditions including

TM); Palattao v. Sec'y of Health & Hum. Servs., No. 13-591V, 2019 WL 989380, at *37 (Fed. Cl. Spec. Mstr. Feb. 4,

2019) (“[M]any of the existing Program decisions in which TM has been found to be caused by a vaccine rely on a

mechanism” of molecular mimicry.); Hitt, 2020 WL 831822 (flu vaccine caused TM/MS); Mura v. Sec’y of Health &

Hum. Servs., No. 08–819V, 2012 WL 2402590 (Fed. Cl. Spec. Mstr. May 30, 2012) (flu vaccine caused ADEM);

Jane Doe 93 v. Sec’y of Health & Hum. Servs., 2011 WL 2326966 (Fed. Cl. Spec. Mstr. May 9, 2011) (flu vaccine

causing TM); Moore v. Sec’y of Health & Hum. Servs., No. 07-0645V, 2010 WL 5113199 (Fed. Cl. Spec. Mstr. Aug.

31, 2010) (flu vaccine causing TM); Schmidt v. Sec’y of Health & Hum. Servs., No. 07-20V, 2009 WL 5196169 (Fed.

Cl. Dec. 17, 2009) (flu vaccine causing TM); Raymo v. Sec'y of Health & Hum. Servs., No. 11-0654V, 2014 WL

1092274, at *21 (Fed. Cl. Spec. Mstr. Feb. 24, 2014) (Molecular mimicry is a “biologically probable” explanation of

how the tetanus vaccine can cause TM.); Roberts v. Sec'y of Health & Hum. Servs., No. 09-427V, 2013 WL 5314698,

at *6-7 (Fed. Cl. Spec. Mstr. Aug. 29, 2013) (entitlement found in a Tdap/TM case with the theory of molecular

mimicry). Compare Palattao, 2019 WL 989380, at *35-37 (denial of entitlement in a TM case where the facts did not

support application of molecular mimicry), with I.J. v. Sec'y of Health & Hum. Servs., No. 16-864V, 2022 WL 277555,

at *4-7 (Fed. Cl. Spec. Mstr. Jan. 4, 2022) (entitlement found on remand in a Tdap/TM case that relied upon the theory

of molecular mimicry).

21

Agmon-Levin contained a risk period of several days and up to three months. Pet. Ex. 11 at 13; Pet.

Ex. 14. 63 While Schonberger, et al. focused on the five weeks following vaccination, the authors

noted that the risk period lasted approximately for 9-10 weeks or 70 days post-vaccination for

GBS. Pet. Ex. 28 at 1, 9. 64

Dr. Donofrio argues that 63 days is too long a timeframe for onset. The Vaccine Table

provides for a 3- to 42-day onset for GBS, although he agreed that Langmuir proposed up to “8

weeks or 56 days.” Resp. Ex. A at 5; Resp. Ex. D at 1; 65 Resp. Ex. E at 1-2.

The table in Langmuir shows that there were those who developed GBS up to nine and ten

weeks after vaccination. Resp. Ex. D at 13. 66 Experts in the Program generally rely on either or

both Schonberger and Langmuir since Langmuir analyzed the findings of Schonberger but on a

smaller group of patients, with both analyzing the onset of weakness following influenza

vaccination. Resp. Ex. D at 1-3; 67 Resp. Ex. E at 1.

The Federal Circuit in Paluck cautioned against set deadlines for onset of injuries following

vaccination. 786 F.3d at 1383-84. In Paluck, the court advised that, given the high degree of

difference between cases of even the same disorder, “hard and fast deadline[s]” are inapposite for

the onset of symptoms post-vaccination. Id. at 1384. While the Vaccine Table sets a timeframe of

3 to 42 days for flu/GBS cases to be qualified as Table injuries, the Program does not preclude a

case from proceeding as a causation in fact case where the onset is less than three days or more

than 42 days. Id. (finding that “the fact that [petitioner’s] first clinically evident sign” was

documented slightly outside the Table timeframe “does not preclude a finding” of causation).

Cases in the Program have found entitlement, albeit rarely, in TM, ADEM, and GBS cases

up to 65 days after vaccination. 68 Sixty-three days falls within the timeframe of prior decisions.

Based on the facts of this case, the medical records, extensive testing, opinions of her

treating physicians, and medical literature, I find that preponderant evidence exists to support an

onset of TM 63 days after receipt of the flu vaccine as medically appropriate. That is not to say

that there is no limit for onset of demyelinating disease following vaccination or infection, only

that literature supports that on rare occasion, onset TM and/or ADEM which are diseases of the

central nervous system may be up to 65 days due to individual differences. See Resp. Ex. D. 69

63

Agmon-Levin et al., supra note 7.

64

Schonberger et al., supra note 12.

65

Langmuir et al., supra note 13.

66

Id.

67

Id.

68

See, e.g., Brown v. Sec’y of Health & Hum. Servs., No. 09-426V, 2011 WL 5029865, at *43-44 (Fed. Cl. Spec.

Mstr. Sept. 30, 2011) (onset of ADEM 60 days after flu vaccine based on Schonberger, et al. and Langmuir); Doe v.

Sec’y of Health & Hum. Servs., 2010 WL 4205677, at *25 (Fed. Cl. Spec. Mstr. Oct. 20, 2010), vacated sub nom. on

other grounds Doe 93 v. Sec’y of Health & Hum. Servs., 98 Fed. Cl. 553 (2011) (onset of TM 65 days after flu vaccine);

Spayde v. Sec’y of Health and Hum. Servs., No. 16-1499V, 2021 WL 686682, at *19 (Fed. Cl. Spec. Mstr. Jan. 27,

2021) (60 days is “reasonable and appropriate” in a flu/GBS case); Cooper v. Sec'y of Health & Hum. Servs., No. 18-

1885V, 2024 WL 1522331, at *20 (Fed. Cl. Spec. Mstr. Mar. 12, 2024) (60-day onset acceptable period for causation

in a Prevnar/GBS case).

69

Langmuir et al., supra note 13.

22

Petitioner has satisfied Althen prong three.

C. Althen Prong Two

Under Althen prong two, petitioner must prove by a preponderance of the evidence that

there is a “logical sequence of cause and effect showing that the vaccination was the reason for the

injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278). “[P]etitioner must show

that the vaccine was the ‘but for’ cause of the harm . . . or in other words, that the vaccine was the

‘reason for the injury.’” Pafford, 451 F.3d at 1356 (internal citations omitted).

It is undisputed that petitioner suffers from TM. Having established that the influenza

vaccine can cause demyelinating disease, that TM is a demyelinating disease, and that onset of

TM, while rare, can take place 63 days post-inciting event, there is little to dispute that a logical

sequence of cause and effect exists showing that petitioner’s flu vaccine was the cause of her TM.

Dr. Donofrio previously acknowledged that demyelinating diseases, which include TM,

can be caused by infection and vaccination. Hitt, 2020 WL 831822, at *10 (Fed. Cl. Spec. Mstr.

Jan. 24, 2020) (“Dr. Donofrio agreed that the medical theories that flu vaccine could cause either

transverse myelitis or multiple sclerosis were ‘valid.’”); Resp. Ex. A at 5 (A urinary tract infection

“would be sufficient to serve as the inciting event for TM.”) In this case, he argued that petitioner’s

TM was caused by an undiagnosed UTI. Resp. Ex. A at 5. As further discussed below, the

contemporaneous medical records and objective testing do not support a finding of a UTI. Further,

Dr. Donofrio provided no persuasive support that a UTI, specifically, could cause TM.

By themselves, treating physicians’ references in their records to a temporal relationship

of a vaccine with the onset of disease or injury do not advance proof of causation or logical

sequence of cause and effect. But where they mention the two without any other potential

contributing factor or, as here, caution against receipt of additional flu vaccines, their records

garner some weight. See Capizzano, 440 F.3d at 1326 (“[T]reating physicians are likely to be in

the best position to determine whether ‘a logical sequence of cause and effect show[s] that the

vaccination was the reason for the injury.’”) (internal citations omitted); Andreu, 569 F.3d at 1375

(finding that, where petitioner satisfies prongs one and three of Althen, the testimony of treating

physicians is “quite probative.”) (internal citations omitted).

Here, petitioner’s treating physicians noted petitioner’s flu vaccine weeks prior to her onset

of TM on several occasions. Pet. Ex. 5 at 53; Pet. Ex. 2 at 114; Pet. Ex. 34 at 105. She was also

advised not to receive additional flu vaccines. Pet. Ex. 6 at 9-10; Pet. Ex. 31 at 16-17.

Accordingly, I find that petitioner has satisfied her burden under Althen prong two.

D. Urinary Tract Infection as an alternative cause for Petitioner’s TM.

1. The Expert Opinions

Dr. Donofrio argued that petitioner had a UTI because “[h]er urinalysis from [November

26, 2016] showed 11 white blood cells, 2 red blood cells, and an elevated white blood cell esterase

23

25 (reference negative)” which is indicative of active infection. Resp. Ex. A at 5; Pet. Ex. 5 at 37.

Agmon-Levin, et al. shows that 40% of TM is associated with preceding infection. Resp. Ex. A at

5; Pet. Ex. 14. 70 Therefore, petitioner had an undiagnosed UTI, and her UTI was a sufficient and

more likely inciting event for TM than the flu vaccine. Resp. Ex. A at 5.

Dr. Tornatore disagreed, pointing out the November 26, 2016, urinalysis was negative for

bacteria, showed no need for repeat testing, and petitioner had no complaints or symptoms of a

urinary tract infection. Pet. Ex. 27 at 2; Pet. Ex. 5 at 218. Dr. Tornatore explained a phenomenon

called sterile pyuria, in which patients with a systemic autoimmune process can have benign white

blood cells, called pyuria, in their urine in the absence of infection. Pet. Ex. 27 at 2. Petitioner’s

post-vaccinal immune activation could have resulted in white blood cells spilling into the bladder.

Id. Dr. Tornatore submitted that in over 40 years of practice he has seen this phenomenon many

times in the TM patients he has treated. This phenomenon is reported in lupus patients as well. Id.;

Pet. Ex. 29. 71

Dr. Donofrio disagreed that petitioner had sterile pyuria, arguing that Dr. Tornatore did not

mention what systemic autoimmune disease petitioner suffered from; indeed, she did not suffer

from any systemic autoimmune disease. Resp. Ex. E at 2. Dr. Donofrio relied on Stamm in support

of his opinion that petitioner suffered from a UTI which was the cause of her TM. Id. at 1.

Dr. Tornatore countered, citing to the table in Stamm which he argued demonstrated that

pyuria is actually found in 1.6% of asymptomatic, abacteriuric patients, not less than 1% as opined

by Dr. Donofrio. Additionally, 3.1% of asymptomatic, abacteriuric patients have sterile pyuria,

like petitioner. Therefore, Stamm supports rather than rebuts the argument that sterile pyuria can

exist in a patient with WBC>10wbc/mm. Pet. Ex. 32 at 4; Resp. Ex. F. 72 Further, “[l]eukocyte

esterase is evidence of leukocytes, not infection.” Pet. Ex. 32 at 4.

Dr. Tornatore referenced the Rahman study to show that sterile pyuria is frequently seen

in lupus patients and at a higher rate than seen in the normal population. Pet. Ex. 29 at 1, 4.73

Isolated sterile pyuria was defined as >5 white blood cells per high powered field in the absence

of urinary infection and other renal manifestations. Id. at 1. The study found that isolated sterile

pyuria are manifestations of active lupus. Dr. Donofrio did not address the Rahman study.

2. Analysis

Once petitioner satisfies her burden on each of the three Althen prongs, “she is entitled to

recover unless the government can show by a preponderance of the evidence, that the injury was

in fact caused by factors unrelated to the vaccine.” Althen, 418 F.3d at 1278 (cleaned up) (citations

omitted). “[T]he standards that apply to a petitioner’s proof of actual causation in fact in off-table

cases should be the same as those that apply to the government’s proof of alternative actual

causation in fact.” Knudsen, 35 F.3d at 549. The petitioner having met her burden on each of the

70

Agmon-Levin et al., supra note 7.

71

P. Rahman et al., Significance of Isolated Hematuria and Isolated Pyuria in Systemic Lupus Erythematosus, 10

Lupus 418 (2001), filed as “Pet. Ex. 29.”

72

Stamm, supra note 39.

73

Rahman et al., supra note 70.

24

three Althen prongs, shifts the burden to respondent to demonstrate that the alleged undiagnosed

UTI was the “sole substantial factor in bringing about” petitioner’s TM. de Bazan, 539 F.3d at

1354.

The subject urinalysis results for November 26, 2016, revealed:

Pet. Ex. 5 at 37. Notably the urinalysis lists “Bacteria NEGATIVE”. Petitioner was also noted to

have no fever or viral or bacterial infection on blood work and CSF testing. Id. at 36, 53, 121, 176.

The Stamm article distinguished bacteriuria and pyuria, defining bacteriuria as indicating

“either urinary colonization (replication of bacteria in urine without evidence of tissue invasion)

or urinary tract infection (bacteriuria associated with clinical, histologic, or immunologic evidence

of host injury).” Resp. Ex. F at 1. 74 The study stated, and Dr. Donofrio quoted, that “10

leukocytes/mm3 or greater occur in less than 1 percent of asymptomatic, nonbacteriuric patients

but in greater than 96 percent of symptomatic men and women with significant bacteriuria.” Resp.

Ex. F at 1; Resp. Ex. E at 1. However, the study cautioned that bacteriuria arises for many reasons

including contamination of the urine specimen, colonization of the urine, or urinary tract infection.

Resp. Ex. F at 1. Colonization and infection can be distinguished by, among other things, the

presence of symptoms or signs indicating tissue invasion. Id. at 2. Of the patients studied, the data

suggested that a portion of the patients with asymptomatic bacteriuria “actually ha[d] a transient,

self-limited colonization state rather than true infection.” Id. at 3. Transient bacteriuria can last one

or two days with spontaneous resolution; in some cases, it may not be associated with pyuria,

suggesting that not all asymptomatic bacteriuria is actually infection. Id. Due to the many variables

involved, Stamm concluded that the measurement of pyuria in routine clinical practice “needs

reassessment.” Id. at 5.

74

Stamm, supra note 39.

25

Relying on Stamm, Dr. Donofrio argued that what Dr. Tornatore called sterile pyuria was

in fact evidence of an acute infection, a diagnosis that was not made by her treating physicians.

Resp. Ex. E at 1-2. However, Stamm did not support the reliability of that testing in asymptomatic

patients due to the many variables that could affect the accuracy of the testing and the findings.

Stamm noted that the most commonly used method for measuring pyuria does not correlate well

with the leukocyte excretion rate for this reason. Resp. Ex. F at 3. 75

There is insufficient evidence in the record and objective testing to show that petitioner

suffered from an asymptomatic, undiagnosed UTI on November 26, 2017, when she presented to

the hospital with symptoms of TM. She underwent extensive testing which did not reveal any

bacterial or viral infection, and her urinalysis was negative for bacteria. Pet. Ex. 5 at 37, 53, 79.

Further, Dr. Donofrio failed to provide any persuasive evidence that a UTI can cause TM.

While up to 40% of TM cases are preceded by infections, the infections associated with

TM include but are not limited to influenza, measles, mumps, rubella, cytomegalovirus, and

Epstein-Barr virus. Pet. Ex. 14 at 2. 76 Further, most cases of TM begin after the patient has

recovered from the infection. TM is believed to be the result of an autoimmune response triggered

by infectious antigens not the result of the infection itself. Id. Assuming petitioner did have an

active UTI as suggested by Dr. Donofrio, that would not be the cause of her simultaneous TM.

Simply raising an alternative cause without showing that it can cause and did cause that

alternative condition within a medically accepted timeframe does not satisfy respondent’s burden

of an alternative cause. To meet this standard, respondent must “present sufficient evidence to

prove that the alternative factor was the sole substantial factor in bringing about the injury.”

Deribeaux ex rel. Deribeaux v. Sec’y of Health & Hum. Servs., 717 F.3d 1363, 1367 (Fed. Cir.

2013) (citing de Bazan, 539 F.3d at 1352). The Vaccine Act limits the scope of unrelated factors

by excluding any “idiopathic, unexplained, unknown, hypothetical, or undocumentable cause,

factor, injury, illness, or condition.” § 13(a)(2)(A). “In other words, alternative causes that are

‘idiopathic, unexplained, unknown, hypothetical or undocumentable’ cannot overcome a

petitioner’s prima facie case.” Doe, 601 F.3d at 1357 (quoting § 13(a)(2)(A)).

Respondent has not provided preponderant evidence to support a UTI as the sole substantial

cause of petitioner’s TM.

VII. Conclusion

Upon careful evaluation of all the evidence submitted in this matter, including the medical

records, affidavit of the petitioner, expert reports, and medical literature, I find that petitioner has

shown that she is entitled to compensation under the Vaccine Act. Accordingly, this matter shall

proceed to damages with a separate damages order to issue.

IT IS SO ORDERED.

75

Stamm, supra note 39.

76

Agmon-Levin et al., supra note 7.

26

s/ Mindy Michaels Roth

Mindy Michaels Roth

Special Master

27