Astle v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: May 15, 2018

* * * * * * * * * * * * * * * PUBLISHED

MADISON ASTLE, *

* No. 14-369V

Petitioner, *

*

v. * Chief Special Master Dorsey

*

SECRETARY OF HEALTH * Intracranial Hypertension; Chronic

AND HUMAN SERVICES, * Headaches; Pseudotumor Cerebri;

* Varicella Vaccine.

Respondent. *

*

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

Clifford J. Shoemaker, Shoemaker, Gentry & Knickelbein, Vienna, VA, for petitioner.

Glenn Alexander MacLeod, U.S. Department of Justice, Washington, D.C., for respondent.

RULING ON ENTITLEMENT1

I. Introduction

On April 30, 2014, Stephanie Astle filed a petition for compensation under the National

Vaccine Injury Compensation Program (“the Program”),2 on behalf of her then minor daughter,

Madison Astle (“petitioner”), in which she alleged that the human papillomavirus (“HPV”) and

varicella vaccinations that Madison received on January 16, 2012, caused her to develop severe

1 This decision will be posted on the website of the United States Court of Federal Claims’

website, in accordance with the E-Government Act of 2002, 44 U.S.C. § 3501 (2012). This

means the Decision will be available to anyone with access to the internet. As provided by

42 U.S.C. § 300aa-12(d)(4)B), however, the parties may object to the published Decision’s

inclusion of certain kinds of confidential information. Specifically, Under Vaccine Rule 18(b),

each party has 14 days within which to request redaction “of any information furnished by that

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

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

constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b). Otherwise, the

whole decision will be available to the public in its current form. Id.

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

Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended,

42 U.S.C. §§ 300aa-1 to -34 (2012) (“Vaccine Act” or “the Act”). All citations in this decision

to individual sections of the Vaccine Act are to 42 U.S.C. § 300aa.

headaches and increased spinal fluid pressure.3 Petitioner stated that since her vaccinations, she

has “continued to experience headaches, and [] cannot handle noise, crowds or stress.” Petition

(“Pet.”) at ¶2. Subsequently, petitioner filed an amended petition specifying that one or both of

the vaccines cased “a cerebral venous thromboembolic event, which resulted in increased

cerebrospinal fluid pressures resulting in a pseudotumor cerebri-like condition that has led to

Madison’s continued headaches and other problems.” Amended Pet. at ¶ 2.

Respondent recommended against compensation, stating that petitioner failed to present

adequate evidence to show that Madison’s vaccinations caused any injury. See Respondent’s

Rule 4(c) Report (“Resp. Rept.”) at 2, 11.

The parties filed expert reports in support of their respective positions. Petitioner filed

two expert reports from neurologist Carlo Tornatore, M.D. Petitioner’s Exhibits (“Pet. Exs.”) 27

and 36. Respondent filed two expert reports from neurologist Peter M. Bingham, M.D. Resp.

Exs. A, C. An entitlement hearing was held on November 7, 2017, in Washington, D.C., during

which petitioner and the parties’ respective experts testified.

After carefully analyzing and weighing all of the evidence and testimony presented in

this case in accordance with the applicable legal standards, I find that petitioner has provided

preponderant evidence that her varicella vaccination more likely than not caused her injuries,

which satisfies her burden under Althen v. Sec’ y of Health & Human Servs., 418 F.3d 1274,

1280 (Fed. Cir. 2005). Accordingly, I find that petitioner is entitled to compensation.

II. Issues to be Decided

The parties set forth the following facts in dispute: Whether petitioner’s post-vaccine

chronic headache syndrome is caused by intracranial hypertension; and, whether petitioner

suffered a “cerebral venous thromboembolic event,” following her January 16, 2012

vaccinations. Amended Joint Prehearing Submissions (“Am. Prehrg Sub.”) dated Nov. 3, 2017

(ECF No. 96) at 1.

Further, the parties asked the undersigned to resolve whether petitioner has shown by

preponderant evidence that her January 16, 2012 vaccinations caused her chronic headache

syndrome. First, as required under Althen Prong 1, whether petitioner presented a medical

theory showing that the HPV and/or varicella vaccine(s) can result in chronic headache

syndrome due to persistent intracranial hypertension. Am. Prehrg Sub. at 1-2. Second, whether

there is a logical sequence of cause and effect under Althen Prong 2 showing the HPV and/or

varicella vaccination(s) caused Madison to suffer “a cerebral venous thromboembolic event” that

resulted in persistent intracranial hypertension and subsequent chronic headache syndrome. Id.

at 2. Third, whether petitioner has shown a proximate temporal relationship between her HPV

and varicella vaccinations and her chronic headache syndrome under Althen Prong 3. Id.

3Since the filing of the petition, Madison has reached the age of majority, and the case is now

captioned in her name.

III. Procedural History

Petitioner filed this case on April 30, 2014, alleging that Madison suffered, and continues

to suffer from headaches, and has a decreased tolerance to noise, crowds, and stress, as a result

of receiving the HPV vaccination on January 16, 2012. Petition at 1-2, ¶¶ 2-3. Petitioner filed

the first set of medical records on May 16, 2014, and made subsequent filings of medical records

on June 24, June 26, June 27, and July 31, 2014. Petitioner also filed a statement of completion

on July 31, 2014. Petitioner then filed an Amended Petition on August 28, 2014, alleging that

Madison continues to suffer from headaches and other issues as a result of a vertebral venous

thromboembolic event, which increased cerebrospinal fluid pressures resulting in a pseudotumor

cerebri-like condition. Am. Petition at 1-2, ¶¶ 3, 4. Respondent addressed petitioner’s claims in a

report filed pursuant to Vaccine Rule 4(c), wherein respondent argued that petitioner was not

entitled to compensation under the Program. Resp. Report at 2.

The parties also filed expert reports in support of their respective positions. On March 27,

2015, petitioner filed an expert report from neurologist Dr. Carlo Tornatore along with his

curriculum vitae. Dr. Tornatore concluded that “the vaccinations that Madison received on

January 16, 2012, resulted in intracranial hypertension with subsequent chronic headaches.” Pet.

Ex. 27 at 18. Thereafter, on September 9, 2015, respondent filed an expert report from

neurologist Dr. Peter M. Bingham along with his curriculum vitae. Supplemental expert reports

were also filed by petitioner on February 8, 2016, and by respondent on July 12, 2016.

Thereafter, petitioner filed additional medical records on September 2, and September 8, 2016,

the latter accompanied by an amended statement of completion.

Petitioner filed her prehearing submission on September 11, 2017, and respondent filed

his prehearing submission on October 6, 2017. The parties also filed a joint prehearing

submission outlining the facts and issues that were and were not in dispute on October 16, 2017.

As stipulated by the parties, there are no disputed facts in this case, and the parties adopt the facts

as set forth in the respondent’s Rule 4(c) Report. Joint Prehearing Submission at 1. The parties

agree that Madison’s alleged injury is not set forth on the Vaccine Injury Table, nor do they

dispute whether she received these vaccines in the United States. Additionally, the parties do not

contest that Madison has suffered from the residual complications of the vertebral venous

thromboembolic event for more than six months since the administration of the HPV

vaccination.

IV. Summary of Medical Records 4

4 Although the undersigned considered the record as a whole in reaching this decision, this

section provides only a brief summary of relevant facts. A more detailed recitation of the facts

may be found in respondent’s Rule 4(c) Report and the parties’ expert reports. Also, petitioner

submitted several affidavits, including Pet. Ex. 48 (affidavit of Stephanie Astle) and Pet. Ex. 49

(affidavit of Madison Astle). The undersigned reviewed the affidavits, but in forming her

opinions, she generally relied on the facts set forth in the contemporaneous medical records, as

she finds these records to be reliable. See Reusser v. Sec’y of Health & Human Servs., 28 Fed.

Cl. 516, 523 (Fed. Cl. 1993) (holding that “[W]ritten documentation recorded by a disinterested

person at or soon after the event at issue is generally more reliable than the recollection of a party

In their amended joint prehearing submissions filed on November 3, 2017, the parties

stipulated to the medical summary and facts set forth in the Respondent’s Rule 4(c) Report,

however, the parties did not limit the relevant facts to those solely set forth in the report. The

undersigned also find the following facts to be relevant to her decision.

Madison and her twin sister were born on December 26, 1998, at 30 weeks gestation.

Their APGAR Scores were 7 and 9, respectively. Madison’s weight at birth was 2.75 pounds,

but by February 1, 1999, she weighed 4.2 pounds. Pet. Ex. 22 at 85. During her early childhood,

she was diagnosed with asthma, sinusitis, and gastroesophageal reflux disease, but otherwise

Madison had no significant health problems. Id. at 69-85. By age 12, Madison’s only health

issue was asthma, which was treated with medications. Id. at 64-67.

On January 16, 2012, at age 13, Madison received her second HPV vaccine and a

varicella vaccine. Pet. Ex. 22 at 3. Two days later, on January 18, 2012, she presented to her

pediatrician with complaints of a painful, red and swollen right arm at the site of vaccination.

Madison had a “quarter size erythema” at the vaccination site. At that visit, Madison’s diet was

ok, and she was sleepy. There was no mention of headache. Treatment with Tylenol and Motrin

was recommended. Id. at 11. Madison returned to her pediatrician for a follow-up visit on

January 24, 2012. At this visit, Madison’s arm remained red and swollen, and the area of

redness extended below her elbow. For the first time since vaccination, Madison also

complained of headaches, decreased appetite, and sleep disruption. Id. at 9. She was diagnosed

with cellulitis of the arm post-vaccination and was treated with antibiotics. Id. On January 25,

2012, a telephone call from Madison’s family indicated that the area of redness on her arm was

getting larger, and prednisone was ordered. Id. at 98.

Madison was next seen by her pediatrician on January 30, 2012. She was “taking

ibuprofen around the clock, unable to concentrate, had intermittent neck pain, was not eating

well, and sleeping more than usual.” Pet. Ex. 22 at 9. The area of redness at the vaccine site was

improved, but she still had discoloration and bruising at the site. Id. Diagnostic tests were

ordered, including magnetic resonance imaging (“MRI”) and magnetic resonance venography

(“MRV”). Id. MRI performed on February 3, 2012, was normal except for “left sphenoid

sinusitis.” Pet. Ex. 10 at 26. MRV5 performed the same day, however, showed “question of

upper left jugular vein thrombosis or occlusion. Clinical correlation suggested.” Id. at 63.

Two days later, on February 5, 2012, Madison was seen in the emergency room (“ER”) at

Sinai Hospital of Baltimore, and she was admitted to the hospital by pediatric neurologist Dr.

Edward Gratz. His report provided a thorough history, and is set forth below, as follows:

History of Present Illness:

to a lawsuit many years later.”).

5 A MRV is an “imaging modality for the evaluation of the venous system,” similar to a MRI but

used to look at blood vessels, specifically venous blood vessels. IMAGING OF THE

CARDIOVASCULAR SYSTEM , THORAX, AND ABDOMEN 115 (Luca Saba ed., 2017).

This is the [first] Sinai Hospital of Baltimore admissio n for this 13-year-old,

right-handed girl who was in her usual state of excellent health until [January 17,

2012], one day after receiving each [HPV] [v]aricella injection, right deltoid. She

developed a local reaction with erythema, warmth and local tenderness. She

experienced the onset of headache at that time described as a bilateral frontal

pressure-like discomfort, throbbing and pounding, intermittent. The headache was

worsened with routine activity, and she preferred to lie down and rest, but denied

significant sensitivity to light or noise. There was no associated dizziness or

nausea. She, however, was unable to participate in her usual activities and has not

attended school since [January 18, 2012]. There are no preceding or

accompanying visual, motor, or sensory symptoms. The headache has remained

continuous, but fluctuating in severity, but has always remained moderate to

severe. Local reaction was initially treated with Benadryl and hydrocortisone

cream for several days, without improvement. She initially was treated with a

[five] day course of Bactrim and subsequently a ten day course of clindamycin

which was discontinued on [February 2, 2012]. Because of the persistent

headache, she was seen in the emergency room at Sinai Hospital on [February 3,

2012]. Her headache initially did not respond to IV Toradol 30mg, two doses at

approximately [six] hours apart. Because of concerns regarding thrombophilia

associated with [HPV] vaccine, an MRI of brain and MR venogram were obtained

and normal by report.[6 ] She was also seen by ophthalmology consultant who

noted healthy ophthalmological examination without evidence of papilledema.

Returning from MR imaging studies, she was given metoclopramide 10 mg IV,

followed by DHE 0.25mg, with decrease in the severity of her headache from

[seven] to [eight out of ten] to approximately [one out of ten]. She went home

from the emergency room at approximately 05:00 a.m., on [February 4, 2012].

She slept; however, by approximately 2:00 p.m., the headache recurred and has

remained [eight out of ten] since that time. She returned to the emergency room

and [was] subsequently admitted for treatment of headache. There had been no

history of previous significant headache or migraine. No reported family history

of migraine.

Pet. Ex. 10 at 93.

Madison was discharged from Sinai Hospital on February 9, 2012. Several weeks later,

on February 22, 2012, Madison returned to the ER at Sinai Hospital and was again seen by Dr.

Gratz. He noted that about one week after her prior hospital discharge, Madison’s headache

became more severe and over the past 48 hours, her headache caused pain described as 8/10,

with intermittent throbbing, some nausea, and was worse with activity. She also had sensitivity

to light and noise. Her physical exam was normal. Dr. Gratz ordered IV Toradol and valproic

acid, as well as metoclopramide and dihydroergotamine (“DHE”). A small dose of morphine

was also administered. After treatment, Madison’s headache improved, and she was discharged

6In fact, the report by Dr. Frachtman states: “Question of upper left jugular vein thrombosis or

occlusion.” Pet. Ex. 10 at 68.

to outpatient management to continue on preventative therapy with topiramate and Depakote, as

well as tapering doses of prednisone, and analgesics. Pet. Ex. 6 at 8-11.

Madison was seen by Dr. Gratz for follow- up care on March 16, 2012. Despite

medication, she continued to have chronic daily headaches which worsened with routine activity

and which prohibited her from attending school. 7 Several times weekly, her headaches were

more severe, usually in the evenings. Madison’s severe headaches were bifrontal in location and

characterized by throbbing pain, with sensitivity to sound. Dr. Gratz adjusted Madison’s

medication. Pet. Ex. 10 at 60-62.

Due to persistent headache, Dr. Gatz readmitted Madison to Sinai Hospital on March 27,

2012, for a lumbar puncture, in order to evaluate the possibility of pseudotumor cerebri without

papilledema. The lumbar puncture was performed and noted to be “mildly traumat ic.” Opening

pressure was 30 [cmH2O]. CSF revealed approximately 4000 red blood cells, 5 white blood

cells, and elevated protein of 50. Lyme antibody studies and Epstein-Barr titers were all

negative. Pet. Ex. 10 at 77-80. Madison did not experience relief of her headaches after the

lumbar puncture procedure. Dr. Grazt diagnosed her with chronic persistent headache, and he

initiated treatment with 250 mg of Diamox twice daily for “presumptive therapy of pseudotumor

cerebri without papilledema.” Pet. Ex. 10 at 77-80. Dr. Grazt also requested consultation by

pediatric infectious diseases. Infectious disease consultant, Dr. Susan Lipton, evaluated Madison

and reported that she had “subjective, debilitating, severe headaches since vaccinations with

human papillomavirus and Varicella on 01/16/2012.” Like Dr. Gratz, Dr. Lipton noted, “There

is evidence of pseudotumor with the increased intracranial pressure even though there is no

funduscopic evidence of this.” Id. at 90.

A repeat MRV performed March 28, 2012, showed, “minimal peripheral irregularities in

the left sigmoid sinus, similar to the prior examination on February 3, 2012, which can denote

chronic changes versus anatomic variant. There is now interval recanalization of the left distal

internal jugular vein. The left distal jugular internal vein is smaller in caliber in comparison to

the right.” Pet. Ex. 10 at 66.

Subsequently, Madison was evaluated by a pediatric endocrinologist, Dr. Judith

McLachlan, due to a decreased calcium level reported from her prior laboratory results (calcium

decreased at 7.9 on February 28, 2010). Repeat labs drawn April 23, 2012, confirmed that

Madison had a low calcium level of 8.7, as well as decreased parathyroid hormone level less than

3, which was very low. Pet. Ex. 10 at 52-53. These findings suggested that Madison had

hypoparathyroidism and Hashimoto’s thyroiditis. Id. at 52; Tr. 197. An ophthalmology consult

was also obtained, and Madison had a normal exam with no evidence of papilledema.8

7 Madison has never returned to school and instead received home schooling. Tr. 16.

8 Papilledema is optic disc swelling caused by increased intracranial pressure. It is the “hallmark

of PTCS”.” Resp. Ex. D6 at 2. Dr. Bingham also referred to it more simply as a “swollen optic

nerve.” Tr. 182. However, pseudotumor cerebri can occur in the absence of papilledema,

although generally patients without papilledema may have lower lumbar puncture opening

pressures. Pet. Ex. 56 at 2.

Madison next followed-up with Dr. Grazt on May 3, 2012, where it was noted that she

continued to have “intractable chronic daily headaches.” She had not been able to return to

school since January 18, 2012, but did have a home school teacher. Madison reported

exacerbation of her headaches with activity such as homework, meeting with her teacher, or

walking. She also reported increasing insomnia. Dr. Grazt concluded that Madison had “chronic

persistent headaches with associated elevated increased intracranial pressure suggesting the

possibility of pseudotumor cerebri without papilledema. Pseudotumor cerebri has been reported

to occur secondary to hypoparathyroidism, although the pathophysiology was not well

understood.” Pet. Ex. 10 at 56-59.

Madison was evaluated by Dr. Howard Jacobs at the University of Maryland Pediatric

Headache Clinic on December 13, 2012. Pet. Ex. 22 at 158. At this time, Madison was 14 years

old and continued to experience daily headaches, with her pain rated as 7/10 up to 9/10. She had

been out of school since January 2012 due to headache. She had taken a number of medications,

including tramadol, Aleve, amitriptyline, Lexapro, Depakote, acetazolamide, Topamax,

Migranal, Treximet, and Maxalt. She was diagnosed with chronic migraine, and Dr. Jacobs

noted that she “may also have a high-pressure component to her headache although she does not

have pseudotumor cerebri.” Pet. Ex. 22 at 159. Dr. Jacobs initiated treatment with propranolol,

Amerge, and prednisone.

At her primary care visit on January 18, 2013, Madison was noted to have lost 20 pounds

over the last year. In February 2014, she was again seen by her primary care physician with a

complaint of headaches. At that time, she was taking tramadol for her headaches.

In May 2014, now age 15, Madison was seen at Johns Hopkins Bayview Clinic by

neurologist Dr. Abhay Rajeshwar Mogheker. After reviewing her history, Dr. Mogheker

questioned whether Madison might have intracranial hypertension without papilledema, given

her opening pressures reported at her initial lumbar puncture. Dr. Mogheker wanted to confirm

if sedation was used during the lumbar puncture procedure since sedation “can artificially elevate

intracranial pressure…and opening pressure of 30 cm under sedation …would not be considered

elevated.” Dr. Mogheker diagnosed Madison with “possible intracranial hypertension without

papilledema and chronic daily headache.” Pet. Ex. 11 at 4-6, 8.

Madison first saw Dr. Carlo Tornatore, her expert neurologist, on October 6, 2014, who

noted that she continued to suffer debilitating headaches. Pet. Ex. 41 at 2. He recorded that she

had daily headaches with diffuse pain which ranged from a four out of ten to a ten out of ten on

the pain scale. Id. At that visit, he diagnosed her with “benign intracranial hypertension” and

prescribed Diamox 225 mg per day. Id. at 3. At a follow up with Dr. Tornatore on November

13, 2014, he noted that Madison experienced paresthesia in her arms and legs after taking

Diamox, and thus he adjusted her medications. Id. at 5. At a visit on April 16, 2015, Dr.

Tornatore noted that Madison’s headache was better after taking pain medications and that she

took Diamox twice per day on Monday, Wednesday, and Fridays, and that she took up to four

tabs of Tramadol at a time, up to four times per day. Id. at 12. He indicated that he wanted to

taper her off Tramadol, as this could cause secondary headaches. Id. at 13. Madison continues

to follow up with Dr. Torantore every few months. See Pet. Exs. 41, 44.

Significant to the undersigned’s decision are the results of Madison’s four MRVs, which

were performed between February 3, 2012, and August 29, 2012. The first study performed on

February 3, 2012, was interpreted by Dr. Richard Frachtman. Dr. Thelma D. Lopes interpreted

the other three studies, and she also reviewed the first study, as a basis for comparison. The

dates and pertinent findings of the studies are as follows:

February 3, 2012 MRV: Dr. Frachtman writes, “Severe [headache] [two] weeks after

varicella and HPV immunizations[.] [Rule out] pseudotumor cerebri[.] [Rule out] sinus

thrombosis …. Comparison: None …. The right internal jugular vein is visualized, but the left

internal jugular is not well seen, particularly in the upper portion. This could be technical, but I

cannot exclude thrombosis in this area …. Impression: …. Question of upper left jugular vein

thrombosis or occlusion. A preliminary report was called to Dr. Schuester.” Pet. Ex. 10 at 68.

March 28, 2012 MRV: Dr. Lopes observed, “13 year old female presented with

headache. Comparison is made to prior examination dated 2/3/2012. There is minimal

peripheral irregularities in the left sigmoid sinus, similar to the prior examination which can

denote chronic changes vs. anatomic variant. There is now recanalization of the left distal

internal jugular vein.” Pet. Ex. 10 at 66.

July 24, 2012 MRV: Dr. Lopes noted, “Since prior examination dated [March 28, 2012],

there is worsening [of] the irregularity involving the left sigmoid sinus. There is minimal

irregularity of the right sigmoid sinus that it new since prior examination …. Impression: There

is interval progression of irregularities involving the left sigmoid sinus as well as development of

minor irregularities involving the right sigmoid sinus …. I discussed this case with Dr. Gratz on

[July 24, 2012].” Pet. Ex. 10 at 24.

August 29, 2012 MRV: Dr. Lopes stated, “Since prior examination [on July 24, 2012],

there is improved appearance of the left sigmoid sinus now with normal flow. There are no signs

of sinus thrombosis.” Pet. Ex. 10 at 28.

V. Intracranial Hypertension

Intracranial hypertension, also referred to as pseudotumor cerebri (“PTC”) and idiopathic

intracranial hypertension (“IIH”), is a clinical syndrome (“PTCS”) characterized by signs and

symptoms of increased intracranial pressure. Pet. Ex. 31 at 1. The condition was first used to

describe patients who had increased intracranial pressure in the absence of a brain tumor, thus

the word “pseudotumor” was coined. Id. at 5. PTC may be used interchangeably with idiopathic

intracranial hypertension (“IIH”), although IIH is not the technically appropriate name for

patients who have an “identifiable secondary cause” of intracranial hypertension. Resp. Ex. D6

at 1. Thus, Friedman9 and others recommend the umbrella term of PTCS over IIH. Id. They

also recommend that patients be subdivided into “primary vs. secondary PTC… [and that the]

9 Friedman, Deborah et al., “Revised Diagnostic Criteria for the Pseudotumor Cerebri Syndrome

in Adults and Children,” 81 N EUROLOGY 1159-65 (2013) [Resp. Ex. D6].

Id. The mean duration of treatment described by Per et al., was 9 months. Id. Visual loss has

been reported in up to 38% of patients. Id. Patients may relapse or continue to experience

headaches, even after normalization of intracranial pressure. Ex. 56 at 2.

VI. Expert Testimony

A. Standards of Adjudication for a Causation Claim

To receive compensation under the Vaccine Act, petitioner must prove either (1) that she

suffered a “Table Injury” – i.e., an injury falling within the Vaccine Injury Table – corresponding

to one of the vaccinations in question, or (2) that her injury was actually caused by a vaccine (a

“non-Table injury”). See §§ 300aa-13(a)(1)(A), 11(c)(1); § 300aa-14(a) as amended by 42

C.F.R. § 100.3; 300aa-11(c)(1)(C)(ii)(I); see also Moberly v. Sec’y of Health & Human Servs.,

592 F.3d 1315, 1321 (Fed. Cir. 2010); Cappizzano v. Sec’y of Health & Human Servs., 440 F.3d

1317, 1320 (Fed. Cir. 2006). Since no Table Injury is alleged in this case, petitioner must prove

causation in fact.

Petitioner bears the burden of demonstrating actual causation by a preponderance of the

evidence. See Cedillo v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1321 (Fed. Cir.

2010); § 300aa-13(a)(1). To do so, petitioner must provide: “(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 the vaccination and injury.” Althen, 418 F.3d at 178. The preponderance of

the evidence standard requires a petitioner to demonstrate that it is “more likely than not” that the

vaccine caused her injury. Moberly, 592 F.3d at 1322 n.2. Proof of medical certainty is not

required. Bunting v. Sec’y of Health & Human Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). In

particular, petitioner must demonstrate that the vaccine was “not only [a] but for cause of the

injury but also a substantial factor in bringing about the injury.” Moberly, 592 F.3d at 1321

(quoting Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999));

Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). The

undersigned must consider the record “as a whole” and may not rule in petitioner’s favor solely

based on petitioner’s own claims “unsubstantiated by medical records or medical opinion.” §

13(a)(1).

Causation is determined on a case by case basis, with “no hard and fast per se scientific

or medical rules.” Knudsen v. Sec'y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir.

1994). The Althen court noted that a petitioner need not necessarily supply evidence from

medical literature supporting petitioner's causation contention, so long as the petitioner supplies

the medical opinion of an expert. Id. at 1279–80. The court also indicated that, in finding

causation, the fact-finder may rely upon “circumstantial evidence,” which the court found to be

consistent with the “system created by Congress, in which close calls regarding causation are

resolved in favor of injured claimants.” Id. at 1280. In other words, any close calls regarding

causation must be resolved in favor of the petitioner. Althen, 418 F.3d at 1280.

B. Expert Reports and Testimony

In Vaccine Act cases, expert testimony is usually evaluated according to the factors for

analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579,

594-96 (1993); see also Cedillo, 617 F.3d at 1339 (citing Terran v. Sec’y of Health & Human

Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999). “The Daubert factors for analyzing the reliability

of testimony are: (1) whether a theory or technique can be (and has been) tested; (2) whether the

theory or technique has been subjected to peer review and publication; (3) whether there is a

known or potential rate of error and whether there are standards for controlling the error; and (4)

whether the theory or technique enjoys general acceptance within a relevant scientific

community.” Terran, 195 F.3d at 1316 n.2 (citing Daubert, 509 U.S. at 592-95). In Vaccine

Program cases, these factors are used in the weighing of the scientific evidence actually

proffered and heard. Davis v. Sec'y of Health & Human Servs., 94 Fed. Cl. 53, 66–67 (Fed. Cl.

2010) (“uniquely in this Circuit, the Daubert factors have been employed also as an acceptable

evidentiary-gauging tool with respect to persuasiveness of expert testimony already admitted”),

aff'd,420 F. App'x 923 (Fed. Cir. 2011). The flexible use of the Daubert factors to determine the

persuasiveness and/or reliability of expert testimony in Vaccine Program cases has routinely

been upheld. See, e.g., Snyder v. Sec'y of Health & Human Servs., 88 Fed. Cl. 706, 742–45

(2009).

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

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

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

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

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

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

data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743 (quoting Gen. Elec. Co. v. Joiner, 522

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

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

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

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

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

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

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

Vaccine Act”).

In the present case, two experts testified at the hearing, Dr. Tornatore for petitioner and

Dr. Bingham for respondent. The experts’ respective qualifications and opinions are

summarized below.

i. Petitioner’s Expert, Dr. Carlo Tornatore

Dr. Carlo Tornatore received a Bachelor of Arts in neurobiology from Cornell Univers ity,

and he completed a Master’s of Science at Georgetown University in the Department of

Physiology. Pet. Ex. 28 at 2. He attended Georgetown University School of Medicine in

Washington, D.C., and completed his residency in neurology at Georgetown University Hospital.

Id. After his residency, Dr. Tornatore worked as a Senior Staff Fellow at the National Institutes

of Health in the Section on Molecular Virology and Genetics in the Laboratory of Viral and

Molecular Pathogenesis. Id. He is board certified in neurology by the National Board of

Psychiatry and Neurology, and he is licensed to practice medicine in the District of Columbia. Id.

at 1. Dr. Tornatore currently serves as an associate professor of neurology at Georgetown

University Medical Center, and he is a member of the American Academy of Neurology, the

American Association for the Advancement of Science, and the American Society for Neural

Transplantation. Id. at 5. He also serves as an ad hoc reviewer for five medical journals and has

published numerous articles on neurology over the course of his career. Id. at 5-16.

1. Diagnosis of Intracranial Hypertension

Dr. Tornatore opined that Madison had intracranial hypertension based on her elevated

spinal fluid pressure, abnormal MRV studies, and the fact that her treating physicians considered

this diagnosis. Tr. 33-34. He opined that this condition triggered Madison’s chronic headaches.

Id. at 35. The medications she began taking for her chronic headaches may also have contributed

to her chronic headaches. Id. at 35-36.

Prior to receiving the vaccines at issue here, Madison was healthy. Her growth chart

shows that she was approximately 75% for weight, based upon her age and height. After her

vaccinations, her weight dropped off dramatically. Tr. 11-12. Pre-vaccination, Madison’s

scholastic record was very good, and she had no prolonged school absences. She had a variety

of interests, and was a “very engaged and vibrant” adolescent. Id. at 15. She did experience

occasional headaches prior to her vaccinations, but these were associated with sinus infections or

chronic sinus problems. Id. 19-20. Before the vaccines, Madison had facial pain under her eyes,

or in the back of her head. Id. 20-21. After she underwent sinus dilation, she improved. Id. at

21. After the vaccines, her pain was in the back of her head and neck, and her headaches became

significantly worse. Id. at 22.

On March 28, 2012, Madison had a lumbar puncture, and her opening pressure was 30

cmH20, which Dr. Tornatore opined was elevated. Tr. 33; Pet. Ex. 23 at 209-210. A significant

question raised by Madison’s treating physicians, and the experts, was whether her opening

pressure of 30 cm was diagnostic for increased intracranial pressure. Dr. Tornatore cited several

articles in support of his position that an opening pressure of 30 cm did indicate increased

intracranial pressure.

In the Gerstl paper,15 twelve patients between the ages of five and seventeen were

studied. The diagnosis of intracranial hypertension was based on papilledema, visual symptoms,

dizziness, headache and nausea, and a lumbar puncture opening pressure of greater than 25 cm.

Ten of the patients were sedated. Lumbar puncture opening pressures ranged from 21 to 50 cm.

Eight of the children had an opening pressure of 28 cm or greater. The authors discussed their

concern about the strict revised criteria published by Friedman, in which the threshold elevation

for an opening pressure was ≥ 28 cm. They believed that the Friedman threshold of ≥28 cm

could lead to missed diagnoses of PTC in children, especially in the absence of papilledema.

15 Gerstl et al., 21 EUR. PAED. NEUROL. SOC. 833 [Pet. Ex. 51].

Pet. Ex. 51 at 5. Gerstl advocated an opening pressure “range of ≥20 to 30 cm” should be

adopted instead. Id. at 9.

In another 2017 study, by Inger et al.,16 of 50 children, the authors defined an elevated

opening pressure of ≥ 28, or ≥ 25, if the child was not sedated and not obese. By this measure,

ten of the children did not have an elevated opening pressure, although they had a clinical course

consistent with intracranial hypertension. And in the Digre17 article, 353 patients were studied.

The mean opening pressure was 309 mm (30.9 cm) in those patients who did not have

papilledema.18 Pet. Ex. 38 at 1.

In addition to the abnormal opening pressure, Dr. Tornatore testified that Madison also

had abnormalities of her CSF fluid. Specifically, she had an elevated protein of 50, elevated red

blood cells of 4000, and five white blood cells. Tr. 105-06. Dr. Tornatore attributed the red and

white blood cell abnormalities to the fact that the procedure was “a little traumatic,” resulting in

bleeding. Dr. Tornatore explained that for every 1,000 red blood cells, there is usually one

“tagalong” white blood cell, which explains Madison’s count of five white blood cells. As for

the elevated protein, Dr. Tornatore explained that some increase in the CSF protein would be

attributable to the red blood cells caused by the traumatic nature of the procedure. However, he

did not think that this explained all of the increase. He opined that at least part of the

abnormally-elevated protein was a “bona fide elevation” consistent with his mechanistic theory.

Tr. 202-03.

Madison did not have papilledema, and she had spontaneous venous pulsations (“SVP”).

Both experts testified about whether there can be a diagnosis of PTC in the absence of

papilledema and the presence of SVP. Tr. 204. Papilledema is a swollen optic nerve, a classic

finding in intracranial hypertension. SPV is the presence of pulsing in the veins overlying the

front of the optic nerve. If the pressure in the brain is very elevated, it will impinge on these

blood vessels to prevent them from pulsing. Tr. 136. Thus, the lack of pulsing is a diagnostic

sign of intracranial pressure. Id.

Dr. Tornatore emphasized that the absence of papilledema and the presence of SVP does

not preclude the diagnosis of intracranial hypertension. Tr. 204-05. He cited a study by Digre et

al., in support of his opinion. In Digre, the authors studied 353 patients with intracranial

hypertension and found that 5.7% did not have papilledema, and of those, 75% had SVP. Pet.

Ex. 38 at 1. The authors concluded that while less common, intracranial hypertension can occur

in the absence of papilledema and the presence of SVP. Id. at 6. Another study published in

16Inger, Hilliary E. et al., “Diagnostic Criteria in Pediatric Intracranial Hypertension,” J. AAPOS

(2017). [Pet. Ex. 50].

Digre, Kathleen B. et al., “A Comparison of Idiopathic Intracranial Hypertension With and

17

Without Papilledema,” 49 HEADACHE 185 (2009) [Pet. Ex. 38; Resp. Ex. D4].

18 Papilledema is “an edema of the optic disk (papilla), most commonly due to increased

intracranial pressure, malignant hypertension, or thrombosis of the central retinal vein.”

Dorland’s at 1372.

2017 by Gerstl also supports the proposition that intracranial hypertension can occur in the

absence of papilledema. In Gerstl, six of the 12 children studied did not have papilledema. Pet.

Ex. 51 at 3.

Dr. Tornatore explained that the changes on Madison’s MRVs show changes in the veins

that can be associated with cranial hypertension. Tr. 33. Serial MRVs performed in February,

March, May, July, and August 2012 were abnormal and showed abnormalities in the venous

anatomy of the brain. The first MRV, February 3, 2012, raised a question of “upper left jugular

vein thrombosis.” Tr. 55. The right internal jugular vein was visualized but the left jugular was

not well seen, and thrombosis could not be excluded. Pet. Ex. 10 at 63. Dr. Tornatore explained

that on MRV, if a vessel is not seen, it is because there is no blood flow through the vessel or

there is a technical problem. Tr. 56-57. On March 28, 2012, Madison’s MRV showed minimal

peripheral irregularities of the left sigmoid sinus similar to the prior study. It also showed

“interval recanalization of the left internal vein.” Id. at 26. Dr. Tornatore explained that the

suggestion of recanalization indicates that the left internal vein may have previously been

occluded by an embolus or clot. Id.

In addition to the elevated opening pressure at the time of initial lumbar puncture and the

abnormal MRV studies, Dr. Tornatore was also influenced by the opinions of Madison’s treating

physicians. On March 27, 2012, Madison was admitted to Sinai Hospital where Dr. Gratz

diagnosed her with “chronic persistent headache, possibly secondary to intracranial hypertension

without papilledema.” Pet. Ex. 10 at 77-80. Dr. Gratz again questioned the diagnosis of

intracranial hypertension when he saw Madison at her follow-up appointment on May 3, 2012.

At that visit, he concluded that she had “chronic persistent headaches with associated elevated

increased intracranial pressure suggesting the possibility of pseudotumor cerebri without

papilledema. Pseudotumor cerebri has been reported to occur secondary to hypoparathyroidism,

although the underlying pathophysiology is not understood.” Pet. Ex. 10 at 56-59.

Dr. Gratz made the same diagnosis when he saw Madison again on July 18, 2012.

Pediatric infectious disease specialist, Dr. Susan Lipton, who saw Madison in March 2012, noted

that “There is evidence of pseudotumor even though there is no funduscopic evidence of this.”

Pet. Ex. 10 at 88-91. These physicians did not attribute Madison’s condition to her varicella

vaccination, but they consistently raised the diagnosis of intracranial hypertension as the cause of

Madison’s headaches.

In the literature cited by Dr. Tornatore, patients with headaches due to intracranial

hypertension usually have resolution of their headaches following treatment (i.e. administration

of diuretic or lumbar puncture to drain cerebrospinal fluid) to reduce intracranial pressure.

Madison’s headaches, however, did not resolve after treatment. Dr. Tornatore testified that once

her intracranial pressure normalized, her headaches continued and became chronic due to a

number of factors. Tr. 76. After her first lumbar puncture, her intracranial pressure decreased so

quickly that she had what is known as a “spinal tap headache.” Id. at 95. Dr. Tornatore also

opined that Madison’s medications, and analgesic overuse, especially long term use of Tramadol,

contributed to her ongoing headaches. Id. Lastly, in some patients, chronic headaches are very

difficult to treat. The electrical system of the brain is “so dysregulated” that it will not return to

normal. Id. at 96-97. Given her history, Dr. Tornatore explained that Madison’s headaches will

probably not go away. Id. at 104. He opined that some of Madison’s headaches are caused by

her use of Tramadol, and if she would wean off that medication, her headaches may not be as

debilitating. Tr. 104. However, he testified that 30 to 35% of patients still have chronic daily

headaches when weaned off medication like Tramadol. Id. at 105.

2. Causation and Althen Prongs

Dr. Tornatore explained that the varicella vaccine contains a live attenuated virus19 , and

for reasons that are not clear, Madison had a “profound” reaction to the virus. Tr. 36-37. The

varicella virus is “neurotropic” – that is, it is known to infect nerves and the nervous system. Dr.

Tornatore proposed two alternative causal mechanisms. The first mechanism is that the virus

infected nerves in the brain, causing them to become inflamed and swollen, which increased

intracranial pressure. Tr. 38. His second proposed mechanism is that the varicella virus infected

the blood vessels and the walls of blood vessels in the back of the brain so that the vessels

became inflamed and irritated. Id. Varicella can infect the walls of blood vessels and inflame

and irritate them, causing clots to form, or blood vessels to narrow. Id. at 38, 58. CSF drains

into these veins, and when the veins are irritated, or occluded, the spinal fluid fails to properly

drain into them, which increases intracranial pressure. Id. at 90.

Spinal fluid is constantly produced in the brain, at the rate of approximately 30 ml of

fluid per hour, and this fluid is constantly draining out of the brain and into the venous sinuses

(veins) of the brain. If there is an obstruction in the venous system, then the spinal fluid is

unable to properly drain, which creates a backup of spinal fluid in the brain. This increase of

spinal fluid pushes on the brain and blood vessels, causing headache. Tr. 90-91. The skull is a

confined space – if the amount of spinal fluid increases, something else has to give. The brain

does not have pain receptors but blood vessels in the brain do - blood vessels have nerves which

sense pressure, and the increased pressure caused by the brain pushing on the blood vessels

creates pain. Tr. 91. The spinal fluid pressure is elevated like it would be if there were a tumor,

but because there is no actual tumor, the condition is referred to as “pseudotumor”. Tr. 28.

Referencing the Farb article,20 Dr. Tornatore provided demonstrative evidence of the

normal venous anatomy of the sagittal, transverse, and sigmoid sinuses, as illustrated in the

diagram below:

19 The Physicians’ Desk Reference entry for the VARIVAX varicella vaccine states that it is “a

live, attenuated varicella-zoster vaccine . . . .” Pet. Ex. 58 at 3.

20Farb, R.I. et al., “Idiopathic Intracranial Hypertension: The Prevalence and Morphology of

Sniovenous Stenosis,” 60 NEUROLOGY 1418 (2003) [Pet. Ex. 30].

Figure 2A, Pet. Ex. 30 at 2.

The sagittal sinus vein comes across the top of the brain, down to the back of the skull

and drains into the transverse veins, which then drain into the sigmoid sinuses, which then drain

into the (internal) jugular veins. Tr. 81. The sigmoid and internal jugular veins were not well

visualized in Madison’s MRV studies. Id. Dr. Tornatore opined that in Madison’s first MRV

study, the left internal jugular vein was occluded. Subsequent MRVs also showed irregularities

in the sigmoid sinus, and in her last study, these abnormalities were gone. Id. at 81-82. The

irregularities seen in the veins on MRV may occur when the lumen of the veins are narrowed.21

Blood flow through a vein is more turbulent due to narrowing, and clotting can occur in the

narrowed areas. Narrowing may also be referred to as stenosis. Id. at 83. Stenosis can be

profound, in which case an occlusion may occur, resulting in no blood flow. Id. at 83-84. When

a virus infects a blood vessel, an inflammatory response occurs, causing stenosis and clotting, or

results in irregularities of the veins, as described above. Id. at 86. Dr. Tornatore testified that he

had seen this mechanism in his clinical practice, particularly in patients with otitis media, or

infection of the middle ear, who developed focal inflammation of the sigmoid sinus as a result of

their infection. Tr. 94.

The factual background also includes Madison’s unrecognized pre-existing

hypoparathyroidism and hypocalcemia, known risk factors for intracranial hypertension. Pet.

Ex. 27 at 17. Dr. Tornatore opined that Madison’s hypoparathyroidism may have put her at risk

of developing pseudotumor. Id. at 18; Tr. 41.

In support of his opinions as to causal mechanisms, Dr. Tornatore referenced a number of

articles. First, he cited articles to support his opinion that varicella infection can lead to

intracranial hypertension, and thus this aspect of his proposed mechanism is a “well recognized

phenomenon.” Pet. Ex. 27 at 17. In an article published in 2014, Gilad 22 and his colleagues

describe a case report of a 13 year-old girl who had headaches for two weeks associated with

increased intracranial pressure. Pet. Ex. 32. Lumbar puncture opening pressure was 42 cmH2O,

the patient had papilledema, and CSF showed mildly-elevated protein (57 mg/dL). Polymerase

21 The lumen is “the cavity or channel within a tube or tubular organ.” Dorland’s at 1077.

22 Gilad, Oded et al., “Primary Varicella Infection Presenting with Headache and Elevated

Intracranial Pressure,” J. CHILD NEUROL. 1 (2014) [Pet. Ex. 32]

chain reaction (“PCR”) of CSF was positive for varicella zoster virus although the child did not

have any rash or vesicles characteristic of varicella infection.23

The Gilad authors reported seven other cases of varicella infection associated with

increased intracranial pressure in children ranging in age from ages six to 15, as described in the

literature. All seven children had headache, papilledema, and lumbar puncture opening pressures

ranging from 26cm to 42cm. Four of the children had a recent history of varicella infection and

three did not. All had “high titers of IgG antibodies to varicella zoster virus.” Pet. Ex. 32 at 3.

The authors concluded that “primary varicella zoster infection may present solely with headache

and elevated intracranial pressure.” Id. A summary of the seven cases described in the medical

literature is set forth below:

Table 1, Pet. Ex. 32 at 2.

These case reports described by Gilad, Ravid, and others validate Dr. Tornatore’s opinion

that varicella infection can lead to increased intracranial pressure and that this is a recognized

complication reported in the medical literature.

As to the mechanism at play, Gilad recognizes that the exact pathogenesis is not known,

but research suggests that increased intracranial pressure may be caused by “venous outflow

abnormalities…low-grade inflammation, [or] vascular clotting.” Pet. Ex. 32 at 2. Similarly,

Ravid et al.24 state that while the “precise pathogenesis of intracranial hypertension remains

23 Madison did not undergo PCR testing.

24Ravid, Sarit et al., “Reactivation of Varicella Presenting as Pseudotumor Cerebri: Three Cases

and a Review of the Literature,” 46 PED. NEUROL. 124 (2012) [Pet. Ex. 33].

unknown, [ ] proposed theories include venous outflow abnormalities.” Pet. Ex. 33 at 2. Ravid

also suggests that the mechanism may be “direct [infection] or immune- mediated vasculopathy.”

Id.

Lahat et al.25 also describe the example given by Dr. Tornatore of ear infections causing

intracranial hypertension. Before the wide-spread use of antibiotics, increased intracranial

hypertension secondary to middle ear infections was commonplace. The mechanism was

probably “thrombosis of one or more of the dural sinuses, specifically the lateral one.” Ex. 34 at

2. Lahat suggests that intracranial hypertension associated with varicella infection “may have a

vasculitic or immune- mediated pathogenesis.” Id. Similarly, Konrad et al.,26 concur in their

case report of “deep venous thrombosis and [PTC] after chickenpox in an 8 year old,” who also

had a protein S deficiency. Pet. Ex. 35 at 1. Konrad states that there “have been repeated reports

about thrombotic complications during recovery from chickenpox.” Id. at 2. While Konrad

discusses the interplay of contributing conditions, such as protein S auto-antibodies,

anticardiolipin antibodies, and streptococcal co-infection, the case studies in the more recent

articles by Gilad and Ravid do not suggest that contributing conditions or coagulation

abnormalities are necessary for a varicella infection to be causally associated with intracranial

hypertension.

Dr. Tornatore also cited the package insert for VARIVAX27 , which warns against contact

with high risk individuals who may be susceptible to varicella because of possible transmission

of the virus after vaccination. Ex. 27 at 17. Pet. Ex. 58 at 3. This adds support for Dr.

Tornatore’s opinion that the varicella vaccine can cause infection, a cornerstone to his causal

theory.

To summarize Dr. Tornatore’s explanation of a logical sequence of cause and effect,

Madison had pre-existing low calcium levels due to her hypoparathyroidism. She was

vaccinated with varicella, a live virus known to cause increased intracranial pressure via the

mechanism described above. She then developed abnormalities in the dural sinus veins, the

veins in the back of her brain, causing clots to form, or the vessels to narrow, with a resulting

elevation of intracranial pressure. Madison’s elevated intracranial pressure caused the onset of

severe and chronic headaches. Tr. 38-41.

With regard to onset, Madison received her vaccines on January 16, 2012. The first

documented reference in the medical records to headaches was January 24, 2012. See Pet. Ex.

22 at 11. Dr. Tornatore testified that the onset, or temporal relationship of her headaches, was

25Lahat, E. et al., “Pseudotumor Cerebri Complicating Varicella in a Child,” 87 ACTA PAEDIATR.

1310 (1998) [Pet. Ex. 34].

26Konrad, D. et al., “Psuedotumor Cerebri After Varicella,” 157 EUR. J. PEDIATR. 904 (1998)

[Pet. Ex. 35].

27VARIVAX is “a preparation of the Oka/Merck strain of live, attenuated varicella virus.” Pet.

Ex. 58 at 6.

about 10 days28 after vaccination, which is “perfect” given his proposed mechanism of infection.

Tr. 48. Based on the serial MRV studies, Dr. Tornatore opined that Madison’s intracranial

pressure probably normalized by the time of her August 29, 2012 MRV. That study no longer

showed that her blood vessels were occluded or narrowed, and thus, it is probably “the most

objective point where [one] can say that there is changes that would fit.” Tr. 75, citing Ex. 10 at

28.

ii. Respondent’s Expert, Dr. Peter Bingham

Dr. Bingham graduated with a Bachelor of Arts in Biology from Harvard College, and he

received his M.D. from the Columbia College of Physicians and Surgeons in New York City.

Resp. Ex. B at 1. He completed his residencies in pediatrics and neurology at the Children’s

Hospital of Philadelphia. Id. Dr. Bingham is licensed in neurology and child neurology and

currently serves as a Professor of Neurology and Pediatrics at the University of Vermont. Id. He

serves on a number of healthcare committees, and he is also a member of the American

Academy of Neurology. Id. at 1-2. Dr. Bingham has also authored numerous publications and

has contributed to a number of neurology symposia. Id. at 4-10.

1. Diagnosis of Petitioner’s Condition

Dr. Bingham agreed that Madison developed an acute reaction to vaccinations, in that she

had cellulitis at the site of the vaccine, and he also opined that she developed a headache within

eight to 24 hours of vaccination.29 Tr. 128. He agreed that Madison’s headache was debilitating

and kept her from attending school. Id. at 128-29. Madison described her headache as pressure

that was intermittent, bilateral and throbbing. Id. at 129; see also Resp. Ex. A at 3. However,

Dr. Bingham opined that Madison had migraine headaches, not intracranial hypertension. See

Pet. Ex. 36 at 4.

Dr. Bingham gave several reasons for his opinion that Madison suffered from migraines

and opined that they can be distinguished from PTC based on a patient’s history. First, he

believed that the characterization of Madison’s pain fit the diagnostic criteria of a migraine. See

Resp. Ex. A at 8. Often migraines involve nausea, gastrointestinal upset, and light and/or sound

sensitivity. Tr. 130. Second, he testified that migraines often have an acute presentation, within

minutes to an hour, which is different from PTC, where a throbbing headache is not expected at

28 Dr. Tornatore appears to be off by two days. Madison’s headaches were first documented

January 24, 2012, eight days after vaccination. Dr. Tornatore also testified as to mechanisms

that could explain Madison’s headaches, assuming an earlier onset (one to two days after

vaccination). The undersigned finds, however, that onset occurred on or before January 24,

2012, approximately one week after vaccination, based on initial entries in the contemporaneous

medical records.

29 Dr. Bingham testified that Madison developed a headache 8 to 24 hours post vaccination. The

medical records created at the time of these events by the pediatrician, however, do not reference

a headache until January 24, 2012. See Pet. Ex. 22 at 9-13. Dr. Bingham may be relying on later

records, which are less clear as to onset of headaches. See Pet. Ex. 10 at 93.

the initial presentation. Id. at 147. Dr. Bingham agreed, however, that there was an overlap of

symptoms shared by both conditions. Id. at 130.

Dr. Bingham also testified that Madison suffered from migraines prior to her

vaccinations. Tr. 147. Prior to her vaccines, Madison had a headache associated with nausea,

which Dr. Bingham did not necessarily attribute to a migraine. Tr. 148; see Pet. Ex. 22 at 235.

She also had headaches associated with sinusitis, which were not attributable to migraines. Tr.

148. But in 2011, Madison had a headache described as a tension headache, and Dr. Bingham

thought this might have been a migraine. Id. at 150-51. Pain fibers that contribute to migraine

pain are not in the brain, but throughout the sinuses, and caused by a local inflammatory

response. Id.

Secondly, in disagreement with Dr. Tornatore, Dr. Bingham was impressed by the

presence of SVP. He stated that Madison had venous pulsations documented by an

ophthalmology examination on February 3, 2012, which he described as “compelling evidence of

normal intracranial pressure.” Tr. 135-136. Dr. Bingham agreed that the presence or absence of

SVP is not an “infallible sign” of increased intracranial pressure, but he finds it to be a useful

marker. Tr. 182. 30

Third, and also in disagreement with Dr. Tornatore, Dr. Bingham opined that Madison’s

opening lumbar puncture pressure of 30 cmH2O was within the accepted range of normal in

children and not a definitive sign of increased intracranial pressure. Tr. 134. To the extent that

30 cmH2O may have been on the higher range of normal, or even considered to be elevated, Dr.

Bingham attributed any such elevation to the sedative given for the procedure. Dr. Bingham also

noted that one of Madison’s treating physician, Dr. Abhay Moghekar, also questioned whether

the elevation was due to sedation.31 Id. at 134-35. Dr. Bingham cited an article by Avery32 for

the position that opening pressures can be higher in children. Id. at 166-67. While the authors of

Avery state that an opening pressure of ≥28 cm is normal for most children (Madison had an

opening pressure of 30 cm), they recommend that the number be interpreted in concert with other

clinical information. Resp. Ex. D2 at 284. Avery specifically looked at the factors of age and

influence of sedation, especially ketamine, which was not used in Madison’s procedure. They

did not study other factors, such as the abnormal MRV findings here. Avery did advocate

looking at the full concert of information, and seemed to guard against reliance on the opening

pressure alone to make a diagnosis.

30 Dr. Tornatore disagreed with Dr. Bingham on this point, citing Digre et al. In Digre, out of 20

patients who met the criteria for PTC without papilledema, 12 (75%) had SVP. Resp. Ex. D4 at

3.

31Dr. Moghekar noted that the diagnosis of PTC “depends on an accurate measurement of

opening pressure[,] and it maybe [sic] worthwhile repeating the lumbar puncture without

sedation to exclude this diagnosis.” Pet. Ex. 11 at 6.

32Avery, R. A., “Interpretation of Lumbar Puncture Opening Pressure Measurements in

Children,” 34 J. N EURO-O PTHALMOLOGY 284-87 (2014) [Resp. Ex. D2].

As for Madison’s MRV studies, Dr. Bingham testified that the results were “not

compelling.” Tr. 141. He opined that in order for the reported abnormalities to be significant, the

abnormalities in the veins or sinuses should have been bilateral, not just unilateral. Instead, Dr.

Bingham believed that Madison’s studies showed unilateral abnormalities of unknown

significance. Id. at 137.

Citing the Farb study,33 Dr. Bingham testified that 27 of the 29 patients had substantial

bilateral stenosis, not just unilateral stenosis seen in Madison’s studies. Dr. Bingham also cited

an article by Alper34 which reported that 24% of the normal population has anatomical

asymmetry of their transverse sinuses. Tr. 166. He conceded, however, that the Farb and Alper

findings only applied to the transverse sinus, not the (internal) jugular or sagittal sinuses. Id. at

184. As such, he agreed that the findings are not directly applicable to Madison’s studies, which

showed abnormalities in the sagittal sinuses and internal jugular, and not the transverse sinus,

which were not studied by Farb or Alper.

Dr. Bingham also cited the Farb study for the point that technical artifacts on MRVs can

appear as areas of stenosis, and he suggested that the abnormalities seen on Madison’s studies

were technical artifacts. Tr. 168. Dr. Bingham emphasized that the important point of Alper and

Farb is that there can be technical issues which call into question the consistency of MRV

interpretations. Id. at 185.

Dr. Tornatore testified there would be less reader variability, and thus greater consistency

in Madison’s MRV interpretations since the same person reviewed all of the studies. Tr. 201.

Dr. Bingham agreed, and he testified that it was reasonable to give more emphasis to Dr. Lopes’

interpretation of the MRV studies, since she reviewed all of them. Id. at 196. Notably, when

interpreting the studies, Dr. Lopes questioned whether the abnormalities were signs of

thrombosis or simply anatomic variations. Over the course of her review, from February to

August 2012, Dr. Lopes reported on the progression of irregularities that suggested occlusion or

thrombosis involving the left internal jugular vein and left sigmoid sinus, which improved by

August 2012.

Also relevant to Dr. Bingham’s opinion is the response that Madison had to

dihydroergotamine (“DHE”). He testified that it is unusual for a patient with increased

intracranial pressure to respond to this medication, and thus, this fact weighs against a diagnosis

of pseudotumor. Tr. 142. However, this did not seem to be a strong point, and there was no

compelling evidence introduced to support it.

Additionally, Dr. Bingham disagreed with the import given by Dr. Tornatore to the fact

that Madison’s treating physicians diagnosed her with PTC without papilledema. Dr. Bingham

33 Farb et al., 60 NEUROLOGY 1418 [Pet. Ex. 30; Resp. Ex. D5].

34Alper, Fatih et al., “Importance of Anatomical Asymmetries of Transverse Sinuses: An MR

Venographic Study,” 18 CEREBROVASC. DIS. 236-39 (2004) [Resp. Ex. D1].

believed that Madison’s treating physicians were tentative in their diagnosis of pseudotumor, and

thus he opined that there was never a firm diagnosis of pseudotumor. Tr. 145.

Lastly, Dr. Bingham cited Friedman diagnostic criteria for PTC without papilledema, and

testified that Madison did not meet these diagnostic criteria. Tr. 169. He acknowledged,

however, that Friedman’s criteria were “stringent” and that others had contested that “stringency

of [the] diagnostic criteria.” Tr. 168-69.

Dr. Bingham testified that for all of the above reasons, especially the presence of SVP,

and the fact that Madison’s opening pressure was borderline, it more likely than not that Madison

did not have intracranial hypertension following her vaccinations. Tr. 170.

2. Response to Petitioner’s Theory of Causation and Althen

Prongs

Dr. Bingham opined that there was “no substantial evidence” that the vaccinations

Madison received either could cause, or did cause, her intracranial hypertension. Resp. Ex. A at

11. Citing a number of medical articles, Dr. Bingham emphasized several points. He cited a

CDC publication35 about the significant pathological differences between the wild varicella

virus, and the attenuated vaccine virus. Tr. 157. The article, however, confirms that attenuated

viruses, like those in vaccines, can cause disease, although usually in a milder form. R’s. Ex. E-

3 at 5. It also notes that “severe reactions are possible” with live attenuated vaccines. Id. at 4.

Dr. Bingham also cited Gilden,36 for the proposition that because the author, a known

varicella expert, did not mention or discuss varicella infection and pseudotumor, that a causal

relationship may not exist. Tr. 158. However, Dr. Bingham’s reliance on the article and the

point he makes are misplaced. The stated purpose of Gilden’s article is to review neurological

complications caused by reactivation of the varicella zoster virus as a sequela after primary

infection. It is not a discussion of the neurological complications caused by primary varicella

infection. The article is noteworthy in that varicella zoster virus reactivation can cause so many

diverse and significant illnesses, including but not limited to shingles, post-herpetic neuralgia,

meningo-encephalitis, cerebellitis, and ocular disorders. After primary infection, the virus

“becomes latent in ganglionic neurons along the entire neuraxis.” Resp. Ex. E5 at 1. Thus,

“zoster can develop anywhere in the body.” Id.

Gilden also discusses vasculopathies which may occur due to reactivation, although the

discussion related to arterial vasculopathies which cause strokes, not venous vasculopathies. Dr.

Bingham agreed that in its wild form, varicella zoster virus can cause vasculopathy in arteries but

35 Centers for Disease Control and Prevention, “Principles of Vaccination,” available at

http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/prinvac.pdf, last visited Sept. 8, 2015

[Resp. Ex. E3].

36Gilden, Don, “The Variegate Neurological Manifestations of Varicella Zoster Virus Infection,”

13 CURR. NEUROL. N EUROSCI. REP. 374 (2013) [Resp. Ex. E5].

he did not believe that the same applied to veins. Tr. 185. He conceded, however, that he did

not know whether the immunopathology that occurs in arteries due to varicella could also occur

in veins. Id. at 187.37

Citing the DeSimone38 article, Dr. Bingham testified that he sees and treats patients who

have pseudotumor and then develop chronic migraines. Dr. Bingham testified that “it’s

understood that this sequence can occur.” Tr. 167; Resp. Ex. D3. In DeSimone, patients with

chronic headache had MRV studies to look for flow gaps or aplasia 39 or evidence of sinus

stenosis. Out of a total of 56 patients, 52 had unilateral or bilateral segmental flow gaps or

aplasia seen on MRV. The authors posit that intracranial hypertension is caused by increased

resistance to CSF outflow in the cerebral venous blood system. Resp. Ex. D3 at 2. They suggest

that sinus stenosis plays a causal role in PTC mechanisms. Id. at 3. The main finding of the

study is that the large majority of patients with chronic migraine may actually suffer from a

chronic headache due to PTC without papilledema. Id. at 4. While Dr. Bingham agreed that this

mechanism may occur, he did not believe that the HPV or varicella vaccines could trigger

intracranial hypertension. Resp. Ex. A at 7-8.

Lastly, Dr. Bingham disagreed with the temporal association aspect of Dr. Tornatore’s

theory. Unlike Dr. Tornatore, Dr. Bingham opined that Madison had a rapid onset of headache,

within eight to twenty-four hours after vaccination.40 Dr. Bingham testified that while it might

be possible, it was very unlikely that rapid growth of a virus could cause an increase in

intracranial pressure within 24 hours, as posited by Dr. Tornatore. Tr. 154. Instead, Dr.

Bingham believed the process would take at least a week. Id. at 155. However, Dr. Bingham

conceded that the immunopathogenesis of how viral infection can cause an inflammatory

response is outside the scope of his expertise. Tr. 154.

VII. Analysis of Factual Disputes

a. Legal Framework

The Vaccine Act established the Program to compensate vaccine-related injuries and

deaths. 42 U.S.C. § 300aa-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-

37For articles discussing vasculitis in the context of the dural sinuses due to varicella, see Lahat,

87 ACTA PAEDIATR. 1310 [Pet. Ex. 34 at 2]; and Konrad, D. et al., “Pseudotumour Cerebri After

Varicella,” 157 EUR. J. PEDIATR. 904-06 (1998) [Pet. Ex. 35].

38DeSimone, R. et al., “Intracranial Pressure in Unresponsive Chronic Migraine,” 261 J.

NEUROL. 1365-73 (2014) (Resp. Ex. D3].

39 Aplasia is “lack of development of an organ or tissue.” Dorland’s at 116.

40 For reasons previous stated, the undersigned finds onset of headache was not within eight to

twenty-four hours, but instead was approximately one week post vaccination, consistent with

Madison’s visit to her pediatrician on January 24, 2012.

related injured persons. The Program was established to award ‘vaccine-injured persons quickly,

easily, and with certainty and generosity.’” Rooks v. Sec’ y of Health & Human 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).

Petitioners’ burden of proof is a preponderance of the evidence. 42 U.S.C. § 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, 592 F.3d at 1322 n. 2. Proof of medical certainty is not

required. Bunting, 931 F.2d at 873. A petitioner 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 factors unrelated to the administration of the vaccine.” §300aa-

13(a)(1)(B).

b. Elements of Petitioner’s Claim

When a petitioner alleges that an injury listed on the Vaccine Injury Table (“the Table”)

occurs within the time frame set forth in the Table, then petitioner’s vaccine claim is deemed a

Table claim, and a presumption of vaccine causation attaches. See § 300aa-14; see also 42

C.F.R. § 100.3. If, however, a petitioner alleges an injury that is not listed on the Table (such as

the injury alleged in this case), the vaccine claim is deemed a non-Table case, and there is no

presumption of causation. Rather, petitioner must satisfy his burden of proof. See § 300aa-

13(a)(1)(A).

To receive compensation under the Program, petitioner must prove either: (1) that

Madison 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 the varicella vaccine. See 42 U.S.C. §§ 300aa-13(a)(1)(A) and 11(c)(1); Capizzano,

440 F.3d at 1319-20. Petitioners must show that the vaccine was “not only a but-for cause of the

injury but also a substantial factor in bringing about the injury.” Moberly, 592 F.3d at 1321

(quoting Shyface, 165 F.3d at 1352-53).

Because petitioners do not allege that Madison suffered a Table injury, they must prove

that the varicella vaccine Madison received caused his injury. To do so, they must establish, by

preponderant evidence: (1) a medical theory causally connecting the vaccine and Madison’s

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 (“Althen Prong Three”). Althen, 418 F.3d at

1278; 42 U.S.C. § 300aa–13(a)(1) (requiring proof by a preponderance of the evidence).

Because the causation theory must relate to the injury alleged, a petitioner must provide a

reputable medical or scientific explanation that pertains specifically to the vaccinee’s case,

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

Knudsen, 35 F.3d at 548-49. Petitioners cannot establish entitlement to compensation based

solely on their assertions. Rather, a vaccine claim award must be supported either by medical

records or by the opinion of a competent physician. § 300aa-13(a)(1). In determining whether

petitioners are entitled to compensation, the special master shall consider all material contained

in the record, § 300aa-13(b)(1), including “any . . . conclusion, [or] medical judgment . . . which

is contained in the record regarding . . . causation . . . of the petitioner’s illness.” §300aa-

13(b)(1)(A). Thus, the undersigned must weigh the submitted evidence and the testimony of the

parties’ offered experts and rule in petitioners’ favor when the evidence weighs in their favor.

Moberly, 592 F.3d at 1325-26 (“Finders of fact are entitled—indeed, expected—to make

determinations as to the reliability of the evidence presented to them and, if appropriate, as to the

credibility of the persons presenting that evidence”); Althen, 418 F.3d at 1280-81.

c. Factual Disputes

There are two factual disputes: whether petitioner’s post-vaccine headache syndrome is

caused by intracranial hypertension and whether she suffered a “cerebral venous

thromboembolic event” following her January 16, 2012 vaccinations.

The Federal Circuit has made clear that “identifying [the petitioner’s] injury is a

prerequisite” to the Althen analysis. Broekelschen, 618 F.3d at 1346. However, it is not

necessary to diagnose an exact condition. In Lombardi, the Federal Circuit explained: “[t]he

function of a special master is not to ‘diagnose’ vaccine-related injuries, but instead to determine

‘based on the record evidence as a whole and the totality of the case, whether it has been shown

by a preponderance of the evidence that a vaccine caused the petitioner’s injury.” Lombardi v.

Sec’y of Health & Human Servs., 656 F.3d 1343, 1351 (Fed. Cir. 2011) (citing Andreu v. Sec’y

of Health & Human Servs., 569 F.3d 1367, 1382 (Fed. Cir. 2009)). Furthermore, neither the

Vaccine Act nor Althen burdens petitioner with establishing a specific diagnosis. See Kelley v.

Sec’y of Health & Human Servs., 68 Fed. Cl. 84, 100 (2005) (“The Vaccine Act does not require

petitioners coming under the non-Table injury provision to categorize their injury; they are

merely required to show that the vaccine in question caused them injury – regardless of the

ultimate diagnosis.”)

In determining the petitioner’s injury, the undersigned considered the record as a whole.

§ 13(a)(1). She reviewed and relied on statements in the medical records, as medical records are

generally viewed as trustworthy evidence, since they are created contemporaneously with the

treatment of the vaccinee. Cucuras v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528

(Fed. Cir. 1993). In addition, the treating physicians’ opinions are “quite probative,” as treating

physicians are in the “best position” to evaluate the vaccinee’s condition. Capizzano, 440 F.3d at

1326 (Fed. Cir. 2006). However, no treating physician’s views bind the special master, per se;

rather, their views should be carefully considered and evaluated. § 300aa-13(b)(1); Snyder, 88

Fed. Cl. at 745 n. 67. Each opinion from a treating physician should be weighed against other,

contrary evidence present in the record – including conflicting opinions from other treating

physicians. Hibbard v. Sec’y of Health & Human Servs., 100 Fed. Cl. 742, 749 (Fed. Cl. 2011),

aff’d, 698 F.3d 1355 (Fed. Cir. 2012); Caves v. Sec’y of Health & Human Servs., 100 Fed. Cl.

119, 136 (Fed. Cl. 2011), aff’d, 463 Fed. Appx. 932 (Fed. Cir. 2012); Veryzer v. Sec’y of Health

& Human Servs., No. 06-522V, 2011 WL 1935813 at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011),

aff’d, 100 Fed. Cl. 344 (2011).

After careful review of petitioner’s medical records, the undersigned finds preponderant

evidence that Madison’s post-vaccine headache syndrome was caused by intracranial

hypertension. This finding is based on the entire clinical presentation, including the initial

opening pressure at lumbar puncture of 30 cmH2O, abnormal MRV studies, medical literature,

and most significantly, the fact that Madison’s treating physicians diagnosed her with increased

intracranial pressure. It is important to note that intracranial hypertension is rare in children, and

that the majority of cases are not idiopathic but are caused by trauma, endocrine abnormalities,

infection, or medications. Infections associated with the condition include those caused by the

varicella virus.

A significant question raised by Madison’s treating physicians and the experts was

whether her opening pressure of 30 cmH2O at her initial lumbar puncture was diagnostic for

increased intracranial pressure. The studies by Gerstl and Inger persuasively illustrate the point

raised by Dr. Tornatore that previously recommended diagnostic criteria may be too restrictive.

Further, the value must be read in context with other relevant evidence.

The most compelling evidence that Madison’s headaches were caused by intracranial

hypertension are the opinions documented in her medical records by Dr. Gratz. Dr. Gratz treated

Madison beginning in February 2012, early in the course of her illness. He was her treating

physician when she had her lumbar puncture, MRVs, and other diagnostic procedures. His

work-up was comprehensive and his documentation was very thorough. In March 2012, Dr.

Gratz initiated treatment with Diamox for “presumptive therapy of pseudotumor cerebri without

papilledema.” Pet. Ex. 10 at 77-80. In May 2012, Dr. Gratz documented that Madison had

“chronic persistent headaches with associated increased intracranial pressure. . . .” Id. at 56-59.

For these reasons, I find that Madison’s post-vaccine headache syndrome was caused by

intracranial hypertension.

The second fact in dispute is whether Madison suffered a “cerebral venous thrombotic

event” following her January 16, 2012 vaccinations. Dr. Frachtman reviewed the first MRV on

February 3, 2012, and reported that he was unable to see the left internal jugular vein and thus

questioned whether there was a thrombosis or occlusion of the vein. In the next study, on March

28, 2012, Dr. Lopes reviewed both the February and March studies and concluded that the March

study showed “recanalization of the left distal internal jugular vein.” Pet. Ex. 10 at 66. This

suggests that the vein had been previously occluded by a thrombus but there was now blood flow

through the vessel. The reasonable interpretation is that the occlusion was caused by a clot or

thrombus.

In addition to the occlusion of the left internal jugular vein, Dr. Lopes describes a

progression of irregularities involving the left sigmoid sinus. In March, Dr. Lopes describes

these changes as minimal, and in July, the abnormality in the left sigmoid sinus has “worsened,”

and now there is also an abnormality in the right sigmoid sinus. In August, Dr. Lopes describes

improvement, with normal flow in these vessels. In August, Dr. Lopes concludes for the first

time, “There is no sign of sinus thrombosis.” She does not document such a conclusion in her

reports in the earlier studies. Thus, there may have been narrowing and abnormality of the right

and left sigmoid sinuses, but unlike the internal jugular, they were not occluded by a thrombus.

The medical literature filed by respondent’s expert, Dr. Bingham, points out a number of

valid concerns when interpreting the MRV studies, especially the problems caused by

misinterpreting artifact as pathology. However, given that Madison had serial MRV studies and

given the progression of pathology described by Dr. Lopez, this weighs against the likelihood

that the abnormalities were artefactual. Dr. Bingham agreed that the fact that the serial MRVs

were reviewed by the same physician was significant, and that there would be less concern about

inconsistency in interpretation. Tr. 196.

In summary, the undersigned finds preponderant evidence of an occlusion involving the

left distal internal jugular vein and evidence of irregularity or abnormal flow of the left sigmoid

sinus, and some minor irregularity of the right sigmoid sinus. Thus, the undersigned finds that

Madison suffered a cerebral venous thromboembolic event following her January 16, 2012

vaccinations.

d. Althen Analysis

i. Althen Prong One: Petitioners’ Medical Theory

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. Under this

prong, petitioner must make a showing that the received vaccine “can” cause the alleged injury.

Pafford, 451 F.3d at 1355-56.

Petitioner’s theory of causation need not be medically or scientifically certain, but it must

be informed by “sound and reliable medical or scientific explanation.” Knudsen, 35 F.3d at 548-

495; see also Veryzer v. Sec ’y of Health & Human Servs., 98 Fed. Cl. 214, 223 (2011) (noting

that special masters are bound by both § 300aa-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 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 Broekelschen v.

Sec’y of Health & Human Servs., 618 F. 3d 1339, 1347 (Fed. Cir. 2010) (“The special master’s

decision often times is based on the credibility of the experts and the relative persuasiveness of

their competing theories.”); Perreira v. Sec’y of Health & 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)).

As framed by the parties, the relevant question as to Althen Prong One is whether

petitioner has established preponderant evidence of a medical theory showing that HPV and/or

varicella vaccination can result in chronic headache syndrome due to persistent intracranial

hypertension.

As explained by Dr. Tornatore, the varicella vaccine contains a live attenuated virus

known to infect nerves and blood vessels in the brain. Once infected, blood vessels become

inflamed and irritated, causing clots to form or blood vessels to narrow. CSF drains into these

blood vessels, and when there is obstruction of venous blood flow, there is a corresponding

effect on the drainage of CSF fluid, creating a backup of fluid in the brain. The increase of

spinal fluid in a confined space creates an increase in intracranial pressure.

Varicella infection is known to cause this phenomenon, as illustrated by the case reports

described by Gilad,41 Ravid,42 Lahat43 and Konrad.44 While the exact mechanism is not known,

Gilad posits that varicella infection may cause venous outflow abnormalities, low grade

inflammation, or clotting. Pet. Ex. 32 at 2. Ravid also suggests that venous outflow

abnormalities may cause intracranial hypertension. Pet. Ex. 33 at 2. Lahat describes PTC seen

due to middle ear infections, prior to the use of antibiotics. Pet. Ex. 34 at 2.

The DeSimone article, cited by both experts, discusses venous stenosis and resulting

intracranial hypertension due to increased resistance of CSF outflow. Resp. Ex. D3 at 1; Tr. 167.

DeSimone explains that “[i]ntracranial hypertension results from an increased resistance to the

CSF outflow into the cerebral venous blood collectors.” Resp. Ex. D3 at 2. Moreover,

DeSimone states that PTC without papilledema “should be considered in all patients with almost

daily migraine pain, with evidence of sinus stenosis and unresponsive to medical treatment. Id.

at 4.

For all of these reasons, the undersigned finds that petitioner has provided preponderant

evidence that the varicella vaccine45 can cause chronic headache syndrome due to persistent

intracranial hypertension.

ii. Althen Prong Two: Logical Sequence of Cause and Effect

Althen Prong Two requires proof of a logical sequence of cause and effect, usually

supported by facts derived from the vaccinee’s medical records. Althen, 418 F.3d at 1278;

Andreu, 569 F.3d at 1375-77; Capizzano, 440 F.3d at 1326; Grant, 956 F.2d at 1148. 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

(“medical records and medical opinion testimony are favored in vaccine cases, as treating

physicians are likely to be in the best position to determine whether a ‘logical sequence of cause

and effect show[s] that the vaccination was the reason for the injury’”) (quoting Althen, 418 F.3d

at 1280). Medical records are generally viewed as trustworthy evidence, since they are created

contemporaneously with the treatment of the vaccinee. Cucuras, 993 F.2d at 1528. The

petitioner need not make a specific type of evidentiary showing, i.e., “epidemiologic studies,

rechallenge, the presence of pathological markers or genetic predisposition, or general

acceptance in the scientific or medical communities to establish a logical sequence of cause and

41 Gilad, J., CHILD N EUROL. 1 [Pet. Ex. 32]

42 Ravid et al., 46 PED. N EUROL. 124 [Pet. Ex. 33].

43 Lahat et al., 87 ACTA PAEDIATR. 1310 [Pet. Ex. 34].

44 Konrad et al., 157 EUR. J. PEDIATR. 904 [Pet. Ex. 35].

45 Petitioner failed to show by preponderant evidence that HPV vaccination can cause

intracranial hypertension. Thus, the undersigned’s decision is based solely on Madison’s receipt

of the varicella vaccine.

effect.” Capizzano, 440 F.3d at 1325. Instead, petitioner may satisfy her burden by presenting

circumstantial evidence and reliable medical opinions. Id. at 1325-26.

The second question relevant to the analysis of causation is whether petitioner has shown

by preponderant evidence a logical sequence of cause and effect that the varicella vaccination

caused petitioner to suffer a cerebral venous thromboembolic event that resulted in persistent

intracranial hypertension and subsequent chronic headache syndrome. The undersigned finds

that petitioner’s clinical course, the elevated opening pressure for her initial lumbar puncture, her

serial MRV results, and the opinions of her treating physicians, expert, and the medical literature

provide preponderant evidence of a logical sequence of cause and effect. Dr. Tornatore’s

opinions, coupled with the opinions of the treating physicians and the medical case reports cited

were persuasive. Dr. Gratz concluded that Madison’s opening pressure of 30 was elevated. Dr.

Lopes’ interpretations of the MRV studies suggested thrombosis, occlusion, and irregularities of

Madison’s venous outflow system. Dr. Gratz, Dr. Lipton, and Dr. Tornatore all agreed there was

evidence of PTC without papilledema. Madison’s clinical course was also consistent with the

facts set forth in the medical literature and case reports.

The undersigned thus finds that the facts of the case, when viewed in concert with

petitioner’s mechanism of causation, demonstrate a logical sequence of cause and effect

sufficient to satisfy petitioner’s burden under Althen Prong Two.

iii. Althen Prong Three: Is There a Proximate Temporal Relationship?

Althen Prong Three requires petitioner to establish a “proximate temporal relationship”

between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been

equated to mean a “medically acceptable temporal relationship.” Id. The petitioner 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 & Human Servs., 539 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 & Human Servs. 773 F.3d 1239, 1243 (Fed. Cir. 2014); Shapiro v. Sec’y of

Health & Human Servs., 101 Fed. Cl. 532, 542 (2011), recons. den’d after remand, 105 Fed. Cl.

353 (2012), aff’d mem., 2013 WL 1896173 (Fed. Cir. 2013).

Madison received her varicella vaccine on January 16, 2012, and the first reference in the

contemporaneous medical records to headaches was approximately one week later, January 24,

2012. Dr. Tornatore testified that this was a “perfect” onset for his proposed mechanism. Tr. 47.

In the case reports of patients with intracranial hypertension associated with varicella infection

described by Gilad, three patients had a recent history of primary varicella infection, ranging

from 5 days prior to three weeks prior to the presentation of intracranial hypertension. Pet. Ex.

32 at 2-3; See also Pet. Ex. 33 at 2. Ravid notes that “high levels of immunoglobulin G can be

detected within a few days (usually 10-14 days) of the acute infection.” Pet. Ex. 33 at 3.

Although Dr. Bingham conceded that immune-pathogenesis was outside his area of

expertise, he opined that based on petitioner’s proposed mechanism of infection, onset would be

approximately a week. Tr. 154-55. Thus, both experts opined that a temporal association of a

week to 10 days would be appropriate. Medical literature supports onset of five days or more.

The undersigned finds onset to be approximately one week based on the records and thus finds

preponderant evidence of a medically acceptable temporal association in satisfaction of

petitioner’s burden under Althen Prong Three.

e. Alternative causation

Because the undersigned concludes that petitioners have established a prima facie case,

they are entitled to compensation unless respondent can put forth preponderant evidence “that

[Madison’s] injury was in fact caused by factors unrelated to the vaccine.” Whitecotton v. Sec’y

of Health & Human Servs., 17 F.3d 374 (Fed. Cir. 1994), rev’d on other grounds sub nom.,

Shalala v. Whitecotton, 514 U.S. 268 (1995); see also Walther v. Sec’y of Health & Human

Servs., 485 F.3d 1146, 1151 (Fed. Cir. 2007). While Dr. Bingham discussed alternate causes for

chronic headache in Madison, the undersigned did not find the testimony persuasive given the

facts and circumstances of this case.

VIII. Conclusion

For the reasons discussed above, the undersigned finds petitioner is entitled to

compensation. A separate damages order will issue.

IT IS SO ORDERED.

s/ Nora Beth Dorsey

Nora Beth Dorsey

Chief Special Master