Eilan v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 15-381V

Filed: February 23, 2021

PUBLISHED

Special Master Horner

MAJED EILAN and SHAMS EILAN

parents and next friends of A.E., a

minor, Entitlement; Acute

Disseminating

Petitioner, Encephalomyelitis (ADEM);

v. Measles Mumps Rubella (MMR)

vaccine; Varicella vaccine

SECRETARY OF HEALTH AND

HUMAN SERVICES,

Respondent.

Richard Gage, Richard Gage, P.C., Cheyenne, WY, for petitioners.

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

RULING ON ENTITLEMENT 1

On April 15, 2015, petitioners filed a petition under the National Childhood

Vaccine Injury Act, 42 U.S.C. § 300aa-10-34 (2012), 2 alleging that haemophilus

influenza type B (“Hib”), measles mumps and rubella (“MMR”), pneumococcal, and

varicella vaccines, that their daughter, A.E., received on April 27, 2012 caused her to

suffer acute disseminated encephalomyelitis (ADEM). (ECF No. 1.) For the reasons

set forth below, I conclude that petitioners are entitled to compensation for A.E.’s

ADEM.

1 Because this decision contains a reasoned explanation for the special master’s action in this case, it will

be posted on the United States Court of Federal Claims’ website in accordance with the E-Government

Act of 2002. See 44 U.S.C. § 3501 note (2012) (Federal Management and Promotion of Electronic

Government Services). This means the decision will be available to anyone with access to the

Internet. In accordance with Vaccine Rule 18(b), petitioner has 14 days to identify and move to redact

medical or other information the disclosure of which would constitute an unwarranted invasion of privacy.

If the special master, upon review, agrees that the identified material fits within this definition, it will be

redacted from public access.

2Within this decision, all citations to § 300aa will be the relevant sections of the Vaccine Act at 42 U.S.C.

§ 300aa-10-34.

I. Applicable Statutory Scheme

Under the National Vaccine Injury Compensation Program, compensation

awards are made to individuals who have suffered injuries after receiving vaccines. In

general, to gain an award, a petitioner must make a number of factual demonstrations,

including showing that an individual received a vaccination covered by the statute;

received it in the United States; suffered a serious, long-standing injury; and has

received no previous award or settlement on account of the injury. Finally – and the key

question in most cases under the Program – the petitioner must also establish a causal

link between the vaccination and the injury. In some cases, the petitioner may simply

demonstrate the occurrence of what has been called a “Table Injury.” That is, it may be

shown that the vaccine recipient suffered an injury of the type enumerated in the

“Vaccine Injury Table,” corresponding to the vaccination in question, within an

applicable time period following the vaccination also specified in the Table. If so, the

Table Injury is presumed to have been caused by the vaccination, and the petitioner is

automatically entitled to compensation, unless it is affirmatively shown that the injury

was caused by some factor other than the vaccination. § 300aa-13(a)(1)(A); § 300 aa-

11(c)(1)(C)(i); § 300aa-14(a); § 300aa-13(a)(1)(B).

In many cases, however, the vaccine recipient may have suffered an injury not of

the type covered in the Vaccine Injury Table. In such instances, an alternative means

exists to demonstrate entitlement to a Program award. That is, the petitioner may gain

an award by showing that the recipient’s injury was “caused-in-fact” by the vaccination

in question. § 300aa-13(a)(1)(B); § 300aa-11(c)(1)(C)(ii). In such a situation the

presumptions available under the Vaccine Injury Table are inoperative. The burden is

on the petitioner to introduce evidence demonstrating that the vaccination actually

caused the injury in question. Althen v. Sec’y of Health & Human Servs., 418 F.3d

1274, 1278 (Fed. Cir. 2005); Hines v. Sec’ of Health & Human Servs., 940 F.2d 1518,

1525 (Fed. Cir. 1991). Because ADEM is not listed as an injury on the Vaccine Injury

Table, petitioners must satisfy this burden of proof.

The showing of “causation-in-fact” must satisfy the “preponderance of the

evidence” standard, the same standard ordinarily used in tort litigation. § 300aa-

13(a)(1)(A); see also Althen, 418 F.3d at 1279; Hines, 940 F.2d at 1525. Under that

standard, the petitioner must show that it is “more probable than not” that the

vaccination was the cause of the injury. Althen, 418 F.3d at 1279. The petitioner need

not show that the vaccination was the sole cause of the injury or condition, but must

demonstrate that the vaccination was at least a “substantial factor” in causing the

condition, and was a “but for” cause. Shyface v. Sec’y of Health & Human Servs., 165

F.3d 1344, 1352 (Fed. Cir. 1999). Thus, the petitioner must supply “proof of a logical

sequence of cause and effect showing that the vaccination was the reason for the

injury;” the logical sequence must be supported by “reputable medical or scientific

explanation, i.e., evidence in the form of scientific studies or expert medical testimony.”

Althen, 418 F.3d at 1278; Grant v. Sec’y of Health & Human Servs., 956 F.2d 1144,

1148 (Fed. Cir. 1992). A petitioner may not receive a Vaccine Program award based

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solely on his or her assertions; rather, the petition must be supported by either medical

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

In what has become the predominant framing of this burden of proof, the Althen

court described the “causation-in-fact” standard, as follows:

Concisely stated, Althen’s burden is to show by preponderant evidence

that the vaccination brought about her injury by providing: (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 proximate temporal relationship

between vaccination and injury. If Althen satisfies this burden, she is

entitled to recover unless the [government] shows, also by a

preponderance of the evidence, that the injury was in fact caused by

factors unrelated to the vaccine.

Althen, 418 F.3d at 1278 (citations omitted). 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, a Program

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.

II. Procedural History

On April 15, 2015, petitioners filed their petition, alleging that ten days after their

daughter, A.E., received the HIB, MMR, pneumococcal, and varicella vaccinations, A.E.

started experiencing intermittent high fevers and ultimately, suffered ADEM that was

caused-in-fact by the vaccinations A.E. received on April 27, 2012. (ECF No. 1.)

This case was first assigned to Special Master Millman. (ECF No. 4.) During the

initial status conference on June 29, 2015, petitioners’ counsel stated that “this claim

was filed near the expiration of the statute of limitations, and as a result, he has not yet

obtained many of the medical records.” (ECF No. 8.) Petitioners subsequently filed

medical records in support of their claim and a Statement of Completion. (ECF Nos. 7,

9, 13.)

On January 25, 2016, respondent filed his Rule 4 report, recommending against

compensation. (ECF No. 17.) Respondent stated that A.E. was not diagnosed with

ADEM and the alleged 10-day onset was not reflected in the medical records filed. (Id.

at 10-11.) Instead respondent indicated that the medical records showed that A.E.

started having fevers 25 days after vaccination and started experiencing developmental

regression 50 days after vaccination. (ECF No. 17, n.11.)

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In response to respondent’s Rule 4 report recommending against compensation,

petitioners filed an expert report from neurologist Marcel Kinsbourne, M.D. (ECF No.

25; Ex. 12.) Respondent filed a responsive expert report from neurologist Michael

Kruer, M.D. (ECF No. 40, Ex. A.) On September 25, 2017, petitioners filed a

supplemental expert report from Dr. Kinsbourne, responding to Dr. Kruer. (ECF No. 42;

Ex. 36.) Petitioners filed an amended statement of completion on July 17, 2018. (ECF

No. 45.)

On July 25, 2018, Special Master Millman issued an Order, indicating that

“[w]hen this case is transferred to another special master upon [her] retirement, the new

special master will schedule a hearing date.” (ECF No. 46.) Thereafter, the case

largely remained dormant until it was reassigned to my docket on June 7, 2019. (ECF

No. 48.)

On June 11, 2019, I ordered the parties to confirm how they wished to proceed

and to select mutually agreeable hearing dates in February 2020, if needed. A two-day

entitlement hearing was ultimately scheduled to commence February 19, 2020. (ECF

Nos. 49, 65.) In the interim, respondent filed a supplemental expert report from Dr.

Kruer on July 25, 2019 and petitioner filed a second supplemental expert report from Dr.

Kinsbourne on November 19, 2019. (ECF Nos. 53, 64; Exs. C, 48.) A two-day

entitlement hearing was held on February 19 and 20, 2020. (See ECF Nos. 92-93,

Transcript of Proceedings (“Tr”).). Drs. Kruer and Kinsbourne testified.

Following the hearing, the parties attempted to informally resolve the case;

however, on December 2, 2020, respondent advised that informal resolution would not

be possible. (ECF No. 103.) Petitioners subsequently confirmed on January 21, 2021,

that the case is ripe for resolution. (ECF No. 105.)

III. Factual History

a. Medical Records

i. Pre-Vaccination Records

A.E. was born on April 23, 2011 and was admitted into NICU at Lehigh Valley

Pediatric Associates due to jaundice. (Ex. 2, pp. 240-44, 250.) A.E. stayed at NICU for

five days for phototherapy. (Ex. 2, p. 310; Ex. 43, pp. 523-27.) A.E. was discharged

home with her parents in good condition on April 29, 2011. (Ex. 2, p. 240-41.) On July

1, 2011, she was seen for a routine well check and was reported to have achieved her

milestones of “Palmar grasp, Regards face, Follows with eyes and social smile.”

Additionally, she could lift her head briefly erect when held upright and cooed and

responded to loud sounds. (Ex. 2, p. 251.) On September 9, 2011, petitioners brought

A.E. back for another routine well check. (Ex. 2, p. 254.) At this visit, A.E. received

DTaP, HIB, IPV, pneumococcal, and rotavirus vaccinations. (Ex. 2, p. 255; Ex. 3.) At

her 6-month routine well check, A.E. continued to achieve developmental milestones

and received another round of vaccinations including DTaP, HIB, pneumococcal, and

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rotavirus. (Ex. 2, p. 264; Ex. 3.) On February 10, 2012, A.E. had her 9-month well-child

visit and was reported to have achieved her developmental milestones including

crawling, sitting without support, pulling to stand, imitating speech sounds, self-feeding,

and playing “Pat-A-Cake.” (Ex. 2, p. 266.) At this visit, additional laboratories were

ordered, including a lead screening, and A.E. received additional routine vaccinations.

(Ex. 2, p. 267.)

ii. Vaccination and Initial Treatment

On April 27, 2012, A.E. received the HIB, MMR, pneumococcal, and varicella

vaccinations during her first-year child wellness checkup. (Ex. 2, p. 274-75; Ex. 3.) Her

exam was normal, and she was continuing to achieve developmental milestones such

as pulling to stand, walking without support, pincer grasping, pointing, saying one to

three works, looking for hidden objects, and crawling. (Ex. 2, p. 274.)

Subsequently, petitioners brought A.E. to see her pediatrician, on June 7, 2012,

reporting that petitioners “were in the ER for 1-1/2 hours last night and they did nothing.

[A.E. has been] sick for 17 days, high fever for 3 days, balance off, hold right ear.” (Ex.

2, p. 277.) Physical examination was normal. (Ex. 2, pp. 277-78.) A.E. was assessed

to have a sore throat and unspecified viral infection; however, lab results revealed A.E.

tested negative for strep. (Ex. 2, p. 278.) Petitioners were advised to treat fever and

pain with acetaminophen and ibuprofen as needed. (Ex. 2, p. 278.)

On June 20, 2012, A.E. returned to her PCP’s office with complaint of “fever for

28 days on and off.” (Ex. 2, p. 279.) It was reported that A.E. had a temperature of up

to 102 and also that she had symptoms of cough, fatigue, and loss of appetite. (Id.)

Upon physical examination, there was no abnormal findings and A.E. was assessed

with fever that comes and goes. (Ex. 2, p. 280.) Two days later, A.E. returned with a

complaint of fever again. (Ex. 2, p. 285.) Again, physical examinations recorded

normal findings; however, A.E. was then assessed with unspecified fever, prescribed

antibiotics, and had a bladder catheterization. (Id. at 285-86.)

On June 28, 2012, A.E. was seen by her PCP again and this time, in addition to

continuing intermittent fevers up to 104, A.E. was also reported to have regressed in

motor developments where “she used to pull up to stand and cruised around furniture

but now she rolls over and tries to pull herself up and cannot.” (Ex. 2, p. 289.) On

physical examination, A.E. had “head lag when pulled up and flopped over when sat up.

Muscle tone appear[ed] normal but reflexes appear[ed] decreased.” (Ex. 2, p. 290.)

A.E. had elevated testing results and was then admitted to Lehigh Valley Hospital for

evaluation and work-up. (Id.) According to petitioners’ health plan inpatient admissions

report, A.E. was admitted to Lehigh Valley Hospital for infectious ADEM. (Ex. 2, p.

297.)

A.E. was then examined by Dr. Claudia F. Busse at Lehigh Valley Hospital. (Ex.

4, pp. 1-4.) As part of A.E.’s history of present illness, it was recorded that “6 weeks

ago started to have fevers,” but A.E. was seen at the emergency room and “reassured.”

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Also, three or four days after the onset of fevers, petitioners noted that A.E. showed loss

of balance and A.E. was seen by her PCP and “reassured” regarding such symptom.

(Ex. 4, p. 1.) A.E.’s admission records also indicated that petitioners noted progressive

loss of truncal strength, loss of words, and ability to sit or stand, and that A.E. had

drainage from both ears. (Id.) Dr. Busse admitted A.E. with an initial diagnoses of

developmental regression with loss of truncal tone/head control and fevers. (Ex. 4, p.

4.) She also listed “tumor, encephalitis, GBS, metabolic [disorder]” as differential

diagnoses. (Id.)

Upon admission, A.E. had a neurology consultation with Dr. Muhammed Sheikh

for loss of milestone and poor trunk control. (Ex. 2, p. 291-92; Ex. 4, pp. 21-22.) Dr.

Sheikh reported that A.E. started having a fever six weeks ago that only subsided when

ibuprofen was used. (Ex. 2, p. 291.) He also noted that A.E. was seen by her PCP

several times and A.E. was “felt to have otitis media and were prescribed an antibiotic.

However the child did not improve and were seen by the pediatrician, again.” (Id.)

Petitioners told Dr. Shiekh that A.E., in the last two weeks, had significantly regressed,

where she was no longer able to sit or cruise, had a spacey look, and was not babbling

as much. (Id.) Upon examination, Dr. Shiekh noted that A.E. had a spacey look, her

pupils appeared to be a little dilated, her movements appeared to be a little sluggish,

and she was unable to sit independently without support. (Id. at 292.) Dr. Shiekh’s

impression was that A.E. had signs of spasticity in the lower extremities with significant

poor truncal tone and balance and history of significant regression in association with a

febrile illness. He recommended an MRI and spinal tap, seeking to rule out ADEM,

metabolic conditions, and encephalitis. (Id.)

On June 29, 2012, A.E.’s condition was found unchanged and was evaluated by

a speech pathologist and pediatric nutritionist, where they found that A.E. had

significant swallowing difficulty and poor oral skills. (Ex. 4, pp. 102, 106-08.) A.E.’s

June 28, 2012 MRI revealed evidence of brain atrophy, poor myelinization in the

anterior limbs of the internal capsules, the genus of the corpus callosum, the corona

radiata and the centrum semi-ovale. (Ex. 2, p. 303; Ex. 4, pp. 101, 118.) Dr. Busse

stated that A.E.’s MRI findings were “concerning for underlying neurodegenerative

disorder versus encephalitis.” (Ex. 2, p. 303; Ex. 4, p. 101.)

A.E. was febrile overnight on June 30, 2012, but was eating better than before.

(Ex. 4, p. 137.) A.E. also had a spinal tap which yielded normal cytology results, her

culture remained negative, and enterovirus detection was also negative. (Ex. 2, p. 303.)

A.E.’s lab study for protein CSF results on June 29, 2012 was 121. (Ex. 4, p. 111.)

Additionally, Dr. Busse noted that A.E.’s CSF WBCs were 13. (Ex. 2, p. 303, Ex. 4, p.

204.) Dr. Busse’s impression indicated “brain atrophy [rule out] mixed white/gray matter

disease” and “fever with neurofocal exam.” (Ex. 4, p. 138.) Dr. Busse wanted to wait on

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lyme testing results 3 and planned to insert a PICC line 4 for possible IVIG treatment.

(Id.) A PICC line was placed under sedation on July 1, 2012. 5 (Ex. 4, p. 157.)

By July 1, 2012, A.E. was afebrile overnight and appeared to improve in head

control, but showed no improvement of muscle tone of lower extremities. (Ex. 4, p.

162.) On July 2, 2012, A.E. was able to sit in a highchair and was moving her legs,

indicating a “big improvement.” (Ex. 4, p. 181.) Petitioners wanted a second opinion

and arrangements to transfer A.E. were made. (Ex. 2, p. 303.)

On July 3, 2012, 6 A.E. was discharged from Lehigh Valley Hospital with

diagnoses of West Nile virus encephalitis and developmental regression. (Ex. 2, p.

303.) During her hospitalization, “she continued to spike fevers to a max of 101.” (Id.)

Dr. Busse noted that “[a]fter a transfer, West Nile virus antibodies results, indicating

recent West Nile virus infection, with West Nile virus encephalitis being the most likely

diagnosis.” (Id.) A.E. was then transferred as an inpatient to St. Christopher’s Hospital

in Philadelphia. (Ex. 2, p. 303.) According to petitioners’ health plan inpatient

admissions report, A.E. was admitted to St. Christopher’s Hospital for infectious ADEM.

(Ex. 2, p. 297.)

A.E. was transferred to Dr. Douglas Thompson at St. Christopher’s Hospital on

July 3, 2012 with the diagnosis of “fever unknown origin.” (Ex. 5, p. 21.) Upon

admission and preliminary examinations from various physicians, the assessment was

that A.E. was a 14-month female with weeks of intermittent fevers and rapid regression

of developmental milestones. (Ex. 5, p. 52, 54.) The initial diagnoses included post-

infectious etiologies, metabolic disorder or neurodegenerative disorder, and given her

history of fevers and possible improving symptoms, post-infectious “seems more likely

[at] this time.” (Ex. 5, p. 52, 56.)

Later that day, A.E. had a consultation with infectious disease specialist, Dr.

Janet Chen, for intermittent fever for six weeks and loss of milestones. (Ex. 1, p. 1.) As

part of the history of present illness, Dr. Chen recorded that A.E. began having daily

fevers six weeks prior to being transferred to St. Christopher’s Medical Center from

Lehigh Valley Hospital. (Id. at 1.) Additionally, initially after one day of continued fever,

A.E. went to the emergency room and was discharged with a viral disease. Then, A.E.

saw her PCP, who came to the same diagnosis, but after 10 days of persistent fevers,

A.E. visited a different doctor who diagnosed her with left acute otitis media and treated

3 Lyme titre results were negative. (Ex. 4, p. 182.)

4PICC line is a peripherally inserted central catheter that’s for long term use. (PICC Line, STEDMANS

MEDICAL DICTIONARY, at 504750.)

5 Additionally, at St. Christopher’s Hospital, a clamp and new cap was placed on PICC line on July 3,

2012. (Ex. 5, p. 17.)

6 There were some records that indicated A.E. was discharged on July 2, 2012, but the majority of the

records from Lehigh Valley Hospital listed the discharge date as July 3, 2012. Additionally, there were

records from St. Christopher’s Hospital that were dated July 2, 2012. (Ex. 5, pp. 1-8.) The admitting

records indicate that A.E. was examined on July 3, 2012 at 3:50AM. (Ex. 5, p. 52.)

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her with antibiotics. (Id.) Dr. Chen also noted that 15 days prior to being transferred to

St. Christopher’s, A.E. began having increasing weakness. (Id. at 2.) Notably, upon

physical examination, Dr. Chen indicated A.E. was positive for head lag, had some

head control when upright, low truncal tone, and was unable to sit unassisted. (Id. at 5.)

Dr. Chen’s impression was that A.E. was a 14-month female with no significant past

medical history “presenting with [six] weeks of intermittent fevers [and two] weeks of

neurological regression, with slight improvement in past [two] days. Doesn’t appear to

have acute infectious process but cannot rule out post-infectious etiology or neurologic

causes.” (Ex. 1, p. 5.) Dr. Chen recommended further testing including a need to

review A.E.’s brain MRI and “evaluate for acute disseminated encephalomyelitis before

discussing possibility of steroid or IVIG.” (Id. at 5-6.) Included in her notes was a

discussion of ADEM, in which Dr. Chen explained that:

Acute disseminated encephalomyelitis, or ADEM, is usually a monophasic

inflammatory demyelinating disease that involves the central nervous

system [and] usually occurs after a nonspecific illness or more rarely, after

vaccination. Diagnosis is based on clinical finding [and] abnormalities

detected on MRI. ADEM is responsible for clinical encephalitis in a

substantial percent of cases in the first 2 years of life. Multiple neurological

signs develop over days. It often follows respiratory infections, like

influenza [and] mycoplasma pneumoniae. Incidence has declined since

MMR [and] varicella vaccines were implemented. Rarely, vaccines can

cause postinfectious encephalitis. In the US, <1 in 1 million doses of

measles vaccines is estimated to cause ADEM. History of illness 2-3

weeks within onset of ADEM is seen in 50-80% of cases … With lack of

evidence of ongoing infection along with the usual timelapse of a few

weeks [between] symptoms of illness - onset of ADEM makes it more

likely that it is a post-infectious autoimmune process . . . The characteristic

of ADEM occur over a mean of 5 days.

(Id. at. 6-7.)7

On July 4, 2012, A.E. had an EEG, which showed normal sinus rhythm. (Ex. 5,

p. 86.) The next day, A.E. was examined by Dr. Maria Begel who noted that A.E. had

waxing and waning ability to lift her head but no new symptoms regarding her loss of

developmental milestones. (Id. at 99.) Additionally, A.E. remained afebrile. (Id.)

During her stay at St. Christopher’s Hospital, A.E. received speech therapy and medical

nutrition therapy, and consultations for occupational therapy and physical therapy. (Id.

at 100-08, 152-53, 181.) A.E. also saw Dr. Chen again and was noted to be “clinically

stable with infectious evaluation negative thus far.” (Id. at 110.) However, on July 6,

2012, A.E. had a follow-up examination with infectious disease specialist Dr. Long, who

had the impression of “unlikely acute infection of CNS or post-infectious CNS. Cannot

exclude either. West Nile encephalitis possible.” (Ex. 5, p. 117.)

7 The last page of Dr. Chen’s note – page 8 – was not initially filed as part of Exhibit 1. That page was

later filed separately as Exhibit 59.

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During her time at St. Christopher’s Hospital, she remained afebrile and her

truncal hypotonia improved. (Ex. 2, p. 296, 305.) Dr. Thompson stated that A.E.’s MRI

at Lehigh Valley Hospital showed “diffuse white matter disease and was suggestive of a

possible adrenoleukodystrophy with infection a lesser possibility,” and “[s]erologies

came back positive for West Nile virus IgG and negative for IgM,” where the

“discrepancy was felt to be non-diagnostic, but left West Nile virus a possibility.” (Id. at

305.) Dr. Thompson stated that upon discharge, confirmatory testing, including repeat

lumbar puncture with serum and CSF and metabolic studies were still pending. (Id.)

A.E.’s physical examination at discharge did not note any abnormal findings. (Id.)

A.E.’s CSF lab report showed “cellular CSF with lymphocytes, macrophages and few

RBC. No malignant cells seen.” (Ex. 5, p. 203.) On July 10, 2012, A.E. was discharged

from St. Christopher’s Hospital to be transferred to a rehabilitation facility, with the

diagnoses of central hypotonia, acute flaccid paralysis, post-infectious encephalitis

versus metabolic disorder, and West Nile IgG. (Ex. 2, p. 305; Ex. 5, p. 35.)

Upon discharge from St. Christopher’s Hospital, A.E. was transferred to Good

Shepherd Rehabilitation Hospital “for comprehensive rehabilitation regarding significant

hypotonia and loss of developmental milestones secondary to post infectious

encephalitis versus metabolic disorder.” (Ex. 2, p. 308.) Although A.E.’s generalized

weakness had improved, “she remains significantly regressed in her milestones” and

upon admission, overall, A.E. had limited mobility and was very hypotonic. (Id. at 309.)

A.E.’s rehabilitation diagnoses were nontraumatic brain injury, ADEM versus metabolic

disorder, central hypotonia, generalized debility and weakness from acute illness,

impaired mobility, regression of development milestones, impaired communication, and

impaired oral motor skills. (Id. at 312.) A.E. spent more than three months at Good

Shepherd Rehabilitation Hospital and was discharged on October 29, 2012. (Id. at

313.)

During her time at Good Shepherd, A.E. underwent comprehensive occupational,

physical, speech, and recreational therapy. (See generally, Ex. 7.) Her goals of

therapy included “optimize nutrition and hydration. Watch spasticity,” and “[i]mprove

overall strength and endurance working towards age appropriate development skills.

Maintain [range of motions], prevent contractures.” (Ex. 7, p. 1.) Throughout July 2012,

A.E. had “good night[s]” and did not experience any fevers. (Id. at 145-47, 152, 156.)

Additionally, A.E.’s social interactions and engagement also showed signs of

improvement. (Id. at 168-76.) A.E. continued to have poor oral intake, but showed

some continuing improvement. (Id. at 162, 165, 168, 176, 179.)

On a report dated July 27, 2012, Center for Disease Control and Prevention

reported no evidence of infection with any of the viruses tested. This report listed onset

date as May 16, 2012. (Ex. 2, p. 314-15.) On September 8, 2012, petitioners submitted

a VAERS report, stating that adverse onset was June 7, 2012, where A.E. started to

have fevers and by June 28, had severe neurological symptoms that petitioners

believed were caused by the MMR, Varicella, HIB, and pneumococcal vaccines. (See

Id. at 321.)

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Throughout August 2012, A.E.’s oral feedings showed improvement. (Ex. 7, pp.

208-30.) Additionally, A.E. continued having good nights without new concerns,

improved in tone and spasticity, and tolerated her therapies. (Id. at 233-59.) Although

A.E.’s tone showed steady improvement, her spasticity “remain[ed] a barrier to

acquisition of functional skills. Parents remain[ed] reluctant to pharmacologic

intervention for tone.” (Id. at 242.) A.E.’s August 3, 2012 progress note indicated for

the first time that she tested negative for West Nile virus. (Id. at 208.) By August 24,

2012, A.E. had better trunk and head control and her hands were more open. (Id. at

59.) At the end of August 2012, A.E. had “an erupting right lower molar (an eruption

cysts burst extruding yellow and bloody fluid),” and developed small “rashes on her

trunk. They look like heat rashes on exam. [However,] The arthropod bites [were]

disappearing.” (Id. at 272, 275.)

In September 2012, A.E. continued to “demonstrate steady improvement in

function,” and did not develop any “new medical concerns.” (Ex. 7, pp. 1-29, 281-286.)

Of note, on September 13, 2012, A.E. “[had] runny nose, clear mucus. Some cough. No

fever. No [respiratory] distress. Tone remains variable but is slight only this morning.

Mother reports that she observes much improvement with [A.E.’s] fine motor skills.” (Id.

at 309.) Additionally, her viral lab results were negative. (Id. at 311-15.) Aside from

that, A.E. continued to have good nights with no new concerns. (Id. at 319-25.) On

September 28, 2012, A.E. was started on medication, Baclofen, for her spasticity. (Id.

at 30, 33.) Throughout October 2012, A.E. continued to show improvement, including

being alert, smiling, reaching, better overall tone, holding her head up, and eating her

meals. (Id. at 40-69.) Baclofen dosage was changed because A.E. “was noted to be

more sluggish.” (Ex. 7, p. 50.) However, there were some concerns about her diet,

weight, and nutrition, and in early October, A.E. had some congestion. (Id. at 45, 47,

54, 58-63.) By mid-October, A.E. was still having problems eating and her weight

gradually decreased, but petitioner-mother was against any tube feeding at night. (Id. at

74, 78.) Regarding her occupational and physical therapies, A.E. was improving her

gross and fine motor functions. (Id. at 86.)

On October 25, 2012, A.E. had another brain MRI, which showed “[a]bnormal

patchy symmetric FLAIR/T2 signal hyperintensity within the periventricular and

subcortical white matter, probably reflect[ing] hypomyelination or postinfectious

demyelination. Suggestion of some improvement in demyelination pattern along the

posterior deep white matter tracts of the centrum semiovale and corona radiata. Mild

persistent intracerebral volume loss.” (Ex. 7, p. 33; Ex. 8, p. 1.) On October 26, 2012,

A.E. was prescribed with pediasure, enteral pump, and NG tube for her post infectious

encephalitis, spastic quadriparesis, and poor oral intake. (Ex. 2, p. 328; Ex. 7, p. 118.)

A.E. was later discharged on October 29, 2012. (Ex. 2, p. 329.) Her physical

therapist, Cindi Hobbes reported on A.E.’s discharge summary that A.E. “has made

slow [and] steady progress towards her goal during this admission.” (Ex. 7, p. 125.) PT

Hobbes recommended A.E. continue physical therapy, early intervention programs,

seating and equipment evaluation for customer stroller. (Id.) A.E.’s speech language

pathologist added that A.E. had difficulty with oral motor and swallowing skills,

10

secondary to overall deficits in motor control and coordination. (Id. at 128.) A.E.’s

recreational therapist reported that A.E. made “significant progress during her

admission. [A.E.] now able to sit in long sit to play for at least [10 minutes].” (Id. at 129.)

Additionally, Dr. Rosauro Dalope described A.E.’s course while admitted at Good

Shepherd in the discharge summary, stating that “upon admission, [A.E.] underwent

comprehensive OT, PT, ST evaluation and treatment and pediatric psychiatry, pediatric

neuropsychology, and nutrition were consulted.” (Ex. 2, p. 329.) Dr. Dalope stated that

At the time of discharge, [A.E.] continued to have global hypotonia and

hypertonia with activity and persistent strong extension pattern for

movement. She did demonstrate ability to weight shift in prone with the

upper extremity reaching and rolling. She persisted with marked motor

planning and motor control deficits. She continued to have poorly graded

movement. She did have bilateral increased tone. She did demonstrate

purposeful grasp and release of toys and emerging self feeding skills.

Overall she had made significant improvement in fine motor and self help

skills since admission.

(Id. at 329-30.) Upon physical examination at discharge, Dr. Dalope noted spasticity on

the elbows, knees, and ankles. (Id. at 330.) Additionally, “[a] repeat MRI in October

2012 did not show any progression of the lesions. Some areas were showing

demyelination.” (Id. at 331; Ex. 7, p. 136.) Dr. Dalope stated that “[g]iven that there are

now changes in the milestones, the patient’s findings are concerning for underlying

neurodegenerative disorder.” (Ex. 2, p. 331.)

iii. Post Initial Treatment Records 8

Petitioners continued bringing A.E. to visit her pediatrician, Dr. Oscar A. Morffi,

for follow up appointments after being discharged from Good Shepherd Rehabilitation

Center, throughout the rest of 2012 and throughout 2013.

On November 15, 2012, A.E. had an appointment at St. Christopher’s Metabolic,

Program, Neurology Section with Dr. Reena N. Jethva for “further consideration of

metabolic/genetic causes.” (Ex. 2, p. 9-13.) A.E.’s history of present illness reported

that “[a]round 12 months, she received MMR vaccination and she initially seemed well.

After about 5-10 days, she started to be more fussy and not as interactive. She

developed a fever about 15 days after the MMR immunization, up to 104.7 F,

fluctuating.” (Id. at 9.) Further, A.E. “had CSF studies that were unremarkable with

white blood cell count of 2, red blood cell count of 144, clear fluid, glucose 48 and

protein 20.” (Id. at 9.) On physical examination, it was noted that A.E. had generalized

motor weakness, truncal ataxia, head lag but hypertonic body, abnormal fluence speech

and abnormal naming ability. (Id. at 11.) A.E. was assessed with chronic

leukodystrophy, but further testing was ordered to consider other diagnoses in the

differential. (Id. at 12.) Also, A.E.’s developmental regression improved as she was

8 From this point forward, specific discussion of appointments for routine childhood illnesses are omitted.

11

regaining some skills and her “[t]one somewhat improved but still with significant

peripheral hypertonia/spasticity and central hypotonia.” (Id. at 12.) On November 23,

2012, A.E. returned to see her PCP regarding her persistent nasal congestion. (Ex. 2,

pp. 30-31.) At this visit, A.E. was diagnosed with acute sinusitis. (Id. at 31.)

On November 26, 2012, A.E. underwent an early intervention program

evaluation 9 and A.E. was found eligible to receive early intervention services. (Id. at 16-

27.) On January 28, 2013, A.E. had her wellness visit with Dr. Morffi. (Id. at 50.) A.E.’s

neurological evaluation revealed normal coordination and normal tone and power in all

four extremities. (Id. at. 51-52.) A.E. returned to her pediatrician’s office on March 29,

2013 in order to have forms completed and to obtain a refill on medication. (Id. at 65.)

Petitioner-mom stated that A.E. was apparently making slow progress. At this

appointment, Dr. Deshpande “spent time reassuring mom and encouraging her to

continue to work with” A.E. (Ex. 2, p. 65.)

On June 17, 2013, A.E. had a check-up visit regarding her leukodystrophy with

Dr. Agustin Legido. (Id. at. 76.) Upon physical examination, A.E. had poor

coordination, had inaccurate fine motor movements, had difficulty swallowing, was

unable to bear weight on her legs, and was unable to speak. (Id. at 78.) A.E.’s

diagnosis continued to be leukodystrophy of unknown etiology and was instructed to

continue taking Baclofen and undergo a follow up MRI. (Id.)

During A.E.’s two-year well-child visit on June 21, 2013, it was reported that A.E.

has not achieved some of her milestones including, walking unassisted, pulling to stand,

saying words, and self-feeding. (Id. at 72.) Physical examination revealed normal

findings, except for A.E.’s gait was described as waddling with assistance, and at this

visit, A.E. received a DTaP vaccination. (Id. at 73-74.)

On July 26, 2013, A.E. had a follow up MRI. (Ex. 2, p. 88; Ex. 8, p. 3.) In

comparison to her October 25, 2012 study, again the “T2 FLAIR imaging are areas of

abnormal hypersensitivity within the cerebral white matter” and such “degree of

hyperintensity is abnormal suggesting leukoencephalopathy and this can include

leukodystrophy as suggested in the clinical history.” (Ex. 2, p. 88.) Similar

hyperintensity was found within the cerebral peduncles; however, there were stable

findings in many regions of the cerebral hemispheres and “there may be slight

progression within the frontal lobes.” (Id.)

9 A.E. had a subsequent evaluation in November 2013, where she was found to be eligible to received

continued early intervention services. (Ex. 2, pp. 151-62.) The reports in both evaluations revealed that

A.E. had at least a 25% delay below the mean in one or more areas of development and showed a need

for specially designed intervention. (Ex. 2, pp. 25, 160.) A.E. continued receiving early intervention

services throughout 2014 and 2015, but it was determined that she did not need preschool special

education services during scheduled breaks. (Ex. 34, p. 53.) However, for 2016, she was eligible for

scheduled breaks based on A.E.’s reasonable educational progress and that she “has been able to

maintain and recoup skills in a reasonable amount of time following breaks.” (Ex. 34, p. 84.)

12

On September 11, 2013, A.E. saw her PCP for a follow-up appointment

regarding her encephalitis. (Id. at 97.) A.E. was reported as improving where her tone

was better, and she was standing and being more social. (Id.) A review of systems

indicated that A.E. experienced tremors; however, on physical examination, A.E.’s

neurological findings were normal including normal coordination, normal tone and power

in all four extremities. (Id. at 97-98.) Dr. Morffi’s impression was that A.E.’s condition

was improving, but also referred A.E. for further neurology consultation and physical

therapy evaluation. (Id. at 98.)

On September 13, 2013, A.E. also saw Pediatric Nurse Practitioner, Harriot G.

Silliman and Dr. Charles Brill at Nemours Dupont Pediatrics. (Ex. 8, pp. 7-12.) Dr. Brill

found that A.E. “demonstrated increased tone in the extremities with extensor posturing

and low truncal tone.” (Ex. 2, p. 104; Ex. 8, p. 11.) Both NP Silliman and Dr. Brill

suggested A.E. continue her therapeutic services and referred her to white matter

specialist, Dr. Sarah Hopkins. (Ex. 2, p. 104; Ex. 8, pp. 10-12.) At their

recommendation, an updated EEG was performed on September 26, 2013, and A.E.’s

results were normal. (Ex. 2, p. 113.)

On October 9, 2013, A.E. had a consultation with Dr. Sarah Hopkins for a second

opinion regarding white matter changes. (Ex. 2, pp. 137-44; Ex. 8 pp. 16-20.) Under

history of present illness, Dr. Hopkins recorded that “2 weeks after her 12 month shots

(MMR, varicella, PVC7, and HiB) … A.E. began to seem more ‘lazy,’ and didn’t want to

run around as much as usual [and] around that time she began to have fevers that were

recurrent and without clear batter and began to have loss of developmental milestones.”

(Ex. 2, p. 137.) Additionally, Dr. Hopkins noted that when A.E. was admitted to Lehigh

Valley Hospital, A.E.’s “work-up was significant for elevated protein in the CSF and

white matter abnormalities on MRI.” (Id.) Petitioners reported to Dr. Hopkins that there

was no further regression since being discharged from Good Shephard Rehabilitation

facility and that A.E. has been regaining skills. (Id.) Additionally, baclofen has

significantly helped A.E. with the spasticity in her extremities. (Id.)

Dr. Hopkins indicated that neuroradiologist, Dr. Kandula, reviewed A.E.’s past

three brain MRIs, and found, “[t]he radiological differential would include a subacute

sclerosing panencephalitis (SSPE), progressive multifocal leukoencephalopathy (PML),

or nonviral encephalitis.” (Id. at 139.) On neurological and motor exams, Dr. Hopkins

noted that A.E. had “decreased bulk and increased tone in the extremities, with

markedly decreased truncal tone and decreased tone in face [and she had] difficulty

holding her head up.” (Ex. 2, p. 140.) Dr. Hopkins’s impression “is that the initial event

was inflammatory, most likely infectious or parainfectious, but a metabolic disorder or

leukodystrophy exacerbated by infection cannot be entirely ruled out.” (Id.) In coming

to this conclusion, Dr. Hopkins consulted with a neuroradiologist and infectious disease

specialist, and through her review of the medical records, she highlighted that A.E. had

increased CSF protein and increased ESR, A.E.’s imaging revealed progression of

myelination, and A.E. has since made developmental progress. (Id.) Dr. Hopkins also

noted that “[w]hile ADEM can follow vaccination and present with fever and

encephalopathy the pattern of white matter involvement is atypical.” (Id.) As part of her

13

recommendations, Dr. Hopkins suggested petitioners file a VAERS report since they

had concerns about A.E.’s vaccinations, but Dr. Hopkins also indicated that she was

unable to definitively connect the event to the vaccine, only that the case bears

investigating. (Id. at 141.) Dr. Hopkins further recommended repeated imaging on a

yearly basis to assess for stability and to obtain CSF for full metabolic studies if

petitioners were concerned about further progression of disease. (Id.)

A.E. had a follow-up appointment with Dr. Legido on October 14, 2013. (Ex. 2, p.

122.) Petitioner-mom reported that “since the last visit in April 2013, [A.E.] has

improved in regards to her milestones. [A.E.] is able to walk with the help of a walker,

able to speak 2 syllables, feed [herself]. Spasticity has remained stable.” (Id.) A.E. was

undergoing physical therapy three times a week, occupational therapy twice a week,

speech therapy twice a week, and early intervention at home. 10 (Id.) Dr. Legido

ordered A.E. to continue her therapy sessions and ordered mitochondria testing. (Id. at

124.)

On November 18, 2013, A.E. underwent spine thoracolumbar imaging which

revealed mild reverse S-shaped scoliosis thoracolumbar spine with mild right inferior

pelvic tilt, but no osseous lesion, fracture, or subluxation. (Ex. 2, p. 163.) A certificate

of medical necessity filled out by her PCP on December 16, 2013 indicated that A.E.

needed occupational therapy for her diagnoses of encephalitis, flaccid paralysis, and

developmental regression. (Id. at 168.)

A.E. had a two-year well-child visit on January 31, 2014 with Dr. Morffi. (Id. at

183.) A.E. had still not met certain milestone such as walking unassisted, pulling to

stand, and saying three to six words, but her physical examination revealed normal

findings including normal coordination, tone, and power in all four extremities, and gait.

(Id. at 183-84.) On May 23, 2014, A.E. visited Dr. Morffi for a three-year well-child

check-up. (Id. at 202.) A.E. could walk unassisted, pull to stand, and say words, but

was still unable to meet her milestones as to crawling upstairs, walking up steps,

running, and saying short phrases. (Id.) A.E. had allergic rhinitis and less BMI for her

age. (Ex. 2, p. 204.) About a week later, A.E. returned to her PCP’s office with a

complaint of an acute one-day fever. (Id. at 206.) Again, she was treated as having

acute otitis media and upper respiratory infection. (Id. at 207.)

A.E. continued to have occasional office clinic visits from Good Shepherd

Rehabilitative Hospital and received frequent outpatient speech, occupational, and

physical therapy from OP Pediatric Rehabilitation Program Health and Technology

Center after she was formally discharged in October 2012. (See Exs. 11, 51.) A.E.’s

first return to Good Shepherd was on November 9, 2012, where her listed diagnoses

now stated Acute demyelinating encephalomyelitis first. (Ex. 11, p. 1.) It was noted that

10 According to A.E.’s therapy plan after an initial assessment at OP Pediatric Rehabilitation Program

Health and Technology Center, A.E. was recommended to receive intensive speech, occupational, and

physical therapy 2-3x/week. (Ex. 11, p. 39.) According to A.E.’s physical and occupational therapy

notes, it appears that A.E.’s insurance approved physical therapy twice a week and occupational therapy

three times a week. (See e.g., Ex. 11, pp. 202, 599, 924.)

14

since her discharge, A.E. was doing “fairly well.” (Id.) After physical examination, Dr.

Dalope assessed that, “[A.E. was now] 18 months old with a diagnosis of postinfectious

acute demyelinating encephalomyelitis. She is still showing some slow but steady

progress. She has maintained most of her functions that she had when she left here.”

(Id. at 2.) A.E. was to continue physical, occupational, and speech therapy as well as

continue Baclofen for her spasticity. (Id. at 2-3.) However, during A.E.’s next visit on

February 25, 2013, she was assessed by Dr. Dalope to be a “22-month-old female with

a history of acute onset of encephalopathy with diffuse brain damage of unknown

etiology, which has left her with spastic quadriparesis and global developmental delay.”

(Id. at 5.) Dr. Dalope, however, was “extremely impressed today in the 4 months since

[A.E.’s] discharge [with] how interactive and alert she is and the gains that she has

made including independent sitting, standing with assistance, using more signs.” (Id.)

A.E.’s subsequent visit records presented A.E. with spastic quadriplegia secondary to

unknown etiology affecting the white matter. (Ex. 11, pp. 14-24.) During her August 7,

2014 visit, A.E. received Botox injections to her legs bilaterally. (Id. at 22.) A.E.

continued receiving Botox injections subsequently. (Id. at 28, 34.)

Since November 2012, A.E. has been receiving physical, occupational, and

speech therapy, varying from twice to three times a week for each respective session.

(Exs. 11, 51.) The medical diagnosis remained “NTBI, post infectious encephalitis” or

“NTBI, encephalopathy” for the majority of her treatment and A.E. was making progress

towards her short-term and long-term goals. In August 2014, A.E.’s physical therapist

noted that, “[s]ince her Botox she demonstrates improved tolerance to bracing and

therefore improved assisted gait.” (Ex. 11, p. 1401.) A.E. started wearing braces

around her legs and continued with aquatic therapy and balance exercises. (Id. at

1107, 1119-26.) In October 2014, A.E. was crawling on hands and knees, meeting her

new goals; however, A.E. was reported sick for several weeks and due to that “she has

demonstrated significant deconditioning as a result of being sick.” (Id. at 1478.) During

A.E.’s physical session on November 7, 2014, petitioner-mom reported that A.E.’s MRI

showed improvement, however her medical diagnosis was never changed or updated.

(Id. at 1536.) A.E. continued showing steady progress and was benefitting from Botox

injections in 2015. (Id. at 1847.)

On October 31, 2014, a brain MRI was performed and as compared to A.E.’s

July 26, 2013 results, “the degree of signal abnormality in central white matter is less.

However, there appears to be a greater degree of signal abnormality and subcortical

white matter especially in the temporal lobes.” (Ex. 6, p. 1.) The MRI report further

stated that the “improving appearance raises the question of ADEM rather than

leukodystrophy. Clinical correlation is recommended.” (Id. at 2.)

Following her October 31, 2014 MRI, A.E. visited Dr. Legido for a “[f]ollow up of

ADEM.” (Ex. 43, p. 274; Ex. 44, p. 174). In giving a full history of present illness, Dr.

Legido wrote that, after five to ten days of receiving the MMR vaccination when she was

12 months, A.E. started to become more fussy and not as interactive. Then about 15

days after MMR vaccination, A.E. developed a fever and about when she was 14-15

months, she started experiencing developmental regression. (Ex. 44, p. 174.)

15

Additionally, he wrote that when she was hospitalized, she had unremarkable CSF

studies, and it “was felt that an infectious etiology could not be found and that other

etiologies had to be investigated. She was [diagnosed] with ADEM.” (Id.) Dr. Legido

assessed A.E. with infectious ADEM and wrote that she was making slow progress with

language, fine, and gross motor skills. He recommended that she continue supportive

therapies. (Id. at 177.)

Throughout 2015, 2016, and 2017, A.E. went to her PCP’s office for various

complaints including persistent fevers, sore throat, earache, cough, nasal congestion,

and wellness check-up. (See Id. at 1-51.) Dr. Vilas Deshpande wrote a note on

September 16, 2016, indicating that A.E. is not receiving the second MMR, DTaP, and

IPV vaccines because of a bad reaction and that A.E. has been diagnosed with

encephalitis. (Ex. 43, p. 225; Ex. 44, p. 125.)

In September 2016, A.E. began kindergarten and had an IEP in place. (Ex. 35,

p. 2.) A.E. was categorized with orthopedic impairment and speech and language

impairment. (Id. at 7.) A.E. was eligible for specially designed instruction in order to

make gains in the general education curriculum. (Id. at 32.) A.E.’s IEP recommended

“supplemental physical support, physical therapy as a related service, speech and

language support as related services, OT as a related service, transportation as a

related service (life van), and PCA [personal care assistant] as a related service.” (Id. at

32.) A.E. had an eye exam on November 30, 2016 with Dr. Mark S. Trachtman. (Ex.

45; Ex. 44, p. 107.) Dr. Trachtman described A.E. as a “five-year-old who has a history

of cerebral palsy.” (Ex. 45, p. 4.) A.E. was “found to definitely be myopic and could

benefit from corrective glasses.” (Id.)

A.E. saw her PCP for several office visits throughout 2018 and 2019, where her

assessments listed ADEM. (Ex. 47, pp. 1-11.) On September 10, 2018, A.E. visited Dr.

Legido for ADEM follow-up for the first time since November 2014. Although A.E. was

still taking Baclofen, it “doesn’t seem to help,” but the Botox was working better and

managing the stiffness. (Id. at 35.) Dr. Legido found that A.E. has “presumptive ADEM

(based on improving white matter changes on repeat MRI brain and improving clinical

status).” (Id. at 38.) Dr. Legido discussed with petitioners that “there is no current

treatment to reverse the damage to the brain,” and that he was “unsure of specific

cause of ADEM.” Additionally, Dr. Legido noted that in A.E.’s case it was “viral versus

post vaccine.” (Id. at 38.) Additionally, A.E. continued with physical and occupational

therapy. (Ex. 51.) Her 2018 occupational therapy records indicated the medical

diagnosis as “Encephalitis, Developmental Regression, Leukodystrophy,” while her

2018 physical therapy records maintained the same medical diagnosis, “NTBI, post

infectious encephalitis.” (See e.g., Id. at 1-4, 49-53.) A.E. also had speech therapy

sessions between May 2019 and August 2019, where her medical diagnosis was now

spastic quadriparesis cerebral palsy. (Id. at 120-37.) She was discharged from skilled

speech therapy services after having met her short term goals. (Id. at 121.)

16

IV. Expert Opinions

a. Petitioners’ Expert, Dr. Marcel Kinsbourne

In support of their claim, petitioners presented an expert opinion by neurologist

Marcel Kinsbourne, M.D. Dr. Kinsbourne has served as a senior fellow at the Center for

the Study of Aging and Human Development at Duke University, an adjunct professor of

neurology at Boston University School of Medicine, a research professor at the Center

for Cognitive Studies at Tufts University, and a professor of psychology at New School

University. (Ex. 13, p. 2.) Dr. Kinsbourne obtained his B.M.B. Ch. from Oxford

University Medical School in 1955 and his medical degree from State of North Carolina

in 1967. (Id. at 1.) According to his curriculum vitae, Dr. Kinbourne sits on various

editorial boards relating to neurology and psychology. He has numerous publications

relating to various neurological disorders. (Id. at 3-33.) He has largely been retired

from clinical practice since the early 1990’s. (Tr. 95-96.)

In his first report, Dr. Kinsbourne opined that it is biologically plausible that both

the MMR vaccine and the varicella vaccine can cause ADEM, and here, a temporal

relationship existed between A.E.’s vaccinations and the onset of A.E.’s ADEM.

Specifically, Dr. Kinsbourne stated that:

ADEM is an immune-mediated demyelinating disorder of the central

nervous system, which commonly presents with fever and sometimes

headache. These prodromal events are followed by the emergence of

neurological findings, including motor deficits, and lowered level of

consciousness, coupled with evidence of multifocal lesions of

demyelination on neuroimaging, “that usually occurs a few days or weeks

following vaccine administration or virus-like disease.”

(Ex. 12, p. 4 (citing Inst. of Med. (US) Vaccine Safety Comm., Adverse Events

Associated with Childhood Vaccines: Evidence Bearing on Causality (Kathleen R.

Stratton, Cynthia J. Howe & Richard B. Johnston Jr. eds., 1994)).) Moreover, Dr.

Kinsbourne stated that a wide range of bacterial and viral antigens are capable of

causing ADEM and, citing to various medical literature, MMR vaccination has been well

documented as a cause of ADEM and other neurological disorders. Dr. Kinsbourne

relied on articles by Garg, Weibel, and Landrigan. (Ex. 12, p. 5.) Additionally, Dr.

Kinsbourne indicated that the varicella vaccine, as a member of the herpes family, has

been reported to cause encephalitis. (Id. at 6.) Although “[a] variety of mechanisms

have been suggested as the means by which infections can initiate autoimmune

diseases,” Dr. Kinsbourne focused on molecular mimicry. But ultimately, he indicated

that it is challenging to identify the exact mechanism and therefore, it is medically

reasonable to assume that one or more mechanism was responsible for A.E.’s ADEM.

(Id. at 6-7.)

Dr. Kinsbourne also opined that the interval between A.E.’s MMR and varicella

vaccination and the onset of her fevers and ataxia “is consistent with medical literature

17

as to temporal intervals between provocative events, notably infections, and the onset

of ADEM.” (Id. at 7.) Addressing A.E.’s diagnosis, Dr. Kinsbourne explained that:

ADEM is an inflammatory disorder and in some three-quarters of cases,

the onset of ADEM occurs in the wake of an identifiable febrile prodromal

illness or immunization and with prominent constitutional signs and

encephalopathy of varied degrees. The febrile prodrome may last three

weeks or more. It abates as the neurological deficits take hold.

(Id. at 4.) Thus, Dr. Kinsbourne opined that the “conspicuously febrile onset” of A.E.’s

disorder and the “initially elevated sedimentation rate and liver function test levels” were

consistent with A.E.’s ADEM diagnosis. Dr. Kinsbourne, using the Brighton

Collaboration Encephalitis Working Group diagnostic definitions, opined that A.E.

satisfied four of the nine categories of neurological deficits, further supporting her ADEM

diagnosis. Dr. Kinsbourne stated that:

[A.E.’s] case abundantly satisfies these criteria as regards (1) to

encephalopathy, (6) motor weakness, (7) altered deep tendon reflexes

and (9) cerebellar dysfunction; ataxia. MRI findings displaying multifocal

white matter lesions on T2 weighted sequences, and these features, as

well as the monophasic course of her illness confirm the ADEM diagnosis.

These criteria were intended to inform the diagnosis of ADEM in cases of

alleged vaccine injury.

(Ex. 36, p. 2.)

Additionally, Dr. Kinsbourne stated that “[e]vidence is absent for alternative

causation.” (Ex. 12, p. 8.) Dr. Kinsbourne reported that “the clinical diagnosis of

leukodystrophy was never supported by neuroradiological, clinical laboratory or genetic

finding,” and that ADEM is A.E.’s current diagnosis as established by her treating

physicians, Dr. Sarah Hopkins and Dr. Kimberly Kuchinski, 11 and A.E.’s most recent

neuroimaging study on October 31, 2014. (Id. at 3, 7.)

In his supplemental expert reports, in response to Dr. Kruer’s challenging A.E.’s

ADEM diagnosis, Dr. Kinsbourne addressed A.E.’s elevated liver enzymes, the

possibility of blood contamination causing elevated CSF proteins, and A.E.’s

neuroimaging study results. Dr. Kinsbourne concluded that “elevated liver enzyme

levels neither favor nor disfavor the diagnosis of ADEM,” since “elevated liver enzymes

are frequently found without any known cause.” (Ex. 48, p. 1.) Dr. Kinsbourne also

maintained that A.E.’s CSF protein was elevated even when accounting for blood

contamination and further stated that “[c]orrection of CSF levels for blood found in CSF

to be widely practiced.” (Ex. 36, p. 1; Ex. 48, pp.1-2.) Regarding A.E.’s neuroimaging,

Dr. Kinsbourne agreed that A.E.’s diffuse symmetric brain lesions, pre-existing cerebral

atrophy, and delayed myelination are not typical or features of ADEM, but Dr.

11From the rehabilitation records, it appears that Dr. Kuchinski replaced Dr. Dalope as A.E.’s primary

doctor at Good Shepherd.

18

Kinsbourne asserted that these aspects do not rule out ADEM. (Ex. 36, p. 2; Ex. 48, pp.

2-3.) Dr. Kinsbourne thought that the neuroimaging studies were more important in

ruling out leukodystrophy and showing lessened white matter abnormalities in

supporting a diagnosis of ADEM. (Ex. 48, p. 2.)

Additionally, Dr. Kinsbourne stated that “remission is consistent with the

monophasic trajectory observed in ADEM,” and emphasized that A.E.’s most updated

medical records show that A.E.’s “development has slowly but steadily continued to

improve.” (Ex. 36, p. 2; Ex. 48, p. 3.) Dr. Kinsbourne maintained that A.E.’s “relentless

stable, slow progress” indicates that her condition is monophasic, which ADEM typically

is, and therefore, “ADEM is the only medically reasonable diagnosis in evidence.” (Ex.

48, p. 3.)

With regard to the temporal relationship, Dr. Kinsbourne maintained that a three

week onset and the duration of A.E.’s fevers are not inconsistent with ADEM.

Specifically, Dr. Kinsbourne stated that although the timing of A.E.’s fever was not

typical of a post immunization fever, “the fever may have been a marker of a subacute

onset of the ADEM,” and that “[t]here is no established time limit for the duration of fever

in ADEM,” but “[r]elevant publication note that it can be prolonged.” (Ex 36, p. 1; Ex. 48,

p. 1.)

b. Respondent’s Expert, Dr. Michael Kruer

Respondent presented an expert opinion from pediatric neurologist, Michael

Kruer, M.D. Dr. Kruer is board certified in pediatric neurology and trained in clinical

neuroimmunology. Dr. Kruer established the Sanford Pediatric Neuroimmunology Clinic

in Sioux Falls and currently serve as a specialist consultant in pediatric

neuroimmunology at Phoenix Children’s hospital, where he is also co-director of the

hospital’s Neurogenetics Program. Dr. Kruer has treated both adult and pediatric

patients with ADEM, multiple sclerosis, autoimmune encephalitis, and related disorders.

(Ex. A, p. 1.)

Dr. Kruer opined that “the constellation of fever starting so long after vaccine

administration, elevation of liver enzymes, and prolonged fever all argue against

vaccine-mediated injury.” (Id. at 3.) First, Dr. Kruer stated that “fever onset 3 weeks

later attributable to immunization is unheard of and is clinically and immunologically

implausible.” (Id. at. 2.) Additionally, Dr. Kruer stated that vaccines are not known to

cause elevations of liver enzymes12 or prolonged fevers as the facts in A.E.’s case

provide. (Id. at 2.)

Further, Dr. Kruer contested A.E.’s ADEM diagnosis, emphasizing that there was

no laboratory evidence to support an ADEM diagnosis and A.E.’s neuroimaging was not

consistent with ADEM. (Id. at 3.) Specifically, Dr. Kruer found that Dr. Kinsbourne’s

characterization of A.E.’s levels of white blood cells in her cerebrospinal fluid (CSF) as

12 During the hearing, Dr. Kruer later clarified that the elevated liver enzymes are “of unknown

significance” and do not “clearly point us away” from an ADEM diagnosis. (Tr. 200-01.)

19

abnormal to be misleading, when, according to Dr. Kruer, A.E.’s protein levels were

within normal value and therefore, not showing any CNS inflammation. (Id. at. 3.)

Additionally, with regard to neuroimaging, A.E.’s symmetric pattern of involvement is not

suggestive of ADEM and her diminished cerebral volume and delayed demyelination

suggest that “another process (distinct from ADEM) is at work.” (Ex. A, pp. 3-4.)

Additionally, Dr. Kruer opined that A.E.’s prolonged fever was “inconsistent with ADEM-

associated fever, which typically abates once the neurological symptoms begin.” (Id. at.

4.) Dr. Kruer also found the fact that A.E.’s primary treating physicians did not treat her

with ADEM therapeutics as supportive against a diagnosis of ADEM. (Id. at 3.)

Ultimately, Dr. Kruer contested the diagnosis based on timing of A.E.’s fevers, the

duration of her prolonged fevers, the elevated liver enzymes, the unreliable presence of

elevated CSF protein, and lesions revealed in A.E.’s neuroimaging. (See Exs. A, C.)

Dr. Kruer agreed that A.E. did not have leukodystrophy, but “[t]here are scores of other

disorders which might present with the symptoms that AE did in the context that they

occurred without invoking either ADEM or leukodystrophy.” (Ex. A, p. 4-5.)

In his supplemental expert report, Dr. Kruer continued to challenge A.E.’s

diagnosis, stating that “there are more factors arguing against ADEM than arguing for

the diagnosis.” (Ex. C, p. 3.) Dr. Kruer maintained that A.E.’s pattern of demyelination

is crucial in diagnosing ADEM and that there exists a unifying diagnosis that explains

A.E.’s baseline cortical atrophy and delayed myelination as well as her other symptoms.

(Id. at 3-4.) In his opinion, it is “[m]ore likely, AE does NOT have ADEM and does NOT

have a classic leukodystrophy (as captured in the medical records) but she does

instead have a (likely neurogenic) disorder that features developmental delay, cortical

atrophy, delayed myelination, and a waxing and waning of symptoms.” (Id. at 3)

(emphasis original).)

V. Discussion

Acute disseminated encephalomyelitis or “ADEM” is an immune-mediated

demyelinating disorder of the central nervous system, often seen in childhood and

generally considered to be monophasic. (Daniela Pohl et al., Acute Disseminated

Encephalomyelitis, 87 NEUROLOGY S38 (2016) (Ex. A, Tab 4, p. 1).) It shares some

characteristics with multiple sclerosis and often occurs post-infectiously. (Id.) It is

generally understood as a syndrome of brain inflammation and demyelination occurring

in temporal association to an antecedent event. (James J. Sejvar et al., Encephalitis,

myelitis, and acute disseminated encephalomyelitis (ADEM): Case definitions and

guidelines for collection, analysis, and presentation of immunization safety data, 25

VACCINE 5771, 5775 (2007) (Ex. 30, p. 5).) It shares many features with encephalitis,

but is distinguished from acute encephalitis based on the predominance of

demyelinating rather than cytotoxic injury. (Id.) Clinically, however, ADEM can be

difficult to distinguish from encephalitis. (Id.) The “hallmark” of ADEM is the

demonstration of scattered, focal or multifocal (disseminated) areas of inflammation and

demyelination within the cerebral subcortical and deep cortical white matter. (Id.)

20

In this case, there is actually no dispute as to whether A.E.’s MMR and varicella

vaccines can cause ADEM. Respondent’s expert, Dr. Kruer, has agreed that they can.

Rather, the primary focus of this case has been the question of whether A.E. actually

suffered ADEM at all. Absent a diagnosis of ADEM, petitioners have not otherwise

articulated any basis for concluding that A.E.’s injury was vaccine-caused. In resolving

this question, I turn first to the disputed point of whether A.E.’s treating physicians

diagnosed ADEM. Concluding that they did, I then separately consider whether that

diagnosis was sound based on Drs. Kinsbourne’s and Kruer’s discussions of the

relevant diagnostic criteria. Concluding that there is preponderant evidence favoring the

diagnosis of ADEM, I then apply the three Althen prongs to the facts of A.E.’s case.

Last, I examine whether respondent has established any causal factor unrelated to

vaccination.

a. A.E.’s Treating Physicians Did Diagnose ADEM

As a threshold matter, a key aspect of respondent’s defense in this case is his

assertion that A.E.’s treating physicians never moved beyond a differential diagnosis to

“definitely” or “conclusively” diagnose A.E. with ADEM. (ECF No. 74, pp. 13-14.)

Although A.E.’s presentation clearly presented her physicians with a difficult diagnosis,

respondent’s line of reasoning is unpersuasive for two reasons. First, respondent

downplays the seriousness with which A.E.’s treating physicians initially considered

ADEM and post-infectious etiologies. Second, respondent does not give sufficient

weight to the fact that the treaters ultimately concluded with the fullness of time that

ADEM was her likely diagnosis.

Both respondent and Dr. Kruer assert that none of A.E.’s treating physicians

actually diagnosed her with ADEM. (Id.; Tr. 161-62.) However, this is not accurate. As

Dr. Kinsbourne addressed in his recitation of the medical records, A.E.’s later medical

records include the explicit diagnosis of ADEM by Drs. Totlani (Ex. 47, p. 2), a

pediatrician, and Legido, a neurologist. (Ex. 66, pp. 5-9; Tr. 73-76.) Dr. Legido’s

neurology record in particular included a complete recitation of A.E.’s prior history,

including her presenting symptoms, hospital transfer, and reference to the difficulty in

reaching a diagnosis. 13 (Ex. 66, pp. 5-6.) He diagnosed ADEM of either viral or post-

13In his prehearing brief, respondent notes that there is a reference in A.E.’s Good Shepherd

Rehabilitation records to a discharge diagnosis of ADEM made at St. Christopher’s Hospital. (ECF No.

74, p. 14, n.11 (citing Ex. 2, p. 329.) Respondent indicates that this is a mischaracterization, because

A.E. was discharged from St. Christopher with only a differential diagnosis. (Id. (citing Ex. 2, p. 305.).)

Respondent’s observation is correct with regard to that specific notation, however, other assessments in

the Good Shepherd records refer to the complete list of differential diagnoses. (Ex. 2, pp. 308-13.) In

any event, this isolated reference is not a factor in this analysis. Nor is there evidence that this notation

unduly influenced subsequent records. Dr. Legido’s record also includes an abbreviated notation that

characterizes A.E. as having been diagnosed with ADEM at St. Christopher’s. (Ex. 66, p. 6 (“she was dx

with ADEM.”).) However, there are several reasons for understanding this notation as interpretive rather

than mistaken. First, Dr. Legido is himself affiliated with St. Chistopher’s and therefore a part of A.E.’s

overall team of care providers that reached this differential diagnosis. Second, even though he was first

consulted after A.E.’s hospitalization, he includes a substantive description of A.E.’s hospital course at St.

Christopher’s, clearly evidencing he is aware of her complete history and is not basing his opinion merely

on the fact of a discharge diagnosis. (Id.) Third, the competing aspect of the differential diagnosis at St.

21

vaccine etiology. (Id. at 8.) Dr. Legido first became a part of A.E.’s care when she was

seventeen months old. (Id. at 1.)

Dr. Legido’s ultimate assessment was the culmination of a long history in which

ADEM or post-infectious etiology more generally remained a durable aspect of a difficult

differential diagnosis in contrast to other types of disorders, such as metabolic

disorders, leukodystrophies, or other neurodegenerative conditions, all of which were

eventually ruled out. (See, e.g., Ex. 2, p. 297 (pediatrician recording hospital transfer to

Lehigh Valley Hospital for “infectious ADEM”); Ex. 4, p. 4 (initial differential diagnosis

including encephalitis); Ex. 2, p. 292 (initial neurology consultation indicates ADEM will

need to be ruled out); Ex. 4, p. 101 (following first MRI, differential diagnosis including

postinfectious encephalitis versus neurodegenerative disorder); Ex. 2, p. 303 (Lehigh

Valley Hospital discharge diagnosis of West Nile virus encephalitis); Ex. 2, p. 297

(pediatrician recording hospital transfer to St. Christopher’s Hospital for “infectious

ADEM”); Ex. 5, p. 52 (upon initial evaluation at St. Christopher’s Hospital noting of

differential diagnosis that “post-infectious [etiology] seems more likely”); Ex. 1, p. 6-7

(discussing ADEM at length and noting of A.E. that she “doesn’t appear to have acute

infectious process but cannot rule out post-infectious process or neurologic causes.”);

Ex. 5, p. 117 (“unlikely acute infection of CNS or post-infectious CNS. Cannot exclude

either.”); Ex. 5, p. 35 (discharged from St. Chrisopher’s with differential diagnosis of

post-infectious encephalitis versus metabolic disorder); Ex. 7, p. 33 (second MRI

interpreted as possibly including postinfectious demyelination); Ex. 2, pp. 138-40

(second opinion from neurologist Dr. Hopkins indicating after three MRIs that “the initial

event was inflammatory, most likely infectious or parainfectious, but a metabolic

disorder or leukodystrophy exacerbated by infection cannot be entirely ruled out.”); Ex.

6, p. 1-2 (final MRI report indicating that “improving appearance raises the question of

ADEM rather than leukodystrophy.”).) Dr. Kruer explained during the hearing that, while

ADEM, post-infectious encephalitis, and encephalitis, are different concepts, usage of

the terminology is “a little bit inconsistent” and “the terms are used a little bit loosely by

different practitioners.” (Tr. 163.) He agreed that “ADEM is often thought to be post-

infectious.” (Tr. 164.)

Dr. Kruer did acknowledge that later records include the diagnosis of ADEM, but

suggested that he “can’t say with certainty” why that diagnosis was made and that his

impression is that it was merely “carried forward” due to the lack of a clear alternative

diagnosis. (Tr. 164-65.) In light of his own opinion that A.E.’s diagnostic possibilities

should have been broadened to include evaluation for neurogenetic conditions, Dr.

Kruer sought to explain this narrowing of A.E.’s differential diagnosis as merely “chart

lore.” (Tr. 162-65.) That is, Dr. Kruer suggests that once a set of potential diagnoses

are charted by a group of physicians, those diagnoses take undue precedence in the

minds of the physicians moving forward as acute care gives way to chronic

Christopher’s was a metabolic disorder and Dr. Legido’s reference to the prior ADEM diagnosis was

immediately followed by his confirmation that a subsequent metabolic workup by Dr. Jethva was normal.

(Id.) Fourth, the implicit crux of Dr. Legido’s record as a whole is that he is closing out the differential

diagnosis in favor of ADEM. He specifically indicates in his impression that A.E. now carries a

“presumptive” diagnosis of ADEM in consideration of her repeat MRIs and improving clinical picture. (Id.

at 8.)

22

management of symptoms. (Id.) Importantly, however, while this may be a relevant

concern in the medical community, it is not axiomatic. It is not inherently bad for a

physician treating residual effects or sequela to give weight to the direct observations or

conclusions of another physician involved contemporaneously in earlier diagnosis and

treatment. Especially in light of the St. Christopher records as a whole, including both

Dr. Chen’s initial “extensive” consideration of ADEM during hospitalization (Exs. 1, pp.

1-7, 59) and Dr. Legido’s later explicit culminating diagnosis (Ex. 66, pp. 5-9), both of

which are supported by records which reveal their thinking, Dr. Kruer’s blanket

skepticism is not persuasive. Effectively, Dr. Kruer’s citation to chart lore in this case is

a restatement of his disagreement with the treating physicians under a different guise

and does not cast doubt on the fact of A.E.’s ADEM diagnosis as contained in the

medical records

Dr. Kruer is correct, however, that during her hospitalizations and initial

evaluations none of A.E.’s treating physicians conclusively diagnosed her with ADEM in

light of ongoing evaluation. Dr. Kruer does acknowledge that ADEM was referenced

throughout this medical history, and also that infectious disease specialist Dr. Chen

considered the diagnosis “extensively.” (Tr. 161-62.) Nonetheless, he opines that

these assessments must be given less weight because treatment for ADEM was not

initiated, opining that this constitutes “strong evidence” against the diagnosis having

been made. (Tr. 138-40, 165, 183-84.) Dr. Kinsbourne in contrast opined that the

hesitance in administering IVIG and steroids was due to the fact that these treatments

are not free of risk or side effect and in the case of IVIG also expensive. (Tr. 103-04.)

He also proposed that these treatments were not pursued later because A.E. was

already improving. (Tr. 106.) Dr. Kruer disagreed, however, and stressed that IVIG and

steroids are so low risk that the lack of treatment must signal the lack of a diagnosis.

(Tr. 138-40, 183-84.) Neither expert’s view finds strong support in the medical records.

In her consultation, Dr. Chen explained the basis for steroids and IVIG as

treatments for ADEM and included discussion of such treatment among her

recommendations. (Ex. 59; Ex. 1, p. 6.) She noted, however, that further review of

A.E.’s MRIs should first be completed to confirm ADEM. (Ex. 1, p. 6.) Nonetheless, Dr.

Kinsbourne persuasively noted, based on Dr. Chen’s full discussion of the condition,

that she must have intended ADEM to be part of her diagnostic impression, stating “I

don’t see how else you can interpret her train of thought and her complete emphasis on

ADEM.” (Tr. 104-06.) The recommended steroid and IVIG treatments were not

subsequently administered at St. Christopher’s, yet A.E.’s discharge indicated a

differential diagnosis of “postinfectious encephalitis vs metabolic disorder,” meaning that

following Dr. Chen’s consultation ADEM was explicitly not ruled out during A.E.’s

subsequent hospitalization at St. Christopher’s. 14 (Ex. 5, p. 35.) Dr. Chen did

specifically stress in her discussion of steroids and IVIG treatments for ADEM that

14

Dr. Chen herself appears to have used ADEM and “postinfectious encephalitis” interchangeably, writing

in her discussion of ADEM that “[r]arely, vaccines can cause postinfectious encephalitis.” (Ex. 1, pp. 6-7.)

As noted above, Dr. Kruer confirmed that these terms are used loosely by different practitioners. (Tr.

163-64.)

23

“[t]here are no controlled clinical trials on treatments,” perhaps providing some basis for

suspecting Dr. Chen was doubtful of the efficacy of these treatments. (Ex. 59.) In any

event, the medical records do not reveal any specific reason IVIG or steroids were not

administered. Notably, both experts focused exclusively on the value of steroids and

IVIG in treating ADEM and neither expert addressed what effect, if any, these

treatments would have on a metabolic disorder, which was the other side of the

differential diagnosis at St. Christopher’s.

One additional clue exists in the truncation of A.E.’s hospitalization at Lehigh

Valley Hospital when she was transferred to St. Christopher’s Hospital. While still at

Lehigh Valley Hospital, A.E. had a PICC line installed for the purpose of administering

IVIG. (Ex. 4, pp.138, 157.) Shortly thereafter, the physicians at Lehigh Valley consulted

Dr. Shulman at Children’s Hospital of Philadelphia. (Id. at 181-82.) It was Dr. Shulman

who recommended that Lehigh Valley not proceed with the IVIG in anticipation of the

fact that A.E. would be transferred and additional infectious disease work up, likely

including serum and antibody testing, would be explored. (Id.) During the hearing, Dr.

Kruer confirmed his understanding that this was the reason that IVIG treatment was

halted before being administered. (Tr. 186-88.) He explained that, because IVIG

treatment introduced donor antibodies into the patient, it would confound any

subsequent serum or antibody testing. (Id.) Once A.E. was transferred to St.

Christopher’s Hospital, she was seen for consultation by infectious disease specialist

Dr. Chen. (Ex. 1; Ex. 59). As noted above, Dr. Kruer acknowledges that Dr. Chen

“extensively considered” ADEM. (Tr. 162.) However, A.E. was still undergoing work up

for a possible infectious etiology for her condition. (Ex. 1, 59.) Though Dr. Chen linked

IVIG treatment to review of A.E.’s MRI, consistent with Dr. Kruer’s explanation of Dr.

Shulman‘s recommendation, Dr. Chen also felt that serum testing for Epstein Barr virus

and cytomegalovirus was warranted, suggesting another reason Dr. Chen may have

withheld IVIG treatment, at least initially. (Ex. 1, pp. 5-6.)

In sum, the record as a whole does not provide any meaningful discussion of why

these treatments were not administered and both experts’ explanations as to the

motives of A.E.’s treating physicians are speculative. In contrast to Dr. Kruer’s

interpretation, the medical records reflect that A.E.’s IVIG treatment plan may be better

understood as delayed or inchoate due to facility transfer and subsequent testing rather

than never having been contemplated and the fact that A.E. did not receive IVIG or

steroid treatment therefore does not appear to illuminate her physicians’ thinking as to

her correct diagnosis. “Since medical records typically record only a fraction of all that

occurs, the fact that reference to an event is omitted from the medical records may not

be very significant.” Murphy v. Sec’y of Health & Human Servs., 23 Cl. Ct. 726, 733

(Fed. Cl.1991), aff'd, 968 F.2d 1226 (Fed. Cir. 1992) (citing Clark v. Sec'y of Dep't of

Health & Human Servs., No. 90-45V, 1991 WL 57051 (Cl. Ct. Mar. 28, 1991)). Because

A.E. was treated by multiple physicians at multiple facilities, all of whom were struggling

with a challenging differential diagnosis, the medical records are inscrutable for any

precise reason IVIG or steroids were not administered.

24

On the whole, petitioners persuasively contend that “[t]he medical records

support the diagnosis of ADEM. The process by which the diagnosis was derived was

lengthy, but that is simply the nature of this neurologic injury . . . [the treating physicians]

simply followed a conservative path to the correct diagnosis.” (ECF No. 84, p. 3.) In

that regard, Dr. Kinsbourne repeatedly stressed that A.E.’s presentation in the longer

course confirmed the monophasic course of A.E.’s condition. (Tr. 34-35, 38-39, 40-43,

68, 77, 89, 99-102, 107-08.) While Dr. Kruer stressed that ADEM is not the only

monophasic condition that could potentially explain a course such as A.E.’s (Tr. 142-44,

194), Dr. Kinsbourne noted that the other specific conditions previously identified in

A.E.’s differential diagnosis tended to be progressive (Tr. 61, 68, 89). In that regard it is

significant that Dr. Legido likewise confirmed that his diagnostic opinion was specifically

informed in part by “improving white matter changes on repeat MRI and improving

clinical signs.” (Ex. 66, p. 8.)

Accordingly, while this remains a difficult case and A.E.’s treating physicians did

struggle to move beyond a differential diagnosis for a considerable period, the medical

records, when viewed as a whole, include preponderant evidence that her treating

physicians did ultimately, albeit remotely, arrive at a diagnosis of ADEM. This is

significant because medical records are generally viewed as particularly trustworthy

evidence created contemporaneously with the treatment of the patient. Cucuras v.

Sec'y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993). Though neither

binding nor sacrosanct, treating physician opinions are probative and are often afforded

considerable weight in themselves. Andreu ex rel. Andreu v. Sec’y of Health & Human

Servs., 569 F.3d 1367, 1376 (Fed. Cir. 2009); Capizzano v. Sec’y of Health & Human

Servs., 440 F.3d 1317, 1326 (2006) (“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).

b. Expert Analysis of A.E.’s Correct Diagnosis Further Supports

Petitioners’ Claim

i. Diagnostic Criteria at Issue

Turning to the expert presentations regarding diagnosis, the basic tenets of

ADEM diagnosis are not meaningfully disputed. While Drs. Kinsbourne and Kruer cite

to different diagnostic rubrics (by the Brighton Working Group Collaboration for Dr.

Kinsbourne and by the International Pediatric Multiple Sclerosis Study Group for Dr.

Kruer) the ultimate diagnostic requirements are essentially the same. The Brighton

Working Group Collaboration includes multiple degrees of diagnostic certainty, but the

International Pediatric Multiple Sclerosis Study Group sets forth a single list of findings,

all of which must be present to render a diagnosis. However, under either approach, the

basic elements of diagnosis are as follows:

• A polyfocal clinical CNS event with presumed inflammatory demyelinating

cause; and

25

• Encephalopathy; and

• Brain MRI abnormalities consisting of diffuse or multifocal white matter

lesions; and

• A monophasic pattern to illness; and

• No clear alternative diagnosis.

(Lauren B. Krupp et al., International Pediatric Multiple Sclerosis Study Group criteria for

pediatric multiple sclerosis and immune-mediated central nervous system demyelinating

disorders: revisions to the 2007 definitions, 19 MULTIPLE SCLEROSIS J. 1261 (2013) (Ex.

A, Tab 1); Pohl et al., supra, at Ex. A, Tab 4; Sejvar et al., supra, at Ex. 30.)

Applying this diagnostic framework, the experts both agree that A.E.

demonstrated a monophasic pattern of illness. (Tr. 38-39, 197-98.) They also agree

that A.E.’s initial presentation constituted a polyfocal clinical CNS event. Specifically, Dr.

Kinsbourne highlighted a loss of milestones and especially a regression in motor skills

and truncal hypotonia. (Tr. 19-23.) Dr. Kruer agreed more broadly that it is reasonable

to consider A.E.’s presentation as a polyfocal clinical CNS event. (Tr.129.) The experts

also agree that A.E.’s MRI showed abnormalities affecting white matter, specifically in

the corona radiata and central semiovale, areas commonly affected by ADEM. (Tr. 58-

59, 208.) Dr. Kruer also agreed that none of the specific alternative diagnoses

proposed by the diagnostic literature fit A.E.’s case. (Tr. 144, 206.) Additionally, Dr.

Kruer in particular stressed that there is no “gold standard test” for ADEM and that it is a

clinical diagnosis. (Tr. 137-38.)

Where the experts disagree is on several finer points. Specifically, Dr. Kruer

disagrees that there is evidence that A.E.’s polyfocal clinical CNS event had an

inflammatory demyelinating cause and further disagrees that there is evidence of

encephalopathy. Dr. Kruer also disagrees that A.E.’s specific MRI abnormalities are

consistent with the accepted characteristics of ADEM lesions. And, finally, he opines

that an unspecified neurogenetic disorder is more likely. Each of these points is

discussed separately below. The evidence preponderates, albeit closely, in favor of the

ADEM diagnosis on each point. Accordingly, despite being a close case and a

somewhat atypical presentation, A.E.’s condition can be said to fit both the

requirements of the International Pediatric Multiple Sclerosis Study Group framework

favored by Dr. Kruer and the highest level of diagnostic certainty under the Brighton

Working Group Collaboration’s standard as favored by Dr. Kinsbourne.

ii. Polyfocal Clinical CNS Event with Presumed Inflammatory

Demyelinating Cause

As noted above, Dr. Kruer agreed that it is reasonable to characterize A.E.’s

presentation as a polyfocal CNS event. (Tr. 129, 157.) However, he does not agree

that A.E.’s presentation is consistent with an inflammatory demyelinating event. (Tr.

129, 194-95.) The MRI evidence of demyelination is discussed separately below.

26

Turning to the question of clinical signs of inflammation, there are two possible

indicators of CNS inflammation in this case, fever, and elevated protein in CSF. 15

1. Fever

Dr. Kinsbourne opined that A.E.’s fever was in itself a neurological indicator and

constituted the first manifestation of A.E.’s ADEM. (Tr. 121-22.) This is consistent with

the literature filed in this case that recognizes fever as a prodromal symptom of ADEM.

(Pohl et al., supra, at Ex. A, Tab 4, p. 3.) He also opined that the fever represents the

inflammatory aspect of the condition. (Tr. 48-49.) This is likewise supported by the

Brighton Working Group Collaboration, which explained in discussing CNS inflammation

broadly that “[f]ever, while non-specific, is an easily measurable and reliable indicator of

an inflammatory process; in the presence of the various additional criteria provided for

nervous system dysfunction, it could allow for identification of likely cases of

encephalitis without being overly specific.” 16 (Sejvar et al., supra, at Ex. 30, p. 4.)

Dr. Kruer agreed that fever can be a prodrome symptom of ADEM preceding

other symptoms (Tr. 140) and did not dispute that as a general matter fever is evidence

consistent with the type of inflammation diagnostic of a relevant polyfocal clinical CNS

event in ADEM. He did, however, opine that the timing and duration of A.E.’s own fever

was inconsistent with the typical presentation of ADEM. 17 (Ex. A, p. 3; Ex. C, p.1; Tr.

140-41.) Dr. Kinsbourne agreed that the fever presentation would be atypical but

stressed that it would still be within the ADEM diagnostic framework. (Ex. 36, p. 1; Tr.

102, 117-18.) A.E.’s neurologist, Dr. Hopkins, likewise explicitly provided a second

opinion concluding that A.E.’s initial presentation was inflammatory as evidenced by her

fever. (Ex. 2, pp. 139-40.)

Dr. Kinsbourne is correct in his assertion that the relevant diagnostic literature

relied upon by the experts do not establish specific limiting factors for the duration of a

prodromal fever in ADEM. (Ex. 36, p. 1; Sejvar et al., supra, at Ex. 30; Krupp et al.,

supra, at Ex. A, Tab 1; Pohl et al., supra, at Ex. A, Tab 4.) Moreover, both experts

15 Dr. Hopkins also identified A.E.’s elevated erythrocyte sedimentation rate (“ESR”) as an indicator that

A.E. experienced an inflammatory process at onset. (Ex. 2, p. 140.) Dr. Kruer acknowledged the fact of

the elevated ESR finding (Ex. A, p. 2), but the experts did not otherwise discuss the clinical value of the

finding.

16 Under the diagnostic criteria established by the Brighton Working Group, inflammation is not required

as a diagnostic criterion demonstrating CNS inflammation in ADEM because it is often absent. (Sejvar et

al., supra, at Ex. 30, p. 5.)

17 In his supplemental report at Exhibit C, Dr. Kruer noted that Dr. Kinsbourne had responded only to his

discussion of the atypicality of the duration of A.E.’s fever and left unaddressed his comment that the

fever was too remote from vaccination to have been a vaccine reaction. (Ex. C, p. 1.) In response, Dr.

Kinsbourne clarified that he is not of the opinion that A.E.’s fever was a post-immunization fever, but

rather a marker of subacute onset of her ADEM. (Ex. 48, p. 1.) During the hearing, Dr. Kinsbourne

further confirmed that his opinion is not that the fever itself was vaccine-related, but rather that the fever

was caused by A.E.’s ADEM which was caused by her vaccination. (Tr. 96.)

27

stressed that ADEM is clinically heterogenous. (Tr. 84-85 (Kinsbourne), 136-37

(Kruer).) Additionally, Dr. Kinsbourne supported his view by citation to three separate

case reports wherein the authors arrived at an ADEM diagnosis following prolonged

fever. (Tr.45-51; Nahid Khosroshahi et al., Acute Disseminated Encephalomyelitis in a

5-Month Old Infant, 2 IRANIAN J. OF CHILD NEUROLOGY 53 (2008) (EX. 63); George

Imataka & Osamu Arisaka, An infant with steroid-refractory cytomegalovirus-associated

ADEM who responded to immunoglobulin therapy, 18 EUR. REV. FOR MED.

PHARMACOLOGICAL SCIENCES 2148 (2014) (EX. 64); Margherita Di Costanzo et al., Acute

Disseminated Enephalomyelitis Presenting as Fever of Unknown Origin: Case Report,

11 BMC PEDIATRICS 103 (2011) (EX. 65.) Dr. Kruer disputed the ADEM diagnosis in two

of the three, but suggested he could not entirely dismiss the third. 18 (Tr. 191-93

(discussing Khosroshahi et al., supra, at Ex. 63; Imataka & Arisaka, supra, at Ex. 64; Di

Costanzo et al., supra, at Ex. 65.) Ultimately, nothing in the record, apart from Dr.

Kruer’s own clinical judgment, rules out the possibility of a prolonged fever being

associated with ADEM. Moreover, although he called the prolonged fever a clinical “red

flag,” Dr. Kruer was careful to couch his opinion in terms of what is typical of ADEM

rather than what is more rarely seen in ADEM. (Tr. 140.) In that regard Dr. Kruer also

acknowledged that “[i[t’s hard to argue on the basis of symptoms alone that a child does

not have ADEM, because ADEM can do quite a bit in term of what symptoms it can

cause.” (Tr. 137.)

An additional consideration is the relationship between onset of the fever and

onset of the other symptoms of neurological damage. Dr. Kruer initially suggested that

the fact that A.E.’s fever continued after onset of her neurological symptoms means her

presentation is not explainable as ADEM. (Ex. A, p. 3.) Dr. Kinsbourne disagreed,

citing a small retrospective study of 42 children diagnosed with ADEM. That study found

that 67% of subject patients had a fever and 24% were febrile during hospitalization.

(John A.D. Leak et al., Acute Disseminated Encephalomyelitis in Childhood:

Epidemiologic, Clinical and Laboratory Features, 23 THE PEDIATRIC INFECTIOUS DISEASE

J. 756, 759 (2004) (Ex. 52, p. 4).) Ultimately, Dr. Kruer testified regarding fever in

ADEM that “[w]hen it is encountered, it can precede the onset of neurological

symptoms, but not always.” (Tr. 140.)

Finally, Dr. Kruer suggests that fever is in itself a nonspecific and common

symptom and that in A.E.’s case it may be explained by an infectious illness. (Tr. 141,

195.) In A.E.’s specific case, however, her fever was recorded as being of unknown

origin and an infectious etiology was never confirmed despite significant investigation.

18It is often noted that “[C]ase reports ‘do not purport to establish causation definitively, and this

deficiency does indeed reduce their evidentiary value’…. [but] ‘the fact that case reports can by their

nature only present indicia of causation does not deprive them of all evidentiary weight.’” See Paluck v.

Sec'y of Health & Human Servs., 104 Fed. Cl. 457, 475 (2012) (quoting Campbell v. Sec'y of Health &

Human Servs., 97 Fed. Cl. 650, 668 (2011). Here, I note that these case reports are not offered to prove

causation, but only to reflect that the clinical presentation of certain symptoms at issue can be associated

with the diagnosis of ADEM. In this context, case reports have a greater potential to be illuminating.

Even if fully crediting Dr. Kruer’s challenge as to the correctness of the ADEM diagnosis contained in

each case report, they would still constitute some evidence suggesting that members of the relevant

medical community agree that prolonged fever can potentially be viewed as consistent with ADEM.

28

Moreover, even if an infectious illness was present, that does not in itself call the

diagnosis of ADEM into question as ADEM often follows infection. (E.g., Tr. 164.) In

any event, even if fevers are generally nonspecific and common, A.E.’s own fever

presentation occurred in a specific context, namely as prelude to a developmental

regression. From the time of her initial hospitalization, A.E.’s fevers were considered a

part of her overall clinical presentation rather than as a separate, coincidental illness.

For example, upon admission to Lehigh Valley Hospital, Dr. Busse recorded:

Diagnoses:

- Neurodevelopmental

Regression w/ loss of

Truncal tone/head control

- Fevers

D[ifferential] D[iagnosis] tumor, encephalitis, GBS, metabolic [disorder]

(Ex. 4, p. 4.) In the same record she indicated “amoxicillin to be stopped/no evidence of

active infection.” (Id.)

Accordingly, there is preponderant evidence that A.E.’s fever, though prolonged,

was a symptom of her ADEM. Additionally, there is preponderant evidence that A.E.’s

fever constitutes evidence of a presumed inflammatory cause of her polyfocal clinical

CNS event as required by the diagnostic criteria.

2. CSF test results

A more specific method of detecting CNS inflammation in ADEM is

demonstration of leukocytes in the cerebral spinal fluid. (Sejvar et al., supra, at Ex. 30,

pp. 3-4.) Dr. Kinsbourne did initially cite elevated white blood cells upon A.E.’s lumbar

puncture. (Ex. 12, p. 2.) Specifically, while still at Lehigh Valley Hospital, a CSF test of

June 29, 2012 showed 13 WBCs/cmm, 25, 111 RBCs/cmm and protein of 121 mg/dl.

(Ex. 4, p. 79.) However, Dr. Kruer explained that A.E.’s CSF sample was contaminated

by blood and her test result, though it “appears to be abnormal,” actually lacks clinical

value. (Ex. A, p. 3.) Dr. Kinsbourne concurred as to the white blood cell count, but

contended that A.E. also had elevated protein in her CSF, which could be adjusted to

account for the blood contamination and remained “substantially” elevated after

adjustment. (Ex. 36, pp. 1-2 (citing Dean A. Seehusen et al., Cerebrospinal Fluid

Analysis, 68 AM. FAM. PHYSICIAN 1103 (2003) (Ex. 40).) Dr. Hopkins recorded the same

observation when she offered her second opinion indicating that A.E.’s initial

presentation was inflammatory. (Ex. 2, p. 140.)

Dr. Kruer indicated in response that “[c]orrections can be helpful, but they are

notoriously unreliable.” (Ex. C, p. 1.) In support of that contention, however, Dr. Kruer

cited a 1986 missive by Dr. Ryan Anbar primarily cautioning against ruling out a

condition based on a traumatic tap with adjusted white blood cell count. (Ryan D. Anbar,

Pitfalls in Interpretation of Traumatic Lumbar Puncture Formula, 140 AM. J. OF DISEASES

OF CHILDREN 737 (1986) (Ex. C, Tab 1).) In any event, during the hearing, Dr. Kruer

29

characterized A.E.’s lab results as being less helpful in reaching his opinion. (Tr. 138.)

He acknowledged that CSF lab results are helpful in confirming CNS inflammation, but

“not absolutely required for a diagnosis of ADEM.” (Id.)

While Dr. Kruer notes a need for caution that may temper the weight that can be

placed on this finding, Dr. Kinsbourne is correct that A.E.’s CSF showed elevated

protein even after adjusting for the traumatic tap. Balancing the competing opinions, it

appears that A.E.’s CSF result does provide some additional and “helpful,” albeit non-

specific, evidence supporting the conclusion that her initial polyfocal CNS event had an

inflammatory cause.

iii. Encephalopathy

For purposes of diagnostic criteria, “[t]he term ‘encephalopathy’ was defined by

consensus and refers to an alteration in consciousness (e.g. stupor, lethargy) or

behavioral change unexplained by fever, systemic illness or postictal symptoms.”

(Krupp et al., supra, at Ex. A, Tab 1, p. 3.) In that regard, Dr. Kinsbourne explained that

A.E.’s records, including her initial hospital intake, reflect multiple explicit notations that

A.E. was experiencing lethargy. (Tr. 17-19 (discussing Ex. 2, p. 285), 20-21 (discussing

Ex. 4).) A later history also described A.E.’s initial presentation as being “less

interactive.” (Tr. 30-31 (discussing Ex. 2, pp. 9-13).) Additionally, Dr. Kinsbourne

explained that these findings of lethargy did not track with the course of A.E.’s fever and

therefore the fever could not explain the lethargy. (Tr. 118-20.)

Dr. Kruer did not agree that A.E.’s medical records contained evidence of

encephalopathy. (Tr. 129-30.) He agreed that the lethargy recorded by the treating

physicians is consistent with encephalopathy, but opined that it is nonspecific and

inadequate to constitute a diagnosis of encephalopathy. (Tr. 131.) Instead, Dr. Kruer

felt that because encephalopathy was directly relevant to the diagnostic assessment of

ADEM, had the treating physicians felt encephalopathy was present, they would have

explicitly recorded encephalopathy instead of only noting lethargy. (Tr. 131, 154-55.)

Dr. Kruer agreed, however, that for a 13-month old like A.E., determining the presence

of an encephalopathy would be a “series of observations” looking for appropriate

responses. (Tr. 154.)

It is difficult to separate this aspect of Dr. Kruer’s diagnostic impression from his

overall interpretation of the medical records as not containing any ADEM diagnosis,

which is a conclusion against the weight of preponderant evidence. This does warrant

some consideration in weighing the competing expert opinions. See, e.g., Milik v. Sec'y

of Health & Human Servs., 822 F.3d 1367, 1381 (Fed. Cir. 2016) (finding that the

special master did not abuse his discretion in weighing expert testimony based in part

on one expert’s “flawed assumption” regarding onset). Contrary to Dr. Kruer’s

assessment, though much doubt remained at the time of A.E.’s initial presentation, the

treating physicians on the whole seriously considered the possibility of ADEM during

A.E.’s hospitalization and also ultimately, and much later, diagnosed ADEM. In light of

the clear and well-established diagnostic standards, this necessarily includes a

30

judgement that an encephalopathy was likely present. Accordingly, the description of

symptoms contained in the contemporaneous records should be viewed in that context.

Specific reference to lethargy first appears in the record by parental report to the

pediatrician. (Ex. 2, p. 289.) That exam does not appear to confirm the finding, but did

result in a consultation with Dr. Shaikh. (Id. at 290.) Looking closely at Dr. Sheikh’s

subsequent record of his initial neurology consultation with A.E., he initially elicited a

parental report of A.E. “becoming more lethargic.” (Ex. 4, p. 21.) He then indicates that

he “interrogat[ed]” the parents to further reveal that she had stopped cruising, regressed

in babbling and speaking, had balance issues, and “has a spacey look.” (Id.) These

observations are potentially consistent with altered consciousness, lethargy, confusion,

or general malaise, which is how Dr. Kruer characterized encephalopathy. 19 (Tr. 154-

55.) Dr. Sheikh then performed a neurological exam in which he noted A.E. to be “alert

and awake,” but also specifically recorded that he had confirmed that “she had a very

spacey look,” directly paralleling the parental observation, and also “appeared to be a

little sluggish” in her movements. 20 (Ex. 4, p. 22.) A.E. was afebrile at the time of this

exam. (Id. at 21.) Following this examination and history, Dr. Sheikh specifically

indicated as part of this same record that the condition of ADEM, which, as discussed

above, diagnostically includes encephalopathy, would need to be ruled out. (Id. at 22.)

In sum, Dr. Sheikh elicited and recorded a parental history consistent with

encephalopathy, confirmed that history with parallel language in his examination notes,

and ultimately included the encephalopathic condition at issue in his differential

diagnosis. Although Dr. Kruer is correct that a specific notation of encephalopathy

would have been helpful, considering this neurology consultation as a whole and in the

context of the complete medical records, the history, exam, and resulting impression, all

point, albeit circumstantially, to the conclusion that Dr. Sheikh found or suspected the

presence of an encephalopathy.

Accordingly, considering the medical records as a whole, there is preponderant

evidence that A.E. suffered an encephalopathy consistent with the relevant diagnostic

criteria.

19 A.E.’s simultaneous, but separate, motor skill regression makes it more difficult to assess the reason(s)

why A.E.’s activity level declined. For example, the fact that she stopped cruising and was having

balance issues was likely related to her muscle tone issues. (Ex. 4, pp. 21-22.) However, the specific

reports of lethargy, loss of babbling, and spacey look cannot reasonably be explained in relation to her

motor skills. Dr. Kinsbourne did, however, separately suggest that A.E.’s loss of words may have been

related to motor function issues, though this would be less easily applied to mere babbling. (Tr. 52-53.)

20 Dr. Shaikh also noted on his physical exam that “[p]upils appear to be a little dilated, however, they

were briskly reactive to light.” (Ex. 4, p. 22.) During the hearing, I asked both experts about this finding.

Neither expert opined that the finding was significant in A.E.’s own case, but both agreed that it is

generally a nonspecific finding potentially consistent with encephalopathy. (Tr. 120-21 (Kinsbourne), 156-

57 (Kruer).)

31

iv. MRI studies

Interpretation of A.E.’s MRIs represents the closest and most difficult question in

her diagnostic picture. From June of 2012 to October of 2014, A.E. underwent MR

imaging on five separate occasions. (Ex. 4, p. 118; Ex. 8, p. 18; Ex. 8, p. 3; Ex. 60, p. 1;

Ex. 6, p. 1.) Each of the five MRI studies was reviewed and interpreted by a different

radiologist or neuroradiologist. Additionally, Dr. Kruer reviewed all of the MRI studies

and offered testimony regarding the first and last. 21 (Tr. 168.) A.E.’s diagnosing

neurologist, Dr. Legido, also based his diagnostic impression on A.E.’s repeat MRIs.

(Ex. 66, p. 8.) Additionally, A.E. received an additional neurology opinion from Dr.

Hopkins, who reviewed four of the MRIs in consultation with a sixth neuroradiologist, Dr.

Chowdury. (Ex. 2, pp. 139-41.)

The first MRI study of June 28, 2012 was conducted at Lehigh Valley Hospital

and was interpreted by Dr. Joshua Bemporad. (Ex. 4, pp. 117-19.) Dr. Bemporad is a

neuroradiologist. 22 As interpreted by Dr. Bemporad, this study was “concerning for

volume loss” and also showed “decrease in the expected amount of myelination.” (Id. at

118.) Dr. Bemporad’s impression was that the study was “concerning for underlying

neurodegenerative disorder.” (Id.) Dr. Kinsbourne stressed, however, that Dr.

Bemporad’s impression as recorded is premised on a mistaken understanding that A.E.

had not lost milestones. (Tr. 54-56.) Indeed, Dr. Sheikh’s neurological consultation of

the same date, which prompted the first MRI study, confirmed “significant regression.”

(Ex. 4, p. 22.) Dr. Kinsbourne also stressed more generally that the areas of decreased

myelination implicated by A.E.’s MRIs, the corona radiata and centrum semiovale, are

areas commonly affected by ADEM. (Tr. 58-59.) As noted above, Dr. Kruer likewise

agreed these areas are commonly affected by ADEM. (Tr. 208.)

Comparing selected T2 weighted axial cuts of A.E.’s first MRI to an example of

an ADEM-affected brain from Pohl, et al, Dr. Kruer opined that A.E.’s imaging showed

hypomyelination, as developmental feature, rather than an inflammatory demyelinated

lesion as expected in ADEM. (Tr. 173-76; Ex. D, p. 6.) Dr. Kruer highlighted two facets

of comparison. First, the ADEM exemplar showed a developmentally “normal” brain as

evidenced by the dark appearance of the white matter. (Tr. 174; Ex. D, p. 6 (right

image).) In contrast, Dr. Kruer opined that A.E.’s image is not as dark as would be

developmentally expected, meaning that there is hypomyelination. (Tr. 175-76; Ex. D,

p. 6 (left images).) Interestingly, whereas Dr. Bemporad based his interpretation in part

on the suggestion that A.E. had not lost milestones and further recommended additional

21Dr. Kruer testified that he reviewed all of the MRI studies that were conducted; however, he

misidentified the number of studies as four rather than five. (Tr. 168.) The specific images he presented

testimony regarding were from the studies dated June 28, 2012 and October 31, 2014. (Ex. 4, p. 118;

Ex.6.)

22 The medical record does not specify whether Dr. Bemporad is a neuroradiologist; however, his

qualifications are listed on the Lehigh Valley Health Network website. See

https://www.lvhn.org/doctors/joshua-bemporad, last accessed February 5, 2021.

32

clinical correlation, Dr. Kruer indicated that delayed myelination should not require

clinical correlation. (Tr. 176.)

Second, in comparing A.E.’s T2 weighted imaging to the exemplar, Dr. Kruer

opined that A.E.’s imaging lacks comparable “fluffy kind of confluent cloud-like white

matter lesions.” (Tr. 174.) On later questioning, however, he acknowledged that

additional images in his presentation that have undergone post-processing by FLAIR

(fluid attenuated inversion recovery) do provide evidence of white matter lesions. (Tr.

178-79.) However, he opined that these remain inconsistent with ADEM due to having

a symmetrical presentation. (Id.)

The second MRI study of October 25, 2012 was conducted on behalf of Nemours

Dupont Hospital at Lehigh Magnetic Imaging Center and was interpreted by Dr. Jason

Zicherman, a neuroradiologist. 23 (Ex. 8, p. 1.) In this second MRI, volume loss was still

noted, but characterized as mild. (Id.) Dr. Zicherman observed patchy, but “fairly

symmetric,” hypomyelination. In contrast to Dr. Bemporad, Dr. Zicherman felt the

clinical history suggested that the finding could represent postinfectious demyelination

rather than hypomyelination. (Id.) There is no specific indication this second MRI study

was compared to the first, though Dr. Zicherman did reference a “suggestion of some

improvement in demyelinating pattern.” (Id.) Dr. Kruer did not discuss the specific

finding of this study in either his reports or his testimony.

The third MRI study was conducted on July 26, 2013, again at Lehigh Valley

Magnetic Imaging Center on behalf of Neumours Dupont Hospital. (Ex. 8, p. 3.)

However, this study was interpreted by Dr. Elliot Shoemaker, who is listed as a

radiologist. 24 In this instance, comparison was made to the prior October 25, 2012

study. (Id.) Dr. Shoemaker indicated that the white matter hyperintensity is

“nonspecific” in appearance, but felt it could be consistent with leukodystrophy, which

was noted to be consistent with A.E.’s history. (Id.) Dr. Shoemaker mostly focused on

the degree of hyperintensity and did not address whether the abnormality was

symmetrical. (Id.) The report includes no discussion of volume loss. Dr. Kruer did not

discuss the specific finding of this study in either his reports or his testimony.

The fourth MRI study was conducted on behalf of Neumours Dupont Hospital by

an unspecified outside facility on September 18, 2013 and was interpreted by

neuroradiologist Dr. Kandula. (Ex. 60, pp. 1-4; Ex. 2, pp. 137-141.) Comparison was

made to the first and second MRI studies of June 28, 2012 and October 25, 2012

respectively, but not to the third study. (Ex. 60, p. 1.) Here, the hyperintensities are

specifically noted to be both asymmetrical and patchy. (Id.) Mild volume loss is noted.

(Id. at 2.) The findings were considered “nonspecific,” but the differential diagnosis

23 As with Dr. Bemporad, there is no indication of the face of A.E.’s medical record that Dr. Zicherman is a

neuroradiologist; however, his qualifications are listed on the Lehigh Valley Health Network website. See

https://www.lvhn.org/doctors/jason-zicherman, last accessed on February 5, 2021.

24Qualification in neuroradiology cannot be confirmed for Dr. Shoemaker based on the record of this case

or on the relevant facility’s website.

33

included nonviral encephalitis with clinical correlation recommended. (Id.) Dr.

Kinsbourne testified that nonviral encephalitis would include ADEM and that the other

conditions listed in the differential diagnosis (SSPE and PML) are inflammatory

demyelinating disorders, but could not explain A.E.’s condition because they are

progressive and that has not been her course. (Tr. 60-61.) Dr. Kruer did not discuss

the specific findings of this MRI study, but did agree that A.E.’s course was monophasic

rather than progressive. (Tr. 197-98.)

The fifth and final study was performed on October 31, 2014 by the Lehigh Valley

Health Network and was interpreted by Dr. Mark A. Osborne, a radiologist. 25 (Ex. 6, pp.

1-2.) Comparison was made to the third MRI study of July 26, 2013. (Id. at 1.)

According to Dr. Osborne, A.E.’s brain was of “normal size, configuration.” (Id.) He

indicated “[a]s previously on FLAIR scan there are too numerous to count ill-defined,

patchy high signal intensity in cerebral white matter.” (Id.) Dr. Osborne also observed

that the white matter abnormalities were improving and therefore opined that “[t]his

improving appearance raises the question of ADEM rather than leukodystrophy. Clinical

correlation is recommended.” (Id. at 2.) Dr. Kinsbourne stressed during his testimony

the fact that Dr. Osborne was provided a history of leukodystrophy, which was the

impression provided on the prior MRI study to which Dr. Osborne compared his study.

(Tr.61-63; Ex. 8, p. 17.) According to Dr. Kinsbourne, the fact that Dr. Osborne

suggested ADEM in contrast to the provided history should carry extra weight. (Tr. 61-

63.)

Dr. Kruer opined that this final MRI demonstrated some interval improvement in

myelination, but that delayed myelination persists in the posterior area. (Tr. 177; Ex. D,

p. 7.) However, he opined that “this shows that there has been interval improvement,

there has been positive development, radiologically, but again, I think it stands in sharp

contrast to what's typical for ADEM, which is where one has a developmentally

appropriate brain upon which are superimposed these fluffy cloud-like lesions. So to

me, again, this is fundamentally not consistent with ADEM from a radiological

standpoint.” (Tr. 177.)

Among those interpreting A.E.’s MRI studies, a majority suggested that her

imaging is potentially consistent with ADEM. Dr. Osborne explicitly referenced ADEM,

while Dr. Kandula’s prior September 18, 2013 radiology report included nonviral

encephalitis in the differential diagnosis and noted the findings to be patchy and

asymmetrical. (Ex. 8, p. 17; Ex. 60, pp. 1-4.) Dr. Zicherman felt that postinfectious

demyelination was possible in preference to hypomyelination. (Ex. 8, p. 1.) Upon

review of A.E.’s repeat MRIs, Dr. Legido likewise concluded that A.E.’s diagnosis was

ADEM. (Ex. 66, p. 8.) Dr. Hopkins and Dr. Chowdury reviewed four of the five MRIs

and stressed the lack of progression. (Ex. 2, p. 140.) Dr. Hopkins opined that the

pattern of white matter involvement is “atypical” of ADEM, but stressed that ADEM fit

25 Dr. Osborne’s qualifications as listed on the facility’s website do not indicate any additional qualification

in neuroradiology. See https://www.lvhn.org/doctors/mark-osborne, last accessed on February 5, 2021.

34

the clinical history of a post-vaccination inflammatory event with encephalopathy and

further noted the likelihood of an infectious or parainfectious etiology. (Id.)

Only Dr. Bemporad offered any kind of confidence that A.E.’s MRIs reflected

hypomyelination and not demyelination. However, Dr. Kinsbourne reasonably calls Dr.

Bemporad’s impression into question based on his misapprehension of the clinical

history. (Ex. 4, pp. 117-19; Tr. 54-56.) In any event, Dr. Kruer did ultimately

acknowledge that A.E.’s first MRI evidenced white matter lesions in addition to what he

interpreted as hypomyelination. (Tr. 178-79.) To the extent Dr. Shoemaker

alternatively favored leukodystrophy, Dr. Kruer disagreed that A.E. suffered

leukodystrophy. (Tr. 144.)

Dr. Kruer’s basis for rejecting the white matter lesions seen in A.E.’s MRI as

evidence of ADEM was that they were symmetrical in appearance. (Tr. 178-79.)

However, this interpretation was not shared by the treating radiologists on the whole.

The September 18, 2013 report specifically noted the lesions to be asymmetrical. (Ex.

60, pp. 1-4.) Dr. Osborne additionally characterized the lesions as “too numerous to

count” and “ill-defined,” characteristics that call into question any clear delineation of

symmetry, and also specifically raised the question of ADEM in his report. (Ex. 6, p. 1.)

Even Dr. Zicherman, the one radiologist that specifically cited symmetrical lesions was

equivocal in describing them as “fairly” symmetrical. (Ex. 8, p. 1.) Importantly, the

confirmed monophasic course of A.E.’s condition indicates that the radiologists were all

interpreting the same lesions, albeit with interval improvement.

The other notable finding discussed by Dr. Kruer is the presence of volume loss;

however, this finding neither supports nor contradicts petitioners’ claim. To the extent

Dr. Bemporad described atrophy, Dr. Kruer would disagree. (Tr. 180.) However, as

with the hypomyelination he observed, Dr. Kruer did opine that this finding is more in

keeping with a developmental abnormality than ADEM. (Id.) Dr. Kruer indicated that

the improvement in A.E.’s volume loss from the time of her first MRI to her last is

consistent both with a developmental process and potentially with the type of

neurogenetic condition he posits. (Tr. 180-81.) Dr. Kruer also agreed as a general

matter that ADEM can result in atrophy, but opined that the severity necessary for that

finding to be present is not comparable to A.E.’s case. (Tr. 180.) Importantly, however,

there was not agreement among the reviewing radiologists as to the significance of

these findings. Some opined that A.E.’s imaging reflected demyelination rather than

hypomyelination. Moreover, the finding of volume loss did not prevent Drs. Zicherman

and Osborne from specifically invoking ADEM. In any event, even if A.E. did have

features of developmental abnormality inclusive of hypomyelination and volume loss,

Dr. Kruer acknowledged that A.E. additionally had white matter lesions. (Tr. 178-79.)

Accordingly, while the interpretation of the MRIs as showing developmental abnormality

may partially inform Dr. Kruer’s overall assessment, it does not invariably lead to the

conclusion that ADEM was not also present based on the presence of additional lesions

consistent with ADEM. 26

26 On this specific point, Dr. Kruer cited to Occam’s razor as a central tenet of clinical diagnosis. (Ex. C,

p. 2.) Specifically, he notes that “[a]pplied to diagnosis, Occam’s razor indicates that A.E. is more likely to

35

It is important to note Dr. Kruer is not a radiologist, but does review MRI imaging

in his clinical practice. 27 (Tr. 166-67.) In that regard, petitioners objected during the

hearing to the presentation of Dr. Kruer’s testimony regarding the MR imaging as expert

testimony. (Tr. 166.) Petitioners stressed that Dr. Kruer is not a radiologist and not

specifically trained in radiology. (Id.) Petitioners distinguished between the ability of a

physician to review MRIs in clinical practice and the qualification necessary to offer

expert testimony criticizing the opinions of board-certified radiologists. (Id.) Petitioners

raise an important point; however, a treating neuroradiologist’s opinion is not per se

controlling as to the correct interpretation of an MRI study. Nuttall v. Sec’y of Health &

Human Servs., 122 Fed. Cl. 821 (2015) (finding the special master did not abuse his

discretion by weighing expert opinion more heavily than the report of a treating

neuroradiologist), aff’d 640 Fed. Appx. 996 (Fed. Cir. 2016). Accordingly, I advised

petitioners during the hearing that I would permit Dr. Kruer’s testimony, but consider

their argument with regard to the weight of that testimony. (Tr. 166.)

Here, Dr. Kruer’s testimony provides important additional explanation regarding

the diagnostic considerations that are attendant to interpretation of MR imaging relative

to ADEM. His testimony is persuasive on those points and this is information not easily

discernable from the face of the radiology reports. However, in terms of exercising

interpretive, clinical judgment with respect to the specific images themselves, Dr. Kruer

has acknowledged that this is a very difficult case radiologically speaking and that the

many different radiologists and neuroradiologists consulted in A.E.’s care differed in

their interpretations of the same findings. (Tr. 209.) Also significant is that Dr. Kruer

offered opinions only as to two out of five MRI studies conducted in this case. 28 In that

regard, A.E.’s diagnosing neurologist, Dr. Legido, arrived at his ultimate and competing

have a single unifying diagnosis that explains her baseline cortical atrophy and delayed myelination as

well as the symptoms she developed in June 2012 than she is to have both random cortical

atrophy/delayed myelination AND ADEM. (Id. at 2-3 (emphasis original).) While this represents a

reasonable guiding principle, at some point the principle of parsimony envisioned by Occam’s razor must

give way to a difficult or unusual diagnostic picture where simple or usual explanations are exhausted,

especially where no other unifying diagnosis has been identified. Occam’s razor holds in effect that the

simplest explanation is usually the best. In that regard, in addition to testifying that A.E.’s imaging was

not consistent with ADEM in his opinion, Dr. Kruer did also testify that A.E.’s imaging was “unusual” and

“not a classic, common presentation” more generally and without reference to any specific diagnosis. (Tr.

209.) In effect, this aspect of Dr. Kruer’s opinion is premised on the idea that it is too unlikely that a

developmentally delayed child would experience ADEM from a post-infectious process. While this may

find support in a general statistical sense, Dr. Kruer has offered no opinion that it is impossible or

improbable in a pathophysiological sense. In fact, Dr. Kruer did separately opine that a reasonable

alternative explanation would be that A.E. had underlying neurological dysfunction brought to attention or

“unmasked” by her acute illness, raising the very question of whether that acute event could nonetheless

be ADEM. (Tr. 143.)

27He also suggested that his interpretation of MRI images has been subjected to peer review insofar as

he has included MRI imaging in prior papers he has published. (Tr. 167.)

28 I also asked Dr. Kruer to confirm whether the specific images of axial cuts he presented during the

hearing were the best views to capture the findings at issue. He indicated that they were “very

reasonable” but not beyond argument. (Tr. 208.)

36

impression of ADEM based on the clinical significance of the repeat MRI findings. (Ex.

66, p. 8.) Given the closeness of this case and the number of qualified individuals who

have interpreted the same images with inconsistent results, there is no basis for giving

outsized weight to Dr. Kruer’s interpretation as compared to the other interpretations

present in this record. 29

Based on all of the above, and in consideration of Dr. Kruer’s testimony as well

as the opinions of all of the neurologist, radiologists, and neuroradiologists to have

reviewed A.E.’s MRI studies, there is preponderant evidence that A.E.’s imaging

demonstrates diffuse or multifocal demyelinating white matter lesions consistent with a

diagnosis of ADEM.

v. Alternative diagnoses

In addition to the above, respondent may also present evidence relating to an

alternative cause to demonstrate the inadequacy of petitioner’s evidence supporting her

case in chief. de Bazan v. Sec'y of Health & Human Servs., 539 F.3d 1347, 1353 (Fed.

Cir. 2008). Moreover, the diagnostic criteria for ADEM suggest that ADEM is itself a

“diagnosis of exclusion.” (Pohl et al., supra, at Ex. A, Tab 4, p. 2.) In that regard, Dr.

Kruer has opined that he believes that A.E. has a neurogenetic condition and that whole

exome sequencing would be appropriate. (Tr. 135-36.) Critically, however, “the

Vaccine Act does not require the petitioner to bear the burden of eliminating alternative

causes where the other evidence on causation is sufficient to establish a prima facie

case.” Walther v. Sec'y of Health & Human Servs., 485 F.3d 1146, 1150 (Fed. Cir.

2007). The Court of Federal Claims has also similarly observed that petitioners do not

bear a burden to “discount every potential cause that exists within the entire realm of

possibility.” Pafford ex rel. Pafford v. Sec'y of Dep't of Health & Human Servs., 64 Fed.

Cl. 19, 35 (2005) (emphasis original), aff’d 451 F.3d 1352 (Fed. Cir. 2006).

In this case, Dr. Kruer does not suspect any specific neurogenetic condition that

may be present. Nor has A.E. undergone any genetic testing that would reveal such a

condition. Instead, Dr. Kruer opines in effect that advances in genetic testing make

exploration of such conditions medically reasonable. (Tr. 135-36, 204-05.) The

diagnostic criteria Dr. Kruer prefers as authoritative, Pohl et al., provides further

guidance relevant to the exploration of differential diagnoses. (Pohl et al., supra, at Ex.

A, Tab 4.) Pohl et al. includes a table of “red flags for a diagnosis of ADEM and

possible differential diagnoses.” (Pohl et al., supra, at Ex. A, Tab 4, p. 4 (Table 3).)

Consistent with Dr. Kruer’s opinion in this case, that table lists “genetic/metabolic

disorders” as possible causes of diffuse, symmetrical brain lesions upon imaging. (Tr.

204-05; Pohl et al., supra, at Ex. A, Tab 4, p. 4 (Table3).) However, Pohl et al., also

includes a further table that more specifically provides for “Differential diagnosis of

29 Notably, this case presents a far different scenario than what was examined in the prior Nuttall case. In

Nuttall, the special master had to distinguish between two detailed competing expert presentations that

focused on distinctions of clinical judgment well beyond what was discernable from the radiology reports.

Nuttal v. Sec’y of Health & Human Servs., No. 070810V, 2015 WL 691272 (Fed. Cl. Spec. Mstr. Jan. 20,

2015), aff’d 640 Fed. Appx. 996 (Fed. Cir. 2016). Moreover, there were far fewer radiology and

neuroradiology records in that case. Id.

37

ADEM guided by MRI.” (Pohl et al., supra, at Ex. A, Tab 4, p. 4 (Table 4).) This table

provides a further list of specific conditions that may be implicated by atypical MRI

findings. (Id.) During the hearing I confirmed with Dr. Kruer that he agrees that none of

the listed conditions are implicated by A.E.’s own medical history as reflected in her

medical records. (Tr. 206.) This also includes leukodystrophies, which was referenced

as part of A.E.’s own differential diagnosis. (Tr. 144.)

I also asked Dr. Kruer to explain more generally the interplay between his opinion

as to the need to explore neurogenetic conditions and the idea of ADEM as a diagnosis

of exclusion. He testified:

ADEM is a diagnosis of exclusion in the sense that ADEM is not an

appropriate diagnosis if there's a different distinct specific diagnosis that

seems to fit better. So it's a diagnosis of exclusion in that context, but I think

it's also a diagnosis of inclusion. That's why they have these criteria,

because it's not simply that anything that has new onset neurological

symptoms as ADEM until proven otherwise. ADEM is a specific entity that's

been shown over time to be diagnostically specific, and it has to pass the

common sense test. It has to look like ADEM, it has to present like ADEM,

it has to act like ADEM, it has to have the imaging consistent with ADEM.

And so if you don't have these things, then I think it fundamentally questions

whether ADEM is present. I believe your question is if I think ADEM is there,

do I look for neurogenetic conditions. No, I don't. If I believe that ADEM is

the fundamental diagnosis, I'll treat it as ADEM. I'll reasonably go through

some of these alternative diagnoses with some testing, but if it looks and

acts like ADEM, I'll treat it like ADEM.

(Tr. 207-08.)

Dr. Kruer has confirmed that none of the specific alternative diagnoses

suggested by the relevant diagnostic criteria are implicated. Moreover, in light of the

preceding analysis, there is preponderant evidence that A.E.’s condition is consistent

with the diagnostic criteria for ADEM. Although he would disagree with the latter

conclusion, Dr. Kruer’s above testimony confirms that in that context he would not

necessarily search for a neurogenetic condition. Accordingly, petitioner has no burden

to exclude the possibility of any neurogenetic condition either as a function of the

generally accepted diagnostic criteria for ADEM or the specific legal requirements of this

program.

vi. Dr. Kinsbourne’s Testimony is Credible and Reliable

Implicit in respondent’s counsel’s questioning during the hearing is an argument

by respondent that Dr. Kinsbourne’s qualification to opine in this case should be

doubted relative to Dr. Kruer. Respondent stresses that Dr. Kinsbourne has been retired

from clinical practice for a considerable amount of time. (Tr. 95-96.) Although this point

is clearly reasonable in a general sense, it is of reduced significance in the specific

38

context of this case. The nature and circumstances of Drs. Kinsbourne’s and Kruer’s

opinions in this case inform this conclusion.

Especially because, as described above, I have found that A.E.’s treating

physicians did ultimately reach a diagnosis of ADEM, this case in many ways presents a

contrast of Dr. Kruer versus the treating physicians rather than Dr. Kruer versus Dr.

Kinsbourne. Dr. Kinsbourne has not presented any assessment of diagnosis and

causation that is distinct from those of the treating physicians. Nor, for that matter, has

respondent meaningfully disputed through Dr. Kruer that the MMR and varicella

vaccines are capable of causing ADEM as a matter of general medicine. (Tr. 210.)

Rather, the role of Dr. Kinsbourne’s opinion in this evaluation has largely been related to

(1) assessing and further explaining the record notations demonstrating why the treating

physicians felt A.E.’s presentation was potentially consistent with ADEM and (2)

providing further explanation linking A.E.’s presentation to the relevant diagnostic

medical literature that has been filed in this case.

While Dr. Kruer has stressed that the last ten years “have been an exciting time”

in pediatric neurogenetics, that discussion focused in significant part on advancements

in whole exome sequencing that have allowed for the discovery of additional

neurogenetic disorders. (Tr. 132-34.) Significantly, however, in light of the fact that

A.E. never had such testing performed, Dr. Kruer’s reports and testimony regarding

these more recent advances were never more specific than to identify the fact of this

method of testing as being available and hypothetically revealing. With regard to the

more concrete and specific diagnostic considerations of ADEM, Dr. Kruer did prefer

newer diagnostic criteria from 2013 by the International Pediatric Multiple Sclerosis

Study Group (and subsequent update by Pohl, et al) to Dr. Kinsbourne’s reliance on the

criteria developed in 2007 Brighton Working Group Collaboration; however, Dr. Kruer

described the newer criteria only as a more concise and conceptual evolution of the

relevant criteria. (Tr. 145-46.) Although Dr. Kruer indicated that his own reliance

material was “authoritative” and “up-to-date,” he did not indicate that the Bright Working

Group criteria are wrong or antiquated, that the different sets of diagnostic criteria

render different results, or that Dr. Kinsbourne’s reliance on the Brighton criteria is

unreasonable. (Id.)

Where both parties 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 ex rel. Snyder v. Sec'y of Health & Human Servs., 88 Fed. Cl. 706, 742-43

(2009) (quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146, 118 S.Ct. 512, 139 L.Ed.2d

508 (1997)); see also Isaac v. Sec'y of Health & Human Servs., No. 08–601V, 2012 WL

3609993, at *17 (Fed. Cl. Spec. Mstr. July 30, 2012), mot. for review den'd, 108 Fed. Cl.

743 (2013), aff'd, 540 Fed. Appx. 999 (Fed. Cir. 2013) (citing Cedillo v. Sec’y of Health

39

& Human Servs., 617 F.3d 1328, 1339 (2010)). 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 ex rel. Moberly v. Sec’y of Health & Human Servs.,

592 F.3d 1315, 1325–26 (2010) (“[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 determining whether a particular expert's testimony was reliable or credible, a

special master may consider whether the expert is offering an opinion that exceeds the

expert's training or competence. Walton v. Sec'y of Health & Human Servs., No. 04–

503V, 2007 WL 1467307, at *17–18 (Fed. Cl. Spec. Mstr. Apr. 30, 2007)

(otolaryngologist not well suited to testify about disciplines other than her own

specialty). While (in keeping with the liberality with which evidence offered in Vaccine

Program cases is treated) all testimony of the experts offered at the entitlement hearing

was heard and considered, a special master may properly evaluate, and give

appropriate weight to, whether certain testimony is beyond a particular expert's purview.

See e.g., King v. Sec'y of Health & Human Servs., No. 03–584V, 2010 WL 892296, at

*78–79 (Fed. Cl. Spec. Mstr. Mar. 12, 2010) (petitioner's expert far less qualified to offer

opinion on general causation issues pertaining to autism than specific issues pertaining

to the petitioner's actual medical history, given the nature of the expert's qualifications).

With that standard in mind, I would not place Dr. Kinsbourne’s opinion on equal

footing with Dr. Kruer with regard to clinical judgments, such as the validity of

neurogenetic testing or MRI interpretation, that are directly affected by medical

advancements of the last several decades. However, petitioner has not presented Dr.

Kinsbourne to opine on these points. Dr. Kruer’s testimony is effectively unrebutted

regarding neurogenetic conditions more broadly and Dr. Kinbourne deferred to A.E.’s

medical records regarding interpretation of her MRI results. In contrast, respondent has

not substantiated that advancements in medicine since Dr. Kinsbourne’s retirement

have left him unable to interpret medical records, recognize core neurologic signs or

symptoms of encephalopathy, or review and appreciate relevant medical literature

regarding diagnostic standards. And significantly, Dr. Kinsbourne has testified that he

does have prior experience (albeit remote) in the clinical setting treating the specific

condition at issue. (Tr. 5-6.)

Accordingly, Dr. Kinsbourne is qualified to offer the opinion that he has presented

in this case and I see no reason to doubt that his opinion as offered in this case is

credible and reliable. This is consistent with my prior experience with Dr. Kinsbourne.

In a prior case involving infantile spasms, I was critical of Dr. Kinsbourne for presenting

a theory beyond his expertise and questioned the quality of his testimony. 30

Kottenstette v. Sec'y of Health & Human Servs., No. 15-1016V, 2020 WL 4197301 (Fed.

Of note, I was not the special master who presided over that hearing. Rather, due to that special

30

master’s retirement, I addressed that case for the first time on remand.

40

Cl. Spec. Mstr. June 2, 2020), review denied, decision aff'd, No. 15-1016V, 2020 WL

4592590 (Fed. Cl. July 27, 2020). However, in another case, I accepted his opinion

testimony regarding the basic neurologic injury of radial neuritis and explained that I

found him to be a “conscientious” reviewer of the medical records. Kirby v. Sec'y of

Health & Human Servs., No. 16-185V, 2019 WL 6336026 (Fed. Cl. Spec. Mstr. Nov. 1,

2019), review granted, decision rev'd on other grounds, 148 Fed. Cl. 530 (2020).

c. Petitioner Has Satisfied the Althen Test with Respect to ADEM

i. Althen Prong One

Under Althen prong one, petitioners must provide a “sound and reliable” medical

theory, demonstrating that the vaccine received can cause the type of injury alleged.

Boatmon v. Sec’y of Health & Human Servs., 941 F.3d 1351, 1359 (Fed. Cir. 2019). In

this case there is no dispute as to Althen prong one. In his first report, Dr. Kinsbourne

opined that both the MMR and varicella vaccines can cause ADEM. (Ex. 12, pp. 5-6;

see also Tr. 86-87.) During the hearing, Dr. Kruer likewise agreed that these two

vaccinations can cause ADEM as a matter of general medicine. (Tr. 210.) Two of A.E.’s

treating physicians also indicated that ADEM can be vaccine-caused. (Ex. 1, pp. 6-7

(Chen, infectious disease); Ex. 66, p. 8 (Legido, neurology).) Dr. Chen specifically

identified the MMR vaccine as a rare cause of ADEM. (Ex. 1, pp. 6-7.) Accordingly,

petitioners have satisfied Althen prong one.

ii. Althen Prong Two

The second Althen prong requires proof of a logical sequence of cause and

effect, usually supported by facts derived from a petitioner's medical records. Althen,

418 F.3d at 1278; Andreu, 569 F.3d at 1375–77; Capizzano, 440 F.3d at 1326; Grant v.

Sec'y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). In establishing

that a vaccine “did cause” injury, the opinions and views of the injured party'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). However, medical records and/or

statements of a treating physician's views do not per se bind the special master to adopt

the conclusions of such an individual, even if they must be considered and carefully

evaluated. See Section 13(b)(1) (providing that “[a]ny such diagnosis, conclusion,

judgment, test result, report, or summary shall not be binding on the special master or

court”); Snyder, 88 Fed. Cl. at 746 n.67 (“there is nothing ... that mandates that the

testimony of a treating physician is sacrosanct—that it must be accepted in its entirety

and cannot be rebutted”).

Here, for all the reasons discussed above there is preponderant evidence that

A.E. did have ADEM rather than any unspecified neurogenetic condition. This

conclusion is based both on the opinions of A.E.’s treating physicians as well as the

41

above assessment of the parties’ expert presentations. Further, there is preponderant

evidence that A.E.’s presentation, including her prolonged fever, is itself consistent with

onset of ADEM. Additionally, both Dr. Kruer and Dr. Kinsbourne agreed that ADEM can

be caused by an antecedent event, including vaccination. (Tr. 86-87, 121, 202-03,

210.) Dr. Kinsbourne further provided an affirmative opinion that A.E.’s own

presentation is consistent with a logical sequence of cause and effect demonstrating

A.E.’s ADEM to be vaccine-caused. A.E.’s treating physicians likewise concluded that

A.E.’s ADEM may have been vaccine caused. Dr. Chen and Dr. Legido both

specifically considered that possibility and Dr. Legido ultimately concluded in finalizing

A.E.’s diagnosis that the etiology of A.E.’s ADEM could not be distinguished as between

infection or vaccination. (Ex. 66, p. 8.) Notably, however, no specific infectious agent

was ever confirmed. In any event, because A.E.’s clinical history presents a logical

sequence of cause and effect consistent with vaccine causation, petitioners would not

bear a burden of eliminating infection as an alternative cause. 31 Walther, 485 F.3d at

1151 (stating that “the petitioner generally has the burden on causation, but where there

are multiple independent potential causes, the government has the burden to prove that

the covered vaccine did not cause the harm.”). Accordingly, in light of all of the above,

petitioners have satisfied Althen prong two.

iii. Althen Prong Three

The third Althen prong requires establishing a “proximate temporal relationship”

between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term

has been equated to the phrase “medically-acceptable temporal relationship.” Id. A

petitioner must offer “preponderant proof that the onset of symptoms occurred within a

timeframe which, given the medical understanding of the disorder's etiology, it is

medically acceptable to infer causation.” de Bazan, 539 F.3d at 1352. Here, there is no

debate as to what constitutes a medically acceptable temporal relationship. The experts

both agreed that onset of ADEM within four weeks of an antecedent event is medically

reasonable. (Tr. 78-81 (Kinsbourne), 203 (Kruer).) Accordingly, A.E.’s varicella and

MMR vaccinations having been administered on April 27, 2012, onset of vaccine-

caused ADEM should be evidenced by about May 25, 2012.

Dr. Kinsbourne identified both fever and ataxia as presenting symptoms for

ADEM. (Tr. 51-52; 121-22.) As addressed above, Dr. Kruer disagreed that A.E.’s fever

was attributable to ADEM, but did agree that fever can be a prodrome of ADEM. (Tr.

140.) Although there are some inconsistencies in the notations addressing onset of

A.E.’s fever course and other neurologic symptoms, the earliest record places onset of

illness broadly at 17 days prior to June 7, 2012, or approximately May 21, 2012, with

“high” fever beginning three days prior, or about June 4, 2012. (Ex. 2, p. 277.) At this

visit there is also the report of a symptom of likely ataxia (i.e. a notation of “balance off”).

(Ex. 2, p 277; Tr. 13-14.) No separate onset is recorded for the loss of balance. (Ex. 2,

31 Even if a viral illness had operated in conjunction with A.E.’s vaccinations to cause ADEM, petitioners

would still be able to meet their burden of proof. Shyface, 165 F.3d at 1353 (explaining that although the

Shyfaces did not prove that the DPT vaccine was the only or predominant cause of his death, the

requirements of the Vaccine Act are met prima facie upon proof of the substantial factor criterion.).

42

p. 277.) At the next appointment fever onset is placed at 28 days prior to June 20,

2012, or approximately May 23, 2012. (Id. at 279.)

This places the likely onset of A.E.’s ADEM occurring no later than May 23, 2012,

which is about 26 days following her April 27, 2012 vaccinations and within the four-

week timeframe discussed by both experts. Accordingly, petitioners have satisfied

Althen prong three.

d. Respondent Has Not Met His Burden of Establishing that A.E.’s

Injury Was Caused by Any Factor Unrelated to Vaccination

Once petitioners have met their prima facie burden, respondent may still defeat

petitioners’ claim by coming forward with preponderant evidence that A.E.’s injury was

due to factors unrelated to vaccination. § 300aa-13(a)(1)(B). This raises two separate

questions.

First, respondent raises an argument to the extent of contending that A.E.’s

condition is better explained diagnostically as an otherwise unspecified neurogenetic

condition. As presented in this case the presence of ADEM and a neurogenetic

condition are mutually exclusive explanations of A.E.’s clinical presentation. In that

regard I have considered this possibility of an alternative neurogenetic condition in the

context of whether A.E. was properly diagnosed with ADEM. Because I have concluded

there is preponderant evidence that A.E. suffered ADEM, respondent necessarily fails to

establish that there is preponderant evidence that her injury is otherwise explained by a

neurogenetic condition. In any event, A.E.’s treating physicians apparently did not

believe genetic testing to be warranted by her presentation and A.E. never underwent

any genetic testing in the course of her extensive treatment history, leaving Dr. Kruer’s

suggestion of an unspecified alternative neurogenetic condition hypothetical. Conditions

or other factors that are “idiopathic, unexplained, unknown, hypothetical, or

undocumentable” cannot defeat a petitioner’s claim. § 300aa-13(a)(2); Knudsen v.

Sec’y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994).

Second, some of the medical records suggested that A.E. may have been

experiencing an illness or infection around the time her neurologic symptoms first

presented. Her treating physicians specifically considered whether her condition, if

ADEM, could have been explained by such infection. Ultimately, that possibility was not

entirely ruled out, but no infectious etiology was found to support the suspicion. (Ex. 44,

p. 174.) The Federal Circuit has rejected the contention that the presence of a viral

infection can per se be considered a factor unrelated to vaccination. Knudsen, 35 F.3d

at 548-50. Rather, respondent bears a burden of proving not only that there was a viral

infection, but also that the infection was principally responsible for causing petitioner’s

injury. Id. Ultimately, Dr. Legido indicated that the etiology of A.E.’s ADEM could not be

distinguished as between infection and vaccination. (Ex. 66, p. 8.) In any event, Dr.

Kruer’s causal opinion was primarily premised on his assertion that A.E. did not have

ADEM. (Tr. 136.) To the extent there is preponderant evidence that A.E. did suffer

ADEM, Dr. Kruer did not opine that her ADEM would have been caused by infectious

43

illness. Accordingly, there is not preponderant evidence that A.E.’s ADEM was caused

by a factor unrelated to vaccination.

e. This is a Close Case

Finally, I note that this is a very close case in which petitioner’s treating

physicians appear to have struggled to reach a diagnosis. I also note that, as explained

above, the initial burden of proof rests with petitioner and respondent is not obligated to

prove an alternative diagnosis. Dr. Kruer was a cogent witness and many of the points

he raised were reasonable, though simply outweighed by other record evidence in the

context of a difficult diagnostic picture in which subjective clinical judgments were key.

On the whole, Dr. Kruer applied a framework that he described as constituting a

“common sense” approach, where he looked for classic or typical indicators of ADEM

even while acknowledging that ADEM has a heterogenous clinical presentation. (Tr.

84-85 (Kinsbourne), 136-37 (Kruer).) As noted above, Dr. Kruer summarized his

approach by explaining “ADEM is a specific entity that's been shown over time to be

diagnostically specific, and it has to pass the common sense test. It has to look like

ADEM, it has to present like ADEM, it has to act like ADEM, it has to have the imaging

consistent with ADEM.” (Tr. 207.) Without doubting that this represents sound clinical

judgment, in a close case in this legal setting it is far more difficult to accept such a

judgment as being consistent with petitioner’s preponderant burden of proof. This is

especially so because, as described above, both experts agreed that ADEM has a

clinically heterogenous presentation and because A.E.’s own treating physicians

ultimately concluded that she suffered ADEM. Dr. Kinsbourne was persuasive in

opining on the whole that A.E.’s presentation, though somewhat atypical, still fit within

diagnostic tolerances. This case presented a series of close questions; however, as

explained above, petitioners did come forward with record evidence supporting their

claim on each critical point.

The closeness of this case is also reflected in the fact that there remains a

significant degree of uncertainty even in Dr. Kruer’s own opinion. During the hearing,

Dr. Kruer was specifically asked how he would proceed if A.E. were his own patient and

his response was very measured:

So I don’t think it’s completely – I don’t think it’s obvious, by any stretch,

what specific condition A.E. has. With that said, I am often in a position,

either with wearing my hat as a neuroimmunologist or a neurogeneticist,

that I am performing second or third opinions. In that context, if I had

reviewed A.E.’s case, I would be very suspicious that ADEM was not the

correct diagnosis, for all the reasons that I have outlined.

(Tr. 135.)

“The Vaccine Act does not contemplate full blown tort litigation in the Court of

Federal Claims. The Vaccine Act established a federal ‘compensation program’ under

44

which awards are to be ‘made to vaccine-injured persons quickly, easily, and with

certainty and generosity.’” Knudsen, 35 F.3d at 549. (quoting H.R.Rep. No. 99–908,

99th Cong., 2d Sess. 18, reprinted in 1986 U.S.C.C.A.N. 6344.) Accordingly, the

Federal Circuit has suggested that this program represents a “system created by

Congress, in which close calls regarding causation are resolved in favor of injured

claimants.” Althen, 418 F.3d at 1280. I do stress that there is preponderant evidence

supporting petitioners’ claim. However, I also note that the outcome in this case is

consistent with the Federal Circuit’s guidance regarding the generous and remedial

nature of this program.

VI. Conclusion

Accordingly, for all the reasons described above, petitioners are entitled to

compensation for A.E.’s ADEM which was caused-in-fact by her MMR and/or varicella

vaccinations received on April 27, 2012. A separate Damages Order will issue setting

forth additional steps for the damages phase of this case.

IT IS SO ORDERED.

s/Daniel T. Horner

Daniel T. Horner

Special Master

45