Irwin v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: January 23, 2024

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

GUY IRWIN, *

*

Petitioner, * No. 16-1454V

*

v. * Special Master Gowen

*

SECRETARY OF HEALTH *

AND HUMAN SERVICES, *

*

Respondent. *

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

Renee J. Gentry, The Law Office of Renee J. Gentry, Washington, D.C., for petitioner.

Adam N. Muffett, U.S. Department of Justice, Washington, D.C., for respondent.

RULING ON ENTITLEMENT1

On November 4, 2016, Guy Irwin (“petitioner”) filed a petition for compensation under

the National Vaccine Injury Compensation Program.2 Petition (ECF No. 1). Petitioner alleges

that as a result of receiving an influenza vaccine on November 7, 2014, he suffered a stroke and

its sequelae. Petition (ECF No. 1). After a review of the record and an entitlement hearing,

petitioner has established by preponderant evidence that he is entitled to compensation.

I. Procedural History

Petitioner filed his claim for compensation on November 4, 2016. Petition. Petitioner

filed medical records to support his claim on January 4, 2017. Petitioner (“Pet.”) Exhibits

(“Exs.”) 1-12) (ECF Nos. 6 & 7). Petitioner continued to file additional medical records in 2017

and 2018. See Pet. Exs. 13-23.

1

Pursuant to the E-Government Act of 2002, see 44 U.S.C. § 3501 note (2012), because this opinion contains a

reasoned explanation for the action in this case, I intend to post it on the website of the United States Court of

Federal Claims. The Court’s website is at http://www.uscfc.uscourts.gov/aggregator/sources/7. Before the opinion

is posted on the Court’s website, each party has 14 days to file a motion requesting redaction “of any information

furnished by that party: (1) that is a trade secret or commercial or financial in substance and is privileged or

confidential; or (2) that includes medical files or similar files, the disclosure of which would constitute a clearly

unwarranted invasion of privacy.” Vaccine Rule 18(b). An objecting party must provide the Court with a proposed

redacted version of the opinion. Id. If neither party files a motion for redaction within 14 days, the opinion will

be posted on the Court’s website without any changes. Id.

2

The National Vaccine Injury Compensation Program is set forth in Part 2 of the National Childhood Vaccine

Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended, 42 U.S.C. §§ 300aa-10 to 34 (2012)

(hereinafter “Vaccine Act” or “the Act”). Hereinafter, individual section references will be to 42 U.S.C. § 300aa of

the Act.

1

On April 10, 2019, petitioner filed an expert report from Carlo Tornatore, M.D.3 and

supporting medical literature. Pet. Exs. 24-27 (ECF Nos. 46 & 47). On January 13, 2020,

respondent filed a Rule 4(c) report recommending against compensation. Respondent (“Resp.”)

Report (“Rept.”) (ECF No. 62). Respondent also filed an expert report from Steven Messé,

M.D.4 and accompanying medical literature. Resp. Exs. A (ECF Nos. 63-65).

I held a Rule 5 status conference on October 6, 2020. During the status conference, I

explained that petitioner’s expert, Dr. Tornatore, had proposed a medically plausible theory of

vaccine causation, however, there was also litigative risk for petitioner as well. Rule 5 Order

(ECF No. 74). I recommended that the case be resolved in ADR. The parties were unsuccessful

in resolving the case in ADR. See Order Concluding ADR Proceedings (ECF No. 85).

Petitioner filed a supplemental expert report from Dr. Tornatore on October 27, 2021.

Pet. Ex. 48 (ECF No. 89). On November 10, 2021, the parties filed a joint status report

requesting that an entitlement hearing be set. Joint Status Rept. (ECF No. 90). Respondent filed

a supplemental expert report from Dr. Messé and a report from Steven Hedrick, M.D.5 on

February 9, 2022. Resp. Ex. B & C (ECF No. 93).

3

Dr. Carlo Tornatore is a Professor and Chair of the Department of Neurology at Georgetown University Medica

Center. Pet. Ex. 25. Dr. Tornatore received his undergraduate degree at Cornell University in 1981 and received his

medical degree from Georgetown University in 1986. Id. at 2. He did a Residency in Neurology at Georgetown

University Hospital, followed by a Fellowship in Molecular Virology at the National Institute of Neurological

Disorders and Stroke at the National Institute of Heath. Id. Following his fellowship, Dr. Tornatore joined the

faculty at Georgetown University Medica Center and he has been the Director of Multiple Sclerosis Center for 18

years. Id.; Pet. Post-Hearing Brief at 16. The MS Center is involved in 23 clinical trials for treatment of various

forms of MS and have been involved in over 62 clinical trials over the past 20 years. Pet. Post-Hearing Brief at 16.

Dr. Tornatore is an ad hoc reviewer for the Annals of Neurology, Neurology, Medical Virology, the Journal of

Neurovirology, and Gene. Pet. Ex. 25 at 7. Dr. Tornatore has been the lead author on multiple medical articles that

focus on the intersection of the immune responses to viruses and the brain. Id. at 9-15. Further, Dr. Tornatore has

treated patients with different neurological disease, including neuromyelitis optica, transverse myelitis, nervous

system vasculitis, and stroke patients. Tr. 6-7; Pet. Post-Hearing Brief at 16. Dr. Tornatore was admitted as an

expert in neurology and immunology. Tr. 13.

4

Dr. Steve Messé is currently an Associate Professor of Neurology at the Hospital of the University of

Pennsylvania, School of Medicine. Resp. Ex. B at 1. He received his undergraduate degree from Yale University in

1993 and he graduated from the University of Michigan School of Medicine in 1998. Id. Dr. Messé did his

residency at the Hospital of the University of Pennsylvania. Id. He is board certified in Psychiatry and Neurology,

as well as in Vascular Neurology. Id. Dr. Messé serves as an ad hoc reviewer for many publications, including the

Nature Clinical Practice Neurology, European Journal of Neurology, Journal of Neuroimaging, and Cardiovascular

Therapeutics. Id. at 2. Dr. Messé has been the lead author or co-authored numerous medical articles that discuss

neurology and cardiology. Id. at 8-25. Dr. Messé does clinical work at the Hospital at the University of

Pennsylvania which focuses primarily on stroke patients. Tr. 98. Dr. Messé was admitted as an expert in neurology

and vascular neurology. Tr. 102.

5

Dr. Stephen Hedrick is currently an emeritus professor at the University of California San Diego, CA. Tr. 54;

Resp. Ex. E at 1. He received his undergraduate degree from the University of California and his Ph.D. in molecular

biology and biochemistry from the University of California in Irvine, California. Resp. Ex. E at 1. Dr. Hedrick did

his post-doctoral fellowship at the Laboratory of Immunology at the National Institute of Health. Id. Following his

fellowship, he began working at the University of California in San Diego, CA in the Department of Biology. Id.;

Tr. 55. Dr. Hedrick became the Department Chairman for the Department of Biology for seven years. Tr. 55. Dr.

2

On May 12, 2022, an entitlement hearing was held, where Dr. Carlo Tornatore testified

for petitioner and Drs. Steven Messé and Stephen Hedrick testified on behalf of respondent.

Both parties filed post-hearing briefs. Pet. Post-Hearing Brief (“Pet. Brief”) (ECF No. 110);

Resp. Post-Hearing Brief (“Resp. Brief”) (ECF No. 111). This matter is now ripe for

adjudication.

II. Evidence Submitted

a. Summary of petitioner’s medical history

Petitioner, who was 62 years old at the time, received the flu vaccine on November 7,

2014 at a CVS pharmacy in Leesport, Pennsylvania. Pet. Ex. 1. Petitioner stated that he felt ill

on the evening of November 7, 2014, and went to bed early. Pet. Affidavit (“Aff.”) ¶ 7. The

following day, Saturday, November 8, 2014, petitioner and his wife travelled to Philadelphia,

Pennsylvania to see family. Id. ¶ 8. Petitioner stated that he had an upset stomach and he was

irritable. Id. at ¶ 7. Petitioner’s wife had to complete the drive to Philadelphia and drive the

entire way home because he felt so ill. Petitioner stated that during the visit with family, he

“slept on the sofa during almost all the visit.” Id. at ¶ 8. He stated that his irritability continued

during the car ride home and he went to bed immediately when they got home. Id.

On Sunday, November 9, 2014, petitioner went to church, where he was the Building and

Grounds Manager, to help prepare for the Sunday services. Pet. Aff. ¶ 9-10. He stated that

between the first and second service of the morning, he began to feel strange and had difficulty

controlling his movements and keeping his balance. Id. A registered nurse who was a

parishioner recognized the symptoms of a stroke and called an ambulance to the church at

approximately 10:00 AM. Pet. Ex. 6 at 3. According to the ambulance report, petitioner

reported, “The pressure in my head is too high,” and he had developed pain on the front left side

of his head. Id. Petitioner was transported to Reading Hospital Medical Center. Id.; see also

Pet. Ex. 10 at 11.

In the emergency department of the Reading Hospital Medical Center, petitioner reported

headache, dizziness and visual changes. Pet. Ex. 10 at 11. Petitioner reported that he was ill

“yesterday” and “attributed” it to the flu shot he had received on Friday. Id. Around 10:00 AM,

petitioner began to have a headache on the left side [of his head] with some visual changes, in

the right lower visual field and some decreased vision in the periphery. Id. During his

neurological exam, petitioner was unable to recount the month and “unable to name a pen.” Id.

at 13. Petitioner was admitted for further evaluation for a stroke. Id. at 15.

Dr. Ian Goonewardene evaluated petitioner upon admission on November 9, 2014. Pet.

Ex. 10 at 16. He noted that petitioner had a NIH stroke scale of 6.6 Id. Dr. Goonewardene

Hedrick has authored or co-authored numerous articles about immunology, but specifically about T-cells. Resp. Ex.

E at 2-11. Dr. Hedrick was admitted as an expert in immunology. Tr. 58.

6

The NIH Stroke Scale is a validated, standardized neurologic assessment providing a measure of stroke severity

with scores ranging from zero (normal) to 38 (coma). A score less than 5 is considered a mild stroke. 6 is

3

assessed petitioner with “acute ischemic stroke.” Id. at 18. He wrote, “The onset was sudden

and associated with true visual field deficits.” Id. Petitioner had an MRI the same day which

showed, “Moderate sized, acute infarct involving the posterior medial temporal lobe, and

occipital lobe on the left. A small component of the infarct involves the posterolateral left

thalamus.” Pet. Ex. 4 at 19.

Petitioner was evaluated by neurologist Dr. Karen Hoerst. Pet. Ex. 10 at 35. During this

evaluation, petitioner reported “concern that he received [the] flu shot on Friday and is

concerned that his stroke is related to this.” Id. The physical exam revealed a right

homonymous hemianopia. Id. at 37. Dr. Hoerst recommended that petitioner have a cardiology

evaluation, including a transthoracic echocardiogram to look for the source of the thrombus. Id.

at 38.

Petitioner was discharged on November 12, 2014. Pet. Ex. 10 at 3. His discharge

diagnoses were hypertension, acute left PCA stroke, and hyperlipidemia. Id. Petitioner was

discharged to the Reading Hospital rehabilitation facility. Id. at 4. He was in the rehabilitation

facility until November 20, 2023.

Petitioner had a consult with cardiologist, Dr. William Finneran on December 15, 2014.

Pet. Ex. 5 at 4. At this appointment, petitioner was being evaluated for a “loop recorder due to

[his] recent left occipital CVA with PCA infarct accompanied by right-sided weakness and

expressive aphasia, as well as visual field cut.” Id. Petitioner did not have any chest pain or

shortness of breath. Dr. Finneran wrote that petitioner was “post-Holter monitor on 12/01/2014

which showed over 1000 PACs (premature atrial contractions) with 5 atrial pairs with one 4-beat

run of ventricular tachycardia and 577 PVCs (premature ventricular contractions).” Id. at 5.

Further, petitioner reported that “he had a flu shot the day before his stroke,” and that “he is not

convinced that his stroke was not from this flu shot.” Id. Petitioner declined the loop recorder at

that time.

On January 19, 2015, petitioner had a follow-up appointment with neurologist, Dr.

Hoerst. Pet. Ex. 9 at 4. At this appointment, Dr. Hoerst wrote, “The patient reported that he was

in his usual state of health until approximately 2 days prior to the stroke when he received his flu

shot, then began to feel ill for approximately 2 days and then his wife noticed a significant

change in his personality the day prior to coming into the hospital. On arrival to the hospital a

plain head CT showed mild edema in the left occipital lobe and he was not given IV tPA due to

his CT findings and duration of symptoms….MRI showed a left PCA infarct with evidence of a

left P2 cut off.” Id. Further, Dr. Hoerst recommended that petitioner undergo an evaluation by

cardiology for placement of an implantable loop recorder to look for underlying occult atrial

fibrillation. Id. Dr. Hoerst assessed petitioner with “left PCA infarct of unclear etiology,” and

wanted to evaluate petitioner for “other etiologies of stroke.” Id. at 6. Petitioner did not want to

have additional workup.

On March 27, 2015, petitioner had another appointment with cardiologist, Dr. Finneran.

Pet. Ex. 5 at 7. Dr. Finneran wrote that petitioner “presents today to discuss loop recorder

moderated. Resp. Ex. A at 2; Petitioner’s score in the emergency room was separately recorded as 3. Pet. Ex .6 at

13, 6.

4

implantation to evaluate for his palpitations and possible paroxysmal atrial fibrillation.” Id.

Further, Dr. Finneran stated that petition was “without further complaints of stroke or TIA

symptoms but has now decided to go forward with loop recorder implantation.” Id. Under

petitioner’s “Past Cardiac, Medical and Surgical History,” it was recorded that petitioner had

“(1) left occipital CVA with posterior cerebral artery infarct on 11/09/2014; (2) hypertension; (3)

hyperlipidemia; (3) PACs, paroxysmal atrial tachycardia, nonsignificant ventricular tachycardia

on Holter monitor 12/01/2014.” Id. Petitioner had an EKG which showed “normal sinus

rhythm, normal EKG, and nonspecific ST wave changes.” Id. at 8. Petitioner opted to have a

loop recorder implantation, which occurred on April 10, 2015.

On August 22, 2015, petitioner was taken to the emergency department at the Reading

Hospital when he was found unresponsive by his wife. Pet. Ex. 10 at 168. The record states that

petitioner was “found by wife on floor with snoring respirations. No signs of trauma. [Patient]

vomiting upon arrival. [Patient] is nonverbal, not responding. History of CVA.” Id. His

Glasgow Coma Scale score was 7.

At a follow-up appointment with Dr. Finneran on October 15, 2015, petitioner reported

that he had been hospitalized for a seizure in August 2015. Pet. Ex. 5 at 9. He had been

experiencing some visual field cuts, from approximately 12:00 pm to 3:00 pm. Id. Petitioner

had an in-office ECG which showed “sinus bradycardia with a rate of 59 beats per minute.” Id.

at 10. Additionally, Dr. Finneran reviewed petitioner’s loop recorder which showed “three

symptom episodes and one tachycardia episode….The first symptom episode was a single PAC.

The second symptom episode showed two single PACs and the third was negative for arrhythmia

or extra beats.” Id. Under “Impression/Plan,” Dr. Finneran wrote, “(1) Cryptogenic stroke post-

loop recorder with no evidence of arrythmias. He was originally maintained on a full-dose

aspirin. He had a recent DVT and PE. We will have him drop his aspirin down to 81 mg now

that he is fully anticoagulated on Coumadin.” Id.

Petitioner had a follow-up appointment with Dr. Finneran on October 20, 2016. Pet. Ex.

30 at 6-7. Dr. Finneran wrote that petitioner has been without complaints of repeat stroke or TIA

symptoms and that he had been on Coumadin until September 2016. Id. at 6. Petitioner’s loop

recorder had one episode of atrial fibrillation lasting for 36 hours on September 2, 2016, but

petitioner was asymptomatic. Id. Dr. Finneran performed an ECG in the office which showed

normal sinus rhythm at a heartrate of 71. Id. Petitioner was diagnosed with “left occipital

cerebrovascular accident with posterior cerebral artery infarct with left-sided weakness with mild

expressive aphasia Nov. 9, 2014, hypertension, hyperlipidemia, history of deep vein thrombosis

and pulmonary embolus for which petitioner completed one year of Coumadin therapy, and

suspected sleep apnea. Id. It was recommended that petitioner continue Coumadin for stroke

prophylaxis, and he was encouraged to diet and exercise. Id.

Petitioner continued to regularly have check-ups for various conditions, including a

sunburn and acute sinusitis. See generally Pet. Ex. 29. On April 25, 2019, petitioner had a

follow-up with his primary care physician to review his chronic medical conditions and labs

results. Pet. Ex. 29 at 80. It was noted that petitioner’s sleep study showed that he had “severe

sleep apnea” but that he refused to wear CPAP. Id. The record also noted that petitioner had

5

“stable chronic medical problems” and that he was using aspirin and Coumadin. Id. Petitioner

was asked to follow-up in three months. These are the most up-to-date records.

b. Petitioner’s expert’s opinion on vaccine causation

Petitioner’s expert, Dr. Carlo Tornatore, opined that the flu vaccine petitioner received on

November 7, 2014 was the cause of petitioner’s ischemic stroke that occurred on November 9,

2014. Pet. Ex. 24 at 6. Dr. Tornatore opined that the influenza vaccine induces “an

inflammatory response with a subsequent pro-thrombotic state,” which can result in an acute

cerebral ischemic event. Id.

During the hearing, Dr. Tornatore testified that the influenza vaccine is intended to

induce an inflammatory response. Tr. 15. The immune response to the influenza vaccine, “via

cytokines, chemokines, or even cellular elements…led to an inflammation of the endothelium or

the inside of a blood vessel and that caused a blood clot to form which stopped the blood flow to

the…brain and caused an ischemic event.” Tr. 16. In other words, “there was an inflammatory

response to the vaccine that resulted in a clot to form in a blood vessel.” Id. In his opinion, the

onset of petitioner’s symptoms beginning 24-hours after vaccination is an appropriate timeframe

for an inflammatory response to lead to a pro-thrombotic state. Pet. Ex. 24 at 7.

Dr. Tornatore referenced a case report by Thoon, which described a 10-year-old girl who

developed a stroke one day after receiving a flu vaccine. Pet. Ex. 26.7 The case report explains

that the child presented to the hospital with “acute-onset vertiginous giddiness, blurred vision,

headache, and non-bilious vomiting,” that began six-hours prior to admission. Id. at 2. The

child did not have any hearing loss, focal numbness or weakness and there was no history of

head trauma, but she did receive an influenza vaccine the day before the symptoms began. Id.

The authors of Thoon noted that a “review of literature revealed two recent reports of stroke

temporally associated with influenza vaccination in adults; however, both reported cases had

underlying co-morbidities that substantially increased their predisposition to developing a

stroke.” Id. at 3. In the Thoon case, no underlying prothrombotic or autoimmune conditions

were found. Id. Dr. Tornatore acknowledged that the authors of Thoon were “careful to say that

[they] were not a hundred percent sure that [the flu vaccine and the stroke] were related to the

vaccine. But stroke in the young is exceedingly rare, and to have that very striking temporal

relation of vaccination and then an infarct in the posterior circulation, not unlike the same

distribution that [petitioner] had is unusual.” Tr. 17.

Dr. Tornatore referenced another case report by Lin et al., which described a 75-year-old

man who suffered a posterior circulation ischemia after receiving an influenza-A vaccination.

Pet. Ex. 27.8 The patient in this case report received an influenza vaccine at 10:00 AM, went

home and took a nap from noon until 5:00 pm. Id. The patient woke up with dizziness, asthenia,

7

Thoon, K. et al., Childhood Stroke After Influenza Vaccination, 21 Proc. of Sing. Healthcare 298 (2012). [Pet. Ex.

50].

8

Lin, Yi-Pin et al., Ischaemic stroke and influenza A H1N1 vaccination: a case report, 7(2) Arch Med Sci, 345-348

(2011). [Pet. Ex. 27].

6

(weakness) unsteady gait with deviation on the left side, and the inability to hold objects by hand

properly. Id. at 2. These symptoms subsided thirty minutes later but occurred three or four times

daily for approximately seven days before the patient presented to the hospital. Id. An MRI

showed “high DWI and low ADC intensities scattered in the left cerebellum compatible with

infarctions within the vascular territory of the posterior inferior cerebella artery.” Id. Lin

explained that “Our patient’s infarction is compatible with small-to-medium size artery occlusion

which is also seen in other ischaemic stroke patients after vaccination.” Id. The authors also

reviewed VAERS data and found that, “the leading vaccine reported to be complicated with

ischaemic stroke is seasonal flu, followed by hepatitis A and B virus, pneumococcus,

diphtheria/pertussis/tetanus toxoid, poliomyelitis, and Haemophilus influenzae.” Id. They found

that 164 individuals reported ischaemic stroke after receiving the seasonal flu vaccine and 18

after the influenza A/H1N1 vaccine. Id. The authors explained that in these patients,

“…ischaemic stroke occurs within the first day in 22% and 18% of subjects receiving

vaccination with influenza A/H1N1 and seasonal flu vaccine, respectively.” Id. Furthermore,

the authors wrote:

Vaccination can induce inflammatory and immunological responses. A flare-up of lupus

has been reported. A generation of temporary inflammatory reactions with an elevation

of cytokines after vaccination with Salmonella typhi vaccine, increase of blood

antiphospholipid antibodies with influenza vaccine, and vasculitis with a couple of

vaccines have been identified. In our patient, we did not detect an abnormal alteration of

immune and coagulation function or angiopathy, but that does not completely exclude

their participation.

Id. at 4; Tr. 21.

Lin also observed that “nearly half of ischaemic stroke children have concomitant stroke

risk factors, such as cardiac disease, autoimmunity disorders, vasculopathy, or coagulopathy,”

which led the authors to opine that “vaccination may promote a pre-existing prothrombotic

condition,” and that “vaccination should be carefully evaluated and monitored in individuals

associated with old age or stroke risk factors.” Id. at 4; see also Tr. 21-22. Dr. Tornatore stated

that the authors of Lin recognized the same “biological mechanism….that an inflammatory

cascade could have been the etiology of the infarct,” that occurred in this case. Tr. 21.

Dr. Tornatore stated that an immune stimulus, such as vaccination, can stimulate the

coagulation system and/or impair the endothelial-dependent dilation of blood vessels in the

brain. Tr. 21; see also Pet. Ex. 48 at 2. He referenced an article by Hingorani et al, which

explored how endothelial dysfunction “underlies the association between an acute inflammatory

episode and the transiently increased risk of a cardiovascular event by examining the effects of

an experimental inflammatory stimulus on endothelium-dependent vasodilation.” Pet. Ex. 49.9

In Hingorani, the authors vaccinated subjects with the salmonella typhi vaccine to “initiate a

systemic inflammatory response.” Id. at 3. The authors found that the “plasma concentration of

the proinflammatory cytokine IL-6 increased.” Id. Additionally, the authors explained:

9

Hingorani, A. et al., Acute Systemic Inflammation Impairs Endothelium-Dependent Dilation in Humans, 102

Circulation, 994-99 (2002). [Pet. Ex. 49].

7

….in relation to cardiovascular risk, the elevation of IL-6 is of particular interest because

IL-6 is presumed to be an important, if not the principal, stimulus to the synthesis of C-

reactive protein, and elevated C-reactive protein seems to be predictive of risk of

cardiovascular events.

Id. at 3.

They found that the “mild systemic inflammatory response,” to the vaccine, “was

associated with profound, but temporary suspension of endothelium-dependent relaxation.” Id.

Hingorani stated that, “These findings demonstrate that even a relatively mild systemic

inflammatory response is associated with significant alteration in the endothelial function of a

type commonly thought to be associated with increased cardiovascular risk.” Id.

Dr. Tornatore observed that in the Hingorani study, “blood vessel dilation was

depressed,” as early as eight hours after vaccination, but returned to normal by 32-hours post-

vaccination. Pet. Ex. 48 at 2. He explained that in Hingorani, the authors used the vaccine as a

model to study inflammation in cardiovascular disease, not study infection level. Tr. 23.

Instead, according to Dr. Tornatore, the authors were using “a vaccine model as a proxy to look

at inflammation,” because it can recapitulate what we see with infection. Id. In his report, he

stated, “Hingorani and colleagues did…feel that the post-vaccinal endothelial dysregulation

‘might explain the association between infection and inflammation and the enhanced risk of an

acute cardiovascular event.’ ” Pet. Ex. 48 at 2. He testified that the vaccine model as

demonstrated by Hingorani provides a valid model to show what happens in infection and

vaccination and that the mechanism is the same in terms of increasing cardiovascular risk. Tr.

23-24. Further, he explained that not only does Hingorni validate the vaccine model, but that the

mechanisms for how the inflammatory process can change the vascular tree by either vaccination

or infection are comparable. Id. He explained that in an individual, such as the petitioner, who

may have pre-existing factors for vascular disease, such as hypertension, the wall of the vascular

tree may have atherosclerotic luminal narrowing and diminished vasoreactivity, putting the

individual at further risk for a vascular occlusion “by virtue of a narrowed lumen of the vessel.”

Tr. 25.

Dr. Tornatore stated that petitioner’s medical records demonstrated that he began to have

systemic symptoms almost immediately after receiving the flu vaccine. Tr. 26. He observed that

petitioner’s admission history notes that petitioner had “generalized malaise and irritability,” for

the two-days after he received the flu vaccination. Tr. 26; see also Pet. Ex. 10 at 6. Dr.

Tornatore explained that generalized malaise is a systemic response that is caused by the

elevation in proinflammatory cytokines in response in this case to the flu vaccine. Pet. Ex. 48 at

2; Tr. 29. Dr. Tornatore referenced the article by Christian et al., which explored the relationship

between subjective side effects and serum proinflammatory cytokines after vaccination. Pet. Ex.

50.10 The authors vaccinated subjects with the trivalent flu vaccine and then measured

proinflammatory cytokines in the subjects and the subjective side effects. Id. at 1. The authors

found that subjects who reported systemic symptoms, such as headaches, nausea, tiredness or

10

Christian et al., Proinflammatory cytokine responses correspond with subjective side effects after influenza virus

vaccination, 33 Vaccine 3360-3366 (2015). [Pet. Ex. 50].

8

mild achiness, had marginally higher IL-6 cytokine levels compared to baseline. Id. at 6.

Additionally, they found that TNF-α was elevated one-day post-vaccination in patients that

reported systemic symptoms. Id. at 5. Further, the authors found that MIF, another pro-

inflammatory cytokine was elevated in the subjects that reported systemic symptoms two days

post-vaccination. Id. Dr. Tornatore explained that the Christian article demonstrates that

systemic symptoms correlated with elevations of pro-inflammatory cytokines. Tr. 29; see also

Pet. Ex. 48 at 2. R.

Dr. Tornatore stated that both the Hingorani and Christian articles when read together

showed that “cytokine and chemokine networks are stimulated [following vaccination] and that

they then impair endothelial dilation or just affect the vascular tree.” Tr. 29; Pet. Ex. 48 at 2. He

testified that the authors of Hingorani noted that vaccination can cause inflammation and that

inflammation “increases the risk of a cardiovascular event.” Tr. 30. Dr. Tornatore stated that the

vaccine can cause endothelial dysregulation which “may explain the association between

infection and inflammation and the enhanced risk of an acute cardiovascular event.” Tr. 30. He

further explained how in a susceptible individual with pre-existing vascular disease could be

more at-risk of a thrombotic stroke, stating:

…because if somebody has underlying vascular disease, the inner lining of their blood

vessel is not normal. They probably have some degree of atherosclerotic disease.

There’s already some embedded inflammation in the wall of the blood vessel…and then

you add another inflammatory event on top of that with maybe some narrowing of the

blood vessel, and then you’ll get a thrombus formation in the situ.

Tr. 30.

Dr. Tornatore, responding to Dr. Hendrick’s contention that the flu vaccine does not

trigger a sufficient inflammatory event to result in a thrombotic event, acknowledged that

cytokine and chemokine levels after vaccination may not be as high as after a wild-type

infection, however, they present in a “comparable pattern.” Tr. 33. He asserted that both wild

infection and vaccination result in cytokine stimulation. Id. Dr. Tornatore argued that the Talaat

et al. paper, submitted by respondent, demonstrated that inflammatory cytokines are triggered

rapidly by the flu vaccine. Tr. 33; see Resp. Ex. C, Tab 10.11 The authors studied serum

cytokine and chemokine changes after administration of the influenza vaccine and found that

IFN-γ and IP-10 were significantly elevated beginning 7 hours post-vaccination and remained

elevated 44 hours after vaccination. Resp. Ex. C, Tab 10 at 6. Further, the authors found that

there were “significant differences in median cytokine/chemokine levels…at one or more time

points for all of the proinflammatory and chemokine analytes….[h]owever, it was difficult to

categorize patterns of change over time for many of the analytes due to considerable

interindividual variability.” Id. at 3-4. Dr. Tornatore observed that the authors of Talaat

identified one individual (subject 8) who reported both myalgia and injection site pain post-

vaccination, also had a “distinctive, early cytokine response profile which included IL-6, IL-8,

IP-10, MCP-1, TNF-α, TARC, and MCP-4.” Tr. 34; Resp. Ex. A, Tab 10 at 1, 6. Dr. Tornatore

11

Talaat, K. et al., Rapid changes in serum cytokines and chemokines in response to inactivated influenza

vaccination, 12 Influenza and Other Respiratory Viruses, 202-210 (2018) [Resp. Ex. C, Tab 10].

9

opined that subject 8 was a “super responder, when exposed to the influenza vaccine [and] had a

response that was markedly different than the others and had a marked response within 3 to 7

hours.” Tr. 35. Talaat explained that Subject 8 of the study not only had a markedly higher

proinflammatory response earlier after vaccination, but also had higher antibody response to all

three strains of the influenza virus in the vaccine. Resp. Ex. A, Tab 10 at 4. The authors

theorized that Subject 8’s strong antibody response to the vaccine components suggested a

memory response to the vaccine. Id. Dr. Tornatore stated that Talaat shows that some

individuals can have a proinflammatory response to the vaccine that is comparable to a response

generated by the wild-type infection, particularly in individuals who have been previously

vaccinated or had an infection. Tr. 37.

In response to respondent’s experts’ assertion that epidemiological studies, such as the

Smeeth et al. article, demonstrate that there is “no increase in the risk of vascular events” after

vaccination, Dr. Tornatore explained that such studies may not actually identify rare events

because of modeling and the rarity of the event. Tr. 40; see Resp. Ex. A, Tab 5.12 He explained

that the Smeeth et al. article is using a statistical model to try to answer the question of whether a

rare event can occur and that “the modeling [being used] is not powered to be able to identify the

rare event. Id. Smeeth et al. studied “the risks of myocardial infarction and stroke after common

vaccinations and naturally occurring infections,” based off of data provided by the United

Kingdom General Practice Research Database. Resp. Ex. A, Tab 5. The authors found that

acute lower respiratory tract infections and urinary tract infections are associated with a transient

increased risk of a vascular event and that there was “no increase in the event rate after influenza,

tetanus, and pneumococcal vaccines.” Id. at 6. However, finding no increase in the event rate

does not mean that no adverse events occurred after vaccination. For example, the authors

identified 76 cases of stroke 1-3 days after vaccination, compared to 244 cases of stroke in the

same time period after a “systemic respiratory tract infection.” Id. at 5. These numbers were

identified after the authors excluded 12,572 cases of stroke because of “uncertain vaccination

dates.” Id. Dr. Tornatore stated that excluding such a large number of cases could have impacted

the outcome of the study, but more importantly, epidemiologic studies cannot exclude the

occurrence of a rare event, such as a vaccine-related neurologic injury. Pet. Ex. 48 at 4. He

stated that “trying to use an epidemiologic tool to exclude a rare event doesn’t make sense from

an epistemological standpoint.” Tr. 42. Later, Dr. Tornatore testified that “there’s always going

to be a rare event,” and there will be some people, like the patient in the Talaat article that have

“a very profound response to the influenza vaccination that others in the cohort did not.” Tr.

143.

Dr. Tornatore also explained that the Smeeth article does not show that the vaccine has a

protective effect against stroke. Tr. 138. He stated that respondent’s experts were

misinterpreting the article’s findings. Id. Dr. Tornatore observed that while Smeeth did not find

an increased risk of stroke after vaccination, the “protective effect….may have been due to the

administration of vaccination when people were in periods of relatively good health.” Tr. 138;

Resp. Ex. A, Tab 5 at 7. Dr. Tornatore testified that the authors recognize that “the protective

effect was not due to the vaccination itself, but it could have been the behavior,” of the patient.

12

Liam Smeeth, Ph.D. et al., Risk of Myocardial Infarction and Stroke after Acute Infection or Vaccination, 351

New Eng. J. Med. 2611-8 (2004). [Resp. Ex. A, Tab 5].

10

Tr. 140. Further, the “protective effect of the vaccine” is not that the vaccine actually prevents

stroke, but it prevents influenza which is a risk factor for stroke. Tr. 142.

Dr. Tornatore asserted that petitioner’s clinical presentation of the ischemic stroke

occurring two days post-vaccination fits his theory of vaccine causation. Tr. 44. Dr. Tornatore

explained that the rapid onset of petitioner’s systemic symptoms, such as the headache and

malaise, are consistent with a rapid cytokine release. Tr. 45. Dr. Tornatore also associated

petitioner’s convulsive episode that occurred on August 22, 2015 as “late sequelae” of

petitioner’s initial stroke. Tr. 43.

He testified that petitioner received the flu vaccine on November 7, 2014 and he began to

have systemic symptoms. Tr. 42. Dr. Tornatore observed that such systemic symptoms included

headache, generalized malaise, and irritability. Pet. Ex. 24 at 2; see also Pet. Ex. 10 at 16. By

November 9, 2014, two days after the vaccination, petitioner had visual changes and a localized

headache on his left side and his NIH stroke score was a 6. Pet. Ex. 10 at 13. Dr. Tornatore

stated that petitioner was diagnosed with an acute ischemic stroke. Tr. 42; Pet. Ex. 10 at 18. Dr.

Tornatore acknowledged that a heart loop recorder petitioner had implanted in April 2015, well-

after the initial stroke, identified some atrial fibrillation, but at the time of petitioner’s stroke, he

did not suffer from atrial fibrillation. Tr. 43. On August 22, 2015, petitioner suffered from a

convulsive episode which was associated with petitioner’s initial stroke. Tr. 43; Pet. Ex. 10 at

156, 168 (“patient suffered seizure activity second to a recent left PCA stroke from November

2014.”).

Additionally, Dr. Tornatore explained that petitioner’s underlying history of hypertension

contributed to his increased risk of a stroke, but it was not the cause of petitioner’s stroke on

November 7, 2014. Tr. 46. Dr. Tornatore testified that hypertension causes changes in the

endothelial walls triggered by inflammation. Id. With pre-existing hypertension, petitioner

likely had some inflammatory changes in the wall of the vessel[s] in the form of atherosclerotic

disease, and then another stimuli, the flu vaccine, led to increased inflammation leading to the

thrombus formation. Id. Dr. Tornatore recognized that petitioner was “clearly at risk” with pre-

existing hypertension, but noted that the case report described in Thoon, where a child developed

a stroke after receiving the influenza vaccine demonstrates that this injury can occur

“independent of any previous vascular injury.” Tr. 46.

Finally, Dr. Tornatore opined that the onset of petitioner’s stroke symptoms, occurring

within 24-hours of receiving the influenza vaccination was within an appropriate time-period for

an inflammatory response to lead to a pro-thrombotic state. Pet. Ex. 24 at 7; Tr. 47. He testified

that the onset of petitioner’s stroke was consistent with the case reports described in Thoon and

in Lin, where neurological deficits associated with stroke were found within 24 hours after

administration of the influenza vaccination. See Pet. Ex. 26 & 27. In Thoon, the 10-year old girl

developed blurred vision, a headache, and new-onset vertiginous giddiness one day after

receiving the flu vaccine. Pet. Ex. 26 at 2. In Lin, the 75-year-old man developed “neurological

deficit” seven hours after administration of the influenza A/H1N1 vaccination. Pet. Ex. 27 at 2.

Dr. Tornatore stated that in the present case, petitioner’s malaise and headache, which began the

same day of the vaccination were likely related to an increase in cytokine and chemokines,

11

consistent with the findings of the Christian article, but that petitioner’s personality changes that

occurred the following day could have been from the stroke. Tr. 48.

c. Respondent’s experts’ opinions on vaccine causation

1. Dr. Steven Messé, neurologist

Dr. Steven Messé, respondent’s neurology expert, provided two expert reports and

testified during the entitlement hearing. Resp. Ex. A; Resp. Ex. B. Dr. Messé agreed that

petitioner suffered a posterior cerebral artery ischemic stroke. Resp. Ex. A at 4. However, he

opined that petitioner’s stroke was unrelated to the influenza vaccine because there was a lack of

evidence for a pro-thrombotic state post vaccination, that cryptogenic or stroke of unknown

cause is common, and that petitioner had risk factors for stroke including hypertension. Resp.

Ex. A at 6-7.

Dr. Messé explained that 80 percent of ischemic strokes occur due to a vascular

mechanism, which can be a “blockage that reduces blood flow or a ruptured blood vessel and

hemorrhage.” Tr. 102. He stated that the “vast majority of strokes are related to atherosclerosis,

or “hardening of the arteries,” which occurs in the large or small arteries. Resp. Ex. A at 4; Tr.

103. Dr. Messe stated that approximately 20-25% of strokes are caused by clots that form in the

heart and that “[a]trial fibrillation is the most common arrhythmia that adults experience and one

of the leading mechanisms of stroke.” Resp. Ex. A at 4. He noted that there are cryptogenic

strokes, which mean that “there was no clear cause identified after a thorough work-up,” and that

it is one of the “most common conclusions reported in stroke cases.” Id. at 6; Tr. 104. Dr.

Messé’s opinion was that the influenza vaccine was not likely the cause of petitioner’s stroke,

but instead his “difficult to control hypertension and evidence of vascular disease,” were more

likely to have been the cause of the stroke. Tr. 107.

Dr. Messé opined that the influenza vaccine is protective against stroke and that it is

associated with a reduced, not increased risk of stroke. Resp. Ex. A at 4; Tr. 104. He cited an

article by Grau et al. which studied whether the flu vaccine reduces the odds of a stroke. Resp.

Ex. A, Tab 2.13 The authors stated that “acute and chronic infections may contribute to stroke

risk,” and that “During influenza epidemics, hospitalizations for stroke and cardiac disease

increase.” Id. at 1. Thus, the purpose of the study was to determine if the influenza vaccine is

associated with a reduction of risk for stroke. Id. The authors noted that other case-control

studies showed that acute influenza infection is a trigger factor for stroke and that the “influenza

vaccine may protect from stroke by preventing infections with influenza viruses and

superimposed bacterial infections.” Id. at 5. Furthermore, the authors stated that “pro-coagulant

mechanisms, fever, dehydration, and proteolytic lesions to the vessel wall are mechanisms that

could increase the risk of ischemic and hemorrhagic stroke after infections.” Id. The authors

found that the “odds of ischemic stroke were reduced significantly and the odds of hemorrhagic

stroke but not TIA tended to be reduced by recent influenza vaccination.” Id. at 4. Dr. Messé

asserted that this study, along with others, demonstrates that the influenza vaccine is preventative

13

Armin J. Grau et al., Influenza Vaccination Is Associated with a Reduced Risk of Stroke, 36 Stroke 1501-1506

(2005). [Resp. Ex. A, Tab 2].

12

and protective against stroke, which would mean that if there was as an association between the

vaccine and stroke, “it would be extremely rare and unlikely.” Tr. 106.

Dr. Messé also referenced the Smeeth et al. article, which examined whether acute

infection and vaccination increase the short-term risk of vascular events. Resp. Ex. A, Tab 5.14

He acknowledged that vaccinations limit wild-influenza infection, which would be protective

against stroke, but he also asserted that the Smeeth article shows that the vaccination is

protective in the first few days to a month after vaccination. Tr. 106. Dr. Messé stated that the

Smeeth article found “that stroke rates were actually reduced in the period immediately

following vaccination, extending up to 28 days after, with incidence ratios ranging from 0.72 up

to 0.88.” Id. at 5. He stated that “if vaccination induced strokes in some, it is extremely unlikely

that this protective effect would have been seen.” Id. However, Dr. Messé acknowledged that it

is difficult to say that it is “impossible” that a stroke would occur after vaccination. Tr. 108. He

stated that it would have to be “extremely rare” for a person who is more susceptible to develop a

stroke after vaccination because the Smeeth article demonstrates that the flu vaccine is protective

against stroke in the “early period after vaccination.” Tr. 109.

During the hearing, Dr. Messé further explained the Smeeth article compared the risk of

stroke or heart attack after vaccination to the risk of these conditions after an infection and found

that the risk of a stroke or heart attack after infection is higher compared to vaccination. Tr. 113.

He stated that the authors found that “within the first three days of getting a vaccination, the risk

of stroke incident ratio is almost 25 percent less.” Tr. 114. Dr. Messé did not address the

identification of 76 cases of stroke post-vaccination in the first three days after the influenza

vaccination. Importantly, the authors of Smeeth found that there is transient increase in the risk

of a vascular even after the first few days of infection. Resp. Ex. A, Tab 5 at 6. Furthermore, the

authors hypothesized that the “small protective effect seen after vaccination may have been due

to administration of vaccination when people were in periods of relatively good health.” Id. at 7.

On re-direct examination, Dr. Messé conceded that the “protective finding” the authors of

Smeeth identify is not that the flu vaccine itself reduces stroke and agreed with Dr. Tornatore

that the flu vaccine “is not necessarily protective in the short-term.” Tr. 145. He stated that he

interpreted the article to show that it was not harmful and that there was no “increases of stroke

in 20,000” people who received the flu vaccine. Id. He testified, “And so that, to me, is very

reassuring, and if, it is a risk factor, it is extremely rare and unlikely.” Id.

Dr. Messé opined that Dr. Tornatore’s theory of how the influenza vaccine can cause an

inflammatory response leading to a pro-thrombotic state that causes stroke lacks quality evidence

and is “unlikely.” Resp. Ex. A at 7; Tr. 119. More specifically, Dr. Messé stated that the

influenza vaccine does not generate an inflammatory response “remotely similar to what you get

from a wild-type infection,” and, therefore, it is extremely unlikely that the vaccine could lead to

a stroke. Tr. 119. He explained that the response to the vaccine, in his opinion, is a “less broad,”

and “less intense” response from a vaccination compared to a wild-infection. Tr. 120. Dr.

Messé testified that if it were the case that the influenza vaccine could cause a stroke, he would

“expect to see it” more because the influenza vaccine is being administered to the people at the

highest risk of stroke. Id.

14

Liam Smeeth, et al., Risk of Myocardial Infarction and Stroke after Acute Infection or Vaccination, 351 N. Engl.

J. Med. 2611-2618 (2004). [Resp. Ex. A, Tab 5].

13

Dr. Messé agreed that all vaccines could cause neuroinflammatory diseases. Tr. 135. He

testified that he believes that there is a “weak association” between the flu vaccine and Guillain-

Barre syndrome (“GBS”), a neuroinflammatory disease, and that there is “some evidence” that

the COVID vaccines that use the adenovirus “can probably increase the risk of GBS,” and “very

rarely cause clotting events.” Tr. 135.

Turning to Dr. Tornatore’s theory of how the flu vaccine could cause a stroke, Dr. Messé

agreed that inflammation can contribute to the risk of clotting events occurring. Tr. 120. He

reiterated that “there is increased risk of stroke if you develop the flu,” but that “there is evidence

for….stroke being less after vaccination.” Tr. 121. However, he argued that “there is no

evidence to suggest that such a pro-thrombotic state occurs after vaccination,” and if such a state

occurred after vaccination, “[one] would expect to see an association between vaccination and

other thrombotic events.” Resp. Ex. A at 6; Tr. 122. Dr. Messé noted that the Vickers et al.

article did not show an increased risk for venous thromboembolism in the 1 to 10 days following

flu vaccination. Resp. Ex. C, Tab 11 at 5.15 The authors noted that known increased risk factors

for venous thromboembolism include hypertension and metabolic disorders. Id. at 1. Further,

they explained that “research has indicated that there is also a higher risk of VTE following

influenza-like illness,” and that the mechanism for VTE after infection was due to endothelial

inflammation.” Id. Vickers observed that the “[i]nfluenza vaccination has been shown to cause a

transient increase in pro-inflammatory cytokine production,” and that is why they sought to study

the risk of VTE following influenza vaccination.” Id. Dr. Messé testified that the Vickers article

did not find any clotting event post-vaccination. Tr. 122.

Dr. Messé opined that petitioner’s stroke was more likely caused by his pre-existing

hypertension. Tr. 127; Resp. Ex. A at 6. He stated that petitioner required multiple drugs to

control his hypertension and that he had “evidence of end-organ injury,” which is “suggestive of

pre-existing atherosclerosis.” Resp. Ex. A at 6. Dr. Messé also stated that petitioner’s MRI

showed evidence of central nervous injury from ischemia which means that petitioner had prior

vascular disease. Tr. 127. However, he acknowledged that the MRI finding is a common

finding on MRIs in older adults, particularly ones with high blood pressure. Tr. 128.

Dr. Messé also opined that the atrial fibrillation that was found on petitioner’s loop

recorder a year and half later could have also been the cause of petitioner’s stroke. Tr. 130.

However, he testified, “Whether or not it caused the stroke that we are talking about today, I

don’t know. I certainly wouldn’t say that’s definitely the answer, but I also think it’s definitely

possible.” Tr. 130. He explained that “intermittent Afib causing stroke” is much more likely

than the vaccination causing petitioner’s stroke. Id. He noted that one of petitioner’s doctors

associated petitioner’s stroke to atrial fibrillation, albeit five years after the stroke. Id.; see also

Pet. Ex. 34 at 29 (“Left PCA stroke most likely secondary to atrial fibrillation on chronic

warfarin status post loop recorder placement with residual superior right quadrant anopia and

cognitive changes.”). However, Dr. Messé also conceded that while petitioner was initially

hospitalized for his stroke, the treating physicians did not find evidence of atrial fibrillation. Tr.

147. He explained that sometimes patients present with atrial fibrillation and stroke, but in other

15

Elizabeth R. Vickers, et al., Risk of Venous Thromboembolism Following Influenza Vaccination in Adults aged 50

years and older in the Vaccine Safety Datalink, 35 Vaccine 5872-5877 (2017). [Resp. Ex. C, Tab 11].

14

patients the atrial fibrillation is found later in time. Id. The finding of atrial fibrillation even a

year after a stroke “is a very reasonable thing to say that probably caused [the] stroke.” Id.

Dr. Messé testified that in petitioner’s case, there are more alternative causes of his

stroke, such as his pre-existing hypertension or later found atrial fibrillation, than evidence in

support of vaccine causation. Tr. 148. It was his opinion that there is an association between the

influenza infection and stroke, but that the influenza vaccine would not cause the same type of

immune stimulus as a wild-infection such that it would lead to a stroke. Id.

2. Dr. Stephen Hedrick, immunologist

Respondent’s immunology expert, Dr. Stephen Hedrick submitted one expert report and

testified during the entitlement hearing. Resp. Ex. C. Dr. Henrick opined the immune response

to the flu vaccine petitioner received does not elicit a systemic inflammatory response sufficient

to elicit a blood coagulation response resulting in an ischemic event. Resp. Ex. C at 5. He

testified “showing [vaccine] causation in this case is very difficult.” Tr. 59.

Dr. Henrick stated that “there is strong evidence to support a causal relationship between

an immune response to an infection leading to a cardiovascular event, but he disagreed that the

immune responses to different antigens in the vaccine are equivalent or have the same

physiological effects [as a wild-infection]. Resp. Ex. C at 2; Tr. 70-2. Dr. Henrick described the

mechanism for how a viral infection can lead to blood clots as follows,

…influenza A and influenza B, can directly induce the expression of Tissue Factor (TF),

an inciting event leading to the cascade of coagulation…TF is constitutively expressed on

cells that are physically separated from blood circulation. In the event of vascular

damage, serum factors gain access to TF and the coagulation cascade begins.

Alternatively, in the presence of inflammation, TF is expressed de novo on cells in

contact with blood circulation. The basis for TF induction is most prominently the

inflammatory cytokine known as Tumor Necrosis Factor (TNF) that is produced by many

cells secondary to viral and bacterial infections.

Resp. Ex. C at 2; Tr. 65.

Dr. Hedrick testified that medical literature Dr. Tornatore relied upon to demonstrate that

the flu vaccine could cause an increase in proinflammatory cytokines, does not actually show a

significant enough increase in certain cytokines, such as TNF. Tr. 66-67. He testified that the

Hingorani et al. article did not find a detectable increase in TNF. Tr. 65. Dr. Hedrick

acknowledged that the Hingorani authors “did find an expected vascular effect,” of the

proinflammatory cytokines, but that the authors did not determine if there was any relevance to

an ischemic event and that their conclusion was in the context to explain the association between

infection and inflammation and the enhanced risk of acute cardiovascular event. Tr. 66. Dr.

Hedrick also noted that the authors of Hingorani used a polysaccharide vaccine “that’s known to

cause inflammation at least on a low level,” and that the typhoid vaccine is “very different from

the split virus influenza vaccine that has not been shown to have the same effects.” Tr. 68.

15

Dr. Hedrick asserted that the Christian article “did not actually demonstrate inflammatory

markers comparable to what is seen in a wild-type infection,” as asserted by Dr. Tornatore.

Resp. Ex. C at 2; Tr. 69-70. In his report, Dr. Hedrick acknowledged that the Christian article

did find a “small, but statistically significant difference in two inflammatory cytokines following

receipt of the influenza vaccine,” but that the authors “did not attempt to compare this to an

actual influenza infection.” Resp. Ex. C at 2; Tr. 70. Dr. Hedrick testified that the authors

found a significant increase in migration inhibition factor (MIF), which is “an inflammatory

factor” involved in the innate immune system. Tr. 69. However, he did not mention in his

testimony that those who reported systemic symptoms also had an increase in TNF-α one day

post-vaccination. See Pet. Ex. 50 at 5. He explained that his main point was that “you can’t

equate a very moderate, almost undetectable inflammatory response, with what you would see

with an actual infection, which can be huge.” Tr. 70. Although, he did concede that while there

is a “significant correlation between stroke and an influenza infection,” which is likely to be

picked up in epidemiological studies, a “more mild elevation that could trigger a rare event,

particularly in someone who is susceptible,” is not eliminated. Tr. 71. Later in his testimony,

Dr. Hedrick also conceded that there are a smaller number of adverse events associated with

vaccination than with the wild infection and that sometimes those rare events are “small enough

so that you can’t even detect it in terms of looking at tens of thousands of patients.” Tr. 78.

Dr. Hedrick stated, “…the magnitude of an immune response to an infectious agent is

different than the magnitude of an immune response to a vaccine.” Tr. 72. He stated that,

“There is no doubt that the inflammatory response associated with the influenza virus infections

differ both quantitatively and qualitatively from those elicited by a (semi) purified influenza

vaccine. Resp. Ex C at 3. He wrote, “Many studies highlight the positive correlation between

influenza and cardiovascular events, but I have not found a single study that showed an

association between influenza vaccination and cardiovascular events. On the contrary, available

studies show that influenza vaccination is protective.” Id.; Tr. 73.

One of the many studies Dr. Hedrick referenced to support his opinion that the flu

vaccine is protective against cardiovascular disease after a flu infection was the Behrouzi paper.

Tr. 86; Resp. Ex. C, Tab 16.16 The article reviewed other medical literature that examined the

association between the flu, the flu vaccine and cardiovascular disease. Resp. Ex. C, Tab 16.

The authors stated, “The latest meta-analysis of the cardioprotective effects of influenza vaccine

found a 25% reduced risk of all-cause death.” The articles provides that “heart disease has been

the leading cause of the death in the U.S., with a 5% increase from 2019 to 2020 alone….Now,

because of the Coronavirus Disease 2019 pandemic, it has never been more apparent to the

public that there exists a vicious cycle between viral respiratory infections and cardiovascular

disease.” Resp. Ex. C, Tab 16 at 1. Furthermore, Behrouzi wrote, “[Viral respiratory infections]

can create a systemic inflammatory environment that is conducive to major adverse

cardiovascular events.” Id. at 1-2. The authors noted that two recent studies found that “almost

one in eight adult patients hospitalized with laboratory-confirmed influenza infection

experienced an acute cardiovascular event,” and that these patients had a median length of stay

of 5 days in the hospital, a third required intensive care, and 7.3% died in the hospital. Id. at 2.

16

Bahar Behrouzi & Jacob A. Udell, Moving the Needle on Atherosclerotic Cardiovascular Disease and Heart

Failure with Influenza Vaccine, 23 Current Atherosclerosis Repts. https://doi/org/10.1007/s11883-021-00973-w

(2021). [Resp. Ex. C, Tab 16].

16

The authors wrote, “Of those who died, 25% had an associated acute cardiovascular event, which

may have been preventable had the initial influenza infection been averted.” Id. Additionally,

the authors stated that, “…several large meta-analyses of observational and trial data have shown

that influenza vaccination is associated with a reduction in mortality and other adverse outcomes,

including those of cardiovascular etiology, in adults with influenza infection.” Id. at 4. Dr.

Hedrick stated that the “whole point of this [study] was to give both practitioners and patients

more evidence to support giving vaccines to patients at risk.” Tr. 87.

Dr. Hedrick agreed that the flu vaccine is intended to elicit an immune response,

however, the magnitude of the immune response to vaccine is “very, very different,” than to the

wild infection. Tr. 73. He explained that the infection from a virus expands and takes over a

“good number of the cells of the epithelium of the lung and makes a huge number of cells and

activates every possible mechanism of innate and adaptive immunity,” which differs from the

immune system’s response to the vaccine which is, “limited to the injection site, for the most

part. And while the inflammation could be felt systemically, it’s much more of a limited

stimulus.” Tr. 74. Dr. Hedrick, referencing an article by Christiaansen et al., which examined

the efficacy of vaccines to induce antigen-specific T-cells, asserted that it demonstrated that the

proliferation of T-cells in the peripheral blood “does not compare to the proliferation and

activation that [one] could get form an actual virus.” Tr. 75; Resp. Ex. C, Tab 8.17 Dr. Hedrick

stated that the authors found that the vaccine patients were inoculated with caused a fivefold

increase in peripheral blood T-cells and the vaccine with the adjuvant caused a nearly tenfold

increase in peripheral blood T-cells. Tr. 75. When Dr. Hendrick was asked by the Court as to

why the discussion of T-cells was relevant to Dr. Tornatore’s theory of vaccine causation, he

responded that the influenza vaccine is likely to produce a “T-cell recall response within hours,”

and that “T-cells are typically the cells that produce a large number of inflammatory cytokines.”

Tr. 77. He also testified that as for the body’s innate immune response to the vaccine it is not the

same as the innate immune response to an influenza infection, and that even if there was a rapid

recall T-cell response coupled with an innate response to the vaccine, it would still be “moderate

in the amount compared to an infection.” Tr. 77-8. However, Dr. Hedrick conceded that the

vaccine does stimulate a similar immune response to a vaccine, albeit at a “lower magnitude,” to

develop immune memory. Tr. 78. Additionally, Dr. Hedrick testified that “some of the same

mechanisms are involved in vaccine-mediated immune activation compared to infection-

mediated vaccination, but they are not equivalent.” Tr. 89. He also agreed that a stroke after a

wild flu infection is common enough to be found in epidemiological studies, but that does not

eliminate the possibility that a more mild inflammatory elevation could trigger a rare event,

particularly in someone who is susceptible. Tr. 71.

Dr. Hedrick also referenced the article by L’Huiller et al., which examined the T-cell

response in organ transplant patients to a wild influenza infection or the flu vaccination, to

support his opinion that the flu vaccine does not generate an inflammatory response as

significant as the wild infection. Resp. Ex. C, Tab 9.18 He stated that vaccines show a “very

17

Allison F. Christiaansen et al., CD11a and CD49d Enhance the Detection of Antigen-Specific T cells Following

Human Vaccination, 35 Vaccine 4255-4261 (2017). [Resp. Ex. C, Tab 8].

18

Arnaud G. L’Huiller et al., T-cell Response Following Natural Influenza Infection or Vaccination in Solid Organ

Transplant Recipients, 10 Nature 10104, https://doi.org/10.1038/s41598-020-67172-6. [Resp. Ex. C, Tab 9].

17

poor expansion and activation of a pathogen-specific T cell populations after vaccination,” and

that exposure to the wild infection “often results in an expansion of the virus-specific T-cell

population on the order of 10,000-fold in a matter of days.” Resp. Ex. C at 3. Dr. Hedrick

testified that the article showed that there was almost “zero response” to the vaccine by the CD4

T-cells, which produce most of the inflammatory cytokines, and that the response to the H3N2

vaccine only produced a small amount of cytokines. Tr. 81. He interpreted L’Huiller to show

that “the magnitude of the effect of inflammation in an infection is, in some cases, infinite over

that which you get with the vaccination.” Tr. 82. However, he conceded that the vaccine does

produce “some” inflammatory response, but that it is “difficult to measure.” Id. As Dr.

Tornatore observed, the L’Huiller article also showed that in those who were vaccinated against

the H3N2 component, the vaccine stimulated a similar pattern of elevation in IFNγ, TNFα, and

IL-2 as did the wild infection albeit at a lower level. Tr 32; Resp. Ex. C, Tab 9 at 5.

Dr. Hedrick testified that Dr. Tornatore’s theory of how the flu vaccine could cause a

stroke was not supported by the medical literature. Tr. 59. He stated that Dr. Tornatore

acknowledged that there is no medical literature that shows an increased incidence of stroke

following the flu vaccination. Id. He testified that there is a stroke occurring every four minutes

in the United States and that there are approximately 40 million doses of influenza vaccine given

every year and thus, one could always find that a stroke occurs in proximity to the administration

of a flu vaccination. Tr. 60. Dr. Hedrick stated that there has been “no trend….between

influenza vaccine…and ischemic stroke.” Id. He asserted that the Lin article, which is a case

report of an older gentleman experiencing an ischemic stroke and an analysis of VAERS

reporting of stroke post-vaccination, does not really demonstrate causation between the influenza

vaccine and a stroke. Tr. 62. Instead, he argued that the paper only shows a very rare

occurrence of strokes after flu vaccination and that it only demonstrates a temporal association

between the flu vaccine and an ischemic event. Id. He stated that the paper demonstrates that

“of the patients reporting an ischemic event, 18 percent occurred within the first 24 hours. So

the timing is fine. There’s no issue with the timing, but it doesn’t show anything about

causation.” Id. Furthermore, Dr. Hedrick stated that the authors of Lin are “uncertain if an

enhancement of the inflammatory immunological activity after vaccination is sufficient,” to

cause a symptomatic vascular occlusion. Id.

Similarly, Dr. Hedrick asserted that the Thoon article, a case report of child experiencing

a stroke shortly after receiving the flu vaccine, only shows a temporal association between the

vaccine and stroke. Tr. 63. He also stated that the authors of Thoon did not change their

recommendation for all children to receive the seasonal flu vaccine. Id. When asked by the

Court whether “there’s a difference between saying that the data supports recommending

vaccination for all people, because for most people…it’s safe to receive, but [there] could still be

a rare adverse event,” Dr. Hedrick responded, “Yes,” and that Thoon article does not specifically

address that issue.

Dr. Hedrick testified that it was his opinion that the flu vaccine does not generate a

sufficient systemic inflammatory response sufficient to result in a thrombotic event. Tr. 93. He

stated that it was his opinion that the immune response to infection compared to vaccinations are

“overwhelmingly different.” Dr. Hedrick stated that there is no way to make a causal

relationship between the flu vaccine and a stroke, given how commonly strokes occur and the

18

number vaccines administered. Tr. 92. On cross-examination, Dr. Hedrick appeared to concede

that the seasonal flu vaccine can cause Guillain-Barre syndrome, a neuroinflammatory injury.

Tr. 95.

III. Legal standard for entitlement

The Vaccine Act was established to compensate vaccine-related injuries and deaths.

Section 10(a). “Congress designed the Vaccine Program to supplement the state law civil tort

system as a simple, fair and expeditious means for compensating vaccine-related injured persons.

The Program was established to award ‘vaccine-injured persons quickly, easily, and with

certainty and generosity.’” Rooks v. Sec’y of Health & Hum. Servs., 35 Fed. Cl. 1, 7 (1996)

(quoting H.R. Rep. No. 908 at 3, reprinted in 1986 U.S.C.C.A.N. at 6287, 6344).

Petitioner’s burden of proof is by a preponderance of the evidence. Section 13(a)(1). The

preponderance standard requires a petitioner to demonstrate that it is more likely than not that the

vaccine at issue caused the injury. Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315,

1322 n.2 (Fed. Cir. 2010). Proof of medical certainty is not required. Bunting v. Sec’y of Health

& Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). In particular, the petitioner must prove that

the vaccine was “not only [the] but-for cause of the injury but also a substantial factor in

bringing about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health &

Hum. Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999)); see also Pafford v. Sec’y of Health &

Hum. Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). A petitioner who satisfies this burden is

entitled to compensation unless respondent can prove, by a preponderance of the evidence, that

the vaccinee’s injury is due to “factors unrelated to the administration of the vaccine.” Section

13(a)(1)(B).

To receive compensation through the Program, petitioner must prove either (1) that he

suffered a “Table Injury”— i.e., an injury listed on the Vaccine Injury Table— corresponding to

a vaccine that she received, or (2) that he suffered an injury that was actually caused by a

vaccination. See Sections 11(c)(1), 13(a)(1)(A); Capizzano v. Sec’y of Health & Hum. Servs.,

440 F.3d 1317, 1319-20 (Fed. Cir. 2006). Where as here, the petitioner does not allege a Table

Injury, the petitioner must prove that the vaccine received actually caused the injury. To do so,

the petitioner must establish, by preponderant evidence: (1) a medical theory causally connecting

the vaccine and the injury (“Althen Prong One”); (2) a logical sequence of cause and effect

showing that the vaccine was the reason for the injury (“Althen Prong Two”); and (3) a showing

of a proximate temporal relationship between the vaccine and the injury (“Althen Prong Three”).

Section 13(a)(1); Althen, 418 F.3d at 1278.

The causation theory must relate to the injury alleged. The petitioner must provide a

sound and reliable medical or scientific explanation that pertains specifically to this case,

although the explanation need only be “legally probable, not medically or scientifically certain.”

Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994). In

Kottenstette, the Federal Circuit reiterated that proof of causation does not “require identification

and proof of specific biological mechanisms[]” Kottenstette v. Sec’y of Health & Hum. Servs.,

861 Fed. Appx. 433, 441 (Fed. Cir. 2021) (citing Knudsen, 35 F.3d at 549). Causation “can be

found in vaccine cases…. without detailed medical and scientific exposition of the biological

19

mechanisms.” Knudsen, 35 F.3d at 549. It is not necessary for a petitioner to point to conclusive

evidence in the medical literature linking the vaccine to the injury, as long as the petitioner can

show by a preponderance of evidence that there is a causal relationship between the vaccine and

the injury, whatever the details of the mechanism may be. Moberly v. Sec’y of Health & Hum.

Servs., 592 F.3d 1315, 1325 (Fed. Cir. 2010).

The petitioner cannot establish entitlement to compensation based solely on his

assertions; rather, a vaccine claim must be supported either by medical records or by the opinion

of a medical doctor. Section 13(a)(1). In determining whether the petitioner is entitled to

compensation, the special master shall consider all material in the record, including “any . . .

conclusion, [or] medical judgment . . . which is contained in the record regarding . . . causation.”

Section 13(b)(1)(A).

In Vaccine Act cases, expert testimony may be 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 also Cedillo, 617 F.3d at 1339 (citing Terran v. Sec’y of Health & Hum.

Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999). In Vaccine Program cases, the Daubert analysis

has been used in the weighing of the scientific evidence actually proffered and heard, rather than

as a tool for the pre-trial exclusion of expert testimony. Davis v. Sec'y of Health & Hum. Servs.,

94 Fed. Cl. 53, 66–67 (Fed. Cl. 2010) (“uniquely 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”), aff'd, 420 F. App'x 923 (Fed. Cir. 2011). The flexible use of

the Daubert factors to determine the persuasiveness and/or reliability of expert testimony in

Vaccine Program cases has routinely been upheld. See, e.g., Snyder v. Sec'y of Health & Hum.

Servs., 88 Fed. Cl. 706, 742–45 (2009).

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

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

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

Lampe v. Sec’y of Health & Hum. Servs., 219 F.3d 1357, 1362 (Fed. Cir. 2000)). However,

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

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

data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743 (quoting Gen. Elec. Co. v. Joiner,

522 U.S. 146 (1997)). Weighing the relative persuasiveness of competing expert testimony,

based on a particular expert's credibility, is part of the overall reliability analysis to which special

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

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

determinations”); see also Porter v. Sec'y of Health & Hum. Servs., 663 F.3d 1242, 1250 (Fed.

Cir. 2011) (“this court has unambiguously explained that special masters are expected to

consider the credibility of expert witnesses in evaluating petitions for compensation under the

Vaccine Act”).

Close calls regarding causation must be resolved in favor of the petitioner. Althen, 418

F.3d at 1280 (holding that Congress created a system in which “close calls regarding causation

are resolved in favor of injured claimants”); Knudsen, 35 F.3d at 551 (“If the evidence (on

20

alternative cause) is seen in equipoise, then the government has failed in its burden of persuasion

and compensation must be awarded.”).

IV. Discussion and application

a. Althen prong one

Under Althen prong one, petitioner must provide a “reputable medical theory,”

demonstrating that the vaccine received can cause the type of injury alleged. Pafford v. Sec’y of

Health & Human Servs., 451 F.3d 1352, 1355-56 (Fed. Cir. 2006). Such a theory must only be

“legally probable, not medically or scientifically certain.” Knudsen, 35 F.3d 548-49. Petitioner

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

demonstration of a specific mechanism, or a generally accepted medical theory. Andreu v. Sec’y

of Health & Human Servs., 569 F.3d 1367, 1378-79 (Fed. Cir. 2009) (citing Capizzano, 440 F.

3d 1325-26). However, “[a] petitioner must provide a ‘reputable medical or scientific

explanation for [his] theory. While it does not require medical or scientific certainty, it must still

be ‘sound and reliable.’ ” Boatmon v. Sec’y of Health & Human Servs., 941 F.3d 1351, 1359

(Fed. Cir. 2019) (quoting Knudsen, at 548-49).

Here, petitioner’s expert, Dr. Tornatore proposed that the influenza vaccine induces an

inflammatory response, leading to a pro-thrombotic state and an acute cerebral ischemic event.

Pet. Brief at 17; Pet. Ex. 24 at 7. Dr. Tornatore supported his theory with several medical

articles.

First, Dr. Tornatore observed that two articles describe case reports of strokes occurring

in the first two days after flu vaccination. Tr. 16-18; Pet. Ex. 24 at 6-8; Pet. Exs. 26,27. The

Thoon article, which described a case of a 10-year-old girl who developed a cerebellar stroke one

day after receiving the flu vaccine. Pet. Ex. 26 at 2. The Thoon authors observed that the 10-

year-old girl did not have MRA findings of cerebral angiopathy to explain the nature of her

ischemic stroke, which had been seen on imaging of a four-year-old with an acute ischemic

stroke following a wild influenza infection. Id. at 4. Dr. Tornatore testified that petitioner’s

infarct was in the same distribution as that of the 10-year-old girl described in Thoon. Tr. 17.

Dr. Tornatore also noted that the 10-year-old did not have any underlying conditions that would

put her at risk for a stroke. Tr. 17.

The other case report Dr. Tornatore referenced, Lin et al, described a 75-year-old-man

who developed an ischemic stroke shortly after receiving the flu vaccine. Pet. Ex. 27 at 1. The

authors of Lin noted that the patient developed neurological deficit approximately seven hours

after vaccination. Id. at 2. Furthermore, Lin observed that the patient also had underlying stroke

risk factors, such as hypertension, similar to petitioner’s pre-existing hypertension. Id. In Lin,

the authors also opined as to the cause of an ischemic event after vaccination, stating that “an

inflammatory/immunological response after vaccination may trigger thrombosis superimposing a

pre-existing prothrombotic state.” Id. at 4. The authors stated that “the leading vaccine reported

to be complicated with ischemic stroke is the seasonal flu vaccine,” noting that 164 people

reported having a stroke after administration of the seasonal flu vaccine in VAERS. Id. at 2.

Furthermore, the authors explained that the VAERS data that they reviewed showed that of those

21

who suffered an ischemic stroke after a flu vaccine, 18% suffered the stroke in the first day after

the vaccination. Id. at 4. They opined that the “rapid onset of symptomatic thrombosis may

indicate a hypersensitive reaction in our patients.” Id. Dr. Tornatore testified that the case

reports by Lin and Thoon highlight rare events. Tr. 16. Lin also recognized the possible

“underestimation of vascular complications after vaccination” in patients with multiple risk

factors. Pet. Ex. 27 at 2. Dr. Tornatore stated, “If somebody has hypertension, diabetes,

hyperlipidemia, then their blood vessels may be already more prone to a thrombotic event or

ischemic event.” Tr. 20.

While these two articles are case reports and do not establish vaccine causation by

themselves, “case reports by their nature only present indicia of causation but that does not

deprive them of all evidentiary weight.” Campbell v. Sec’y of Health & Human Servs., 97 Fed.

Cl. 650 (Fed. Cl. 2011); see also Coleman v. Sec’y of Health & Human Servs., No. 18-352V,

2021 WL 1291677 (Fed. Cl. Sec. Mstr. Feb. 16, 2021) (“While case reports cannot establish

causation, they do provide some evidence of causation.”).

However, Dr. Tornatore did not rely on case reports alone to support his theory that

petitioner’s stroke was caused by an inflammatory response to the influenza vaccine. The

Christian article showed that the flu vaccine generates a transient pro-inflammatory response, as

it is intended to do, which corresponds with subjective side effects. Pet. Ex. 50. The authors of

Christian found that patients who reported common systemic side effects, such as a headache,

fatigue, nausea, achiness, or mild fever, had significantly higher MIF, a pro-inflammatory

cytokine, two-days post-vaccination and elevated TNF-α one day post-vaccination. Id. at 4-5.

The authors stated that their study indicated that “subjective symptoms…correspond with

inflammatory responses following influenza vaccination, as indicated by serum proinflammatory

cytokine levels and body temperature.” Id. at 6. Dr. Tornatore testified that petitioner

experienced the type of systemic symptoms within 24-hours after the flu vaccine, which likely

corresponded with a rise in inflammatory cytokines, as demonstrated by the Christian article. Tr.

29.

Then Dr. Tornatore persuasively explained how a transient inflammatory response to a

vaccine could impair endothelial function in a susceptible individual, leading to a cardiovascular

event by impairing vascular relaxation Pet. Ex. 48 at 2; Tr. 22. The Hingorani article lends

significant support for Dr. Tornatore’s opinion. In Hingorani, the authors tested “the hypothesis

that a mild systemic inflammatory response (generated by the administration of a vaccine)

impairs endothelium-dependent dilation in the arterial circulation.” Pet. Ex. 49 at 1. The authors

administered a polysaccharide typhoid vaccine and then tested plasma concentration of

proinflammatory cytokines. Id. at 3. They found that the inflammatory cytokine IL-6 increased

in the 8 hours after vaccination. The authors wrote, “…in relation to cardiovascular risk, the

elevation of IL-6 is of particular interest because IL-6 is presumed to be an important, if not the

principal stimulus to the synthesis of C-reactive protein, and elevated C-reactive protein seems to

be predictive of risk of cardiovascular events.” Id. at 3. While Hingorani did not find an

increase in IL-1β, as observed by respondent’s experts, they did find that the IL-1Ra (receptor

antagonist), which is usually synthesized in response to the elevation of IL-1β, rose by 191%

from baseline in the three hours after vaccination. Id. The authors explained that the increase in

IL-1Ra suggests that “significant local cellular or tissue generation of cytokines can occur

22

without an increase in circulating concentrations. Therefore, we cannot exclude the possibility

that the IL-1β and TNF-α were synthesized after vaccination.” Id.

Furthermore, Hingorani found that intramuscular injection of the vaccine produced a

“mild systemic inflammatory response in healthy volunteers that was associated with profound,

but temporary, suppression of endothelium-dependent relaxation in forearm circulation” and that

their findings “demonstrate that even a relatively mild systemic inflammatory response is

associated with significant alteration in endothelial function of a type commonly thought to be

associated with increased cardiovascular risk.” Id. at 4. The study measured the effects of the

vaccine on the production of bradykinin (“BK”) and acetycholine (“Ach”), which measures the

ability of the endothelium to generate vasodilation through the stimulation of nitric oxide in the

vascular bed. Hingorani found that BK and ACh had decreased efficacy or potency in patients

with a variety of cardiovascular disease, including hypertension, which was an indication of

endothelial dysfunction. Id. When they tested BK and ACh potency post-vaccination, they

found that BK was suppressed by almost 65% and the ACh response was also diminished.

Similar suppression was not seen in non-vaccinated controls. Id. In the case of BK, the defect in

endolthelium dependent relaxation had returned to baseline by 32 hours post-vaccination. Id.

Hingorani explained “the endothelium is an important transducer of physical and chemical

signals from the lumen of the vessel, and experiments in animals and in vitro suggest that

changes reported here could alter vascular behavior to contribute to the disruption of tissue

oxygenation, increased platelet and white cell adhesion to the vessel wall and predispose to

vasospasm.” Id. at 5. The transient suppression of BK may be particularly important because it

plays a role in vascular homeostasis. Id. They concluded that “even a mild inflammatory

reaction disturbs endothelial regulation of vascular tone in the arterial circulation.” Id.

Dr. Tornatore testified that Hingorani used the vaccine-model to recreate what is seen

with infection to demonstrate that changes in the vascular system were related to generation of

inflammation and they demonstrated that the immune response to a vaccine can cause the same

type of response as the wild infection. Tr. 24. Dr. Tornatore opined that in a susceptible

individual with pre-existing vascular disease, like hypertension, the impairment of the

endothelial relaxation of the blood vessels caused by the inflammatory response to the vaccine

could cause a thrombotic stroke. Tr. 30; Pet. Ex. 48 at 2. He explained:

…if somebody has underlying vascular disease, the inner lining of their blood vessel is

not normal. They probably have some degree of artherosclerotic disease, there’s already

some embedded inflammation in the wall of the blood vessel, and then you add another

inflammatory event on top of that with maybe some narrowing of the blood vessel, and

then you’ll get a thrombus formation in situ.

Tr. 30. The Hingorani paper substantially supports Dr. Tornatore’s theory of vaccine causation.

First, the authors found increased inflammatory cytokines hours of vaccination. See Pet. Ex. 49

at 2. Then the authors found an association between the mild increase in inflammation and

profound suppression of endothelium-dependent relaxation in circulation. Id. at 3. Finally, the

authors found that in those with pre-existing hypertension, the endothelial function was further

impaired by the inflammation initiated by the vaccination, just as Dr. Tornatore opined. Id.; see

also Tr. 30.

23

The respondent’s experts, Dr. Hedrick and Dr. Messé disagreed with Dr. Tornatore’s

proposed mechanism, mainly arguing that the flu vaccine does not generate a sufficient

inflammatory response to induce a “cascade of coagulation which could lead to a cardiovascular

event, such as stroke,” and that there is no epidemiological evidence that supports an increased

risk of stroke post-vaccination. Resp. Ex. A at 7; Resp. Ex. C at 3. Drs. Hedrick and Messé

argued that the medical literature supports an association between a wild influenza infection and

an increased risk for a cardiovascular event, but there is no such association between the flu

vaccine and stroke in epidemiological studies. Resp. Ex. B at 1-2; Resp. Ex. C at 2. They also

recognized that it is the immune response to the infection, not the infection itself that increases

the risk of the cascade of coagulation, that could lead to a stroke. Id. Dr. Hedrick explained in

his report, “I acknowledge that there is strong evidence to support a causal relationship between

immune responses elicited by virulent infectious agents and vascular coagulation that could

potentially lead to a cardiovascular event.” Resp. Ex. C at 2. However, he stated that the

inflammatory response elicited by the vaccine is not equivalent to the inflammatory response to

the wild infection and therefore, could not give rise to result in a thrombotic stroke. Id. at 4.

Furthermore, both experts asserted that the flu vaccine is “protective” against stroke. Tr. 59,105.

There is no doubt that various studies filed in this case indicate that ischemic strokes are

more common after the flu or other infections than after vaccination. See Resp. Ex. A, Tab 5 at

1. Further, these studies also indicate that the cause of the cardiovascular event is likely due to

the robust immune response to the infection. See Resp. Ex. A, Tab 4 at 2 (“Influenza infection

can activate systemic inflammatory responses and increase the sympathetic tone that plays a

crucial role in the pathogenesis of atrial fibrillation.”) see also Resp. Ex. C, Tab 15 at 1

(“Research has indicated that there is also a higher risk of venous thromboembolism…including

pulmonary embolism following influenza-like illness.”). Here, petitioner did not have the flu

infection prior to his stroke. Instead, he was a susceptible individual with hypertension who

received a flu vaccine, then experienced a stroke. The task of petitioner’s expert, Dr. Tornatore,

was to demonstrate a sound and reliable theory for which the flu vaccine could cause a stroke,

which he did.

Furthermore, petitioners are not required to demonstrate a specific biologic mechanism

that caused their disease, nor are they required to present medical literature or epidemiological

studies in support of their theory. See Kottenstette v. Sec’y of Health & Human Serv., 861 Fed.

Appx. 433 (Fed. Cir. 2021) (citing Knudsen, 35 F.3d at 548-49)(reaffirming the principle that

“proof of causation does not ‘require identification and proof of a specific biological

mechanism[.]’” Andreu, 569 F.3d at 1378-79. However, a petitioner’s prong one theory must be

sound and reliable. See Boatmon v. Sec’y of Health & Human Servs., 941 F.3d 1351, 1359 (Fed.

Cir. 2019). The lack of epidemiological studies to demonstrate an association between the flu

vaccine and stroke is not necessary for petitioner to prevail on Althen prong one, and the lack of

epidemiological studies did not persuasively rebut petitioner’s theory. Additionally, the articles

cited by respondent’s experts did not find that there were no incidences of stroke after the flu

vaccine, but only that there was not an increased risk compared to a wild infection.

The Smeeth article, filed by respondent, identified 76 cases of stroke occurring 1–3-day

post-influenza vaccination. Resp. Ex. A, Tab 5 at 6. Furthermore, Smeeth stated that

24

intermittent changes to inflammation “may be linked to an increase in the risk of vascular

events.” Resp. Ex. A, Tab 5 at 1. The authors opined that inflammation may affect endothelial

dysfunction, leading to a cardiovascular event. Id. Even though the authors concluded that there

did not appear to be “a detectable increase in the risk of vascular events” after vaccination, they

also endorsed Dr. Tornatore’s theory stating that the vaccination can cause “mild transient

inflammation and associated suppression of endothelium-dependent relaxation.” Id. at 7-8.

Furthermore, when asked by the Court if the epidemiological studies eliminate the possibility

that a “more mild elevation in inflammation could trigger a rare event, particularly in someone

who is susceptible,” Dr. Hedrick conceded the epidemiological studies could not fully eliminate

a rare event. Tr. 71. Thus, the risk of a stroke occurring after a wild infection may be greater in

the wake of a wild flu infection than after the influenza vaccine, but this does not mean that that

a rare event, such as the present case cannot occur.

In summary, Dr. Tornatore’s theory is supported by the medical literature filed by both

petitioner and respondent in this case. I find that petitioner has demonstrated a sound and

reliable medically theory to explain how the flu vaccine can cause a stroke. Accordingly, the

requirements of Althen prong one have been satisfied.

b. Althen prong three: temporal association

Althen prong three contains two parts: first petitioners must establish the “timeframe for

which it is medically acceptable to infer causation,” and second, they must demonstrate that the

onset of the disease occurred in this period. Shapiro v. Sec’y of Health & Human Servs., 101

Fed. Cl. 532, 542-43 (2011), recons. denied after remand on other grounds, 105 Fed. Cl. 353

(2012), aff’d without op., 503 F.App’x 952 (Fed. Cir. 2013).

Although a temporal association alone is insufficient to establish causation, under the

third prong of Althen, a petitioner must show that the timing of the injury fits with the causal

theory. See Althen, 418 F.3d. at 1278. The special master cannot infer causation from temporal

proximity alone. Thibaudeau v. Sec’y of Health & Human Servs., 24 Cl. Ct. 400, 403-04 (1991);

see also Grant v. Sec’y of Health & Human Servs., 956 F.2d 1144 (Fed. Cir. 1992) (“[T]he

inoculation is not the cause of every event that occurs within the ten[-]day period…[w]ithout

more, this proximate temporal relationship will not support a finding of causation.” (quoting

Hasler v. U.S., 718 F.2d 202, 205 (6th Cir. 1983)).

Petitioner’s stroke symptoms began one day after receiving the flu vaccine. Petitioner’s

medical records and his affidavits consistently reflect this window of onset. See Pet. Ex. 10 at

16-18. Petitioner reported feeling poorly since receiving the flu vaccine two days before going

to the hospital, reflecting the initial inflammatory response to the vaccine described in Christian.

See Pet. Aff. ¶ 7. Then he began to develop personality changes, which Dr. Tornatore explained

were likely early symptoms of the stroke. Tr. 47. By Sunday, two days after vaccination,

petitioner developed more evident physical symptoms, that caused a nurse at his congregation to

recognize that he was having a stroke and called an ambulance. Pet. Aff. ¶ 10. Dr. Hoerst, a

treating neurologist, also summarized petitioner’s history, writing, “…yesterday, the patient had

a drastic, acute change in personality. This persisted today, but while he was at work, he

additionally developed some vision changes and noted that he was bumping into things,” and

25

that she suspected that “some degree of his stroke began yesterday with his acute personality

change as this was clearly a significant change noted by the wife.” Id. at 36-37.

Dr. Tornatore opined that onset of stroke symptoms 24-hours after vaccination is

appropriate due to an inflammatory response to the flu vaccine. Pet. Ex. 24 at 7; Tr. 47. Dr.

Tornatore stated that petitioner’s symptoms began one day after the vaccination, which

manifested as a change in personality and irritability. Tr. 47. He testified that the Talaat article,

along with the Christian article show that cytokines and chemokines can be activated “well-

within seven hours post-vaccination” and that the Hingorani article shows that mild

inflammation can lead to a change in vascular tone within a day of vaccination. Tr. 48; see Pet.

Ex. 24 at 7;Pet. Ex. 48 at 4; see also Pet. Ex. 50 (finding an association between increased

cytokines such as TNF-α and MIF one- and two-day post-vaccination and reporting of subjective

side effects of vaccination); and Resp. Ex. C, Tab 10 (finding that certain cytokine increases

occurred within 24 hours after influenza vaccination, and one patient had a “distinctively robust

change in IL-6, IL-2, IL-8, IP-10, and MCP-1 in response to the influenza vaccination at 3 and 7

hours” post-vaccination.). All of these are reviewed in conjunction with the recognition of

vasosupression within hours when the effects of a vaccine were measured on the vasculature of

healthy volunteers by Hingorani.

Furthermore, the onset of petitioner’s symptoms, beginning one day post-vaccination was

consistent with the case reports Dr. Tornatore referenced. The Lin article described the case of a

75-year-old male who received the flu vaccine in the morning and began to experience

neurological deficits approximately seven hours later. Pet. Ex. 27 at 2. The authors noted that

their patient had other stroke risk factors, including hypertension, however, they opined that the

vaccine may promote a pre-existing prothrombotic condition, which could lead to a stroke. Id. at

4. After reviewing the VAERS data, Lin observed that 18% of reported ischemic strokes after

the seasonal flu vaccine occurred one day post-vaccination. Id. at 4. The Thoon article

described a case of a 10-year-old developing a cerebellar stroke one day after receiving the

seasonal flu vaccine. Pet. Ex. 26 at 2. Thoon explained that the 10-year-old developed acute

onset “vertiginous giddiness, blurred vision, headache, and non-bilious vomiting,” approximately

one-day after receiving the flu vaccine. Id. The girl’s MRI showed two areas of restricted

diffusion in the left cerebellar hemisphere. Id. at 2.

Dr. Hedrick testified that onset of stroke either 24-48 hours after vaccination is

problematic because “[t]here is a stroke occurring in the United States every four minutes,” and

with 40 million doses of the influenza vaccine administered every year, “you will always find

something that common….in proximity.” Tr. 60. Dr. Messe testified that there is not any

“temporal association” between vaccination and “major clotting events,” such as “heart attack,

stroke, venous thromboembolism.” Tr. 122.

Both Drs. Hedrick and Messe’s opinions regarding Althen prong three are based on their

general disagreement about Dr. Tornatore’s theory that the flu vaccine can generate a sufficiently

significant inflammatory response that results in a prothrombotic state, leading to a stroke.

Relying on the Smeeth article, Dr. Messé stated that “stroke rates were actually reduced in the

period immediately following vaccination, extending up to 28 days after,” when compared to

incidences of stroke after the confirmed diagnosis of an upper respiratory infection. Resp. Ex. A

26

at 5. However, the Smeeth article still did identify 76 cases of stroke occurring 1-3 days after the

flu vaccine was administered and the authors also explained that “[t]he small protective effect

seen after vaccination may have been due to the administration of vaccination when people were

in periods of relatively good health.” Resp. Ex. A, Tab 5 at 5-6. Furthermore, even if the

authors did not find a statistically detectable increase in the risk of a vascular event post-

vaccination, the authors still identified 76 cases of stroke occurring in the short time-period Dr.

Tornatore stated was a medically acceptable timeframe for a stroke to occur post-vaccination.

Additionally, the Talaat article, filed by respondent, showed that there is an increase in

inflammatory cytokine activity as early as three hours post-influenza vaccination. Resp. Ex. C,

Tab 10 at 1. The authors found that IFN-ƴ and IP-10, which are inflammatory cytokines, “were

significantly elevated 7 hours after vaccination,” and remained elevated between 16 and 24 hours

after administration. Id. One subject, who reported moderate myalgias and injection site pain

after vaccination, “displayed a distinctive, early cytokine response profile which included IL-6,

IL-2, IL-8, IP-10, MCP-1, TNF-α, TARC and MCP-4.” Id. Dr. Tornatore testified that Talaat

shows that “there are individuals who have very brisk immune responses even within 7 or 8

hours, not unlike the response that the petitioner had, and that can lead to an acute injury…within

a 24-hour period of time because of the chemokine/cytokine chemical network that develops.”

Tr. 45. He also reiterated that the Hingorani article, which showed how a moderate change in

inflammation, can cause endothelial vasodilator dysfunction, leading to changes in vascular tone

within a day, which could result in a stroke. Tr. 48.

Based on the medical literature filed by petitioner and respondent, in conjunction with

Dr. Tornatore’s opinion, I find that an onset of 24-hours post-vaccination is a medically

acceptable timeframe to infer causation. Dr. Tornatore provided persuasive testimony, supported

by medical literature, to show how the flu-vaccine can cause a rapid and substantial cytokine

inflammatory response, which can result in changes to endothelial function. He demonstrated

that especially in a susceptible individual this can lead to a stroke. Although the Smeeth article,

along with other articles, assert that the risk is greater for individuals to develop a stroke after a

wild infection, these articles still identified cases of stroke occurring within 24-hours after

vaccination, even if the risk was classified as “not statistically significant.” Finally, Dr. Hedrick

conceded that the epidemiological studies which found a correlation between the flu infection

and stroke, do not eliminate the possibility that a mild elevation of inflammation triggered by the

flu vaccine may result in a rare event, particularly in a susceptible individual. Tr. 71. As such,

petitioner has satisfied the third Althen prong.

c. Althen prong two: logical sequence of cause and effect

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

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

injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278). The sequence of cause

and effect must be “‘logical’ and legally probable, not medically or scientifically certain.”

Althen, 418 F.3d at 1278. The petitioner need not make a specific type of evidentiary showing,

i.e., “epidemiologic studies, rechallenge, the presence of pathological markers or genetic

predisposition, or general acceptance in the scientific or medical communities to establish a

logical sequence of cause and effect.” Capizzano, 440 F.3d at 1325. Instead, petitioner may

27

satisfy his burden by presenting circumstantial evidence and reliable medical opinions. Id. at

1325-26.

With respect to Althen prong two, I find that petitioner has provided preponderant

evidence that the November 7, 2014 flu vaccination caused his stroke. This finding is based on

the petitioner’s medical records, the statements of petitioner and his wife’s, Dr. Tornatore’s

expert opinion, and the biological mechanisms described by Hingorani, Christian and Talaat.

Petitioner’s medical records establish that prior to receiving the flu vaccine, he had

hypertension, but he was taking Lisinopril and Ziac to control it. Pet. Ex. 10 at 4. Through

affidavits, petitioner stated that the same day he received the flu shot, he began to feel sick and

went to bed early. Pet. Aff. ¶ ¶ 6-7; Pet. Ex. 23 at ¶ 9. Petitioner stated that the next day, when

they went to visit his wife’s cousin outside of Philadelphia, Pennsylvania, he still felt sick and

spent most of the visit resting. Pet. Aff. ¶ 8. His wife described significant personality changes

in him later in the day. On November 9, 2014, two days after the vaccination, while at his church

helping to prepare for service, he began to have difficulty controlling his body movements and

keeping his balance. Pet. Aff. ¶ 10. An ambulance was called for him and it took him to the

emergency department of Reading Hospital. While in the hospital, petitioner reported that he

was ill the day before and that he had received a flu shot on Friday. Pet. Ex. 10 at 11.

Petitioner’s primary symptoms were a headache, dizziness, and visual changes. Pet. Ex.

10 at 11. Petitioner had an echocardiogram in the emergency department which showed,

“normal sinus rhythm at 68 beats per minute,” and there was “normal intervals, no acute ST

elevations nor ST segment depressions.” Id. at 18. When Dr. Karen Hoerst, neurologist,

examined petitioner later that day, she wrote that petitioner was a 62-year-old male with a

“history of hypertension who presented to the emergency department with vague complaints of

feeling unwell x 1 day. He reports that he did not feel like himself. Then today, developed

headache, feeling of dizziness but not vertigo, and possible right sided visual

changes….Speaking to his wife, she notes that yesterday, the patient had a drastic, acute change

in personality (typically a kind and gentle person, he became angry and very short with her,

which she reports she has never before seen, even if he is not feeling well)….His CT showed

early edema in the left occipital lobe. Given the acute personality change since yesterday with

progressive symptoms in conjunction with the CT findings, he was not given IVTPA. He

underwent stat MRI/MRA imaging. He was found to have a left PCA infarct.” Id. at 34-35. Her

assessment was that petitioner had a PCA stroke which appears large vessel in etiology. Id. at

37. Additionally, she stated that she “suspect[ed] that some degree of his stroke began yesterday

with his acute personality change as this was clearly a significant change noted by his wife.” Id.

Petitioner had a follow-up with Dr. Hoerst on January 19, 2015. Pet. Ex. 9 at 4. At this

appointment, she indicated that petitioner had undergone a transesophageal echocardiogram

while in the hospital, which showed “no evidence of arrhythmia.” Id. She did recommend that

petitioner be evaluated by a cardiologist for placement of an implantable loop recorder to “look

for underlying occult atrial fibrillation.” Id. After the physical examination, she wrote that

petitioner had a “left PCA infarct of unclear etiology,” and that “certainly hypertension is a risk

factor for stroke, but given that the remainder of his intracranial vasculature overall looks good, I

28

think we must evaluate him for other etiologies of stroke.” Id. at 6. Dr. Hoerst repeated her

recommendation for a loop recorder. Id.

Petitioner had a loop recorder placed on April 10, 2015. Pet. Ex. 5 at 7-8. On August 22,

2015, petitioner was admitted to Reading Hospital after his wife found him laying down,

unresponsive. Pet. Ex. 10 at 168. Petitioner was diagnosed with a “new onset seizure, likely

secondary to left PCA stroke.” Id. at 156. Furthermore, it was noted that petitioner’s

hypertension was “well controlled on….Norvasc, Ziac, and lisinopril.” Id. A brain MRI taken

on August 23, 2015 showed a “chronic left PCA distribution infarct,” but no change. Id. at 160.

Petitioner was discharged to acute rehabilitation until August 31, 2015. See Pet. Ex. 10 at 281.

All of the experts agreed that he likely suffered a seizure secondary to his original stroke at this

time. Tr. 43, 129.

On October 15, 2015, at a follow-up cardiology appointment, the loop recorder showed

“three symptom episodes and one tachycardia episode.” Pet. Ex. 5 at 10. The tachycardia event

was interpreted as “noise,” but that the first symptom episode was a single “PAC,” and that the

“second symptom episode showed two single PACs and the third was negative for arrhythmia or

extra beats.” Id. The Impression was “cryptogenic stroke, status post loop recorder with no

evidence of arrhythmias. He was originally maintained on a full-dose aspirin. He had a recent

DVT and PE. We will have him drop down to 81 mg now that he is fully anticoagulated on

Coumadin.” Id.

Petitioner had a follow-up appointment with neurologist, Dr. Hoerst on October 19, 2015.

Pet. Ex. 9 at 12-13. Under Chief Complaint it noted that the appointment was for a “follow-up

left PCA infarct, presumed embolic stroke of unknown source.” Pet. Ex. 9 at 12. Dr. Hoerst

wrote that “petitioner was admitted to the hospital in September after being found unresponsive,

postiical from a [p]resumed seizure….He has not had any seizures or events since

hospitalization.” Id. at 13. Dr. Hoerst’s impression was, “63-year-old-man who had a left PCA

infarct in November of 2014, with a prior history of hypertension, but no definitive etiology to

his large vessel stroke, now complicated by presumed seizure.” Id.

I do not find Dr. Messé and Dr. Hedrick’s opinions that petitioner’s stroke was caused by

his underlying hypertension or much later diagnosed atrial fibrillation persuasive. First, Dr.

Messe acknowledged in his first report that it would be “difficult to conclude with confidence

that [the atrial fibrillation] was the proximate cause of [petitioner’s] stroke,” because of the

“duration of time between the stroke and identification of the atrial fibrillation.” Resp. Ex. A at

6-7. Further, Dr. Tornatore explained that at the time of the stroke, petitioner did not

demonstrate atrial fibrillation and it was only identified on his loop recorder in September 2016,

nearly two years after the stroke. See Pet. Ex. 30 at 5.

Additionally, prior to the onset of petitioner’s stroke, the medical records demonstrate

that petitioner was experiencing systemic symptoms in response to the vaccination, including

fatigue, nausea, and upset stomach. See Pet. Ex. 10 at 16 (“He has been feeling somewhat poorly

since receiving a flu vaccine about 2 days ago. Generalized malaise, and irritability.”); see also

Pet. Aff. at ¶ 7-8. The symptoms the petitioner reported to medical professionals and described

in his affidavit are classified as “systemic symptoms” to the flu vaccine as described in the

29

Christian article. See Pet. Ex. 50 at 1. Dr. Tornatore testified that the symptoms petitioner

described were evidence that he was having an immune response to the vaccine and that the

reason for his symptoms were because of the production of inflammatory chemokines and

cytokines. Tr. 29.

Dr. Tornatore acknowledged that petitioner was likely a susceptible individual, with pre-

existing hypertension, being controlled with medication. Tr. 45; Pet. Ex. 48 at 2. He testified

that hypertension is associated with endothelial dysfunction. Tr. 45-46. Furthermore, he

testified endothelial dysfunction may be triggered by inflammation, which would affect

endothelium dependent dilation in arterial circulation. Id.; see also Pet. Ex. 49 at 1. Dr.

Tornatore explained that petitioner’s likely pre-existing inflammation in the blood vessel walls

was exacerbated by the inflammation generated by the flu vaccine which could lead to a

thrombus formation, resulting in a stroke one day post-vaccination. Tr. 46.

The mechanism explained by Dr. Tornatore, and supported by Hingorani, Christian, and

Talaat, also lend support to a finding of a logical sequence of cause and effect. As noted above,

petitioner initially described the more common inflammatory type symptoms described in

Christian within the early hours after the vaccination. The following day petitioner began to

develop symptoms that Dr. Tornatore and Dr. Hoerst believe were more likely secondary to the

stroke, and then on the second day he demonstrated significant signs and symptoms that led to

his hospitalization and the diagnosis of an MRI confirmed, posterior cerebral artery stroke. Tr.

47. This evolution of initially more general inflammatory symptoms, to stroke symptoms

affecting the posterior cerebrum more distinctly in the territory supplied by the PCA, appears to

be quite consistent with the underlying mechanism described by Hingorani and endorsed by Dr.

Tornatore. As Dr. Tornatore testified, Hingorani demonstrated that a transient increase in

inflammatory cytokines after a vaccination caused a profound reduction in the vasodilator

mechanisms in the vasculature leading to vasospasm or thrombus formation. See Pet. Ex. 49.

Additionally, Dr. Tornatore pointed to the variability in immune response between different

people and to the potential for a stronger immune response than average as occurred in the super

responder in Talaat. Resp. Ex. C, Tab 10 at 1. While it is not necessary to conclude that

petitioner was a super responder to the vaccine, the variability in immune response occurs along

a spectrum and he may well have had a greater than average response.

Dr. Hedrick essentially proposed a theory of coincidence when he pointed to the

frequency of strokes and vaccination in the population at large to negate vaccine causation.

However, “the Vaccine Act does not require the petitioner to bear the burden of eliminating

alternative causes where the other evidence on causation is sufficient to establish a prima facie

case.” de Bazan v. Sec’y of Health of Human Servs., 485 F.3d 1146, 1150 (Fed. Cir. 2007).

Additionally, petitioners do not bear a burden to “discount every potential cause that exists

within the entire realm of possibility.” Pafford v. Sec’y of Health & Human Servs.,64 Fed. Cl.

19, 35 (2005), aff’d 451 F.3d 1352 (Fed. Cir. 2006). Here, petitioner has demonstrated a sound

and reliable theory to explain how the flu vaccine could cause a stroke. Further, petitioner’s

medical course was also consistent the case reports described in Thoon and Lin, where stroke

symptoms began one-day after vaccination. Additionally, the Smeeth article filed by the

respondent also found that 18% of reported strokes occurred within one day of vaccination.

Resp. Ex. A, Tab 5; Tr. 62. While the literature indicates that strokes occur more often after a

30

wild flu infection, that statistic does not overcome the logical explanation for a less frequent

adverse event after receipt of the flu vaccine that has been presented in this case. Finally,

respondent’s expert, Dr. Hedrick conceded that the epidemiological studies filed in this case

would not identify a case where mild inflammation would trigger a rare cardiovascular event,

particular in someone is who susceptible, as was the petitioner. See Tr. 71.

When a petitioner has established that vaccination can cause a given condition and has

demonstrated that the timing prong has been met, it allows the petitioner to establish that

vaccination was the but-for cause of his condition. Cobb v. Sec’y of Health & Human Servs.,

No. 17-1123V, 2023 WL 6457568, at * 24. “Evidence demonstrating petitioner’s injury

occurred within a medically acceptable time frame bolsters a link between the injury alleged and

the vaccination at issue under the “but-for” prong of the causation analysis.” Capizzano, 440

F.3d at 1326 (finding medical opinions that explain how a vaccine can cause the injury alleged

coupled with evidence demonstrating a close temporal relationship “are quite probative” in

proving actual causation.); Pafford, 451 F.3d at 1358; see also Contreras, 107 Fed. Cl. at 295

(finding that there is a “logical overlap between the three Althen prongs, and that evidence that

goes to one prong may also be probative for another prong.”).

Here petitioner has demonstrated that his course after receiving the flu shot on November

7, 2014 was consistent with the theory proposed by Dr. Tornatore and there was not sufficient

evidence in the record to establish an alternative cause to petitioner’s stroke. Thus, petitioner has

demonstrated by preponderant evidence Althen prong two.

V. Conclusion

Upon review of the evidence submitted in this matter, including the medical records, the

experts’ opinions, the medical literature, and the testimony, I conclude that petitioner has

provided preponderant evidence in support of his claim that the flu vaccine caused him to

develop a stroke shortly after his vaccination. Petitioner is therefore entitled to compensation

under the Vaccine Act. A separate damages order will be issued.

IT IS SO ORDERED.

s/Thomas L. Gowen

Thomas L. Gowen

Special Master

31