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# In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS Filed: May 13, 2014

************************************* PUBLISHED CASSANDRA BURCHETT, *

* No. 12-119V Petitioner, * Special Master Dorsey

* v. * Entitlement denied; Human Papillomavirus * Vaccine (“HPV”); Gardasil; Guillain-Barré SECRETARY OF HEALTH * Syndrome (“GBS”); Alternative Causation; AND HUMAN SERVICES, * Significant Aggravation; Gastroenteritis; * Upper Respiratory Infection (“URI”). Respondent. *

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

Mark Theodore Sadaka, Esq., Englewood, NJ, for petitioner. Darryl J. Wishard, U.S. Department of Justice, Washington, DC, for respondent.

DECISION DENYING ENTITLEMENT 1

I. Introduction

On February 22, 2012, Cassandra Burchett (“petitioner”) filed a petition for compensation under the National Vaccine Inju ry Compensation Program (“the Program”) 2 in which she alleged that a human papillomavirus (“HPV” or “Gardasil”) vaccine she received on March 26, 2010, caused her to develop Guillain-Barré Syndrome (“GBS”). Petition (“Pet.”) at 1- 2. Respondent recommended against compensati on, arguing that petitioner had not presented

1 Because this published decision contains a reason ed explanation for the action in this case, the undersigned intends to post this decision on the website of the United States Court of Federal Claims, in accordance with the E-Government Act of 2002 § 205, 44 U.S.C. § 3501 (2006). In accordance with the Vaccine Rules, each party has 14 days within which to request redaction “of any information furnished by that party: (1) that is a trade secret or co mmercial or financial in substance and is priv ileged or confidential; or (2) that includes medical files or similar files, the

disclosure of which would const itute a clearly unwarra nted invasion of privacy.” Vaccine Rule 18(b). Further, consistent with the rule requ irement, a motion for redaction must include a proposed redacted decision. If, upon review, the undersigned agrees that the iden tified material fits within the requirements of that provision, such material will be deleted from public access.

2 The Program comprises Part 2 of the Na tional Childhood Vaccine Injury Act of 1986, 42 U.S.C. §§ 300aa-10 et seq. (“the Act”). Hereafter, individual section references will be to 42 U.S.C. § 300aa.2 adequate evidence to show that the Gardasil vaccine had caused her GBS. See Respondent’s Report (“Resp’t’s Rep’t), filed July 11, 2012, at 8- 15. Further, respondent alleged that petitioner had an antecedent gastrointestinal and/or uppe r respiratory infection which “support[ed] a viral

or infectious basis for the onset of [petitioner’s] GBS.” Id. at 10. The parties submitted expert reports and an entitlement hearing was he ld in Washington, DC, on October 9, 2013, during which the parties’ experts test ified. Petitioner filed her pos t-hearing brief on December 13, 2013, and respondent filed her post-hearing brief on January 6, 2014. This matter is now ripe for adjudication.

Respondent does not dispute that petitioner was diagnosed with GBS on April 1, 2010. See Joint Submission, dated September 4, 2013 (“Jt . Sub.”) at 2. The issues to be decided, therefore, are: (1) whether peti tioner has presented preponderant evidence that the HPV vaccine she received on March 26, 2010, was a substantial c ontributing factor to th e onset of her GBS, and (2) even if so, whether respondent has presen ted preponderant eviden ce that an alternative cause, such as antecedent infection, was the sole factor for her GBS. See Jt. Sub. at 2-3.

After a review of the entire record, see § 300aa-13(a)(1), the undersigned finds that petitioner has failed to provide pr eponderant evidence that the Gardasil vaccine caused her GBS. Because petitioner did not meet her burden of proof on causation, respondent does not have the burden of establishing a factor unrelated to the vaccination caused petitioner’s injuries. See Doe v. Sec’y of Health & Human Servs., 601 F.3d 1349, 1359 (Fed. Cir. 2010) (“[petitioner] Doe never established a prima facie case, so the bur den (and attendant restrictions on what ‘factors unrelated’ the government could argue) never shif ted”). Nevertheless, respondent has proven by preponderant evidence an alternative cause of pet itioner’s GBS, namely, an antecedent infection.

Therefore, even if petitioner had established her case by a preponderance of the evidence, her arguments fail because respondent has proven that petitioner’s anteced ent infection, not her vaccination, was the sole cause of her GBS. Accordingly, petitione r is not entitled to compensation and her petition must be dismissed.

II. Factual Background

A. Issues to be Decided

Prior to the hearing, the part ies filed a joint submission identifying (1) facts not in dispute; (2) facts in dispute; (3) issues not in dispute; and (4) issues in dispute. Jt. Sub. at 1-2.

These are addressed in turn below.

i. Facts Not In Dispute

Petitioner had her first episode of GBS when she was a child, and that episode of GBS is not in dispute. She was diagnosed with GBS on November 29, 1999, when petitioner was five years old. Jt. Sub. at 1.

The parties also stipulate th at petitioner was diagnosed with and treated for viral gastroenteritis on March 19, 2010. Jt. Sub. at 1. Petitioner received the subject Gardasil3 vaccination on March 26, 2010, at the office of he r primary care physician, Dr. Andrew Gellady. Id. On March 26, 2010, the day that the vaccine was administered, Dr. Gellady also diagnosed petitioner with “possible bacterial co njunctivitis bilaterally.” Id.

On March 30, 2010, petitioner saw Dr. Ge llady for headache, numbness of the extremities, and body aches that began on March 28, 2010. Id. Dr. Gellady’s assessment, based on these symptoms, was “reac tion HPV vaccine – arthralgia 3 or early viral.” On March 31, 2010, petitioner presented to Dr. Gellady with si gnificant pain, inability to walk, extremity numbness, muscle cramping, and weakness. Jt. Sub. at 1. At this point, Dr. Gellady was concerned about GBS, questioned whether petiti oner’s symptoms were secondary to the HPV vaccine, ordered lab tests, and started petitioner on analgesics. Id.

On April 1, 2010, petitioner was admitted to All Children’s Hosp ital (“ACH”) “with a history of upper respiratory inf ection three weeks prior, acute ga stroenteritis two weeks prior, and receipt of the HPV vaccine on March 26, 2 010 .... a four-day history of progressive body muscle weakness, trouble walking, and a headache .... [as well as] emesis for the past day” Jt. Sub. at 2. At ACH, petitioner underwent a lumbar puncture to obtain a ce rebral spinal fluid (CSF) sample. Assessment at th at time was “lower extremity weakness, absent deep tendon reflexes, intact sensation, incr eased protein in the CSF, findi ngs which are consistent with Guillain-Barré syndrome...secondary to her recen t viral illness and of note she did have a Gardasil vaccine 1 week ago.” Id.; Petitioner’s Exhibit (“Pet’r’s Ex.”) 1.7 at 466. Petitioner was started on IVIG therapy. Jt. Sub. at 2.

Finally, the parties stipulate that petitione r was treated by Dr. Bunch, a neurologist, while hospitalized at ACH; that she developed a s yndrome of inappropriate antidiuretic hormone secretion (SIADH), hemolytic an emia, adverse effects attribut able to the IVIG treatment requiring a transfusion, and that he r discharge diagnosis was GBS. Jt. Sub. 2; Pet’r’s Ex. 1.7 at 471-72; Pet’r’s Ex. 1.8 at 539, 541-42.

ii. Facts in Dispute

The parties dispute whether petitioner suffe red from an upper respiratory infection between March 1 and March 19, 2010.

iii. Issues Not in Dispute

The parties stipulate that peti tioner received a vaccine as set forth on the Vaccine Injury Table; that she was vaccinated in the United States; that she wa s diagnosed with GBS on April 1, 2010; that she suffered from the residual effects of her GBS for more than 6 months; and that she has not previously collected an award or set tlement in a civil acti on regarding her alleged vaccine injury of GBS. Jt. Sub. at 2.

3 “Arthralgia” is defined as “pai n in a joint.” Dorland’s Illust rated Medical Dictionary (32d ed. 2012) (“Dorland’s”) at 150.4 iv. Issues in Dispute

The parties dispute whether petitioner has pr esented preponderant evidence under Althen v. Sec’y of Health & Human Servs., 418 F.3d 1275, 1278 (Fed. Cir. 2005), that the HPV vaccine she received on March 26, 2010, was a substantial f actor in causing her to develop GBS that was diagnosed on April 1, 2010. Jt. Sub. at 2. Moreover, assuming petitioner has proven a prima facie case under Althen, the partie s dispute whether respondent has presented preponderant

evidence “that a viral infection wa s the sole substantial factor for her GBS.” Id. at 3.

B. Additional Relevan t Medical History

In addition to the facts to which the parties stipulated, the followi ng facts are relevant. Some of the above facts are repeated to provide context and continuity.

Petitioner was born full term on August 13, 1994, and had no chronic medical problems in early childhood. Pet. at 1; Pet’r’s Ex. 1.9 at 630. In November of 1999, when she was five years old, petitioner began experiencing lower ex tremity weakness which caused her to limp, to fall down repeatedly, and to be unable to get up after falling. Pet’r’s Ex. 1.9 at 628. On November 29, 1999, petitioner was admitted to ACH, where she was started on IVIG therapy. Id. After 4 days of this therapy, petitioner’s neurologic deficits bega n to diminish and she regained the reflexes and strength in her legs . Id. at 628-29. She was discharged on December 2, 1999, with a diagnosis of GBS. Id. at 628. Ho spital records note that petitioner had suffered from an upper respiratory trac t infection several weeks prior to her admission. Id. at 628. A lumbar puncture with CSF analysis revealed elev ated protein level of 199 (normal 15-45). Id. at

643.

For the next ten years, petitioner had period ic infections, but there is no indication in her medical records that her GBS symptoms recurr ed. For example, on May 22, 2007, when she was 12 years old, petitioner was diagnos ed with tonsillitis. See, Tr. 39-41; Pet’r’s Ex. 2.1 at 14. And on November 18, 2009, when she was 15, petitioner was diagnosed with a “viral syndrome.” Ex.

2.1 at 11.

Petitioner was diagnosed with and treated for viral gastroenteritis by Dr. Gellady on March 19, 2010. Ex. 2.1 at 10. Her symptoms included vomiting, diarrhea, and headaches. She denied cough or head congestion. Id. On March 26, 2010, petitioner presented to Dr. Gellady’s office with red eyes and was diagnosed with possibl e “bilateral conjunctivitis bilaterally.” Id. at 9. Antibiotic eye drops were prescribed. Jt. Sub. at 1; Pet’r’s Ex. 2 at 9. At that visit on March 26, 2010, petitioner received her firs t Gardasil vaccine. Id.

Four days later, Tuesday, March 30, 2010, peti tioner presented to Dr . Gellady. Pet’r’s Ex. 2.1 at 7. Her symptoms were noted as beginni ng on “Sunday [March 28, 2010] – Headache; feet started going numb. Whole body aches – muscles. Hips and back. Both hands numb – tingles. Feet also.” Id. at 7. Examination showed 1 + deep tendon reflexes in the arms and knees and 1⁄2

+ in the ankles with muscle stre ngth 5/5. Id. Sensation in her feet was intact. Dr. Gellady’s

assessment was “reaction HPV vaccine - ar thralgia early viral.” Id.5 The next day, March 31, 2010, petitioner return ed to see Dr. Gellady. Pet’r’s Ex. 2.1 at 6. Dr. Gellady noted that petitioner was “in a lot of pain. Can’t walk. Hands and feet are numb. Back muscles are cramping. Legs are very sore .... [a]rms slightly sore. Can’t bend over to

touch her toes.” Id. Dr. Gella dy also noted that petitioner had “some nasal congestion”. Id. A neurological examination revealed that petiti oner had no deep tendon reflexes, though it is not clear what area was tested. Dr. Gellady’s a ssessment was “myalgia weakness” and he documented “HPV?”. Id. The exact wording of Dr. Gellady’s notes from March 31, 2010, is unclear but the parties agree that he appears to have considered the HPV vaccine as a possible cause of petitioner’s symptoms. Dr. Gellady also documented that he doubted that petitioner had

a recurrence of her GBS. Id.

On April 1, 2010, petitioner’s condition worsened and she was admitted to ACH. Pet’r’s

Ex. 1.7 at 464. Initial handwritt en patient history and physical documented that “3 wks (weeks)

ago → URI sx (symptoms) → cough/rhinnhea [sic][rhinorrhea]”. Pe’t’r’s Ex. 1.9 at 608. The diagnosis was GBS, “possibly 2° to recent Giardi sil [sic] vaccine and/or recent URI/AGE.” Id. at 611. The author’s sign ature is illegible.

A history and physical admission note by Dr. Leslie F. Carroll on April 1, 2010, documented the following pertinent history:

This is a 15-year-old...with a 4-day hist ory of progressive body muscle weakness accompanied with trouble walking, headache, and emesis...Of note, she received a Gardasil vaccine on 03/26/2010 and 2 days follo wing started to have severe headaches with lower back pain. On the following day, the patient experienced trouble walking and described pain in her feet associated with numbness and tingling. She had URI symptoms 3 weeks ago and acute gastroen teritis 2 weeks ago which lasted for 24 hours...lumbar puncture...revealed C SF protein level of 210.

Pet’r’s Ex. 1.7 at 464-65.

Dr. Carroll performed a neurologic exam which showed that petitioner’s upper extremities had strength 5/5 bilaterally with reflex es 2+ and symmetric, but no reflexes could be obtained in the lower extremities and motor strength in the lower extremities was diminished at

3/5 to 4/5. Pet’r’s Ex. 1.7 at 466. Dr. Carroll ’s impression was GBS. “This may be secondary

to her recent viral illness and of note she did ha ve a Gardasil vaccine 1 week ago.” Id. Dr. Carroll order IVIG therapy and a neurology consult. Id.

A neurology consultation was performed on April 2, 2010, by Dr. Shirley Terri Bunch. Pet’r’s Ex. 1.7 at 471. Dr. Bunch noted that pe titioner had a history of a URI 3 weeks ago, and gastroenteritis symptoms lasting for 24 hours two weeks prior to admission. Id. at 472. Dr. Bunch also noted that petitioner had received the Gardasil vaccine on March 26, 2010, and that 2 days later she began having headaches with low back pain. Id. Dr. Bunch considered the possibility of recurrent GBS and ordered that the IVIG be conti nued. Id. at 472-73.

On April 4, 2010, Dr. Bunch documented that petitioner presented with “ascending weakness and loss of deep tendon reflexes after 2 viral illnesses in quick succession along with a6 Gardasil vaccination.” Pet’r’s Ex. 1.8 at 535. On April 7, 2010, Dr. Bunch noted that petitioner developed GBS, “thought to be related to a Gard asil infection.” Id. at 528. And on April 9, 2010, Dr. Bunch wrote that petitione r “lost her reflexes...approximate ly 5 days after receiving a

Gardasil immunization.” Id. at 529.

Petitioner was discharged from the hosp ital on April 15, 2010, and was ordered to continue with physical and occupational therap y. Pet’r’s Ex. 1.8 at 543, 562. The discharge summary was documented by Dr. Stefany B. Honi gbaum, who wrote that petitioner had been admitted with a “presumed diagnosis of [GBS], given her CSF findings. This was thought to possibly be secondary to her recent URI illness, as well as her acute gastro and perhaps in part to

the Gardasil vaccine received 1 w eek prior to this.” Id. at 541. On discharge, petitioner was alert and oriented with normal speech. Id. at 543. But the deep tendon reflexes of both her upper and lower extremities had not returned, and her ga it was unsteady, although she was able to walk

with the aid of a walker. Id.

Petitioner saw Dr. Bunch for a follo w-up office visit on May 6, 2010, for ongoing management of her GBS. Pet’r’s Ex. 3 at 4. At this visit, Dr. Bunch documented that petitioner had GBS “secondary to a [sic] immunization with gardicil [sic].” Id. On June 10, 2010, petitioner returned to see Dr. Bunch, who noted that petitioner was able to walk independently in the house, but otherwise still required the use of her walker. Id. at 1. She continued to have physical and occupational therapy. Petitioner’s deep tendon reflexes and motor strength had improved. Id. at 2. By July 27, 2010, petitione r’s condition had vastly improved. Her gait was normal and the strength in her upper extremities had returned to 5/5 and the strength in her lower extremities was improved at 4/ 5. Pet’r’s Ex. 8 at 3.

C. Resolution of Facts In Dispute

The parties dispute whether petitioner suffe red from an upper respiratory infection between March 1 and March 19, 2010. Based on a review of the record s and the testimony at hearing, the undersigned finds th at petitioner did suffer from an upper respiratory infection approximately three weeks prior to the onset of her GBS. See Jt. Sub. at 2. On April 1, 2010, petitioner was admitted to ACH “with a history of upper respiratory infect ion three weeks prior, acute gastroenteritis two weeks prior, and r eceipt of the HPV vaccine on March 26, 2010 ....”); Pet’r’s Ex. 1.9 at 628 (hospital re cords note that petitioner had su ffered from an upper respiratory

tract infection seve ral weeks prior to her admission); Pe t’r’s Ex. 1.7 at 472 (Dr. Terri Bunch, petitioner’s treating neurologi st noted in her April 2, 2010 neurology consultation that “[a]pproximately 3 weeks ago, [petitioner] had wh at was thought to be a URI and 2 weeks ago had gastroenteritis symptoms la sting for approximately 24 hours.”); Pet’r’s Ex. 1.8 at 541. (In the ACH discharge summary, Dr. Stefany Honigbaum noted that “[petitioner] was admitted to ACH with a presumed diagnosis of Guillain-Barré syndrome, given her CSF findings. This was thought to possibly be secondary to her recent UR I illness, as well as her acute gastro and perhaps in part to the Gardacil [sic] vaccine rece ived 1 week prior to this”); Pet’r’s Ex. 10 at 1 (On March 19, 2010, petitioner had symptoms of a “diffuse viral infec tion, initially with symptoms of URI and subsequently with gastroen teritis”). While the undersigned finds that petitioner suffered from an upper respiratory infe ction approximately thre e weeks prior to the7 onset of her GBS, the undersigned does not pinp oint an exact date upon which the onset of the upper respiratory inf ection occurred.

D. Guillain-Barré syndrome

GBS is a “rapidly progressive ascending motor neuron paralysis of unknown etiology, frequently seen after an enteric or re spiratory infection.” Dorland’s at 1832. Individuals afflicted with GBS present:

with parenthesis of the feet, followed by fl accid paralysis of the entire lower limbs, ascending to the trunk, upper limbs, and face; othe r characteristics include slight fever . . . absent or lessened tendon reflexes, and in creased protein in the cerebrospinal fluid without a corresponding increase in cells.

Id.

The cause of GBS has not been definitively established but “[a]n autoimmune mechanism following viral infection has been postulated.” Dorland’s at 1 832. There is an “autoimmune attack on peripheral nerves...thought to be generated by an immune response against components of various stimuli which ...overlap with antigens in the peripher al nerves.” Tr. 19. The condition is rare and is a response to a “vir al syndrome” or “occasionally a vaccination.” Tr.

at 20.

The symptoms of GBS “usually develop over several days.” Tr. 16. The majority of cases are diagnosed based on clinical presentatio n, but electrodiagnostic a nd spinal fluid testing may also confirm the diagnosis. Tr. 18. The onset of the condition is confirmed by objective motor or autonomic dysfunction found on neurolog ical examination, such as loss of deep tendon

reflexes and motor weakness. Tr. 98; Pet’r’s Ex. 14 at 1.

GBS is generally a monophasic illness, meaning that it occurs only once. Tr. 34. There are, however rare, cases of recurre nt GBS. Tr. 34. In a Kaiser Permanente study of 550 verified cases of GBS, there was an incidence of 1.47 cases of GBS per 100,000 persons. Resp’t's Ex. G

at 3. 4 Of those, only six individuals had recurrent GBS (1.1% of the 550). Id. Of the 550 cases of GBS, 18 had onset within six weeks of a trival ent inactivated influenza vaccine. Id. at 1. None of the six persons with r ecurrent GBS had any exposure to v accines within the two months prior to the onset of recurrent GBS. Id.

III. Discussion

The Vaccine Act established the Program to compensate vaccine-related injuries and deaths. § 300aa-10(a). “Congress designed the Vaccine Program to supplement the state law civil tort system as a simple, fair and e xpeditious means for compensating vaccine-related injured persons. The Program was established to award ‘vaccine-injured persons quickly, easily,

44 Roger Baxter et al., “Recurrent Guillain-B arré Syndrome Following Vaccination,” 54(6) Clinical Infectious Diseases 800-04 (2012).8 and with certainty and generosity.’” Rooks v. Sec’y of Health & Human Servs., 35 Fed. Cl. 1, 7 (1996) (quoting H.R. Rep. No. 908 at 3, repr inted in 1986 U.S.C.C.A.N. at 6287, 6344).

A. Standards for Adjudication

Petitioner’s burden of proof is a preponderan ce of the evidence. § 300aa-13(a)(1). The preponderance of the evidence standard, in turn, has been interpreted to mean that a fact is more likely than not. Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1322 n. 2 (Fed. Cir. 2010). Proof of medical cer tainty is not required. Bun ting v. Sec’y of Health & Human Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). A petitione r who satisfies this burden is entitled to compensation unless the government can prove, by a preponderance of the evidence, that the vaccinee’s injury is “due to f actors unrelated to the administration of the vaccine.” § 300aa13(a)(1)(B).

B. Petitioner’s Prima Facie Case under Althen

To receive compensation under the Program, petitioner must prove either: (1) that she suffered a “Table Injury”—i.e., an injury list ed on the Vaccine Injury Table—corresponding to a vaccine that she received, or (2) that she suffere d an injury that was actually caused by the HPV vaccine. See §§ 300aa-13(a)(1)(A) and 11(c)(1); Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1319-20 (Fed. Cir. 2006). Petiti oner must show that the vaccine was “not only a but-for cause of the injury but also a subs tantial factor in bringi ng about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface v. S ec’y of Health & Human Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999)).

Because petitioner does not allege she suffere d a Table injury, she must prove that the HPV vaccine she received caused her injury. To do so, she must establish, by preponderant evidence: (1) a medical theory causally connec ting the vaccine and her injury (“Althen Prong One”); (2) a logical sequence of cause and effect showing that the vaccine was the reason for her injury (“Althen Prong Two”); and (3) a showing of a proximate temporal relationship between the vaccine and her injury (“A lthen Prong Three”). Althen, 4 18 F.3d at 1278; § 300aa–13(a)(1).

The causation theory must relate to the inju ry alleged. Thus, a petitioner must provide a reputable medical or scientific explanation that pertains specif ically to the vaccinee’s case, although the explanation need only be “legally probabl e, not medically or scie ntifically certain.” Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994). Petitioner cannot establish entitlement to compensation base d solely on her assertio ns. Rather, a vaccine claim must be supported either by medical reco rds or by the opinion of a medical doctor. § 300aa-13(a)(1). In determining whether petitioner is entitled to compensa tion, the special master

shall consider all material c ontained in the record, § 300aa- 13(b)(1), including “any . . . conclusion, [or] medical judgment . . . which is cont ained in the record regarding . . . causation . . . of the petitioner’s illness.” § 300aa-13(b)(1)(A). The undersigned must weigh the submitted evidence and the testimony of the pa rties’ offered experts and rule in petitioner’s favor when the evidence weighs in his favor. See Moberly, 592 F.3d at 1325-26 (“Finders of fact are entitled— indeed, expected—to make determin ations as to the reliability of the evidence presented to them and, if appropriate, as to the credibility of the persons presenting that evidence”); Althen, 418 F.3d at 1280-81 (“close calls” are re solved in petitioner’s favor).9 (1) Althen Prong One: Petitioner’s Medical Theory

Under Althen Prong One, petitioner must se t forth a medical theory explaining how the received vaccine could have caused her alleged injury. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1375 (Fed. Cir. 2009). Under th is prong, petitioner must make a showing

that the received vaccine can cause the alleged injury. Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355-56 (Fed. Cir. 2006).

Petitioner’s theory of causation must be in formed by a “sound and reliable medical or scientific explanation.” Knudsen, 35 F.3d at 548; see also Veryzer v. Sec’y of Health & Human Servs., 98 Fed. Cl. 214, 223 (2011) (noting thatspecial masters are bound by both § 300aa13(b)(1) and Vaccine Rule 8(b)(1) to consider only evidence that is both “relevant” and “reliable”). If petitioner reli es upon a medical opinion to suppor t her theory, the basis for the opinion and the reliability of that basis must be considered in the determination of how much weight to afford the offered opinion. See Broe kelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (“The special mast er’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 & Human Servs., 33 F.3d 1375, 1377 n.6 (Fed. Cir. 1994) (“An expert opinion is no better than the soundness of the reasons supporting it.”) (citing Fehrs v. United States, 620 F.2d 255, 265 (Ct. Cl. 1980)).

a. Petitioner’s Expert, Dr. Allan E. Rubenstein

Dr. Allan E. Rubenstein is a neurologist and c linical professor of ne urology in pediatrics at New York University (NYU) Langone Medical Cent er in New York City. Pet’r’s Ex. 11 at 5; Tr. 6. He obtained his medical degree from Tu fts University Medical School in Boston and completed his internship and neurology reside ncy at Columbia Presbyt erian Medical Center, New York Neurological Institute, New York City. Pet’r’s Ex. 11 at 1; Tr. 7-8. Dr. Rubenstein had postgraduate training in neurogenetics as we ll. Pet’r’s Ex. 11 at 1; Tr. 10. He was an associate professor of neurology at Mt. Sinai School of Medicine from 1974 until 2009, at which

time he moved to the NYU Medical Center. Pet’r’s Ex. 11 at 3; Tr. 8-9. Wh ile at Mt. Sinai, he developed the autonomic function laboratory, and also st arted a clinic for neurofibromatosis, a genetic disease of the nervous system. Id. At Mt . Sinai, he spent approximately 50% of his time seeing and treating patients. I d. At NYU Medical Ce nter, Dr. Rubenstein continues to see patients as well as teach medical students, residents and fellows. Tr. 10. Dr. Rubenstein is board certified in neurology. Pet’r’s Ex. 11 at 1; Tr. 11. He has a faculty a ppointment in pediatric neurology at NYU Medical Center. Pet’r’s Ex. 11 at 5; Tr. 21. He sees adult and pediatric patients in his clinical practice and he has tr eated patients with GBS. Tr. at 21, 23. Dr.

Rubenstein has also authored an article on GBS. 5 Tr. at 23.

5 Dr. Rubenstein has testified in court approximate ly 15 times over the past four years. Tr. 23. In one of those cases, Melnick v. Consolidat ed Edison, 959 N.Y.S. 2d 609 (Sup. Ct. 2013). Dr. Rubenstein’s testimony was found by the court to be unreliable. Tr. 23-24. Dr. Rubenstein opined in that case that a child’s “autism and developmental delay had stemmed from the low birth weight...of the premature birth of the ch ild” triggered by the mother’s “slip and fall accident.” Tr. 24. The judge in the Melnick cas e questioned Dr. Rubenstein about whether there10 Here, Dr. Rubenstein reviewed petitioner’s medical records, includ ing records from her first episode of GBS when she wa s five years old. Pet’r’s Ex. 10 at 3. Dr. Rubenstein agreed that petitioner had an upper resp iratory infection (URI) about two weeks prior to her first episode of GBS in 1999. Id. at 1; Tr. 73. Moving forwar d to 2010, Dr. Rubenstein agreed that on March 19, 2010, when petitioner saw Dr. Gellady, she repor ted that she had been vomiting, and had symptoms of a gastrointestin al infection, beginning on March 18, 2010. Tr. 73. Dr. Rubenstein agreed that petitioner had a diagnos is of gastroenteritis at that time. Tr. 74. Dr. Rubenstein also agreed that petitioner had na sal congestion as noted by Dr. Gellady on March 31, 2010. Tr. 76- 77. And Dr. Rubenstein agreed that petiti oner’s treating physicians reference both upper respiratory and gastrointestinal infections as viral sources for her GBS. Tr. 77.

Dr. Rubenstein’s causation theory in this case is that petitioner had a viral infection (URI and/or GI), that the viral infection initiate d the process of GBS recurrence via molecular mimicry, and that the HPV vaccine also contribu ted to the development of petitioner’s recurrent GBS through some “unclear mechanism.” Tr. 35- 36; 62-63; 72. Dr. Rubens tein testified that Gardasil was “a contributing factor of unclear mech anism, but likely relate d to its induction of [the] immune response.” Tr. 63-64, 112.

In his expert report, Dr . Rubenstein opined that

It is well-known that vaccines can wo rsen or induce problems in patients with autoimmune disease, presumably by presenting an antigen which stimulates an overactive or dysfunctional immune system. In Cassandra’s case she was likely sensitized to an tigens which cross react with CNS nervous systems components at an earl y age, and the subsequent use of Gardasil vaccine, possibly in combina tion with a viral infection, caused a new autoimmune event, resulting in a severe mixed form of GBS.

Pet’r’s Ex. 10 at 2.

Dr. Rubenstein emphasized several times th at he did not know the medical theory whereby petitioner’s recurrent GBS was “stimulated or enhanced or somehow advanced” by the vaccination. Tr. 113. “[S]omehow – and I don’t know exactly how – [the vaccine] likely stimulated the immune system to ...recurrent [GBS ].” Tr. 113. “[T]his patient had an -- as do most if not all patients with [GBS], an exposur e to a virus which, for reasons unclear, as opposed to other viral involvement, somehow had the pot ential to induce an autoimmune response against peripheral nerves and that the vaccination, in the process of promoting an immune response, not necessarily because there is a cr ossreacting antigen to Gardasil . . . . but likely the two – the two

was a precedent for his theory that trauma c ould cause developmental delay. Dr. Rubenstein conceded that there was no such precedent. Tr. 93. Even though Dr. Rubenstein believed that the trauma of the mother’s fall caused her to go into premature labor resu lting in the child being born prematurely, causing the child’s developm ental problems, the j udge “took a very narrow

view” and “threw the case out.” Tr. 93.11 were both likely contributing factors, in my opinion, based upon the temporal relationship to onset.” Tr. 62-63. “[W]hether [the mechanism] is due to stimulating the immune system to respond in a hyperactive way or encouraging the crosstalk between viral- induced responses in myelin components, I don’t know the molecu lar mechanism, and I don’t think that anybody does, but I think that there’s a ny one of a number of possible a nd not unreasonable explanations to provide a theory for why the tw o [events (vaccination and virus)] are not coincidental.” Tr. at

116.

In addition, Dr. Rubenstein tes tified that molecular mimicry di d not play a role between a component of the HPV vaccine and petitioner’s pe ripheral myelin, but rather, any mimicry that

occurred stemmed from a vi ral infection. Tr. at 72.

Petitioner presented no research to support Dr. Rubenstein’s theory that petitioner’s GBS was stimulated or enhanced by the vaccination. Tr . 62-63. Dr. Rubenstein te stified that “there’s no research on such, but likely the two [both viral infection plus vaccination] – the two were both likely contributing factors, in my opinion, based upon the temporal relationship to onset.” Tr.

62-63. Dr. Rubenstein cites an ar ticle by Souayah, see Pet’r’s Ex. 12, 6 for the proposition that “molecular mimicry and other immune system s timulation mechanisms may play a role in mediating GBS after Gardasil vaccination.” Pe t’r’s Ex. 12 at 888; Tr. 118-19. The Souayah

article addresses the relationshi p between GBS and the HPV vaccine based on information from the Vaccine Adverse Event Reporting System (V AERS), but Souayah did not draw conclusions about HPV vaccine-related GBS. In addition, th e Souayah article did not address the theory proposed by Dr. Rubenstein, namely that GBS associated with or caused by antecedent viral exposure may be further stimulated by the HPV vaccine.

Moreover, Dr. Rubenstein conceded that if petitioner had not received the Gardasil vaccination, then his testimony woul d be that petitioner developed recurrent GBS from a viral infection. See Tr. 81, 84-85. Dr. Rubenstein also admitted that, based on his own experience, he has never heard the theory that he proposes in this case, see Tr. 114, nor has he seen GBS following HPV vaccination in his practice. Tr. 120.

b. Respondent’s Expert, Dr. Michael Kohrman

Dr. Michael Kohrman is a pediatric neurologis t at the University of Chicago. Resp’t’s Ex. E at 1; Tr. 132. He obtained his medical de gree from Rush Medical College and completed his internship and neurology training at the Un iversity of Chicago, and had some additional neurophysiology training at the University of Illinoi s in Chicago. Resp’t’s Ex. E at 1-2; Tr. at 132-33. Dr. Kohrman is board certified in pediat rics and neurology, with a special competency in child neurology and added qualifications in clinical neurophysiology and sleep medicine. Resp’t’s Ex. E at 3; Tr. at 132. At the University of Chicago, his work is about 80% clinical and 20% scholarly, and he sees pediat ric patients almost exclusively. Tr. at 133-34. Dr. Kohrman is currently the editor of the Journal of Pediatric Epilepsy and is on the editorial board of three other publications. Resp’t’s Ex. E at 11; Tr. at 134-35. Dr. Kohrman testified that he has seen

6 Souayah et al., “Guillain-Barré syndrome afte r Gardasil vaccination: Data from Vaccine Adverse Event Reporting System 2006-2009,” 29 Vaccine 886-89 (2011).12 over 100 children with GBS over the last 20 years, though he has never seen a case of recurrent GBS. Tr. at 133-34. His primary research ar ea is pediatric epilepsy. Tr. at 135.

Dr. Kohrman opined that petitioner’s recurrent GBS was caused by a viral infection via the theory of molecular mimicry. Tr. 139, 140-41, 145-46. He disagreed with Dr. Rubenstein’s theory that Gardasil can cause an immune enhan cement of virally-induced GBS, and he testified

that he is not aware that such a theory has ever been discus sed in the neurology or pediatric neurology community. Tr. 159. Moreover, he tes tified that there are no animal models to support Dr. Rubenstein’s theory. Tr. 87-88, 160.

Further, as to the HPV vaccine, Dr. Korhma n testified that there is “no evidence of homology...to lead to molecular mimicry to pr oduce [GBS].” Tr. 146; 151. But Dr. Kohrman conceded that he lacks a complete wo rking knowledge on the issue of homology and acknowledged that the medical community has not researched whether there is homology

between certain antecedent infecti ons thought to be causally related to GBS. Tr. 173-74, 175-76.

Based on the findings described in the ar ticle by Slade, Resp’t’s Ex. K at 756, 7 Dr.

Kohrman testified that the incidence of GBS in females ages nine to 26 was lower in patients

who received the HPV vaccine than the risk of GBS in unvaccinated patients, and less than the risk in the general population. Tr. 147-48. Dr. K ohrman disagreed that th e Souayah article cited by Dr. Rubenstein supported petitioner’s theory th at the HPV vaccine was associated with GBS.

Tr. 149. Dr. Korhman also testified that the Slad e article summarizes th e deficiencies of the Souayah article. Id. The article by Slade stat ed that Souayah overestimated the number of Gardasil vaccine doses actually administered and included patients who had symptoms beginning less than three days after vaccination, wh ich did not meet the criteria for acute new onset, which was four to five days. Slade conclu ded that the data referenced by Souayah did not support Souayah’s conclusions that there may be a risk of GBS following HPV vaccination. Tr. 149-50, 152; Resp’t’s Ex. D at 5-6.

In summary, Dr. Korhman disa greed with Dr. Rubenstein’s theory that the HPV vaccine caused a “significant immune stimulus” leading to GBS because there is no increased risk of GBS in patients receiving the HPV vaccine. Dr . Kohrman was not aware of any immune system

stimulation mechanism known to cause GBS after the HPV vaccine. Tr. 152. Dr. Korhman cited the Chao article, Resp’t’s Ex. C, 8 for the proposition that there is no increase in autoimmune markers and in immune signals a ssociated with the HPV vaccine, except for a slightly increased risk of thyroiditi s, which is not relevant to this case. Resp’t’s Ex. D. at 4; Tr.

at 156. Dr. Korhman also cited the Slade article for the propos ition that the HPV vaccine was “remarkably nonreactive” in terms of a ny serious adverse events. Id.

7 Slade at al., “Postlicensure Safety Surveilla nce for Quadrivalent Human Papillomavirus Recombinant Vaccine”, 302( 7) JAMA 750 (Aug. 19, 2009).

8 C. Chao et al., “Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine,” 271 J. Intern. Med. 193-203 (2012).13 c. Petitioner’s Treating Physicians

Several of petitioner’s trea ting physicians documented the te mporal association between the onset of petitioner’s GBS and both the vi ral infections and the HPV vaccination.

Dr. Terri Bunch, petitioner’s treating neurologist at AC H, noted in her April 2, 2010 neurology consultation that “[a]pproximately 3 w eeks ago, [petitioner] had what was thought to be a URI and 2 weeks ago had gastroenteritis sy mptoms lasting for approximately 24 hours. On 3/26/10, she received Gardasil vaccine and 2 days following the vaccination began having headaches with low back pain.” Pet’r’s Ex. 1.7 at 472. On Apr il 3, 2010, in a Neurology Progress Note, Dr. Bunch noted, “[a]pproximately 2 days after her vaccination with Gardasil, she began having numbness and tingling on her feet. She additionally had at least 2 viral syndromes and presented to the emergency room with blurre d vision and weakness in he r legs.” Pet’r’s Ex.

1.8 at 536.

In a Neurology Progress Note on April 4, 2010, Dr. Bunch noted “[t]he patient ... presented with ascending weakness and loss of d eep tendon reflexes after 2 viral illnesses in quick succession along with Gard asil vaccination.” Pet’r’s Ex. 1.8 at 534. In a progress note on April 6, 2010, Dr. Bunch noted that just prior to her first symptoms, petitioner “had 2 significant

viral illnesses and then received her Gardasil vaccination.” Id. A nd on April 7, 2010, Dr. Bunch noted, “[t]he patient is a 15-year-old Caucasia n female who developed a GBS ... thought to be

related to a Gardasil vaccination.” Id. at 528. In an April 9, 2010, Neurology Progress Note, Dr. Bunch noted, “[s]he lost her re flexes both knee, ankle, and ar ms approximately 5 days after receiving a Gardasil immunizati on.” Id. at 529. Finally, on May 6, 2010, Dr. Bunch described petitioner as a “female who is seen in follow up after a presentation [at] all Children’s Hospital with Guillain-Barré syndrome secondary to a[n] immunization with gardicil (sic).” Pet’r’s Ex. 3

at 4.

Similarly, Dr. Leslie F. Carroll noted that petitioner’s GBS “may be secondary to her

recent viral illness and of note she did have a Ga rdasil vaccine 1 week ago.” Pet’r’s Ex. 1.7 at 466. In the ACH discharge summary, Dr. Stef any Honigbaum noted that “[petitioner] was admitted to All Children’s with a presumed di agnosis of Guillain-Barré syndrome, given her CSF findings. This was thought to possibly be secondary to her rece nt URI illness, as well as her acute gastro and perhaps in part to the Gardacil [sic] vaccine received 1 week prior to this.”

Pet’r’s Ex. 1.8 at 541.

During the hearing, Dr. Kohrman called into question the treating phys icians’ findings as to the statements suggesting an association betw een the vaccine and petitioner’s GBS, suggesting that Dr. Bunch “may not have read the entire chart prior to writing he r [progress notes],” and criticizing Dr. Honigbaum because she ordered prednisone for petitioner even though it has been known to worsen GBS symptoms. Tr. 178-80.

d. Evaluation of the Evidence

Althen Prong One requires a petitioner to se t forth a medical theory explaining how the received vaccine could have caused the alleged in jury. In this case, pe titioner has failed to14 postulate a theory by which the HPV vaccine allegedly “enhanced” her pre-existing virallyinduced recurrent GBS. In attempting to articul ate the “enhancement” aspect of his causation theory, Dr. Rubenstein conceded that his theo ry was unknown and that the HPV vaccine was “a contributing factor [to peti tioner’s immune response] of unclear mechanism.” Tr. 63.

Likewise, none of petitioner’s treating physicians documented any theory or mechanism whereby the HPV vaccine enhanced the viral infec tions leading to petitioner’s recurrent GBS, as proposed by Dr. Rubenstein. Nor did any treatin g physician set forth any other theory for how the HPV vaccination alone, or in concert with th e viral infections, caused petitioner’s GBS. The treating physicians merely documented a temporal association between peti tioner’s receipt of the

HPV vaccine and the onset of her recurrent GBS. Dr. Kohrman testified that he has not heard of Dr. Rubenstein’s “enhancement” theory disc ussed in the neurology or pediatric neurology community, Tr. 159, and that there are no animal models to support the theory. Tr. 87-88, 160.

Without evidence of a medical theory, the te mporal relationship is not enough. See Grant v. Sec’y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992) (holding “a proximate temporal association alone does not suffice to s how a causal link between the vaccination and the injury”). For all of these reasons, petitioner has not established by a preponderance of the evidence a medical theory explaining how the HP V vaccine can cause GBS in a patient who had

antecedent viral infections.

(2) Althen Prong Two: Logical Sequence of Cause and Effect

Under Althen Prong Two, a petitioner must pr ove 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 (citing Althen, 418 F.3d at 1278). “Pe titioner 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 (c itations omitted).

a. Petitioner’s Expert, Dr. Rubenstein

In his expert report, Dr. Rubenstein opines th at “it is more likely than not that Gardasil vaccination was the determining event...possibly promoting an autoimmune event initially induced by a viral infection” which led to petitioner’s GBS. Pet’r’s Ex. 10 at 2. He explains that “[i]t is well known that vaccines can worsen or induce probl ems in patients with autoimmune disease, presumably by presenting an antigen wh ich stimulates an overactive or dysfunctional immune system.” Id. As such, petitioner was

likely sensitized to antigens which cross reac t with CNS nervous system components at an early age, and the subsequent use of Gard asil vaccine, possibly in combination with a viral infection, caused a new autoimmune event, resulted in a severe mixed form of GBS.

Id. Based on Dr. Rubenstein’s theory, petitione r had the antecedent viral infection which led to

her recurrent GBS before her va ccination and, thus, she would ha ve developed GBS even if she

had not received the vaccine.15 As discussed in Althen Prong One (above), how ever, Dr. Rubenstein admits in his report that the medical theory by which this event ha ppens is only “possible.” At the hearing, however, Dr. Rubenstein testified that petitioner’s Gardasil vaccine was “more likely than not” and/or “substantial contributing factor” to her recurrent GBS which occurred in March 2010. Tr.

35-36.

Dr. Rubenstein testified that the fact that petitioner had a prior epis ode of GBS put her at risk for recurrence, Tr. 39, and any viral upper respiratory or gast rointestinal infection could be

associated with a recurrence of GBS. Tr. 40. He noted that after petiti oner’s initial episode of GBS, from 1999 until March 2010, she had subsequent viral infections but she did not develop a

recurrence of her GBS. Tr. 40-45.

On March 19, 2010, petitioner had symptoms of a “diffuse viral infection, initially with symptoms of URI and subsequently with gastroente ritis.” Pet’r’s Ex. 10 at 1. On the evening of March 18, 2010, she had vomiting, diarrhea and headache. She was seen by Dr. Gellady on March 19, 2010, and diagnosed with viral gastroente ritis. Pet’r’s Ex. 2.1 at 10; Tr. 44, 74. A week later, on March 26, 2010, petitioner received the HPV vaccine. On that same day, petitioner was noted to have very red eyes and was diagnosed with “possible bacterial conjunctivitis bilaterally.” Pet’r’s Ex. 2.1 at 9. Four days later, on March 30, 2010, Dr. Gellady documented that petitioner had nasal congestion, and exudate and redness of her tonsils (tonsil 1+ exudate and red). Id. at 7. On March 31, 2010, petitioner had some “nasal congestion” and she had developed “diffuse motor weakness and nu mbness.” Pet’r’s Ex. 10 at 1. Petitioner was admitted to the hospital where she was diagnosed with GBS and treated with IVIG. Id.

Based upon the above chronology, Dr. Rubenstein opined that petitioner had her second episode of GBS, “2 weeks post viral symptomatology and within 5 days of Gardasil

vaccination.” Pet’r’s Ex. 10 at 2. Dr. Rubenste in’s opinion that petitioner’s Gardasil vaccine

contributed to her GBS is based on three reasons: (1) Gardasil is a rare but known antecedent to GBS; (2) petitioner’s clinical course following Ga rdasil was “totally different from her first presentation” of GBS; and (3) an onset five days after vaccination is “consistent with previously reported cases of GBS following Gardasil.” Id.

b. Respondent’s Expert, Dr. Kohrman

Dr. Kohrman opined that petitioner’s HPV vaccine did not cause her GBS. Tr. 139. Instead of the vaccination, Dr. Kohrman believed that one of the viral infectio ns that occurred in

the three weeks before onset was the most likel y cause of petitioner’s GBS. Tr. 141. When petitioner had her initial episode of GBS in 1999, the antecedent even t was also a viral infection; namely, an upper respiratory infection. Tr. 141. Dr. Kohrman testified that in someone with recurrent GBS, like petitioner, where a virus initi ated the process, it would be unlikely that a vaccine would play any causal role. Tr. 148. In hi s expert report, Dr. Kohrman states that he can

“find no evidence in the literature that there is a cross reactivity between HPV vaccine and peripheral myelin.” Resp't’s Ex. D at 7. In addition, Dr. Kohrman st ates that there “is no evidence of significant aggravation of [petitioner’s] recurrence of Guillain-Barré Syndrome by the vaccination with Gardasil.” Id. He notes that most of petitioner’s problems during her hospitalization were due to the hi gh doses of IVIG treatment that she received. Id. Other than16 the temporal association between vaccine and GBS, Dr. Kohrman stated that there was no

evidence of a causal rela tionship between petitioner’s vaccine and her GBS. Id.; Tr. 148, 172.

c. Evaluation of the Evidence

Dr. Rubenstein admits that the mechanism is unclear by which the HPV vaccine, in this factual context, can cause GBS, and he could not articulate a logical sequence of cause and effect as to how the vaccine could cause and did cause pe titioner’s recurrent GBS. Dr. Rubenstein did not point to specific facts about petitioner’s clinical course, or to any medical literature, to support his theories. Dr. Rubenstein’s thr ee reasons for why petitioner’s HPV vaccine contributed to her GBS lack foundational support. As for the first reason that Gardasil is a known antecedent to GBS, Dr. Rubenstein relies on the Souayah article. But as noted above, the Souayah article does not speak to the situation where GBS occurs af ter two viral infections and a vaccination. As for his second reason, that peti tioner’s clinical course following Gardasil was “totally different from her first presentation,” Dr. Rubenstein does not ex plain his assertion of how or why petitioner’s second epis ode of GBS was different from he r first episode. Even if one assumes this statement to be true, Dr. Rubens tein does not explain w hy it matters, or how it supports his theory of causation. As for the te mporal association betw een vaccination and onset, this fact alone is insufficient upon which to co nclude that the vaccination caused petitioner’s GBS. See Grant, 956 F.2d at 1148 (Fed. Cir. 199 2) (holding “a proximate temporal association

alone does not suffice to show a causal link between the vaccination and the injury”).

Accordingly, the undersigned finds that pe titioner has failed to provide preponderant evidence that there is a logical sequence of cause and effect s howing that the HPV vaccination was the reason for petitioner’s recurrent episode of GBS.

(3) Althen Prong Three: Proximate Temporal Relationship

Under Althen Prong Three, petitioner must provide “preponderant proof that the onset of symptoms occurred within a timeframe for wh ich, given the understanding of the disorder’s etiology, it is medically acceptable to infer causati on-in-fact.” De Bazan v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1352 (citing Pafford, 451 F.3d at 1358). The acceptable temporal association will vary according to the particular medical theory advanced in the case. See Pafford, 451 F.3d at 1358.

a. Petitioner’s Expert, Dr. Rubenstein

Dr. Rubenstein opined that petitioner had a recurrent episode of GB S “2 weeks post viral symptomatology and within 5 days of Gardasil vacci nation.” Pet’r’s Ex. 10 at 2. Dr. Rubenstein testified that the symptoms of petitioner’s GBS started to develop on March 30, 2010, Tr. 50, 53- 54, and that petitioner had an “objective onset” of GBS on March 31, 2010, when a neurological examination showed that petitioner had no deep tendon reflexes, which would put the onset at five days. Tr. 98-100; Pet’r’s Ex. 2.1 at 6.

In his expert report, Dr. R ubenstein, citing the Souayah artic le, states that the onset of GBS “within 5 days of vaccination is consistent with previously reported cases of GBS following17 Gardasil.” Pet’r’s Exhibit 10 at 2. With a viral gastroenteritis, Dr . Rubenstein also testified that one would expect onset of GBS symptoms within five days to se veral weeks. Tr. 70. In cases of recurrent GBS, however, Dr. Rubens tein testified that onset can be shorter, with a range from two to three days to six weeks. Tr. 68, 71. Dr. Rubenstein did not offer testimony about a medically acceptable timeframe specific to his th eory that petitioner’s GBS was caused by viral infection and enhanced by the Gardasil vaccination.

b. Respondent’s Expert, Dr. Kohrman

Dr. Kohrman testified that typically, in non-recurrent GBS cases, onset is “five-plus” days after an antecedent event. Tr. 153. Dr . Kohrman explained that the immune response requires time for the presentation of an antigen, fo r the antigen to be processed, and for there to be synthesis of antibodies. Tr. 153.

To opine about onset in cases involving recurrent GBS, Dr . Kohrman relied on the Slade article (4-42 days) and the Institu te of Medicine (“IOM”) report (five days to six weeks). Resp’t’s. Ex D at 6-7. Dr. Ko rhman explained that petitioner received her vaccine on March 26, 2010, and began having symptoms on March 28, 2010. He believes that the “two day interval” between petitioner’s vaccination on March 26, 2010, and her first symptoms on March 28, 2010, is too short and inconsistent with the findings in th e above-cited articles regarding onset. Id. at 7. Dr. Korhman opined that the gastroenteritis and URI that occurred in the 2-3 week window prior

to onset are more consistent with th e expected onset time frame. Id.

c. Evaluation of the Evidence

The undersigned finds that the onset of pe titioner’s recurrent GBS was approximately March 31, 2010, when a neurological examination s howed definitive symptoms in that petitioner had no deep tendon reflexes. Thus, onset occurre d approximately three weeks after petitioner’s URI symptoms, two weeks after acu te gastroenteritis, and five days after the HPV vaccination

was administered. These onset timeframes woul d be medically acceptable if petitioner’s GBS were caused by a viral infection via th e mechanism of molecular mimicry.

Here, however, petitioner failed to provi de testimony of a medically acceptable timeframe for onset given petitioner’s theory that both a viral infection and the vaccine played a causal role. Even assuming that the onset would be the same under petitioner’s proposed theory, thus meeting her burden under Althen Prong Three, petitioner has failed to make a prima facie case under Althen Prongs One and Two, and she is therefore not entitled to compensation.

C. Respondent’s Alternative Causation Theory

Petitioner’s medical records establish, and th e parties do not dispute, that petitioner was diagnosed with and treated for viral gastroenteritis on March 19, 2010. See Jt. Sub. at 1; Pet’r’s

Ex. 2 at 10. Petitioner also suffered from a URI th ree weeks prior to the ons et of her GBS. See supra II(C). Respondent and her expert, Dr. Kohr man, consistently maintained that petitioner’s antecedent viral gastroenteritis or upper respir atory tract infection was the sole cause of18 petitioner’s recurrent GBS. See Resp’t’s Pre- Hearing Submission at 15; Resp’t’s Post-Hearing

Brief at 14.

Under the Vaccine Act, compensation shall be awarded where the petitioner demonstrates the requirements set forth under the Act by a pre ponderance of the evidence, and “there is not a preponderance of the evidence that the . . . inju ry . . . is due to factors unrelated to the administration of the vaccine.” § 300aa-13(a )(1)(A)-(B). The Act provides that “factors

unrelated to the administration of the vaccine” are those “which are shown to have been the agent . . . principally responsible for causing the petitioner’s illne ss, disability, injury, condition or death.” Id. § 300aa-13(a)(2)(B). To satisfy her burden of showing an alternative cause of petitioner’s injuries, respondent is “‘required not only to prove the existence of [a factor unrelated], but also to prove by a preponderan ce of the evidence that the [factor unrelated] actually caused’ the alle ged injury.” Knudsen, 35 F.3d at 549. Furthermore, [respondent] . . . . also ha[s] to present sufficient evidence to pr ove that the alternative factor was the sole

substantial factor in br inging about the injury.” Deribeaux v. Sec’y of Health & Human Servs., 717 F.3d 1363, 1367 (Fed. Cir. 2013) (citing de B azan, 539 F.3d at 1354). “Thus to establish alternative causation . . . [respondent] must sati sfy the three prongs of Althen.” Deribeaux v. Sec’y of Health & Human Servs., No. 05-306V , 2011 WL 6935505 (Fed. Cl. Spec. Mstr. Dec. 9, 2011) (citations omitted), aff’ d, 717 F.3d 1363 (Fed. Cir. 2013).

(1) Althen Prong One: Respondent’s Medical Theory

Both parties’ experts agree that a viral in fection initiated petiti oner’s recurrent GBS via molecular mimicry. Tr. 72, 115-16, 161-62. Responde nt’s expert, Dr. Kohrman, further opined that a viral infection was the sole cause of petit ioner’s GBS recurrence, a nd that the HPV vaccine had no causal effect. See Resp’t’s Ex. D at 8; Tr. 140-41. During the hearing, Dr. Kohrman described the molecular mimicry mechanism by wh ich an infection alone can cause GBS. Tr. 144-45. Specifically, Dr. Kohrman testified th at molecular mimicry is sequence and/or conformational homology between an exogenous agen t (foreign antigen) and self antigen leading to the development of tissue damage and clinical disease from antibodies and T cells. Resp’t’s Ex. L at 1. According to Dr. Kohrman, one of petitioner’s antecedent viruses had a homology with her peripheral myelin. Tr. 170. And Dr. Rubenstein conceded that, had no vaccination taken place, his conclusion would also have been that petitioner’s recu rrent GBS stemmed from

a viral infection. Tr. 84-85.

Through testimony and expert reports, both expe rts have identified molecular mimicry as a causal mechanism in this case and have agreed that, after being initiated by an infection, molecular mimicry can lead to recurrent GB S. Accordingly, the undersigned finds that respondent has proven, by a prepon derance of the evidence, that one of petitioner’s viral

infections caused her GBS to recu r. See Resp’t’s Exhibit G at 1. 9

9 Roger Baxter et al., “Recurrent Guillain-B arré Syndrome Following Vaccination,” 54(6) Clinical Infectious Diseases 800-4 (2012).19 (2) Althen Prong Two: Logical Sequence of Cause and Effect

In support of her argument that a viral infect ion was the sole cause of petitioner’s injury, respondent notes that when pe titioner initially contracted GBS in 1999, she had suffered a respiratory infection about two weeks prior. Resp ’t’s Post Hearing Brief at 15; Jt. Sub. at 1. Respondent’s expert, Dr. Kohrman, notes in his re port that recurrent GBS is usually triggered by an upper respiratory infection. Resp’t’s Ex. D at 5 (citing Mossberg article). 10 During the hearing, Dr. Kohrman explained how, through mol ecular mimicry, an upper respiratory infection

could cause GBS. Tr. 144-45. Specifically, Dr. Kohrman testif ied that one of petitioner’s antecedent viruses had a homology with her peri pheral myelin which led to an autoimmune response resulting in GBS. Tr. 170.

Respondent also notes that petitioner’s GBS did not recur after any of the numerous vaccinations she received between 1999 and 2010. Resp ’t’s Post Hearing Brief at 15. Therefore, Dr. Kohrman opined that one of petitioner’s docum ented infections (upper respiratory infection, acute gastroenteritis) which occurred during the three weeks preceding GBS onset, was the “predisposing factor causing the recurrence of Ca ssandra’s polyneuropathy.” Resp’t’s Ex. D at

8.

The medical literature also indicates th at there is a well-known cause and effect relationship between upper respiratory tract infecti ons and GBS. In the Mossberberg article cited by respondent (Resp’t’s Ex. H – see fn. 9), patie nts with recurrent GBS were examined to determine the long term course of the disease and to search for factors predisposing the patients to recurrence. Resp’t’s Ex. H at 157. Of the 11patients with recurrent GBS that were examined, six had a preceding upper respirator y tract infection prior to the ons et of their second recurrence. Of the total episodes of GBS that occurred, 24 of the 32 episodes were preceded by an upper respiratory tract infection. Id.

The undersigned finds that respondent has proven, by a preponderance of the evidence, that one of petitioner’s antecedent infections wa s the “but for” cause of petitioner’s recurrent

GBS.

(3) Althen Prong Three: Proximate Temporal Relationship

Both parties’ experts agree that the timing for a viral source for petitioner’s recurrent GBS is medically appropriate. Dr . Rubenstein testified that, in cas es of recurrent GBS, onset can take place within two to three da ys to six weeks. Tr. 68, 71. Dr. Kohrman opined that onset of recurrent GBS happens either from four to five days to six weeks. Resp’t’s Ex. D at 6-7.

The medical literature the parties submitted addr esses the issue of timing. The authors of

the Slade article stated that “8 of the confirmed cases [of Guilla in-Barré syndrome] were within the 4- to 42 day window of biologica l plausibility.” Resp’t’s Ex. K at 5; Resp’t’s Ex. D at 6-7. Likewise, the “Institute of Medi cine determined that the plausi ble range of post-exposure latency

10 N Mossberg et al., “The recurr ent Guillain-Barré syndrome: a long-term population-based study,” 126 Acta Neurol Scand 154-161 (2012)20 for GBS to be 5 days to 6 weeks.” Resp’t’s E x. D at 6. In the Mossber g article, the authors found that the time from the trigge ring infection to the onset of RGBS [recurrent GBS] showed a tendency to shorten in successive ep isodes...” Resp't’s Ex. H at 4.

As noted above, the onset of petitioner’s GBS was March 31, 2010. The parties stipulate that petitioner was diagnosed with and treated for viral gastroenteriti s on March 19, 2010. Jt. Sub. at 1. Thus, onset took place between nine a nd fourteen days after petitioner was diagnosed with viral gastroenteritis.

Regarding the upper respiratory infection, the undersigned has found that petitioner experienced the URI approximately three week s prior to the onset of her GBS on March 31, 2014. Thus, the timeframe as supplied by both pe titioner’s and respondent ’s expert is also medically appropriate for a URI.

In light of the above, the undersigned fi nds that respondent ha s provided preponderant proof that the onset of petitioner’s recurrent GBS occurred within a medically timeframe in

relation to one of her an tecedent infections.

IV. Conclusion

For the reasons discussed above, the undersigne d finds that petitione r has not established entitlement to compensation and her petition must be dismissed. In the absence of a timely filed motion for review filed pursuant to Vaccine Rule 23, the clerk is directed to enter judgment

consistent with this decision.

IT IS SO ORDERED.

s/Nora Beth Dorsey Nora Beth Dorsey Special Master