# Eilan v. Secretary of Health and Human Services

> United States Court of Federal Claims · March 22, 2021

URL: https://www.frixlaw.com/law-library/cases/4670277

## Case

- **Court:** United States Court of Federal Claims
- **Decided:** March 22, 2021
- **Precedential status:** Published
- **Opinion:** Opinion
- **Judges:** Daniel T. Horner
- **Cited by:** 0 later opinions in the Frix Law Library

## Citator (automated)

- No negative treatment found by the automated citator. That is not the same as a confirmation that the case is good law; read the citing cases.
- Full citator and citing cases: https://www.frixlaw.com/law-library/cases/4670277

## How later opinions describe it (automated extraction)

- 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.
- 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
- 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.”

## Opinion text

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.)

3
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

4
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.”

5
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

6
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.)

7
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.

8
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.)

9
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 o

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Source: Frix Law Library, https://www.frixlaw.com/law-library/cases/4670277. Public record. Not legal advice.