# In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: March 17, 2022

* * * * * * * * * * * * * * * * * * * * * * * * * MARY MALONEY, * PUBLISHED

* Petitioner, * No. 1 9

- 1713 V

*

v. * Special Master Nora Beth Dorsey

*

SECRETARY OF HEALTH * Ruling on Entitlement ; Pneumococcal

AND HUMAN SERVICES, * Conjugate ( “ Prevnar 13 ” ) Vaccine;

* Guillain

- Barr é Syndrome (“GBS”)

. Respondent. *

*

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

Jeffrey S. Pop

, Jeffrey S. Pop & Associates

, Beverly Hills, CA

, for petitioner. Colleen Clemons Hartley

, U.S. Department of Justice, Washington, DC, for respondent.

RULING ON ENTITLEMENT 1

On November 4 , 201 9

, Mary Maloney (“ p etitioner”)

, 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 alleging that she suffered Guillain

- Barr é Syndrome (“GBS”)

as the result of a pneumococcal conjugate (“ Prevnar 13 ”) vaccination she received on July 7,

2017. Petition at Preamble (E CF No. 1)

. Respondent argued against compensation, stating “ th is

case [ was ] not appropriate for compensation under the terms of the Act.” Respondent’s Report (“Resp. Rept.”) at 2 (ECF No. 30 ).

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) (Fe deral 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 othe r 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 ind ividual sections of the Vaccine Act are to 42 U.S.C. § 300aa.2 After carefully analyzing and weighing the evidence presented in this case in accordance with the applicable legal standards, the undersigned finds that p etitioner has provided preponderant evide nce that her proper diagnosis was GBS, and that the Prevnar 13 vaccine she

received caused her GBS, s atisfying her burden of proof under Althen v. Secretary of Health &

Human Services , 418 F.3d 1274, 1280 (Fed. Cir. 2005). Accordingly, p etitioner is entitled to compensation

.

I. ISSUES TO BE DECIDED

Diagnosis is at issue. Petitioner’s expert s , Dr. Steven Sykes and Dr. Lawrence Steinman

, opine d that petitioner’s correct diagnosis is GBS, whereas respon dent’s expert

, Dr. Vinay Chaudhry disagree d

. Petitioner’s Exhibit (“Pet. Ex.”) 65 at 3; Pet. Ex. 36 at 4; Resp. Ex. A at

13

- 15. Dr. Chaudhry opine d that petitioner ’s clinical presentation and diagnostic studies were

not consistent with GBS. Resp. Ex. A at 13

- 15; Resp . Ex. C at 14.

The parties also dispute causation. Petitioner does not allege a Table injury, and thus, she must prove causation

- in

- fact by preponderant evidence

. Petitioner contend ed that she has provided preponderant evidence of the Althen criteria, and r espondent disagree d

. Pet. Motion for a Ruling on the Record and Brief in Support Thereof (“Pet. Mot.”), filed Dec. 24, 2020, at

13

- 24 (ECF No. 41); Resp. Response to Pet. Mot. (“Resp. Response”), filed May 10, 2021, at 17

- 22 (ECF No. 52). R espondent argue d that even if petitioner had GBS, she failed to (1) provide a reliable scientific or medical theory establishing that the Prevnar 13 vaccine can cause GBS, (2) provide evidence of a logical sequence of cause and effect between petitioner’ s Prevnar 13

vaccine and her alleged GBS, and (3) establish a medically appropriate temporal relationship between petitioner’s Prevnar 13 vaccine and her alleged GBS. Resp. Response at 15

- 22.

II. BACKGROUND

A. Procedural History

In November 2019, pe titioner filed her petition , medical records, and a declaration. Petition; Pet. Exs. 1

- 13. This case was reassigned to the undersigned on November 19, 2019. Notice of Reassignment dated Nov. 19, 2019 (ECF No. 12). Petitioner filed additional declarations on March 16, 2020. Pet. Exs. 14

- 19.

Petitioner filed an expert report from Dr. Steven Sykes on March 24, 2020. Pet. Ex. 20. On August 11, 2020, respondent filed an expert report from Dr. Vinay Ch audhry. Resp. Ex. A.

On August 25 , 2020, r espondent filed his Rule 4(c) Report, stating “this case [was] not appropriate for compensation under the terms of the Act.” Resp. Rept. at 2.

Thereafter, the undersigned held a Rule 5 conference on November 10, 2020. Rule 5 Order dated Nov. 16, 2020 (ECF No. 34). The undersigned agree d with the treating physicians’ diagnosis of GBS , and preliminarily found petitioner would likely be able to satisfy all Althen

prongs. Id. at 3

- 5. Given petitioner’s age, and in order to expediate a ruling, the unders igned and parties agreed to resolve entitlement through a ruling on the record. Id, at 5.3 In December 2020, petitioner filed a supplemental expert report from Dr. Sykes , an expert report from Dr. Lawrence Steinman, and a motion for a ruling on the record. Pet. Exs. 30, 36; Pet. Mot. On April 9, 2021, respondent filed a supplemental expert report from Dr. Chaudhry along with an expert report from Dr. J. Lindsay Whitton. Resp. Exs. C

- D. Respondent filed a response to petitioner’s motion for a ruli ng on the record on May 10, 2021. Resp. Response. On June 9, 2021, petitioner filed a reply to respondent’s response, along with supplemental expert reports from Drs. Steinman and Sykes. Pet. Reply Brief (“Pet. Reply”), filed June 9, 2021 (ECF No. 55); Pet. Exs. 56, 65.

A status conference was held on June 29, 2021, upon request from respondent. Order dated June 29, 2021 (ECF No. 56). The undersigned set deadlines for supplemental expert reports and sur

- reply briefs from both parties. Id. at 1

- 2.

Respondent filed supplemental expert reports from Drs. Chaudhry and Whitton in August 2021, and petitioner filed a supplemental expert report from Dr. Steinman in October 2021. Resp. Exs. G

- H; Pet. Ex. 66. Thereafter, both parties filed sur

- reply brief s

. Resp. Sur Reply Brief (“Resp. Sur

- Reply”), filed Nov. 29, 2021 (ECF No. 61); Pet. Second Reply Brief (“Pet.

Sur

- Reply”), filed Nov. 29, 2021 (ECF No. 62).

Th is matter is now ripe for adjudication.

B. Medical Terminology

GBS “is an acquired disease of the peripheral nerves that is characterized by rapidly progressing (with peak of [less than] 4 weeks) ascending paralysis with paresthesias.” Resp

. Ex. A at 12 (citing Resp. Ex. A, Tab 1 at 1; 3 Resp. Ex. A, Tab 2 at 2

- 3)

. 4 T he condition is “ r elatively

r ar e, with a reported incidence of 0.89

- 1.89 cases per 100,000 person

- years in Western countries,” affecting all ages, with an increased risk in older adults. Pet. Ex. 20 at 2

- 3 (citing Pet. Ex. 22 at 1)

. 5 Weakness is the pro minent manifestation. Id. at 3. Other s ymptoms may include “sensory disturbances, cranial nerve palsies, and dysautonomia

. ” 6 Id. ; see also Resp. Ex. A at

12. Generally , weakness is progressive “over a period of 12 hours to 28 days before reaching a plateau.” Pet. Ex. 20 at 3. Deep tendon reflexes a re usually decreased or absent. Id.

3 H ugh J. Willison et al., Guillain

- Barré Syndrome , 388 Lancet 717 (2016)

.

4 Francine J. Vriesendorp, Guillain

- Barré Syndrome in Adults: Clinical Features and Diagnosis

, UpToDate, https://www.uptodate.com/contents/guillain

- barre

- syndrome

- in

- adults

- pathogenesis

clinical

- features

- and

- diagnosis (last updated Dec. 4 , 2018).

5 Nobuhiro Yuki & Hans

- Peter Hartung, Guillain

- Barré Syn drome , 366 New Eng. J. Med. 2294 (2012).

6 Dysautonomia is “malfunction of the autonomic nervous system.” Dysautonomia , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=15146 (last

visited Feb. 7, 2022 ).4 In GBS, “ [ t ] he myelin portion of the peripheral nerve is affected by inflammation

. . . resulting in [] motor and/or sensory dysfunction.” Pet. Ex. 20 at 3. Diagnosis is based on

clinical history, physical examination, especially the neurological exam ination , and results of diagnostic tests, including electromyography / ner ve conduction velocity (“ EMG /NCV ”) testing 7
and lumbar puncture with analysis of cerebrospinal fluid (“CSF”)

. Id. Lumbar puncture usually

reveals albuminocytological dissociation , or CSF with elevated protein and otherwise normal cell

counts. Id. ; Resp. Ex. A at 12; Resp. Ex. A, Tab 1 at 6. GBS is treated with intravenous immune globulin (“ IVIG ”) or plasma exchange. Pet. Ex. 20 at 3; Resp. Ex. A at 12.

The causes of GBS are not known, however, it “is thought to be an autoimmune process

that is triggered by antigenic stimulation, resulting in demyelination and destruction of peripheral nerves.” Resp. Ex A

, Tab 9 at 1. 8 GBS is thought to be “triggered by infections or

immunizations .” Pet. Ex. 20 at 3. “[A]proximately two

- thirds of all cases are preceded by a gastrointestinal or respiratory infection within the prior 3 months.” Resp. Ex. A

, Tab 9 at 1.

GBS has also been reported after several different vaccinations, including influenza , hepatitis B,

Me nactra, measles

- mumps

- rubella , polio, and varicella. Pet. Ex. 20 at 3. It usually occurs within six weeks after vaccination, with the highest incidence reported one to three weeks post

vaccination. Id

.

“Molecular mimicry has been proposed to be a pathogenic mechanism . . . based on epidemiological, clinical, and experimental evidence of the association of infectious agents with

autoimmune diseases and an observed cross

- reactivity of antibodies raised by microbial components with host ‘self’ antigens.” Resp. Ex. C, Tab 13 at 1. 9 The underlying etiology of GBS, although not known, “ is considered to be an immune

- mediated disorder resulting from generation of autoimmune antibodies and/or inflammatory cells which cross

- react with epitopes on peripheral nerves and roots, leading to demyelination or axonal damage or both.” Resp. Ex. A, Tab 13 at 2. 10 In an article filed by respondent, the way infection and vaccines may cause

GBS is describe d below:

7 An EMG is “ an electrodiagnostic technique for recording the extracellular activity (action potentials and evoked potentials) of skeletal muscles at rest, during voluntary contractions, and during electrical stimulation. ” Electromyography , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=15 854 (last visited Feb. 7, 2022). NCV

tests “ the speed, in meters per second, at which an impulse moves along the largest fibers of a peripheral nerve .” Nerve Conduction Velocity , Dorland’s M ed. Dictionary Online, https://www.dorlandsonline.com/dorland/ definition?id=117402 (last visited Feb. 7, 2022).

8 Roger Baxter et al., Lack of Association of Guillain

- Barré Syndrome with Vaccinations , 57 Clinical Infectious Diseases 197 (2013).

9 Nobu hiro Yuki, Ganglioside Mimicry and Peripheral Nerve Disease , 35 Muscle & Nerve 691 (2007).

10 James J. Sejvar, Guillain

- Barré Syndrome and Fisher Syndrome: Case Definitions and Guidelines for Collection, Analysis, and Presentation of Immunization Safety Data , 29 Vaccine 599 (2011).5 Antigenic challenge by an antecedent infection or immunization leads to antigen

- specific humoral and/or cellular immunity, and as such, this immune stimulation could theoretically result in GBS through a number of possible mechanisms. The concep t of “molecular mimicry” involves a situation in which epitopes of a pathogen or vaccine protein could initiate development of antibodies

and/or T

- cells that could cross

- react with epitopes on peripheral nerve myelin or axonal glycoproteins or ganglioside moieties. Activated macrophages could potentially be targeted to antigens on the myelin sheath and subsequently invade the basement membrane resulting in demyelination or, alternatively, invade at the nodes of Ranvier to result in axonal damage.

Id. at 3

. 11 Furthermore, “GBS has been associated temporally with numerous vaccines; however, such temporal association must be differentiated from causality. In general, specific biological

markers indicative of a cause

- and

- effect associated with a particular path ogen or vaccine are

absent in GBS.” 12 Id.

C. Summary of Medical Records 13

1. Pre

- Vaccination History

Petitioner was born on October 13, 1927, and was 89 years of age at the time of the vaccination at issue. Pet. Ex. 3 at 3. Her past medical history was significant for hypothyroidism, hypertension

, possible stroke in April 2016 when she had an episode of dizziness, slurred speech, and mild facial asymmetry , and left

- sided facial paralysis in January

2017

. Id. at 3, 12; Pet. Ex. 5 at 111 5

. At the time of the vaccination at issue, she was living independently, able to drive

, and able to care for herself. Pet. Ex. 3 at 3; Pet. Ex. 1 at ¶ 4

. Petitioner had regular visits to her primary care physician , Dr. Yub e lkis Tinoco

, to monitor her blood pressure and for preventative care, including vaccinations.

2. Vaccination on July 7, 2017

On July 7, 2017, petitioner presented to Dr. Tinoco for a routine follow up visit

. Pet. Ex.

3 at 3. At that visit, Dr. Tinoco documented that petitioner was driving and independent, and had

no current health concerns. Id. Her hypertension was well control led on medication. Id. She had no current complaints. Id. Review of symptoms was negative for any neurological problems, including weakness. Id. at 5. Dr. Tinoco performed a neurological examination and documented that petitioner was “alert and oriented to person, place and time ,” “ ha[d] normal

11 Additional possible mechanisms are described in the article, but they do not involve molecular mimicry, or the theories proposed here. See Resp. Ex. A, Tab 13

.

12 There is evidence to support cause and effect in the instance of GBS following Campylobacter
jejuni (“ C. jejuni ”) infection. See, e.g.

, Resp. Ex. A, Tab 1 at 1

- 2; Resp

. Ex. A, Tab 2 at 1

- 2.

13 For a thorough medical chronology, see Resp. Ex. A at 2

- 12.6 strength

, ” and h ad no sensory deficit. Id. at 5

- 6. She also had “ [ g ] ood mobility and balance .”

Id. at 6. Petitioner receive d a Prevnar 13 vaccine at that visit. Id. at 6

- 7.

3. Post

- Vaccination Care

On July 18, 2017, petitioner was transported by ambulance to Martin Health System Emergency Department (“ED”)

. Pet. Ex. 5 at 81. ED triage note was documented by Registered

Nurse (“RN”) Stephen Baldwin, who noted “[ chief complaint ] of slurred speech since 7am, [patient] [states] some weakness also, weakness started yesterday but was worse this am.” Id. at

80. She was seen by emergency room (“ER”) physician Dr. Karl Weller, who also noted petitioner’s chief complaint of aphasia 14 a nd complaint of left lower extremity weakness. Id. at

73. His NIH stroke scale examination of petitioner revealed “[n]o aphasia” and “[m]ild

- to moderate dysarthria.” 15 Id. at 76

- 77. Thereafter, a neurology consult was done by Dr. Lara Fix to evaluate p etitioner for transient ischemic attack (“TIA”)

. 16 Id. at 81

- 82, 148. Dr. Fix’s history

, taken at approximately 10:30 AM

, stated that petitioner presented with

slurred speech and left>right leg weakness for 2.5 hours prior to arrival. She did

note some weakness of the bilateral lower extremities yesterday and ha d difficulty walking. Upon awakening this morning [,] she had even more difficulty ambulating and util ized a cane. In the ED, she reports the leg weakness has improved and while the slurred speech has improved she does not feel it has

returned to baseline.

Id. at 148. Dr. Fix’s note continued, stating that “[s]he reports that she was diagnosed with

14 Aphasia is “ a large group of language disorders involving defect or loss of the power of expression by speech, writing, or signs, or of comprehending spoken or written language, due to injury or disease of the brain or to psychogenic causes.” Aphasia , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/ dorland/definition?id= 3694 (last visited Feb. 7, 2022).

15 Dysarthria is “a speech disorder consisting of imperfect articulation due to loss of muscular control after damage to the central or peripheral nervous system.” Dysarthria , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id= 15144 (last visited Feb. 7, 2022).

16 TIA is “a brief attack (from a few minutes to an hour) of cerebral dysfunction of vascular origin, with no persistent neurologic deficit.” Transient Ischemic Attack , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=59631 (last visited Feb. 7, 2022).7 pneumonia last week and has not fully recovered her strength and energy.” 17 Id. at 149. I n review of systems petitioner reported no fever, chills, nausea

, or vomiting. Id. at 150. She had no nasal discharge, hemoptysis, 18 or pleurisy. 19 Id. Physical exam ination revealed that petit i oner’s lungs were clear bilaterally. Id. Mentally, petitioner was awake, alert

, and oriented

to person, place, and time. Id. Dr. Fix noted that petitioner had “ [ v ] ery subtl e dysarthria which may even be attributed to malaise and sleep

- deprivation.” Id

. Dr. Fix ’s assessment was TIA

. Id.

at 151. P etitioner’s “stroke

- like symptoms” had “nearly resolved.” I d

. Petitioner was not a

candidate for tissue plasminogen activato r (“ TPA ”) treatment 20 due to her improvement and

resolution of her symptoms. Id. at 79. CT scan showed no intracranial abnormality. Id.

While in the ED on July 18

, at 1:45 PM, RN Dawn M. Maynard also took a history from petitioner

. Pet. Ex. 5 at 80. Ms. Maynard wrote, “[ patient ] report s a progressive, generalized weakness over 1 week after receiving pneumonia vaccine.” Id. She added that petitioner noted slurred speech and severe left lower extremity weakness that was new that morning. Id. At 3:51

PM

, Ms. Maynard conducted a physical assessment, finding that petitioner had weakness in all four extremities during the musculoskeletal exam. Id. at 105.

On July 18, p etitioner was also evaluated by Occupational Therapist (“OT”) Marisa

Mueller

, who wrote “ patient states her w eakness started after receiving a [ pneumonia ] shot several days ago.” Pet. Ex. 5 at 96. Ms. Mueller assessed petitioner with “ generalized weakness and decreased ability to perform mobility tasks independently.” Id. at 97. Petitioner was also seen by P hysical T herapist (“PT”) Michaela Bundy

, who observed that petitioner had an unsteady gait, decreased functional mobility, decreased balance and strength, and required a rolling walker for ambulation. Id. at 10 0

- 0 1.

17 On July 23, Dr. Fix wrote “[i]t is now lear ned that apparently [petitioner] received a pneumonia vaccine 1 week prior to admission after which she began to have progressive, generalized weakness with an acute change the day of admission including dysarthria and [lower leg extremity] weakness which prompted presentation to the hospital.” Pet. Ex. 5 at 303. Dr. Fix

added that petitioner “exhibited only subtle dysarthria, no lower extremity weakness” when arriving to the ED. Id.

18 Hemoptysis is “expect oration of blood or of blood

- stained sputum.” Hemoptysis , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id= 22096 (last visited Feb. 7, 2022).

19 Pleurisy is “inflammation of the pleura, ” or lining of the lungs

. Pleurisy , Dor land’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id= 39590 (last visited Feb. 7, 2022). “S ymptoms includ e localized chest pain and dry cough

. . . . ” Id.

20 T issue plasminogen activato r, or TPA, is “a serine endopeptidase s ynthesized by endothelial cells, the major physiologic activator of plasminogen ; when bound to fibrin clots it catalyzes the

conversion of plasminogen to plasmin by hydrolysis of a specific arginine

- valine bond.” Tissue Plasminogen Activator , Dorland’s Me d. Dictionary Online, https://www.dorlandsonline.com/

dorland/definition?id= 54759 (last visited Feb. 7, 2022).8 Petitioner was admitted for observation for possible TIA versus cerebrovascular accident (“ CVA ”)

. 21 Pet. Ex. 5 at 108. Admitting history and physical examination was completed by Phy sician Assistant (“PA”) Peter Vo on July 18. Id. at 113. He wrote, “ [ p ] atient reported since she received her pneumo [nia] vaccine a week ago on Monday, July 10, 2017, [ 22 ] she started not feeling very well. Last night on July 17, 2017, she felt acute weakness lower extremity more right than left with q uestionable slurred speech earlier this morning around 7 AM

. . . .” Id. at 108. Mr. Vo noted that petitioner’s speech was normal during his examination. Id. at 110

. Chest X

- ray was performed, and no acute abnormalities were reported. Id. at 112. Adm itting

assessment was “? TIA (transient ischemic attack) vs reaction to pneumovax [ 23 ] given on Monday 7/10/2017.” Id.

O n July 21, 2017, a neurosurgery consult was performed by Dr. Oszkar Szentirmal and Brian Foster, PA

. Pet. Ex. 5 at 142. Chief complaint was bilateral lower extremity weakness.

Id

. Dr. Szentirmal n oted that petitioner had an “acute onset of bilateral lower extremity

weakness after aerobics class.” Id. MRI showed severe lumbar stenosis but no myelopath y. Id. History documented by Mr. F oster, stated that petitioner’s “legs started to feel weak and heavy and walking became very difficult” this week. Id. at 143. He added, “during this admission [,] her symptoms have steadily worsened to the point that she does not feel she can stand or walk at

all.” Id. Mr. Foster’s physical exam ination documented 4

- to 4/5 strength throughout, sensory perception was decreased to pinprick slightly in a stocking pa ttern bilaterally, and reflexes were trace to 1+ and symmetrical. Id. at 146. Petitioner’s lungs were clear bilaterally and she had no labored breathing or shortness of breath. Id. His assessment was bilateral lower extremity

weakness. Id. at 147. Du e to petitioner’s “ global weakness, ” he recommended further workup, including EMG testing and neurology work up. Id.

On July 23, petitioner was noted to have acute diarrhea. Pet. Ex. 5 at 302. But

, by the following day, July 24, her medical records note d her diarrhea improved. Id. at 296.

Dr. Jason P. Stabley conducted a n EMG/ NCV on July 24, 2017. Pet. Ex. 5 at 297. He noted that petitioner had “onset of progressive bilateral lower extremity and upper extremity weakness, sensory loss and legs [ 24 ] beginning within several days of receiving pneumococcal

21 CVA , or stroke, is “a condition with sudden onset caused by acute vascular lesions of the brain, such as infarction from hemorrhage, embolism, or thrombosis, or rupturing aneurysm. It may be marked by any of a variety of symptoms . . . including hemiparesis, vertigo, numbness, aphasia, and dysarthria.” Stroke Syndrome , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=111462 (last visited Feb. 7, 2022 ).

22 Petitioner’s correct date of vaccination was July 7, not July 10

, 2017

. Even tho ugh Mr. Vo

reference d the incorrect vaccination date, t he undersigned finds Mr. Vo’s note supports a finding that petitioner’s weakness began several days after vaccination and prior to her hospital

admission on July 18.

23 Petitioner rece ived the Prevnar 13 vaccine, not the Pneumovax vaccine.

24 Dr. Stabley may have meant to write “sensory loss in legs.”9 vaccine. ” Id. His c linical exam ination “ reveal [ed] significant neck flexor weakness, bilateral upper and lower extremity proximal and distal weakness, areflexia [,] [ 25 ] and stocking distribution sensory loss to pinprick to the level of the mid calves .” Id. CSF revealed cytoalbuminologic

dissociation , wit h an elevated protein of 11 2 mg/dL (normal 15

- 40) and elevated glucose of 88 mg/dL (normal 40

- 70)

. Id. at 297 , 393

- 95. Petitioner’s clinical diagnosis was GBS. Id. at 297. Dr. Stabley interpreted the EMG as “consistent with acute inflammatory demyelinating polyneuropathy ” (“AIDP”), also known as G BS

. Id. Petitioner was treated for GBS with a five

day course of IVIG. Id. at 115.

Dr. Devang Patel performed a pulmonary consult on July 24, 2017

. Pet. Ex. 5 at 136. He

wrote petitioner had progressive weakness bilaterally in lower and upper extremities, and had sensory loss that began with the legs. Id. at 138. Dr. Patel’s diagnos es were weakness of both

lower extremities and GBS. Id. at 140

- 41. Review of systems was also significant for shortness

of breath. Id. Physical examination found p etitioner’s lung sounds were diminished and she had

“ [ s ] cattered rhonchi.” 26 Id. at 139. Dr. Patel assessed petitioner with “respiratory insufficiency”

and “bibasilar atelectasis.” 27 Id. at 141. His diagnosis was “lower respiratory infection” and he ordered ceftriaxone and repeat chest X

- ray. Id. On July 26, petitioner’s chest X

- rays showed “low lung volumes with basilar scarring or sub segmental atelectasis .” Id. at 158.

On July 25, Dr. Paul Gaeta examined petitioner. Pet. Ex. 5 at 280. Under history of present illness, he noted petitioner “received a pneumonia vaccine [] prior to admission,” and “[a]bout a week later,” she develop ed weakness in her lower extremities and then developed slurred speech on the day of admission. Id. Petitioner “also noticed that she developed some

weakness of the hands.” Id. At the time of his examination, GBS was suspected

, and petitioner

was recei ving IVIG. Id. One of petitioner’s daughters stated petitioner “usually has irritable bowel syndrome” but she did not remember petitioner complaining of “ loose or worse bowel movements prior to coming into the hospital.” Id. Dr. Gaeta’s physical examination revealed

decreased sensation in lower extremities. Id. at 281. Assessment was “[w]eakness of both lower extremities suspected [GBS] at this time on 2 IgG.” Id. at 282.

On July 30, Dr. Jean Vickers performed a renal consult and observed that petitioner’s urinary retention “seem [ed] to be a long

- standing problem.” Pet. Ex. 5 at 202. Later that day,

Dr. Gaeta examined petitioner again and his diagnos is remained “[ w ] eakness of both lower extremities secondary to [ GBS ]

. ” Id. at 193. On July 31, a progress note authored by a medical

25 Areflexia is the absence of reflexes. Areflexia , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?i d=4 035 (last visited Feb. 7, 2022).

26 Rhonchus is “ a whistling or snoring sound heard on auscultation of the chest when the air channels are partly obstructed .” Rhonchus , Merriam

- Webster Dictionary, https://www.merriam

webster.com/dictionary/rhonchus (last visited Feb. 7, 2022).

27 Atelectasis is the “incomplete expansion of a lung or a portion of a lung; it may be a primary (congenital), secondary, or otherwise acquired condition.” Atelectasis , Dorland’s Med. Dictionary Online, https://www.dorlandso nline.com/dorland/definition?id=4646 (last visited Feb. 7, 2022).10 student and co

- signed by Dr. Gaeta stated that petitioner’s “symptoms started a week prior to admission with fatigue and malaise. [T]he precipitating cause was believed to [be the] pneumonia vaccination.” Pet. Ex. 6 at 79.

Physical therapy notes on July 31 , show ed that petitioner had l eft and right lower extremity buckling and an ataxic gait , consistent with GBS

. Pet. Ex. 5 at 189. After petitioner ’s diagnostic work up, her medical records contain multiple references to her diagnosis of GBS. See, e.g. , Pet. Ex. 5 at 51, 114

- 15, 173, 177, 181, 185, 194, 197, 201, 211, 215, 220, 227, 242,

275 , 293

.

Studies on petitioner’s CSF were conducted to determine the etiolog y of her GBS. Gram stain and cultures were negative, and varicella zoster and herpes simplex virus es were not detected. Pet. Ex. 5 at 439, 441. Acid

- Fast Bacillus (“ AFB ”) stain, fungal culture, cytomegalovirus, enterovirus, venereal disease research labo ratory (“ VDRL ”) , and antinuclear antibodies (“ ANA ”) studies were a lso negative. Id. at 390, 395, 411

- 12, 43 2

- 37

.

Petitioner was discharged to a rehabilitation fac ility on August 2, 2017. Pet. Ex. 6 at 153.

P etitioner’s diagnosis on admission to the rehabilitation facility was “[GBS] d/t [ 28 ] Pneumonia

Vaccine.” Id. With rehabilitation, p etitioner’s strength improved but her physical limitations prevented her from returning home. Pet. Ex. 9 at 92

- 112. Since her hospital discharge i n 2017, petitioner has resided at several assisted living facilities, and her records reveal that she moved to Bethel Park Senior Living facility in 2018 . Pet. Ex. 1 at ¶ ¶ 10

- 15

.

D. Declarations

1. Petitioner

Before petitioner received the Prevnar 13 vaccine on July 7, 2017, she “ did not have any difficulty walking or weakness in [her] arms or legs ,” and she “was very active

. ” Pet. Ex. 1 at ¶

4. She would walk regularly with her neighbors, attend aerobic classes, play bridge, and “ was independent in all areas of [her] life and was able to drive and care for [herself] and [her] home. ”

Id. ; see also Pet. Ex. 14 at ¶ 2.

A few days after vaccinati on, petitioner became fatigued , “but was back to [her] normal energy level and routine within a few days

. ” Pet. Ex. 14 at ¶ 3; see also Pet . Ex. 1 at ¶ 6. Between July 7, the date of vaccination, and July 18, 2017, petitioner initially felt some fatigue, but otherwise felt healthy. Pet. Ex. 14 at ¶ 4. She did not have a cough, runny nose, fever, or pneumonia. Id. Petitioner also remained active during th is time. Id.

On July 17, 2017, petitioner had no health concerns. Pet. Ex. 14 at ¶ 7. On July 18, 2017, when she woke up around 7 AM, she was unable to move her legs, unable to walk, could not feel her feet, and had pain in her legs. Id. ; Pet. Ex. 1 a t ¶¶ 7

- 8. She was hospitalized from July 18 to August 2, 2017. Pet. Ex. 1 a t ¶ 9. She underwent a lumbar puncture and EMG/NCV,

28 The abbreviation d/t means “due to.”11 which confirmed GBS diagnosis. Id. She received five days of IVIG infusions, as well as physical therapy and occupational th erapy. Id.

Thereafter, she was discharged to an acute rehabilitation facility , Solaris HealthCare . Pet.

Ex. 1 at ¶¶ 9

- 10. Petitioner “was bedbound and unable to turn or feed [herself]. [She] was able to get out of bed only with the assistance of a mechanical lift and the assistance of two

attendants. ” Id. at ¶ 10. Petitioner also needed a catheter and was frequentl y incontinent. Id. After one week at Solaris, petitioner was transferred to Water’s Edge Extended Care on August 8, 2017 for daily rehabilitation. Id. at ¶¶ 10

- 11. On admission, she was still unable to get out of bed on her own, was unable to turn hers elf, and needed continue care to assist with bowel

mo vements. Id. at ¶ 11. “[She] had daily physical therapy, occupational therapy, and speech therapy.” Id. A few days before her discharge on September 22, 2017, her catheter was

removed. Id. She was sent to Grand Oaks of Jensen Beach assisted living facility. Id. at ¶¶ 11

- 12.

Petitioner lived at various assisted living facilities until November 2018, whe n she moved

to a retirement home . Pet. Ex. 1 at ¶¶ 1 2

- 1 5. As of the date of her first declaration

, October 31, 2019, petitioner continue d to have intermittent numbness and tingling in her hands and feet , and fatigue d easily

. Id. at ¶ 20. She was no longer able to drive or live independently. Id.

2. Sharon Newton

Sharon Newton is the daughter of petitioner. Pet. Ex. 15 at ¶ 4. She has worked as a RN

since 1974. Id. at ¶ 3. Ms. Newton noted petitioner was “remarkably active for a person of her age,” and petitioner “was well enough to care for her home on her own and to travel independently.” Id. at ¶ 6.

In July 2017, Ms. Newton lived in a different state than petitioner, b ut they would speak on the phone at least twice per week. Pet. Ex. 15 at ¶ 5. Because of petitioner’s planned travel later that month, Ms. Newton was in close contact with petitioner. Id. at ¶ 9. Petitioner told Ms. Newton that after her vaccination, s he was exhausted, but was otherwise feeling back to normal the following day. Id. Ms. Newton stated petitioner was in her usual state of good health. Id. at ¶ 11. In the week before her hospitalization on July 18, 2017, petitioner told Ms. Newton that she was going to aerobics class, playing bridge, and getting her hair done. Id. at ¶ 10.

On July 18, 2017, Ms. Newton received a call from petitioner and her cousin informing her that petitioner “ lost the ability to walk due to weakness and numbness in both[] of her feet.”

Pet. Ex. 15 at ¶ 12. Ms. Newton arrived in Florida on July 23, 2017, and stayed for five weeks.

Id. at ¶ 13.

Ms. Newton stated petitioner “gradually regained her ability to walk and to care for he r own personal hygiene needs[,] but it was a long and difficult process. [Petitioner] never regained her energy to live without extensive assistance.” Pet. Ex. 15 at ¶ 15. As of March 8, 2020, the date in which Ms. Newton executed her declaration, petit ioner intermittently suffer [ed] from the feeling of pins and needles, require [d] a cane or walker for balance when she got tired , and

“continue [d] to be an extreme fall risk.” Id. at ¶ 16.12 3. Erin Fortunato

Petitioner is the mother of Erin Fortunato . Pet. Ex. 17 at ¶ 4. Ms. Fortunato lives in Pennsylvania. Id. at ¶ 1. She speaks with petitioner on the phone about two to three times per

week. Id. at ¶ 4. Prior to petitioner’s GBS diagnosis, Ms. Fortunato remembers petitioner going on a daily neighborhood walk and driving to various activities including hair appointments, bridge games, aerobics classes, church, school events for petitioner’s grandniece and grandnephew, the bank, and grocery shopping. Id. at ¶ 5.

Ms. Fortunato recalls petitioner feeling tired shortly after her Prevnar 13 vaccine, “but that she felt back to normal a few days later.” Pet. Ex. 17 at ¶ 6. She spoke to petitioner on the phone on the evening of July 17, 2017, and petitioner t old Ms. Fortunato that she went on a walk and to her aerobics class that day. Id. at ¶ 8. Petitioner “was healthy and did not have any cold symptoms at this time.” Id.

Ms. Fortunato received a call from petitioner at about 7:30 AM on July 18, 2017. Pe t.

Ex. 17 at ¶ 9. Ms. Fortunato stated petitioner was screaming that she could not stand or walk, and Ms. Fortunato called the police to have an ambulance dispatched. Id. On Wednesday, July 19, 2017, Ms. Fortunato received a call from petitioner, where petitioner stated she was not doing well

, and her symptoms were worsening. Id. at ¶ 11. Petitioner also told her sh e was not sure she would live through the night and requested Ms. Fortunato to come to Florida. Id. Ms. Fortunato and her daughter arrive d in Florida at 9:10 AM on July 20, 2017, and went straight to the hospital to visit petitioner. Id. at ¶¶ 12

- 13.

On arrival, Ms. Fortunato explained petitioner’s situation was a mess. Pet. Ex. 17 at ¶ 13. Ms. Fortunato’s sister, Ms. Newton, asked Ms. Fortunato to have the doctors test petitioner for

GBS. Id. at ¶ 14. Three days later, petitioner tested positive for GBS. Id. at ¶¶ 14

- 15. Ms. Fortunato explained that petitioner, after six days in the hospital without a proper diagnosis, was

hallucina ting and having difficulty breathing. Id. at ¶ 17. After petitioner’s first treatment, Ms. Fortunato saw petitioner’s treatment was helping

. Id. at ¶ 18

.

Ms. Fortunato stated petitioner has not fully recovered and has been unable to full y return to the active life she had prior to her GBS diagnosis. Pet. Ex. 17 at ¶ 19. As of March 9, 2020, the date in which Ms. Fortunato executed her declaration, petitioner remained less active than she was pre

- GBS, and continued to suffer from instabil ity with walking and standing. Id. at ¶ 20.

4. Joan Lohrer

Joan Lohrer was petitioner’s neighbor in Florida. Pet. Ex. 18 at ¶ 5. She would go on daily walks with her dogs and petitioner. Id. at ¶ 6. Ms. Lohrer does not recall petitioner being sick before her hospitalization. Id. at ¶ 8. Ms. Lohrer “thought [petitioner] was in pretty good shape.” Id. She visited petitioner once in the hospital. Id.13 5. Kathleen Maloney

Kathleen Maloney is petitioner’s niece. Pet. Ex. 19 at ¶ 4. She lived ten minutes from petitioner’s home in Florida. Id. at ¶ 5. She would see petitioner several times per month, and would talk to her regularly on the phone. Id. Ms. Maloney stated th at before petitioner’s hospitalization on July 18, 2017, petitioner was “very active,” always doing daily activities. Id.

at ¶ 7. Petitioner would also come to Ms. Maloney’s house for dinner and attend Ms. Maloney’s

children’s school functions. Id. Ms. Maloney spoke to petitioner one to two weeks prior to her hospitalization, and saw her a few weeks earlier. Id. at ¶ 8. To h er knowledge, petitioner was healthy before her hospitalization. Id. at ¶ 11.

On the morning of July 18, 2017, Ms. Maloney was at church when she received a call from petitioner stating that she could not move her legs. Pet. Ex. 19 at ¶ 12. Ms. Maloney arrived at petitioner’s home before the paramedics. Id. at ¶ 13. After petitioner was hospitalized, she visited her regularly, and continued to visit petitioner at her assisted living facilities before petitioner moved to Pennsylvania. Id. at ¶ 14.

E. E xpert Reports 29

1. Petitioner’s Expert, Dr. Steven Sykes

a. Background and Qualifications

Dr. Sykes is board certified in clinical neurophysiology and neurology. Pet. Ex. 21 at 1. After receiving his B.S. in n euroscience from the University of California, Los Angeles, he attended University of Michigan School of Medicine where he received his M.D. Id. He completed an internship in internal medicine, a residency in neurology, and a fellowship in clinical neurophysiology. Id. Dr. Sykes currently works as an Attending Neurologist at Cedars

Sinai Medical Group, where he practices general neuro logy and clinical neurophysiology, and an

Assistant Clinical Professor at Cedars

- Sinai Medical Center. Id. He is also the Neurology P anel

L ead er in the Cedars

- Sinai Medical Care Foundatio n. Id. ; Pet. Ex. 20 at 1

. “ The majority (over 85%) of [his] practice is dedicated to clinical practice and includes the diagnosis and management of peripheral nervous system disorders (such as [GBS]).” Pet. Ex. 20 at 1.

b. Opinion

i. Diagnosis

Dr. Sykes opine d that, to a reasonable degree of medical certainty, the “vaccine administered to [petitioner] on July 7, 2017 caused an abnormal activation of her immune

system ” leading to the development of GBS. Pet. Ex. 20 at 4 ; see also Pet . Ex. 30 at 4

. The majority of Dr. Sykes ’ opinion focused on the debated issue of petitioner’s diagnosis of GBS,

29 This Ruling does not include every detail of each expert’s opinions. Instead, the undersigned focuses on the material opinions, as they relate to the two relevant issues, diagnosis and

causation.14 and he generally deferred to Dr. Steinman’s immunology expertise regarding any detailed discussion of the applicable biological mechanism. Pet. Ex. 65 at 1.

Regarding diagnosis, Dr. Sykes opine d that petitioner ’s clinical presentation, diagnost i c testing, and opinions of her treating physicians support the diagnosis of GBS

. Pet. Ex. 65 at 3.

While Dr. Sykes agree d that petitioner’s initial presentation on July 18, 2017 included left lower extremity weakness and slurred speech ( dysarthria ), which warranted a workup for stroke, “the evolution of [petitioner’s ] generalized weakness, findings reported on her neurological exam (including hyporeflexia), elevated CSF protein, and findings on EMG/ [NCV] [were] all consistent with a GBS diagnosis.” Id.

In contrast, r espondent’s expert, Dr. Chaudhry, opine d that petitioner’s presentation was

not consistent with G BS for several reasons , including documentation of aphasia, the acute onset of her symptoms, the references to the diagnosis of stroke, the timing of her elevated CSF protein, EMG results, presence of urinary retention, and other potential causes that could explain

her weakness. Resp. Ex. A at 13

- 15. Each of these factors were addressed by Dr. Sykes.

W hen the petitioner arrived at the ED , a diagnosis of stroke/TIA was considered due to petitioner’s prior history of stroke and the asymmetry of her weakness. Pet. Ex. 30 at 2.
However, Dr. Sykes emphasized that petitioner ’s primary symptom was generalized weakness,

characteristic for GBS , and her diagnostic workup for stroke was negative

. Id. Moreover, petit i oner’s weakness was not “markedly or persistently asymmetric and [] therefore not atypical

for [ GBS ]

. ” Id. While Dr. Sykes agreed that petitioner initially had some asymmetr ic wea kness

in her lower extremities , her condition evolved to the point that she had severe weakness in both legs, specifically described by Dr. Fix as symmetrical. Id. ( citing Pet. Ex. 5 at 278, 292, 318,

329 )

. Further, the fact that the NIH stroke scale was used to evaluate petitioner for a stroke, an issue raised by Dr. Chaud h ry, does not mean that petitioner had a stroke. Pet. Ex. 65 at 2.

In his supplemental expert report, Dr. Chaud h ry opine d that petitioner had resolution of

her stroke

- like symptoms, characteristic of a TIA , and thus, he opine d that her initial presentation

was not due to GBS but to TIA or stroke. Resp. Ex. C at 2

- 4 . Dr. Sykes emphasize d the point that while early on petiti oner may have had symptoms of a TIA or stroke, these diagnoses would not explain the “ evolution of generalized weakness in a manner quite typical for GBS.” Pet. Ex.

65 at 2 ( citing Pet. Ex. 5 at 240

- 42, 329

- 30 )

.

Next, Dr. Chaud h ry opine d that petitioner had aphasia , which is inconsistent with GBS. Resp. Ex. A at 13. When petitioner presented on July 1 8 , 2017, the ED records describe her chief complaint as “aphasia

. ” Pet. Ex. 5 at 73. H owever, Dr. Sykes explain ed that what petitioner had was “dysarthria

, ” a symptom that is commonly seen in GBS. Pet. Ex. 30 at 1

- 2. Dr. Sykes define d “aphasia” as “the loss of the ability to produce or understand language. ” Id. at 1. In contrast, dysarthria is slurred speech, caused by “ weakness of muscl es involved in producing speech, including muscles of the tongue

, mouth , and/or palate .” Id. Dr. Sykes

reference d a number of citations from the medical records supporting his opinion on this point.

See id. (citing Pet. Ex. 5 at 73, 75, 83, 95, 138, 148 , 207).15 Further, Dr. Sykes point ed to Dr. Weller ’s physical examination

, where he s pecifically

state d that petitioner had “ [n] o aphasia

, ” but that she had “ [ m ] ild

- to

- moderate dysarthria.” Pet. Ex. 30 at 1 (quoting Pet. Ex. 5 at 77) . Dr. Sykes also reference d a n ursing assessment on July 18, 2017, documenting that petitioner had no “expressive or receptive aphasia

, ” but that she had “dysarthria.” Id. (citing Pet. Ex. 5 at 104 ) . Dr. Fix’s neurological exam noted “[n] aming, comprehension [,] and repetition [w ere ] intact ,” which Dr. Sykes explained means aphasia was absent, and petitioner had “dysarthria. ” Id. (quoting Pet. Ex. 5 at 1 50)

. 30 A fter reviewing petitioner’s medical r ecord s , Dr. Sykes found no physical examination that described aphasia,

“ whereas dysarthria/slurred speech is documented repeatedly in the records.” Id. at 2.

Another reason that Dr. Chaud h ry argue d that petitioner did not have GBS is based on the

“acute” onset of her symptoms. Resp. Ex. A at 13. In response, Dr. Sykes explain ed that GBS is

an “acute inflammatory demyelinating neuropathy ,” or AIDP, which by its nature is an acute

illness. Pet. Ex. 30 at 2. Dr. Sykes also opin ed that the evolution o f petitioner’s course, including the progression of h er weakness over a period of several days, is consistent with GBS.

Id.

Dr. Chaud h ry also suggested that the fact that p etitioner had elevated protein in her CSF

“within the first week of symptoms,” weigh ed against a diagnosis of GBS , and cited to Willison et al. in support

. Resp. Ex. A at 14 (citing Resp. Ex. A, Tab 1). Dr . Sykes disagree d and opine d that an elevated protein in CSF is common, even early in the course of the illness. Pet. Ex. 30 at

2. Dr. Sykes state d that the Willison et al. article reference d by Dr. Chaud h ry does not state that

CSF is generally nor mal in the first week of symptoms, but instead state s that a normal CSF protein level during the first week of symptoms does not make the diagnosis of GBS unlikely.

Id. at 3 (citing Resp. Ex. A, Tab 1 at 6 (“[N] ormal protein level (especially when determined in

the first week after onset of disease) does not make the dia gnosis unlikely or even exclude [GBS]

. ”))

.

Dr. Sykes cite d to a New England Journal of Medicine article authored by Yuki & Hartung, another article referenced by Dr. Chaud h ry , in which the authors state d that

“ albuminocytologic dissociation is present in no more than 50% of patients with [GBS] during

the first week of illness.” Pet. Ex. 30 at 3 (quoting Pet. Ex. 22 at 3 ). Thus, Dr. Sykes observe d

that the takeaway from these articles is that an absence of elev ated protein does not exclude a diagnosis of GBS, although the finding of protein elevation in CSF is common in the first week of symptoms. Id.

Regarding the EMG/NCV test, Dr. Chaud h ry question ed the findings of AIDP because

“no data [was] provided to support the interpretation.” Resp. Ex. A at 14. In response, Dr.

30 Dr. Sykes explained that the reason that the word “aphas ia” appeared so often in the medical records is a result of the “‘copy forward’ function clinicians routinely use when documenting in the electronic medical record . . . , which often perpetuates misinformation (or outdated information) in the medical reco rd.” Pet. Ex. 30 at 1.16 Sykes found “no reason to doubt the interpretation of the test by a board

- certified neurologist [ 31 ]
when the clinical features of pr ogressive generalized weakness (regardless of asymmetry early in the course), generalized hyp or eflexia, and elevated CSF protein are present.” Pet. Ex. 65 at 3 (citing Pet. Ex. 5 at 297, 303

- 04 )

.

Next , Dr. Chaud h ry opine d that petit i oner’s urinary retention is not characteristic of GBS

. Resp. Ex. A at 14. Dr. Sykes acknowledged that Willison et al. noted “bladder dysfunction at onset or severe and persistent bladder dysfunction

. . . would suggest an alternate diagnosis.”

Pet. Ex. 30 at 3 (citing Resp. Ex. A, Tab 1 at 5)

. However, he counter ed by explaining that dysautonomia is seen in GBS, and it can lead to urinary retention. Id. Moreover, petitioner had

pre

- existing urinary retention, prior to the onset of her GBS. Id. Thus, Dr. Sykes opine d that it

was a chronic issue for her. Id. (citing Pet. Ex. 5 at 202).

Lastly, Dr. Chaud h ry suggested alternate reasons for petitioner’s weakness, including diarrhea, urinary tract infection, and abnormal potassium and phosphate levels. Resp. Ex. A at

14

- 15. Dr. Sykes agreed that while these factors may have contributed to petitioner’s weakn ess, they would be unlikely to cause the “protracted course of weakness” that petitioner experienced.

Pet. Ex. 30 at 3 ; Pet. Ex. 65 at 2.

ii. Causation

With regard to Althen Prong One, Dr. Sykes generally deferred to Dr. Steinman, due to

his specialize d expertise. Pet. Ex. 65 at 1. However, h e opine d that molecular mimicry is the “mechanism underlying the autoimmune and inflammatory responses affecting the peripheral nervous system that can occur following vaccination.” Pet. Ex. 20 at 4. D r. Sykes explain ed that the “antigens of a vaccine can resemble ‘host’ antigens ” and that “activation of an [] immune response by the vaccine can result in an attack against those host antigens. If those antigens reside on cells of the peripheral nervous system, an autoimmune response occurs, with inflammation occurring in and around the peripheral nerves.” Id. at 3

- 4.

In support of his opinion that petitioner’s Prevnar 13 vaccine cause d her GBS, Dr. Sykes

note d that GBS has been reported after pneumococcal infections. Pet. Ex. 30 at 3. He cited the

El Khatib et al. 32 case report , where “antigens associated with the pneumococcal bacteria

. . .

‘ triggered an immune response and cross

- reacted with peripheral nervous system surface components due to molecular mimicry. ’ ” Id. at 4 (quoting Pet. Ex. 32 at 2)

.

31 The EMG/NCV was performed by Dr. Jason Stabley, who, according to the Cleveland Clinic Martin Health website, is a neurologist who completed his Residency in Neurology at Pennsylvania State University College of Medicine and hi s Fellowship in Neurology at Milton S. Hershey Medical Center

- Penn State University. Jason Stabley, DO , Cleveland Clinic Martin Health, https://www.martinhealth.org/jason

- stabley

- do (last visited Feb. 22, 2022). He is board certified in Neurology by the American Osteopathic Board of Neurology and Psychiatry. Id.

32 Hassan El Khatib et al., Case Report: Guillain

- Barre Syndrome with Pneumococcus

– A New

Association in Pediatrics , 11 IDCases 26 (2018).17 Dr. Sykes also note d that GBS was reported after the Prevnar 13 vaccine in a case report
authored by Ravishankar. 33 Pet. Ex. 30 at 4 (citing Pet. Ex. 35). In Ravishankar, a 66

- year old

female received a Prevnar 13 vaccine in January 2015 and a 23

- valent pneumococcal polysaccharide vaccine 34 in August 2015. Pet. Ex. 35 at 1. In September 2015, she was unable to move her legs, and by November 20 15

, her symptoms worsened. Id. A lumbar puncture showed albuminocytologic dissociation, and an EMG/NCV “showed evidence of mixed axonal and demyelinating sensorimotor polyradiculopathy.” Id. at 2. Thereafter, she was diagnosed

with GBS. Id.

Dr. Sykes opine d that the onset of petitioner’s development of neurological symptoms of weakness approximately ten days after vaccina tion “ is consistent with the range observed in other cases of vaccination preceding the development of [GBS].” Pet. Ex. 20 at 4.

2. Petitioner ’s Expert, Dr. Lawrence Steinman

a. Background and Qualifications

Dr. Steinman is board certified in neurology and has practiced neurology at Stanford University for over 40 years

. Pet. Ex. 36 at 1; Pet. Ex. 39 at 2. He received his B.A. from Dartmouth College in 1968 and his M.D. from Harvard University in 1973. Pet. Ex. 39 at 1. Thereafter, he compl eted an internship in surgery, residency in pediatrics, and residency in pediatric and adult neurology from Stanford University Hospital, as well as three fellowships

. Id. He currently works as a Professor at Stanford University. Id. Dr. Steinman is also “actively involved in patient care” and has cared for hundreds of adults and children with various inflammatory neuropath ies, including GBS , transverse myelitis, acute disseminated encephalomyelitis, neuromyelitis optica

, and multipl e sclerosis ( “ MS ” ). Pet. Ex. 36 at 1. He has

authored or co

- authored over 500 publications. Pet. Ex. 39 at 5

- 47.

b. Opinion

i. Diagnosis

Dr. Steinman opine d that petitioner was diagnosed with GBS

, as confirmed by EMG testing, lumbar puncture, use of IVI G for treatment, and supported by her treating physicians and Dr. Sykes

. Pet. Ex. 36 at 4 ; Pet. Ex. 56 at 2 ; Pet. Ex. 66 at 32

- 33 . The lumbar puncture and CSF analysis revealed “albumin

- cytologic diss ociation characteristic of GBS with elevated protein

. . . and normal cell counts and glucose. ” Pet. Ex. 56 at 2.

33 Nidhi Ravishankar, Guillain

- Barre Syndrome Followin g PCV Vaccine , 2 Clinics Surgery 1413 (2017).

34 The undersigned acknowledges that petitioner did not receive this vaccine. However, as described in further detail below, the Prevnar 13 and 23

- valent pneumococcal polysaccharide

vaccines contain some of the same components. Additionally, the package insert for Pneumovax

23 , a 23

- valent pneumococcal vaccin e, reported GBS as an adverse event during post

- approval

use. Pet. Ex. 70 at 6

- 7.18 Dr. Steinman cited the EMG/NCV report by Dr. Stabley that was abnormal, “consistent

with [AIDP] ( [GBS] ) .” Pet. Ex. 56 at 2 (quoting Pet. Ex. 5 at 29 7)

. The report states as follows:

Clinical history: 89

- year

- old female with onset of progressive bilateral lower extremity weakness and upper extremity weakness , sensory loss and legs beginning within several days of receiving pn eumococcal vaccine. Clinical exam reveals significant neck flexor weakness, bilateral upper and lower extremity proximal and distal weakness, areflexia and stocking distribution sensory loss to pinprick to the level of the mid calves. CSF revealed cy to al buminologic

dissociation.

Clinical diagnosis GBS [

. ]

Nerve conductions and electromyography performed of right upper and lower

extremities.

Electrodiagnostic impression: Study consistent with acute inflammatory demyelinating polyneuropathy [GBS.]

Pet. Ex. 5 at 297 (emphasis omitted).

Further evidence that p etitioner ’s diagnosis was GBS , important to Dr. Steinman, was the

fact that she was prescribed and underwent treatment for five days with IVI G , which is an “FDA approved therapy for GBS. ” Pet. Ex. 5 6 at 2; Pet. Ex. 66 at 33 . Moreover, Dr. Stein man agree d with the treating physicians’ diagnosis of GBS. Pet. Ex. 66 at 33.

ii. Causatio n : Althen Prong One

T he focus of Dr. Steinman’s expert reports is how the Prevnar 13 vaccine can trigger

GBS via molecular mimicry, a mechanism whereby shared structures “ in a vaccine can trigger a

cross

- reactive response to self.” Pet. Ex. 36 at 4. He p ropose d two mechanisms whereby molecular mimicry can trigger GBS following Prevnar 13 vaccination. The first involve d homology between “ [ p ] hosphoglycerol [ 35 ] [] present in serotypes 18C and 23F in the Prevnar 13 vaccine,” and phospholipids 36 in the human myelin sheath

. Pet. Ex. 36 at 5

- 6; Pet. Ex. 56 at 13 ;

35 Phospho

- is a “prefix[] indicating the presence of phosphorus in a compound.” Stedman’s Medical Dictionary 1486 (28 th ed. 2006). Glycerol is “[a] sweet viscous fluid obtained by the saponification of fats and fixed oils; used as a solvent, as a skin emollient, . . . and as a vehicle and sweetening agent.” Stedman’s a t 820.

36 Phospholipid is defined as “any lipid that contains phosphorus, including those with a glycerol backbone (phosphoglycerides and plasmalogens) . . . . Phospholipids are the major form of lipid

in all cell membranes.” Phospholipid , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=38759 (last visited Feb. 22, 2022).19 Pet. Ex. 66 at 1 2 . The second involve d homology between CRM 197 37 in the vaccine and

C ontactin

- 1

, 38 a protein found in humans. Pet. Ex. 66 at 25

- 32

.

1. Phosphoglycerol in S erotypes 18C and 23F

“Prevnar 13 has 13 complex sugars, chemically modified into saccharides from [ Streptococcus p n eumonia e (“ S. pneumonia e ”)] then linked chemically to CRM 197

. . . . ” Pet.

Ex. 66 at 1. That is, t he vaccine contains “saccharides of the capsular antigens of (13 different serotypes of) [ S. ] pneumonia [ e ]

. . . linked to non

- toxic diphtheria CRM 197 protein [carrier].”

Pet. Ex. 36 at 5. Two of the 13 serotypes (18C and 23F) contain phosphoglycerol. Pet. Ex. 66 at

1.

Based upon information obtained from the vaccine p atent, 39 Dr. Steinman explain ed that the glycerol phosphate side chains in the vaccine are necessary for its immunogenicity

. 40 Pet.

Ex. 66 at 5 (citing Pet. Ex. 55)

. Both vaccine components 18C and 23F have a phosphoglycerol moiety

. 41 Id

. at 5

- 6 (citing Pet. Ex. 67 at 1 )

. 42 “ Phosphoglycerol is linked to the saccharide

moieties and the whole complex is linked to CRM 197 by reductive amination.” Id. at 19. Dr.

Steinman stresse d the fact that the phosphoglycerol component s are retained during the process

37 Protein carrier “CRM 197 is a nontoxic variant of diphtheria toxin isolated from cultures of Corynebacterium diphtheriae strain C7 (β197) grown in a casamino acids and yeast extract

based medium or in a chemically

- defined medium.” Pet. Ex. 48 at 25 ( Prevnar 13 package

inse r t).

38 Contactin

- 1 , or CNTN1, “is a key axonal adhesion molecule, which interacts with CNTNAP1 (previously known as Caspr1) on the axon and neurofascin

- 155 on the glial side, and is essential for the formation of the paranodal septate

- like junction.” Pet. Ex. 73 at 2 (Yumako Miura et al., Contactin I IgG4 Associates to Chronic Inflammatory Demyelinating Polyneuropathy with Sensory Ataxia , 138 Brain 1484 (2015)).

39 The patent is filed as petitioner’s exhibit 55. The description of the glycerol phosphate side chain in 18C can be found at page 34, and a diagram of the chemical structure is at page 6.

40 Immunogenicity is defined as “the property that endows a substance with the capacity to provoke an immune response, or the degree to which a substance possesses this property. ” Immunogenicity , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/

defin ition?id= 24893 (last visited Feb. 22, 2022).

41 Moiety is defined as “any part or portion.” Moiety , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id= 31829 (last visited Feb. 22, 2022).

42 Kang Yu et al., Synthesis of the Biological Repeating Unit of Streptococcus pneumoniae Serotype 23F Capsular Polysaccharide , 14 Organic & Biomolecular Chemistry 11462 (2016).20 of conjugating the vaccine 43 because they are necessary for the vaccine to be immunogenic. 44 Id.

at 12, 19

- 2 1

.

Dr. Steinman cite d a paper by Chang et al. 45 to support his opinion that the phosphoglycerol component is preserved during the process of making the vaccine. Chang et al.

wrote “it is shown that glycerol

- phosphate must be preserved for conserving adequate antigenicity of the 18C capsular polysaccharide .” Pet. Ex. 51 at 1

.

In addition to the evidence regarding component 18C in Chang et al.

, Dr. Steinman state d

there is evidence “ that humans make antibodies targeting the phosphoglycerol regions” in the 23F serotype. Pet. Ex. 66 at 11

- 12. He cite d an article by Bryson et al.

, 46 which show ed X

- rays of antibodies targeting the 23F component of S. pneumonia e

. Id. at 12 (citing Pet. Ex. 63)

. Dr. Steinman explained that Bryson et al. “ show [ed] that a human antibody response to 23F, contained in the Prevnar 13 vaccine, is mounted.” Id. While the Bryson et al. study involved only the Pneumovax 23 vaccine, b oth Pneumovax 23 and Prevnar 13 contain 23F , and therefore,

Dr. Steinman stated that the Bryson et al. findings also apply to Prevnar 13. Id. at 1 2

- 16. “[T]he 23F target is the same serotype regardless of whether the vaccine is Prevnar 13 or Pn e umovax 23.” Id. at 12. Dr. Steinman assert ed that “[ Bryson et al.] show [ ed ] that phosphoglycerol is directly targeted by the core of the two human antibodies targeting 23F.” Id. at 13

.

Summarizing the information from the patent, Yu et al

. , and Bryson et al.

, Steinman

found “ compelling support

. . . that the immune response to serotypes 18C and 23F in Prevnar 13 targets the phosphoglycerol moiety in those serotypes.” 47 Pet. Ex. 66 at 16. He conclude d by

assert ing the Bryson et al. study “demonstrate [ d ] unequivocally that the immune response to the serotype 23F comp on ent of P neum ovax 23 targets the pho s phoglycerol in serotype 23F.” Id. ( emphasis omitted)

.

43 A conjugate vaccine is “a vaccine composed of an immunogenic polysaccharide conjugated with a protein carrie r.” Conjugate Vaccine , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id= 116508 (last visited Feb. 22, 2022).

44 For a detailed explanation of the evidence cited by Dr. Steinman to support his position that the phospho glycerol components are necessary for immunogenicity of the vaccine, see Pet. Ex.

36 at 7

- 10; Pet. Ex. 66 at 20

- 21.

45 Janoi Chang et al., Relevance of O

- acetyl and Phosphoglycerol Groups for the Antigenicity of

the Streptococcus pneumoniae Serotype 18C Capsular Polysaccharide , 30 Vaccine 7090 (2012).

46 Steve Bryson et al., Structures of Preferred Human IgV Genes

– Based Protective Antibodies Identify How Conserved Residues Contact Diverse Antigens and Assign Source of Specificity to CDR3 Loop Variation , 196 J. Immunology 4723 (2016).

47 Dr. Steinman reference d the X

- ray images from Bryson et al. and opine d t hat they

“ demonstrate [ d ] that the immune response to the phosphoglycerol in the polysaccharide capsule of serotype 23F is critical to the human immune response to serotype 23F.” Pet. Ex. 66 at 15 (citing Pet. Ex. 63).21 Dr. Steinman explain ed how the data from the vaccine patent and the studies described

above relate to the pathogenesis of GBS. He opine d that phospholipids are the targets of

antibodies in GBS. Pet. Ex. 36 at 5. He assert ed that antibodies to phosphoglycerol structures

inter act with myelin components triggering GBS. Id. at 9. Based on his own research, Dr.

Steinman explain ed that “phospholipids are components of the myelin sheath in humans, and they are targeted by antibodies ” leading to neuroinflammation and GBS

. Id

. at 6.

In support of this part of his opinion, Dr. Steinman relie d on several articles . The first

was authored by Ho et al., 48 and Dr. Steinman is also a named author. See Pet. Ex. 45. T he

authors showed that in the demyelinating disease MS

, autoantibodies “ target a phosphate group

, ” with the primary target a phosphoglycerol component of myelin. Pet. Ex. 36 at 6. The “ findings

indicate [d] that myelin phospholipids are targeted by autoimmune response s in MS.” Pet. Ex. 45

at 9.

In Gilburd et al., 49 the authors “ studied the reactivity of GBS sera with various phospholipids which are known to be important constituents of myelin, and serve as autoantigens

in other autoimmune conditions. ” Pet. Ex. 49 at 1. Six of the 16 patients with GBS had

autoantibodies to various phospholipids. Id. at 1, 5. However, the authors suggested this was “probably [] a result of [] myelin damage rather than [the] cause of demyelination

. ” Id. at 1, 6

.

I n another study by Nakos et al., 50 all nine GBS patients in the study had anti

phospholipid antibodies and no such antibodies were detected in the nine control subjects . Pet.

Ex. 50 at 1. The authors “ detected a wide range of anti

- phospholipid antibodie s in patients with idiopathic GBS ,” and “[a] ll nine GBS patients developed anti

- phospholipid antibodies directed against at least on e lipid during the course of the disease.” Id. at 5. They wrote “[t]he

association of GBS and certain autoimmune diseases, including systemic lupus erythematosus, is well recognized ,” and they noted “[h] igh levels of anti

- phospholipid antibodies were expressed in a patient with lupuslike syndrome who developed seconda ry GBS. ” Id. at 6. The authors explained that “[i] t is thought that whenever polyneuropathy occurs in the context of

autoimmune disease s , mainly in systemic lupus erythematosus, where anti

- phospholipid activity already exists, these antibodies can cross

- react with phospholipids and mediate damage in neural structures containing the particular phospholipids.” Id. Of note, the GBS patients in the Nakos

et al. study had primary GBS, not the secondary form like that which occurs in patients with lupus. Id. The authors also observed anti

- ganglioside antibodies, but only in 44% of the patients. Id. T hey conclude d that,

48 Peggy P. Ho et al., Identification of Naturally Occurring Fatty Acids of the Myelin Sheath

That Resolve Neuroinflammation , 4 Sci. Translational Med. 1 (2012).

49 B. Gilburd et al., Autoantibodies to Phospholipids and Brain Extract in Patients with the

Guillain

- Barre Syndrome: Cross

- Reactive or Pathogenic? , 16 Autoimmunity 23 (1993).

50 G. Nakos et al., Anti

- Phospholipid Antibodies in Serum from Patients with Guillain

- Barré Syndrome , 31 Intensive Care Med. 1401 (2005).22 It is not well understood whether these anti

- phospholipid antibodies play a role in the pathogenesis of the polyneuropathy or represent a part of a more

extensive immunoreaction that takes place in the GBS. However, immunopathology in autopsies suggests t hat antibody mediated injury is a predominant disorder in the demyelinating form of GBS. The immune attack is directed against components of Schwann cell membrane and is accompanied by

the characteristic feature of vesicular demyelination

. Therefore, it is crucial to investigate how anti

- phospholipid antibodies are related to specific antigens in

Schwann cell membrane

.

. . . .

Our findings suggest that in GBS there is a more extensive immune reaction, beyond the well known antiganglioside production, which has been related to the demyelination of the peripheral nerves.

Id. at 6

- 7.

In summary, Dr. Steinman ’s theory is based on molecular mimicry, and he posit ed that

antibodies to the phosphoglycerol structures present in the components of Prevnar 13 interact

with phospholipids in the myelin components of peripheral nerves

, triggering GBS. Pet. Ex. 36

at 9

, 11

.

2. CRM 197 and Contactin

- 1

The second homology posited by Dr. Steinman is between t he protein carrier in the vaccine, CRM 197 , and C ontactin

- 1, a protein found in humans . Pet. Ex. 66 at 25. Prevnar 13 is a conjugate vaccine, in which the individual polysaccharides of the capsular antigens of S.
pneumoniae are linked to a non

- toxic diphtheria CRM 197 protein. Pet. Ex. 36 at 5. “ CRM 197 is a

nontoxic variant of diphtheria toxin,” used as a protein carrier which makes the vaccine more immunogenic. Pet. Ex. 66 at 5, 1 7 (quoting Pet. Ex. 48 at 25 )

. “ CRM 197 differs from diphtheria toxin by only one amino acid,” and therefore, it “ is no t toxic, though like diphtheria toxoid [

, ] it is quite immunogenic.” Id. at 17.

Based on his own research, Dr. Steinman opine d that molecular mimicry might occur

between CRM 197 and C ontactin

- 1, a molecule that has been identified in patients with GBS. Pet.

Ex. 66 at 2 5. Dr. Steinman relie d on Miura et al

., a study done on patients with chronic inflammatory demyelinating polyneuropathy ( “ CIDP ” )

. Id. at 25

- 26 (citing Pet. Ex. 73). Prior

to the Miura et al. study

, another group of researchers reported finding autoantibodies against

C ontactin

- 1 in patients with CIDP. Pet. Ex. 73 at 1. The patients had an aggressive onset and did not respond well to t reatment with IVIG

. Id. Based on th e findings reported in that study,

Miura et al. set out to replicate the finding of C ontactin

- 1 autoantibodies and determine the relevance of the findings. Id. Miura et al

. focused their research on patients with CIDP, but used sera from patients with GBS, MS , and healthy patients as controls. Id. at 2

. A nti

- Contactin

- 1 IgG antibodies were foun d in 16 of the 533 patients with CIDP

, with 13 of the 533 CIDP patients23 (2.4%) having anti

- Contactin

- 1 IgG4 antibodies

. Id. at 3, 5 , 6 tbl.2

. They also found that f ive of the 200 patients with GBS had anti

- C ontactin

- 1 IgG antibodies. Id. at 3, 6 tbl.2.

The Miura et al. authors did not reach any conclusions about the presence of the anti

C ontactin

- 1 antibodies in the patients with GBS. See Pet. Ex. 73. But they did explain the theory of pathogenesis relevant here to Dr. Steinman’s theory, as it relates to C ontactin

- 1 . They

state d,

Cell adhesion molecules play a crucial role in the formation of the nodes

of Ranvier [ 51 ] and in the rapid propagation of the nerve impulses along myelinated

axons. In the peripheral nerves, the domain organization of myelinated axons depends o n specific axo

- glia l contacts between the axonal membrane and

Schwann cells [ 52 ] at nodes, paranodes [,] and juxtaparanodes. Recently, we showed that some of the patients with CIDP present IgG autoantibodies directed against the nodes of Ranvier or the paranodal axo

- glial apparatus. Notably, we

identified . . . c ontactin 1 (CNTN1) as [one of ] the targets of aut oantibodies in some patients with CIDP

.

Id. at 2.

Based on this information about the potential importance of C ontactin

- 1 , Dr. Steinman conducted a BLAST search, to determine whether there was homology between CRM 197 in the

vaccine and C ontactin

- 1

. 53 Pet. Ex. 66 at 26. H e found a sequence 54 that “might be capable of inducing a neuroinflammatory disease.” Id. at 29. He found “it is an epitope in diphtheria toxin, which provides the basis for CRM 197 .” Id. at 30. After additional research, Dr. Steinman

51 Nodes of Ranvier are “ constrictions occurring on myelinated nerve fibers at regular intervals of about 1 mm; at these sites the myelin sheath is absent and the axon is enclosed only by Schwann cell processes .” Nodes of Ranvier , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/def inition?id= 93095 (last visited Feb. 22, 2022).

52 Schwann cells are “large nucleated cells whose cell membrane spirally enwraps the axons of myelinated peripheral neurons and is the source of myelin; a single Schwann cell supplies the myelin sheath between two nodes of Ranvier .” Schwann Cell , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id= 66407 (last visited Feb. 22, 2022).

53 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 conducted his BLAST searches

, see Pet. Ex. 66 at 25

- 32.

54 The sequence is “ WEQAKALSVE, ” which “ has five of ten identical amino acids.” Pet. Ex.

66 at 29

.24 identified another sequence 55 that “has known cross

- reactivity with epitopes described in

humans ” on the Corynebacterium diphtheriae microbe. Id.

As further support, Dr. Steinman found that the se two regions of mimicry between

C ontactin

- 1 and CRM 197 in Prevnar 13 vaccine have been studied. Pet. Ex. 66 at 31. Dr.

Steinman cite d Raju et al. 56 to show that “[h]umans have been shown to mount T cell

responses [ 57 ] to these regions of the diphtheria molecule, WEQAKALSVE and EYMAQACAGNRVRR. ” Id. (citing Pet. Ex. 79 at 2 fig.1). Dr. Steinman opine d that the two sequences are also present in in the diphtheria toxin , stating “a correlation with detailed studies

on the human immune response to diphtheria toxin, differing in only one amino acid from

C RM.” Id. Thus, he conclude d that “[ t ] he theory provides actual detailed data for molecular

mimics in the CRM in the Prevnar 13 vaccine received by [p] etitioner. It shows how these mimics could trigger inflammatory neuropathy culminating in GBS.” Id. at 31

- 32 (emphasis omitted)

.

iii. Causation : Althen Prong s Two and Three

With regard to Althen Prong Two, a logical sequence of cause and effect, Dr. Steinman

state d that “ [t] he vaccine has constituents that induce antibodies known to cross

- react with myelin and that are found in patients with GBS.” Pet. Ex. 36 at 11.

Dr. Steinman agree d that petitioner’s onset of GBS symptoms was several days after vaccination, which is “ consistent with the timing known for GBS and the 1976 swine [ influenza ] immunization, often used as a surrogate in such cases.” Pet. Ex. 36 at 11. In support of this opinion, he cite d Schonberger et al., 58 wh o looked at 1,098 patients that developed GBS between October 1, 1976 and January 31, 1977

, and found 532 of the patients received a A/New Jersey

influenza vaccination prior to onset of GBS. Pet. Ex. 24 at 1

- 2, 5. Of the 532 patients, 71% developed GBS within four weeks after vaccinat ion, with 5 2 % developing GBS in the second

and third weeks after vaccination. Id. at 6. They found the largest percentage of cases (10%) occurred 16 and 17 days post

- vaccination. Id. at 6

- 7, 8 fig.5.

55 The second sequence is EYMAQACAGNRVRR. Pet. Ex. 66 at 30.

56 Raghavanpillai Raju et al., Epitopes for Human CD4 + Cells on Diphtheria Toxin: Structural Features of Sequence Segments Forming Epitopes Recognized by Most Subjects , 25 Eur. J. Immunology 3207 (1995).

57 T cells, or lymphocytes, are “cells primarily responsible for cell

- mediated immunity.” T Lymphocytes

, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/ definition? id=87562 (last visited Feb. 22, 2022 ). “When activated by antigen, T lymphocytes proliferate and differentiate into T memory cells and the various types of regulatory an d effector

T cells.” Id.

58 Lawrence B. Schonberger et al., Guillain

- Barré Syndrome Following Vaccination in the National Influenza Immunization Program, United States , 1976

- 1977 , 110 Am. J. Epidemiology 105 (1979).25 Dr. Steinman also cite d the Haber et al. 59 article, which reported onset of GBS after

Prevnar 1 3 , up to 42 days post

- vaccination. Pet. Ex. 34 at 1, 5. Haber et al. found 11 cases of GBS following Prevnar 13 vaccine

. 60 Id. at 4

- 5. “The median onset interval of symptoms was 9 days” with a range o f 2 to 34 days. Id. at 4

.

3. Respondent’s Expert, Dr. Vinay Chaudhry

a. Background and Qualifications

Dr. Chaudhry is board certified in neurology, neuromuscular diseases, electrodiagnostic medicine, and clinical neurophysiology. Resp. Ex. A at 1; Resp. Ex. F at 1 . He received his

M.B. and B.S. in India

, and then completed an internship

, residency in neurology, and fellowship

in neuromuscular diseases . Resp. Ex. F at 1

- 2 . He is currently a Nominated Clinical Professor at UNC Chapel Hill School of M edicine

. Id. at 2 . Dr. Chaudhry specialize s in the field of neuromuscular diseases. Resp . Ex. A at 1. He has an active clinical practice where he sees over 2,000 patients per year. Id. ; Resp. Ex. F at 50. He has authored or co

- authored over 200 publications. Resp. Ex. F at 4

- 2 2

.

b. Opinion

i. Diagnosis

Dr. Chaudhry opine d that petitioner’s symptoms, testing, and treatment were not consistent with a presentation of GBS based on several different factors. Resp. Ex. A at 13

- 15.

He assert ed that “there is no conclusive evidence that [petitioner] had GBS.” Resp. Ex. H at 4.

The factors enumerated by Dr. Chaudhry , which he argue d weigh against a diagnosis of

GBS

, are addressed in turn. First, he note d that the medical records document petitioner’s chief complaint as “aphasia,” which “ is not a presenting feature of GBS.” Resp. Ex. A at 13. He explain ed that “[ s ] udden onset of aphasia

. . . or sudden onset of dysarthria . . . are common [in] presentati on of stroke or impending stroke ( [TIA] ) rather than GBS.” Resp. Ex. C at 2 (emphasis omitted) . In support of his opinion , Dr. Chaudhry cite d to information from the National Institute of Neurological Disorders and Stroke , which states “symptoms of a stroke include

. . . trouble speaking or understanding speech.” Id. (quoting Resp. Ex. C, Tab 1 at 1). 61 Dr.

59 Penina Haber et al., Post

- Licensu re Surveillance of 13

- Valent Pneumococcal Conjugate Vaccine (PCV13) in Adults Aged ≥ 19 Years Old in the United States, Vaccine Adverse Event Reporting System (VAERS), June 1, 2012

– December 31, 2015 , 34 Vaccine 6330 (2016).

60 One of the 11 cases also received a n influenza vaccine prior to onset. Pet. Ex. 34 at 4.

61 Nat’l Inst. Neurological Disorders & Stroke, Nat’l Inst

. Health, Stroke Information Page

, https://www.ninds.nih.gov/Disorders/All

- Disorders/Stroke

- Information

- P age (last modified Mar. 27, 2019).26 Chaudhry reference d pages in the petitioner’s medical records that identif ied aphasia as the “chief complaint.” Resp. Ex. A at 13.

The second factor asserted by Dr. Chaudhry is that petitioner had acute symptoms, starting at 7 AM on July 18, 2017

, which is n ot characteristic of GBS

. Resp. Ex. A at 13. He explain ed that GBS pres ents with progressive weakness that occurs “over a period of hours to days to weeks.” Resp. Ex. C at 2; see also Resp. Ex. A at 12

- 13

. Further, because petitioner had a “sudden onset, her treating physicians considered the possibility of stroke or [TIA] .” Resp. Ex.

A at 13. Dr. Chaudhry note d that petitioner’s treating physicians considered CVA or TIA “ as the most likely diagnosis based on [petitioner’s] presentation and at least until [July 20, 2017]

, ” and

he cited portions of petitioner’s medic al records for support. Resp. Ex. C at 2 , 5

. He opine d that the treating physicians’ records document ed symptoms that began at 7 AM, which resolved by approximately 10:30 AM

, is not GBS, but “ is consistent with CVA/TIA. ” Resp. Ex. H at 1

- 2.

In addition to the medical records, Dr. Chaudhry cite d portions of petitioner’s affidavit, as well as affidavits of family members, that establish petitioner had acute symptoms and was unable to move her legs, stand, or walk when she woke the morning of Ju ly 18 , 2017

. Resp. Ex.

C at 4. Dr. Chaudhry emphasize d that petitioner and her family members all describe an acute onset of symptoms, which he contend ed occurs with CVA /TIA

, and not GBS. Resp. Ex. H at 1.

Dr. Chaudhry opine d that it was not until July 20, 2017, “three days after reversible left sided weakness and aphasia, [ that petitioner] complained of generalized bilateral lower extremit[y] [weakness].” Resp. Ex. A at 13. Petitioner was seen by a neurosurgeon, and “[s] ignificant spine disease w as confirmed

. . . on MRI.” Id. Petitioner was treated with steroids.

Id. Dr Chaudhry emphasize d that th ese facts are inconsistent with GBS. Id. He further state d

that “ GBS is a symmetrical disorder,” and that petitioner had weakness of one side, whi ch “ is typically not seen in GBS. ” Id.

Next, Dr. Chaudhry opine d that petitioner’s diagnostic tests were not typical for GBS. Resp. Ex. A at 14. On July 23, 2014, petitioner’s CSF revealed an elevated protein level of 112.

Id. Dr. Chaudhry explain ed that in GBS, protein levels are usually normal within the first we ek after onset of symptoms. Id. He also assert ed that an elevated protein level is not specific for

GBS. Id. ; see also Resp. Ex. C at 14. As for the EMG /NCV findings, Dr. Chaudhry agree d that the study was reported as consistent with AIDP, but because the underlying test data was not provided, he was unable to verify the interpretation. Resp. Ex. A at 14. Additionally, he opine d

that “[ i ] n GBS, nerve conduction abnormalities are most pronounced [two] weeks after start of illness,” whereas peti tioner’s test showed abnormalities “within 4

- 5 days of onset of lower extremity weakness, which is [] not typical for GBS.” Id.

Another feature of petitioner’s presentation that Dr. Chaudhry opine d was inconsistent with GBS was urinary retention. Resp. Ex. A at 14. He opine d that urinary retention is not usually associated with GBS , but can been seen with spine disease

. Id. Petitioner also had degenerative spine disease, and was seen by neurosurgery specialists, who considered surgery,

which Dr. Chaudhry note d weighs against a diagnosis of GBS. Resp. Ex. H at 2

- 3 . Petitioner received steroid treatment for her degenerative s pine condition

. Id.27 Lastly, Dr. Chaudhry note d that petitioner had other confounding features including hypophosphatemia (low phosphate), hypokalemia (low potassium), and diarrhea. Resp. Ex. A at

14 ; Resp. Ex. C at 14 . He assert ed that these problems c an cause weakness and fatigue

. Resp.

Ex. A at 14.

In summary, Dr. Chaudhry conclude d that the records are inconclusive, although he

agree d there was a “possi bility ” that petitioner “initially had a TIA from which she recovered.” Resp. Ex. A at 14. H e also opine d that petitioner had “lumbar stenosis and cervical radiculopathy, hypokalemia, and hypophosphatemia

. ” Id. However, he concede d that petitioner may have “suffered from ‘pa raparetic form of GBS

, ’ ” which is a “ regional form of GBS in which the motor nerves of the legs are most severely affected

. ” Id. at 14

- 15. He explain ed that this type of GBS usually ha s a “faster and more complete recovery ” and a “ relatively good

outcome.” Id. at 15.

ii. Causation

Dr. Chaudhry does not dispute that molecular mimicry is a recognized mechanism for how some infectious agents, like C. jejuni , can cause GBS. Resp. Ex. A at 20. He agree d that in

th e context of infection

, “ [ a ] n immune response against [ an ] infectious agent [] will cross

- react
with the peripheral nerve because of this antigenic sharing.” Resp. Ex. C at 8. But he disagree d

that vaccination, through the theory of molecular mimicry, can cause GBS. Resp. Ex. A at 20.

H e opine d that “ there is n o epidemiological or biological evidence to support that [the ] pneumococcal vaccine can cause GBS.” Resp. Ex. H at 4 (emphasis omitted)

.

Citing an article from Yuki, Dr. Chaudhry identifie d four criteria that “must be satisfied to conclude that a disease is triggered by molecular mimicry.” Resp. Ex. C at 9 ( quoting Resp. Ex. C, Tab 13 at 1 )

. The four criteria are (1) “ establishment of an epidemiological association

between the infectious agent and the immune

- mediated disease; ” (2) “ identification of T cells or

antibodies directed against the patien t’ s target antigens; ” (3) “ identification of microbial mimics of the target antigen; ” and (4) “ reproduction of the disease in an animal model. ” Resp. Ex. C, Tab 13 at 1; Resp. Ex. C at 9.

According to Dr. Chaudhry

, these criteria have been met for “only one infect ions agent, [ C. ] jejuni

, and only for one [] disease, that of acute motor axonal neuropathy (AMAN) form of GBS.” Resp. Ex. C at 9. He opine d that here, Dr. Steinman’s two proposed molecular mimics are not supported by evidence. Id. at 9

- 10.

Regarding epidemiological studies, Dr. Chaudhry cite d Baxter et al

. , 62 who evaluated the relationship between GBS and vaccinations , including the 23

- valent pneumococcal polysaccharide vaccine , but not Prevnar 13

. Resp. Ex. A

, Tab 9 at 1, 4 . In Baxter et al., the

authors reviewed records of 415 hospitalized patients diagnosed with GBS from 1995 to 2006

. Id. at 1. Of these, 25 had received a vacci ne within a six

- week period prior to onset of their

GBS. Id. at 4. The vaccines include d influenza (18 patients), 23

- valent pneumococcal

62 Roger Baxter et al., Lack of Association of Guillain

- Barré Syndrome with Vaccinations , 57 Clinical Infectious Diseases 197 (2013).28 polysaccharide (2 patients), tetanus

- diphtheria combination (3 patients), and hepatitis A and B (3 patients)

. Id. “[ U ] sing a case

- centered method to control for seasonality and other time

- varying confounders, [the y ] found no evidence of an increased risk of GBS following any vaccination.”

Id. at 5. The authors acknowledged that the study had “limited power to fully assess the risk of GBS following vaccination due to the rarity of the outcome

. ” Id. at 7. They concluded that the

results “ provide reassurance that the risk of GBS following any vaccine

. . . is extremely low.”

Id.

The second study relied on by Dr. Chaudhry was from Haber et al. , who studied vaccine adverse event reports in adults related to the Prevnar 13 vaccine that were reported to the Vaccine Adverse Event Reporting Systems ( “ VAERS ” ) from June 2012 to December 2015. Pet.

Ex. 34 at 2. During that time period, there were 2

, 976 total reports

. Id. Most of the reports related to injection site adverse events (injection s ite pain, redness, and swelling). Id. at 3 tbl.1. There were eleven cases of GBS reported following Prevnar 13 vaccination , and in ten of those,

the Prevnar 13 vaccine was the only vaccine administered. Id. at 4. One patient also received a n influenza vaccine. Id. The authors concluded that their “data mining analysis noted no disproportionate reporting for GBS.” Id. at 5. Dr. Chaudhry conclude d that Haber et al. does not support an associat ion between Prevnar 13 and GBS, since the rate of GBS following vaccination was lower than the background rate for the disease. 63 Resp. Ex. C at 7

- 8, 11.

About Dr. Steinman’s first molecular mimicry theory, based on phosphoglycerol

components of the Prevnar 13 vaccine, Dr. Chaudhry raise d several objections. First, Dr. Chaudhry disagree d that literature cited by Dr. Steinman support s the theory. Resp. Ex. C at 10.

Dr. Steinman cite d Nakos et al. as support for the proposition that anti

- phospholipid s have been

found in patients with GBS

. Id. (citing Pet. Ex. 50). Dr. Chaudhry took issue with Dr. Steinman’s interpretation. He cite d Nakos et al. where the authors state d “ [ i ] t is not well

understood whether these anti

- phospholipid antibodies play a role i n the pathogenesis of the polyneuropathy or represent a part of a more extensive immunoreaction that takes place in []

GBS.” Pet. Ex. 50 at 6.

Next, Dr. Chaudhry question ed whether the Gilburd et al. paper supports an association

between anti

- phospholipid antibodies ( antibodies to phosphatidyl

- ethanolamine, phosphatidyl

choline, or phosphatidyl serine) and GBS. Resp. Ex. C at 9

. He quote d the authors of Gilburd et
al. who state d “ no significant association was found between the presence of specific anti [

- ] phospholipid antibodies

. . . and GBS when compared to controls.” Id. (quoting Pet. Ex. 49 at

5 )

. Thus, Dr. Chaudhry emphasize d that neither Nakos et al. nor Gilburd et al. “conclude that phosphoglycerol is the pathogenic antigen in GBS.” Resp. Ex. H at 5.

According to Dr. Chaudhry , “ [ t ] he specific antibody in [the] AIDP form [of GBS] has not

be en identified.” Resp. Ex. C at 10. He did not agree that either the bacteria S. pneumonia e or the Prevnar 13 vaccine share homology with gangliosides (the often

- cited theoretical target in

63 It is not clear whether the authors of Haber et al. used background rates for the in cidence of GBS in the population to arrive at their conclusion. They “applied empirical Bayesian data mining methods to identify disproportionality of vaccine

- adverse event pairs and stratified by age group, sex, and by year the reports [ were ] received.” Pet. Ex. 34 at 2.29 GBS) or otherwise induce injury. Id. Even if they did, Dr. Chaudhry argue d that “finding

similar conformational structure between an exogenous agent and a self

- antigen alone [ i s] not sufficient to prove that molecular mimicry is the pathogenic mechanism for a disease. M any such homologies exist, and the vast majority of these are not associated with biologically relevant autoimmune phenomena or actual human disease.” Id. ( citing Resp. Ex. C

, Tab 16 at

10 )

. 64

As for the case report by Ravishankar, cited by both Dr. Sykes and Dr. Steinman, Dr. Chaudhry opine d that the patient described in the report had an “ evolution of symptoms over five

months ,” which he disagreed supported a diagnosis of GBS. Resp. Ex. C at 10

- 11 (citing Pet. Ex. 35); see also Resp. Ex. H at 5

. Similarly

, Dr. Chaudhry disagreed with Dr. Steinman as to the significance of the El Khatib et al. article, disputing that the patient had GBS, and instead Dr. Chaudhry opined that the patient had S. pneumonia e which led to septicemia and death. Resp. Ex. C at 11; Resp. Ex. H a t 6.

Regarding Althen Prong Two, while Dr. Chaudhry question ed whether petitioner had GBS, he believed that if she did, there were more likely causes other than vaccination. Resp. Ex. A at 15. He point ed to two other causes, a diarrheal illness or upper respiratory tract infection.

Id. Dr. Chaudhry state d that petitioner’s “records do not pinpoint when she suffered from diarrhea although multiple references are made to this during her admission.” Id. He quote d petitioner’s treating p hysician, who note d that “acute diarrhea resolved and unfortunately Campylobacter [testing] was never done as patient did not have stool sample.” Id. (quoting Pet.

Ex. 5 at 264 ) . Dr. Chaudhry opine d that “ Campylobacter is the most well described infection preceding GBS.” Id.

In support of his opinion that another likely cause of petitioner’s GBS was an upper respiratory tract infection, Dr. Chaudhry cite d to an affidavit from a daughter of petitioner and

medical records. Resp. Ex. A at 15. Petitioner’s daughter , Erin Fortunato, submitted a

declaration in which s he describe d her recollection of her mother’s condition prior to her illness.

See Pet. Ex. 17. Dr. Chaudhry does not specify wh ich specific sta tements in the declaration support his opinion that petitioner had a n upper respiratory illness. See Resp. Ex. A at 15.

Presumabl y , it is the reference that petitioner “ started to have labored breathing” on Sunday. 65

Pet. Ex. 17 at ¶ 15 . Petitioner’s daughter told the doctor about petitioner’s “trouble breathing.”

Id. at ¶ 17. By the next day, the daughter observed that the treatment h er mother received for her GBS had “helped to stop the progression of her deterioration.” Id. at ¶ 18.

The m edical records cited by Dr. Chaudhry include a consultation note by neurologist

, Dr. Fix

, dated July 18, 2017, in which Dr. Fix wrote

, “ [petitioner] reports she was diagnosed with pneumonia last week and has not fully recovered her strength and energy.” Pet. Ex. 5 at 149. In review of systems, Dr. Fix noted that petitioner did not report fever or chills, and she had

64 Inst. of Med., Evaluating Biological Mechanisms of Adverse Events

, in Adverse Effects of

Vaccines: Evidence and Causality 57 (Kathleen Stratton et al. eds., 2012).

65 Based on the sequence of events described in the declaration, Sunday would have been July 23, 2017 , approximately five days after petitioner’s admission to the hospital

.30 no pleurisy. Id. at 150. Ph y sic al examination showed that respiratory rate and oxygen saturation

was normal. Id. Lungs were “clear to auscultation bilaterally.” Id.

Additionally, Dr. Chaudhry cite d records of a pulmonary consult and treatment with IV

antibiotics . Resp. Ex. A at 15 ( citing Pet. Ex. 6 at 121 )

. 66 The pulmonary consult was conducted by Dr. Patel on July 24 , 2017

. Pet. Ex. 5 at 136

- 42. He diagnosed petitioner with bibasilar atelectasis and lower respiratory infection. Id. at 1 40

- 41.

Dr. Chaudhry also opine d that other causes, “such as hypophosphatemia and hypokalemia contributed to [petitioner’s] symptoms.” Resp. Ex. A at 15. He state d that petitioner had low phosphate blood levels from July 25 to July 29, 201 7

, 67 and that

“ [ g ] eneralized muscle weakness is the most common symptom” of this condition. Id. at 14. Dr. Chaudhry also opine d that “dysarthria

. . . can be a manifestation of low phosphorus.” Id. Petitioner also had low potassium, or hypokalemia , which Dr. Chaudhry op ined “is a common

cause of weakness.” Id. He assert ed that petitioner’s potassium was low on July 23, when it was 3.1 (normal range 3.5

- 5.0 mEq/L). Id. Dr. Chaudhry attribute d petitioner’s low potassium to petitioner’s diarrhea , and stated that “ascend ing weakness has been described with hypokalemia.” Id.

4. Respondent’s Expert, Dr . Lindsay Whitton

a. Background and Qualifications

Dr. Whitton received his B.Sc. in molecular biology, his M.B., Ch.B. in medicine, and his Ph.D. in herpesvirus transcription from the University of Glasgow in Scotland. Resp. Ex. E at 1. He also completed internships in medicine and surgery, and held var ious professor positions since 1986. Resp. Ex. A at 1; Resp. Ex. E at 1. He currently works as a Professor in the Department of Immunology and Microbial Science at Scripps Research Institute in California. Resp. Ex. E at 1. Dr. Whitton is a member of v arious professional societies and editorial boards,

and has authored or co

- authored almost 200 publications. Id. at 1

- 15.

b. Opinion

Dr. Whitton did not opine as to p etitioner’s diagnosis, or take a position on whether the diagnosis of GBS is appropriate. Resp. Ex. D at 3. Instead, he focused on the issue of causation :

66 The record cited by Dr. Chaudhry does not document a pulmonary consult or antibio tic
treatment. However, after a review of the records, the consult appears at Pe t. Ex. 5 at 13 6

- 4 2

.

67 Dr. Chaudhry inadvertently wrote the year as 2015.31 whether the Prevnar 13 vaccine can cause GBS. 68 See Resp. Exs. D, G. Dr. Whitton opine d that

“ Pre vnar 13 has an excellent safety record, and [he] is not aware of any evidence that associates it with GBS.” Resp. Ex. D at 18. He raise d a litany of objections about Dr. Steinman’s opinions

. H is primary criticisms are addressed below, with responses by Dr. Steinman.

First, Dr. Whitton believe d that it is inaccurate for Dr. Steinman to conclude that anti

phospholipid antibodies play a role in disease causation. Resp. Ex. D at 11

- 12. While Dr. Whitton agree d that that these antibodies “ may be the cause of disease ,” he opined that they may also be “ the result of the disease ” or “ irrelevant to the disease.” Id. at 12. Dr. Whitt on , like Dr. Chaudhry

, quote d Nakos et al., who state d that “ [i] t is not well understood whether these anti

phospholipid antibodies play a role in the pathogenesis of the polyneuropathy or represent a part of a more extensive immunoreaction that takes place in [] GBS.” Id. ( Pet. Ex. 50 at 6 ).

Instead of phospholip ids, Dr. Whitton opine d that “gangliosides

. . . are the targets of autoimmunity in GBS.” 69 Resp. Ex. D at 13 ; see also Resp . Ex. G at 5 . While Dr. Steinman did not disagree with the generally accepted proposition that gangliosides may be targeted in GBS,

he did not believe that “gangliosides are the only immune target in GBS.” Pet. Ex. 66 at 25 ; see also Pet. Ex. 56 at 17

- 18

. For support, Dr. Steinman cited Kanter et al

., 70 a nd his own research, in support of this point

. Pet. Ex. 66 at 22

- 25 (citing Pet. Ex. 44) ; Pet. Ex. 56 at 16

- 18 (citing, e.g, Pet. Exs. 44, 49

- 50)

. According to Kanter et al., “[l]ipids comprise over 70% of the myelin

sheath

, and a growing number of reports have shown T

- cell and antibody reactivity in [MS] .”

68 Dr. Whitton’s criticism s of Dr. Steinman’s expert reports include many issues, some of which

are no t material to the undersigned’s findings and conclusions. For example, Dr. Whitton

identifi ed many flaws in the Ravishankar case report cited by Dr. Steinman. See Resp. Ex. D at

15

- 16; Resp. Ex. G at 6. However, t he undersigned does not rely on the Ravi shankar article in her analysis , and therefore, does not discuss this aspect of Dr. Whitton’s opinions. For the sake of brevity and clarity, the undersigned discusses the material reasons for reaching her findings

and conclusions and omits discussion of c ollateral matters.

69 Dr. Whitton and Dr. Steinman engage d in a colloquy about a paper written by Kanter et al.

, where Dr. Steinman is a named author

. See Pet. Ex. 56 at 17

- 18; Pet. Ex. 66 at 22

- 25; Resp. Ex.

D at 12

- 13; Resp. Ex. G at 5

- 6; Pet. Ex. 44 at 1 . The pertinent statement is, “[a]utoimmune responses directed against phospholipids and gangliosides contribute to the pathogenesis in systemic lupus [] and [GBS], respective ly.” Pet. Ex. 44 at 1 . Dr. Whitton suggest ed that the statement is an acknowledgement by Dr. Steinman that in GBS, autoimmune responses are directed against gangliosides, not phospholipids. Resp. Ex. D at 13; Resp. Ex. G at 5. After Dr. Steinman explai ned the basis and origin of the statement in a subsequent report, Dr. Whitton wrote that Dr. Steinman tried to “disown his peer

- reviewed statement.” Resp. Ex. G at 5 (e mphasis omitted). Dr. Whitton further wrote that “ Dr. Steinman’s attempt to disown [th e]

statement

. . . is risible, and is based on a demonstrable falsehood.” Id. at 7. The undersigned finds such rhetoric excessive, and takes no position on the debate, as its resolution is not

necessary to determine entitlement in this case

.

70 Jennife r L. Kanter et al., Lipid Microarrays Identify Key Mediators of Autoimmune Brain

Inflammation

, 12 Nature Med. 138 (2006).32 Pet. Ex. 44 at 1. The study by Kanter et al. showed antibody reactivity against myelin lipids in patients with MS

. Id. They concluded that the data suggest s that lipid

- specific responses can

“ contribute to the pathogenesis of autoimmune demyelinating disease.” Id. at 5.

Dr. Whitton also object ed to Dr. Steinman’s reference s to articles like the Kanter et al. study, where the disease is MS , because that is not the disease at issue here. Resp. Ex. D at 12 ; Resp. Ex. G at 5

. Dr. Steinman acknowledge d that “ MS and GBS are different diseases,” and that MS is not a model for GBS. Pet. Ex. 66 at 22. He explain ed , however, that research on

imm une responses in MS show “that there is vigorous immunity to polar head groups in myelin [,] including immunity to phosphoglycerol and phosphoryl choline chemical structures .”

Id. ( c iting Pet. Ex. 45).

As for “ Dr. Steinman’s reliance on glycerol phosph ate,” and reference to Chang et al.,

which illustrat es the “phosphate head group

, ” Dr. Whitton ha d several observations . Resp. Ex. D

at 13

- 14

. First, Dr. Whitton suggest ed that the more likely explanation for the importance of the phosphate group in the vaccine is “related to its role in defining the overall shape of the polysaccharide

, ” which is “distinguishable by the immune system.” Id. In turn, Dr. Steinman

reiterate d his opinion that glycerol phosphate is important for the robust immune response and ability to elicit antibodies to components 18C and 23F of the vaccine

. See Pet. Ex. 66 at 12

- 16.

Secondly, Dr. Whitton state d that the phosphate groups in the vaccine are “very small molecular structures that are ubiquitous in biological materials.” Resp. Ex. D at 14. “ [W] hile there is no doubt that antibodies can be (and are) directed against large molecules that contain a few phosphate groups, ” Dr. Whitton “suspect [ed] ” that “ an antibody response [] focused solely

on this small

, and ubiquitous

, molecule would

. . . have extremely widespread effects on the

host.” Id. (emphasis omitted)

.

And thirdly, Dr. Whitton’s observed that if Dr. Steinman is right, “the glycerophosphate group of one strain [ of S. p neumoniae ] would induce an antibody response that would recognize the glycerophosphate group in a different strain ,” but there is no such antibody cross reactivity. Resp. Ex . D at 14

. Dr. Whitton assert ed that “antibodies against S. pneumoniae polysaccharides are exquisitely serotype

- specific, which means that antibodies against strain 18C do not recognize polysaccharides of other strains. Thus, Dr. Steinman’s speculation regarding antibodies that specifically target phosphoglycerol is invalid .” Resp. Ex. G at 4. In response, Dr.

Steinman agree d that “antibodies to the specific sugar serotypes are highly specific to those sugars,” but explain ed that he was “not referring only to the serotype specific antibodies.” Pet.

Ex. 66 at 17. Dr. Stei nman explain ed “that immunity to Prevnar 13 is polyclonal and encompasses adaptive immune responses to components including phosphoglycerol, the 13 saccharides including 18C and 23F which are known to contain phosphoglycerol, and CRM 197 , the protein carrie r that includes diphtheria toxi n modified by one amino acid.” Id.

In his second report, Dr. Whitton raise d additional objections to Dr. Steinman’s reliance on phosphoglycerol. D r. Whitton interpret ed Dr. Steinman’s opinion as suggesting that “the 13 different polysaccharides in Prevnar 13 are attached (conjugated) to CRM 197 using phosphoglycerol as the link.” Resp. Ex. G at 4. Dr. Whitton question ed whether that was possible since m ost of the polysa ccharides do not contain phosph o glycerol. Id. It is not clear33 whether Dr. Steinman respond ed to this point directly ; i nstead, he reiterated the importance of pho s phoglycerol as it relates to the immunogenicity of 18C, based on Chang et al

. Pet. Ex. 66 at

12

- 16. Dr. Steinman also emphasize d the finding of antibodies targeting 23F, described by Bryson et al

. Id. Dr. Steinman believe d th ese studies provide “compelling support

. . . that the

immune response to serotypes 18C and 23F in Pre vnar 13 targets the [phosphoglycerol] moiety in those serotypes.” Id. at 16.

Dr. Whitton also criticize d Dr. Steinman’s use of the phrase “phospholipid linkage,” as well as reliance on such a linkage as a tenet of petitioner’s theory. Resp. Ex. G at 4. According to Dr. Whitton, th e concept of “phospholipid linkage” was created by Dr. Steinman, and not Chang et al. Id. Dr. Whitton argue d that “[ i ] f the phosphoglycerol of 18C were used for conjugation

. . . , that chemical reaction would alter the phosphoglycerol, thereby destroying the immunogenicity of the 18C polysaccharide. ” Id. at 4

- 5 (emphasis omitted)

. Dr. Steinman disagree d and stated that “[p]hosphoglycerol is linked to the saccha ride moieties and the who l e comple x is linked to CRM 197 by reductive amination.” Pet. Ex. 66 at 19. Dr. Steinman cite d to the patent for the Prevnar 13 vaccine, and stated that “the 13 different saccharides are covalently

linked to CRM 197 .” Id. at 20. “Once activated, each capsular polysaccharide is separately conjugated to a carrier protein to form a glycoconjugate.” Id. Dr. Steinman contend ed that the process of reductive amination which links sugars to CRM 197 , “ does not ‘ dest r oy ’ the phosp hoglycerol. Instead, it allows successful conjugation to CRM

, the vital protein carrier.”

Id. at 21. According to Dr. Steinman, the importance of the phosphogl y cerol to immun ogen icity as demonstrated by the patent weighs against any argument that it is destroyed in the process of conjugation. Id.

Next, Dr. Whitton criticize d Dr. Steinman’s reliance on Haber et al., which discusse d

case reports of GBS after Prevnar 13 vaccination. Resp. Ex. D at 10

- 11, 16. Dr. Whitton note d

that while Haber et al. identified cases of G BS after vaccination , they did not conclude that there

was a causal association. Id. at 10. Instead, they conclude d that the data “noted no disproportionate reporting for GBS.” Id. at 11 (quoting Pet. Ex. 34 at 5)

. Dr. Steinman respond ed that while his theory “does not encompass epidemiology ,” the case reports described

in Haber et al. “ provide additional evidence that [the ] vaccin e could cause GBS.” Pet. Ex. 56 at

3

- 4 (emphasis omitted)

. Further, Dr. Steinman assert ed that t he authors ’ finding that the rate of GBS cases was not disproportionate does not mean that the vaccine could not cause GBS. Pet.

Ex. 66 at 36. He noted that the authors were “ more cautious about attributing ‘ absolute safety ’

or ‘ safety ’ regarding the vaccine ,” and they d id not define the phrase “disproportionate reporting.” Id. Lastly, Dr. Steinman note d that “[ f ] or rare diseases, it is difficult to know what is disproportionate. ” Id. at 36

- 37.

Dr. Whitton similarly opine d that the case reports by El Khatib et al

. and White et al. 71 do not support petitioner’s expert s’ opinions. Resp. Ex. D at 16

- 17. El Khatib et al. describe d the case of a teenage boy who developed sepsis a nd “acute respiratory distress syndrome” due to pneumococcal infection, not vaccination

. Id. at 16 (citing Pet. Ex. 32 at 1). A ccording to Dr. Chaudhry , to whom Dr. Whitton defer red as to diagnosis, the diagnosis of GBS in the report is

71 B. White et al., A Novel Pneumococcus with a New Association , 9 Travel Med

. & Infectious Disease 84 (2011).34 suspect , and Dr. Whitton agreed

. Id. ; Resp. Ex. C at 11; Resp. Ex. H at 6 . White et al

. describe d

another case of GBS following S. pneumoniae infection, not vaccination , and again, the diagnosis of GBS was questioned by respondent’s experts. Resp. Ex. D at 17.

White et al. described a case of systemic S. pneumoniae bacteremia which caused meningitis, pneumonia, and endocarditis. Pet. Ex. 33 at 1. The patient also developed an atypical form of GBS ( acute motor

- sensory axonal neuropathy) , not previously reported to be associated with pneumococcal bacteria. Id. at 1

- 2

. The authors conclude d that “ [ t ] his new association between invasive pneumococcal disease and an atypical form of [GBS] may help to provide further hypotheses regarding the antigenic triggers of GBS, and whether there is a target

on the pneumococcal surface capable of inducing ‘ molecular mimicry ’ as is seen in [ C ampylobacter ] infections.” 72 Id. at 3.

Irrespective of the two case reports by El Khatib et al. and White e t al., Dr. Whitton opine d that gram positive 73 bacteria like S. pneumoniae “ [are] not generally considered to be causally associated with GBS.” Resp. Ex. D at 8

- 10

, 18. Dr. Whitton cite d an article by Jasti et al., 74 listing 39 infections that may precede GBS

. Id. at 8 (citing Resp. Ex. D, Tab 16 at 2). He

observe d that S. pneumoniae was not on the list. Id. at 9.

Dr. Whitton also argued that GBS has no causal association with any other gram positive

bacteria because they “lack the [] molecules necessary to trigger GBS.” Resp. Ex. D at 8

- 10. Dr. Steinman disagreed and opined that gram positive bacteria are associa ted with GBS. Pet. Ex.

56 at 10

- 13. Dr. Steinman cited a paper by Yuki and Hirata 75 and stated that “though far less

common tha n C. jejuni , gram positive bacteria, including pneumococcus and streptococcus [,] are

72 The pneumococcal isolates from the patient’s blood and CSF were serotype 6A, not one of the serotypes relevant to Dr. Steinman’s theory. Pet. Ex. 33 at 2. Of interest in White et al. was the

fact that the bacteria had a unique genotype, not seen before. Id. at 2

- 3. That part of the case report is not discussed here.

73 Gram

- positive bacteria “retain[] the stain . . . in the Gram method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidoglycan with

attached teichoic acids.” Gram

- Positive , Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=20907 ( last visited F e b. 22, 2022).

74 Anil K. Jasti et al., Guillain

- Barré Syndrome: Ca uses, Immunopathogenic Mechanisms and

Treatment , 12 Expert Rev. Clinical Immunology 1175 (2016). Dr. Whitton referred to this article as Dr. Gershwin’s paper; Dr. Gershwin is one of the author s

. See Resp. Ex. D at 8; Resp. Ex. D, Tab 16 at 1.

75 Nobuhiro Yuki & Koichi Hirata, Fisher’s Syndrome and Group A Streptococcal Infection , 160 J. Neurological Scis. 64 (1990)

. For Dr. Whitton’s complete response to Dr. Steinman’s

assertion based on the Yuki & Hirata article regarding whether gram positive bacteria can cause GBS, see Resp. Ex. G at 2.35 implicated in GBS and its variants like Fisher Syndrome .” 76 Id. at 12 (emphasis omitted and

added ) (citing Pet. Ex. 58 )

. Dr. Steinman agreed that the Prevnar 13 vaccine and the infection which it protects against, S. pneumonia e , are very different. Pet. Ex. 66 at 5. In the context of

th e issues relevant to the causal theory, however, Dr. Steinman found Dr. Whitton’s emphasis on S. pneumonia e “misplaced.” Id.

Dr. Whitton also disagree d that Dr. Steinman’s reference to Conn e r et al.

, 77 a presentation by a medical student at the American College of Chest Physicians

, constitutes evidence in support of causation. Resp. Ex. G at 2 (citing Pet. Ex. 57). Conner et al. presented

on a 61

- year

- old male who reported tingling in his feet that progressed to his knees and

associated weaknes s. Pet. Ex. 57 at 2. The patient received the Prevnar 13 vaccine two weeks prior to hospital admission, and he denied upper respiratory infections and diarrhea. Id. Physical examination and testing were consistent with GBS, and the patient was started on IVIG. Id. The authors acknowledge d that “[t]he underlying etiology of GBS remains unclear, but the pathophysiology in most cases of GBS is due to stimulation of autoimmunity that produces auto

immune antibodies that attack the myelin sheath of the ner ves in the peripheral nervous system.”

Id. They also noted “[t]here is inconclusive data that the greater immunogenicity of [Prevnar 13] leads to a higher incidence of immune reactions potentially leading to GBS.” Id.

Regarding a temporal association between petitioner’s Prevnar 13 vaccinatio n and her GBS, Dr. Whitton state d that “ the two can be temporally associated

. . . but t his most certainly is not proof of causation.” Resp. Ex. D at 16.

III. 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 inju red 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 inju ry. Moberly v. Sec’y of Health & Hum

. Servs. , 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010). Proof of medical certainty is not required. Bunting v. Sec’y of Health

& Hum

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

76 The undersigned acknowledges the disagreement, but does not find it necessary to resolve it, since neither of Dr. Steinman’s mechanisms implicate lipo

- oligosac charides ( “ LOS ” ) or lipopolysaccharides ( “ LPS ” ) referenced by Dr. Whitton. See Resp. Ex. D at 8

- 10.

77 Chad Conn e r et al., 13

- Valent Pneumococcal Conjugate Vaccine

- Induced Guillain

- Barré Syndrome , 158 Allergy & Airway A59 (2020).36 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 Paffor d 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 unles s 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).

B. Factual Issues

A petitioner must prove, by a preponderance of the evidence, the factual circumstances surrounding h er 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 & Hu m

. 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 are presumed to be

accurate. See Cucuras v. Sec’y of Health & Hum

. Servs. , 993 F.2d 1525, 1528 (Fed. Cir. 1993). To overcome the presumptive accuracy of medical records, a petitioner may present testimony which is “consistent, clear, cogent, and compelling.” Sanchez v. Sec’y of Health & Hum

. S ervs. , No. 11

- 685V, 2013 WL 1880825, at *3 (Fed. Cl. Spec. Mstr. Apr. 10, 2013) (citing Blutstein v. Sec’y of Health & Hum

. Servs. , No. 90

- 2808V, 1998 WL 408611, at *5 (Fed. Cl. Spec. Mstr. June 30, 1998)).

There are situations in which compelling testim ony 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 v. Sec’y of Health & Hum

. Servs. , 23 Cl. Ct. 726, 733 (1991 ), aff’d per curiam , 968 F.2d 1226 (Fed. Cir. 1992))). 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, 137 9 (Fed. Cir. 2009); Bradley v. Sec’y of Health & Hum

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

Despite the weight afforded medical records, special masters are not bound rigidly by those records in determining onset of a petitioner’s symptoms. Vale nzuela 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) “mus t 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”).37 C. Causation

To receive compensation through the Program, petitioner must prove either (1) that she suffered a “Table Injury”

— i.e., an injury listed on the Vaccine Injury Table

— corresponding to a

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

vaccination. See §§ 11(c)(1), 13(a)(1)(A); Capizzano v. Sec’y of H ealth & Hum

. Servs. , 440 F.3d 1317, 1319

- 20 (Fed. Cir. 2006). Because petitioner does not allege she suffered a Table Injury

, s he must prove a vaccine she received cause d h er 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. The petitioner must provide a sound and reliable medical or scientific explanation that pertains specifically to this case, although the explanation need only be “le gally 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 h er 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 petitioner is entitled to compensation, the special master shall

consider all material in the recor d, including “any . . . conclusion, [or] medical judgment . . . which is contained in the record regarding . . . causation.” § 13(b)(1)(A). The special master must weigh the submitted evidence and the testimony of the parties’ proffered experts and rule in petitioner’s favor when the evidence weighs in h er 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 cre dibility of the persons presenting that evidence.”); Althen , 418 F.3d at 1280 (noting that “close calls” are resolved in petitioner’s favor).

IV. ANALYSIS

A. Diagnosis

As Federal Circuit precedent establishes, in certain cases it is appropriate to determine the nature of an injury before engaging in the Althen analysis. Broekelschen v. Sec’y of Health &

Hum. Servs. , 618 F.3d 1339, 1346 (Fed. Cir. 2010). Since “each pro ng of the Althen test is decided relative to the injury[,]” determining facts relating to the claimed injury can be significant in a case like this, where petitioner’s diagnosis is not clear. Id. Thus, before determining if petitioner has met each prong of Althen , the undersigned addresses whether petitioner has established, by a preponderance of the evidence, that petitioner suffers from GBS.

The undersigned finds that there is preponderant evidence that petitioner’s diagnosis following vaccination was GBS . This finding is based on the opinions of petitioner’s treating physicians, her clinical presentation, diagnostic testing, and the opinions of petitioner’s experts.

While Dr. Chaudhry is correct in concluding that petitioner’s initial presentation suggested a TIA38 or stroke , those symptoms resolved within seve ral hours of her arrival to the hospital. Dr. Chaudhry also accurately explains th e confounding factors that clouded petitioner’s clinical picture and may have made it more difficult to diagnosis GBS. However, after petitioner was hospitalized and her sy mptoms progressed, her physicians suspected GBS, which was confirmed by diagnostic testing.

According to the literature , weakness is the prominent manifestation of GBS. See , e.g. , Pet. Ex. 2 2 at 2 . When she presented to the hospital on July 18, 2017, petitioner reported to Ms. Maynard , RN, that she had experienced “progressive, generalized weakness over 1 week after receiving pneumonia vaccine.” Pet. Ex. 5 at 80. Superimposed on that background, petitioner also had new left leg weakness that began that morning. Physical examination by Ms. Maynard revealed that petitioner had weakness in all four of her extremities.

Also on July 18, neurologist Dr. Fix documented that petitioner “ report [ed] t hat she was diagnosed with pneumonia last week .” Pet. Ex. 5 at 149. However, t here is no evidence in the

record to support the statement that petitioner was diagnosed with pneumonia the week prior to

her admission. Subsequently, o n July 23, 2017, Dr. Fix wrote, “[i]t is now learned that apparently [petitioner] received a pneumonia vaccine 1 week prior to admission after which she began to have progressive, generalized weakness with an acute change the day of admission including dysarthria and [lower leg extremity] weakness which prompted presentation to the hospital.” Id. at 303.

In addition, on July 18, Dr. Fix noted petitioner reporte d bilateral lower extremity weakness the day prior, and that petitioner had an acute change, which began that morning, of more difficulty ambulating. Additionally, Dr. Fix, after physical examination noted petitioner’s

“stroke

- like symptoms” had “nearly r esolved.” Id. at 151.

Again on July 18, Ms. Bundy , PT, documented that petitioner had an unsteady gait and decreased balance and strength.

On July 21, Mr. Foster, PA, documented that petit i on e r reported that her legs felt weak

and heav y , and that walking had become difficult that week. Mr. Foster’s physical examination

revealed reduced strength throughout, sensory perception decreased slightly in a stocking pattern bilaterally, and abnormal reflexes noted to be trace to 1+ symmetrically . Due to petitioner’s global weakness, he recommended a neurology work up and EMG.

On July 24, Dr. Stabley took a history and performed a physical examination in

association with con ducting an EMG /NCV. He noted that petitioner had “onset of progressiv e bilateral lower extremity and upper extremity weakness

. . . beginning within several days of receiving pneumococcal vaccine. ” Pet. Ex. 5 at 297. His c linical examination “ reveal [ed] significant neck flexor weakness, bilateral upper and lower extremity proximal and distal weakness, areflexia [,] and stocking distribution sensory loss to pinprick to the level of the mid

calves .” Id. CSF revealed cytoalbuminologic dissociation , with an elevated protein of 11 2 mg/dL (normal 15

- 40). Petitioner’s clinical diagnosis was GBS. Dr. Stabley interpreted the

EMG as consistent with AIDP /GBS.39 The diagnosis of GBS was repeated by Dr. Patel on July 24 , and petitioner was treated for

GBS with a f ive

- day course of IVIG. On July 30, Dr. Gaeta’s diagnosis was GBS. Additionally, on July 31, 2017, physical therapy notes showed petitioner had left and right lower extremity buckling and an ataxic gait , consistent with GBS . After petitioner ’s diagnosti c work up, her medical records contain multiple references to her diagnosis of GBS.

Further, petitioner’s diagnostic tests were consistent with her diagnosis of GBS. Dr. Stabley performed an EMG/ NCV and interpreted the study to be consistent with AIDP/GBS

. There is no reason to suspect that his interpretation of the testing was erroneous. 78 Moreover, CSF testing showed an abnormally elevated protein level in the context of a normal cell count,

which is also consistent with GBS. 79

Based upon the evidence summarized above , the undersigned finds that petitioner has proven by preponderant evide nce that she suffered from GBS following her Prevnar 13

vaccination.

B. Causation

1. 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 scientifi cally certain, but it must be informed by a “sound and reliable” medical or scientific explanation. Boatmon v. Sec’y of Health & Hum

. Servs. , 941 F.3d 1351, 1359 (Fed. Cir. 2019); see also Knudsen , 35 F.3d at 548; Veryzer v. Sec’y of Health & Hum

. Servs.

, 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 h er theory, the basis for the opinion and the reliability of that basis must be considered in the

determination o f how much weight to afford the offered opinion. See Broekelschen , 618 F.3d at 1347 (“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

78 Dr. Chaudhry observed that the data underlying the petitioner’s EMG/NCV was not contained

in her medical record s . The undersigned notes that based on her experience in reviewing medical records in many similar cases, it is common that the EMG/NCV report interpreting the

data b e contained in the record, but not the data itself. Presumabl y, the underlying data could have been obtained pursuant to a specific request or subpoena for it, but neither party requested such discovery.

79 Dr. Chaudhry also observed that petitioner’s urinary retention was not consistent with GBS.
However, Dr. Vickers , during a renal consult

, observed that petitioner’s urinary retention

“seem [ed] to be a long

- standing problem.” Pet. Ex. 5 at 20 2 . This not e weighs against Dr. Chaudhry’s interpretation that petitioner had acute urinary retention and that it was inconsistent with her diagnosis of GBS.40 soundness of the reasons supporting it” (citing Fehrs v. United States , 620 F.2d 255, 265 (Ct. Cl. 1980))).

For the following reasons, t he undersigned finds p etitioner has provided by preponderant

evidence a sound an d reliable theory that the Prevnar 13 vaccine can cause GBS

, and therefore, petitioner has satisfied the first Althen prong.

Molecular mimicry has long been invoked a s the causal mechanism for many different autoimmune diseases, including GBS. M any of the articles filed in this case support the mechanism as the leading hypothesis for the etiology of GB S

. See, e.g. , Resp. Ex. C, Tab 13 at

1

. The theory has been extended from infectious agents to vaccine

- associated autoimmune illnesses, including GBS. See , e.g. , Pet. Ex. 22; Pet. Ex. 32; Resp. Ex. A, Tab 2

.

M olecular mimicry has been accepted as a sound and reliable theory in many demyelinating conditions , including GBS, in the Vaccine Program , forming the basis for petitioners to be entitled to compensation. See, e.g.

, Conte v. Sec’y of Health & Hum. Servs.

, No. 17

- 403V, 2020 WL 5743696, at *23 (Fed. Cl. Spec. Mstr. July 27, 2020) (noting the theory of molecular mimicry in a GBS case is “well

- established and well

- settled in the Vaccine Program”); Barone v. Sec ’ y of Health & Hum

. Servs. , No. 11

- 707V, 2014 WL 6834557 , at *8

- 9 (Fed. Cl. Spec. Mstr. Nov. 12, 2014) (noting molecular mimicry “ has been accepted in other Program cases as a reliable medical explanation for how various autoimmune conditions could develop after the receipt of different kinds of vaccinat ions ”) ; Koller v. Sec’y of Health & Hum.

Servs. , No. 16

- 439V, 2021 WL 5027947 , at *18 (Fed. Cl. Spec. Mstr. Oct. 8, 2021); Pierson v. Sec’y of Health & Hum. Servs. , No. 17

- 1136V, 2022 WL 322836 , at *31 (Fed. Cl. Spec. Mstr. Jan. 19, 2022) ; Deshler v. Sec’y of Health & Hum. Servs. , No. 16

- 1070V, 2020 WL 4593162

, at
*19 (Fed. Cl. Spec. Mstr. July 1, 2020). 80

Dr. Chaudhry asserts that four criteria that must be met to establish whether a vaccine can cause GBS via molecular mimicry. These criteria include supportive epidemiology, identification of antibodies directed against human antigens, identification of the mimics of the

target ant igen, and reproduction in an animal model. Given the state of current knowledge, a petitioner cannot satisfy these criteria. Fulfilment of these criteria 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”).

Dr. Whitton takes a different tack . He c riticizes the fact tha t peti t ioner has not invoked a causal mechanism that implicates gangliosides as the targets of autoimmunity. However, the literature filed by the parties does not support the notion that gangliosides are the only player in the game of molecular mimicry

.

T here is scientific support for Dr. Steinman’s theories. To use the language in the criteria

cited by Dr. Chaudhry

, Dr. Steinman has identified components of a vaccine that could initiate

80 The undersigned acknowledges that the first two cases in this string cite involve a different vaccine, al though the same illness.41 development of antibodies that could cross

- react with epitopes on peripheral nerve myelin or axonal glycopro t eins. H e has identified components of the Prevnar 13 vaccine protein that could trigger a human antibody response.

Regarding petitioner’s theory based on pho s phoglycerol in serotypes 18C and 23F in the vaccine, Dr. Steinman provides evidence in the Bryson et al. paper showing the antibodies that target 23F. There is an immune response that targets the pho s phoglycerol moiety in the 23F serotype in the vaccine. Dr. Steinman produced papers to show t hat in MS, myelin phospholipids are targeted by an immune response. He has also shown that myelin is comprised of phospholipids, and that phospholipids can serve as autoantigens in autoimmune disorders

. He

has show n that patients with GBS ha ve autoantibodies to phospholipids. In the Gilburd et al. study, the autoantibodies were thought to be due to myelin destruction. However, in the Nak o s et al. article, the researchers had a different view. They suggested that anti

- phospholipids either

“ pl ay a role in pathogenesis of the polyneuropathy o r represent a part of a more extensive

immunoreaction that takes place in GBS

. ” Pet. Ex. 50 at 7. In summary, there is sound support from reputable medical studies for each foundational aspect of th e phosp hoglycerol theory.

T here is also evidence to support Dr. Steinman’s second theory based on CRM 197 and

C ontactin

- 1 . Dr. Steinman identified sequences of shared homology between the proteins in the

vaccine and those in C ontactin

- 1. However, the study by Raju et al. shows that the sequence in

CRM 197 differs, albeit by one amino acid, from the sequence in the diphtheri a toxin. Thus, the foundation for this theory is less sound.

Moreover, the causal theory proffered by Dr. Steinman here has previously been accepted

as sound and reliable in two recent cases, decided by two different special masters. See Koller

, 202 1 WL 5027947 ; Pierso n , 2022 WL 322836. While prior decisions are not binding on the undersigned, they can be considered by the undersigned in forming her opinions

. See Hanlon v. Sec’y of Health & Hum. Servs. , 40 Fed. Cl. 625, 630 (1998), aff’d , 191 F.3d 1344 (Fed. Cir. 1999) ; Boatmon

, 941 F.3d at 1358.

Further, petit i oner’s evidence here is stronger than that presented in Koller

. Here, Dr.

Steinman cited the Bryson et al. study

, which showed human antibodies targeting serotype 23F,

one of the S. pneumonia e serotypes included in the Prevnar 13 vaccine.

In a third decision addressing the Prevnar 13 vaccine and GBS, the proffered causal theory was unsupported by evidence, and th e Chief Special Master found that peti ti oner was not entitled to compensation

. Deshler , 202 0 WL 4593162

. There, the petitioner relied on molecular mimicry , and suggested that there was homology between polysaccharide components of the vaccine and the myelin sheath, but evidence was insufficient to establish the scientific soundness of the theory. Id. at *19

- 21. Due to the lack of supportive evidence, respondent’s expert

, Dr. Whitton, was effective in establishing that the polysaccharides in the vaccine “do not share structural homology with self

- structures of the peripheral nervous system, and therefore do not contribute to the pathogenesis of GBS.” Id. at *20. The theo ry proffered here is far more well

developed and based on supportive foundational evidence from scientific studies.42 For all of the se reasons , the undersigned finds that peti tioner has proven by preponderant evidence a sound and reliable causal theory esta blishing that the Prevnar 13 vaccine can cause

GBS , satisfying Althen P rong O ne

.

2. Althen Prong Two

Under Althen Prong Two, petitioner must prove by a preponderance of the evidence that there is a “logical sequence of cause and effect showing that the vaccination was the reason for the injury.” Capizzano , 440 F.3d at 1324 (quoting Althen , 418 F.3d at 1278). “Petit ioner 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 t o 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 t hey are created contemporaneously with the treatment of the vaccinee. Cucuras , 993 F.2d at 1528

. While the medical records and opinions of treating physicians must be considered, they are not binding on the special master. The Vaccine Act specifically p rovides that the “diagnosis, conclusion, judgment, test result, report, or summary shall not be binding on the special master or court.” § 13(b)(1)(B).

The petitioner need not make a specific type of evidentiary showing, i.e., “epidemiologic studies, re challenge, 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 h er burden by presenting circumstantial evidence and reliable medical opinions. Id. at 1325

- 26.

There are three principal reasons why t he undersigned finds preponderan t evidence of a logical sequence of cause and effect establishing that the Prevnar 13 vaccination administered to

p etitioner on July 7, 2017, was the cause of h er GBS

. First, petitioner was appropriately diagnosed with GBS, and petitioner has proffered a sound and reli able mechanism of vaccine

causation

.

Secondly, petitioner’s treating physicians’ statements provide circumstantial evidence in

support of vaccine causation. On July 23, 2017, Dr. Fix wrote, “[i]t is now learned that apparently [petitioner] received a p neumonia vaccine 1 week prior to admission after which she began to have progressive, generalized weakness with an acute change the day of admission.” Pet. Ex. 5 at 303. The next day, July 24, Dr. Stabley stated that petitioner had “onset of progressive bilateral lower extremit y and upper extremity weakness

. . . beginning within several days of receiving pneumococcal vaccine.” Id. at 297. Dr. Fix and Dr. Stabley are neurologists, and as such, they diagnos e and treat peripheral neuropathy disorders such as GBS

.43 In addition to petitioner’s neurologists, her other treating physicians also noted an

association between her vaccination and GBS. O n July 2 4, 2017, Dr. Patel documented that petitioner received “ a pneumonia shot a week prior to this episode. The patient underwent nerve conduction study and was found to [have] [AIDP] . . . .” Pet. Ex. 5 at 136. The next day, July 25, Dr. Gaeta referenced petitioner’s “pneumonia vaccine [] prior to admission.” I d. at 280. On July 31, a progress note authored by a medical student stated that petit i oner’s “symptoms started a week prior to admission with fatigue and malaise. [ T ] he precipitating cause was believed to [be the] pneumonia vaccination.” Pet. Ex. 6 at 79. And on August 2, 2017, petitioner’s diagnosis on admission to the rehab i litation facility was “ [GBS] d/t Pneumonia Vaccine.” Id. at 153. Individually and collectively, these statements constitute circumstantial evidence that the petitioner’s treatin g physicians associated her vaccine with the development of her GBS.

Third, the evidence does not support an alternate cause for petit i oner’s GBS. Dr. Chaudhry raised two potential causes, a diarrheal illness and upper respiratory tract infection. However, a close review of the medical records does not support either of these as potential culprits because the evidence does not show that either occurred prior to the onset of petitioner’s

GBS.

Here, because petitioner’s clinical history presents a logical sequence of cause and effect consistent with vaccine causation, she need not eliminate other potential alternative cause s

. See Walther v. Sec’y of Health & H um. Servs. , 485 F.3d 1146, 1149

- 52 (Fed. Cir. 2007) (finding petitioner does not bear the burden of eliminating alternative independent potential causes). While respondent has argued that petitioner’s illness was caused by an antecedent diarrheal

illness and/or upper respiratory tract infection , he has failed to provide evidence that she had either or that she had either before the onset of petitioner’s GBS , and therefore, has failed to prove that petitioner’s GBS was caused by something other than her vac cination.

On her admission to the hospital on July 18, petitioner was assessed by physicians and

nurses. The se assessment s have no reference to diarrhea. Likewise, p etit i oner’s history was taken by several health care providers. There is no mention of a diarrheal illness in the histories taken by any of the ph ysicians or other health care providers who saw petitioner the first several days of her hospital stay. On July 2 3, there is a reference to “ [ a ] cute diarrhea.” Pet. Ex. 5 at 302. However, on July 24, the records note that petitioner’s diarrhea had improved. Id. at 296.

Most importantly, o n July 25, 2017, Dr. Gaeta documented that he questioned one of petitioner ’s daughter about whether petitioner had diarrhea prior to her admission. Petitioner’s daughter reported that her mother had a history of irritable bowel syndrome ; however, her mother did not complain of loose stools or worsening bowel movements prior to her hospitalization. So, while Dr. Chaudhry is correct in noting that petitioner had diarrhea in the hospital, Dr. Gaeta specifically asked whether peti ti on e r had any diarrheal illness prior to her hospital admission and the answer was no. Further, t he re is no indication that any of petitioner’s physicians attributed her GBS to the diarrhea petitioner may have had after she was admitted to the hospital.

Moving to the issue of upper respiratory infection, Dr. Chaudhry cites to a declaration

from one of petitioner’s daughters and petitioner’s medical records to support his opinion that an44 upper respiratory infection caused petitioner’s GBS. Petitioner’s da ughter , Erin Fortunato,

submitted a declaration in which s he describes h er mother’s “ labored breathing ” and “trouble breathing.” Pet. Ex. 17 at ¶¶ 15, 17 . The medical records cited by Dr. Chaudhry include a consultation note on July 18, 2017, in which Dr. Fix writes, “ [ s ] he reports she was diagnosed with pneumonia last week and has not fully recovered her strength and energy.” Pet. Ex. 5 at 149. However, in that same note, Dr. Fix wrote that peti tioner did not report fever or chills, and she had no pleurisy. Petitioner’s respiratory rate and oxygen saturation was normal. Her l ung sounds were clear. The reference in Dr. Fix’s note about petitioner’s report of having pneumonia

the week before her hospitalization appears to be the only one of its kind. There is no other

evidence to corroborate this statement. Instead, all the other records consistently state that petitioner reported that she had a pneumonia vaccine th e week before she came to the hospital

. And in fact, on July 23, Dr. Fix wrote, “[i]t is now learned that apparently [petitioner] received a pneumonia vaccine 1 week prior to admission .” Id. at 303.

Additionally

, on July 18 , shortly after petitioner arrived at the hospital, Ms. Maynard

wrote that the petitioner “report[ed] a progressive, generalized weakness over 1 week after receiving pneumonia vaccine.” Pet. Ex. 5 at 80. P etitioner was evaluated by Ms. Mueller

, an OT, who noted petitioner’s “weakness started after receivi ng a [ pneumonia ] shot several days ago.” Id. at 96. PA Mr. Vo wrote, “since she received her pneumo [nia] vaccine a week ago

. . . , she started not feeling very well.” Id. at 108. These records all consistently document that petitioner reported feeling bad following her pneumonia vaccine, not that she had been ill with pneumonia or diagnosed with pneumonia.

Further, there are no records from any health care provider evidencing that petitioner sought treatment for an upper respiratory infection or was diagnosed with any infection or illness prior to her hospitalization.

In support of his opinion , Dr. Chaudhry cites records of a pulmonary consult and treatment with IV Rocephin. Resp. Ex. A at 15 ( citing Pet. Ex. 6 at 121 ) . However, the records do not suggest that petitioner had an upper respiratory infection prior to her hospital ization

. A

chest X

- ray done on admission on July 18 showed no acute abnormality. The physical

examinations on admi ssion reveal ed clear lung sounds. However, after petitioner had been hospitalized for approximately six days

, a pulmonary consult was done by Dr. Patel on July 24,

2017 . He observed decreased breath sounds. He assessed petitioner with respiratory

insuff iciency and atelectasis and diagnosed her with “lower respiratory infection.” Pet. Ex. 5 at

1 4 1

. There is no evidence that petitioner had an upper respiratory infection prior to or on her

admission to the hospital . Instead, all of the evidence points to a lower respiratory illness which petitioner may have developed well after her admission to the hospital. Therefore, there is no

evidence of an antecedent infection which could have been the cause of her GBS.

Dr. Chaudhry also opines that other causes, such as hypophosphatemia and hypokalemia

, contributed to petitioner’s symptoms. While Dr. Chaudhry opines that low levels of phosphate and potassium “contributed” to petitioner’s condition, he does not opine that they likely caused

her GBS.45 During her hospitalization, petitioner underwent diagnostic studies of her CSF to investigate the cause of her GBS. The studies were all negative for any other cause. The only causal association documented in the petitioner’s medical record was her P revnar 13 vaccine.

In conclusion, the undersigned finds that p etitioner has proven by preponderant evidence a logical sequence of cause and effect establishing that the Prevnar 13 vaccination caused her

GBS and has satisfied the second Althen prong.

3. 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 phrase has been

defined as a “medically acceptable temporal relationship.” Id. The petition er must offer “preponderant proof that the onset of symptoms occurred within a timeframe which, given the medical understanding of the disease’s etiology, it is medically acceptable to infer causation

- in

fact.” de Bazan v. Sec’y of Health & Hum. Servs. , 5 39 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for what is a medically acceptable time frame must also coincide with the theory of how the relevant vaccine can cause the injury alleged (under Althen Prong One). Id. ; Koehn v. Sec’y of Health & Hum. Servs. , 773 F.3d 1239, 1243 (Fed. Cir. 2014); Shapiro v. Sec’y of

Health & Hum. Servs. , 101 Fed. Cl. 532, 542 (2011), recons. den’d after remand , 105 Fed. Cl. 353 (2012), aff’d mem. , 503 F. App’x 952 (Fed. Cir. 2013).

The respondent’ s experts do not disagree that there is a temporal association between petit i oner’s vaccination and onset of her GBS. Dr. Chaudhry does not offer an opinion on the issue of temporal association. D r. Whitton states that proof of a temporal association “is not proof of causation.” Resp. Ex. D at 16

.

On July 18, petitioner was evaluated by numerous medical professionals and reported an

onset of weakness after her Prevnar 13 vaccine. P etitioner “ report [ed] a progressive, generalized

weakness over 1 week a fter receiving pneumonia vaccine” to Nurse Maynard. Pet. Ex. 5 at 80.

D uring an occupational therapy evaluation, “[petitioner] state[ed] her weakness started after receiving a [pneumonia] shot several days ago.” Id. at 96. A dditionally, petitioner reported to

Mr. Vo that she did not feel well “since she received her pneumo[nia] vaccine a week ago ” and that she developed acute weakness the ni ght of July 17. Id. at 108. This history provided by petitioner when she presented to the hospital on July 18 places onset of extremity weakness approximately one week post

- vaccination.

On July 21, Mr. Foster notes t hat peti tioner reported her “legs started to feel weak and heavy and walking became difficult” this week. Pet. Ex. 5 at 143. P etit i o ner reported that “during this admission [,] her symptoms have steadily worsened to the point that she does not feel

she can stand or walk at all.” Id

. Physical exam at that time revealed that petitioner’s sensory perception was decreased in a stocking pattern bilaterally, and her reflexes were diminished to

tra c e to 1+ and symmetrical. EMG performed on July 24 confirmed the diagnosis of GBS

. Additio nally, CSF revealed cytoalbuminologic dissociation, with an elevated protein of 112 mg/dL (normal 15

- 40)

.46 Based on this timeline, the onset of petitioner’s weakness was approximately one week after vaccination, or around July 14, and her weakness and ab normal physician exam ination on July 21 were characteristic of GBS. Thus, the range for onset is from July 14 to July 21, one to two weeks following vaccination

. Although petitioner’s initial presentation on July 18 at admission was not clearly GBS, by July 21, CVA and TIA had been ruled out

, and petitioner’s

assessment was bilateral lower extremity weakness. And by July 24, petitioner’s GBS diagnosis

was confirmed

.

This time frame of one to two weeks post

- vaccination is appropriate given the theory of molecular mimicry, as demonstrated in the Haber et al. article , which found 11 cases of GBS following Prevnar 13 vaccine, with a median onset interval of 9 days.

This temporal association is also consistent with the onset period of 3 to 42 days as set
fo rth in the Vaccine Injury Table for GBS following influenza vaccination. 42 C.F.R. § 100.3(a)(XIV)(D).

Further, this time frame has been acknowledged as appropriate in other V accine P rogram cases in which molecular mimicry has been proffered as the causal mechanism. See, e.g.

, Koller

, 2021 WL 5027947, at *23 (finding a GBS onset of 12 days after Prevnar 13 vaccination to be “within the medically accepted timeframe consistent with peti tioner’s theory of molecular mimicry [and] that has been accepted in other Vaccine Program cases

. ”); Barone , 2014 WL 6834557, at *13 (“[S]pecial masters have never gone beyond a two

- month (meaning eight week) interval in holding that a vaccination caused a demyelinating illness.”).

Therefore, undersigned finds that petitioner has met her burden of proof as to Althen Prong Three.

V. 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. 199 4), rev’d on other grounds sub

nom. , Shalala v. Whitecotton , 514 U.S. 268 (1995); see also Walther , 485 F.3d at 1151. As discussed above in the analysis related to Althen Prong Two, the undersigned found respondent

failed to establish evidence to show tha t petitioner’s GBS 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

Based on the record as a whole

, and for the reasons discussed above

, the undersigned

finds t here is preponderant evidence to satisfy all three Althen prongs and to establish that

p etitioner’s Prevnar 13 vaccination caused h er GBS

. Thus, the undersigned finds that p etitioner is entitled to compensation. A separate damages order will issue.47 IT IS SO ORDERED.

s/Nora Beth Dorsey Nora Beth Dorsey Special Master