Le v. Secretary of Health and Human Services

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
Filed: March 30, 2023
*************************
MINH LE, * PUBLISHED
*
Petitioner, * No. 16-1078V
*
v. * Special Master Nora Beth Dorsey
*
SECRETARY OF HEALTH * Entitlement; Tetanus-Diphtheria-Acellular
AND HUMAN SERVICES, * Pertussis (“Tdap”) Vaccine; Transverse
* Myelitis (“TM”).
Respondent. *
*
*************************
Maximillian J. Muller, Muller Brazil, LLP, Dresher, PA, for Petitioner.
Alec Saxe, U.S. Department of Justice, Washington, DC, for Respondent.
RULING ON ENTITLEMENT1
I. INTRODUCTION
On August 29, 2016, Minh Le (“Petitioner”) filed a petition for compensation under the
National Vaccine Injury Compensation Program (“Vaccine Act” or “the Program”), 42 U.S.C. §
300aa-10 et seq. (2012).2 Petitioner alleges that he developed transverse myelitis (“TM”) as the
result of a tetanus-diphtheria-acellular pertussis (“Tdap”) vaccination administered on May 20,
2014. Petition at 1 (ECF No. 1). Respondent argued against compensation, stating that “this
1
Because this Ruling contains a reasoned explanation for the action in this case, the undersigned
is required to post it on the United States Court of Federal Claims’ website in accordance with
the E-Government Act of 2002. 44 U.S.C. § 3501 note (2012) (Federal Management and
Promotion of Electronic Government Services). This means the Ruling will be available to
anyone with access to the Internet. In accordance with Vaccine Rule 18(b), Petitioner has 14
days to identify and move to redact medical or other information, the disclosure of which would
constitute an unwarranted invasion of privacy. If, upon review, the undersigned agrees that the
identified material fits within this definition, the undersigned will redact such material from
public access.
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). All citations in this Ruling to individual sections of the
Vaccine Act are to 42 U.S.C. § 300aa.
case is not appropriate for compensation under the terms of the Vaccine Act.” Respondent’s
Report (“Resp. Rept.”) at 2 (ECF No. 36).
After carefully analyzing and weighing the evidence presented in this case in accordance
with the applicable legal standards, the undersigned finds that Petitioner has provided
preponderant evidence that his Tdap vaccine caused his TM, satisfying Petitioner’s burden of
proof under Althen v. Secretary of Health & Human Services, 418 F.3d 1274, 1280 (Fed. Cir.
2005). Accordingly, Petitioner is entitled to compensation.
II. ISSUES TO BE DECIDED
Diagnosis is not at issue. See Resp. Pre-Hearing Brief, filed Feb. 25, 2022, at 2 (ECF No.
105) (acknowledging that “[P]etitioner has been diagnosed with [TM]”). The central issue is
causation: “(1) whether the Tdap vaccine can cause [TM]; (2) whether [P]etitioner’s [TM] was
caused by receipt of the vaccination at issue, and; (3) whether the time between [P]etitioner’s
vaccinations and the onset of symptoms would be considered ‘medically acceptable to infer
causation-in-fact.’” Joint Pre-Hearing Submission, filed Feb. 2, 2022, at 2 (ECF No. 98).
Petitioner contends he has provided preponderant evidence that his Tdap vaccine caused his TM,
satisfying all three Althen prongs. Petitioner’s (“Pet.”) Pre-Hearing Brief, filed Jan. 18. 2022, at
8-17 (ECF No. 97). Respondent disagrees and argues that Petitioner failed to provide
“sufficiently reliable evidence of causation that satisfies the elements of Althen.” Resp. Pre-
Hearing Brief at 11-25.
III. BACKGROUND
A. Medical Terminology
TM is “a rare clinical syndrome in which an immune-mediated process causes neural
injury to the spinal cord, resulting in varying degrees of weakness, sensory alterations[,] and
autonomic dysfunction.” Pet. Exhibit (“Ex.”) 8.8 at 1;3 Pet. Ex. 11.6 at 1;4 see also Pet. Ex. 11.9
at 1.5 TM may be an acute process, or a “slow subacute process.” Pet. Ex. 11.1 at 2. 6 In the
acute presentation, symptoms usually “develop over several hours and then worsen over one to
several days.” Id. “Bilateral weakness and sensory symptoms below the level of the [TM] lesion
3
N. Agmon-Levin et al., Transverse Myelitis and Vaccines: A Multi-Analysis, 18 Lupus 1198
(2009). This is also cited by Respondent as Resp. Ex. C, Tab 4.
4
Chitra Krishnan et al., Transverse Myelitis: Pathogenies, Diagnosis and Treatment, 9 Frontiers
Bioscience 1483 (2004). This is also cited by Respondent as Resp. Ex. C, Tab 1.
5
Bruce A.C. Cree & Dean M. Wingerchuk, Acute Transverse Myelitis: Is the “Idiopathic” Form
Vanishing?, 65 Neurology 1857 (2005).
6
Anupama Bhat et al., The Epidemiology of Transverse Myelitis, 9 Autoimmunity Revs. A395
(2010).
2
are typical. . . . Bowel and bladder dysfunction, reflective of autonomic involvement, [can] also
occur.” Id.Many of the references filed by the parties describing TM characterize the presentation at
onset similarly. See, e.g., Pet. Ex. 11.8 at 1 (describing acute TM as being characterized by
“symptoms and signs of neurologic dysfunction resulting in weakness, sensory loss[,] [] and
autonomic dysfunction”);7 Pet. Ex. 8.7 at 2 (noting TM is “characterized by acute or sub acute
motor; sensory; and autonomic (bladder; bowel; and sexual) spinal cord dysfunction”);8 Resp.
Ex. A, Tab 2 at 1 (explaining that inflammatory myelopathies can present as “bilateral weakness
and sensory changes below the spinal cord level of injury, often accompanied by bowel and
bladder impairment”);9 Pet. Ex. 11.3 at 1 (describing a study where “[p]atients were considered
as having severe initial symptoms [of acute TM] if they were unable to walk or had urinary
incontinence or required catheterization”).10
This is consistent with the inclusion criteria developed by the TM Consortium Working
Group which identifies “[d]evelopment of sensory, motor, or autonomic dysfunction attributable
to the spinal cord” as criteria for diagnosis. Pet. Ex. 11.5 at 2 tbl.1.11 Sensory dysfunction is
described as “numbness, paresthesias,[12] or band-like dysesthesias.”13 Id.7
Sean J. Pittock & Claudia F. Lucchinetti, Inflammatory Transverse Myelitis: Evolving
Concepts, 19 Neurology 362 (2006).
8
Avinash Chandra et al., Vaccine Induced Acute Transverse Myelitis: Case Report, 6 J.
Neurology & Stroke 197 (2017).
9
Bruce A.C. Cree, Acute Inflammatory Myelopathies, in 122 Handbook Clinical Neurology 613
(D.S. Goodin ed., 2014).
10
J. de Seze et al., Idiopathic Acute Transverse Myelitis: Application of the Recent Diagnostic
Criteria, 65 Neurology 1950 (2005).
11
Transverse Myelitis Consortium Working Grp., Proposed Diagnostic Criteria and Nosology of
Acute Transverse Myelitis, 59 Neurology 499 (2002). This is also cited by Respondent as Resp.
Ex. A, Tab 1.
12
Paresthesia is “an abnormal touch sensation, such as burning, prickling, or formication, often
in the absence of an external stimulus.” Paresthesia, Dorland’s Med. Dictionary Online,
https://www.dorlandsonline.com/dorland/definition?id=37052 (last visited Mar. 22, 2023).
13
Dysesthesia is the “distortion of any sense, especially of that of touch” or “an unpleasant
abnormal sensation produced by normal stimuli.” Dysesthesia, Dorland’s Med. Dictionary
Online, https://www.dorlandsonline.com/dorland/definition?id=15186 (last visited Mar. 22,
2023).
3
TM can be accompanied by magnetic resonance imaging (“MRI”) signaling abnormality
in the spinal cord, cerebrospinal fluid (“CSF”) pleocytosis,14 and/or oligoclonal bands15 in the
CSF. Pet. Ex. 11.5 at 1.
“The pathogenesis of TM is probably of an autoimmune nature, whether TM presents as
an isolated disorder or as part of a systemic disease.” Pet. Ex. 8.8 at 1. TM has been associated
with viral infections, autoimmune disorders, and vaccinations. Id. at 2-3; Pet. Ex. 11.1 at 2-4;
Resp. Ex. A, Tab 9 at 3.16
B. Procedural History
Petitioner filed his petition, supporting medical records, and a letter from treating
physician, Dr. Wesley Chay, on August 29, 2016. Petition; Pet. Exs. 1-6. Petitioner filed
additional medical records and an expert report by Dr. John Conomy on May 3, 2017. Pet. Exs.
7-8. On August 2, 2017, Petitioner filed his affidavit. Pet. Ex. 10. Petitioner filed an expert
report by Dr. M. Eric Gershwin on August 7, 2017. Pet. Ex. 11. Additional medical records
were filed in August and September 2017.17 Pet. Exs. 10-16. Respondent filed his Rule 4(c)
Report, arguing against compensation, on July 20, 2018. Resp. Rept. at 2. That same day,
Respondent filed an expert report by Dr. Jeffrey Gelfand. Resp. Ex. A.
On September 21, 2018, Respondent filed an expert report from Dr. Thomas Forsthuber.
Resp. Ex. C. Petitioner filed a supplemental report from Dr. Gershwin on January 11, 2019. Pet.
Ex. 18. On June 10, 2019, Petitioner filed an expert report from Dr. Maria Chen. Pet. Ex. 19.
And on November 13, 2019, Petitioner filed a second supplemental report from Dr. Gershwin.
Pet. Ex. 21. On March 27, 2020, Respondent filed a supplemental expert report from Dr.
Forsthuber. Resp. Ex. E. Subsequently, on August 3, 2020, Petitioner filed a supplemental
expert report from Dr. Chen and a third supplemental expert report from Dr. Gershwin. Pet. Exs.
22-23.
The case was reassigned to the undersigned on July 30, 2020. Notice of Reassignment,
filed Aug. 3, 2020 (ECF No. 61). A Rule 5 status conference was held on October 20, 2020.
14
Pleocytosis is the “presence of a greater than normal number of cells in the cerebrospinal
fluid.” Pleocytosis, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/
dorland/definition?id=39556 (last visited Feb. 8, 2023).
15
Oligoclonal bands are “discrete bands of immunoglobulins with decreased electrophoretic
mobility; their appearance in … cerebrospinal fluid when absent in the serum is a sign of
possible multiple sclerosis or other diseases of the central nervous system.” Oligoclonal Bands,
Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=
60106 (last visited Feb. 8, 2023).
16
Roger Baxter et al., Acute Demyelinating Events Following Vaccines: A Case-Centered
Analysis, 63 Clinical Infectious Diseases 1456 (2016).
17
Additional medical records were filed throughout the course of litigation.
4
Rule 5 Order dated Oct. 20, 2020 (ECF No. 65). The undersigned agreed with the parties that
TM was the correct diagnosis. Id. at 1. The undersigned found Petitioner’s experts had
competing theories for a mechanism of causation but preliminarily found molecular mimicry to
be sound. Id. at 2. Additionally, the undersigned preliminarily found onset to be approximately
three days and that it was appropriate given Petitioner’s theory. Id. The undersigned ordered
that the parties consider settlement negotiations, and by February 2021, the case was referred to
the alternative dispute resolution (“ADR”) program. Id.; Order dated Feb. 16, 2021 (ECF No.
73). However, by April 2021, the case was removed from ADR because it could not be resolved
informally “in light of the parties’ positions.” Order dated Apr. 1, 202 (ECF No. 76).
At a status conference on May 20, 2021, the parties agreed to resolve this matter through
an entitlement hearing. Order dated May, 20, 2021 (ECF No. 78); see also Order dated June 21,
2021 (ECF No 82). On July 16, 2021, Petitioner filed a final expert report by Dr. Lawrence
Steinman, and on November 8, 2021, Respondent filed a supplemental expert report by Dr.
Gelfand. Pet. Ex. 25; Resp. Ex. F.
Petitioner filed his pre-hearing brief on January 18, 2022, and Respondent filed his pre-
hearing brief on February 25, 2022. Pet. Pre-Hearing Brief; Resp. Pre-Hearing Brief. An
entitlement hearing was held on March 15 and 16, 2022 via Zoom videoconference. See
Transcript (“Tr.”). Petitioner and Drs. Steinman, Gershwin, Gelfand, and Forsthuber testified.
Tr. 3, 216. Thereafter, additional medical literature was filed by both parties. Pet. Exs. 11.78,
50-51; Resp. Exs. J-L. Petitioner subsequently filed a post-hearing brief. Pet. Post-Hearing
Brief, filed July 15, 2022 (ECF No. 123). Thereafter, Respondent filed a post-hearing brief and
Petitioner filed a reply. Resp. Post-Hearing Brief, filed Sept. 13, 2022 (ECF No. 126); Pet.
Reply to Resp. Post-Hearing Brief (“Pet. Reply”), filed Oct. 13, 2022 (ECF No. 127).
This matter is now ripe for adjudication.
C. Factual History
1. Medical History
On Tuesday, May 20, 2014, at 46 years of age, Petitioner received a Tdap vaccine in his
right deltoid at or around 5:51 PM. Pet. Ex. 1 at 5, 8, 10. Petitioner had presented to the
emergency department (“ED”) for a finger laceration on his left hand caused by a metal object.
Id. at 4, 9-10. There were no other complaints, and on examination, there were no signs of focal
neurologic deficits or other conditions. Id. at 10-11. In addition to the Tdap vaccine, Petitioner
received sutures and was prescribed Keflex.18 Id. at 4, 11-12.
18
Keflex is “trademark for preparations of cephalexin.” Keflex, Dorland’s Med. Dictionary
Online, https://www.dorlandsonline.com/dorland/definition?id=26786 (last visited Mar. 23,
2023). Cephalexin is an antibiotic “effective against a wide range of gram-positive and a limited
range of gram-negative bacteria; administered orally in the treatment of . . . infections of the
genitourinary tract, of bones and joints, and of skin and soft tissues.” Cephalexin, Dorland’s
Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=8629 (last
visited Mar. 23, 2023).
5
Four days later, on Saturday, May 24, 2014, Petitioner presented to the ED for the
inability to walk or feel while urinating. Pet. Ex. 2 at 20. The first history taken appears to be a
Triage note documented at 9:21 AM, which stated that Petitioner began taking an antibiotic “on
Tuesday night and started getting stiffness and pain in lower extremities.” Id. His symptoms
progressively worsened, and he was “now unable to walk or urinate.” Id. A subsequent history
taken by Tiesha McGee, registered nurse (“RN”), at 9:33 AM, noted “[Petitioner] state[d] that he
started new meds on Tues[day], [Petitioner] state[d] that he began having lower back pain and
difficulty walking yesterday.” Id. at 28. Nurse McGee observed that Petitioner’s gait was
unsteady but he was “able to weight bear.” Id. at 29.
Attending ED physician, Dr. Ajay Singhal, along with physician assistant, Christine
Kerrigan, saw Petitioner by 3:01 PM. Pet. Ex. 2 at 29. Ms. Kerrigan documented that Petitioner
reported “[bilateral] [lower extremity] weakness and urinary retention worsening [for] 3 d[ays],
unable to stand or void since 3:00 AM this morning.” Id. at 21, 28 (noting “[a]scending
weakness [in] both legs over last 3 days”). Petitioner described his symptoms as “generalized
weakness” that had been getting progressively worse, and as of 3:00 AM that morning (May 24),
he was unable to stand/walk or urinate, stating “nothing comes out.” Id. at 20-21. He also
complained of associated midback pain. Id. at 21, 28. On physical examination, Petitioner was
“unable to bear weight when standing” and had “decreased sensation up to just above left knee[,]
though [right] leg sensations seem[ed] ok.” Id. at 22, 28.
After the ED physician consulted with neurologist Dr. Joshua Khoury, Petitioner
underwent a lumbar puncture and MRI of the thoracic and lumbar spine that same day, May 24.19
Pet. Ex. 2 at 25, 28. The thoracic spine MRI revealed “a long segment of abnormal central cord
signal extension from T2 down to T9, with slight expansion of the cord at C6-7.” Id. at 4, 78-79.
There was “minimal enhancement of the cord at T6.” Id. The CSF analysis from the lumbar
puncture revealed slightly elevated protein level of 56 and two oligoclonal bands20 that were not
present in the serum. Id. at 6, 14, 28, 42-43. The CSF was negative for Lyme disease,
cytomegalovirus (“CMV”), and other diseases, and the culture did not show any growth,
indicating there were no abnormalities or results consistent with infection. Id. at 43-45.
Petitioner was diagnosed with TM and admitted for further treatment. Id. at 25, 28.
The next day, on May 25, 2014, Petitioner was evaluated by neurologist Dr. Khoury. Pet.
Ex. 2 at 3-4. Dr. Khoury’s history stated that “[t]his past Wednesday, approximately 4 days ago
[Petitioner] began to develop symptoms that he describe[d] as stiffness in the bilateral lower
extremities part. It started distally and moved proximally over a period of several days. He
describe[d] a weakness as well as heaviness in bilateral legs.” Id. at 3. Additionally, Petitioner
19
A computerized tomography (“CT”) scan of Petitioner’s brain was also performed but was
unremarkable. Pet. Ex. 2 at 27.
20
The Oligoclonal Band Report stated, “The patient’s CSF contains 2 well defined gamma
restriction bands that are not present in the patient’s corresponding serum sample. These bands
indicated abnormal synthesis of gammaglobulins in the central nervous system.” Pet. Ex. 2 at
43.
6
reported that “[a]pproximately 2 to 3 days ago, he began to notice that he was unable to void his
urine.” Id. Dr. Khoury noted the finger laceration and Tdap shot Petitioner received
“approximately 5 to 6 days ago.” Id. On physical examination, Petitioner demonstrated a
“reduced vibratory sense in the bilateral extremities” and a “very soft sensory level at
approximately the T10 area.” Id. Petitioner denied any upper extremity symptoms. Id. Dr.
Khoury’s impression was that Petitioner’s MRI was “consistent with an underlying [TM].” Id. at
4. “Whether or not this has to [do] with his recent left-hand laceration, plus-minus, the injection
that he got as to whether or not this was a [Tdap] shot [was] unclear” at the time. Id. Because
Petitioner reported he felt “approximately 20% better compared with yesterday” after starting
with a single dose of intravenous (“IV”) Solu-Medrol, Dr. Khoury recommended continuing that,
1g daily, for five days, followed by a prednisone taper. Id.
Petitioner was also seen by an infectious disease specialist, Dr. Richard Tepper, on May
25, 2014. Pet. Ex. 2 at 5-7. The consultation note by Dr. Tepper indicated that “[f]our days ago,
late in the day, [Petitioner] felt that his feet were stiff. The feeling progressed proximally. He
felt numb. He had difficulty controlling his legs.” Id. at 5. And then “[t]wo days ago,
[Petitioner] developed pressure in his back. He had difficulty moving his legs and . . . was
unable to walk. He was unable to urinate though he felt pressure.” Id. Dr. Tepper agreed with
Dr. Khoury that the MRI results were consistent with TM. Id. at 6. “[Petitioner] has a large
spinal cord lesion, etiology is unclear. It is not clear if this is infectious. [Petitioner] has had no
fever, chills, no rashes.” Id. Dr. Tepper noted where Petitioner lived, that there are occasionally
deer on the property, and that Petitioner mowed his lawn frequently. Id. at 5. Given this, Dr.
Tepper stated “[Petitioner] may have been exposed to Lyme disease” but that “[t]his would
certainly be an unusual presentation for Lyme disease.” Id. at 6. He also noted “[n]othing to
suggest herpes zoster. Herpes simplex [virus (“HSV”)] to be ruled out.” Id. He advised to
“continue with steroids,” but “would not give antibiotics at this time.” Id. Additional laboratory
tests were ordered (including checks for Lyme antibody and HSV) and the results “did not show
any evidence of infection.” Id. at 6, 17.
Dr. Thomas Gillon conducted a follow-up care visit for Petitioner’s finger laceration on
May 27, 2014. Pet. Ex. 2 at 8-10. Petitioner reported “his finger [felt] slightly stiff, but [there
was] no significant pain in his finger.” Id. at 8. He indicated he “was doing well until 5 days
ago. He started feeling stiffness in his feet and then had progressive migration towards his pelvis
and developed urinary retention.” Id. Dr. Gillon noted there was a “potential area of skin
necrosis,” but “no signs of infection other than elevated white count yesterday of 24, which was
elevated from 10 the day before.” Id. at 8-9. On physical examination, Petitioner was able to lift
both legs off the bed. Id. at 9. Petitioner stated he felt “significantly stronger in his lower
extremities since admission.” Id. Dr. Gillon “[did] not believe that the laceration itself would
have played any effect in what sounds like [TM]. . . . However, potential reaction to the [Tdap]
shot could be a potential cause of his [TM].” Id. Petitioner appeared to be getting significantly
better on steroids without antibiotics. Id.
Also on May 27, 2014, Petitioner had a consultation with urologist, Dr. John Rodgers.
Pet. Ex. 2 at 11-12. Petitioner relayed that “[o]ver the last week, he had increasing weakness in
his lower extremities to the point that he was unable to walk” and also “unable to urinate.” Id. at
7
11. A foley catheter had been in place since admission. Id. at 5, 11, 17. Dr. Rogers’ assessment
was “[u]rinary retention due to neurologic situation consistent with [TM].” Id. at 11.
Petitioner was discharged from the hospital on May 30, 2014. Pet. Ex. 2 at 17.
Discharge notes included that Petitioner had an MRI of the lumbar spine and brain,21 that he was
evaluated by neurology and infectious diseases specialists, and that a lumbar puncture was done
“but did not show any evidence of infection.” Id. On being “admitted to the hospital with [TM],
an antibiotic, IV fluid, and steroids [were] instituted.” Id. Petitioner’s condition had “slowly
improved.” Id. He “became more mobile” and had started physical therapy prior to discharge.
Id.
From May 30, 2014 to June 14, 2014, Petitioner received acute inpatient rehabilitation
treatment at Moss Rehabilitation Hospital (“Moss Rehabilitation”). Pet. Ex. 3 at 97-99; Pet. Ex.
6 at 7-9. His rehabilitation physician was Dr. Wesley Chay. Pet. Ex. 3 at 99; see also Pet. Ex. 5.
Following the five-day course of IV Solu-Medrol, Petitioner transitioned to the oral prednisone
taper, as recommended by Dr. Khoury. Pet. Ex. 3 at 97. He remained on this throughout his
inpatient rehabilitation. Id. Petitioner was also taking gabapentin at this time for bilateral leg
stiffness and was instructed to continue to do so upon discharge. Id. at 98. By the date of
discharge, Petitioner was stable and exhibited “moderate independence” with activities of daily
living (“ADL”) and mobility. Id. He was instructed to continue with physical and occupational
therapy in an outpatient setting22 and to follow up with his primary care physician (“PCP”), Dr.
Adam Pasternack, and Dr. Chay. Id. at 99. Petitioner was also instructed to follow up with
neurology and urology. Id. at 97-98.
On June 21, 2014, Petitioner presented to Dr. Pasternack and reported he was “80%
improved.” Pet. Ex. 4 at 3. Dr. Pasternack’s diagnosis was acute myelitis. Id. at 4. He
instructed Petitioner to follow up and to continue rehabilitation. Id.
On July 24, 2014, Petitioner followed up with Dr. Chay. Pet. Ex. 3 at 92; Pet. Ex. 5 at
55. The initial outpatient evaluation documented “[TM] on [May 24, 2014]” as past medical
history. Pet. Ex. 3 at 92. Since discharge from Moss Rehabilitation, Petitioner reported he was
“doing well” and indicated he would “likely be finishing up on his outpatient [physical and
occupational] therapy next week.” Id. Petitioner reported he was managing “self-care and ADLs
independently” but that he was still “limited by fatigue/poor endurance.” Id. Petitioner reported
“some stiffness sensation primarily in the left lower extremity” and that it also felt “swollen.” Id.
He reported he “used to have stiffness in both legs, but the right leg is almost entirely back to
normal, and the left is 30% better than it was.” Id. Regarding his bladder, Petitioner had “been
performing intermittent catheterization around an hour after voiding, . . . usually 3-4 times a
day.” Id. On examination, Dr. Chay noted “improvement in sensory level to T7 (light touch).”
Id.
21
Petitioner had an unremarkable brain MRI on May 29, 2014. Pet. Ex. 2 at 74.
22
On June 16, 2014, Petitioner began outpatient therapy two to three times per week at Moss
Rehabilitation. Pet. Ex. 3 at 60-63; Tr. 22.
8
Petitioner returned to Dr. Chay on August 20, 2014. Pet. Ex. 5 at 53. Dr. Chay cleared
him to return to work on light duty restrictions. Id. at 54. And on November 19, 2014, Petitioner
was cleared to resume full work duties. Id. at 52. At this visit, Petitioner reported that his
“pain/tightness” had improved since the last visit, he had been working on increasing his
endurance, and he was now “catheterizing himself once nightly.” Id. at 51, 53.
On June 8, 2015, Petitioner had a follow-up outpatient evaluation with Dr. Chay. Pet.
Ex. 5 at 45-46. Petitioner reported he had continued getting better and noticed improvement
when increasing the dosage of gabapentin. Id. at 45. He no longer required catheterization. Id.
Petitioner also reported “intermittent difficulty with achieving and maintaining an erection,” and
the “sensitivity ha[d] been decreased since the [TM].” Id. He was prescribed Viagra. Id. at 46.
Petitioner continued to return to Moss Rehabilitation for follow-up visits from 2015 to
2019 for continued “neurogenic sensations.” Pet. Ex. 17 at 6-10, 17-21; see also Pet. Exs. 13,
20. At a visit on December 1, 2016, it was noted that Petitioner’s “[s]ympoms [were] attributed
to nontraumatic spinal cord injury, which occurred on [May 24, 2014] as a result of [TM].” Pet.
Ex. 17 at 6. Records from Petitioner’s PCP in 2020 and 2021 indicated Petitioner continued to
take gabapentin daily. Pet. Ex. 24 at 44, 48.
No additional relevant medical records were provided.
2. Petitioner’s Affidavit and Testimony
Petitioner recalled he received the Tdap vaccine on May 20, 2014, between 5:00 and 6:00
PM. Pet. Ex. 10 at ¶ 3. Prior to and “[a]t the time of vaccination, [he] was a normal, healthy
adult with no neurological medical history.” Id. at ¶ 4; see also Tr. 8, 43.
On the night of May 21, Petitioner “noticed some minor stiffness in [his] feet before [he]
went to bed” at around 11:00 PM. Pet. Ex. 10 at ¶ 5. That was the only symptom he had that
day. Tr. 11. The following day, on May 22, he “experienced some numbness and stiffness in
[his] feet and legs” but still went to work and worked a full day. Pet. Ex. 10 at ¶ 5; see Tr. 11,
38. By Friday, May 23, Petitioner’s “symptoms became worse. The numbness and weakness
had got[ten] worse throughout [his] lower extremities” and he had to leave work early that day.
Pet. Ex. 10 at ¶ 6; see Tr. 12, 39. That night, he was “unable to urinate before going to bed.”
Pet. Ex. 10 at ¶ 6. The next day, May 24, his “symptoms got much worse.” Id. at ¶ 7. He woke
up and for the first time, was “unable to stand up, walk by [him]self, . . . [un]able to urinate, and
[his] foot [was] more stiff.” Tr. 13. The night of May 24, Petitioner went to the ED “because of
spreading numbness and weakness in [his] lower extremities and the inability to urinate.” Pet.
Ex. 10 at ¶ 7. When he got to the ED, he told them he “got . . . the tetanus shot, and day by day,
[he] lost [] feeling.” Tr. 17.
After admission to the hospital, Petitioner underwent various tests was diagnosed with
TM. Pet. Ex. 10 at ¶ 8. He continued to complain of “stiffness” from his stomach down to his
feet as well as “numbness” sensations. Tr. 23, 25, 32, 35, 40-41. As of the date of his testimony,
Petitioner continued to suffer lower extremity weakness, urination issues, and continued to take
gabapentin. Tr. 24, 34-35; see also Pet. Ex. 10 at ¶¶ 12-13.
9
3. Letter from Dr. Wesley Chay
Petitioner filed a letter authored by Dr. Chay dated January 18, 2016. See Pet. Ex. 5. In
his letter, Dr. Chay stated that Petitioner had been under his care since his acute inpatient
hospitalization at Moss Rehabilitation on May 30, 2014. Id. at 1. Dr. Chay summarized
Petitioner’s history as presenting to the ED where he received sutures and a Tdap shot for a
laceration. Id. Petitioner was then discharged home and “after two days, he started developing
tightness and weakness in his legs. This progressed and over the next couple days he also
developed [the] inability to urinate.” Id. Thereafter, he underwent MRIs and a lumbar puncture
which were “consistent with [TM].” Id. Petitioner was treated with IV Solu-Medrol for five
days, transitioned to a prednisone taper, and after stabilizing, was discharged to Moss
Rehabilitation. Id. Dr. Chay reported that Petitioner made “significant progress during his time”
there where he received three hours of occupational and physical therapies daily. Dr. Chay also
saw Petitioner in follow-up visits while receiving outpatient treatment. Id.
Dr. Chay is a “board-certified Spinal Cord Injury Medicine physiatrist” and the Clinical
Director of the Inpatient Spinal Cord Injury Program at MossRehab. Pet. Ex. 5 at 2. In this
capacity, he “see[s] many individuals with spinal cord injury and disease. [He] ha[s] treated
many patients with [TM], and in many cases, a direct link to a prodrome infection or recent
vaccination is present.” Id. He noted the existence of “several cases reported in the medical
literature where individuals who received a [Tdap] shot have subsequently developed [TM].” Id.
Dr. Chay opined, to a reasonable degree of medical and scientific certainty, that “the [Tdap] shot
that [Petitioner] received for a work-related injury was the etiology of [TM] in his case.” Id.
D. Expert Reports
1. Petitioner’s Expert, Dr. John Conomy23
a. Background and Qualifications
Dr. Conomy was a board-certified neurologist. Pet. Ex. 9 at 1. Dr. Conomy received his
M.D. from St. Louis University and J.D. from Case Western Reserve University. Id. At the time
of writing his expert report, Dr. Conomy was a Clinical Professor of Neurology at the Case
Western Reserve University School of Medicine and a clinician at the University Hospitals of
Cleveland. Id. at 1-2. He authored countless publications on neurological conditions and related
topics. Id. at 36-52.
b. Opinion
Dr. Conomy opined, more likely than not, Petitioner’s May 20, 2014 Tdap vaccine
caused him to develop TM via molecular mimicry. Pet. Ex. 8 at 2-5.
23
Dr. Conomy submitted one expert report in this matter. Pet. Ex. 8. He did not testify at the
hearing. Dr. Conomy has since passed away.
10
i. Althen Prong One
Dr. Conomy posited the mechanism of damage to the spinal cord and nervous system in
instances of TM by the Tdap vaccine is the “activation of the body’s immune system to the effect
that immunologically active cells and substances associated with them ‘attack’ the substance of
the spinal cord.” Pet. Ex. 8 at 4-5.
To support his theory of molecular mimicry, Dr. Conomy cited to Siegrist,24 which
described generally how vaccines induce immune responses. Pet. Ex. 8.5. Chandra et al. also
raised molecular mimicry as a hypothesis for vaccine-induced neuroinflammatory and
autoimmune diseases. Pet. Ex. 8.7 at 1. Describing molecular mimicry, Chandra et al. stated
“proteins on microbial pathogens are similar to the human proteins and thus induce immune
response that damage the human cells.” Id.
Because TM is an inflammatory disorder with a suggested autoimmune pathogenesis, Dr.
Conomy stated there are some suggestions it can be vaccine-induced. Pet. Ex. 8 at 3-4; see Pet.
Ex. 8.7 at 1. For example, Agmon-Levin et al. noted “[t]he pathogenesis of [TM] is mostly of an
autoimmune nature, triggered by various environmental factors, including vaccination.” Pet. Ex.
8.8 at 1. Agmon-Levin et al. conducted a systematic review of journals published between 1970
and 2009 to analyze cases of TM following vaccination. Id. at 1-2. Their initial search revealed
43 cases, but six were excluded due to insufficient data. Id. at 2. Of the remaining 37 cases, four
were reported after diphtheria-tetanus-pertussis (“DTP”) or diphtheria and tetanus (“DT”)
vaccines, and one was reported after a multiple vaccine regimen that included DT. Id. at 2, 3
tbl.1. “In most of these cases[,] the temporal association was between several days and 3
months.” Id. at 5. Twenty-seven of the 37 cases (73%) developed symptoms of TM within the
first month after vaccination, three developed symptoms between one and two months after
vaccination, and seven developed symptoms more than two months after vaccination. Id. at 2, 3
tbl.1. For the cases of TM after DTP and DT, onset was between three and 17 days. Id. at 3
tbl.1.
Agmon-Levin et al. discussed mechanisms by which vaccines may induce TM and noted
“molecular mimicry between infectious antigens and self-antigens is the most common
mechanism.” Pet. Ex. 8.8 at 4 (emphasis omitted). They added that a “host’s response to a
vaccine, originally generated to produce protective immunity, is similar to its response to an
infectious invasion.” Id. The authors concluded that “the temporal association between []
vaccines and TM, and the possible mechanism associating these phenomena cannot be ignored.
The rarity of TM makes it a difficult disease to study.” Id. at 5.
24
Claire-Anne Siegrist, Vaccine Immunology, in Plotkin’s Vaccines 17 (7th ed. 2018).
11
Dr. Conomy referenced other instances of TM and related conditions resulting from
vaccines described in the literature. Pet. Ex. 8 at 4, 6.25 For example, Chandra et al. described a
case report of a healthy 38-year-old male who developed TM, characterized by weakness of his
lower extremities, after receipt of measles-mumps-rubella (“MMR”) and influenza vaccinations.
Pet. Ex. 8.7 at 1. The authors noted that approximately five cases of TM had been reported
following tetanus toxoid (“Td”) and DTP vaccinations. Id.
ii. Althen Prongs Two and Three
Dr. Conomy opined that Petitioner’s Tdap vaccine caused his TM through the
autoimmune mechanism described above. Pet. Ex. 8 at 4 (“All of the clinical evidence regarding
[Petitioner] points to an acquired, immune-mediated cause for the damage to his spinal cord.”).
First, Dr. Conomy agreed with Petitioner’s treating physicians and the other experts that
TM was the proper diagnosis. Pet. Ex. 8 at 3. The “configuration of the lesion in his thoracic
spinal cord, the presence of inflammatory cells in his [CSF], elevated spinal fluid proteins[,] and
the presence of immunophoretic bands of protein [immunoglobulin G (“IgG”)] in his [CSF]”
support a diagnosis of TM, an “immune-pathological condition.” Id. at 4. Because the CSF
analysis particularly “connot[es] an immune-mediated, inflammatory condition,” Dr. Conomy
opined it was the Tdap vaccine that directed this response via molecular mimicry. Id. at 3-4.
Next, Dr. Conomy acknowledged that while TM caused by vaccination often manifests
between two weeks and three months post-vaccination, “that latency period should not be taken
as a hard and fast rule.” Pet. Ex. 8 at 6. He pointed out cases of TM that “occurred in a couple
to a few days, not longer,” after vaccination. Id. For example, Agmon-Levin et al. documented
cases of TM with 3-day, 6-day, 7-day, and 17-day onsets. Pet. Ex. 8.8 at 3 tbl.1. Thus, Dr.
Conomy suggested Petitioner’s onset was a matter of days.26 Pet. Ex. 8 at 2, 5-6.
Moreover, Dr. Conomy noted “the absence of the identification of any other causal factor
in spite of an assiduous search for such.” Pet. Ex. 8 at 5. He explained other causes of TM
include bacterial infections, viral diseases, multiple sclerosis (“MS”), malignancies, and vascular
25
In addition to Agmon-Levin et al. and Chandra et al., Dr. Conomy also cited an article by
Kulenkampff et. al., but it was published in 1974, and does not reflect the most up-to-date and
relevant data. Pet. Ex. 8.9 (M. Kulenkampff et al., Neurological Complications of Pertussis
Inoculation, 49 Archives Disease Childhood 46 (1974) (describing neurological complications
following DPT vaccine)).
26
Dr. Conomy did not opine as to a specific date of onset, but it appears he suggested May 24,
2014 (the day Petitioner presented to the ED) as the likely onset. See Pet. Ex. 8 at 2, 4-6; Resp.
Ex. C at 4.
12
disorders. Id. at 3; see Pet. Ex. 8.1;27 Pet. Ex. 8.3.28 However, Dr. Conomy reasoned that
Petitioner “underwent extensive testing for these disorders by history, examination, imaging
studies, [CSF] examination, and numerous blood tests” but they were unrevealing. Pet. Ex. 8 at
3.
2. Petitioner’s Expert, Dr. Maria Chen29
a. Background and Qualifications
Dr. Chen is a board-certified neurologist. Pet. Ex. 19 at 1. Dr. Chen received a Ph.D. in
molecular virology and M.D. from the University of Pennsylvania School of Medicine. Id.; Pet.
Ex. 19.11 at 1. As a licensed physician, Dr. Chen actively sees over 2,000 patients per year. Pet.
Ex. 19 at 1. She has seen over 100 patients in her career with “some form of [TM].” Id. Dr.
Chen is an assistant professor of clinical neurology at the Perlman School of Medicine at the
University of Pennsylvania. Id. She also supervises neurology residents and medical students at
the University of Pennsylvania Hospital and the Penn Presbyterian Hospital. Id. While she does
not currently conduct research, she has authored publications “outlining the mechanisms that
viruses, specifically HIV, injure the nervous system.” Id. at 1-2; Pet. Ex. 19.11 at 2.
b. Opinion
Dr. Chen opined that Petitioner’s Tdap vaccine caused his TM through an allergy or
hypersensitivity immune response. Pet. Ex. 23 at 1. She focused her reports on how TM can
manifest within 24 hours of vaccination through this proposed theory. Pet. Ex. 19 at 1.
i. Althen Prong One
Dr. Chen proposed that TM can be mediated through an allergy and innate response
within 24 hours of vaccine administration. Pet. Ex. 19 at 1. The specific allergic response Dr.
Chen focused on was a hypersensitivity response to drugs or antigens. Id. at 2.
Dr. Chen explained that one mechanism of a hypersensitivity response is “that the drug or
antigen is taken up by antigen present[ing] cells such as dendritic cells. Antigen presenting cells
then process and present the antigen to T and B-cells resulting in production of [immunoglobulin
E (“IgE”)] antibodies.” Pet. Ex. 19 at 2. Then, on future exposure, “the drug or another similar
product to the drug (for cross-reactive drugs) is recognized by IgE antibodies resulting in
crosslinking of IgE. The crossed-linked IgE can then bind to its receptor [] cells of the innate
Timothy W. West, Transverse Myelitis – A Review of the Presentation, Diagnosis, and Initial
27
Management, 88 Discovery Med. 167 (2013).
28
Oded Abramsky & Dvora Teitelbaum, The Autoimmune Features of Acute Transverse
Myelopathy, 2 Annals Neurology 36 (1977).
29
Dr. Chen submitted two expert reports in this matter. Pet. Exs. 19, 23. She did not testify at
the hearing.
13
immune response such as mast cells.” Id. Once mast cells are activated, their “chemical
mediators cause increase in permeability of capillaries allowing for increase access of immune
cells and immune compounds into tissue.” Id. Importantly, Dr. Chen noted that “[c]ells of the
innate immune system such as neutrophils and mast cells have been found in central nervous
system [(“CNS”)] tissue of [neuromyelitis optica (“NMO”)] and [MS] hence implicating the
innate immune system in autoimmune [CNS] diseases.” Id. at 3; see also Pet. Ex. 19.10 at 1;30
Pet. Ex. 23 at 3.
Dr. Chen clarified that when a hypersensitivity immune response is mediated via IgE,
“the IgE is existing from a prior immune response.” Pet. Ex. 23 at 1. For example, the
introduction of the Tdap vaccine “causes cross-linking of existing IgE and this incites a new
immune response. Pre-existing IgE can bind to its originally intended antigen or unintended
antigens which bear similar characteristics (i.e. cross-react).” Id. Then, “[o]nce bound to the
target antigen, the IgE-antigen complex binds and activates mast cells and basophils which
express the IgE receptor. These effector cells then release a multitude of other chemical
mediates to cause an immune response characterized by an immediate hypersensitivity
response.” Id.
Because IgE are already present, Dr. Chen explained “the immune response to the
administration of the Tdap vaccine is immediate and hence, occurs within a day of
administration of the Tdap vaccine.” Pet. Ex. 23 at 1. Citing Stone et al.,31 she stated that the
hypersensitivity reactions can occur rapidly within minutes to hours of exposure. Pet. Ex. 19 at 2
(citing Pet. Ex. 19.3 at 1). “Immunological mechanisms can be dependent on the presence of
IgE, in which case reactions tend to start rapidly after exposure. Alternatively, they may be
independent of IgE, in which case they can occur either rapidly or after many hours, particularly
if the mechanism is T-cell mediated.” Pet. Ex. 19.3 at 2; see also Pet. Ex. 23C at 2 (describing
that immunologically mediated allergic reactions can be delayed and occur within hours or days
after exposure).32
To support her contention that an allergic mechanism can result in immunological CNS
injuries, Dr. Chen referred to a case of a rare form of TM called atopic myelitis, or atopic TM,
reported in Asia. Pet. Ex. 19 at 2; see Pet. Ex. 19.1;33 Pet. Ex. 19.2.34 Atopic TM is defined as a
30
Richard M. Ransohoff & Melissa A. Brown, Innate Immunity in the Central Nervous System,
122 J. Clinical Investigation 1164 (2012).
31
Shelley F. Stone et al., Immediate-Type Hypersensitivity Drug Reactions, 78 Brit. J. Clinical
Pharmacology 1 (2013).
32
Michael M. McNeil & Frank DeStefano, Vaccine-Associated Hypersensitivity, 141 J. Allergy
Clinical Immunology 463 (2018).
33
FA Fasola & OW Aworanti, Hypereosinophilic Atopic Transverse Myelitis, 21 Nigerian J.
Clinical Prac. 816 (2018).
34
Jun-ichi Kira, Atopy and Neural Damage, 41 Internal Med. 169 (2002).
14
localized myelitis in individuals with elevated levels of IgE, which in turn, implicates an allergy
mediated pathway of immune disease. Pet. Ex. 19.1 at 3; Pet. Ex. 19 at 2. “Pathological
evaluation by sampling of the spinal cord tissue has indicated that an immune cell of the innate
immune system call[ed] the eosinophil is directly involved in the immune mediated injury of the
[TM].” Pet. Ex. 19 at 2 (citing Pet. Ex. 19.2 at 2). Dr. Chen opined this example demonstrates
that an adaptive immune response via T-cells and B-cells is not the only mechanism by which
TM can be mediated. Pet. Ex. 23 at 2.
To support her opinion that an allergy or hypersensitivity reaction is a recognized
mechanism for vaccine-associated adverse events, Dr. Chen cited an article by McNeil and
DeStefano, which discussed the “types of immunologically mediated hypersensitivity that can
occur after vaccination.” Pet. Ex. 23C at 2; see Pet. Ex. 23 at 1. However, in contrast to Dr.
Chen’s explanation, the authors noted that “[v]accine antigens themselves rarely, if ever, are the
cause of hypersensitivity reactions. Rather, hypersensitivity reactions after vaccination are
usually due to individual vaccine components” such as adjuvants.35 Pet. Ex. 23C at 3. The
authors noted that “[n]o immediate hypersensitivity reactions have been documented” for
aluminum-containing adjuvants, the most widely used adjuvants in vaccines, including the Tdap
vaccine.36 Id. at 4. Although Dr. Chen identified aluminum phosphate as an adjuvant in Tdap,
she did not explain how it could cause TM given her theory here.
Next, Dr. Chen pointed to anaphylaxis,37 or anaphylactic shock, to support an allergy or
hypersensitivity reaction as a recognized mechanism for vaccine-related adverse events. Pet. Ex.
23 at 1-2. Notably, she noted that anaphylaxis is a Table injury for vaccines containing Td,
including Tdap, in the Vaccine Program. Pet. Ex. 23D at 1. Dr. Chen expressed that if the
Vaccine Program “recognizes and accepts hypersensitivity reaction in its severe form of
anaphylaxis as a[] Table injury, it is not clear why less severe hypersensitivity reactions are not
plausible as a[] vaccine-related adverse reaction,” particularly “if no other immune trigger has
been identified in causing the [TM] which almost always has an immune-mediated cause.” Pet.
Ex. 23 at 2.
While Dr. Chen opined that TM can be mediated through a hypersensitivity response, she
also agreed with Dr. Gershwin’s innate immune response theory, as discussed below. Pet. Ex. 23
at 3. She averred that “Dr. Gershwin’s theory of an innate immune response does not contradict
35
“Adjuvants are incorporated into some vaccine formulations to enhance or direct the immune
response of the vaccinated subject, specifically to boost T-cell immunity and increase helper T-
cell function.” Pet. Ex. 23C at 4.
36
Petitioner received the Adacel Tdap vaccine, which contained an aluminum phosphate
adjuvant. Pet. Ex. 1 at 5; Resp. Ex. 31 (package insert); Pet. Ex. 19 at 3.
37
Anaphylaxis is “a type I hypersensitivity reaction in which exposure of a sensitized individual
to a specific antigen [] results in” rash and swelling, followed by respiratory distress.
Anaphylaxis, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/
definition?id=2577 (last visited Feb. 1, 2023).
15
nor exclude [her] proposed mechanism of a hypersensitive immune response,” and instead, could
even “complement” it. Id.
ii. Althen Prongs Two and Three
Dr. Chen agreed with Petitioner’s treating physicians and the other experts that
Petitioner’s diagnosis is TM. Pet. Ex. 19 at 3.
Dr. Chen opined that “[a]utoreactive IgE present in [Petitioner] and responding to the
Tdap vaccine is a reasonable mechanism of autoimmunity,” as described above. Pet. Ex. 23 at 2.
And “[g]iven that components of the [Tdap] (Adacel) vaccine have been demonstrated to
activate components of the innate immune response,” and “how rapid hypersensitivity responses
can occur, . . . it is plausible that the Tdap vaccination cause[d] symptom onset of [TM] in
[Petitioner] to be within 24 hours.” Pet. Ex. 19 at 1; Pet. Ex. 23 at 2.
3. Petitioner’s Expert, Dr. Lawrence Steinman38
a. Background and Qualifications
Dr. Steinman is a board-certified neurologist and has practiced neurology at Stanford
University for over 40 years. Pet. Ex. 25 at 2; Pet. Ex. 26 at 1. He received his M.D. from
Harvard University. Pet. Ex. 26 at 1. Dr. Steinman is currently a professor in the Department of
Neurology at Stanford University. Id. He is also “actively involved in patient care” and has
cared for hundreds of adults and children with various inflammatory neuropathies, including TM.
Pet. Ex. 25 at 2; see also Tr. 49-50. Dr. Steinman has authored or co-authored over 500
publications on immunology. Pet. Ex. 26 at 5-47; Tr. 47.
b. Opinion
Dr. Steinman opined Petitioner developed TM as a result of the Tdap vaccine through the
mechanism of molecular mimicry. Pet. Ex. 25 at 6-7. Additionally, he opined onset was 48-72
hours post-vaccination, although his theory would “cover even 24 hours” if one attributed
Petitioner’s descriptions of foot stiffness as the initial manifestation of TM. Id. at 6.
i. Althen Prong One
Dr. Steinman proposed molecular mimicry to explain how the Tdap vaccine can cause
TM. Pet. Ex. 25 at 6. Specifically, he opined that the pertussis component of Adacel (the Tdap
vaccine Petitioner received) “contains a molecular mimic of sufficient homology with an antigen
MOG (myelin oligodendrocyte [glyco]protein) that is attacked in [TM]” so as to cause an
immune response to an otherwise susceptible recipient. Id. at 6, 12; see also Tr. 56.
38
Dr. Steinman submitted one expert report and testified at the hearing on March 15 and 16,
2022. Pet. Ex. 25; Tr. 44, 349.
16
Regarding molecular mimicry generally, Dr. Steinman explained that shared structures on
a virus, bacteria, or vaccine (“non-self” or “foreign” antigens) can trigger a cross-reactive
response to oneself. Pet. Ex. 25 at 7; Tr. 104. “In some people, . . . a foreign antigen may
resemble antigen produced by the body. Such molecular mimicry provokes the T cells to attack
the body tissues that contain the self-antigens.” Pet. Ex. 36 at 4.39
More specifically, Dr. Steinman opined that a protein in the vaccine cross-reacted with a
protein in the nervous system (MOG), which can cause TM. Tr. 56. He referenced an article by
Jarius et al.,40 which reported that MOG-IgG was found in serum of some patients with optic
neuritis and/or myelitis. Pet. Ex. 29 at 1-2. Thirteen percent (6/45) of patients with
longitudinally extensive TM (like Petitioner’s) were positive for MOG-IgG. Id. The authors
postulated that MOG- IgG antibodies may play a pathogenic role in disease. Id. at 10-12.
Dr. Steinman used a three-step process to identify protein sequences that could implicate
molecular mimicry. Tr. 58-59. First, he researched the components of the Adacel (Tdap)
vaccine and the components of the pertussis toxin. Pet. Ex. 25 at 7. Next, Dr. Steinman
conducted a BLAST41 search to determine whether there was sequence homology between the
pertussis toxin and MOG.42 Id. at 7-8. He found a pertussis toxin sequence and a MOG
sequence “with 5 identical amino acids in a stretch of 12 consecutive amino acids.”43 Id. at 8.
Relying on medical literature, Dr. Steinman opined the sequence he found was significant
due to the presence of five identical amino acids in a longer sequence. Pet. Ex. 25 at 7. Root-
Bernstein44 found that “[s]imilarities were considered to be significant if a sequence contained at
39
Lawrence Steinman, Autoimmune Disease, 269 Sci. Am. 107 (1993).
40
Sven Jarius et al., MOG-IgG in NMO and Related Disorders; A Multicenter Study of 50
Patients. Part 1: Frequency, Syndrome Specificity, Influence of Disease Activity, Long-Term
Course, Association with AQP4-IgG, and Origin, 13 J. Neuroinflammation 279 (2016).
41
A BLAST (Basic Local Alignment Search Tool) search “finds regions of similarity between
biological sequences. The program compares nucleotide or protein sequences to sequence
databases and calculates the statistical significance.” BLAST,
https://blast.ncbi.nlm.nih.gov/Blast.cgi (last visited Mar. 28, 2023).
42
For a complete explanation of Dr. Steinman’s investigation, including his discussion on the
number of amino acids required for homology relevant to molecular mimicry as well as the
procedure he followed in conducting his BLAST searches, see Pet. Ex. 25 at 8-10.
43
The five identical amino acids Dr. Steinman identified were GGDPG, with GGVIKDGTPGG
as the pertussis epitope and GGLLRDHIPRG as the MOG epitope. Pet. Ex. 25 at 8.
44
Robert Root-Bernstein, Rethinking Molecular Mimicry in Rheumatic Heart Disease and
Autoimmune Myocarditis: Laminin, Collagen IV, CAR, and B1AR As Initial Targets of Disease,
2 Frontiers Pediatrics 1 (2014).
17
least 5 identical amino acids in 10.” Pet. Ex. 40 at 1. Lanz et al.45 found five out of 12 identical
amino acids for molecular mimicry between Epstein-Barr virus and MS. Tr. 66-67; Pet. Ex. 44
at 10. Additionally, papers by Gautam et al. found “5 of 12 amino acids, not even consecutive
amino acids, was sufficient to trigger experimental encephalomyelitis (EAE) with involvement
of the spinal cord.” Pet. Ex. 25 at 7; see also Pet. Ex. 37 at 1;46 Pet. Ex. 39 at 1;47 Tr. 63-64. Dr.
Steinman explained that there can be an autoimmune response with five out of 12 amino acids.
Pet. Ex. 25 at 7 (citing Pet. Ex. 36 at 4); Tr. 64 (explaining the framework needed to be
potentially meaningful using the model system in Guatam et al. was five out of 12).
The third step of his process was to search for the pertussis toxin epitope in the Immune
Epitope DataBase (“IEDB”).48 Pet. Ex. 25 at 8. The epitope appeared on the IEDB, which Dr.
Steinman asserted was evidence that the epitope has been reported in humans. Id. at 9-10; Tr.
353. Dr. Steinman testified that because it was reported in the IEDB, “somebody else studied the
region of the pertussis toxin and found it was an epitope or landing pad for parts of the immune
system.” Tr. 64. Based on this finding, he posited there is “something in the vaccine that has
molecular similarities with something that is attacked by the immune system in cases of [TM].”
Tr. 64-65. And “[f]inding this mimic in an individual who developed [TM] that shares 5 of 12
identical amino acids with MOG is instructive.” Pet. Ex. 25 at 10.
Dr. Steinman acknowledged the limitations to this process of confirming molecular
mimicry and sequence homology.49 On cross-examination, Dr. Steinman conceded that the
protein sequence of the pertussis toxin in the vaccine that activated T cells in the MOG are not
known. Tr. at 94-95. He also agreed that the epitope he identified in the IEDB was not
immunogenic. Tr. 362. Dr. Steinman explained that he could “validate the experiment” and
“advance [the] theory closer to certainty” by performing the assays specific to Petitioner in a lab.
Pet. Ex. 25 at 10; Tr. 59-60, 65. However, because he is unable to perform research on the
45
Tobias V. Lanz et al., Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNNA1
and GlialCAM, 603 Nature 321 (2021).
46
Anand M. Gautam et al., A Polyalanine Peptide with Only Five Native Myelin Basic Protein
Residues Induces Autoimmune Encephalomyelitis, 176 J. Experimental Med. 605 (1992). Dr.
Steinman is a named author in this paper.
47
Anand M. Gautam et al., A Viral Peptide with Limited Homology To a Self Peptide Can
Induce Clinical Signs of Experimental Autoimmune Encephalomyelitis, 161 J. Immunology 60
(1998). Dr. Steinman is a named author in this paper.
48
The IEDB “catalogs experimental data on antibody and T cell epitopes studied in humans,
non-human primates, and other animal species in the context of infectious disease, allergy,
autoimmunity and transplantation. The IEDB also hosts tools to assist in the prediction and
analysis of epitopes.” Immune Epitope Database and Analysis Resource, https://www.iedb.org/
(last updated Mar. 19, 2023). The IDEB is a freely available resource funded by the National
Institute of Allergy and Infectious Diseases. Id.49
For the limitations acknowledged by Dr. Steinman, see Tr. 93-100.
18
Petitioner, he asserted that his three-step process, along with supportive medical literature, is the
“next best thing.” Tr. 59; see also Pet. Ex. 25 at 10.
ii. Althen Prongs Two and Three
Dr. Steinman agreed with the diagnosis of TM and opined “an ingredient in the vaccine
cross-reacted with a protein in the nervous system” and “that was, more likely than not, the basis
for [Petitioner’s TM].” Tr. 53, 56. He stated this was a “primary immune response” since
Petitioner had not received an earlier Tdap vaccine nor been infected with pertussis. Pet. Ex. 25
at 11. Dr. Steinman posited this response typically “begin[s] within the first 24 hours of
exposure to antigen” but he opined that Petitioner’s onset was 48-72 hours post-vaccination. Pet.
Ex. 25 at 11-12; see also Tr. 85, 87.
Petitioner received his first Tdap vaccine (Adacel) on May 20, 2014. Pet. Ex. 25 at 5
(citing Pet. Ex. 11 at 1). The next night (May 21), Petitioner noticed foot stiffness before going
to bed. The following day (May 22), he noticed numbness and stiffness in his feet and legs
which “intensified on May 23.” Id. On May 23, he began experiencing “lower back pain and
difficulty walking,” and by evening, Petitioner could not urinate entirely. Pet. Ex. 2 at 28; see id.By May 24, Petitioner’s lower extremity weakness and numbness worsened, and he presented to
the ED. Pet. Ex. 25 at 5 (citing Pet. Ex. 11 at 1).
While Dr. Steinman believed the “clear onset” of Petitioner’s TM was 48 to 72 hours
after vaccination, he acknowledged that Petitioner reported foot stiffness that occurred earlier
than 48 hours. Pet. Ex. 25 at 11. Dr. Steinman, however, believed the “foot stiffness” was not
related to Petitioner’s TM, although he agreed that it could have been a “harbinger” of the
illness. Id.; Tr. 114. If it was, Dr. Steinman opined that onset would still fit his theory, because
some references recognize an early response (consistent with an immunoglobulin M (“IgM”)
response) which begins within the first 24 hours of exposure to an antigen. Pet. Ex. 25 at 11; Tr.
85, 87, 103-04.
Dr. Steinman initially opined that Petitioner’s CSF showed clonal-like antibody
responses of the IgM type (IgM antibodies) early in his diagnosis. Pet. Ex. 25 at 11; Tr. 79.
However, on cross-examination, after reviewing Petitioner’s CSF results, he acknowledged that
instead of IgM antibodies, Petitioner had oligoclonal bands indicating an IgG response. Tr. 110-
112. He agreed that IgM antibodies form first and IgG antibodies usually form between a week
or two weeks after exposure to an antigen. Tr. 112. However, in his case, Dr. Steinman placed
onset between 48 and 72 hours post-vaccination. Tr. 85, 87; Pet. Ex. 25 at 2, 12.
Further, Dr. Steinman testified that determining the initial manifestation of TM is “a
matter of interpretation.” Tr. 114. For example, onset can be “the first potential sign, . . . the
first definite sign, or . . . when diagnosis is made.” Id. Given Petitioner’s presentation, he
opined that onset was 48 to 72 hours post-vaccination. Id. He believed that Petitioner’s medical
records have some inconsistencies related to onset and symptom progression, and thus, he is
“more comfortable” placing onset on the day that Petitioner began having back pain instead of
when he experienced only foot stiffness. Tr. 115. Dr. Steinman testified, however, that even if
19
onset was earlier, it would still be acceptable as that would be a manifestation of the IgM
response, which is “very important in this disease.” Tr. 114-15.
Ultimately, Dr. Steinman concluded Petitioner’s “foot stiffness” or “sensation in the foot”
is “not determinative one way or the other.” Tr. 364; Pet. Ex. 25 at 6. He placed onset of
Petitioner’s TM at 48-72 hours post-immunization.50 Tr. 87; Pet. Ex. 25 at 6. He emphasized
that Petitioner had oligoclonal bands four days after vaccination, which indicated a “very notable
immune response [was] going on within his brain compartment” that lead to TM. Tr. 365.
Lastly, Dr. Steinman noted he could not find any alternative or non-vaccine factors that
could have contributed to Petitioner’s TM. Tr. 82.
4. Petitioner’s Expert, Dr. M. Eric Gershwin51
a. Background and Qualifications
Dr. Gershwin is board certified in internal medicine, rheumatology, and allergy and
clinical immunology. Pet. Ex. 47 at 1. He completed his M.D. at Stanford University. Id. He
currently works in the Division of Rheumatology, Allergy, and Clinical Immunology at the
University of California Davis School of Medicine as Director of the Allergy-Clinical
Immunology Program and as a professor.52 Id.; Tr. 119. In this position, he still sees patients.
Tr. 120. Dr. Gershwin has held various editor and reviewer positions on medical journals, and
has authored or co-authored over 1,000 publications during his career. Pet. Ex. 47 at 3, 5-137.
b. Opinion
Dr. Gershwin opined, more likely than not, that Petitioner’s Tdap vaccine caused him to
develop TM through an innate immune response (IgM response) and molecular mimicry (IgG
response). Tr. 122; Pet. Ex. 11 at 7. “Over time this IgM response would increase and
ultimately lead to a class switch to IgG autoantibodies.” Pet. Ex. 11 at 7; see also Pet. Ex. 21 at
2; Pet. Ex. 22 at 3. Dr. Gershwin’s reports focused on the pathogenesis of TM and how an innate
immune response could explain a rapid onset (24 hours) between the Tdap vaccine and the
development of TM. Pet. Ex. 18 at 1; Pet. Ex. 21 at 1.
50
Although Dr. Steinman placed onset at 48 to 72 hours, he opined that his opinions would cover
“even 24 hours if one would attribute the foot stiffness before going to bed on May 21 as a
sentinel manifestation of [TM].” Pet. Ex. 25 at 6. He also acknowledged that TM at the levels
described in Petitioner’s MRI could be consistent with some impairment below the belly button.
Tr. 88.
51
Dr. Gershwin submitted four expert reports in this matter and testified at the hearing on March
15, 2022. Pet. Exs. 11, 18, 21-22; Tr. 118.
52
At the time Dr. Gershwin authored his expert reports, he was also Chief of this division. Pet.
Ex. 47 at 1.
20
i. Althen Prong One
Dr. Gershwin explained that TM is a neurological disorder “causing segmental bilateral
acute spinal cord injury as a result of acute inflammation.” Pet. Ex. 11 at 2. He added that
“symptoms typically develop over several hours and then worsen over one to several days.” Id.The “immune response that leads to pathology in [TM] is a loss of tolerance against
neuroantigens.” Id. at 2, 6. And because inflammation is a “critical component” of TM, the
underlying mechanism “would take the form of either autoantibodies or cytotoxic T cells.” Id. at
6.
According to Dr. Gershwin, an innate immune response could explain, among other
things, a rapid onset between the Tdap vaccine and the development of TM. Pet. Ex. 21 at 1.
Important to Dr. Gershwin’s theory is that “one cannot have an adaptive immune response
without an innate immune response.” Id. at 1; see also Pet. Ex. 18 at 1 (“An adaptive immune
response, whether it’s a normal response or an autoimmune response, initially requires an innate
immune response.” (citing Pet. Ex. 18.1));53 Pet. Ex. 22 at 2 (“[T]he innate immune system
always precedes an adaptive response.” (citing Pet. Ex. 22A)).54
Further, he opined that the innate immune response can cause neurological symptoms.
Tr. 135-36. In short, Dr. Gershwin averred a vaccine can cause a rapid release of cytokines and
other mediators upon administration. Pet. Ex. 22 at 2. The mediators, which peak 24 hours after
vaccination, go from the lymph node to the blood and then to the brain, and produce an
inflammatory response. Id.; Pet. Ex. 21 at 2 (explaining an innate response, consisting of antigen
presenting cells, is “capable of intense proinflammatory cytokine production” and thus “begin[s]
not only the initial injury via inflammation but also initiate[s] the subsequent adaptive (and
sustained) immune response”). Dr. Gershwin offered a detailed discussion breaking down the
process of the innate immune system involving IgM autoantibodies, local pathology, and the
rapid occurrence of this mechanism. See Pet. Ex. 11 at 7.
First, he explained the initial response to vaccination is the activation of preformed IgM
autoantibodies. Dr. Gershwin testified that IgM autoantibodies act as “first responder[s]” and are
“naturally occurring.” Tr. 141; see also Pet. Ex. 11 at 7 (citing Pet. Ex. 11.78 at 1) (“[H]uman
anti-GM IgM antibodies are found in the normal antibody repertoire and detected even at one
month of age.”).55 Preformed IgMs are those naturally occurring IgMs that mature and are part
of the immune response—that is they “expand upon antigen stimulation.” Tr. 141. The
preformed IgMs will recognize and cross-react with vaccine antigens and produce inflammation.
53
Basic Concepts in Immunology, in Immunobiology: The Immune System in Health and
Disease 13 (Charles A Janeway et al. eds., 5th ed. 2001).
54
Douglas M Herrin, Comparison of Adaptive and Innate Immune Responses Induced by
Licensed Vaccines for Human Papillomavirus, 10 Hum. Vaccines & Immunotherapeutics 3446
(2014).
55
María E. Alaniz, Normally Occurring Human Anti-GM1 Immunoglobulin M Antibodies and
the Immune Response to Bacteria, 72 Infection & Immunity 2148 (2004).
21
Tr. 135. He noted “IgM can either be [] in resident cells or translocate within the CNS.” Tr.
150; see also Tr. 133 (“IgM could be produced locally. In addition, . . . IgM can get into the
CNS through transcytosis.”).56
During the hearing, Dr. Gershwin referenced Hervé et al.57 to explain “how vaccines
produce reactions.” Tr. 130. “Vaccine antigens and immune enhancers (as adjuvants) injected
into the muscle are [recognized] by the body as potential pathogens and/or danger signals.” Pet.
Ex. 22B at 3 fig.1. This “leads to the stimulation of local cells, followed by the recruitment of
blood immune cells to the local site and the production of different soluble factors including
vasodilators and cytokines, which may trigger the development of signs and symptoms of local
inflammation.” Pet. Ex. 22B at 3 fig.1.
The cross-reactivity of IgM-producing cells initially leads to local cell stimulation
“within the regional lymph nodes adjacent to the injection” and occurs “quite rapidly.” Pet. Ex.
22 at 2; see also Tr. 135 (“There will be bystander cells that get activated, and they will lead to
tissue damage and tissue necrosis.”). Hervé et al. also detailed that after vaccination, toll-like
receptors (“TLRs”) recognize and bind antigens and potential immune enhancers in a vaccine to
trigger inflammation. Pet. Ex. 22B at 4 fig.2. “Resident immune cells, mast cells, monocytes[,]
and macrophages are activated within minutes of injection and release soluble factors,” such as
proinflammatory cytokines, that “allow cell recruitment from blood.” Id.“Once stimulated, the immune system sets off a complex series of innate immune events”
such as “release of inflammatory mediators including chemokines and cytokines, activation of
complement, and cellular recruitment.” Pet. Ex. 22B at 2. The produced cytokines “act both
locally . . . and may act systemically at distant organs.” Id. at 4 fig.2. The “newly recruited
immune cells, mainly composed of blood-born neutrophils, monocytes[,] and T lymphocytes,
also contribute to pain sensation by releasing soluble factors, such as cytokines, . . . that can
directly interact with local sensory receptors.” Id. “These cells will then drain to regional lymph
nodes and traffic throughout the body” in addition to the “passage or production of cytokines
throughout the body.” Pet. Ex. 22 at 2 (citing Pet. Ex. 22B at 2-3). “Several immune-to-brain
signaling pathways may propagate an inflammatory response to the [CNS] after peripheral
activation of the innate immune system . . . leading to the development of fever and sickness
[behaviors].” Pet. Ex. 22B at 4 fig.2. Thus, Dr. Gershwin opined “the innate immune system is
an active and viable immune pathway, not only in the local lymph nodes, but potentially
throughout the body.” Pet. Ex. 22 at 3.
56
Transcytosis is “a means of transporting a substance across a cell, occurring mainly in sheets
of polarized epithelial cells: the substance is taken up by endocytosis, . . . and delivered to the
opposite side of the cell where it is released by exocytosis.” Transcytosis, Dorland’s Med.
Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=50594 (last visited
Mar. 21, 2023).
57
Caroline Hervé et al., The How’s and What’s of Vaccine Reactogenicity, 39 NPJ Vaccines 1
(2019).
22
In all, Dr. Gershwin opined “the immune system can become activated extremely
rapidly” and this initial innate immune response “can occur within a time interval of 24-36
hours.” Pet. Ex. 18 at 1; see also Pet. Ex. 11 at 7. Then, “[o]ver time this IgM response would
increase and ultimately lead to a class switch to IgG autoantibodies.” Pet. Ex. 11 at 7.
Dr. Gershwin stated, “the immune system can become activated extremely rapidly” and
“[a]ctivation of innate immune cells can certainly occur well before 24 hours.” Pet. Ex. 18 at 1;
Pet. Ex. 22 at 3 (citing Pet. Ex. 22A at 1).58 “In the case of memory CD8 T cells, they are
programmed within the first 24 hours of priming.” Pet. Ex. 18 at 1 (citing Pet. Ex. 18.3;59 Pet.
Ex. 18.4).60 Because IgM is naturally occurring, he posited “a brisk IgM response would be
expected and would occur more rapidly.” Pet. Ex. 11 at 7 (citing Pet. Ex. 11.78 at 1). For
example, in a study with mice, these first responder or innate immune cells were “readily found
as early as three hours after immunization.” Pet. Ex. 22 at 2 (citing Pet. Ex. 22B at 3).
To support his position, Dr. Gershwin noted there is considerable literature on vaccines
and TM. Pet. Ex. 11 at 4-5. Like Dr. Conomy, he cited Agmon-Levin et al., which reported 37
cases of TM associated with different vaccines including Tdap. Pet. Ex. 11 at 4 (citing Pet. Ex.
8.8 at 1). Of those, four cases of TM were associated with Tdap vaccines and presented onset of
symptoms within days. Pet. Ex. 8.8 at 4, 3 tbl.1. In addition, Dr. Gershwin cited Riel-Romero61
which described a case of a patient who developed TM after DTaP vaccination. Pet. Ex. 11.35 at
1. He acknowledged literature did not suggest an association between the Tdap vaccine and TM
based on epidemiology. Pet. Ex. 11 at 5. But he noted TM is rare and therefore epidemiological
evidence is less important than case reports. Id.; Tr. 146-48.
Dr. Gershwin disagreed with Petitioner’s expert’s Dr. Chen’s proposed theory and argued
there is “no evidence that IgE mediates any autoimmune disease.” Pet. Ex. 21 at 2.
ii. Althen Prong Two
Dr. Gershwin opined “the initial pathology of TM suffered by [Petitioner] was due to an
innate immune response that was activated by circulating cytokines and prostaglandins, []
including trafficking of mononuclear cells within lymphatic circulation.” Pet. Ex. 22 at 3; see
also Pet. Ex. 21 at 2 (“[A]n innate first response would be a plausible, more likely than not,
58
Douglas M. Herrin et al., Comparison of Adaptive and Innate Immune Response Induced by
Licensed Vaccines for Human Papillomavirus, 10 Hum. Vaccines & Immunotherapeutics 3446
(2014).
59
Reinhard Obst, The Timing of T Cell Priming and Cycling, 6 Frontiers Immunology 563
(2015).
60
Sarah E. Henrickson et al., Antigen Availability Determines CD8+ T Cell-Dendritic Cell
Interaction Kinetics and Memory Fate Decisions, 39 J. Immunity 496 (2013).
61
RMS Riel-Romero, Acute Transverse Myelitis in a 7-Month-Old Boy After Diphtheria-
Tetanus-Pertussis Immunization, 44 Spinal Cord 688 (2006).
23
explanation for [Petitioner’s] [TM].”). This was Petitioner’s first Tdap vaccine, and Dr.
Gershwin observed that “he is somewhat unusual in that he is [] immunologically naïve to Tdap
as an adult.” Pet. Ex. 11 at 7. Because Petitioner had not received the Tdap vaccine before,
Petitioner’s “first response to the vaccine would be an innate response.” Pet. Ex. 21 at 2.
Regarding alternative causes, Dr. Gershwin opined there was no evidence of vascular or
infectious causes for Petitioner’s TM. Pet. Ex. 21 at 1. Further, no environmental etiology was
found. Pet. Ex. 11 at 7. Accordingly, Dr. Gershwin concluded the development of Petitioner’s
TM was “consistent with the vaccination as the immunological challenge.” Id. He
acknowledged Petitioner’s response was “more rapid than most patients,” but maintained that
“there is absence of an otherwise explicable etiology and that the nature of the immune response
makes an onset such as this case plausible.” Pet. Ex. 18 at 2; see also Pet. Ex. 21 at 1-2; Pet. Ex.
22 at 3.
iii. Althen Prong Three
In general, Dr. Gershwin stated acute TM symptoms can “typically develop over several
hours and then worsen over one to several days.” Pet. Ex. 11 at 2. One of the diagnostic criteria
of TM includes progression to nadir between 4 hours and 21 days. Pet. Ex. 18 at 1; Pet. Ex. 11.5
at 2 tbl.1, 3. Dr. Gershwin opined an innate immune response can explain the “rapid onset” of
TM in Petitioner. Pet. Ex. 11 at 7; Pet. Ex. 21 at 1-2; Pet. Ex. 22 at 3; Tr. 132.
In his four expert reports, Dr. Gershwin consistently opined Petitioner’s onset was
approximately 24 hours after vaccination. Pet. Ex. 11 at 7; Pet. Ex. 18 at 1; Pet. Ex. 21 at 2; Pet.
Ex. 22 at 1. However, at the hearing, after listening to Petitioner’s testimony as well as Dr.
Steinman’s testimony, Dr. Gershwin testified Petitioner’s onset was “more likely” 48-72 hours
after vaccination. Tr. 125. He admitted his opinion about onset at the hearing differed from
what was in his reports. Tr. 142. He reasoned, however, that he is not a neurologist, and thus, he
was not aware of the relevant physiology, specifically “that the foot is innervated by a totally
different mechanism or a totally different dermatome distribution than the thoracic spine.” Tr.
142. Further, he testified “it’s very possible that the stiffness had nothing whatsoever to do with
the onset of the [TM]” and “was an incidental complaint secondary to a normal response to a
first vaccination.” Tr. 123. Ultimately, Dr. Gershwin concluded the “stiffness in the foot [was]
probably a red herring.” Tr. 134.
Nonetheless, he testified that his theory provides a logical explanation for an onset of 24-
48 hours in addition to an onset of 48-72 hours, as described by Dr. Steinman. Tr. 125. In
summary, Dr. Gershwin opined that if the pathogenic mechanism is entirely IgM, an onset of 24
hours would be appropriate, and if innate lymphoid cells are also involved, an onset of 48-72
hours would be appropriate, but would also be “compatible” with 24-48 hours. Tr. 127-28, 132.
5. Respondent’s Expert, Dr. Jeffrey Gelfand62
62
Dr. Gelfand submitted two expert reports in this matter and testified at the hearing on March
15, 2022. Resp. Exs. A, F; Tr. 154.
24
a. Background and Qualifications
Dr. Gelfand is a board-certified neurologist. Resp. Ex. A at 1. Dr. Gelfand completed his
M.D. at Harvard Medical School. Id. at 2; Resp. Ex. H at 1. He is currently an Associate
Professor of Clinical Neurology and an attending neurologist at the University of California at
San Francisco, as well as director of the MS Neuroimmunology Fellowship Program. Resp. Ex.
A at 1-2; Resp. Ex. H at 2; Tr. 155-56. Dr. Gelfand’s practice involves diagnosing patients with
demyelinating conditions including TM. Tr. 159. His clinical research and active practice focus
on neuroinflammatory disorders, including TM. Resp. Ex. A at 2; Resp. Ex. H at 3, 19; Tr. 157.
Dr. Gelfand has published articles in this area and is involved in the editorial process of peer-
reviewed journals. Tr. 156-57; Resp. Ex. H at 21-31.
b. Opinion
Dr. Gelfand opined that Petitioner suffered from acute TM but that it was “unrelated to
the Tdap vaccine administered less than 48 hours before clinical onset of the myelitis.” Resp.
Ex. A at 6; see also Tr. 206-07.
i. Althen Prong One
Dr. Gelfand took issue with the proposed mechanism of molecular mimicry. Resp. Ex. A
at 4-5. He stated that neither Dr. Conomy nor Dr. Gershwin provided specific evidence about
what components in the Tdap vaccine, if any, can “cross-react with antigens in the spinal cord
and cause myelitis specifically.” Id. at 5. “[M]olecular mimicry is the theory under which an
infectious or exogenous agent (such as a protein in the Tdap vaccination) is similar enough to a
host antigen that it induces an antigen-specific auto-inflammatory response while evading usual
immune tolerance protections against autoimmunity.” Id. (citing Resp. Ex. A, Tab 5 at 1).63 Yet
Dr. Gelfand averred that they did not explain “how the Tdap vaccine might mimic a self-protein
in the [CNS].” Id. Dr. Gelfand’s own review of published scientific literature returned “no clear
evidence . . . that antigens in the Tdap vaccine mimic [CNS] antigens.” Id.Moreover, he opined that Dr. Gershwin did “not provide specific evidence of how an IgM
response, let alone one specifically provoked by Tdap vaccination, is implicated in the
pathogenesis of acute [TM] as a specific disease entity or how a Tdap provoked IgM response
can cause [TM].” Resp. Ex. A at 5. Further, Dr. Gelfand testified that while IgM may play a
role in the pathogenesis of some types of neuroinflammatory conditions, there are no studies or
research that describe any role for IgM in the etiology of neurological symptoms in patients with
TM. Tr. 188, 200.
Nonetheless, Dr. Gelfand stated that even if molecular mimicry was postulated, “the time
course of a myelitis developing less than 48 hours after Tdap vaccination would be too soon.”
Resp. Ex. A at 5. He testified that “an immune response to vaccination, particularly with an
adaptive immune response like this, would be expected to take several days.” Tr. 189.
63
Lori J. Albert & Robert D. Inman, Molecular Mimicry and Autoimmunity, 341 New Eng. J.
Med. 2068 (1999).
25
He opined Dr. Gershwin did “not provide specific evidence in the medical literature that
[TM] can occur as early as 48 hours after Tdap vaccination.” Resp. Ex. A at 5. Dr. Gelfand
opined “[i]t takes several days, . . . more than five days, for example, to really develop a typical
adaptive immune response.” Tr. 208. For support, he referenced Baxter et al., which used
specific time intervals to measure and compare a possible association of a demyelinating event
following vaccination. Tr. 191-92; Resp. Ex. A, Tab 9 at 1. The authors identified five to 28
days as the most likely interval following vaccination to result in a demyelinating illness if one
were to occur. Resp. Ex. A, Tab 9 at 3. Dr. Gelfand pointed out at the hearing that the authors
“drew a line at two days, at 48 hours, and not at one day or zero days.” Tr. 192. Additionally, he
cited Langer-Gould et al.,64 a case-controlled analysis that measured a small increase in risk of a
[] demyelinating attack within 14 days of [] vaccine exposure.” Resp. Ex. A at 6 (citing Resp.
Ex. A, Tab 8). “[N]o single vaccine (including Tdap) was statistically significantly associated
with a demyelinating event” and Dr. Gelfand found it notable that “Tdap was one of the most
common vaccines administered in the dataset.” Id.Finally, Dr. Gelfand noted medical literature on the association between the Tdap vaccine
and TM is rare. Resp. Ex. A at 6. In Agmon-Levin et al., for example, only four published cases
were associated with DTP or DT and one case with pertussis. Id. (citing Pet. Ex. 8.8 at 3 tbl.1).
Baxter et al. concluded there is “no association between vaccination (including Tdap) and
[TM].” Id. (citing Resp. Ex. A, Tab 9 at 1). Dr. Gelfand conducted a search of medical literature
from 2009 to 2018 and did not find “any clear additional [] cases of [TM] associated with Tdap.”
Id. Moreover, he testified he is unaware of any “research exploring a role for IgM directly
causing neurologic symptoms associated with [TM].” Tr. 188, 200.
ii. Althen Prong Two
Dr. Gelfand questioned whether there was an alternative diagnosis. He agreed that
Petitioner’s “MRI is consistent and in this clinical context [] diagnostic of TM that is
longitudinally extensive.” Tr. 171. Nevertheless, Dr. Gelfand raised NMO spectrum disorder as
a “possible more specific cause of longitudinally-extensive myelitis” and that it cannot be
formally excluded. Resp. Ex. A at 6. He noted that testing for NMO antibody (aquaporin-4 IgG)
“was repeatedly discussed as something to be considered as an outpatient with planned post-
acute neurology follow-up, but there is no record of this being sent or resulted in the available
record.” Id. at 4. Dr. Gelfand opined “this test is important diagnostically as NMO is an
important cause of longitudinally extensive myelitis specifically and relapse risk is high after a
first myelitis if the NMO antibody is positive.” Id. (citing Resp. Ex. A, Tab 4).65
Although he questioned whether there was a possibility that Petitioner had NMO
spectrum disorder, and raised the importance of NMO antibody testing, Dr. Gelfand did not
64
Annette Langer-Gould et al., Vaccines and the Risk of Multiple Sclerosis and Other Central
Nervous System Demyelinating Diseases, 71 JAMA Neurology 1506 (2014).
65
Dean M. Wingerchuk, International Consensus Diagnostic Criteria for Neuromyelitis Optica
Spectrum Disorders, 85 Neurology 177 (2015).
26
identify any alternative cause for Petitioner’s TM by a preponderant evidence standard. Instead,
he agreed that Petitioner had “idiopathic acute [TM],” meaning there is no specifically identified
cause, but the illness is still considered to be inflammatory in nature. Tr. 206.
iii. Althen Prong Three
Dr. Gelfand asserted that the first ED notes support that “Petitioner had symptoms that
had been worsening over a three-day period.” Tr. 167, 170. On this point, he credited the
opinions of Petitioner’s treating physicians. Tr. 175-77. Accordingly, Dr. Gelfand disagreed
with Dr. Steinman’s opinion on onset (48 to 72 hours). Resp. Ex. F at 2. Also, unlike Dr.
Steinman and Dr. Gershwin, Dr. Gelfand opined that Petitioner’s foot stiffness, starting on May
21, 2014, was the first symptom of TM, and he further opined that this symptom progressed over
several days. Id. Dr. Gelfand placed onset between 24 and 48 hours after vaccination. Tr. 169.
He explained “[i]t is very typical [for patients with TM] to have symptoms that start in
the feet and then can ascend up until the level of [] the spinal cord injury.” Tr. 163. This is
because when there is an injury to the spinal cord, it “can affect fibers that control everything
from [the level of the injury] downward.” Tr. 164. Dr. Gelfand testified that in terms of
localization, extensive myelitis from T2 through T9 can present sensory symptoms “from just
above the nipple line all the way down to the feet.” Tr. 172-75. Thus, he opined “an MRI
showing thoracic-level myelitis absolutely can cause lower extremity symptoms, including foot
stiffness.” Tr. 173; see also Resp. Ex. F at 2.
Petitioner’s MRI showed a “long segment of abnormal central cord signal” extending
from T2 to T9. Tr. 171 (citing Pet. Ex. 2 at 78). Dr. Gelfand opined “the [foot] stiffness was
more likely than not from neuropathic involvement from the spinal cord injury,” and he further
“interpret[ed] the early findings of stiffness in the feet, which worsened the next day and then
worsened more and continued to evolve, to be part of the same spectrum of an evolving spinal
cord syndrome rather than something separate or incidental.” Tr. 187-88.
Further, the radiologist noted that Petitioner’s MRI showed “potential minimal
enhancement of the cord at T6 on the sagittal T1 images.” Tr. 171 (citing Pet. Ex. 2 at 78).
Given the MRI findings, Dr. Gelfand opined that Petitioner’s MRI was consistent with and
diagnostic of a “longitudinally extensive [TM].” Id. Regarding the potential minimal
enhancement seen at the T6 level, Dr. Gelfand explained that “[e]nhancement is a breakdown in
the blood-brain barrier . . . often interpreted as a sign of acute inflammation.” Id.Dr. Gelfand reviewed pertinent entries in the medical record which he opined indicated
that Petitioner began to develop stiffness in his bilateral lower extremities on Wednesday, May
21, 2014. Tr. 176-78; see Pet. Ex. 2 at 3 (“This past Wednesday [] [Petitioner] began to develop
symptoms [] describe[d] as a stiffness in the bilateral lower extremities.”); Pet. Ex. 2 at 5
(“[Petitioner] felt that his feet were stiff.”); Pet. Ex. 10 at ¶ 5 (“On the night of May 21st . . .
[Petitioner] noticed some minor stiffness in [his] feet before [he] went to bed. The following
day, [he] experienced some numbness and stiffness in [his] feet and legs.”). Dr. Gelfand opined
that this “evolution of symptoms is consistent with TM . . . [and] the spectrum of clinical
27
symptoms [is] a continuum and [] part of this same evolving neurologic process” and not
“something separate or incidental.” Tr. 178, 188.
Dr. Gelfand cited Baxter et al. for the time intervals and compared a possible association
of a demyelinating event following vaccination. Tr. 191-92 (citing Resp. Ex. A, Tab 9 at 1). In
Baxter et al., the authors identified a range of five to 28 days as the most likely interval following
vaccination for onset of a demyelinating illness. Resp. Ex. A, Tab 9 at 3. However, they also
used a second risk window of two to 42 days to ensure that they did not miss any cases. Id. Dr.
Gelfand acknowledged this secondary risk window at the hearing when he testified that the
Baxter et al. authors “drew a line at two days, at 48 hours, and not at one day or zero days.” Tr.
192.
While Dr. Gelfand first opined that onset of an adaptive response required five days, he
later testified that it would take “more than five days . . . if not longer.” Tr. 208. He concluded
that “24 hours to 48 hours is very fast.” Id.In summary, Dr. Gelfand opined that “Petitioner developed acute [TM] with first clinical
symptoms 24 to 48 hours following Tdap vaccination but that the . . . evidence does not support
the conclusion that the [] vaccination, more likely than not, caused his myelitis.” Tr. 206-07.
6. Respondent’s Expert, Dr. Thomas Forsthuber66
a. Background & Qualifications
Dr. Forsthuber is board certified in anatomical and clinical pathology and has over 25
years of experience in immunology. Resp. Ex. C at 1. Dr. Forsthuber received a Doctor of
Medicine67 in immunology and M.D. at the University of Tübingen in Germany. Resp. Ex. I at
2; Tr. 219. He is licensed to practice medicine in the United States. Resp. Ex. I at 2. Dr.
Forsthuber is a Professor of Immunology and Endowed Chair of Biotechnology at the University
of Texas at San Antonio and an Adjunct Professor of Pathology and Microbiology &
Immunology at the University of Texas Health Sciences Center, San Antonio. Resp. Ex. C at 1.
Dr. Forsthuber’s research focuses on autoimmune disease and T cell immunology. Id.; Tr. 220.
He has published over 100 papers and book chapters relating to immunology and the pathogenic
mechanisms of autoimmune diseases. Tr. 220; Resp. Ex. I at 22-39.
b. Opinion
Dr. Forsthuber opined “to a reasonable degree of medical and scientific probability” that
the Tdap vaccine was not causally related to Petitioner’s neurological condition. Resp. Ex. C at
3, 12.
66
Dr. Forsthuber submitted three expert reports in this matter and testified at the hearing on
March 16, 2022. Resp. Exs. C, E, G; Tr. 216.
67
According to Dr. Forsthuber, this is equivalent to a Ph.D. Tr. 219.
28
i. Althen Prong One
Dr. Forsthuber disagreed with Petitioner’s proposed theories of hypersensitivity response
and molecular mimicry. First, like Dr. Gershwin, Dr. Forsthuber rejected Dr. Chen’s allergy or
hypersensitivity response. Resp. Ex. E at 1-5. He opined there is “no evidence that ‘atopic
myelitis’ is mediated by ‘an innate, allergy response.’” Id. at 3. In fact, Dr. Forsthuber
explained that in TM, the CSF shows evidence of abnormalities which are consistent with
adaptive immunity and not a hypersensitivity response. Id. In this regard, he seemed to agree
that TM involves an adaptive immune response.
While Dr. Forsthuber recognized molecular mimicry as a sound mechanism in some
situations, he opined it is not supported here. Resp. Ex. C at 6-10. And he criticized the medical
literature cited by Dr. Conomy in support of molecular mimicry. Id. at 4-5. He opined that
Chandra et al., Kulenkampff et al., and Agmon-Levin et al. do not provide specific support of a
causal role between the Tdap vaccine and TM. Id. Additionally, he pointed out that the Tdap
vaccine is not the same as the DTP, DT, or Td vaccines, which were analyzed in those articles.68
Id. at 5. Moreover, he stated that Kulenkampff et al., discussed neurological convulsions in
children to which Dr. Forsthuber opined is irrelevant because “TM is mediated by an
autoimmune mechanism, whereas convulsions typically are not.” Id. Moreover, the earliest
onset reported in Agmon-Levin et al. was three days after DT vaccination and six to 17 days
after DTP vaccination. Id. Thus, Dr. Forsthuber opined the literature cited by Dr. Conomy
argues “against a role for the Tdap vaccine and the neurological condition of [Petitioner]” and
that the onset of TM “slightly over 24 hours after vaccination is not consistent” with Tdap
vaccine causation via molecular mimicry.69 Id.Next, Dr. Forsthuber rejected Dr. Steinman’s three-step process supporting his molecular
mimicry theory as “unreliable.” Resp. Ex. G at 3, 22-24.70 He opined that BLAST searches
were not designed to identify molecular mimicry. Id. at 14, 23; Tr. 227. Instead, he stated
“BLAST [searches] [were] designed to reveal evolutionary relationships rather than
immunological ones.” Resp. Ex. G at 23; Tr. 245 (“[I]t’s not possible to do a BLAST search,
compare two proteins with each other and then conclude that a certain similarity is sufficient to
induce [a] T cell response.”).
68
The undersigned agrees that Kulenkampff et al. is an older article, and that the Tdap vaccine
was not at issue there. However, in Agmon-Levin et al., the authors stated that “a safer acellular
pertussis vaccine (DTaP) was introduced in the US in 1991. Nevertheless, four cases of TM
following DT and DTP . . . have been reported since then.” Pet. Ex. 8.8 at 4. Thus, it is not clear
that Dr. Forsthuber is entirely accurate on this point.
69
Dr. Forsthuber acknowledged that molecular mimicry has been proposed as a pathogenic
mechanism in idiopathic TM. Resp. Ex. C at 3.
70
For a full and detailed explanation of Dr. Forsthuber’s opinions about Dr. Steinman’s three-
step process, see Resp. Ex. G at 3-29.
29
Nonetheless, Dr. Forsthuber attempted to replicate Dr. Steinman’s findings by
performing his own BLAST search for the pertussis toxin and the MOG protein sequence. Resp.
Ex. G at 20. His “search yielded the result, ‘no significant similarity found.’” Id. Dr.
Forsthuber concluded that “the MOG sequence claimed by Dr. Steinman as [a] ‘molecular
mimic’ with pertussis toxin was not contained in the MOG protein sequence reported in the []
database.” Id. Therefore, Dr. Forsthuber surmised that Dr. Steinman used an isoform71 of MOG
that “has not been reported in the MS or TM literature as a target of the autoimmune response.”
Id. (citing Resp. Ex. G, Tab 11).72 “The version of the MOG protein [] Dr. Steinman used for his
BLAST searches [was] significantly longer (295 amino acids) than the conventional MOG (247
amino acids . . . ).” Id. He testified that Dr. Steinman used a longer string of amino acids
“outside the conventional canonical MOG sequence.” Tr. 263. For these reasons, Dr.
Forsthuber concluded that the BLAST search did “not reveal molecular mimicry between Tdap
and MOG.” Resp. Ex. G at 23.
Even if BLAST searches were an effective tool for identifying immunological
relationships, Dr. Forsthuber opined that the “insignificant E-values, reveal no meaningful
similarity between pertussis toxin and MOG.”73 Resp. Ex. G at 23. He explained E-values
measure the degree of meaningful similarity between two proteins. Id. at 14; Tr. 233. He
testified an E-value greater than the BLAST cutoff, which is “one times 10 to the minus sixth,
meaning 0.000001,” indicates there is “no meaningful similarity” between the two compared
proteins and that it is just a “random observation.” Tr. 233, 235. Dr. Forsthuber found the
corresponding BLAST E-value for Dr. Steinman’s search was 0.12, indicating “there is no
significant sequence similarity.” Resp. Ex. G at 17, 16 fig.7. He added that “the E-value of Dr.
Steinman’s sequence [] is in the same range as that of E-values of proteins not implicated in
molecular mimicry.” Id. But “no matter how significant the E-values are,” Dr. Forsthuber
opined “sequence similarities revealed by BLAST or LALIGN[74] searches cannot provide proof
that these sequences will rise to the level of molecular mimicry in humans.” Id. at 19.
Ultimately, he averred “there is no scientifically accepted method to substantiate whether a
particular sequence similarity found by BLAST search would rise to the level of molecular
71
An isoform refers to “any of two or more functionally similar proteins that have a similar but
not an identical amino acid sequence.” Isoform, Merriam-Webster, https://www.merriam-
webster.com/dictionary/isoform (last visited Mar. 22, 2023). Dr. Forsthuber opined Dr.
Steinman used isoform 13. Resp. Ex. G at 20.
72
Kathrin Schanda, Differential Binding of Antibodies to MOG Isoforms in Inflammatory
Demyelinating Diseases, 8 Neurology: Neuroimmunology & Neuroinflammation e1027 (2021).
73
For a more detailed explanation of Dr. Forsthuber’s opinion as to the fact that Dr. Steinman
used the wrong MOG protein when performing his BLAST search, see Tr. 262-66.
74
LALIGN (local alignment tool) “can compare two protein or DNA sequences for local
similarity and show the local sequence alignments.” Resp. Ex. G at 15 n.11. Dr. Forsthuber
refined the BLAST results using the LALIGN tool because “it permits better targeted similarity
searches.” Id. at 15. He opined that LALIGN, like BLAST, is designed to identify evolutionary
relationships, not immunological ones. Id. at 21.
30
mimicry or have any relationship to the development of a disease process in [a] human.” Id. at
11.
Next, Dr. Forsthuber criticized Dr. Steinman’s use of Root-Bernstein, Lanz et al., and the
Gautam et al. papers as support for the claim that five out of 12 amino acids constitutes
meaningful sequence similarities.75 Resp. Ex. G at 23, 10; Tr. 228-29. For example, Lanz et al.
did not use a BLAST search to identify molecular mimicry. Tr. 253-54. And “Gautam et al. did
not claim or report a method for identifying molecular mimics based on ‘identity of x of y amino
acids, not even in sequence.’” Resp. Ex. G at 23. Instead, Gautam et al. investigated a known
sequence and showed that specific amino acids need to be in defined positions to react, which is
an “entirely different approach” than that used by Dr. Steinman. Id.; Tr. 239-41. Dr. Forsthuber
opined these “short regions are so frequent that it’s really somewhat questionable whether they
play a role in molecular mimicry.” Tr. 228-29. For support, he cited Trost et al.76 and Kanduc et
al.,77 which demonstrated the commonality of sequence similarities, and Silvanovich et al.,78
which “suggested that homologies based on searches for short amino acid matches of [eight]
amino acids or fewer are a product of chance” and “does not amount to ‘molecular mimicry.’”
Tr. 228-31 (citing Resp. Ex. G, Tabs 1-3); see also Resp. Ex. G at 2, 23. Additionally, he cited
Frankild et al.,79 which “confirmed that central positions of a peptide . . . are important for [T cell
receptor] recognition.” Resp. Ex. G at 26. He explained that it is “inevitable that BLAST
searches will regularly yield amino acids that overlap between proteins simply by chance,” and
“you can’t predict whether a T cell could be activated or not.” Id. at 14, 19; Tr. 247.
Regarding Dr. Steinman’s use of the IEDB database, Dr. Forsthuber opined was
misleading because “[n]either the alleged pertussis toxin epitope [] nor the alleged MOG epitope
[] were reported in the IEDB database” at the time he wrote his report. Resp. Ex. G at 24. Dr.
Forsthuber stated that Dr. Steinman set the IEDB search parameters “such that similar, but not
identical sequences are shown by using the lowest possible stringency setting of 70% for his
searches.” Id. at 24, 25 fig.12. According to Dr. Forsthuber, these are not the same peptides as
the alleged molecular mimic. Id. at 24. He testified this means “an immune response has not
been reported by investigators in IEDB specifically against this peptide.” Tr. 277. Because it “is
75
Dr. Forsthuber also opined that Dr. Steinman’s “matching 5 amino acids are not consecutive”
in the sequence, “but they are spread out over a stretch of 12 amino acids and interspersed with
amino acids that do not match.” Resp. Ex. G at 14; Tr. 249.
76
Brett Trost et al., Bacterial Peptides are Intensively Present Throughout the Human Proteome,
1 Self/Nonself 71 (2010).
77
Darja Kanduc et al., Massive Peptide Sharing Between Viral and Human Proteomes, 29
Peptides 1755 (2008)
78
Andre Silvanovich et al., The Value of Short Amino Acid Sequence Matches for Prediction of
Protein Allergenicity, 90 Toxicological Sciences 252 (206).
79
Sune Frankild et al., Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for
“Holes” in the T Cell Repertoire, 3 PLoS ONE e1831 (2008).
31
only part of much larger peptide, it cannot be predicted if his sequence could have any role in
inducing immune responses in these assays.” Resp. Ex. G at 25; see also Tr. 228. Lastly, Dr.
Forsthuber opined the pertussis toxin epitope does not induce immune responses. Resp. Ex. G at
25 (citing Resp. Ex. G, Tab 13);80 Tr. 282.
Moving to Petitioner’s experts’ opinions related to IgM immune responses, Dr.
Forsthuber criticized their reliance on Villar et al. because in that paper, the authors described the
potential role for IgM in MS but not TM. Resp. Ex. G at 28. Moreover, Dr. Forsthuber asserted
that oligoclonal bands are restricted to the CNS whereas the Tdap vaccine “induces IgM
antibodies in the lymph nodes draining to the injection site, but not in the CNS.” Id. He added,
“IgM antibodies in the CNS are associated with abnormal CD5+ B cells,” but that the Tdap
vaccine “does not induce abnormal CD5+ B cells, and B cells induced by Tdap would not be
restricted to the CNS.” Id. at 28-29 (citing Pet. Ex. 41).
Regarding the opinions of Dr. Gershwin, Dr. Forsthuber agreed that “the initial innate
immune response serves to prime the adaptive immune system.” Resp. Ex. E at 9. But he
opined that the adaptive immune response “initiates and directs” the innate immune response
within the CNS during neuroinflammatory diseases. Id. at 5. Dr. Forsthuber did not agree that
TM could be caused without an adaptive immune response. Id. at 5, 8. He opined that the “cells
of the innate immune system contribute to [TM], but they do not cause this condition without
being first instigated by the adaptive immune system.” Id. at 8; see also Resp. Ex. G at 29
(“[W]ithout an adaptive immune response there would be no molecular mimicry and supposedly
no TM.”).
Dr. Forsthuber outlined key immunological concepts relevant for immune responses after
vaccination and concluded “there is no reliable evidence that immune responses to vaccine[s] are
initiated within the CNS.” Resp. Ex. G at 30-31. “[T]he adaptive immune system . . . recruits
cells of the innate immune system to the CNS, where these infiltrating cells ([] monocytes and
dendritic cells) and local cells . . . become activated and cause tissue pathology via production of
pathogenic mediators (i.e. cytokines, . . .).” Resp. Ex. E at 8.
Next, Dr. Forsthuber opined that “the presence of autoantibodies does not necessarily
equate to induction of autoimmune pathology.” Resp. Ex. C at 11 (citing Resp. Ex. C, Tab 8).81
He averred Alaniz et al., referenced by Dr. Gershwin, illustrates this point. Id. (citing Pet. Ex.
11.78 at 1). Importantly, Dr. Forsthuber stated that IgM antibodies do not penetrate the blood-
brain barrier. Resp. Ex. C at 11; Resp. Ex. E at 4. He explained that the blood-brain barrier
“shields the brain from undesired and potentially toxic molecules and pathogens circulating in
the blood stream,” thus preventing large proteins or hydrophilic molecules from freely entering
80
Wolfgang Schmidt & Alexander Schmidt, Mapping of Linear B-Cell Epitopes of the S2
Subunit of Pertussis Toxin, 57 Infection & Immunology 438 (1988).
81
Eric P. Nagele et al., Natural IgG Autoantibodies Are Abundant and Ubiquitous in Human
Sera, and Their Number Is Influenced By Age, Gender, and Disease, 8 PLoS ONE e60726
(2013).
32
the CSF. Resp. Ex. C at 11 (citing Resp. Ex. C, Tab 10).82 “In strong contrast, IgM antibodies,
which are much larger . . . are usually restricted to blood vessels and essentially do not diffuse
into the CSF.” Id. (citing Resp. Ex. C, Tab 9).83 He concluded that “Dr. Gershwin’s theory of
IgM antibodies as the causative mechanism for inducing TM after Tdap vaccination in
[Petitioner] does not apply because these IgM antibodies, even if they existed, do not cross-over
from the blood into the CNS.” Id. Moreover, Dr. Forsthuber explained that IgM antibodies are
generally “directed against lipids” and the “[p]ertussis toxin is not lipid.” Tr. 300.
Additionally, Dr. Forsthuber criticized the medical literature Dr. Gershwin used to
support his position that the Tdap vaccine induces increased levels of cytokines in the blood.
Resp. Ex. G at 31. Talaat et al.,84 which investigated the flu vaccine not Tdap, found cytokine
levels were so low that they “dwarf in comparison” to those observed in heathy, unvaccinated
individuals. Id. (citing Pet. Ex. 22C). Dr. Forsthuber offered Kleiner et al.85 and Lim et al.86
which found no significant changes in the level of cytokines. Id. at 31-32 (citing Resp. Ex. G,
Tabs 17-18).
Lastly, Dr. Forsthuber addressed Dr. Gershwin’s reliance on Grigg et al.,87 which
discussed pro-inflammatory T cells (ILC3s) in the CNS and their role in “autoimmune
neuroinflammation” relative to the pathogenesis of multiple sclerosis type illnesses. Tr. 307-11;
see Pet. Ex. 48 at 1. Dr. Forsthuber explained that the adaptive immune response
(acknowledging the timing implications) is required for the recruitment of ILC3 cells to the
brain, which then induce neuroinflammation. Tr. 308. He noted several important differences
between the Grigg et al. paper and what was suggested by Petitioner’s expert. In the Grigg et al.
study, the mice that were “immunized with myelin antigen, . . . already ha[d] disease,” and then
82
Guilhem Bousquet & Anne Janin, Passage of Humanized Monoclonal Antibodies Across the
Blood-Brain Barrier: Relevance in the Treatment of Cancer Brain Metastases?, 2 J. Applied
Biopharmaceutics & Pharmacokinetics 50 (2014).
83
Edward A. Neuwelt et al., Osmotic Blood-Brain Barrier Opening to IgM Monoclonal
Antibody in the Rat, 250 Am. J. Physiology R875 (1986).
84
Kawsar R. Talaat et al., Rapid Changes in Serum Cytokines and Chemokines in Response to
Inactivated Influenza Vaccination, 12 Influenza & Other Respiratory Viruses 202 (2018).
85
Giulio Kleiner et al., Cytokine Levels in the Serum of Healthy Subjects, 2013 Mediators
Inflammation 434010.
86
Pei Wen Lim et al., Potential Use of Salivary Markers for Longitudinal Monitoring of
Inflammatory Immune Responses to Vaccination, 2016 Mediators Inflammation 6958293.
87
John B. Grigg et al., Antigen-Presenting Innate Lymphoid Cells Orchestrate
Neuroinflammation, 600 Nature 707 (2021).
33
ILC3s were examined 15 days after immunization. Tr. 310. Freund’s adjuvant,88 a very
aggressive adjuvant not used in humans, and pertussis toxin were also administered to mice. Tr.
310-11. ILCs were not found in the mice that only received pertussis. Tr. 311. Therefore, Dr.
Forsthuber concluded that the paper “disproves the claims that these ILCs have any role in the
Tdap vaccination.” Id.ii. Althen Prongs Two and Three
Dr. Forsthuber opined that the development of adaptive autoimmunity takes more than 24
hours and “therefore it is not feasible that the Tdap vaccine caused TM in [Petitioner] in such a
short period of time.” Resp. Ex. E at 6. He posited Petitioner’s onset was “most likely within
24-48 hours after vaccination and not within 48-72 hours;” however, he did not believe that this
timeframe was “consistent with TM induced by the Tdap vaccine.” Resp. Ex. G at 2, 29; see
also Resp. Ex. C at 10; Resp. Ex. E at 8 (“[T]he argument that Tdap induced the rapid onset of
symptoms in [Petitioner] via the innate immune system is not logical because the adaptive
immune system would have to be activated first.”).
Dr. Forsthuber stated it is critical to note that “it takes a certain period of time for the
adaptive immune system to initiate and orchestrate [an] attack on the CNS in TM.” Resp. Ex. C
at 6-7. He opined it can take several days for the adaptive immune system to “mount a proper
immune response.” Resp. Ex. E at 7. Dr. Forsthuber detailed the sequence of events after
vaccination, concluding that “even if the Tdap vaccine could induce autoimmune responses, and
there is no evidence for this, it is not feasible that the vaccine could cause Petitioner’s TM in 24
hours.” Id.; see also Tr. 284-91. Instead, Dr. Forsthuber opined Petitioner’s onset “would be
much more consistent with an autoimmune process that started at least one to three weeks prior
to his clinical manifestations of TM.” Resp. Ex. C at 10.
Dr. Forsthuber agreed that there was no alternative cause for Petitioner’s TM. Tr. 334-
35. However, he noted that “half of TM cases occur spontaneously without any clearly
identifiable preceding event.” Resp. Ex. C at 6. He therefore dismissed Dr. Conomy’s and Dr.
Gershwin’s argument that the Tdap vaccine had to be the cause of Petitioner’s TM because of the
lack of reasonable alternatives (i.e., there were no other apparent infectious events). Id. at 3, 6;
Tr. 334-35. While it is “unfortunate” that Petitioner developed TM after vaccination, Dr.
Forsthuber testified that it is “human nature to associate bad events with each other.” Tr. 335.
88
Freund’s adjuvant is “a water-in-oil emulsion incorporating antigen, in the aqueous phase, into
lightweight paraffin oil with the aid of an emulsifying agent. On injection, this mixture (Freund
incomplete a.) induces strong persistent antibody formation. The addition of killed, dried
mycobacteria, e.g., Mycobacterium butyricum, to the oil phase (Freund complete a.) elicits cell-
mediated immunity (delayed hypersensitivity), as well as humoral antibody formation.” Freund
Adjuvant, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/
definition?id=37052 (last visited Mar. 23, 2023).
34
IV. DISCUSSION
A. Standards for Adjudication
The Vaccine Act was established to compensate vaccine-related injuries and deaths. §
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. § 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). 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 v. Sec’y of Health & Hum.
Servs., 440 F.3d 1317, 1325 (Fed. Cir. 2006). Instead, Petitioner may satisfy his burden by
presenting circumstantial evidence and reliable medical opinions. Id. at 1325-26.
In particular, 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). The
received vaccine, however, need not be the predominant cause of the injury. Shyface, 165 F.3d
at 1351. 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.” § 13(a)(1)(B). However, if a petitioner fails to
establish a prima facie case, the burden does not shift. Bradley v. Sec’y of Health & Hum.
Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).
“Regardless of whether the burden ever shifts to the [R]espondent, the special master
may consider the evidence presented by the [R]espondent in determining whether the [P]etitioner
has established a prima facie case.” Flores v. Sec’y of Health & Hum. Servs., 115 Fed. Cl. 157,
162-63 (2014); see also Stone v. Sec’y of Health & Hum. Servs., 676 F.3d 1373, 1379 (Fed. Cir.
2012) (“[E]vidence of other possible sources of injury can be relevant not only to the ‘factors
unrelated’ defense, but also to whether a prima facie showing has been made that the vaccine
was a substantial factor in causing the injury in question.”); de Bazan v. Sec’y of Health & Hum.
Servs., 539 F.3d 1347, 1353 (Fed. Cir. 2008) (“The government, like any defendant, is permitted
to offer evidence to demonstrate the inadequacy of the [P]etitioner’s evidence on a requisite
element of the [P]etitioner’s case-in-chief.”); Pafford, 451 F.3d at 1358-59 (“[T]he presence of
multiple potential causative agents makes it difficult to attribute ‘but for’ causation to the
vaccination. . . . [T]he Special Master properly introduced the presence of the other unrelated
contemporaneous events as just as likely to have been the triggering event as the vaccinations.”).
35
B. Factual Issues
A petitioner must prove, by a preponderance of the evidence, the factual circumstances
surrounding her claim. § 13(a)(1)(A). To resolve factual issues, the special master must weigh
the evidence presented, which may include contemporaneous medical records and testimony.
See Burns v. Sec’y of Health & Hum. Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (explaining that a
special master must decide what weight to give evidence including oral testimony and
contemporaneous medical records). Contemporaneous medical records, “in general, warrant
consideration as trustworthy evidence.” Cucuras v. Sec’y of Health & Hum. Servs., 993 F.2d
1525, 1528 (Fed. Cir. 1993). But see Kirby v. Sec’y of Health & Hum. Servs., 997 F.3d 1378,
1382 (Fed. Cir. 2021) (rejecting the presumption that “medical records are accurate and complete
as to all the patient’s physical conditions”); Shapiro v. Sec’y of Health & Hum. Servs., 101 Fed.
Cl. 532, 538 (2011) (“[T]he absence of a reference to a condition or circumstance is much less
significant than a reference which negates the existence of the condition or circumstance.”
(quoting Murphy v. Sec’y of Health & Hum. Servs., 23 Cl. Ct. 726, 733 (1991), aff’d per curiam,
968 F.2d 1226 (Fed. Cir. 1992))), recons. den’d after remand, 105 Fed. Cl. 353 (2012), aff’d
mem., 503 F. App’x 952 (Fed. Cir. 2013).
There are situations in which compelling testimony may be more persuasive than written
records, such as where records are deemed to be incomplete or inaccurate. Campbell v. Sec’y of
Health & Hum. Servs., 69 Fed. Cl. 775, 779 (2006) (“[L]ike any norm based upon common
sense and experience, this rule should not be treated as an absolute and must yield where the
factual predicates for its application are weak or lacking.”); Lowrie v. Sec’y of Health & Hum.
Servs., No. 03-1585V, 2005 WL 6117475, at *19 (Fed. Cl. Spec. Mstr. Dec. 12, 2005)
(“[W]ritten records which are, themselves, inconsistent, should be accorded less deference than
those which are internally consistent.” (quoting Murphy, 23 Cl. Ct. at 733)). Ultimately, a
determination regarding a witness’s credibility is needed when determining the weight that such
testimony should be afforded. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1379
(Fed. Cir. 2009); Bradley, 991 F.2d at 1575.
Despite the weight afforded to medical records, special masters are not bound rigidly by
those records in determining onset of a petitioner’s symptoms. Valenzuela v. Sec’y of Health &
Hum. Servs., No. 90-1002V, 1991 WL 182241, at *3 (Fed. Cl. Spec. Mstr. Aug. 30, 1991); see
also Eng v. Sec’y of Health & Hum. Servs., No. 90-1754V, 1994 WL 67704, at *3 (Fed. Cl.
Spec. Mstr. Feb. 18, 1994) (Section 13(b)(2) “must be construed so as to give effect also to §
13(b)(1) which directs the special master or court to consider the medical records (reports,
diagnosis, conclusions, medical judgment, test reports, etc.), but does not require the special
master or court to be bound by them”).
C. Causation
To receive compensation through the Program, a 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 he received, or (2) that he suffered an injury that was actually caused by a
vaccination. See §§ 11(c)(1), 13(a)(1)(A); Capizzano, 440 F.3d at 1319-20. Petitioner must
36
show that the vaccine was “not only a but-for cause of the injury but also a substantial factor in
bringing about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface, 165 F.3d at 1352-53).
Because Petitioner does not allege he suffered a Table Injury, he must prove a vaccine he
received caused his injury. To do so, Petitioner must establish, by preponderant evidence: “(1) a
medical theory causally connecting the vaccination and the injury; (2) a logical sequence of
cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of
a proximate temporal relationship between vaccination and injury.” Althen, 418 F.3d at 1278.
The causation theory must relate to the injury alleged. 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). 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. § 13(a)(1). In
determining whether a 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.” § 13(b)(1)(A). The undersigned must weigh
the submitted evidence and the testimony of the parties’ proffered experts and rule in Petitioner’s
favor when the evidence weighs in his favor. See Moberly, 592 F.3d at 1325-26 (“Finders of
fact are entitled—indeed, expected—to make determinations as to the reliability of the evidence
presented to them and, if appropriate, as to the credibility of the persons presenting that
evidence.”); Althen, 418 F.3d at 1280 (noting that “close calls” are resolved in Petitioner’s
favor).
Testimony that merely expresses the possibility—not the probability—is insufficient, by
itself, to substantiate a claim that such an injury occurred. See Waterman v. Sec’y of Health &
Hum. Servs., 123 Fed. Cl. 564, 573-74 (2015) (denying Petitioner’s motion for review and
noting that a possible causal link was not sufficient to meet the preponderance standard). The
Federal Circuit has made clear that the mere possibility of a link between a vaccination and a
petitioner’s injury is not sufficient to satisfy the preponderance standard. Moberly, 592 F.3d at
1322 (emphasizing that “proof of a ‘plausible’ or ‘possible’ causal link between the vaccine and
the injury” does not equate to proof of causation by a preponderance of the evidence); Boatmon
v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1359-60 (Fed. Cir. 2019). While certainty is
by no means required, a possible mechanism does not rise to the level of preponderance.
Moberly, 592 F.3d at 1322; see also de Bazan, 539 F.3d at 1351.
V. ANALYSIS
A. Althen Prong One
Under Althen Prong One, Petitioner must set forth a medical theory explaining how the
received vaccine could have caused the sustained injury. Andreu, 569 F.3d at 1375; Pafford, 451
F.3d at 1355-56. Petitioner’s theory of causation need not be medically or scientifically certain,
but it must be informed by a “sound and reliable” medical or scientific explanation. Boatmon,
941 F.3d at 1359; see also Knudsen, 35 F.3d at 548; Veryzer v. Sec’y of Health & Hum. Servs.,
37
98 Fed. Cl. 214, 223 (2011) (noting that special masters are bound by both § 13(b)(1) and
Vaccine Rule 8(b)(1) to consider only evidence that is both “relevant” and “reliable”). If
Petitioner relies upon a medical opinion to support his theory, the basis for the opinion and the
reliability of that basis must be considered in the determination of how much weight to afford the
offered opinion. See Broekelschen v. Sec’y of Health & Hum. Servs., 618 F.3d 1339, 1347 (Fed.
Cir. 2010) (“The special master’s decision often times is based on the credibility of the experts
and the relative persuasiveness of their competing theories.”); Perreira v. Sec’y of Health &
Hum. Servs., 33 F.3d 1375, 1377 n.6 (Fed. Cir. 1994) (stating that an “expert opinion is no better
than the soundness of the reasons supporting it” (citing Fehrs v. United States, 620 F.2d 255, 265
(Ct. Cl. 1980))).
The undersigned finds Petitioner has provided preponderant evidence that the Tdap
vaccine can cause TM through the mechanism of molecular mimicry. The hypersensitivity
theory and innate immune response theory, however, are not supported by preponderant
evidence. The reasons for these findings are described below.
First, as for the mechanistic theory of hypersensitivity, Petitioner offered the opinions of
Dr. Chen, who proposed that TM can be mediated through an allergy and hypersensitivity
response within 24 hours of vaccine administration. However, Dr. Chen offered no reliable
evidence to show that the pathogenesis of TM is a hypersensitivity reaction, or that TM is caused
by an IgE immune mediated response. In this regard, the undersigned finds Dr. Gershwin
persuasive, and he succinctly explained that there is “no evidence that IgE mediates any
autoimmune disease.” Pet. Ex. 21 at 2. In summary, there is not scientific support for Dr.
Chen’s theory, it is not sound or reliable, and there is not preponderant evidence that the Tdap
vaccination can cause TM via a hypersensitivity reaction.
The next causal mechanism offered by Petitioner is Dr. Gershwin’s theory of an innate
immune response, which he offers to explain a rapid onset between the Tdap vaccine and the
development of neurological symptoms which were ultimately diagnosed as TM. Although Dr.
Gershwin’s opinions about the innate immune system and the interplay between it and the
adaptive immune system were persuasive and sound, to the extent that he opined that the innate
immune response alone could cause TM, the undersigned finds those opinions to be
questionable. In short, the undersigned finds that some of Dr. Gershwin’s opinions were
inapposite to established medical literature and prior Vaccine Program cases that have
acknowledged molecular mimicry and the adaptive immune system as the applicable causal
theory implicated in vaccine associated TM.
Dr. Forsthuber persuasively explained why the innate immune response does not fit in the
context of TM. He effectively explained that the blood-brain barrier protects against large
proteins, including IgM antibodies, which form the basis of the immune response suggested by
Dr. Gershwin. Moreover, Dr. Forsthuber explained that IgM antibodies are generally “directed
against lipids” and the “[p]ertussis toxin is not lipid.” Tr. 300.
Moreover, literature cited by Dr. Gershwin does not support his position that the Tdap
vaccine induces increased levels of cytokines in the blood. Lim et al. and Kleiner et al. found no
significant changes in the level of cytokines. Grigg et al. discussed pro-inflammatory T cells
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(ILC3s) in the CNS and their role in “autoimmune neuroinflammation” relative to the
pathogenesis of multiple sclerosis type illnesses. Pet. Ex. 48 at 1. Dr. Forsthuber effectively
explained that the adaptive immune response is required for the recruitment of ILC3 cells to the
brain, which then induce neuroinflammation.
Further, the Hervé et al. article cited by Dr. Gershwin does not explain how a vaccination
can, through an IgM response, cause inflammation within the spinal cord in the span of
approximately 24 hours to cause TM.
For these reasons, the undersigned finds that Dr. Gershwin’s theory based on an innate
immune response is not sound or reliable to explain how the Tdap vaccine causes TM.
Lastly, Petitioner presented the opinions of Dr. Conomy and Dr. Steinman based on
molecular mimicry, along with supportive literature.
Dr. Steinman provided an example of homology using his three-step process employing a
BLAST search and the IEDB database. In response, Dr. Forsthuber methodically and effectively
discredited Dr. Steinman’s example, showing why it was unlikely to illicit an autoimmune
response. Although Dr. Steinman’s example was effectively discredited, this did not invalidate
Petitioner’s experts’ opinions establishing molecular mimicry as a sound and reliable theory
explaining how the Tdap vaccination can cause TM. There are several reasons that the
undersigned finds molecular mimicry is a sound and reliable mechanism here.
First, the medical literature filed by Petitioner establishes that molecular mimicry is a
well-known immune response in immunology that has been identified in medical literature as a
mechanistic theory for how infectious agents and vaccines can cause autoimmune disorders like
TM. Agmon-Levin et al. described the mechanism of molecular mimicry as the “most common”
or postulated mechanism by which infectious agents or vaccinations can cause autoimmune
diseases like TM. Pet. Ex. 8.8 at 4. The authors reviewed 37 cases of post-vaccination TM,
including post-DTP and post-DT vaccination, and found 30 of the 37 cases developed symptoms
of TM within two months after vaccination.
In addition, Petitioner cited case reports of TM associated with DTaP vaccination. Riel-
Romero described a case of a patient who developed TM after DTaP vaccination. The authors
hypothesized that their patient’s TM was caused by vaccination and found an immune-mediated
process to be at play, specifically noting molecular mimicry as a postulated mechanism.
Generally, case reports and literature reviews citing cases are insufficient to prove
causation. However, in the context of rare conditions like TM, they provide some evidence of
causation. And here, where the medical literature reported TM cases associated with vaccines
containing tetanus and/or diphtheria components, this evidence weighs in favor of causation.
Secondly, Petitioner need not make a specific type of evidentiary showing or require
identification of homology to prove that molecular mimicry is a sound and reliable theory by
preponderant evidence. Given the state of current scientific knowledge, there is no way that a
petitioner could satisfy such a requirement. Further, requiring proof of specific homology or
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proof of identical protein sequences between the Tdap vaccine and the CNS to prove causation
would require scientific certainty, which is a bar too high. See Knudsen, 35 F.3d at 549(explaining that “to require identification and proof of specific biological mechanisms would be
inconsistent with the purpose and nature of the vaccine compensation program”).
Regarding Dr. Steinman’s testimony about sequences of similar amino acids, the
undersigned finds that he was providing an example to illustrate homology as a way to explain
the science using readily available resources. Dr. Steinman explained that he could not perform
research on Petitioner. He also explained the limitations of the process that he used. It would be
an extreme response to reject the mechanistic theory of molecular mimicry because Dr. Steinman
offered an example that was disproved. The undersigned is not willing to throw out the
proverbial baby with the bathwater, or disregard applicable medical literature, or ignore her
knowledge and experience, when molecular mimicry has been repeatedly shown by preponderant
evidence to be a sound and reliable theory in the context of vaccine causation.
Lastly, molecular mimicry has been accepted as a sound and reliable theory for many
demyelinating conditions, including TM, in the Vaccine Program. See, e.g., Palattao v. Sec’y of
Health & Hum. Servs., No. 13-591V, 2019 WL 989380, at *35-37 (Fed. Cl. Spec. Mstr. Feb. 4,
2019) (noting “many of the existing Program decisions in which TM has been found to be caused
by a vaccine rely on a mechanism [of] []molecular mimicry”); Raymo v. Sec’y of Health &
Hum. Servs., No. 11-0654V, 2014 WL 1092274, at *21 (Fed. Cl. Spec. Mstr. Feb. 24, 2014)
(former Chief Special Master Denise Vowell concluding that molecular mimicry explained how
the tetanus vaccine can cause TM); Roberts v. Sec’y of Health & Hum. Servs., No. 09-427V,
2013 WL 5314698, at *6-7 (Fed. Cl. Spec. Mstr. Aug. 29, 2013) (finding the Petitioner entitled
to compensation in a Tdap/TM case with the theory of molecular mimicry); see also Bowes v.
Sec’y of Health & Hum. Servs., No. 01-481V, 2006 WL 2849816 (Fed. Cl. Spec. Mstr. Sept. 8,
2006). Compare Palattao, 2019 WL 989380, at *35-37 (Chief Special Master Corcoran denying
entitlement in a TM case where the facts did not support application of molecular mimicry), with
I.J. v. Sec’y of Health & Hum. Servs., No. 16-864V, 2022 WL 277555, at *4-7 (Fed. Cl. Spec.
Mstr. Jan. 4, 2022) (Chief Special Master Corcoran finding Petitioner entitled to compensation
on remand in a Tdap/TM case that relied upon the theory of molecular mimicry).
While the above cases are not binding here, the undersigned agrees with the reasoning of
other special masters who have found molecular mimicry to be a sound and reliable mechanism
to explain how the Tdap vaccine can cause TM. Moreover, the undersigned recently held that
the Tdap vaccine can cause TM via molecular mimicry. See Introini v. Sec’y of Health & Hum.
Servs., No. 20-176V, 2022 WL 16915818 (Fed. Cl. Spec. Mstr. Oct. 19, 2022).
For all of these reasons, the undersigned finds the Petitioner has established by
preponderant evidence that molecular mimicry is a sound and reliable mechanism by which the
Tdap vaccination can cause TM, therefore satisfying Althen Prong One.
B. Althen Prong Two
Under Althen Prong Two, Petitioner must prove by a preponderance of the evidence that
there is a “logical sequence of cause and effect showing that the vaccination was the reason for
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the injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278). “Petitioner must
show that the vaccine was the ‘but for’ cause of the harm . . . or in other words, that the vaccine
was the ‘reason for the injury.’” Pafford, 451 F.3d at 1356 (internal citations omitted).
In evaluating whether this prong is satisfied, the opinions and views of the vaccinee’s
treating physicians are entitled to some weight. Andreu, 569 F.3d at 1367; Capizzano, 440 F.3d
at 1326 (“[M]edical records and medical opinion testimony are favored in vaccine cases, as
treating physicians are likely to be in the best position to determine whether a ‘logical sequence
of cause and effect show[s] that the vaccination was the reason for the injury.’” (quoting Althen,
418 F.3d at 1280)). Medical records are generally viewed as trustworthy evidence, since they are
created contemporaneously with the treatment of the vaccinee. Cucuras, 993 F.2d at 1528.
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 satisfy his burden by presenting
circumstantial evidence and reliable medical opinions. Id. at 1325-26.
Regarding Althen Prong two, the undersigned finds there is preponderant evidence in the
record to support a logical sequence of cause-and-effect showing Petitioner’s Tdap vaccine to be
the cause of his TM because his medical records show evidence that he sustained an autoimmune
illness consistent with the causal theory of molecular mimicry, his physicians supported vaccine
causation, and there is no evidence of any alternative cause.
Petitioner’s experts set out convincing reasons why the facts of the case are consistent
with an autoimmune condition caused by molecular mimicry. The CSF showed the presence of
inflammatory cells, increased protein, and oligoclonal bands indicating an IgG immune response.
Further, the MRI showed enhancement and slight expansion of the spinal cord at T-6.
Additionally, in determining whether Petitioner has put forth preponderant evidence of
Althen Prong Two, the undersigned generally takes into consideration the opinions of the
treating physicians. Treating physician statements are typically “favored” as treating physicians
“are likely to be in the best position to determine whether a ‘logical sequence of cause and effect
show[s] that the vaccination was the reason for the injury.’” Capizzano, 440 F.3d at 1326(quoting Althen, 418 F.3d at 1280). However, no treating physician’s views bind the special
master, per se; rather, their views are carefully considered and evaluated. § 13(b)(1); Snyder v.
Sec’y of Health & Hum. Servs., 88 Fed. Cl. 706, 746 n.67 (2009). “As with expert testimony
offered to establish a theory of causation, the opinions or diagnoses of treating physicians are
only as trustworthy as the reasonableness of their suppositions or bases.” Welch v. Sec’y of
Health & Hum. Servs., No. 18-494V, 2019 WL 3494360, at *8 (Fed. Cl. Spec. Mstr. July 2,
2019).
Here, Petitioner’s treating physicians related Petitioner’s TM to his Tdap vaccine. For
example, Dr. Chay opined that within “a reasonable degree of medical and scientific certainty . .
. the [Tdap] shot . . . was the etiology of [TM].” Pet. Ex. 5 at 2. And Dr. Gillon wrote that a
“reaction to the [Tdap] shot could be a potential cause of his [TM].” Pet. Ex. 2 at 9; see also id.
at 4 (Dr. Khoury questioning whether the Tdap shot had to do with Petitioner’s TM).
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Lastly, there is no evidence of an alternative cause. Petitioner did not have any signs or
symptoms of an infection prior to onset of his TM. Numerous diagnostic studies were performed
on the CSF, including Lyme, CMV, HSV, and others, and the results were normal, and did not
reveal any infectious or other cause for Petitioner’s TM.
Accordingly, the undersigned finds that Petitioner has satisfied his burden under Althen
Prong Two.
C. Althen Prong Three
Althen Prong Three requires Petitioner to establish a “proximate temporal relationship”
between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been
defined as a “medically acceptable temporal relationship.” Id. The Petitioner must offer
“preponderant proof that the onset of symptoms occurred within a time frame for which, given
the medical understanding of the disorder’s etiology, it is medically acceptable to infer
causation-in-fact.” de Bazan, 539 F.3d at 1352. The explanation for what is a medically
acceptable time frame must also coincide with the theory of how the relevant vaccine can cause
the injury alleged (under Althen Prong One). Id.; Koehn v. Sec’y of Health & Hum. Servs., 773
F.3d 1239, 1243 (Fed. Cir. 2014); Shapiro, 101 Fed. Cl. at 542; see also Pafford, 451 F.3d at
1358. A temporal relationship between a vaccine and an injury, standing alone, does not
constitute preponderant evidence of vaccine causation. See, e.g., Veryzer, 100 Fed. Cl. at 356
(explaining that “a temporal relationship alone will not demonstrate the requisite causal link and
that [P]etitioner must posit a medical theory causally connecting the vaccine and injury”).
Petitioner’s experts place onset of his TM at 48 to 72 hours. Dr. Conomy opined that
onset occurred in a “couple to a few days.” Pet. Ex. 8 at 6. Dr. Steinman found onset to be 48 to
72 hours. In contrast, Respondent’s experts place onset at 24 to 48 hours. The undersigned
agrees with Petitioner’s experts’ opinions on this issue, and finds onset was May 22 and/or May
23, approximately 48 to 72 hours after vaccination, for the following reasons.
The literature filed herein describes the presentation of TM; it is characterized by
symptoms and signs of neurologic dysfunction, including motor dysfunction, sensory
dysfunction, and autonomic dysfunction attributable to the spinal cord. Motor dysfunction is
often described as weakness. Autonomic dysfunction is described as bladder impairment.
Sensory dysfunction is described as “numbness, paresthesias, or band-like dysesthesias.” Pet.
Ex. 11.5 at 1. The inclusion criteria developed by the TM Consortium Working Group identifies
“[d]evelopment of sensory, motor, or autonomic dysfunction attributable to the spinal cord” as
criteria for diagnosis. Id. at 2 tbl.1. In summary, the literature and the TM Consortium Working
Group use the triad of motor dysfunction, sensory dysfunction, and autonomic (bladder
impairment) to describe the symptoms which herald TM. Thus, the undersigned uses this
framework to determine onset.
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The experts disagree as to the significance of Petitioner’s “foot stiffness,” which began
late at night on May 21, just over 24 hours after vaccination. Dr. Steinman opined that foot
stiffness is not a typical manifestation of TM. To place onset at the time of this symptom, one
must interpret the word “stiffness” as meaning something more. Respondent’s experts interpret
it to mean “numbness” or “weakness.” See Tr. 162-63, 178, 182. Petitioner’s experts disagree
and express reluctance about using stiffness as a symptom because they argue it is not typical.
The undersigned agrees with Petitioner’s experts. To use it as a benchmark of onset requires
interpretation. Thus, the undersigned declines to use it to mark the initial manifestation of
Petitioner’s TM.
In addition to the quandary about the significance of “foot stiffness,” onset is difficult
because the medical histories provide a summary of events as opposed to a day-by-day
chronology. The histories, while informative for the purpose of diagnosis, do not provide a time-
line to allow a reasonable determination of exactly when Petitioner first experienced motor,
sensory, and autonomic dysfunction. In other words, the events of several days are condensed
into one or two sentences making it difficult to discern what happened when. For example, Dr.
Rodgers documented that “[o]ver the last week, [Petitioner] has had increasing weakness in his
lower extremities to the point that he was unable to walk.” Pet. Ex. 2 at 11. And Ms. Kerrigan
notated Petitioner’s “[bilateral] [lower extremity] weakness and urinary retention worsening [for]
3 d[ays], unable to stand or void.” Id. at 21. Other histories summarized a progressive process
but it is difficult to determine precise onset from them.
The Vaccine Act does not define the meaning of the phrase, “the first symptom or
manifestation of the onset.” § (c)(1)(C)(i). The Vaccine Injury Table does not provide guidance
either. 42 C.F.R. § 100.3(a) (noting “time period in which the first symptom or manifestation of
onset . . . after vaccine administration”). However, there is some guidance from case law.
“‘[T]he first symptom or manifestation of onset’ . . . is the first event objectively recognizable as
a sign of a vaccine injury by the medical profession at large.” Markovich v. Sec’y of Health &
Hum. Servs., 477 F.3d 1353, 1360 (Fed. Cir. 2007). Further, the Federal Circuit held “the statute
of limitations of the Vaccine Act begins to run on the calendar date of the occurrence of the first
medically recognized symptom or manifestation of onset of the injury.” Cloer v. Sec’y of Health
& Hum. Servs., 654 F.3d 1322, 1324-25 (Fed. Cir. 2011) (en banc). Following this guidance, it
is appropriate to place onset at the time of a “medically recognized symptom.”
The undersigned finds that the medical literature and Dr. Steinman offer the most
reasonable and persuasive benchmarks for onset consistent with medically recognized symptoms
of TM based on when Petitioner began having difficulty walking (motor dysfunction) and
bladder dysfunction.89 In several of the medical histories, the health care providers state that
Petitioner had difficulty walking and inability to void on May 23, 2014. Unlike “foot stiffness,”
using these complaints is consistent with the use of “medically recognized symptoms” for onset.
The following records describe Petitioner’s difficulty walking and/or inability to void.
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Dr. Steinman also relied on the onset of Petitioner’s back pain as a marker for onset. The
undersigned does not use this marker. While the medical literature does refer to pain, it is not
part of the initial triad which was consistently used in the literature to describe the clinical
presentation of TM.
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Petitioner received the Tdap vaccine on May 20, 2014 between 5:00 PM and 6:00 PM.
He presented to the ED on the morning of May 24, 2014. An initial history documented on May
24 at 9:33 AM states that Petitioner began having “difficulty walking yesterday.” Pet. Ex. 2 at
28. Based on this note, the onset of Petitioner’s “difficulty walking” began on May 23. On May
25, Dr. Khoury noted that Petitioner received his Tdap vaccination on Tuesday (May 20), and
that two or three days ago (May 22 or 23), Petitioner was unable to void his urine. Id. at 3. Also
on May 25, Dr. Tepper documented that two days ago (May 23) Petitioner experienced difficulty
moving his legs and was unable to walk. Id. at 5.
In summary, contemporaneous records by health care providers place the onset of
Petitioner’s difficulty walking and bladder dysfunction on May 22 and/or May 23, approximately
48 to 72 hours after vaccination.
Having determined onset to be 48 to 72 hours, the next question is whether there is
“preponderant proof that the onset of symptoms occurred within a time frame for which, given
the medical understanding of the disorder’s etiology, it is medically acceptable to infer
causation-in-fact.” de Bazan, 539 F.3d at 1352. Dr. Conomy opined that cases of TM due to
Tdap vaccine via molecular mimicry have occurred within a couple to a few days, which the
undersigned interprets to be two to three days. See Jewell v. Sec’y of Health & Hum. Servs., No.
16-0670V, 2017 WL 7259139, at *3 (Fed. Cl. Spec. Mstr. Aug. 4, 2017) (finding “a few days”
after vaccination to be within 72 hours); Taylor v. Sec’y of Health & Hum. Servs., No. 16-
1403V, 2020 WL 6706078, at *16 (Fed. Cl. Spec. Mstr. Oct. 20, 2020) (finding “few” to mean
two or three days). Similarly, Dr. Steinman opines that an onset of 48 to 72 hours is an
appropriate temporal interval for his proposed mechanism of molecular mimicry. Moreover, an
onset of three days for molecular mimicry is supported by the medical literature as an
appropriate temporal association. In Agmon-Levin et al., post-vaccination TM occurred in a
range of two days to three months. Pet. Ex. 8.8 at 3 tbl.1. And an early onset of two, three, and
four days was reported in three cases.
Additionally, this timing is within the two- to 42-day risk interval used in Baxter et al.
Although the authors found “no statistically significant increased risk” of TM post-vaccination
within the two- to 42-day risk interval, the authors did find cases of TM that occurred within and
outside of this interval. Resp. Ex. A, Tab 9 at 3. Even Respondent’s expert, Dr. Gelfand,
specifically noted that Baxter et al. drew a line for onset at two days or 48 hours. Tr. 192.
While two to three days is an early onset, it is within the onset dates identified in Agmon-
Levin et al. and the two-day risk window in Baxter et al. See Paluck v. Sec’y of Health & Hum.
Servs., 786 F.3d 1373, 1383-84 (Fed. Cir. 2015) (finding the “special master [] erred in setting a
hard and fast deadline . . . between vaccination and [] onset”). Therefore, it reasonable and
appropriate to find that the onset of Petitioner’s TM is within the appropriate timeframe given
the mechanism of molecular mimicry.
Thus, the undersigned finds the temporal association is appropriate given the mechanism
of injury and Petitioner has satisfied the third Althen prong.
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D. Alternative Causation
Because the undersigned concludes that Petitioner has established a prima facie case,
Petitioner is entitled to compensation unless Respondent can put forth preponderant evidence
“that [Petitioner’s] injury was in fact caused by factors unrelated to the vaccine.” Whitecotton v.
Sec’y of Health & Hum. Servs., 17 F.3d 374, 376 (Fed. Cir. 1994), rev’d on other grounds sub
nom., Shalala v. Whitecotton, 514 U.S. 268 (1995); see also Walther v. Sec’y of Health & Hum.
Servs., 485 F.3d 1146, 1151 (Fed. Cir. 2007). Here, the undersigned finds that Respondent
failed to show that Petitioner’s TM was caused by a source other than vaccination. Thus,
Respondent did not prove by a preponderance of evidence that Petitioner’s injury is “due to
factors unrelated to the administration of the vaccine.” § 13(a)(1)(B).
VI. CONCLUSION
For the reasons discussed above, the undersigned finds that Petitioner has established, by
preponderant evidence, that his Tdap vaccine caused his TM. Therefore, Petitioner is entitled to
compensation. A separate damages order will issue.
IT IS SO ORDERED.
s/Nora Beth Dorsey
Nora Beth Dorsey
Special Master
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