Doug Paluck and Rhonda Paluck, as Parents and Natural Guardians on Behalf of Their Minor Son, Karl Paluck v. Secretary of Health and Human Services

In the United States Court of Federal Claims

No. 07-889V

(Filed: October 29, 2013)

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) Vaccine case; petitioners’ challenge to a

DOUG PALUCK and RHONDA ) special master’s decision on remand; off-

PALUCK, as parents and natural ) Table claim stemming from neurological

guardians on behalf of their minor son, ) damage allegedly caused or aggravated by

KARL PALUCK, ) administration of MMR, varicella, and

) Prevnar vaccines to a child with a genetic

Petitioners, ) mitochondrial defect; claim asserting an

) aggravation of a pre-existing condition;

v. ) Loving causation framework; entitlement;

) remand

SECRETARY OF HEALTH AND )

HUMAN SERVICES, )

)

Respondent. )

)

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Sheila A. Bjorklund, Lommen, Abdo, Cole, King & Stageberg, P.A., Minneapolis,

Minnesota, for petitioners.

Lynn E. Ricciardella, Senior Trial Attorney, Torts Branch, Civil Division, United States

Department of Justice, Washington, D.C., for respondent. With her on the briefs were Stuart F.

Delery, Acting Assistant Attorney General, and Rupa Bhattacharyya, Director, Vincent J.

Matanoski, Deputy Director, Catharine E. Reeves, Assistant Director, and Chrysovalantis P.

Kefalas, Trial Attorney, Torts Branch, Civil Division, United States Department of Justice,

Washington, D.C.

OPINION AND ORDER 1

LETTOW, Judge.

Petitioners, Rhonda and Doug Paluck, on behalf of their son Karl Paluck, seek review of

a decision on remand by a special master dated May 10, 2013, denying them compensation under

the National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, § 311, 100 Stat. 3743,

3755-84 (codified as amended at 42 U.S.C. §§ 300aa-1 to -34) (“Vaccine Act”). Petitioners filed

1

In accord with the Rules of the Court of Federal Claims (“RCFC”), App. B (“Vaccine

Rules”), Rule 18(b), this opinion and order will remain sealed for fourteen days, within which

time the parties may propose redactions.

their claim on December 21, 2007, alleging that Karl’s receipt of the measles-mumps-rubella

(“MMR”), varicella, and Prevnar vaccines on January 19, 2005 caused him either to develop an

impairment or to exacerbate a preexisting condition, resulting in severe neurological damage.

The Secretary of Health and Human Services (“the government”) acknowledges Karl’s injury but

contends that its cause is unrelated to the vaccines.

Petitioners’ claim is an off-Table injury claim, requiring proof of causation in fact by a

preponderance of the evidence. The special master assigned to the case initially denied

petitioners’ claim for compensation on December 14, 2011, finding that the Palucks failed to

meet the three-part causation test established in Althen v. Secretary of Health & Human Servs.,

418 F.3d 1274, 1278 (Fed. Cir. 2005). See Paluck v. Secretary of Health & Human Servs., No.

07-889V, 2011 WL 6949326, at *2 (Fed. Cl. Spec. Mstr. Dec. 14, 2011) (“Paluck I”). In

response to a motion by petitioners for review, ECF No. 103, this court rendered a decision on

April 18, 2012, vacating the special master’s findings under all three Althen prongs and

remanding the case to the special master, while “ma[king] no affirmative findings of its own.”

Paluck v. Secretary of Health & Human Servs., 104 Fed. Cl. 457, 484 (2012) (“Paluck II”). In

its decision ordering remand, the court directed the special master and the parties first to reassess

whether petitioners’ claim was a significant-aggravation claim that had to be analyzed under the

six-part test explicated in Loving ex rel. Loving v. Secretary of Dep’t of Health & Human Servs.,

86 Fed. Cl. 135, 143 (2000), which the special master had not applied. See Paluck II, 104 Fed.

Cl. at 468-69. The Loving test combines the three causation factors from Althen with three

additional factors that consider a claimant’s health before and after the vaccination. See id. at

468 n.14. The court also directed the special master to reconsider the record as a whole before

making new findings regarding causation in fact. See id. at 475, 480, 483.

In the remanded proceedings before the special master, no new evidence was submitted

by either party. Supplemental briefing regarding Karl’s developmental delays before and after

the vaccine was completed by September 19, 2012. Paluck v. Secretary of Health & Human

Servs., No. 07-889V, 2013 WL 2453747, at *3 (Fed. Cl. Spec. Mstr. May 10, 2013) (“Paluck

IV”). 2 The statutory period for decision after the remand expired without a resolution, and on

January 30, 2013, petitioners again moved for review by this court because of the delay. Pet’rs’

Mot. for Review, ECF No. 140. On May 3, 2013, the court denied the motion, but directed the

special master to issue a decision within 120 days. Paluck v. Secretary of Health & Human

Servs., 111 Fed. Cl. 160, 169 (2013) (“Paluck III”). The special master issued a decision a week

thereafter, on May 10, 2013, again denying petitioners’ claim. Paluck IV at *1.

Petitioners renewed their motion for review of the special master’s decision by this court,

contending that the special master’s findings of fact and conclusions of law are arbitrary and

capricious, an abuse of discretion, and not in accord with the law. Pet’rs’ Mot. for Review of

Remand Decision (“Pet’rs’ Mot.”) at 2-3, ECF No. 149. The Palucks ask this court to make its

own findings of fact and issue a decision on entitlement in their favor. The government argues

2

Subsequent citations to Paluck IV will refer to the decision as reported in Westlaw, but

will omit reference to “2013 WL 2453747” and will directly designate the starred internal pages.

Similarly, citations to Paluck I will refer to the decision as reported in Westlaw,

omitting reference to “2011 WL 6949326” and directly noting the starred internal pages.

2

that the special master’s decision was premised on adequate findings of fact and conclusions of

law and should be left undisturbed. Resp’t’s Mem. in Resp. to Pet’rs’ Mot. for Review

(“Resp’t’s Opp’n”) at 1-2, ECF No. 151. The Palucks’ motion for review, filed June 10, 2013,

has been fully briefed, and a hearing was held on September 18, 2013.

BACKGROUND

A. Facts

Karl Paluck currently suffers from an unspecified mitochondrial disorder that was most

likely present at birth. At the time of the vaccinations, that disorder had not been detected. After

the vaccinations, Karl became severely disabled, but the parties disagree as to the cause.

Karl was born on January 15, 2004 and showed no apparent signs of disability from birth

through about the first eight months of life. A concern about developmental delay was first

recorded on September 27, 2004 by Ms. Heather Ernst during developmental screening at Karl’s

daycare provider, as part of the North Dakota Right Track Program. See R. Ex. 5, at 111. 3 She

observed delays in his gross and fine motor skills and referred him to an infant development

service, K.I.D.S. See id. 4 K.I.D.S. evaluated Karl on October 21, 2004. R. Ex. 15, at 1. The

evaluation examined areas of fine motor skills, gross motor skills, speech and language skills,

cognition, and adaptive behavior. Id. at 2. Four test protocols were used: Bayley Scales of

Infant Development (“Bayley Scales”), PDMS-2 Developmental Motor Scales — gross and fine

motor scales (“PDMS-2”), Preschool Language Scale-3 (“PLS-3”), and Vineland Adaptive

Behavior Scales (“Vineland”). Id.

The Bayley Scales protocol is generally used to test a child’s cognitive skills (i.e., ability

to remember, problem solve, use and understand language, and identify early number concepts).

R. Ex. 15, at 2; Tr. 99:5-7 (Test. of Dr. Richard Frye, petitioners’ expert). 5 Karl scored “within

normal limits” and was found to have an 11% delay. R. Ex. 15, at 2.

Testing with PDMS-2’s gross motor scales evaluated Karl’s ability to use his large

muscles, and testing with PDMS-2’s fine motor scales evaluated Karl’s ability to use his small

muscles. R. Ex. 15, at 2. Karl showed significant delay in his gross motor skills: 44% delay in

stationary skills (i.e., head and trunk control, sitting), 67% delay in locomotion skills (i.e.,

rolling/crawling and object manipulation), and 67% delay in reflexes (i.e., ability to stay upright

3

Documentary materials made part of the record are cited as “R. Ex. __, at __.”

4

The special master wrongly attributed the referral to K.I.D.S. as having been prompted

by a visit to Karl’s pediatrician, Dr. Stephen McDonough, as a result of an examination at eight

months. Paluck IV at *4. In actuality, Karl was not examined at eight months of age by

Dr. McDonough. Rather, he was examined at four months, six months, and one year by

Dr. McDonough. See R. Ex. 3, at 1, 2, 3.

5

The entitlement hearings took place before the special master in 2010, and the transcript

of those hearings is cited as “Tr. __:__.”

3

and protect against falling). Id. Overall, he ranked in the first percentile for gross motor skills.

Id. He showed less delay in his fine motor skills: 11% delay in grasping and 22% delay in visual

motor integration (i.e., hand-eye control), ranking in the eighth percentile. Id. at 2-3; Tr. 99:16-

17 (Frye). Karl could roll over, but he could not sit without support or crawl. R. Ex. 15, at 4-5.

He could not lift his legs off of the floor while lying on his back. Id. at 5. He was, however,

using a “wide variety” of fine motor skills. Id. at 4. The evaluators could not determine with

certainty the reason for his gross motor delays, but ultimately believed that low muscle tone was

the underlying cause of Karl’s inability to sit and crawl. Id. at 5. 6 The evaluators believed that

Karl presented with elevated tone in his legs because he was using them to compensate for the

instability he felt in his arms and trunk. Id. at 4.

PLS-3 was employed to evaluate Karl’s ability to use and understand language. Karl

showed moderate delays: 33% delay in auditory comprehension and 22% delay in expressive

communication, ranking in the 32d percentile. R. Ex. 15, at 3. He was able to combine sounds

and produce four different consonant sounds, but he was not imitating others’ sounds or

responding to “no, no, Karl.” Id. at 4-5.

Lastly, the Vineland protocol tested Karl’s ability to care for his needs. It looked to his

communication skills, daily living skills, socialization, and motor skills. R. Ex. 15, at 3.

Overall, Karl was evaluated as 14% delayed. Id. He was 22% behind in communication skills,

11% behind in daily living skills, 0% behind in socialization skills, and 33% behind in motor

skills, ranking in the thirtieth percentile overall. Id. Ultimately, K.I.D.S. determined that Karl

presented a “mixed picture” and recommended that he “receive infant development services from

the K.I.D.S. program targeting his speech/language, gross motor, and the delays in fine motor

related to low muscle tone.” Id. at 4, 5.

Both parties’ experts agreed that the K.I.D.S. evaluation was “good and extensive,” Tr.

99:2 (Frye); Tr. 328:24 (Test. of Dr. Robert Snodgrass, respondent’s expert), but they disagreed

as to the significance of the findings relative to Karl’s neurological health.

At the time Karl underwent his first evaluation for his developmental delays, he was

experiencing recurrent bouts of otitis media 7 and rashes that were later identified as erythema

multiforme. R. Ex. 3, at 57, 83. 8 The erythema multiforme was first noticed on October 14,

6

Tone is a measurement of the muscles’ ability to maintain the body in proper posture in

different positions, such as sitting, standing, or being held. Normal tone means the muscles are

maintaining the body in proper posture. Low tone means the muscles do not sufficiently

function to maintain the body in proper posture. See Tr. 109:18-25, 110:24 to 111:8 (Frye).

7

Otitis media is “inflammation of the middle ear,” Dorland’s Illustrated Medical

Dictionary 1351 (32nd ed. 2012) (“Dorland’s”), commonly known as an ear infection.

8

Biopsy results from December 28, 2004 confirmed that the rash was consistent with

erythema multiforme. R. Ex. 9, at 3.

Erythema multiforme, which has rash-like symptoms, is “either of two conditions

characterized by sudden eruption of erythematous papules, some of which evolve into target

4

2004, a week before the K.I.D.S. testing. Id. at 57. Thereafter, the record is replete with visits

and telephone calls to the Dickinson Clinic between October 2004 and January 2005 regarding

Karl’s otitis media and erythema multiforme, documenting no fewer than eleven visits and

telephone calls during those few months. See R. Ex. H, at 3-7. Dr. Robert Snodgrass,

respondent’s expert, 9 sees significance in Karl’s erythema multiforme, not because children with

rashes are rare, but because erythema multiforme is relatively uncommon. Tr. 261:2-12

(Snodgrass). It is a hypersensitivity reaction, and in Karl’s case, it persisted for months. Id.

Moreover, both Dr. Snodgrass and Dr. Richard Frye, petitioners’ expert, 10 testified that it is

evidence of immune activation. Tr. 294:25 to 295:3 (Snodgrass); Tr. 98:11-13 (Frye). It

suggests that Karl was under some immune stress in the months leading up to the vaccinations on

January 19, 2005. See Tr. 446:2-4 (Snodgrass). Notably, the erythema multiforme improved

after a physician, Dr. Amy Oksa, prescribed Orapred, an immune suppressant drug, but recurred

when Karl stopped taking it. R. Ex. 3, at 61-62.

Most of Karl’s medical record in November and December 2004 centers on treating

Karl’s otitis media and erythema multiforme. On December 27, 2004, Karl saw Dr. McDonough

for an ear check. R. Ex. 3, at 5. The record of the visit states that Karl’s recent medical history,

as reported by his parents, was “positive for a fever.” Id. At that time, Dr. McDonough also

lesions consisting of a central papule surrounded by a discolored ring or rings. Both represent

reactions of the skin and mucous membranes to factors such as viral skin infections . . . ; agents

(including drugs) that are ingested or irritate the skin; [or] malignancy.” Dorland’s at 643; see

also Tr. 261:2-12 (Snodgrass).

9

For its arguments, the government relies upon the testimony and reports submitted to the

special master by its expert, Dr. Robert Snodgrass. Dr. Snodgrass is a professor of pediatrics and

neurology at the University of California, Los Angeles School of Medicine. He received a

bachelor’s degree in social relations from Harvard College and an M.D., magna cum laude, from

Harvard Medical School. Dr. Snodgrass is board-certified in neurology, with special

competence in child neurology. He has written dozens of articles and has held professorships at

medical institutions associated with Harvard University, Cambridge University, the University of

Southern California, Stanford University, the University of Mississippi, and the University of

California, Los Angeles. See R. Ex. B.

10

To support their contentions, the Palucks rely upon the testimony and reports submitted

to the special master by their expert, Dr. Richard Frye. Dr. Frye is an assistant professor of

pediatrics and neurology at the University of Texas Houston Health Science Center. See R. Ex.

16; Tr. 37:10-14. He received a bachelor’s degree in psychobiology from C.W. Post of Long

Island University, a master’s degree in biomedical science/biostatistics from Drexel University,

and both a Ph.D. in physiology and biophysics and an M.D. from Georgetown University.

Dr. Frye is board-certified in general pediatrics and in neurology with special competence in

child neurology. He has published numerous articles and has held residencies or professorships

affiliated with Harvard University, Boston University, the University of Miami, the University of

Florida, and the University of Texas. See R. Ex. 17.

5

documented that he had normal muscle tone and no ankle clonus. Id. 11 “He has good head

control and fairly good truncal control but is not pulling himself to stand or crawling yet.” Id.

Dr. McDonough noted “possible mild gross motor delay,” but also noted that Karl was rolling

over, trying to crawl, and had several words. Id. at 5-6.

On January 6, 2005, the daycare noted that the K.I.D.S. Program worked with Karl for

thirty minutes, that Karl cried during “tummy time,” and that he seemed very tired that day. R.

Ex. 22, at 1. The next day, the daycare recorded that he was “crabby” in the afternoon. Id.

There are no other daycare notes describing Karl before the vaccinations.

On January 19, 2005, Karl saw Dr. McDonough for his one year well-child checkup. See

R. Ex. 3, at 3, 7. Dr. McDonough administered DENVER II, a common developmental

screening test. See R. Ex. 5, at 35. The evaluation is recorded on a standardized form on which

the doctor notes whether a child “passes” or “fails” certain developmental skills appropriate for

his or her chronological age. On January 19, Karl passed “imitate activities,” “play ball with

examiner,” “indicate wants,” “bang 2 cubes held by hands,” “thumb finger grasp,” “jabber,” say

“dada/mama specific,” say “single syllables,” “pull to stand,” and “stand holding on.” Id. Karl

failed “get to sitting,” “stand 2 [seconds],” “stand alone,” say “one word,” “wave bye-bye,” and

“play pat a cake.” Id.

Dr. Frye testified that Dr. McDonough incorrectly scored the DENVER II screening for

some skills. Petitioners provided a standard DENVER II chart, which shows that there is a

shaded box behind each skill listed on the form. R. Ex. 38. Dr. Frye explained that only when

that shaded box ends before reaching the child’s chronological age should the child be

considered to have “failed” the skill. Tr. 638:7-11 (Frye). The shaded box indicates what

percentage of children have developed a skill at a certain chronological age. For example, the

skill of saying “one word” is accompanied by a shaded box that extends from about ten months

to fifteen months. See R. Ex. 38. Only when a child turns 15 months and still cannot speak one

word, should a child be noted as having “failed” the skill. Tr. 638:7-11 (Frye). Thus, according

to Dr. Frye’s testimony, Karl’s only true failed skills should have been “get to sitting,” “stand 2

[seconds],” and “play pat-a-cake.” See id.” 12 Dr. Frye also noted that some of the skills Karl

passed were fairly advanced for his age, such as “imitate activities,” which less than 75% of

11

Clonus is “alternate muscular contraction and relaxation in rapid succession.”

Dorland’s at 373. Ankle clonus is “a series of abnormal rhythmic reflex movements of the foot,

induced by sudden dorsiflexion, which causes alternate contraction and relaxation of the . . .

muscle.” Id. Dorsiflexion is “flexion or bending toward the extensor aspect of a limb, as of the

hand or foot,” i.e., the hand or foot bends backwards toward the arm or leg. Id. at 563; see also

Tr. 538:19 to 540:1 (Snodgrass). Ordinarily, when a doctor forces someone’s foot upward, it

stretches the tendon behind the ankle, which causes the calf muscle to contract. The movement

should only cause one muscle contraction, and if there are a series of contractions that is what is

termed clonus. A “beat” of clonus is one up-and-down cycle of the foot caused by the extra

muscle contractions. Tr. 539:25 to 540:1 (Snodgrass).

12

Although Dr. Frye testified that the pat-a-cake box continues through 12 months, and so

Karl should not have failed the skill, see Tr. 638:7-11 (Frye), the box does not extend that far.

6

children can do at that age. Tr. 633:1-7 (Frye). Dr. Frye testified that Karl showed less of a

delay at twelve months than he did at nine months. Tr. 638:20-24 (Frye). He estimated that Karl

was about four or five months delayed in October based on the results of the K.I.D.S. evaluation,

and about three months delayed in January based on the DENVER II evaluation. Id.

At this same appointment, Dr. McDonough made additional findings regarding Karl. On

a chart labeled “physical examination,” Dr. McDonough marked the category “neuromuscular”

as abnormal, noting “muscle tone ↑ . . . upper . . . extremities . . . 2 beats clonus [right ankle].”

R. Ex. 3, at 3. 13 Dr. McDonough checked the category “hips” as normal and wrote next to it

some word or words followed by “ROM,” meaning range of motion. 14 Dr. McDonough also

wrote on the same chart that Karl “doesn’t hold cup well,” circled the word “babbles,” and next

to “1-3 words,” he wrote “no words.” Id. He also circled the word “crawl” and wrote next to it

“4 point” (i.e., hands and knees). 15 Finally, at this same appointment, Karl was given the MMR,

varicella, and Prevnar vaccines. Id.; R. Ex. 5, at 62.

Within two days of receiving the vaccinations, Karl showed signs of irritability, fever,

and fatigue. His daycare recorded that he had a temperature of 101.5 degrees on January 21,

2005 and recorded a temperature of 101.3 degrees seven days later on January 28, 2005. See R.

Ex. 22, at 1-2. Dr. Frye and Dr. Snodgrass disagree over whether the vaccinations caused Karl’s

subsequent and persistent fever. See Tr. 197:1-3 (Frye), Tr. 339:1-2 (Snodgrass).

The daycare records in the two weeks following the vaccination reveal that Karl was

often fussy, did not eat or nap well, and was tired. R. Ex. 22, at 1-2. The only positive note

occurred on February 3, 2005 when the daycare recorded that “Shiela [from the K.I.D.S.

13

There is some confusion over precisely what Dr. McDonough wrote on the

“neuromuscular” line of the chart. Dr. Snodgrass testified as follows on cross-examination:

Q. [I]f you look at that handwritten note of Dr. McDonough, he’s noting muscle

tone increase positive upper. He doesn’t say upper and lower, does he?

A. I think he does. It’s kind of hard to read. Now I wouldn’t criticize anybody

who has trouble reading it, but if you look along that line it says muscle tone and

there’s an arrow pointing up and a plus. Then it says upper and then you go down

to the next line and you see L-O-W-E-R. To the left of the L-O-W-E-R is

something that I think is an ampersand sign, meaning upper and lower, and then I

think you can clearly read extremities after you see lower.

Tr. 466:25 to 467:12 (Snodgrass); see also Tr. 332:9-19 (Snodgrass).

14

Dr. Frye maintained in testimony that the writing preceding “ROM” is the word “full,”

meaning Karl’s hips showed a full range of motion. Tr. 825:9-15 (Frye). In contrast,

Dr. Snodgrass stated that the writing preceding “ROM” indicated decreased range of motion. Tr.

466:18-19 (Snodgrass). The word could also possibly be “good.”

15

Based on other medical records, Dr. McDonough’s notation likely does not mean that

Karl could successfully complete full cross-crawl movements.

7

program] said Karl did very [well] today.” Id. at 2. On February 8, 2005, the daycare noted that

Karl was trying to crawl by “pulling his body.” Id.

On February 7, 2005, the Palucks first took Karl to a chiropractor to address his problems

sitting, crawling, and walking. R. Ex. 12, at 2. 16 On February 9, 2005, the chiropractor recorded

some abnormalities with Karl’s hips on cross crawl. Id. at 5. Karl’s chiropractic record contains

an entry for February 11, 2005 in which is written the word “spastic.” Id. 17 There is significant

disagreement between the parties over whether the chiropractic records suggest decline or

improvement through February and March 2005. The subjective assessments noted in later

entries are variable:

• February 14 – “better mood,”

• February 16 – “less rigid — more comfortable on all 4s”

• February 18 – “less rigid — ‘happier’”

• February 20 – “stiff Mid + T – ‘happy – moving around – til last nite & today’”

• February 21 – “Mid T tite & SOP – irritable”

• February 24 – “Spastic Mid T’s & ↓ Ts”

• March 1 – “No BM yesterday”

• March 4 – “BMs better – less fussy”

• March 8 – “less hypertonicity – [illegible] ↑ on all fours/BMs more regular”

• March 10 – “Not sleeping last night/2AM-5AM/irritable/good day yesterday”

• March17 – “Upper [illegible] skin blotches – back pain.” On this day the chiropractor

also noted, “palpation of spine [painful] baby cries loud when touched.”

• March 27 – “rigid lower extreme. Palp. [illegible] – ‘doing well ‘til yesterday’ ‘took a

few crawl steps’”

• March 30 (record of a phone conversation) – “Phone convers. w/ Brenda [Erie] SCSS Re.

poss. abuse alleg. I responded – No – discussed poss. Adverse Rx/vaccine, CP [cerebral

palsy], Cerebellar Tumor.”

R. Ex. 12, at 5-7. Although these entries are variable, they do not show any significant

improvement. Many of the comments in the records are written in quotes or describe Karl’s

behavior outside his appointment, suggesting that they are descriptions of his mood and behavior

at home, given to the chiropractor by the Karl’s parents. See, e.g., February 18: “happier,”

February 20: “happy,” March 27: “doing well ‘til yesterday,” “took a few crawl steps,” April 2:

“good mood this week” “seeing improvement.” Id.

A telephone conversation record with Dr. McDonough’s office dated March 22, 2005

documents the Palucks’ report that Karl had “some brief crawling” and is “babbling more,” but is

“not sitting on his own,” “leans to one side,” and continues to have intermittent outbreaks of

16

On January 19, 2005, Dr. McDonough had referred Karl to physical and occupational

therapy. See R. Ex. 3, at 3.

17

Spastic means “of the nature of or characterized by spasms[;] hypertonic, so that the

muscles are stiff and the movements awkward.” Dorland’s at 1741. Dr. Frye described

spasticity as “being the extreme for increased tone.” Tr. 725:22-24 (Frye).

8

erythema multiforme. R. Ex. 5, at 72. Dr. Snodgrass found that the notations of Karl’s “brief

crawling” and “babbling more” were signs of progress since Karl’s December 27, 2004 visit with

Dr. McDonough. See id.; see also Tr. 545:18 to 546:24 (Snodgrass). This conclusion by the

government’s expert was contrary to that reached contemporaneously by Karl’s treating

physician, Dr. McDonough, who noted on the same telephone record that he would make a

referral to Dr. Siriwan Kriengkrairut, a pediatric neurologist. R. Ex. 5, at 72. On March 24,

2005, Dr. McDonough wrote the consultation request, citing Karl’s “gross motor delay, global

developmental delay, and hypertonicity” as the reasons. R. Ex. 3, at 7. Global developmental

delay is broader than isolated gross motor delay. “Global developmental delay is when you’re

affected in several areas.” Tr. 651:17-19 (Frye). Dr. McDonough wrote that he “would

appreciate [Dr. Kreingkrairut’s] evaluation and medical investigations into the etiology of

[Karl’s] developmental delay and hypertonicity.” R. Ex. 3, at 7. 18

In mid to late March, Karl developed a cold. On March 28, 2005, he saw Dr. Gary

Peterson at the Dickinson Clinic for “four days of [a] wheezy cough” and a “runny nose for two

weeks.” R. Ex. 3, at 64. The doctor noted early bilateral otitis media and bronchiolitis. Id. He

provided a SVN (nebulizer) treatment in the office and also prescribed one for use at home. Id.

He noted that Mrs. Paluck preferred “no antibiotics be written as yet since he has had the trouble

with erythema multiforme in the past.” Id.

By mid-April, Karl’s health was significantly worse than it was in January 2005. He

continued to suffer from recurrences of otitis media. R. Ex. 3, at 9. Karl saw Dr. McDonough

on April 13, 2005 for a Pre-Anesthesia Evaluation for a magnetic resonance imaging (“MRI”)

test that was to be performed on Karl. Id. He noted “global developmental delay,” including

problems with “speech and fine and gross motor development.” Id. at 9-10. Dr. McDonough

also wrote that Karl’s “hips are tight with decreased hip flexion to about 70 degrees bilaterally

with increased [sic, a word appears to be absent, probably “tone”] in the lower extremities. This

is a change of hip movement over the last couple of months.” Id. at 10. Karl had not had any

evidence of erythema within the past three weeks. Id. at 9.

The neurologist, Dr. Kriengkrairut, examined Karl on April 19, 2005. She documented a

brief history of the onset of Karl’s problems. “According to the father since [the onset of

erythema multiforme in October 2004] the child has regressed. . . . In December of 2004 his

condition got worse. His hands and feet were swelled up. He was given medications. This has

markedly improved from a month ago when he seemed back to his normal. Father reported that

since he has been improving with the skin lesions, he also made progress in terms of

development, but overall he is still behind.” R. Ex. 3, at 83. Following the physical examination,

she reported “truncal hypotonia with marked spasticity of the extremities. The baby has

18

Hypertonicity is “the state or quality of being hypertonic,” Dorland’s at 897, and

hypertonic refers to “exhibiting hypertonia,” id. Hypertonia denotes “excessive tone of skeletal

muscles, so they have increased resistance to passive stretching and reflexes are often

exaggerated; this usually indicates upper motor neuron injury.” Id.

9

tendency to do cortical thumb bilaterally[ 19], worse on the right compared to the left. . . . [B]aby

does not babble. . . . [D]elayed development as well as hypotonia of the extremities may be

secondary to central nervous system pathology.” Id. at 84-85. Overall, she labeled Karl as

having “[g]lobal delayed development.” Id. at 84.

Dr. Frye testified that this report by Dr. Kriengrairut suggests a substantial neurological

regression in Karl since January 2005. Tr. 654:6-25 (Frye). Dr. Snodgrass disagreed that the

problems observed by Dr. Kriengkrairut differed substantially from the problems observed by

Dr. McDonough in January. Tr. 350:1-4 (Snodgrass).

A chiropractic record entry from April 25, 2005, reports decreased range of motion. R.

Ex. 12, at 8. Dr. McDonough saw Karl the next day, on April 26, 2005, and wrote that Karl

“rolls over but does not sit without support. He does not crawl and does not say any words. . . .

Hips are tight on range of motion.” R. Ex. 3, at 12-13. Dr. McDonough again described Karl as

suffering from global developmental delay. Id. at 13.

Dr. Kriengkrairut had recommended an MRI of Karl’s brain, R. Ex. 3, at 84, which was

performed on April 27, 2005, R. Ex. 11, at 276. The results were initially interpreted as normal,

but a reexamination of the results from April 2005 following a more apparently abnormal MRI in

July 2005 discerned evidence of a then-existing brain abnormality – thinning of the corporal

callosum. Id. at 276-77, 280. The parties’ experts disagreed as to when the thinning most likely

began. Dr. Frye opined that it occurred “recent to the [MRI,] after January [2005],” Tr. 109:16

(Frye), whereas Dr. Snodgrass testified that he has “seen similar scans in people who had

prenatal infections,” Tr. 485:2-3 (Snodgrass).

Karl declined further in the ensuing months. While the special master found isolated

instances of slight improvement, see Paluck IV at *43-45 (discussing chiropractic records), these

events contrasted with a general trend of deterioration from April 2005 to July 2005, see Tr.

476:2-17, 523:16-22 (Snodgrass). On May 4, 2005, Karl was evaluated by a speech therapist,

Ms. Trisha Getz. R. Ex. 6, at 5. At that time, Karl had fewer language skills than he had in

October 2004, and his total language score was in the first percentile. See Tr. 114:1-3 (Frye). In

October 2004, he could produce at least four consonant sounds, but by May 2005, he could no

longer produce any consonant sounds, although he could still produce a couple vowel sounds.

By May, Karl’s only gesture was reaching for objects. R. Ex. 6, at 5. Ms. Getz noted, “Karl’s

parents report he had an MRI last week, which has ‘wiped him out’ and they report a decrease in

many skills since undergoing the anesthesia. . . . Mom reports he has had a decrease in speech

production in the last few months.” Id. Her reports through September 8, 2005 indicate little to

19

The word “cortical” means “pertaining to or of the nature of a cortex,” Dorland’s at

421, in this case, the cerebral cortex. See Tr. 584:4-6 (Snodgrass). Thumbing is the action of

maintaining one’s hand in a fist with the thumb held inside the fist. See Tr. 583:6-14

(Snodgrass). Dr. Frye testified that Karl’s thumbing was indeed cortical and a sign of damage to

the brain. Tr. 112:7-8 (Frye). Dr. Snodgrass disagreed, testifying that Karl’s thumbing was not

necessarily cortical and only showed “dysfunction somewhere in the central nervous system

above the level that controls the hand.” Tr. 584:1-2 (Snodgrass).

10

no improvement. Id. at 7 (“very little progress” and “no goals met”). Karl continued to be

unable to approximate sounds or produce any consonants.

Karl suffered a seizure on July 12, 2005, followed by additional seizures over the next

two days. R. Ex. 3, at 17. Dr. McDonough examined Karl on July 16, 2005 and assessed him as

having “[g]lobal developmental delay with seizure disorder, possible deteriorating neurologic

status in that he is unable to do some things that he was able to do previously.” R. Ex. 4, at 15.

On July 19, 2005, Karl was admitted to Children’s Hospital in St. Paul, Minnesota by

Dr. Michael Frost. R. Ex. 11, at 5. While there, MRI results showed furthering thinning of the

corporal callosum, id. at 91, strongly suggesting that Karl was suffering from neurodegeneration,

id. at 56. On October 27, 2005, Karl had another MRI, which showed no significant change in

Karl’s brain since the July 2005 MRI. “[T]he progression of signal changes between [4/27/05

and 7/22/05] may have represented evolution of one toxic/metabolic or hypotoxic ischemic

event.” Id. at 248.

Since July 2005, Karl has lived in a state of severe neurological disability. Earlier in

2013, he was in dire health. “There is a ‘do not resuscitate order now in place’ for him, and ‘[h]e

is bedridden or wheelchair-ridden[,] has a tracheotomy tube[,] and is on a ventilator to breathe

for him.’” Paluck III, 111 Fed. Cl. at 168 (quoting Hr’g Tr. 34:20-22, 35:12-14 (Apr. 10, 2013)).

B. Prior Decisions

1. Paluck I.

The Palucks filed their petition for compensation on December 21, 2007, alleging that

Karl “sustained a permanent injury to his brain and central nervous system as a result of receipt

of his childhood vaccines . . . [and] that the exposure to childhood vaccines caused and/or

aggravated a mitochondrial disorder in Karl.” Amended Pet. at 1, ECF No. 18. Three hearings

in the case were held over the course of 2010. At the hearings, the parties disagreed as to

whether Karl’s vaccines caused or aggravated his neurodegenerative course. Dr. Frye testified

that the vaccines either caused Karl’s injury, or aggravated his condition, according to the

following theory:

[V]accines, by intention, activate the immune system; this in turn leads to the

development of potentially toxic elements within the body, namely reactive

oxygen species (ROS) and reactive nitrogen species (RNS); ROS and RNS are

usually balanced under normal conditions by the (antioxidant) systems of the

body; however, if certain parts of the body, namely the mitochondria, are not

working properly, more toxic elements will be produced and will be unchecked

by antioxidants, resulting in oxidative stress, leading to a cascade of intracellular

events leading to apoptosis or cellular death. Brain cells are more vulnerable to

this process and with death of brain cells, neurodegeneration and developmental

regression are likely.

Paluck I at *8 (quoting Pet’rs’ Post-Hearing Br. at 25-26, ECF No. 90); see also Tr. 54:25 to

81:17 (Frye); see also R. Ex. 16; R. Ex. 26; R. Ex. 30, at 1. Applying the theory to Karl’s case,

11

Dr. Frye testified that Karl had an underlying mitochondrial disorder that prevented him from

coping with the oxidative stress of the vaccines. R. Ex. 16. This led to “decompensation” within

his cells and eventually cellular death, resulting in neurodegeneration. See Tr. 80:4 to 81:18

(Frye).

Dr. Snodgrass disagreed, testifying that “there are problems with [Dr. Frye’s] theory in

general and there are problems with its specific application to the case of Karl Paluck.” Tr.

278:12-15 (Snodgrass); see also Tr. 294:17 to 295:21 (Snodgrass). He criticized Dr. Frye’s

theory generally on the ground of lack of published peer-reviewed literature demonstrating that

vaccines cause oxidative stress in humans, although he acknowledged supporting animal-model

data. See Tr. 282:13 to 283:12, 294:17-20 (Snodgrass); see also R. Ex. BB. In his view also,

Karl’s medical history did not support the idea that vaccines caused or aggravated his condition.

Dr. Snodgrass stated that Karl manifested developmental delays before his vaccinations on

January 19, 2005. See Tr. 326:25 to 331:14, 338:5-9 (Snodgrass). Dr. Snodgrass additionally

stated that between January and April 2005, Karl’s condition fluctuated, but did not worsen, as

would be expected had the vaccines caused Karl’s injury. Tr. 349:24 to 350:4, 358:9 to 359:24,

367:13-23 (Snodgrass).

The special master issued a decision denying compensation on December 14, 2011,

concluding that petitioners had failed to prove by a preponderance of the evidence that the

vaccines administered to Karl on January 19, 2005 caused his injury or significantly aggravated a

preexisting condition. Paluck I at *2. In so holding, the special master applied the three-prong

causation framework set out in Althen, 418 F.3d 1274, which requires a petitioner

to show by preponderant evidence that the vaccination brought about

[the] 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 a proximate temporal relationship between vaccination

and injury.

Paluck I at *6 (alteration in original) (quoting Althen, 418 F.3d at 1278). The special master

found that the Palucks had failed to carry their burden as to any of the three prongs. Id. at *2.

Regarding Althen’s first prong, the special master was not convinced by the evidence

presented that vaccines produce oxidative stress generally, see Paluck I at *11-13, or oxidative

damage particularly in persons with mitochondrial disorders, see id. at *14-16. Regarding

Althen’s second prong, the special master found that Karl’s history did not demonstrate a logical

sequence of cause and effect between the vaccinations and Karl’s injury. See id. at *23.

According to the special master, Dr. Frye’s theory required that Karl’s medical history evidence

a continuous downward trajectory, which “d[id] not match what actually happened to Karl.” Id.

at *22. Instead, the special master credited Dr. Snodgrass’s testimony that Karl’s development

fluctuated between September 2004 and April 2005, with Karl actually improving between the

time of his January 2005 vaccinations and late March 2005. Id. at *20, *22. Regarding Althen’s

third prong, the special master concluded that oxidative damage would have occurred in Karl

within fourteen days, and that Karl’s immediate post-vaccination symptoms — fever, irritability,

12

and, according to his chiropractor, spasticity and hypertonicity — did not evidence such damage.

See id. at *24-26. Finding that Karl did not manifest further neurological regression until April

2005, the special master determined that Karl’s injury fell outside the medically acceptable

timeframe for vaccine injury. Id. at *27.

2. Paluck II.

Petitioners filed a motion for review of the special master’s decision in Paluck I on

January 13, 2012, arguing that the special master’s conclusions on all three Althen prongs were

“arbitrary and capricious, an abuse of discretion, or not otherwise in accord with the law.”

Pet’rs’ Mot. for Review, ECF No. 103, at 2-3; see also 42 U.S.C. § 300aa-12(e)(2)(B). The

government urged affirmance. See Resp’t’s Mem. in Resp. to Pet’rs’ Mot. for Review, ECF No.

109, at 11. Oral argument was held on March 21, 2012. Paluck II, 104 Fed. Cl. at 467. On

April 18, 2012, this court vacated the special master’s findings of fact and conclusions of law,

and remanded the case to the special master for further proceedings. Id. at 484. The court

expressly did not make any affirmative findings of fact of its own. Id. The court reviewed the

special master’s determinations of law de novo, and his findings of fact for clear error. Id. at 467

(citing Andreu ex rel. Andreu v. Secretary of Health & Human Servs., 569 F.3d 1367, 1373 (Fed.

Cir. 2009)).

First, the court directed the special master to reconsider whether petitioners’ claim should

be analyzed as a significant aggravation claim or a new injury claim. The special master had

analyzed it using the standards applicable to a new injury claim without discussion of whether

those standards were most appropriate. Paluck II, 104 Fed. Cl. at 468-69; see Paluck I at *5-6;

see also Paluck IV at *1.

Second, the court addressed the special master’s findings under each of the three Althen

prongs. Regarding Althen’s first prong, a medical theory causally connecting the vaccination

and the injury, the court held that the special master required a higher level of proof, i.e., a higher

level of scientific certainty, than is demanded by the Vaccine Act. The Vaccine Act does not

require that “evidence be medically or scientifically certain.” Paluck II, 104 Fed. Cl. at 473

(quoting Knudsen ex rel. Knudsen v. Secretary of Dep’t of Health & Human Servs., 35 F.3d 543,

548-49 (Fed. Cir. 1994)) (internal quotation marks omitted). To support his theory, Dr. Frye

relied on a peer-reviewed study published in a well-respected medical journal, various studies

showing oxidative stress in animals as a result of vaccines, and a case study. Id. While the

special master correctly determined that none of the evidence was definitive proof of the medical

validity of Dr. Frye’s theory, it was arbitrary and capricious for him to discard it as completely as

he did. See id. at 474. The court also noted that Dr. Snodgrass did not dispute the reputability of

the theory but only noted the dearth of human studies establishing it as fact. Id. The court

vacated the special master’s finding that petitioners failed to show by a preponderance of the

evidence that vaccines can cause oxidative stress and that children with mitochondrial disorders

are particularly vulnerable to oxidative stress and directed the special master to reconsider the

evidence in the record under the correct legal standard. Id. at 476.

The court also vacated the special master’s finding under Althen’s second prong that

petitioners failed to demonstrate, by a preponderance of the evidence, a logical sequence of cause

13

and effect showing that the vaccinations caused Karl’s injury. Paluck II, 104 Fed. Cl. at 480.

The special master had given considerable weight to unexplained notations throughout the record

that Karl was progressing in his ability to prepare to crawl through the months of February,

March, and April, which was something he could not do at the critical appointment on January

19, 2005 with Dr. McDonough, when he was vaccinated. See Paluck I at *20. Karl was never

formally evaluated as being able to crawl. See Tr. 546:14-21 (Snodgrass). At most, there was

evidence that he was making some preparatory crawl motions at times. See Paluck II, 104 Fed.

Cl. at 477. Similarly, the special master concluded that notations of babbling suggested

development throughout the same months, Paluck I at *20, despite evidence that Karl actually

lost language abilities, Paluck II, 104 Fed. Cl. at 478. Moreover, the court opined that the

special master failed fully to consider the chiropractor’s records from February and March and

Dr. McDonough’s referral to a pediatric neurologist in March. Id. at 480. The court held that the

special master’s finding that Karl’s efforts to crawl and babbling signaled improvement,

therefore negating a logical sequence of cause and effect between Karl’s vaccines and injury,

should be vacated due to a failure to consider all of the salient evidence. Id.

Lastly, the court vacated the special master’s finding regarding Althen’s third prong, a

proximate temporal relationship between the vaccination and injury. Paluck II, 104 Fed. Cl. at

483. According to the special master, the medical literature suggested that the medically

acceptable interval between vaccination and the onset of symptoms of neurological injury would

be two weeks. Paluck I at *26. The court rejected this conclusion. Given the medical literature

relied upon by Dr. Frye, including a case study demonstrating neurodegeneration occurring post-

vaccination over a period of several months, R. Ex. 21q, and a published study showing

neurodegeneration occurring following infection in patients with mitochondrial disorders over a

period extending to nineteen days, R. Ex. 21d, it was arbitrary and capricious for the special

master to set a “hard and fast limit of two weeks.” Paluck II, 104 Fed. Cl. at 482. The court

also held that the special master’s finding that Karl did not manifest any symptoms of neurologic

injury within a medically acceptable interval after the vaccination was arbitrary and capricious

because it failed to consider the record as a whole. Id. at 483.

3. Paluck IV.

Before deciding the case on remand, the special master requested supplemental briefing

and any additional evidence from the parties regarding the classification of Karl’s injury as a

new injury or a significant aggravation claim. If the claim were found to be a significant

aggravation claim, then the Loving factors would apply, which combine the three Althen

causation factors with three additional factors that inquire into the claimant’s condition before

and after the vaccination. See Loving, 86 Fed. Cl. at 143 (citing Althen, 418 F.3d at 1278;

Whitecotton v. Secretary of Health & Human Servs., 81 F.3d 1099, 1107 (Fed. Cir. 1996), on

remand from Shalala v. Whitecotton, 514 U.S. 268 (1995)); see W.C. v. Secretary of Health &

Human Servs., 704 F.3d 1352, 1357 (Fed. Cir. 2013) (approving the Loving test). Both parties

submitted supplemental briefs, but neither submitted additional evidence. Paluck IV at *3. The

special master determined that Karl’s claim is one of significant aggravation and must be

analyzed under the six Loving factors because Karl’s developmental delays in the autumn of

2005 strongly suggested pre-existing problems with his central nervous system. Id. at *9.

14

The first prong of Loving requires addressing Karl’s condition prior to vaccination. The

parties agreed that Karl’s mitochondrial defect was likely affecting his health before the

vaccinations. Paluck IV at *12. The parties disagreed over the extent of delay in Karl’s

language skills and the cause of Karl’s gross motor delays. Id. at *14. The special master found

that the “preponderant weight of the evidence favors finding that Karl’s language development

was delayed prior to his vaccination.” Id. at *15. He also found that Karl’s gross motor delays

and language delays, in existence before the vaccinations, were caused by abnormalities in his

central nervous system. See id. at *63. He further determined that Karl’s gross motor skill

delays had worsened between December 27, 2004 and January 19, 2005. Id. at *20.

The second prong concerns Karl’s condition following the vaccination. The special

master extensively summarized Karl’s records in the months following the vaccination. See

Paluck IV at *20-42. He looked to Karl’s daycare records, Karl’s chiropractic record, Dr.

McDonough’s referral to the pediatric neurologist, Dr. Kriengkrairut’s neurological exam, Karl’s

MRI in April 2005, Karl’s speech therapy records, the seizures and hospitalization in July 2005,

and Karl’s other medical visits and mitochondrial testing. Id.

The third prong of Loving asks whether Karl’s current condition constitutes a significant

aggravation of his condition prior to the vaccine. Without elaboration, the special master found

that “by virtually any metric, Karl was worse” after receiving the vaccines. Paluck IV at *42.

The fourth prong of Loving, which correlates to the first prong of Althen, addresses

whether there is a medical theory causally connecting the worsened condition to the vaccine. In

response to this court’s opinion in Paluck II, “[both] parties essentially agreed that the Palucks’

evidence met the standard [for medical plausibility] as defined by the [c]ourt.” Paluck IV at *42.

The special master accepted this apparent concession by the government without discussion,

noting only that this concession does not lessen the petitioners’ burden of proof under Loving

prongs five and six. Id. at *43.

The fifth prong of Loving requires petitioners to establish, by a preponderance of the

evidence, a logical sequence of cause and effect showing that the vaccination significantly

aggravated Karl’s condition. The special master determined that Dr. Frye’s theory “was

predicated on a downhill trajectory.” Paluck IV at *43. Thus, the special master looked for

evidence that Karl’s health declined without any improvement from one day to the next

following the vaccinations on January 19, 2005. In accordance with this court’s order on

remand, the special master considered in detail “[Karl’s chiropractic] records, [Karl’s] treating

doctors’ statements regarding the cause of Karl’s decline, and Dr. McDonough’s referral to a

pediatric neurologist.” Id. (internal quotation marks omitted). In considering the chiropractor’s

notations from February and March, the special master found that it was “difficult to glean much

significance from [them].” Paluck IV at *44. Ultimately, he found that the evidence of decline

was too variable to suggest a linear decline, as he considered Dr. Frye’s theory to require. Id. at

*49.

The final prong of Loving requires the special master to determine a medically acceptable

temporal relationship between the vaccine and the significant aggravation and then determine

whether the claimant’s injuries occurred within that time frame. Upon reconsideration of an

15

article by Dr. Joseph L. Edmonds, the special master lengthened the medically acceptable

temporal interval from two weeks, which he had specified in Paluck I, to three weeks. See

Paluck IV, at *55; see also, R. Ex. 21d, Joseph L. Edmonds et al., The Otolaryngological

Manifestations of Mitochondrial Disease and the Risk of Neurodegeneration with Infection, 128

Archives of Otolaryngology – Head & Neck Surgery 355 (2002). Accordingly, the special

master looked for evidence of neurodegeneration, defined as the loss of a skill, within three

weeks following January 19, 2005, which extended to February 10, 2005. Paluck IV at *56.

Karl’s daycare records and chiropractic records were the only records contemporaneously

created during that period. The special master was persuaded by the government’s expert that

Karl’s fevers and irritability in the ten days following the vaccinations did not constitute

encephalopathy, as Dr. Frye had opined. Id. at *57. Additionally, the special master was

unconvinced by Dr. Frye’s testimony that the chiropractor’s notation describing Karl as “spastic”

on February 11, 2005 was evidence of “a very severe neurological event [suggesting] a very

rapid change in his central nervous system.” Tr. 647:14-18 (Frye); see Paluck IV at *60. The

special master posited three reasons for not relying on the chiropractor’s notation: in his view,

(1) spasticity is closely related to hypertonia, which Dr. McDonough noticed on January 19,

2005, (2) chiropractors are not sufficiently well trained to recognize clinical spasticity in infants,

and (3) the variability of the chiropractor’s records rendered them unreliable. Paluck IV at *59-

60. The special master also placed emphasis on the fact that Karl did not appear to stay home

from daycare in February, nor did he see doctors with the same frequency he had in December,

although he saw the chiropractor frequently. Id. at *60. Overall, the special master concluded

that Karl had not been as sick in February as he was in December. Id. The special master

concluded that the petitioners could not show by a preponderance of the evidence that Karl

manifested evidence of neurological degeneration within the three-week “bound of the

appropriate temporal limit.” Id. at *62.

Based upon a failure of proof respecting the fifth and sixth prongs of Loving, the special

master denied entitlement to compensation. Paluck IV at *63.

STANDARDS FOR REVIEW

Under the Vaccine Act, the court may “set aside any findings of fact or conclusions of

law of the special master found to be arbitrary, capricious, an abuse of discretion, or otherwise

not in accordance with law and issue its own findings of fact and conclusions of law.” 42 U.S.C.

§ 300aa-12(e)(2)(B). The special master’s determinations of law are reviewed de novo. Andreu,

569 F.3d at 1373. The special master’s findings of fact are reviewed for clear error. Id.; see also

Broekelschen v. Secretary of Health & Human Servs., 618 F.3d 1339, 1345 (Fed. Cir. 2010)

(“We uphold the special master’s findings of fact unless they are arbitrary or capricious.” (citing

Capizzano v. Secretary of Health & Human Servs., 440 F.3d 1317, 1324 (Fed. Cir. 2006))).

Under Vaccine Rule 8(b)(1), the special master must “consider all relevant and reliable

evidence.” Vaccine Rule 8(b)(1); see also 42 U.S.C. § 300aa-13(b)(1) (“[T]he special master or

court shall consider the entire record and the cause of the injury, disability, illness, or condition

until the date of the judgment of the special master or court.”). A special master’s findings

regarding the probative value of the evidence and the credibility of witnesses will not be

disturbed so long as they are “supported by substantial evidence.” Doe v. Secretary of Health &

16

Human Servs., 601 F.3d 1349, 1355 (Fed. Cir. 2010) (citing Whitecotton, 81 F.3d at 1105); see

also Porter v. Secretary of Health & Human Servs., 663 F.3d 1242, 1249 (Fed. Cir. 2011).

As this court stated previously,

a deferential standard of review “is not a rubber stamp.” Porter, 663

F.3d at 1256 (O’Malley, J., concurring in part and dissenting in part).

The special master must “consider[] the relevant evidence of record,

draw[] plausible inferences and articulate[] a rational basis for the

decision.” Hines ex rel. Sevier v. Secretary of the Dep’t of Health

& Human Servs., 940 F.2d 1518, 1528 (Fed. Cir. 1991); see 42 U.S.C.

§ 300aa-13(b)(1). . . . And, while the special master need not address

every snippet of evidence adduced in the case, see Doe[, 601 F.3d at

1355], he cannot dismiss so much contrary evidence that it appears that

he “simply failed to consider genuinely the evidentiary record before

him,” Campbell v. Secretary of Health & Human Servs., 97 Fed. Cl. 650,

668 (2011).

Paluck II, 104 Fed. Cl. at 467.

ANALYSIS

There is no dispute that Karl’s claim involves an “off-Table” injury, i.e., an injury or

aggravated condition that is not listed on the Vaccine Injury Table set out at 42 U.S.C. § 300aa-

14(a). See 42 U.S.C. § 300aa-11(c)(1)(C)(ii). Accordingly, petitioners must prove causation in

fact. The special master concluded that petitioners’ claim is most appropriately analyzed as a

significant-aggravation claim governed by the Loving factors. See Paluck II, 104 Fed. Cl. at 408.

Petitioners continue to contest classification of the claim as a significant-aggravation claim rather

than a new-injury claim, notwithstanding the circumstance that the special master found that the

factors related specifically to significant aggravation had been satisfied. See Pet’rs’ Mot. at 4.

Petitioners also contest the special master’s conclusions primarily respecting Loving prongs five

and six, i.e., logical sequence of cause and effect and medically acceptable temporal interval,

respectively. See id. at 14-23. The government urges affirmance of the special master’s

findings. Resp’t’s Opp’n at 1-2.

I. NEW INJURY OR SIGNIFICANT AGGRAVATION

The Vaccine Act defines “significant aggravation” as “any change for the worse in a

preexisting condition which results in markedly greater disability, pain, or illness accompanied

by substantial deterioration of health.” 42 U.S.C. § 300aa-33(4). After giving the parties an

opportunity to file supplemental briefs and giving them an opportunity to present more evidence,

the special master concluded that the preponderance of the evidence weighed in favor of finding

that petitioners’ claim should be analyzed as a significant-aggravation claim. Paluck IV at *8-11.

Petitioners maintain that Karl’s neurodegeneration constitutes a new injury, distinct from any

delays he might have been experiencing in the months before the vaccination. See Pet’rs’ Mot.

at 4-8. The government avers that Karl’s neurodegeneration can only be properly analyzed as a

17

significant-aggravation claim because he already showed signs of developmental delay before

the vaccination. Resp’t’s Opp’n at 7.

Whether petitioners’ claim should be classified as a new injury or significant-aggravation

claim rests on the “the precise definition of Karl’s injury, which is a precondition to identifying

the timing of its symptoms” and “whether indicia of Karl’s neurodegeneration followed the

typical course of a person that suffers from his type of mitochondrial defect.” Paluck II, 104

Fed. Cl. at 468-69. In its remand opinion, this court sought elucidation of whether

developmental delays were the best indicator of neurological injury in someone with a

mitochondrial defect. The special master, on remand, specifically asked the parties to address

Karl’s “neurological, not mitochondrial, symptoms” before the vaccination. Paluck IV at *7

(quoting Paluck II, 104 Fed. Cl. at 469). The government responded that “one cannot separate

‘mitochondrial symptoms’ from the symptoms related to mitochondrial disorder-affected organs,

including the central nervous system.” Resp’t’s Supplemental Br., at 3, ECF No. 125.

Petitioners, however, pointed to pieces of evidence in the record to show that Karl first

exhibited neurological symptoms after the vaccinations, including the chiropractor’s records

from February and March 2005, the K.I.D.S. evaluation, the April 2005 MRI, and the April 2005

neurological assessment. Petr’s’ Supplemental Br. in Resp. to Resp’t’s Supplemental Br.

(“Petr’s’ Supplemental Br.”), at 4, ECF No. 127. The experts disagree about the significance

each of these pieces of evidence.

Petitioners emphasized the October 2004 K.I.D.S. evaluation which found “Karl’s brain

to be functioning within normal limits” and attributed Karl’s gross motor delay to low muscle

tone. Pet’rs’ Supplemental Br. at 2-3. Dr. Frye testified that the K.I.D.S. evaluation was

significant because it showed that Karl’s cognitive abilities were unimpaired in October 2004.

See Tr. 101:8-11 (Frye). In his view, the concern was Karl’s low muscle tone, not his central

nervous system. Id. He further explained that this low muscle tone was most likely due to

Karl’s then-undiagnosed mitochondrial disorder. Tr. 636:8-12 (Frye). Dr. Frye testified that

although Karl’s language skills were below average according to the PLS-3 test, the delay was

minimal. Tr. 100:5-8 (Frye). His combined standard score for the PLS-3 was 96, and Dr. Frye

testified that the average is 100. “[Ninety-six] is very close to 100 on these scales.” Tr. 100:7

(Frye). According to Dr. Frye, “[Karl’s] delays were most prominently gross motor delays,

maybe a little bit of fine motor delays, but cognition, language was absolutely normal.” Tr.

101:9-11 (Frye). “His ability to make language sounds and to interact with others, to be attentive

to what was going on in the room, this was all very important and shows that his brain and

cognition [were] working.” Tr. 102:12-15 (Frye). Dr. Snodgrass disagreed without elaboration.

He opined that describing Karl as “right at the average” was not accurate and that the K.I.D.S.

evaluation did not show Karl’s cognition and language as “absolutely normal,” as Dr. Frye

described. See Tr. 329:3-17 (Snodgrass) (“Q: So would this statement of Dr. Frye’s be true then,

‘Cognition language was absolutely normal[,]’ transcript page 101? A: Well, I think if we refer

to Exhibit 15 we’d have to say no[,] that’s not correct.”).

In turning to the chiropractor’s notation of spasticity in February 2005, the cortical

thumbing noted in April 2005, and the MRI results from April 2005, the experts disagreed over

the significance of all three of these. In short, Dr. Frye found all three to be evidence of sudden

18

neurological regression after the vaccinations, and Dr. Snodgrass found them to be either a

continuation of the same problems that existed before the vaccinations or insignificant.

The experts disputed the value of the chiropractic records in determining Karl’s

neurological state in February and March. In particular, they disagreed over the significance of

the chiropractor’s notation of “spastic” on February 11, 2005. Dr. Frye testified that the

chiropractor’s finding of spasticity “suggests a very severe neurological event, and that suggests

. . . that there was very rapid change in his central nervous system.” Tr. 647:14-18 (Frye); see

also Paluck I at *26 (quoting Tr. 659:25 to 660:10 (Frye)). Dr. Snodgrass saw no special

significance in that record, testifying that “[t]hey [the chiropractic clinic] often say spastic, stiff,

et cetera. So they are reporting on the same general phenomenon which first became evident to

Dr. McDonough in January.” Tr. 337:1-4 (Snodgrass); see also Tr. 543:15-20, 805:14-22

(Snodgrass) (“I think that a chiropractor would have some idea of what spastic means, but not

necessarily the same that a physician would. And I think when you’re talking about a 13 or 14-

month-old child, I don’t think chiropractors are in a position to make any nuanced statements

about them. . . . I don’t believe they are trained to evaluate infants.”).

The experts also disputed the importance of Dr. Kriengkrairut’s finding of cortical

thumbing in April 2005. Dr. Frye called it a “significant sign of advanced upper motor neuron

lesions and something that you don’t see with just some type of change in tone or even mild

spasticity[;] that is a very significant finding.” Tr. 654:22-25 (Frye). He considered that the

cortical thumbing, in addition to being a sign of neurological change, demonstrated an

impairment occurring since December 2004, when Karl was able to open his hands and grab

wrapping paper at Christmas. Tr. 110:6-21 (Frye). Dr. Snodgrass disagreed that the problems

observed by Dr. Kriengkrairut differed substantially from the problems observed by

Dr. McDonough in January 2005. Tr. 350:1-4 (Snodgrass) (“The function recorded in January

by Dr. McDonough is the same function that was recorded by Dr. [Kriengkrairut] in April and by

Dr. McDonough when he again saw Karl in April.”). Dr. Snodgrass testified that cortical

thumbing is not a significant finding and is not one he would have expected Dr. McDonough, a

pediatrician, to note. Tr. 577:17 to 578:3 (Snodgrass). Upon further questioning by the special

master, Dr. Snodgrass stated that thumbing is abnormal in a one-year-old, but in the context of

also seeing increased tone, it is insignificant. Tr. 583:6 to 584:6 (Snodgrass). He further stated

that the thumbing was not necessarily “cortical,” and thus was not necessarily representative of a

brain abnormality. Id.

Lastly, regarding the April 2005 MRI, Dr. Snodgrass and Dr. Frye both concede that it

showed evidence of thinning of the corporal callosum, but Dr. Snodgrass testified that that

thinning could have been present since birth, whereas Dr. Frye testified that it most likely

occurred close in time to the MRI, after the January 2005 vaccinations. Tr. 485:1-4 (Snodgrass);

Tr. 109:12-16 (Frye).

Whether Karl’s severe neurodegeneration would have eventually resulted from his

mitochondrial defect without the vaccinations posed a vexing issue. The government and

petitioners appear to agree that mitochondrial disorders are “a heterogeneous group of disorders

characterized by impaired energy production due to genetically based oxidative phosphorylation

dysfunction.” Paluck IV at *6 (quoting R. Ex. E, at 2, Richard H. Haas et al., Mitochondrial

19

Disease: A Practical Approach for Primary Care Physicians, 120 Pediatrics: Official J. Am.

Acad. Pediatrics 1326, 1326 (2007)). They also agree that manifestations of mitochondrial

diseases are variable. Tr. 286:11-13 (Snodgrass); Tr. 128:22-23 (Frye). The government

maintains that “the aggravation of symptoms as Karl aged stemmed from the natural progression

of the disease.” Resp’t’s Opp’n at 14.

The special master asked Dr. Frye what he would think if a hypothetical child, with

Karl’s same genetic makeup and medical history, experienced the same neurodegeneration as

Karl, without having received any vaccinations. Tr. 241:6 to 242:2. Dr. Frye responded that he

would immediately look for some other trigger, such as a bad infection or a bad viral illness

because it would be very puzzling to see such a regression with no identifiable cause. Tr. 242:6-

11 (Frye). Dr. Snodgrass stated that “[m]itochrondrial problems are heterogeneous. . . . [T]hey

vary enormously.” Tr. 286:11-15 (Snodgrass). The evidentiary record is bereft of any basis for

a natural progression of a mitochrondrial condition to the severely debilitating point Karl

experienced.

The special master acknowledged that it was possible that Karl’s gross motor delays were

purely related to low muscle tone and not his central nervous system, but he believed three

reasons supported finding that Karl had preexisting neurodegeneration allegedly significantly

aggravated by the vaccines. See Paluck IV at *9-10. First, it is generally accepted that there is a

connection between muscle tone and the nervous system. Id. at *9. Second, Karl showed delay

in his expressive language according to the K.I.D.S. evaluation in October 2004. Third, the

special master pointed to the Palucks’ Amended Petition, filed October 17, 2008, stating that

they allege that the vaccines “caused a ‘significant aggravation’ of Karl’s underlying

mitochondrial disorder, leading to . . . subsequent neurodevelopmental regression.” Paluck IV at

*10 (quoting Amended Pet. at 2).

The special master’s reasoning in finding evident neurodegeneration prior to the

vaccinations is partially but not fully supported by the record. The parties accepted that the

central nervous system helps maintain muscle tone, Tr. 111:19-22, 647:12-24 (Frye); Tr. 333:4-6

(Snodgrass), but the experts did not agree that low muscle tone is necessarily a result of a

problem in the central nervous system. Dr. Frye testified that Karl’s gross motor delays were

attributable to “problems with muscle development, and energy that the muscle needs, because

of his [then-undiagnosed] mitochondrial disorder.” Tr. 636:5-12 (Frye). This testimony is

corroborated by the contemporaneous finding by the K.I.D.S. evaluators that Karl’s delays were

likely a result of low muscle tone. See R. Ex. 15, at 4. It is also corroborated by the fact that

Dr. McDonough did not recommend that Karl see a neurologist until late March. See R. Ex. 5, at

45. If low muscle tone was necessarily caused by a problem in the central nervous system, that

would have been evidence that the K.I.D.S. evaluators and Dr. McDonough should have been

and actually were concerned about neurological causes from October 2004 onwards.

Contrastingly, Dr. Snodgrass nonetheless opined that Karl’s gross motor delays and observed

low muscle tone were secondary to undiagnosed problems in his central nervous system. Tr.

420:7-10 (Snodgrass). Although Dr. Snodgrass’s opinion is plausible, it is supported by the

20

contemporaneous medical records only insofar as Dr. McDonough’s examination of Karl on

January 19, 2005 indicated “two beats clonus [right ankle].” See R. Ex. 3, at 3. 20

The special master’s emphasis on Karl’s language delay as evidence of pre-vaccination

neurodegeneration is minimally supported by the record. There is evidence of delay, but the

delay is moderate at most. Petitioners assert there was absolutely no cognitive or language

delay. Pet’rs’ Mot. at 8. Karl tested within normal limits on the Bayley Scales and tested

slightly below average on the PLS-3 scales. See R. Ex. 15, at 2-3. Karl was, however, referred

to speech therapy by the K.I.D.S. program evaluators. Id. at 5. There is room for debate over

whether Karl’s language skills were actually “delayed,” and the special master could have

reasonably concluded that being below average, even just slightly, constitutes delay, but to label

that delay as evidence of then-existing problems in the central nervous system stretches inference

from the evidence too far. In stating that “expressive language tends, at least in the absence of

other identified causes, to be considered a C[entral ]N[ervous ]S[ystem] problem,” the special

master only cites Dr. Snodgrass’s testimony that “alludes” to such a connection between

expressive language and CNS. Paluck IV at *10. Any cognitive and language delays that Karl

had were mild prior to the vaccination and were not of strong concern. See Tr. 636:20-22 (Frye)

(testifying that Karl was one month above his chronological age for the social domain according

to the Vineland test). To find that these delays definitively represented a “CNS problem” is not

supported by substantial evidence.

The special master commented that “special masters ‘can always rule on a factual issue

no matter how scanty the evidence is,’” Paluck IV, at *8 (quoting King v. Secretary of Health &

Human Servs., No. 03-584V, 2008 WL 1994968, at *3 (Fed. Cl. Spec. Mstr. Feb. 7, 2008)), but

that recitation is not a license to ignore the record. In this instance, substantial contemporaneous

medical records exist. The four-month and six-month evaluations by Dr. McDonough, the

records of illness with otitis media and erytherma multiforme, and especially the K.I.D.S.

evaluative results provide significant information about Karl’s condition pre-vaccination. These

records suggest that no one believed or even suspected Karl’s problems were neurological in

nature until after the vaccinations. The special master is not free to decide otherwise in the face

of this evidence.

Despite these flaws, the special master’s conclusion that petitioners’ claim is one of

significant aggravation and not new injury will not be disturbed. It is evident that Karl faced a

multitude of setbacks in the fall. He was not a completely healthy child when he received the

vaccinations. He had an undiagnosed mitochondrial disorder that was causing developmental

delays in some areas, and he was experiencing repeated stresses to his immune system in the

form of persistent otitis media and erythema multiforme. See R. Ex. 3, at 57, 61. Given this

20

Ankle clonus might, but does not necessarily, represent neurological injury. On cross-

examination, Dr. Snodgrass explained that a severely agitated child “who is screaming [his] head

off” might have clonus. Tr. 469:8-11 (Snodgrass). Petitioners’ counsel asked Dr. Snodgrass

whether two beats of clonus is “mild clonus.” Dr. Snodgrass replied, “I think that depends on the

circumstance. I think the basic issue is it’s clonus, which was not present before.” Tr. 468:16-19

(Snodgrass). Upon further questioning, Dr. Snodgrass responded, “Well, it’s — two beats of

clonus is less than say five. But it’s still not normal.” Tr. 468:20-23 (Snodgrass).

21

evidence that Karl’s immune system was not functioning optimally, the court concurs that

petitioners’ claim is more appropriately analyzed as one of significant aggravation. It is not

necessary to find with specificity that Karl’s gross motor delays were neurological rather than

musculoskeletal in nature prior to the vaccinations. If Karl’s problems prior to the vaccinations

on January 19, 2005, were neurological, the impairment was small and not evident to the treating

physicians. Given petitioners’ claim that the vaccine overwhelmed Karl’s immune system

causing cell death, it is enough to find that Karl’s body was under immune stress in the months

leading up to the vaccinations and that his underlying mitochondrial defect made his body less

able to respond to immune stressors. Thus, petitioners’ claim is properly analyzed as one of

significant aggravation and not new injury.

II. LOVING FACTORS

After determining that petitioners’ claim is more properly analyzed as a significant

aggravation claim, the special master applied the Loving test. The court concurs that the Loving

test applies and requires preponderant proof of:

(1) the person’s condition prior to administration of the vaccine,

(2) the person’s current condition (or the condition following the

vaccination if that is also pertinent), (3) whether the person’s

current condition constitutes a ‘significant aggravation’ of the

person’s condition prior to vaccination, (4) a medical theory

causally connecting such a significantly worsened condition to the

vaccination, (5) a logical sequence of cause and effect showing

that the vaccination was the reason for the significant aggravation,

and (6) a showing of a proximate temporal relationship between

the vaccination and the significant aggravation.

Loving, 86 Fed. Cl. at 144.

A. Loving Prong 1: Condition Prior to the Vaccinations

The special master found that “[o]verall, by January 19, 2005, Karl had problems in his

CNS. His pediatrician diagnosed him with gross motor delays, which had worsened in the

preceding three weeks. Karl was also having problems with his language. Finally, Karl was

recovering from the most recent episode of erythema multiforme.” Paluck IV at *20.

Petitioners contest the special master’s findings regarding Karl’s condition before the

vaccinations as arbitrary and capricious and not in accord with the law. First, they challenge the

special master’s interpretation of Dr. Snodgrass’s testimony as meaning that the erythema

multiforme was another possible cause of the neurodegeneration. Pet’rs’ Mot. at 10. Second,

they dispute the special master’s finding that Karl had expressive language delay that, “in the

absence of other identified causes, [is] to be considered a CNS problem.” Paluck IV at *10.

Third, petitioners question the special master’s finding that Karl’s developmental delays

worsened between December 2004 and January 2005, contending that the special master ignored

Dr. Frye’s testimony to the contrary. Pet’rs’ Mot. at 11. The government asserts that the special

22

master’s conclusions of fact, including his conclusion that Karl’s delays prior to January 2005

represented a problem with his central nervous system, are supported by appropriate evidence.

Resp’t’s Opp’n at 1-2.

The special master recounted the evidentiary record in his analysis of Karl’s condition

prior to the vaccinations. He considered both the contemporaneous medical records and the

expert testimony regarding Karl’s recurrent erythema multiforme, finding that it was evidence of

chronic activation of Karl’s immune system. Tr. 294:24 to 295:14 (Snodgrass); Tr. 98:8-13

(Frye). 21

The dispute over whether Karl’s language abilities were delayed poses a different type of

issue. As discussed supra, reasonable minds could differ over whether Karl could or should be

classified as having had a speech delay before the vaccinations. 22 Consequently, the special

master could properly conclude that Karl had speech delays. On the other hand, there is no

evidence that those speech delays were necessarily a result of neurological problems. As

discussed supra regarding the propriety of a significant-aggravation analysis, the

contemporaneous records do not suggest that Karl’s treating physicians and therapists believed

that any extant pre-vaccination speech delay was neurological in nature.

Regarding Karl’s gross motor delays, the special master found that they represented

problems in his central nervous system before the January 19, 2005 vaccinations. In support, the

special master compares Dr. McDonough’s findings in December 2004, that Karl had normal

muscle tone and no ankle clonus, to his findings in January 2005, that Karl had increased tone

and two beats of clonus in his right ankle. Paluck IV at *18-19. This evidence supports the

special master’s conclusion that Karl’s physical condition had worsened between December

2004 and January 2005. A report by the same doctor that Karl went from normal muscle tone to

increased muscle tone and from no ankle clonus to two beats of ankle clonus is compelling.

Again, however, the special master’s conclusion that this worsening is necessarily a result of

problems with Karl’s central nervous system steps beyond the inferences that can permissibly be

drawn from the medical evidence. Although Karl’s medical problems make this case a

significant-aggravation claim rather than a new-injury claim, there is very little direct evidence

21

The special master questioned whether the erytherma multiforme could have caused

Karl’s eventual neurodegeneration but determined that “[r]esolution of this question is not

necessary because . . . Karl did not significantly decline in the weeks immediately following

January 19, 2005, when he both received a set of vaccinations and suffered another bout of

erythema multiforme.” Paluck IV at *13. This latter observation foreshadows the special

master’s analysis of Loving prong six, addressed infra.

22

On December 27, 2004, Dr. McDonough saw Karl when his parents brought him into

the clinic for otitis media and possible erythema multiforme. R. Ex. 3, at 5. Under

“Developmental History” Dr. McDonough recorded, possibly based upon discussion with Karl’s

parents, that “he has several words that he says.” Id. On January 19, 2005, however, he

recorded that Karl had no words, except for “mama” and “dada”. Id. at 3; R. Ex. 5, at 35. No

other evidence suggests that Karl ever had any words beyond “mama” and “dada”, and as such,

the descriptive statement in Dr. McDonough’s report of December 27, 2004 is uncorroborated.

23

that Karl’s condition before the vaccinations had a neurological foundation. Certainly his

treating medical providers did not think it was neurological at the time. 23 Thus, the evidence

shows that Karl had gross motor delays and speech delays, but it does not support finding that

those delays were caused by a significant impairment of his central nervous system. If his

central nervous system was adversely affected, any such disability was not a major one.

B. Loving Prong 2: Condition Following the Vaccinations

Loving prong two inquires into the claimant’s current condition or condition following

the vaccinations. As the special master noted, because Karl’s current condition is not at issue,

the focus turns to his condition in the six months following receipt of the vaccines. Paluck IV at

*20. Two days after the vaccinations, Karl’s daycare recorded that he had a temperature of

101.5 degrees. R. Ex. 22, at 1. For the next week, Karl reportedly acted tired and fussy. Id. On

January 28, nine days after the vaccinations, Karl still had a fever of 101.3, as recorded by his

daycare. Id. at 2. The experts disagree as to the cause of the fever. Dr. Frye testified that the

fever was a symptom of immune activation caused by the vaccinations on January 19, 2005. Tr.

197:1-3, 644:10-13 (Frye). Dr. Frye also opined that Karl’s symptoms in late January and early

February indicated the first signs of the biological processes that eventually led to Karl’s

neurological regression. See Tr. 103:23 to 104:3, 197:12-14, 659:25 to 660:10 (Frye) (describing

Karl’s post-vaccination symptoms as manifesting encephalopathy); see also Tr. 703:22 to 704:2

(Frye). Dr. Snodgrass disagreed, stating that the fever on January 21 manifested too quickly to

be attributed to the vaccines, 24 that the continued fever on January 28 was more likely due to an

outbreak of Karl’s erythema multiforme, 25 and that the fevers in any event were not related to

Karl’s neurological decline. See Paluck I at *21; see also Tr. 338:22 to 339:2, 339:19-25,

346:11-25, 350:1-10 (Snodgrass). Karl’s daycare records, which extend through February 8th,

largely describe him as being tired, irritable, and fussy. See R. Ex. 22, at 1-2.

Karl’s chiropractic records, which begin on February 7, 2005, describe Karl as “irritable”

on February 9th and then “spastic” on February 11, 2005. R. Ex. 12, at 5. The next three visits

suggest some slight progress, but the chiropractor’s assessment of Karl’s condition remained the

same. Id. The following visits noted increased stiffening and spasticity, with the assessment of

Karl’s condition remaining the same. Id. at 6. The first visits of March again indicated some

slight progress, but the remaining three visits in March showed a decline and decreased range of

motion. Id. at 5-7. In April, Karl’s condition continued to be variable. Id. at 7-8. Taken as a

23

The K.I.D.S. evaluation pointed specifically to low muscle tone, R. Ex. 15, at 4, and

Dr. McDonough did not refer Karl to a neurologist until late March 2005, two months after the

vaccination, following reports that Karl was deteriorating further, R. Ex. 3, at 7.

24

Dr. Snodgrass testified that the MMR vaccine introduces a virus into the body that

grows with time. Those viruses “will present a larger stimulus at seven to ten days than they do

on day 1, 2, or 3.” This is unlike a killed bacteria vaccine, which does not multiply in the body

and causes reactions more quickly. Tr. 513:10-17 (Snodgrass).

25

Karl’s daycare noted the reappearance of spots on his arms and legs on January 31,

2005. R. Ex. 22, at 2.

24

whole, the chiropractor’s records document a decline, albeit not a linear one. The observation by

the chiropractor that he was “spastic” is significant. That Karl was a little less spastic or stiff

some days than others does not mean that Karl’s condition improved beyond his initial

appointments in early February. This is consistent with Dr. Frye’s theory that Karl was likely

experiencing changes at the cellular level that would take time to appear at the clinical

observation level.

Moreover, there was a phone conversation between Brenda Erie of Stark County Social

Services and the chiropractor on March 30, 2005, reproduced below, where the chiropractor

discussed possible causes for Karl’s condition, including abuse, adverse reaction to medication

or a vaccine, cerebral palsy, or a cerebellar tumor:

See R. Ex. 12, at 7. The special master read this record as indicating that “[t]he chiropractor

answered ‘No’” to the possibility that an adverse reaction to the vaccination might have caused

Karl’s deteriorating condition. Paluck IV at *46. In the hearing held by the court on September

18, 2013, the government acknowledged that the special master misread this record. The

chiropractor said “No” to child abuse allegations, not to the possibility of an adverse reaction to a

medication, cerebral palsy, or a cerebellar tumor. See Hr’g Tr. 40:23 (respondent’s counsel).

On March 24, 2005, Dr. McDonough referred Karl to a neurologist. This occurred two

days after a phone call between Dr. McDonough and the Palucks, during which the Palucks

reported that Karl had some brief crawling, was not sitting on his own, leans to one side, is

babbling more, and has an intermittent rash. R. Ex. 5, at 72. This is the first time in the record,

that anyone recommended Karl see a neurologist. At that point, Dr. McDonough could not have

thought Karl had improved since the January vaccinations.

On March 28, 2005, Karl had a bout of otitis media and bronchiolitis, documented by

Dr. Gary Peterson. R. Ex. 3, at 64. A week later, Karl’s symptoms were improving in that

regard, and the doctor recommended weaning him off the nebulizer that he had been using to

treat the bronchiolitis. Id. at 66. On April 13, Karl saw Dr. McDonough for a pre-anesthesia

appointment in preparation for his planned MRI. Id. at 9. At that point, Dr. McDonough noted

“increased [tone] in the upper and lower extremities,” no clonus, “decreased hip flexion to about

70 degrees bilaterally,” no speech, and “[g]lobal developmental delay with resolving otitis

media.” Id. at 10. Dr. McDonough described the decreased hip flexion as “a change [in] hip

movement over the last couple months.” Id. He also documented his hope that “the parents

w[ould] agree to evaluation for congenital infections, metabolic disorders, and other tests

requested by Dr. [Kriengkrairut] for his global developmental delay.” Id.

Dr. Frye testified that this examination represented a neurological decline in Karl

“because now he has increased tone in the upper and lower extremities, so – and he says, ‘Global

25

developmental delay with resolving otitis media.’ So here his concerns are that his neurological

exam has gotten worse” since January 2005. Tr. 108:15-22 (Frye). Dr. Frye further opined that

Dr. McDonough’s suspicion of a metabolic disorder was consistent with a finding of increased

tone. Tr. 109:5-7 (Frye). Increased tone suggested damage to the cortex of the brain, which can

be seen in white-matter abnormalities in an MRI. Id. Dr. Snodgrass disagreed that the

examination on April 13th evidenced significant change, stating that while the hip flexion is

more severely limited, it was present in January in any case. Tr. 792:11-12 (Snodgrass).

On April 19, 2005, Karl saw the pediatric neurologist, Dr. Kriengkrairut. She reported

“truncal hypotonia with marked spasticity of the extremities. The baby has tendency to do

cortical thumb bilaterally, worse on the right compared to the left. . . . [B]aby does not babble. . .

. [D]elayed development as well as hypotonia of the extremities may be secondary to central

nervous system pathology.” R. Ex. 3, at 84-85.

Dr. Frye testified that this report by Dr. Kriengkrairut suggests substantial worsening in

Karl. “[This is] a third medical provider talking about spasticity, not just some subtle increases

in tone. [She] actually says on the motor exam[ ‘]marked spasticity.[’] This is very[, ]very

different than just a subtle change in tone.” Tr. 654:6-25 (Frye). Dr. Frye also explained that

hypotonia, cortical thumbing, and cessation of babbling all represent neurological regression. Tr.

110:6-21, 112:17 to 113:2 (Frye). Dr. Snodgrass disagreed. He considered that

Dr. Kriengkrairut’s exam revealed no new neurological problems in Karl. Tr. 350:1-4

(Snodgrass). In his view, cortical thumbing was not a significant finding. Tr. 577:17 to 578:3

(Snodgrass). He also stated that the thumbing was not necessarily “cortical” and thus was not

necessarily representative of a brain abnormality. Tr. 583:6 to 584:6 (Snodgrass).

Dr. Snodgrass’s critical commentary on Dr. Kriengkrairut’s findings appears to have had

two objectives, first, to suggest that Karl’s neurological condition in April 2005 was not

substantially different from his condition before the vaccinations, and, second, to suggest that

Karl’s neurological condition was not deteriorating. Both implications have no support in the

contemporaneous medical records. Karl’s pediatrician, Dr. McDonough, in March had referred

Karl to Dr. Kriengkrairut for a detailed neurological examination because of perceived

neurological abnormalities. Dr. Kriengkrairut found multiple indicia of “central nervous system

pathology.” R. Ex. 3, at 85. What Dr. McDonough had suspected was in fact borne out by

Dr. Kriengkrairut. The spasticity first observed by the chiropractor in early mid-February,

shortly after the vaccinations, was still evident, along with other neurological abnormalities. By

April, Karl was regressing markedly.

In summary, the court finds that Karl had significant signs of neurodegeneration by the

end of April, as evidenced by the marked spasticity, cortical thumbing, and lack of babbling

observed by Dr. Kriengkrairut, the decreased hip flexion and “global developmental delay” noted

by Dr. McDonough, and the belatedly diagnosed abnormal MRI exam from April 27, 2005.

In May 2005, Karl saw a speech therapist. R. Ex. 6, at 5. Karl made no progress

throughout May regarding his speech, and the therapist’s records show that Karl had lost skills

since October 2004. See id. at 5, 25-36. He could no longer produce consonant sounds, but

26

continued to be able to reach for desired toys. Id. at 5-6. Karl’s evaluation in September 2005

stated, “No goals met.” Id. at 7.

On July 12, 2005, Karl experienced his first seizure. R. Ex. 6, at 68. Upon discharge

from the MedCenter One Hospital in Bismarck, Dr. McDonough noted that he had “[g]lobal

developmental delay with seizure disorder, possible deteriorating neurologic status in that he is

unable to do some things that he was able to do previously.” R. Ex. 3, at 18. On July 19, 2005,

Karl saw Dr. Michael Frost at St. Paul Children’s Hospital in Minnesota. R. Ex. 11, at 5. His

medical history from that appointment notes that Karl “has been receiving therapies with some

intermittent [decreased] tone but overall [he is] declining in all areas.” Id. It also notes that by

fourteen months, i.e, March 15, 2005, Karl showed no signs of significant developmental

progress. Id. Dr. Frost noted that Karl was being admitted for a determination of what the

etiology might be for his deteriorating neurological status. Dr. Frost believed, after a second

MRI in July, that Karl was experiencing neurodegeneration. Id. at 56. A third MRI performed

in October 2005 showed that the thinning of Karl’s corporal callosum had stabilized, suggesting

that there may have been a toxic or metabolic event he experienced that had also stabilized. R.

Ex. 11, at 280. In short, Karl’s condition following the vaccinations reflected marked

neurodegeneration.

C. Loving Prong 3: Whether the post-vaccination condition constitutes a significant

aggravation of the pre-vaccination condition

By October 2005, Karl had “no purposeful movements. He had increased tone

throughout and increased deep tendon reflexes throughout with multiple beats of clonus at the

[ankles].” R. Ex. 11, at 279. He had no specific smiling or distinctive eye contact. Id. This

condition starkly contrasts to the previously “very happy” child, R. Ex. 3, at 9, that was “aware

and tuned into faces” and who “enjoy[ed] interactive play,” R. Ex. 15, at 3. The special master

properly concluded that substantial evidence showed that Karl was indisputably worse in the

months following his vaccination. Paluck IV at *42. The parties do not dispute this finding, and

the court concurs that substantial evidence supports the special master’s conclusion.

D. Loving Prong 4 (Althen Prong 1): Whether there is a medical theory causally

connecting the significantly worsened condition to the vaccination

The special master found that petitioners satisfied their burden of proof as to Loving

prong four (Althern prong one), i.e., in showing that a medical theory causally connected Karl’s

worsened condition to the vaccination. The special master succinctly stated that “[i]n briefing

after the [c]ourt’s Opinion and Order, the parties essentially agreed that the Palucks’ evidence

met the standard as defined by the [c]ourt.” Paluck IV at *42. In that connection, the special

master quoted the government’s interpretation of Paluck II as having “hamstrung the special

master from denying compensation under prong one of Althen.” Id. (quoting Resp’t’s Resp. to

Pet’trs’ Status Report Following Remand at 4, ECF No. 120).

On this second review, the government contends that the court in Paluck II

“inappropriately relaxe[d] the Vaccine Act’s requirements.” Resp’t’s Opp’n at 15 (referring to

the court’s observation in Paluck II, 104 Fed. Cl. at 475, “that Dr. Frye’s theory is, while not

27

scientifically certain, under active, continuing scientific investigation by a range of researchers,

showing that it is sufficiently worthy and reliable to merit that extensive scientific injury.”).

The government’s criticism is misplaced. The Federal Circuit has repeatedly emphasized

that preponderant proof of causation does not require scientific certainty, but rather a showing

that the vaccine more likely than not caused the injury. 26 See Althen, 418 F.3d at 1280 (“While

this case involves . . . a sequence hitherto unproven in medicine, the purpose of the Vaccine

Act’s preponderance standard is to allow the finding of causation in a field bereft of complete

and direct proof of how vaccines affect the human body.”); see also Moberly ex rel. Moberly v.

Secretary of Health & Human Servs., 592 F.3d 1315, 1322 (Fed. Cir. 2010) (“A petitioner must

provide a reputable medical or scientific explanation that pertains specifically to the petitioner’s

case, although the explanation need only be ‘legally probable, not medically or scientifically

certain.’” (quoting Knudsen, 35 F.3d at 548-49)); Andreu, 569 F.3d at 1378 (“Requiring

‘epidemiologic studies . . . or general acceptance in the scientific or medical communities . . .

impermissibly raises a claimant’s burden under the Vaccine Act,’” (omissions in original)

(quoting Capizzano, 440 F.3d at 1325)). Even so, the preponderance standard for causation is

not to be confused with a standard requiring only “possible” or “plausible” causation. See

Moberly, 592 F.3d at 1322.

Mitochondrial disorders are only incompletely understood in biomedical science,

although basic mechanisms are known. Those with normally functioning mitochondria have

better antioxidant defenses that allow them to “convert . . . reactive oxygen species to harmless

compounds.” Tr. 65:21-22 (Frye). This is because mitochondria are responsible for the creation

of the energy-carrying molecule, adenosine triphosphate (“ATP”), which is required for the

synthesis of the primary antioxidant, glutathione. Tr. 73:23 to 74:6 (Frye). Contrastingly,

defective mitochondria can have an opposite effect, themselves producing abnormally high

amounts of reactive oxygen species, which can cause damage. Tr. 78:15-25, 79:7-25 (Frye), see

R. Ex. 26, at 5. Thus, people with mitochondrial defects are more vulnerable to oxidative stress.

Tr. 89:18-24 (Frye); Tr. 448:18 to 449:7 (Snodgrass).

Dr. Snodgrass did not disagree with the basic premises behind Dr. Frye’s theory,

but he disagreed that there was evidence, i.e., published peer-reviewed studies, that

normal vaccines given to humans cause oxidative stress. See Tr. 448:18 to 449:7 (“I

would say that if you have a mitochondrial abnormality, you[r] ability to recover [from

excessive reactive oxygen species or reactive nitrogen species] may be less.”), Tr. 482:7

to 484:15 (Snodgrass) (vaccines can affect children with mitochondrial disorders).

Dr. Snodgrass stated that of his about twenty patients with a mitochondrial disorder, none

of them have worsened with immunization, but he admitted that because mitochondrial

disorders are heterogeneous, it is difficult to predict how the same stressor would affect

different people. Tr. 482:9 to 483:1 (Snodgrass). On cross-examination, Dr. Snodgrass

conceded that, in theory, Karl’s otitis media, erythema multiforme, and the vaccines

26

As noted in Althen, 418 F.3d at 1279 n.6, this criterion comes from the Vaccine Act

itself: “Compensation shall be awarded . . . to a petitioner . . . [who] has demonstrated by a

preponderance of the evidence the matters required in the petition by [42 U.S.C. § 300aa-

11(c)(1)].” 42 U.S.C. § 300aa-13(a)(1).

28

administered in January 2005 could have “all worked together and been a substantial

factor in bringing about his neurodegeneration.” Tr. 483:14-25 (Snodgrass). He

maintained, however, that that the theoretical postulate was not established in this case

because Karl did not get worse in January and February after the immunizations. Id.

Nonetheless, whether Karl got worse in January and February after the vaccinations does

not relate to the legal acceptability of Dr. Frye’s theory under Loving prong four, but

instead bears on Loving prongs five and six, i.e., the logical sequence of cause and effect

and a medically acceptable approximate temporal relationship.

Contrary to the government’s reading of this court’s articulation of a standard for

Loving prong four (Althen prong one) in Paluck II, it is not solely because a theory is

under active scientific investigation that it is reputable, worthy, and reliable. The court

instead was stating that the special master could not wholly discount animal studies

showing oxidative stress resulting from vaccinations plus ongoing, continuing scientific

investigation into whether humans also can experience similar oxidative stress resulting

from vaccinations. See Paluck II, 104 Fed. Cl. at 475. Nor could the special master

discredit a peer-reviewed study that suggested oxidative stress in humans resulted from

receipt of the flu vaccine, solely because the researcher used a different biomarker than

he did in a prior study. See id. at 473 (discussing R. Ex. 37a, at 1, Michael Phillips et al.,

Effect of Influenza Vaccination on Oxidative Stress Products in Breath, J. Breath

Research (June 2010), at 1). The court was not relaxing the standard for reliability, but

rather was applying the pertinent and appropriate standard where research was underway

testing reputable theories that were supported by basic knowledge.

E. Loving Prong 5 (Althen Prong 2): Whether there is a logical sequence of cause

and effect showing that the vaccination caused the significant aggravation

Accepting Dr. Frye’s theory of causation that vaccines can activate an overwhelming

immune response in children with mitochondrial defects and lead to neurodegeneration, the next

inquiry is whether, in Karl’s particular case, that process occurred. Similar to the level of proof

required in establishing a medical theory, the sequence of cause and effect must be “logical and

legally probable, not medically or scientifically certain.” Knudsen, 35 F. 3d. at 548-49.

Petitioners contend that the special master put aside expert testimony and

contemporaneous medical records in favor of drawing his own medical conclusions from the

evidence. See Pet’rs’ Mot. at 14-15. Specifically, petitioners challenge his reading of the

chiropractic records, Dr. McDonough’s referral to the neurologist in March 2005, and testimony

regarding the various MRIs. Id. at 14-20.

First, the special master determined that Dr. Frye’s theory requires a linear, downward

decline without any periodic improvements. See Paluck IV at *43. Both the government and the

special master cite this court’s opinion in Paluck II for the proposition that this court approved of

the special master’s prior conclusion that “petitioners’ medical theory predicted a steady,

downward decline in health after vaccination.” Resp’t’s Opp’n at 15 (citing, but not quoting,

Paluck II, 104 Fed. Cl. at 476); see Paluck IV at *43 (“The [c]ourt did not disturb the finding that

Dr. Frye’s theory was predicated on a downhill trajectory”). The citation provided by both the

29

respondent and the special master misapprehends the court’s prior action. This court did not

address the special master’s determination in Paluck I that Karl’s regression could only fit

Dr. Frye’s theory if Karl experienced a “continuous downward slope” of injury. Paluck I at *22.

The decision to require a linear, downward slope is unfounded in the testimony. The

special master in Paluck I interpreted Dr. Frye’s phrase that “[Karl’s progress] looked like it was

just a progressive hill downward for about six months,” to mean “a continuous downward slope.”

Paluck I at *22 (quoting Tr. 231:13 (Frye)). The special master maintained this interpretation in

Paluck IV. See Paluck IV at *49 (“the special master again concludes that Karl’s deterioration

was non-linear”). Dr. Frye, however, never suggested that a child experiencing

neurodegeneration could not have periods of remission or improvement. His use of the word

“progressive” does not mean a continuous linear decline. As a general matter, when used in

describing a disease, progressive means “increasing in extent or severity.” Merriam-Webster’s

Tenth Collegiate Dictionary 932 (1998); see also New Oxford American Dictionary 1396 (2010)

(“(of a disease or ailment) increasing in severity or extent.”). This standard medical usage

allows for a non-linear decline. To fall within Dr. Frye’s theory and the applicable medical

literature, it is sufficient if Karl’s medical records show a decline in condition over time,

notwithstanding periods of remission or modest improvement.

Second, the special master considered the chiropractic records and statements by his

treating physicians regarding Karl’s decline. In the remand, the court ordered the special master

to reconsider the importance of these particular pieces of the record, in conjunction with other

pieces of the record. See Paluck II, 104 Fed. Cl. at 480. Accordingly, this court will consider

the entire record in determining whether petitioners have met their burden of proof under Loving

prong five.

Karl had a fever on January 21, 2005, two days after the vaccinations, that continued to

be evident on January 28, 2005, nine days after the vaccinations. R. Ex. 22, at 1-2. Daycare

notes from the intervening days consistently show that Karl was tired, irritable, and not eating

well. Id. According to Dr. Frye, these are all systemic signs of being sick, that is, signs of

immune activation. Tr. 103:23 to 104:1, 105:3-5, 143:6-15 (Frye). Dr. Frye testified that a fever

any time within two weeks of a vaccination could reasonably be attributed to the vaccination.

Tr. 145:17-18 (Frye). Dr. Snodgrass disagreed that Karl’s fever could have been caused by the

vaccines. He explained that the MMR and varicella vaccines do cause fever in some children,

but fever would not usually appear until the seventh or eighth day. Tr. 338:22 to 339:1, 571:4-12

(Snodgrass). On cross-examination, petitioners’ counsel asked Dr. Snodgrass whether he was

familiar with the packaging insert accompanying the Prevnar vaccine, which states that “15% of

children who receive PCV-7 report fever of greater than 38 degrees centigrade within two days

following vaccination.” Tr. 575:10-17 (petitioners’ counsel). 27 He responded that he was, but

that the packaging insert does not truly prove causation as a scientific matter. Tr. 575:18-24

(Snodgrass). He referred to a study about the MMR vaccine, one of the other vaccines Karl

received, which took 500 sets of identical twins, giving one twin the vaccine and the other a

placebo. Tr. 576:2-10 (Snodgrass). In his view, this type of study better proves that a vaccine

causes fevers. Id. In short, Dr. Snodgrass again looked for medical certainty where none is

27

The packaging insert is in the record as R. Ex. 33.

30

required. It is sufficiently logical that Karl had a reaction to the Prevnar vaccine, manifesting as

a fever within two days. He additionally did not explain why the fever on day nine could not be

attributed to the vaccinations, stating only that Karl’s fevers could have been due to an outbreak

of his erythema multiforme, which reappeared on January 31st. Tr. 339:15-25 (Snodgrass); R.

Ex. 22, at 2. He testified further that fever is very common among children in daycare and may

not specifically indicate oxidative stress. Tr. 291:4-9 (Snodgrass). Similarly, in his view, while

irritability might be an indication of something serious, it is not specific. Tr. 291:12-14

(Snodgrass).

Several points of common ground exist. A fever is usually a symptom of immune

activation; that much was acknowledged by both experts. Tr. 429:4-16 (Snodgrass); Tr. 105:3-5

(Frye). And, the daycare records contemporaneously documented that Karl had lethargy and

irritability along with the fever in the days following the vaccinations. While fever, lethargy, and

irritability might possibly have been caused by something besides the vaccinations, sufficient

evidence exists to indicate that they were in fact caused by the vaccinations. That at least one of

the five vaccines that Karl received, or a combination thereof, caused him to have a fever due to

immune activation is logical and legally probable. A prima facie case to that effect was

established. Accordingly, the burden shifted to the respondent to show another, alternative,

cause. That shifted burden was not met, nor did the respondent attempt to meet it.

Dr. Frye’s theory postulates that immune activation can cause the development of

potentially toxic reactive oxygen species and reactive nitrogen species that, if left unchecked by

the body’s antioxidants, can lead to oxidative stress and cell death. See supra, at 11. Thus, one

would look for evidence of whether Karl experienced cell death. In this case, petitioners contend

that Karl’s neurodegeneration is evidence of brain cell death.

Karl’s health deteriorated in February 2005. The chiropractor noted he was spastic on

February 11, 2005. R. Ex. 12, at 5. As detailed previously, Karl’s later chiropractic records

reflect varying levels of rigidity and tone. Id. at 5-7. Regardless of whether Karl had days in the

subsequent weeks where he was more or less rigid, Karl never appeared to improve above his

initial assessment, and he was still reported as spastic in April by the pediatric neurologist,

Dr. Kriengkrairut. R. Ex. 3, at 84. Upon questioning by the special master regarding the

chiropractic treatment Karl received, Dr. Frye testified that spasticity can be improved by

“pulling the muscles and loosening the muscles so that they have full range of motion.” Tr.

726:9-14 (Frye). This does not solve the upper neuron problem causing the spasticity, but it can

mitigate the symptoms. “[B]y manipulating the muscles you’re resetting the feedback

mechanism that sets the tone of the muscle[s]. . . . When [neurons from the brain] aren’t there

[the] feedback loop becomes or [is] set too high and the muscles have too much tone. . . . By

using physical therapy we start to stretch out the muscles and that can try to reset the feedback

loop that we have in the muscles.” Tr. 726:19 to 727:10 (Frye). That Karl’s tone fluctuated

while he was seeing the chiropractor, see R. Ex. 22, at 2, and the K.I.D.S. therapists, see R. Ex.

12, would be expected.

In asserting that Karl did not decline between January and February, Dr. Snodgrass stated

that “the single most important thing is that we had a lot of calls and doctor visits in November

and December. If Karl had a precipitous decline in January and February, these parents who

31

seem to be responsible parents would have been calling and visiting the doctor, that’s number

one.” Tr. 790:9-14 (Snodgrass). Dr. Snodgrass’s inference and the special master’s reliance on

it, see Paluck IV at *57, are not supported by substantial evidence. Karl’s parents actually were

taking him frequently to a medical provider, i.e., the chiropractor. They took him to the

chiropractor nine times in a three week period in February alone, apparently believing that Karl

had a pinched nerve preventing his development. See R. Ex. 3, at 7. Dr. Snodgrass can disagree

with their course of action, implicitly being critical of treatment by a chiropractor rather than a

physician, but his testimony implying that the Palucks thought medical treatment unnecessary for

Karl is not supported by evidence.

Contrary to the special master’s conclusion, the fact that Karl had few visible signs of

injury other than fever immediately following the vaccinations is in keeping with Dr. Frye’s

theory. See Paluck IV at *49 (“part of the Althen prong 2 analysis may consider whether the

expert’s ‘theory accounted for [the vaccinee’s] injury’” (quoting Hibbard v. Secretary of Health

& Human Servs., 698 F.3d 1355, 1364 (Fed. Cir. 2012))). Dr. Frye testified that changes at the

cellular level would occur first and would take time to become clinically visible. Tr. 232:5-10

(Frye). That the MRI from April 2005 was initially interpreted as normal and only later

reinterpreted as abnormal upon re-examination in July 2005 suggests that the changes were

indeed small at first, but they had been initiated. Id. Because the changes were likely occurring

at a cellular level at first, Karl was probably worsening in February and March even if it was not

linearly progressive. Tr. 730:25 to 731:6 (Frye.). The rate at which that process would occur

would depend on the type and severity of the person’s mitochondrial disorder.

As an example, Dr. Frye pointed to the Hannah Poling case study. Tr. 121:25 to 123:16,

132:21-24 (Frye) (referring to R. Ex. 21q, Jon S. Poling, Richard E. Frye, John Shoffner &

Andrew W. Zimmerman, Developmental Regression and Mitochondrial Dysfunction in a Child

with Autism, 21 J. Child Neurology 170 (2006)). Hannah was a developmentally normal

nineteen-month-old girl who, within 48 hours of receiving several vaccinations, developed a high

fever, inconsolable crying, irritability, and lethargy, and refused to walk. R. Ex. 21q, at 3. Four

days later, she could not walk up stairs. Id. She had a low-grade intermittent fever during the

next twelve days. Id. She continued to decline over the next three months, developing autistic

behaviors and losing all speech. Id. Previously she had been able to say at least twenty words.

Id. It was later discovered that she had a mitochondrial disorder. Id. In 2006, at the time of

publication of the case study, Hannah was six and had greatly improved in her language

functions and sociability, although she still exhibited mild autism. Id. This case study did not

prove causation with any medical certainty, but it hypothesized that “[i]f [mitochondrial]

dysfunction is present at the time of infections and immunizations in young children, the added

oxidative stresses from immune activation on cellular energy metabolism are likely to be

especially critical for the central nervous system, which is highly dependent on mitochondrial

function.” Id. at 4.

Dr. Frye pointed to similarities between Hannah and Karl. First, they have similar

mitochondrial abnormalities. Tr. 122:20-23 (Frye). Both received MMR and varicella

vaccinations, developed a fever around 48 hours later, became noticeably irritable, and

eventually experienced neurological regression. Tr. 122:24 to 123:12 (Frye). Hannah’s decline

occurred more quickly in some ways, but her regression, like Karl’s, appeared to continue over a

32

number of months. Her appetite remained poor for six months, but she began saying a few

words again about four months after the vaccinations. R. Ex. 21q, at 3. In contrast, Karl has

experienced complete neurodegeneration and is not expected to improve. Tr. 123:7-13 (Frye).

Dr. Frye opined that Karl’s pre-existing chronic immune activation may have impaired his ability

to recover as Hannah did. Tr. 704:3-17 (Frye).

Dr. Frye also pointed to a peer-reviewed article by Dr. John Shoffner and others. The

researchers found in a retrospective study that autistic regression occurred twice as often in a

subset of autistic children with mitochondrial disorders after a fever than it did in the general

population of autistic children. See Tr. 124:1 to 125:12 (referring to R. Ex. 21z, John Shoffner et

al., Fever Plus Mitochondrial Diseases Could Be Risk Factors for Autistic Regression, 25 J.

Child Neurology 429 (2010)). 28 Approximately 25% of children with autism will experience

autistic regression before the age of three. R. Ex. 21z, at 1. The researchers defined autistic

regression to mean “a loss of developmental skills that included speech, receptive skills, eye

contact, and social interests in individuals.” Id. at 2. A relationship between fever and

regression was defined as “regression beginning within [two] weeks of a febrile episode without

the suggestion of infection, meningitis, or encephalitis.” Id. In the study, 60.7% of the children

experienced autistic regression, which was a “statistically significant increase” over the

estimated 25% reported in the general autistic population. Id. at 3. A high percentage, 70.6%, of

those who experienced autistic regression did so following a fever. Id. In 33.3% of those who

experienced autistic regression following fever, the fever was associated with response to a

vaccination. Id. The specific vaccine schedule leading to fever in the subjects was not available.

The study acknowledged that “[d]ue to the complexities in mitochondrial disease pathogenesis,

oxidative phosphorylation enzyme defects are highly variable even among groups of individuals

who harbor identical mutations.” Id. at 4. 29 According to Dr. Frye, this study, combined with

the Poling case study, strongly suggested that vaccinations in children with mitochondrial

diseases can cause fever followed by regressive loss of skills. See Tr. 188:11-15, 621:1-6 (Frye).

Dr. Snodgrass cited a number of differences between Karl’s case and Hannah’s case.

First, Hannah’s clinical worsening was much more dramatic than Karl’s. She refused to walk

within 48 hours of receiving the vaccination, a more notable loss of skill than anything Karl

experienced. Tr. 344:1-21 (Snodgrass). Second, there is no evidence that Karl suffered

encephalopathy, and it was agreed that Hannah did. Id. “In Karl’s case we really don’t see that.

28

In this retrospective study, researchers examined the charts of 28 children who they

knew to have autism and mitochondrial disease. They used the charts to determine whether the

children experienced fever followed by autistic regression.

29

Phosphorylation is defined as “the metabolic process of introducing a phosphate group

into an organic molecule.” Oxidative phosphorylation, specifically, is defined as “the formation

of high energy phosphate bonds by phosphorylation of ADP to ATP coupled to the transfer of

electrons from reduced coenzymes (NADH or FADH2) to molecular oxygen via the electron

transport chain. . . . Three molecules of ATP per NADH and two per FADH2 are produced as a

result of a proton gradient created across the mitochondrial inner membrane by the electron

transport chain.” Dorland’s at 1439. Thus, “oxidative phosphorylation enzyme defects” can be

understood as defects in ATP production.

33

Yes, he was irritable. Irritability is not encephalopathy. He was not kept home from day care, he

was not taken to the doctor. So we do not see evidence that Karl had encephalopathy.” Tr.

344:16-20 (Snodgrass). As for Dr. Frye’s reliance on the Shoffner paper, Dr. Snodgrass

criticized its simplicity, questioning how researchers could have known that any particular fever

that a child experienced caused the regression. Tr. 345:15-25 (Snodgrass).

Dr. Snodgrass’s critiques might provide valid points of departure for further scientific

study in this area of medicine, but they do not negate the evidentiary value provided by the

Poling case report or the Shoffner study. 30 Dr. Snodgrass and Dr. Frye agreed that case studies

do not prove causation. But Dr. Frye correctly pointed out that “that’s where science starts is

with case reports.” Tr. 716:1-2 (Frye). Dr. Frye testified that this particular area of medicine is

“emerging and evolving.” Tr. 126:1-6 (Frye). Mitochondrial diseases themselves are difficult to

identify, and their courses of progression are not easily predicted. The effect of fevers on those

with a mitochondrial disorder is even more difficult to assess. The Poling case report and the

Shoffner study nonetheless provide indicia for this case.

In considering the opinions of Karl’s treating doctors as to the cause of Karl’s decline, the

special master considered the chiropractor’s opinion, Dr. McDonough’s referral to the

neurologist, and the MRI reports. First, as discussed supra, the special master’s statement that

the chiropractor did not believe Karl had an adverse reaction to a vaccine simply misread a

handwritten entry in the medical record. Rather, the chiropractor believed it was possible Karl

had an adverse reaction to a vaccine. See supra, at 25. Second, in reviewing Dr. McDonough’s

referral to Dr. Kriengkrairut, the pediatric neurologist, the special master inquired into

Dr. McDonough’s motivations. Aside from desiring more complete testing of Karl’s

neurological system, the special master opined that Dr. McDonough made the referral because he

was “frustrated the Palucks were not following his recommendations for physical therapy,

occupational therapy, and a stimulation program for Karl.” Paluck IV at *47. The special master

criticized petitioners for not raising the argument that Dr. McDonough made the referral because

he believed Karl was getting worse. Id. at *47 n.69. The special master apparently ignored

Dr. Frye’s testimony on direct examination that the referral is “the first indication that we have

that the pediatrician is now concerned [to such] a level that Karl needs to see a neurologist.” Tr.

107:4-6 (Frye). There simply is no evidentiary support for the special master’s hypothesis that

Dr. McDonough made the referral out of frustration with the Palucks.

Third, regarding the MRI reports, the special master concluded that “[t]he Palucks have

not established that Dr. Frye’s conclusion that Karl’s corpus callosum started to thin after the

vaccination is more likely than Dr. Snodgrass’s conclusion that the corpus callosum could have

been thin before the vaccination.” Paluck IV at *48. Accordingly, the special master used his

finding that Karl had problems in his central nervous system before the vaccination as the tie

breaker to determine that the thinning occurred before the vaccinations. Id. This court has

overturned the special master’s finding that Karl definitively had neurological problems before

30

Evidence of causation need not be proven to a medical certainty; it need only be

“logical and legally probable.” Knudsen, 35 F. 3d. at 548-49 (internal quotation marks and

citations omitted).

34

the vaccinations. See supra, at 23-24. The subtlety of the thinning in April, and the clarity of the

thinning in July, suggests that the thinning had only begun in April or shortly before then.

Petitioners have presented sufficient evidence to show that Karl regressed after receiving

the vaccines, and they have provided medical records and medical literature to establish, by a

preponderance of the evidence, that Karl’s pre-existing medical problems were significantly

aggravated by the vaccinations. Karl had a fever shortly after receiving the vaccinations, was

described as “spastic” for the first time on February 11, was referred to a neurologist in March,

and by April had a negative neurological evaluation and an abnormal MRI. Petitioners presented

a peer-reviewed study showing increased regression in children with mitochondrial diseases

following fever. They also presented a case study demonstrating that a young girl with an

underlying mitochondrial disorder lost previously developed skills over the course of months

after experiencing a fever within 48 hours of vaccinations. Petitioners have carried their burden

of proof on this prong.

F. Loving Prong 6 (Althen Prong 3): Whether a medically acceptable proximate temporal

relationship exists between the vaccination and the significant aggravation

The final prong of the Loving analysis requires the court to determine the time frame for

which it is medically acceptable to infer causation and whether the onset of the claimant’s injury

occurred within that time frame.

Petitioners contend that the special master ignored the record in concluding that Karl

exhibited no evidence of neurodegeneration within an acceptable time frame. Pet’rs’ Mot. at 21.

Specifically, they argue that he ignored Dr. Frye’s testimony that evidence of neurodegeneration

occurred within a medically acceptable time. See Tr. 127:15 to 129:14 (Frye). Respondent

maintains that the special master carefully considered all of the evidence and found respondent’s

expert more persuasive than petitioners’, an approach and result that is well within the special

master’s role as a finder of fact. Resp’t’s Opp’n at 18.

In Paluck IV, the special master found that the medically acceptable temporal interval is

three weeks. Paluck IV at *62 (concluding that “the bound of the appropriate temporal limit is

three weeks”). He based this determination largely on an article by Dr. Edmonds entitled The

Otolaryngological Manifestations of Mitochondrial Disease and the Risk of Neurodegeneration

with Infection in the record as R. Ex. 21d. 31 The Edmonds article collected information about 40

patients with mitochondrial diseases. Of these forty patients, eighteen experienced

neurodegenerative events. R. Ex. 21d, at 6. Intercurrent infection was recognized as a

precipitant of neurodegenerative events in thirteen of these eighteen patients. Id. at 4-6. The

article graphically depicts the timing of the onset of neurodegenerative events after the onset of

infection as ranging until nineteen days after infection. Id. at 7; see also Paluck IV at *55.

While the Edmonds article looked for neurodegeneration after infection, not reaction to a

vaccination, both experts agree that it provides a reasonable guideline for neurodegeneration

following immune activation. Tr. 524:1-5 (Snodgrass); see Tr. 619:6-11 (Frye).

31

This article is briefly addressed supra, at 16.

35

The special master also relied on the Shoffner study, which found that a relationship

between fever and autistic regression existed, see Paluck IV at *53-54, but this reliance is

somewhat misplaced because the Shoffner study defined a relationship between fever and

regression as occurring within two weeks, excluding later sequelae, R. Ex. 21z, at 2. Therefore,

by definition, the study could not have found a relationship between fever and regression more

attenuated than two weeks. Thus, while the Shoffner article supports a statement that autistic

regression following fever can occur within two weeks, it cannot equally support a statement that

autistic regression following fever must occur within two weeks. The special master also relied

on the Hannah Poling case study, noting that she had a fever within 48 hours, could not climb the

stairs within seven days, and developed a rash within two weeks. Paluck IV at *55.

The Edmonds article is the most enlightening regarding an acceptable medical time frame

for the onset of neurodegenerative events following immune system activation. The Edmonds

article, however, acknowledges the severe dearth of medical literature in this area: “Because of

the relative novelty of mitochondrial disorders, no reports in the literature have quantified the

risk for neurodegenerative events triggered by infections in patients with mitochondrial disease.”

R. Ex. 21d, at 3. Dr. Bob Naviaux, Co-Director of the Mitochondrial and Metabolic Disease

Center at the University of California, San Diego, expressed a similar sentiment in commenting

on the Shoffner study. See R. Ex. 31, Bob Naviaux, “Commentary on John Shoffner et al., Fever

Plus Mitochondrial Disease Could Be Risk Factors for Autistic Regression, published in 25 J.

Child Neurology 429 (2010).” According to Dr. Naviaux, the temporal relationship between the

triggering event and neurodegeneration is unsettled. There appears to be a more rapid “flare”

response and a more delayed “fade” response. Id. at 2. He credited the Shoffner study with

providing a touchstone for new questions, such as “which kinds of mitochondrial defects lead to

rapid, high-grade fevers in response to infection or vaccination” and “which defects lead to a

failed fever response, or to a low-grade fever, or to a reduced immune response to vaccination?”

Id. at 3.

Dr. Frye accepted the premises of these articles, testifying that the temporal link requires

much further study. He did testify, however, that an adverse reaction to a vaccine is likely to

appear within a week of receiving it. Tr. 127:21-22 (Frye). He further stated that the adverse

reaction can peak several days after the vaccination, and then “lead to . . . metabolic

decompensation, which is an ongoing process . . . [that will] continue until it burns itself out,” if

it is not interrupted. Tr. 128:5-9 (Frye). Dr. Snodgrass and Dr. Frye disagree whether Karl’s

first fever, within two days of the vaccination, could have been caused by the vaccination, but

they apparently agree that any fever around one week following Karl’s vaccinations could have

been caused by the vaccines. See id.; Tr. 513:10-17 (Snodgrass). Thus, at least Karl’s

continuing fever is safely within any type of medically accepted time frame for Karl’s injury.

The special master appeared determined to establish a definitive bound for

neurodegeneration, but the court disagrees that such a bound can be sharply delineated in this

specific area. Neither the medical literature nor the expert testimony stated with any certainty

when neurodegeneration can be expected to begin in all cases. Dr. Snodgrass based his

testimony that a change would have to begin “within a few weeks” on the Edmonds article. Tr.

524:1-6 (Snodgrass). As previously discussed, the Edmonds article is the first of its kind and

cannot be read to suggest a definitive temporal interval for neurodegeneration in response to all

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triggering events for any type of mitochondrial disorder. In response to questioning from the

special master, Dr. Frye testified that the timing for neurodegenerative changes to appear

clinically in a child would depend on the severity and type of mitochondrial disorder. Tr.

128:22-23 (Frye). This is consistent with Dr. Naviaux’s commentary on the Shoffner study.

In this instance, Dr. Frye pinpointed the chiropractor’s notation that Karl was “spastic”

on February 11, 2005 as an identifiable neurodegenerative event. See Tr. 659:23 to 660:10

(Frye). To Dr. Frye, the neurodegenerative process must have begun by then. This event

occurred within the general time frame suggested by both the special master and Dr. Snodgrass.

See Tr. 524:5-6 (Snodgrass) (“The change should come within a few weeks.”). Starting with this

chiropractic notation, the record shows Karl experienced a general decline. His chiropractic

assessment remained the same throughout all of February, even if the subjective descriptions of

Karl’s day-to-day behaviors varied. Karl was losing language throughout this period, and by late

March, Dr. McDonough saw a need for him to be evaluated by a neurologist.

In conclusion, setting a hard and fast time frame in an uncertain area undergoing

sustained scientific investigation is contrary to the precepts governing the Vaccine Act. Karl had

a fever within 48 hours of the vaccinations, accompanied by a week of lethargy, irritability, more

fever, and disrupted sleeping and eating cycles. This prompt reaction is consistent with an

adverse immune reaction to the vaccines. An observation of spasticity followed within a time

that all agreed would have been appropriate for a neurodegenerative event. Karl experienced

total decline within six months, and he did not continue to develop in any way after the

vaccinations. These facts combined with his febrile reaction to the vaccine show, by a

preponderance of the evidence, that Karl’s existing medical setbacks were significantly

aggravated by his receipt of the vaccinations within a medically acceptable time.

CONCLUSION

For the reasons stated, the Palucks’ motion for review is GRANTED, the special master’s

decision of May 10, 2013 denying compensation is VACATED, and the court acts in accord with

42 U.S.C. § 300aa-12(e)(2)(B) to find that petitioners have satisfied each of the six Loving

elements and are entitled to compensation under the Act. 32 The case is remanded to the special

32

The Vaccine Act provides that upon the filing of a motion for review of a special

master’s decision, this court

may thereafter —

(A) uphold the findings of fact and conclusions of law of

the special master and sustain the special master’s decision,

(B) set aside any findings of fact or conclusions of law of

the special master found to be arbitrary, capricious, an abuse

of discretion, or otherwise not in accordance with law and issue

its own findings of fact and conclusions of law, or

37

master to determine compensation.

It is so ORDERED.

s/ Charles F. Lettow

Charles F. Lettow

Judge

(C) remand the petition to the special master for further action

in accordance with the court’s direction.

42 U.S.C. § 300aa-12(e)(2).

38