# In the United States Court of Federal Claims

No. 14-65V (Filed: April 18, 2019) 1 Opinion originally issued under seal on April 2, 2019
HEIDI SHARPE, as legal representative of her minor child, L.M., Petitioner,

v. SECRETARY OF HEALTH AND HUMAN SERVICES, Respondent. ) ) ) ) ) ) ) ) ) ) ) ) ) ) Vaccine; Encephalopathy; Table Significant Aggravation; Off-Table Significant Aggravation; Qualifications and Aids to Interpretation.

Curtis R. Webb , Twins Falls, ID for petitioner. Amy P. Kokot , Civil Division, United States Department of Justice, Washington, D.C., with whom were Joseph H. Hunt , Assistant Attorney General, C. Salvatore D’Alessio , Acting Director, Catherine E. Reeves , Deputy Director, and Heather L. Pearlman , Assistant Director, for respondent.
O P I N I O N
FIRESTONE , Senior Judge Heidi Sharpe (“petitioner”), as the lega l representative of her daughter, L.M.,

1 Pursuant to Rule 18(b) of Appendix B of the Rules of the United States Court of Federal Claims (“RCFC, App. B”), this Opinion was in itially filed under seal on April 2, 2019. The parties had fourteen days from the date of filing of this Opinion to propose redactions of any of the information herein. Neither party submitted any redactions.2 seeks review of the Special Master’s De cision Denying Entitlement under the National Childhood Vaccine Injury Act of 1986, 42 U.S.C. §§ 300a a-1 to -34 (“Vaccine Act” or “Act”), as amended. Sharpe v. Sec’y of Health & Human Servs. , No. 14-65V, 2018 WL 7625360 (Fed. Cl. Spec. Mstr. Nov. 5, 2018) (“Decision” or “Dec.”) (ECF No. 102).
I. BACKGROUND
A. Factual Background The essential facts of this case are se t forth in the Special Master’s Decision, see generallyDec. at 2-7, and may be summarized as follows. L.M. was born on July 26, 2010. Dec. at 2. Over the next six mont hs, she received routin e childhood vaccinations without incident, including Pediarix (dipht heria-tetanus-acellular pertussis (“DTaP”), hepatitis B, and inactivated polio), haem ophilus influenzae type B (“Hib”), pneumococcal conjugate, and rotavirus. Id . On January 17, 2011, L.M. had a well-child visit. Id . Petitioner stated that L.M. had devel oped symptoms of an upper respiratory infection (“URI”) and a rash; she was diagnosed with a viral infection that causes rashes, but she was otherwise healthy. Id . at 2, n.4. L.M.’s vaccinations were postponed due to her illness. Id. at 2. The next day, petitioner br ought L.M. to th e emergency room reporting “inconsolable crying” for one hour; her examination was normal. Id

. On February 2, 2011, petiti oner brought L.M. to her do ctor’s office describing congestion and thick nasal dr ainage for six weeks. Id. at 3 (citing Petitioner’s Exhibit (“Pet. Ex.”) 2 at 8). L.M. was diagnose d with congestion, and an antibiotic was prescribed. Dec. at 3. On February 10, 2011, L.M. received her third DTaP, Hib, and pneumococcal3 conjugate vaccinations. Dec. at 3. Th e next afternoon, pe titioner phoned L.M.’s pediatrician, reporting that L.M. “had ‘dev eloped a fever and [was] whimpery [and] wak[ing] up “screaming.’” 2 Id. (quoting Pet. Ex. 2 at 19). Petitioner stated that L.M. had not reacted to her previous immuniza tions she received in the fall. Id. L.M.’s doctor “proposed ‘that this [was] mostlikely not related to the inje ctions,’ and attributed L.M.’s symptoms to a possi ble viral illness[.]” Id. On February 15, 2011, pe titioner brought L.M. to th e emergency room because she “had ‘suddenly become “stiff all over” [and] unresp onsive,’” which had lasted approximately thirty seconds. Dec. at 3. During the episode, L.M. was afebrile. Id

. Petitioner conveyed that one month earlier, L.M. had “experienced an ‘unexplained episode of sudden flaccidity [and] unresponsiveness’ for appr oximately thirty seconds, followed by several minutes of crying and irritability.” Id .; see also id. at 8 n.10 (stating that petitioner recounted “‘a few other episodes of [L.M.] “spacing out” where she had a strange look in her eye and was not responsive for several seconds’”). L.M.’s temperature was 97.5 degrees Fahr enheit, and she was alert. Id. at 3. Yet she was observed to have “‘floppy’ motor contro l and skills” and poor head control. Id. Later that day, L.M. had another seizure, and she was transferred to St. Vincent Hospital. Id. at 4. During her stay, she had an evaluation with Tarif Bakdash, M.D., a

2 Petitioner contacted L.M.’s docto r’s office and the emergency room earlier in the day as well on February 11, 2011, and she filed phone records to document these calls. See Pet. Ex. 73 at 17; Pet. Ex. 74 at 1-2. She averred that on Fe bruary 12 and 13, 2011, L.M. had a high fever and displayed “floppiness and an unchara cteristic disinterestedness.” Dec. at 3. Petitioner claimed that she phoned the emergency room twice to re port these concerns, and she was “rebuffed,” although no records confirm these calls. Id.4 pediatric neurologist. Id. Petitioner described L.M. as “‘being hypotonic or floppy’ since birth.” Id. Dr. Bakdash summarized L.M.’s seiz ure-like activity, which included three spells over the past twenty-four hours. Id . His impression was that L.M. suffered from a generalized seizure pattern and infantile spasms. Id

. The following day’s electroencephalogram (“EEG”) revealed hypsarrhythmia, a “primary clinical characteris tic of infantile spasms.” Id. On February 17, 2011, L.M. was discharged with a diagnosis of infantile spasms, also known as West Syndrome. Id.

. at 5. Although L.M. had returned to her pre-hospita lization baseline (with some generalized hypotonia), she re turned to the emergency roomon March 21, 2011, due to ongoing seizures and URI symptoms. Id . At that time, L.M. was having five or six seizures per day. Id. Upon discharge, she had no new diagnoses. Id . (citing Pet. Ex. 3 at 57). Throughout the remainder of 2011, L. M. had several appo intments with Dr. Bakdash and with her pediatrician. Id . at 5. Another EEG, pe rformed on April 18, 2011, again showed hypsarrhythmia, as well as new-onset seizure ac tivity in the left temporal region. Id . As of November 8, 2011, Dr. Bakda sh’s differential diagnoses for L.M. included infantile spasms, comp lex partial seizures, and glob al developmental delay. Id. at 6 (citing Pet. Ex. 7 at 8) Other specialists also evaluated L.M. Id . On October 27, 2011, Laura Nicholson, M.D., a developmental and behavioral pedi atrician, “diagnosed L.M. with static encephalopathy with epilepsy.” Id. She concluded that L.M.’s condition “appeared metabolic, ‘with a sudden ons et with the stress of the six month shots, recurrent5 regression with illness . . . [i]t looks like a mi tochondrial disorder . . . but the initial labs do not show acidosis.’” Id. (quoting Pet. Ex. 10 at 357-58). Samuel Yang, M.D., a geneticist, exam ined L.M. on December 8, 2011. Id. at 6. He observed that althou gh L.M.’s EEG was consistent with infantile spasms, “her clinical picture and lack of response to steroids were ‘more typical for complex partial seizures.’” Id . Dr. Yang proposed that L.M. could have a cerebral folate deficiency, and he recommended treatments aimed at addressing the deficiency. Id. L.M. had improved by Ma rch 14, 2012, when she re turned to Dr. Bakdash. Id. Since starting treatment for the folate deficien cy, L.M.’s generalized seizures had ceased, and an EEG showed no hyps arrhythmic changes. Id . Although L.M. still had infantile spasms, petitioner believed they were less frequent. Id . At that time, L.M. was receiving occupational, physical, and speech therapies. Id . On May 1, 2012, Dr. Yang indicated that L.M.’s seizure frequency had decreased, and her spasms occurredonly once or twice per week. Id. Her diagnoses included cerebral fola te deficiency, infantile spasms, global developmental delay, and esotropia. Id. On January 12, 2016, genetic testing reve aled that L.M. was “‘heterozygous for the alteration in the DYNC1H1 [dynein cytoplasmic 1 heavy chain 1] gene.’” Id . at 7; see also id. (quoting respondent’s geneticist: “L.M . is ‘heterozygous for the alteration c.3278T>C (p.F1093S) in DYNC1H1 in exon 13’”). These records conclude that “‘[c]ollectively, the evidence supports th e likelihood that th e alteration in the DYNC1H1 gene . . . is the cause of [L .M.’s] clinical symptoms.’” Id. (quoting Pet. Ex. 42 at 38); see also id. (quoting Pet. Ex. 42 at 40 (“Based on the available evidence, th e clinical overlap6 of this gene with [L.M.’s] reported phenotype is positive. [L.M.’s] overlapping features include infantile spasms, inte llectual disability, ongoing refractory epilepsy, and diffuse hypotonia.”)). Moreover, the report refers to another female patient with the same de

novo mutation who experienced in fantile spasms, intellectual disability, autism spectrum disorder, and reduced muscle tone. Id. at 7, 24. L.M.’s gene ticist confirmed that her “clinical picture is consistent with the centra l nervous system involvement seen with this [genetic] condition, which can include developm ental delays and seizures.” Pet. Ex. 42
at 32. On February 12, 2016, L.M.’s geneticist documented epilepsy, global developmental delay without spee ch, hypotonia, and mental retardation. Dec. at 7; Pet. Ex. 42 at 31-32. To date, L.M. continues to experience seizures and developmental delays. Dec. at 6.
B. Procedural Background On January 27, 2014, petitioner filed for compensation under the Act. Dec. at 1-2. After twice amending the petition, petitioner’s ultimate allegations were that the DTaP and other vaccinations administer ed to L.M. on February 10, 20 11, caused L.M. to suffer: (1) an on-Table injury with regard to the significantaggravation of her underlying condition; and (2) an o ff-Table injury w ith regard to the signifi cant aggravation of her underlying condition. L.M.’s “underlying condition” was characterized as a “brain malformation/white matter defi ciency/other genetic muta tion” that “constituted an encephalopathy.” Id. The petitioner relies on L.M.’s de novo mutation of the DYNC1H1 gene to support her claim that L.M. had a pre-existing encephalopathy.7 In support of L.M.’s petition, petiti oner filed three opinions from pediatric neuropathologist Robert Shuman, M.D., and one from geneticist Richard Boles, M.D. Id

. at 10-21. The Respondent offered two medica l expert reports from pediatric neurologist and epileptologist John Zempel, M.D., Ph.D ., and one from geneticist Maria Descartes,
M.D. Id. at 21-30. 3 An entitlement hearing was held in March 2018. Id . at 31. Drs. Shuman and Boles, as well as L.M.’s parents testified for petitioner, 4 and Drs. Zempel and Descartes testified for respondent. The Special Master issued his D ecision on November 5, 2018, denying compensation. Following a comprehensive re view of the record, the Special Master determined that petitioner failed to establis h that L.M.’s vaccinations significantly aggravated her underlying condition to meet the standards for an on- or off-Table claim. First, the Special Master concluded that L.M. did not suffer from an encephalopathy under the Qualifications and Aids to Interpretation. The Special Master al so found regardless of

3 In addition, on February 26, 2016, petitioner fi led a Motion for a Determination of Law Governing Petitioner’s Table Sign ificant Aggravation Claim. D ec. at 44. Respondent filed a response on April 25, 2016, and petitioner replied on May 13, 2016. Id. at 47 n.45

. The issue concerning the proof needed for petitioner’s on- Table significant aggravation claim will be discussed at length in this opinion.
4 L.M’s parents offered factual testimony regard ing L.M.’s medical history and development prior to her vaccinations on February 10, 2011, as well as their recollections about L.M.’s symptoms over the ensuing days. See Dec. at 8-10. During her testimony, petitioner disputed the accuracy of the records that mentioned seiz ures prior to the vaccinations at issue. See id. at 8 & n.10. She also “denied informing treaters th at L.M. had been floppy or hypotonic since her birth.” Id. at 8. Petitioner further testified th at between February 11 and 15, 2011, L.M. “remained in a distressed condition,” but she did not “opt to bring L.M. in for a visit, maintaining that a nurse had made her feel that she was ove rreacting and that [the pe diatrician’s] office was otherwise booked up.” Id. at 9.8 whether petitioner had met her burden that the respondent had estab lished that a “factor unrelated” to the vaccinations was the cause of L.M.’s current condition. See Dec. at 50- 51, n. 47; 56. Petitioner timely moved for re view of the Special Master’s Decision on December 5, 2018. (ECF No. 104). The respon dent filed a response (ECF No. 108) and on January 18, 2019 the court asked the parties to file s upplemental responses (ECF No. 111). Argument was heard on March 21, 2019.
II. DISCUSSION
A. Legal Standards
1. Standard of Review of Special Master’s Decision The Court of Federal Claims may set aside a Special Master’s findings of fact or conclusions of law only if “arbitrary, capriciou s, an abuse of discretion, or otherwise not in accordance with law.” 42 U.S.C. § 300aa- 12(e)(2)(B); RCFC, App. B, Vaccine Rule 27(b). Under established precedent, this co urt does “not reweigh the factual evidence, assess whether the [S]pecial [M]aster correct ly evaluated the evid ence, or examine the probative value of the evidence or the credibility of the witn esses – these are all matters within the purview of the fact finder.” Porter v. Sec’y of Health and Human Servs. , 663 F.3d 1242, 1249 (F ed. Cir. 2011) (citing Broekelschen v. Sec’y of Health and Human
Servs , 618 F.3d 1339, 1349 (Fed. Cir. 2010)). As long as “t he [S]pecial [M]aster has considered the relevant eviden ce,” “drawn plausible infere nces,” and stated, “a rational basis for the decision,” reversible error is extremely difficu lt to establish. Hines v. Sec’y of Health and Human Servs. , 940 F.2d 1518, 1528 (Fed. Cir. 1991).
2. The Standards for Pr oving On-Table and Off-Table Claims9 In this case, petitioner alleged that L.M .’s vaccinations, admini stered on February 10, 2011, resulted in a significant aggrava tion of a preexisting encephalopathy as the basis for her on-Table and off-Table claims. It is not disputedthat the diphtheria-tetanusacellular pertussis (“DTaP”) is the only vaccin e that could serve as the “the basis for a Table claim alleging significant aggravation of a preexisting encephalopathy.” Dec. at 44 n.44. According to petitioner the DTaP vacc ination caused L.M. to suffer: (1) an onTable injury with regard to the significant aggravation of her underlying condition; and (2) an off-Table injury with regard to the significant aggravation of her underlying condition. The Act provides a pr esumption of vaccine injury “if the petitioners have shown that the injury is ‘on-Table.’” Turner v. Sec’y of Health and Human Servs. , 268 F.3d 1334, 1337 (2001). Once the petitioner has shown that the injury is on-Table and afforded the presumption, th e government may “rebut the presumption of an on-Table injury by showing the injury compla ined of resulted from some factor unrelated to the vaccine.” Id. In order to be afforded the presumption of causation for an on-Table claim with regard to a significant aggravation of an underlying condition, the petitioner had to establish by a preponderance of the evidence that the requisite vaccine “significantly aggravated . . . any illness, di sability, injury, or condition set forth in the Vaccine Injury Table,” and that “the first symptom or manifest ation . . . of the sign ificant aggravation of10 any such illness, disability, injury, or condition . . . oc curred within the time period 5 after vaccine administration set forth in the Va ccine Injury Table.” 42 U.S.C. § 300aa11(c)(1)(C)(i). The Act defines “significant a ggravation” as “any change for the worse in a preexisting condition which results in mark edly greater disab ility, pain, or illness accompanied by substantial deterioration of health.” 42 U.S. C. § 300aa-33(4).
In Whitecotton v. Sec’y of Health and Human Servs. , 81 F.3d 1099, 1107 (Fed. Cir. 1996), the Federal Circuit set out a fou r-part test for analyzing claims alleging significant aggravation of a Table injury. Under Whitecotton , the Special Master must: (1) assess the individual’s condition prior to vaccination; (2) assess the individual’s current condition; (3) determine if the individual’s current condition constitutes a “significant aggravation” of her condition prio r to vaccination withinthe meaning of the statute; and (4) determine whether the first symptom or manifestati on of the significant aggravation occurred within the tim e period specified by the Table. Whitecotton , 81 F.3d
at 1107. In Whitecotton, the Federal Circuit further stated that “the permissible scope of the special master’s inquiry is virtually un limited. Congress desired the special masters to have very wide discretion with respect to the evidence they would consider, and the weight assigned that evidence. . . . Thus, the special master is free to consider evidence from outside the table time period in determin ing whether an individu al suffered the first symptom or manifestation of a significant aggr avation of an injury within the table time

5 The Vaccine Injury Table provides that the a pplicable time period for an encephalopathy to occur in order to meet the Table’s definition is within 72 hours of the administration of the vaccine. 42 U.S.C. §300aa-14(a).11 period.” Id . at 1108. If the petitioner meets thes e tests with a preponderance of the evidence, compensation will be awarded unless the responde nt shows by a preponderance of the evidence that the inju ry was “due to factors unr elated” to the vaccine. See 42 U.S.C. § 300aa-13(a)(1)(B). 6 In deciding whether a petitioner has suffe red either an on-Table injury or a significant aggravation of an on-Table injury, Special Mast ers apply the Qualifications and Aids to Interpretation (“QAI”) set fort h in regulations. 42 U.S.C. § 300aa-14(b). These QAI are read in conjunction with the Table and define its key terms. See 42 C.F.R. § 100.3(b) (effective July 22, 2011, to Ju ly 22, 2015). 7 Pursuant to the QAI, an individual has suffered an ence phalopathy only if she “manifests, with in the applicable period, an injury meeting the description [her ein] of an acute ence phalopathy, and then a chronic encephalopathy persists in such person for more than 6 months beyond the date of vaccination.” 42 C.F.R. § 100.3(b)(2). The QAI set fo rth detailed criteria for both “acute” and “chronic” encephalopathy. See id. § 100.3(b)(2)(i)-(ii). 8 The QAI defines

6 A “factor unrelated” may include “infection, toxins, trauma (inc luding birth trauma and related anoxia), or metabolic disturbances which have no known relation to the vaccine involved, but which in the particular case are shown to have been the agent or agents principally responsible” for causing the petitioner’s injury or death. 42 U.S.C. § 300aa-13(a)(2)(B). 7 The Vaccine Injury Table was amended after th is petition was filed. The amended Table only governs petitions filed on or after March 21, 2017, th e effective date of the final rule. 42 C.F.R. § 100.3(e)(1); 82 Fed. Reg. 11321 (Feb. 22, 2017). Therefor e, citations are to the Table that was in effect when this petition was filed. 8 See also id. § 100.3(b)(2)(iii) (stati ng that “[a]n encephalopathy sha ll not be considered to be a condition set forth in the Table if . . . it is shown by a prepondera nce of the evidence that the encephalopathy was caused by an infection, a toxin, a metabolic disturbance, a structural lesion, a genetic disorder or trauma (wit hout regard to whether the cause of the infection, toxin, trauma, metabolic disturbance, structural lesi on or genetic disorder is known).”).12 “encephalopathy” in relevant part as follows: [A] vaccine recipient shall be co nsidered to have suffered an encephalopathy only if [she] manifests, within the applicable period, an injury meeting the description below of an acute encephalopathy, and then a chronic encephalopathy persists in such person for more than 6 months beyond the date of vaccination. (i) An acute encephalopat hy is one that is sufficiently severe so as to require hospitalization (whether or not hospitalization occurred). (A) For children less than 18 months of age who present without an associated seizure event, an acut e encephalopathy is indicated by a significantly decreased level of consci ousness lasting for at least 24 hours. Those children less than 18 months of age who present following a seizure shall be viewed as having an acute encephalopathy if their significantly decreased level of consciousness pers ists beyond 24 hour s and cannot be attributed to a postictal state [seizure] or medication. Id. The application of the QAI for proving on -Table significant aggravation claims is at issue in this petition. If a petitioner is unable to establish an on-Table claim, a petitioner may seek compensation for pre-existing injuries th at are “significantly aggravated” by a vaccination under the Act as an off-Table claim or causation-in-fact claim. 42 U.S.C. § 300aa-11(c)(1)(C)(ii); id. § 300aa-33(4). The Federal Circuit has explained that a petitioner bears a heavy burden to meet the pr eponderance standard in causation-in-fact

cases. See Althen v. Sec’y of Health and Human Servs. , 418 F.3d 1274, 1280 (Fed. Cir. 2005); see also Hodges v. Sec’y of Health and Human Servs. , 9 F.3d 958, 961 (Fed. Cir. 1993). The elements of proof needed to establish an off-Ta ble claim were set forth by this court in Loving v. Sec’y of He alth and Human Servs. , 86 Fed. Cl. 135, 144 (2009) and endorsed by the Federal Circuit in W.C. v. Sec’y of He alth and Human Servs. , 704 F.3d 1352, 1357 (Fed. Cir. 2013).13 Under Loving , a petitioner who alleges an off-Table significant aggravation claim must by the preponderance of the evidence establish the be low-listed six elements: (1) the person’s condition prior to admi nistration of the vaccine, (2) the person’s current condition (or the conditio n following the vaccination if that is also pertinent), (3) ev idence that the person’s current condition constitutes a “significant aggravation” of the pers on’s condition prior to vaccination, (4) a medical theory causally connecting su ch a significantly worsened condition to the vaccination, (5) a logical sequenc e of cause and effe ct showing that the vaccination was the reason for the significant aggravation, and (6) a showing of a proximate temporal re lationship between the vaccination and the significant aggravation. Loving , 86 Fed. Cl. at 144 (citing Whitecotton , 81 F.3d at 1107; Althen , 418 F.3d at 1278); see also id. (“[T]he appropriate framework fo r determining whether a petitioner has made a prima facie showing that she has a compensable significant-aggravation offTable claim is a combination of the first three prongs of the Whitecotton test with the three-part test articulated in Althen .”). In addition to the foregoin g, for an off-Table claim, the petitioner must prove by a preponderance of the evidence “that the vaccine . . . was the actual cause of the injury.” Munn v. Sec’y of Health and Human Serv. , 970 F.2d 863, 865 (Fed. Cir. 1992). The Special Master must assess whether the pe titioner has established that the vaccine – rather than the natural course of the pre-ex isting condition – is resp onsible for the postvaccination outcome. See Locane v. Sec’y of He alth and Human Servs. , 685 F.3d 1375, 1381 (Fed. Cir. 2012) (upholding the determination th at the petitioner’s “condition was not inconsistent with the disease ge nerally” and unaffected by vaccination); see also Faoro v. Sec’y of Health and Human Servs. , No. 10-704V, 2016 WL 675491, at *27 (Fed. Cl. Spec. Mstr. Jan. 29, 2016). The medi cal theory must be “p ersuasive” – that is,14 specific to the petitioner’s case a nd supported by a “reputable” ( i.e. , reliable) scientific or medical explanation. Moberly v. Sec’y of Human and Health Servs. , 592 F.3d 1315, 1322 (Fed. Cir. 2010). Under Federal Circuit precedent, prov ing causation by the preponderance of evidence does not mean proof to a scientific certainty. See Bunting v. Sec’y of Health and Human Servs. , 931 F.2d 867, 873 (Fed. Cir. 1991 ). The Circuit has explained that the “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,” and a petitioner may use circumstantial evidence to meet her burden. Althen , 418 F.3d at 1280. It is not, however, enough to demonstrate a “plausib le” or “possible” causal link between a vaccination and an injury to meet this standard. LaLonde v. Sec’y of Health and Human
Servs. , 746 F.3d 1334, 1339 (Fed. Cir. 2014); see also W.C. , 704 F.3d at 1356. Rather, “the statutory standard of preponderan ce of the evidence requires a petitioner to demonstrate that the vaccine more likely than not caused the condition alleged.” LaLonde , 746 F.3d at 1339. Thus, a Special Master may conclude that there is simply too great an analytical gap between the data and the opinion proffered, if the petitioner has failed to produce sufficiently reliable evidence. Cedillo v. Sec’y of Health and Human
Servs. , 617 F.3d 1328, 1339 (F ed. Cir. 2010) (quoting Gen. Elec. Co. v. Joiner , 522 U.S. 136, 146 (1997)). Finally, a Special Master may not award compensation “based on the claims of a petitioner alone, unsubstantiated by medical records or by medical opinion.” 42 U.S.C. § 300aa-13(a)(1). The respondent is “‘permitted to offer evid ence to demonstrate the inadequacy of15 the petitioner’s evidence on a requisite elem ent of the petitioner’s case-in-chief.’” Stone v. Sec’y of Health and Human Servs. , 676 F.3d 1373, 1379-80 (Fed. Cir. 2012) (quoting de Bazan v. Sec’y of Health and Human Servs , 539 F.3d 1347, 1353 (Fed. Cir. 2008)). The Special Master may weigh that evidence in determining whether a petitioner has met her burden. See id. ; see also Doe v. Sec’y of Health and Human Servs. , 601 F.3d 1349, 1358 (Fed. Cir. 2010). As with on-Table cases, if a petitioner proves a prima facie case of causation, the burden switches. The respondent, government , then bears the burden of showing by a preponderance of the evidence that some factor other than the vaccine was the actual cause of the injury. Walther v. Sec’y of Health and Human Servs. , 485 F.3d 1146, 1151 (Fed. Cir. 2007).
B. The Special Master’s Decision Was No t Arbitrary, Capricious, an Abuse of Discretion, or Otherwise No t in Accordance with Law. In this case, L.M. was found to possess a de novo mutation of the DYNC1H1 gene, which the petitioner contends is the basis for L.M.’s pre-existing encephalopathic disorder. See Dec. at 2, 7, 22-23, 30. The impact of that diagnosis on her on-Table and off-Table claims is at the heart of the Special Master’s decision denying petitioner’s onTable and off-Table claims. We begin with summarizing the Special Master’s factual findings and then review his denial of pe titioner’s on-Table and off-Table claims.
1. The Special Master’s Review of Expert Testimony The petitioner relied on the expert testim ony of Drs. Robert Shuman and Richard16 Boles. 9 They opined that L.M.’s immunizations significantly aggravated her pre-existing genetic condition stating that her condition wo uld have been milder had she not been vaccinated. Specifically, they opined that L.M.’s post vaccina tion seizures were evidence of a new symptom that she had not previously experienced and proved an aggravation. See, e.g. , Dec. at 16, 21, 51. Dr. Shuman testified that L.M.’s im aging studies revealed “structural deficiencies,” and that she had a type of white matter deficiency known as Perinatal TeloLeukoEncephalopathy (“PNTLE”), whic h “he characterized as ‘part of the preexistent encephalopathy of [L.M.]’s genetic disease.’” Id. at 11-12, 51 (citation omitted). In his view, L.M.’s vaccinations a ggravated these deficiencies and prompted her seizures. Id. at 13. Specifically, Dr. Shuman reasoned that a person like L.M. would be vulnerable to “decompensation” if sh e was hit with the immunologic stress of vaccination. Id. at 16 (citing Tr. at 131). In c oncluding that L.M. suffered from structural deficiencies he re lied on MRIs obtained on February 16, 2011, April 2011, and May 2012 to conclude that L.M.’s brain had PNTLE. Id. at 11-12. In support of the causal relationship between v accination and L.M.’s symptoms , Dr. Shuman relied on the

9 Dr. Shuman is a pediatric neuropathologist with expertise in child neurology. He received his M.D. from Stanford, completed his residency in pediatrics at the University of Colorado, a residency in pathology at the University of Wash ington, and a residency in child neurology at the University of Kentucky. He is board certi fied in pathology, neuropathology, and child neurology. Dec. at 11. Dr. Boles received his M.D. from the Universityof California Los Angeles where he completed a pediatrics residency, followed by a genetics fellowship at Yale University. He was a professor of clinical pediatrics at the University of Southern California from 1993 until 2014. Dec. at 17.17 “National Childhood Encephalopathy Study” performed in the Un ited Kingdom in the late 1970s. Id. at 14 (citing Richard Alderslade et al., The National Childhood Encephalopathy Study: A Report of 1000 Serious Cases of Serious Neurological Disorders in Infants a nd Young Children from th e NCES Research Team, Reports from the Comm. on Safety of Med. & Joint Co mm. on Vaccination & Immunisation (1981)). However, on cross-examination, Dr. Shuman acknowledged that his conclusion that L.M.’s seizure disorder/development prob lems by vaccination were worsened by the vaccination beyond what would otherwise have been expected given her genetic mutation lacked a sufficient basis. Id. at 17 (citing Tr. at 151). Dr. Boles opined that th e mutation’s location on the DYNC1H1 “chromosomal protein chain was critical in determining th e symptoms an individual would experience when the mutation is expressed.” Id . at 17. He hypothesized that because L.M.’s mutation was in the gene’s stem or tail, as opposed to the motor or stalk domain, her outcome should have been less severe. Id. at 17-18. Dr. Boles claimed that L.M.’s vaccinations “worsened the expected, comparativ ely milder course otherwise attributable to her mutation[.]” Id. at 19; see also id. at 51. Dr. Boles reasoned, that the vaccine constituted a sufficient “‘environmental insu lt’” to exacerbate the effects of L.M.’s underlying mutation which made the progress of the encephalopathic disorder more severe than it would have been otherwise. Id. at 20 (quoting Tr. at 188, 220). The Special Master also heard testimony from Dr. Maria Descartes, one of the18 respondent’s two experts, 10 who explained that a DYNC1H1 mutation “impact[s] the function of a gene intended to code the production of dynein, a protein important to cell function[.]” Dec. at 22. She described L.M.’s mutation as rare and severe, as de novo mutations “are more commonly associated with negative outcomes.” Id. at 23. In particular, “[p]atients with de novo DYNC1H1 mutations have been identified with severe intellectual handicaps,” as well as seizures and hypotonia. Resp. Ex. R at 6 (ECF No. 67- 1 at 6); see also Dec. at 23-25 (summarizing literature on DYNC1H1 mutations). Dr. Descartes testified as to literature on L.M.’s mutation which references another female patient who had infantile spasms, like L.M, and had intellectual disabilities, autism spectrum disorder, and reduced muscle tone. Dec. at 24. Dr. Descartes noted that the individual in the literature has a phenotypic presentation “highly similar” to L.M.’s in that she had “infantile spasms coupled with a subsequent epileptic encephalopathy[.]” Id. at 24-25. This patient, as reported in the medical literature, Dr. Descartes emphasized, shows “the commonalities between the [ DYNC1H1 ] mutation and the kinds of symptoms L.M. experienced.” Id. at 25; see also id. at 30, 53. The Special Master also heard add itional testimony from Dr. John Zempel, 11 the

10 Dr. Descartes received her M.D. from the University of Puerto Rico. She completed a residency at San Juan City Hospital in Puerto Ri co as well as fellowship in genetics at Baylor College of Medicine in Houston, Texas. She is board certified in genetic s as well as pediatrics. Dec. at 22.

11 Dr. Zempel received an M.D. and Ph.D. from Washington University in St. Louis. He completed residencies in pediatrics, adult neur ology, and child neurology as well as fellowships in pediatric epilepsy and clinic neurophysiol ogy. He is board certifi ed in neurology, child neurology and psychiatry. Dec. at 26.19 other expert for the respondent, who expl ained that L.M. likely was suffering from seizures prior to her vaccinati on, whether or not the seizures were recognized as such, and that the “course of her illness from before vaccination to the present” was consistent with that of “treatment-nonresponsive” i ndividuals suffering from infantile spasms. Id. at 29, 55. The Special Master found Dr. Zempel’s testimon y regarding prior seizures persuasive, reiterating in his opinion that “p arents often do not recognize initial seizure activity as part of a greater disorder be fore a more alarming seizure incident.” Id. at 55; see also id. at 16. After considering the testimony of all expert s, the Special Master determined that petitioner’s theories regarding both her on-Table and off-Tab le claims lacked reliable scientific support. Dec. at 51-54. He e xplained that Dr. Shuman’s opinion was “the weaker of the two,” particularly because hi s first two reports were filed prior to the discovery of L.M.’s DYNC1H1 mutation, and “thus proposed a theory that did not take into account a significant fact.” Id. at 51. The Special Master explained that Dr. Shuman “did not abandon his initial th eory” at the hearing which th e Special Master found made his opinion questionable. See id. The Special Master also de termined that Dr. Shuman’s opinion that L.M. had a pathogenic brai n malformation was uncorroborated by her records. Id. The Special Master further determin ed that Dr. Shuman’s assertion that L.M. had a white matter deficien cy was not well-supported. Id. The Special Master stated that Dr. Shuman “re lied upon a diagnosis that not only L.M. never received but which elevated a diagnostic concept (PNTLE ) into something that it does not appear medical science recognizes with any degree of trustworthy sufficiency.” Id. ; see also id.20 at 48. 12 Finally, the Special Master determined that Dr. Shuman’s opinion regarding pertussis toxin-containing vacci nes and his contention that th ey could promote seizures was not well supported or pers uasive. The Special Master explained that Dr. Shuman relied on obsolete literature “and/or involved conf lation of the DPT vaccine with the DTaP version L.M. actually received.” Id. at 51. The Special Master found Dr. Boles’ s opinion testimony to be similarly unpersuasive. See Dec. at 52-54. According to the Special Master, Dr. Boles failed to “establish with reliable proof [the] contenti on that location [of the gene mutation] was as outcome-determinative as he maintained[.]” Id. at 52 (emphasis in original). In this regard, the Special Master explained that he found the opinion of the respondent’s expert, Dr. Descartes, that the DYNC1H1 mutation itself matters far more th an its location, was more persuasive. Id. at 52; see id . at 23. Dr. Decartes challenged Dr. Boles’s contention that mutations on the stem or tail domain “were invariablyassociated on ly with more benign outcomes[,]” and she di scussed several articles in support of her opinion. See id. at 23-25, 52-53. Dr. Decartes opi ned that an individual with a DYNC1H1 mutation on the motor or stalk domain can have a mild outco me, and, as here, an individual with a mutation on the stem or tail domain can have one that is more severe. See id. at 52. In this connection, the Special Ma ster found particularly “compe lling” the evidence that the medical literature contained evidence of anot her patient with L.M.’s identical mutation

12 Dr. Zempel noted that PNTLE is “not a comm only-employed diagnostic term,” and it is “subsumed within the category of periventricular leukomalacia,” a common and severe complication of extreme prematurity. Id. at 27. L.M. was not born prematurely. Id. n.31.21 who had similar symptoms with out reference to the location of the gene mutation. Id

. The Special Master found such evidence demonstrates that “the location of a genetic mutation is not alone predictive of mutation outcome.” Id. (describing the individual with the same DYNC1H1 mutation in the stem/tail domai n who suffered from infantile spasms and an epileptic encephalopathy). The Special Master also determined th at neither Dr. Shuman nor Dr. Boles articulated how any of L.M.’s vaccinations, including the DTaP, could interact with her genetic disorder to worsen her outcome significantly. Id. . at 51, 53-54. For example, he found that Dr. Shuman ‘s opinion “lacked a ba sis for the conclusion that L.M.’s seizure disorder/developmental problems were wo rsened by vaccination beyond what would otherwise have been expected given her a lleged encephalopathic brain malformation/ white matter deficiency.” Id. at 17. There, the Special Master cited to Dr. Shuman’s opinion testimony wherein he admitted on cross-examination that he had “no evidence” that L.M’s seizure threshold had been reduc ed and that the vaccination worsened her genetic condition. Tr. 151:15- 22. In addition, the Special Master noted that Dr. Boles offered no reliable support or literature “a ddressing the propensity of any vaccine to exacerbate a disease otherwise attributable to a genetic mutation, a nd this component of his overall opinion had a conclusory character to it, relying more on his ipse dixit than independent evidence.” Id. at 20; s ee also id., n.25 (“Dr. Boles admitted he could not pinpoint which specific vaccine received by L.M. wa s causal of her illness, but proposed awareness that the MMR and DTaP had beenimplicated in other contexts.”).22 2. The Special Master’s Entitl ement Decision Regarding Petitioner’s On-Table Claim After hearing the evidence, the Special Ma ster turned first to the petitioner’s onTable claim. The Special Master began by examining whether pe titioner had suffered a pre-vaccination encephal opathy sufficient to qualify for a post-vaccination aggravation claim. The petitioner argued in her Memorand um In Support of De termination of Law Governing Petitioner’s Table Significant Aggravation Claim (ECF No. 41), that petitioner should only have to establish a pre-existing ence phalopathy cons istent with “the common, ordinary, and acc epted meaning” of encephalopathy and not the definitions of the condition set forth in the QAI. Pet. Me m. of Law (ECF No. 41 ). The respondent in their response to the petitione r’s motion did not challenge th e petitioner’s assertion that L.M. had a preexisting encephalopathy. Re sp. Mem. of Law (ECF No. 44). Rather, respondent argued that the Special Master could not award compensation based on an onTable claim because “there is nothing beyond petitioner’s claim to support a finding that L.M. suffered critical symptoms within sevent y-two hours of her DTaP vaccination, let alone those consistent with an acute encepha lopathy.” Resp. Mem. of Law at 9. In petitioner’s reply, she did not dispute the respondent’s cont ention that L.M. had not met the criteria for an acute encephalopathy as de fined by the QAI within 72 hours of her vaccination. Rather, petitioner argued that it wo uld be enough for her to show that within 72 hours, L.M. began to show some “change for the worse” of her pre-vaccination encephalopathy even if that worsening was no t sufficient to meet the QAI definition of acute encephalopathy. Pet. Reply to Mot. at 2 (ECF No. 47). Specifically, the petitioner23 argued that so long as she can establish that she experienced symptoms of “change for the worse” within 72 hours of the February 10, 2011 DTaP va ccination, “those symptoms need not satisfy the definition of encephalopathy in the Qualifications and Aids to Interpretation[.]” Id. at 4. The Special Master dete rmined that petitioner had not established a prevaccination encephalopathy to support an on-T able claim because she could not meet the definition of encephalopathy in the QAI prior to receiving her vaccinations. Relying on the decision in DeRoche v. Sec’y of Health and Human Servs. , No. 97-643V, 2002 WL 603087, at *25 (Fed. Cl. Spec. Mstr. Mar. 28, 2002), 13 the Special Master determined that to establish an on-Table significant aggrav ation claim the petitioner had to prove “at a minimum that L.M. experienced a pre-vaccina tion ‘acute’ encephalopathy as set forth in the QAIs.” Dec. at 48. Based on his review of the evidence the Special Master concluded that L.M.’s pre-vaccination symptoms ne ver “rose to the level of an ‘acute encephalopathy’” and therefore “Petitioner’s Table claim cannot succeed.” Dec. at 49.

13 In DeRoche , the then-Chief Special Master applied the QAI definition of encephalopathy to the child’s underlying conditi on in denying compensation in the petitioner’s presumptive significant aggravation claim. In DeRoche, the then-Chief Special Master stated, “[T]o prove a Table significant aggravation cl aim brought pursuant to [Section] 11(c)(1)(C)(i), petitioner must first demonstrate an underlying Table injury as that inju ry is defined by the applicable [QAI] ”. DeRoche v. Sec’y of Health & Human Servs., No. 97-643, 2002 WL 603087, *25 (Fed. Cl. Spec. Mstr. Mar. 28, 2002). In applying the QAI defin ition, the Chief Special Master “read out” the phrase “within the applicable period” (of vacci nation) because for a significant aggravation claim, an encephalopathy is necessarily pre- existing and thus cannot arise post-vaccination. Id. at *27, *29. Similarly, he did not apply the “chr onic encephalopathy” component because given the compressed timetable for childhood vaccines, almost always, a child would receive an immunization before six months had elapsed, rendering it difficult to establish a Table encephalopathy. Id. He did, however, require the petitione r to show that there had been an encephalopathy consistent withthe QAI post-vaccination to s upport an on-Table significant aggravation claim. Id at *31-32.24 On appeal, petitioner argues that the Special Master’s on-Table entitlement decision must be set aside because the Special Master applied the wrong legal definition of “pre-vaccination encephalopathy.” See Mot. for Review at 9-17. Petitioner contends she did not have to show that L.M. suffered an “encephalopathy” as defined in the QAI regulations before L.M. received her vaccin ations in order to establish an on-Table significant aggravation claim. Id . at 15-16. 14 She asserts that the Special Master erred in following the approach set forth in DeRoche , and that the Special Master instead should have “relied on the ‘common, ordinary and accepted meaning’ of encephalopathy for the definition of a vaccine recipient’s pre-vaccination en cephalopathy.” Id. at 15; see also
Dec. at 47-48. The respondent does not directly challenge petitioner’s contention that DeRoche is not the appropriate standard to apply for on-T able significant aggravation claims. Rather, the respondent maintains, as it did before the Special Master, that it is not necessary to

14 As noted above, the QAI defines “ence phalopathy” in part as follows ( see 42 C.F.R. § 100.3(b)(2)): [A] vaccine recipient shall be considered to have suffered an encephalopathy only if [she] manifests, within the applicable period, an injury m eeting the description below of an acute encephalopathy, and then a chronic en cephalopathy persists in such person for more than 6 months beyond the date of vaccination. (i) An acute encephalopathy is one that is sufficiently severe so as to require hospitalization (whether or not hospitalization occurred). (A) For children less than 18 months of age who present without an associated seizure event, an acute encephalopathy is i ndicated by a significantly decreased level of consciousness lasting for at leas t 24 hours. Those ch ildren less than 18 months of age who present following a seizure shall be viewed as having an acute encephalopathy if their significantly decreased level of consciousne ss persists beyond 24 hours and cannot be attributed to a postictal st ate (seizure) or medication.25 resolve whether L.M. met the QAI definition of encephalopathy pre-vaccination because petitioner undisputedly failed to meet the QAI definition of acute encephalopathy within 72 hours of her DTaP vaccination as manda ted by the statute. 42 U.S.C. § 300aa11(c)(1)(C)(i). The respondent argues that “ [r]egardless of the definition the Special Master employed for ‘pre-vaccination ence phalopathy’ the outcome does not change.” Resp. Supl. at 3. The petitioner argues that if the Special Master’s pre-vaccination definition of encephalopathy is corrected th at she should prev ail because the statute does not require proof of an encephalopathy meeting the QAI definition within 72 h ours to establish an on-Table significant aggravation claim. The petitioner argues that under the language of the Vaccine Injury Act, she only had to prove that L.M’ s condition “changed for the worse,” citing 42 U.S.C. § 300aa-33(4): For the purposes of this subtitle . . . . . (4) The term ‘significant aggravation’ means any change for the worse in a preexisting condition which results inmarkedly greate r disability, pain, or illness accompanied by substa ntial deterioration of health. To prove an on-Table onset case based on an encephalopathy, the petitioner agrees that she would have had to prove that th e first symptom or manifestation of an encephalopathy as defined by the QAI occurred within 72 hours. See 42 C.F.R. § 100.3(b)(2). But to prove an on-Table significant aggravation claim the petitioner argues, she only needed to show a “change fo r the worse in a preexisting condition which results in markedly greate r disability, pain, or illne ss accompanied by substantial deterioration of health.” 42 U.S.C. § 300aa-33(4). The petitioner argues that the QAI26 definitions of encephal opathy are not relevant to on-Table significant aggravation claims. Petitioner argues that she met he r burden because the first sy mptom or manifestation of L.M.’s significant aggravation occurred within72 hours of her Fe bruary 10, 2011 DTaP vaccination. In addition, petitioner argues th at a comparison of L.M.’s condition before her February 10, 2011 DTaP vaccination to her current condition shows that L.M. suffered a significant aggravation of her pree xisting condition following her February 10, 2011 DTaP vaccination. Petitioner argues her claim is supported by the Special Master’s acknowledgment that L.M’s condition worsened within 72 hours after she rece ived the DTaP vaccination: The record does support the conclusion that L. M.’s condition was worse immediatelypost-vaccination (if compared only to her immediate prevaccination condition). In addition, Petitioner has pointed to evidence from the medical record that L.M. di splayed some motor control issues and diminished responsiveness on February 15, 2011, after the seizure that resulted in her being taken to the hospital . . . Dec. at 50 (emphasis in the original). The petitioner also relies on the affidavit of L.M.’s father in which he describes a healthy baby at six months and compares that description to the Special Master’s description of L.M.’s current condition: At present, L.M. continues to expe rience seizures and developmental delays. Petitioner alleges that, at 7 y ears and 5 months of age, L.M. can crawl, as well as walk with a walker when aided (someone needs to direct her and catch her if she stumbles). Tr. at 60-61. She takes the anticonvulsant Tegretol and a low dos e of CBD oil (medical marijuana) to control her seizures. Tr. at 64. In her prehearing submission, Petitioner asserts that L.M. experiences “oc casional breakthrough seizures” even during periods of relativel y good health, has a poor ly coordinated grasp, suffers from cortical visual impairme nts, and is nonverb al, though she can use a few signs to express ideas such as ‘hungry,’ ‘thirsty,” “I want,”27 “yes,” and “no.” Pet’r’s Pre-Hr’g Br ief at 12, dated De c. 12, 2017, ECF No. 73 (“Pet. Brief”).
Dec. at 6-7. Whether a petitioner must meet the QAI defi nition prior to her vaccination or after the vaccination to make an on- Table significant aggravation cl aim is the key issue to be decided. The respondent argues that it is not necessary to determine whether an encephalopathy meeting the QAI definition prio r to the vaccination is necessary because to establish an on-Table significant aggrav ation claim the petitioner must meet the QAI definition of encephalopathy post-vaccination to meet the on-Table significant aggravation standard. The court agrees with the re spondent that the purpose of on-Table claims is to provide petitioners with a pres umption of causation based ona defined set of symptoms set by regulation in the QAI. If the define d set of QAI symptoms are not met, the Vaccine Act allows for petitioners to seek redress under the procedures for off-Table claims. The respondent correctly argues thatthe significant aggravation standard set in the statute does not mean the QA I definitions of the Table inju ries are irrelevant for the purposes of determining if a petitioner suffere d a significant aggrav ation of an on-Table injury. In fact, the statutor y scheme creating on-Table claims states that in order to recover, the petitioner must experience within the applicable timeframe “the first symptom or manifestation of onset or of th e significant aggravation of such injuries, disabilities, illnesses, conditions, and deaths” as provided for in the Table and as defined by the QAI. 42 U.S.C. § 300aa-14(a). Thus, to prove a significant aggravation on-Table28 claim, the petitioner must be able to show that the vaccine caused a significant aggravation consistent with the QAI defi nition within the time-frames provided on the Table. 15 Here, the petitioner has not met her bur den. The evidence in the record established that L.M. never experienced an encephalopathy meeti ng the QAI definition after she received her vaccina tion (within the relevant 72 -hour period). The petitioner only identified that L.M. had a fever with whim pering and screaming. Pet. Ex. 2 at 19. Indeed, even outside of the 72-hour period pr ovided by the Table, her condition did not meet the QAI definition. When L.M. was ta ken to the emergency room by her mother, the attending doctor stated she “was alert and playful, and althou gh a ‘bit listless,’ she displayed few other alarming clinical symp toms.” Dec. at 3 (citation omitted). Additionally, neither of petitioner’s expert s opined that L.M. suffered an acute encephalopathy consistent with QAI defin ition during this period. Dr. Zempel, the respondent’s expert, on the other hand, statedthat a severe acute encephalopathy was not present at the time of L.M.’s presentation or subsequently through the initial hospital stay. Dec. at 26-28. This opinion wa s not refuted by petitioner’s experts. It is for these reasons that the court finds that petitioner’s objections to the Special

15 The court notes that if it adopted the peti tioner’s argument, the purpose of the on-Table scheme would be undermined. Specifically, if a petitioner was not required to show the manifestation of either an onset or a significant aggravation of a preexisting condition that was consistent with the QAI definition for that on- Table condition, petitioners would be able take advantage of the presumption of causation afford ed by the on-Table scheme without meeting the rigorous definition of the condition that was thought necessary for there to be a presumption of causation.29 Master’s conclusion that petitioner failed to establish an on-Table si gnificant aggravation claim cannot be sustained. Regardless of whether the DeRoche standard is correct, petitioner did not present evidence to sh ow the first symptoms of an acute encephalopathy within 72 hours as require d by the Vaccine Act for a significant aggravation claim. For this reason, L.M. failed to establish that her post-vaccination course constituted a “significant aggr avation” of her prior condition. See 42 C.F.R. § 100.3(a)(II)(B); id. § 100.3(b)(2)(i)-(ii); 42 U.S.C. § 300aa-33(4). Petitioner’s onTable significant aggravation claim fails, a nd the Special Master’s rejection of the onTable significant aggravati on claim is affirmed.
3. The Special Master’s Denial ofPetitioner’s Causation-InFact Aggravation Claim As discussed above, to prevail on an o ff-Table significant aggravation claim, petitioner had to meet the 6 elements set in Loving by the preponderance of the evidence: (1) the person’s condition prior to admi nistration of the vaccine, (2) the person’s current condition (or the conditio n following the vaccination if that is also pertinent), (3) ev idence that the person’s current condition constitutes a “significant aggravation” of the pers on’s condition prior to vaccination, (4) a medical theory causally connecting su ch a significantly worsened condition to the vaccination, (5) a logical sequenc e of cause and effe ct showing that the vaccination was the reason for the significant aggravation, and (6) a showing of a proximate temporal re lationship between the vaccination and the significant aggravation. Loving , 86 Fed. Cl. at 144 (citing Whitecotton , 81 F.3d at 1107; Althen , 418 F.3d at 1278). In rejecting petitioner’s off-Table signifi cant aggravation claim, the Special Master focused on petitioner’s failure to meet elements 3, 4, and 5 of the Loving test.30 Petitioner challenges each of those conclusions and each are examined in turn below. The Special Master, after reviewing the ev idence, found that although the record supported a finding that L.M.’s conditio n worsened immediately following her vaccination, the evidence established that he r “outcome would most likely be as it was regardless of vaccination.” Dec. at 50. Th e petitioner takes issue with that statement arguing that the decision must be reversed be cause the Special Master applied the wrong legal standard. Specifically, petitioner argues that the Special Master erred because he “unambiguously required [the petitioner] to predict [L.M.’s ] current condition” had L.M. not been vaccinated. Mot. for Review at 21. The court finds that this is not a fair re ading of the decision. The Special Master correctly cited precedent for the proposition that to determine whether there was a significant aggravation of a preexisting conditi on, the Special Master had to evaluate what is known about L.M.’s pr eexisting condition. Therefore, the Special Master had to evaluate what can be attributed to her ge netic mutation and what impact the mutation would have on her life withou t the vaccinations. Assessi ng an off-Table significant aggravation claim therefore necessarily involv es asking whether the individual’s “clinical course and outcome [would have been] any different than it wo uld have been if [she] had not been vaccinated[.]” See, e.g. , Oliver v. Sec’y of Health and Human Servs. , No. 10- 394V, 2017 WL 7478 46, at *23 (Fed. Cl. Spec. Mstr. Feb. 1, 2017); Faoro , 2016 WL 675491, at *27 (citing Locane , 685 F.3d at 1375 (upholding the Special Master’s finding that the “petitioner’s condition was not incons istent with the disease generally and not affected by the vaccinations”)).31 A review of the decision demonstrates th at the Special Master did not require petitioner to prove the full trajectory of L. M.’s condition with her mutation to prove causation. Petitioner relied on experts to say th at L.M.’s trajectory should have been mild. Here, a review of the record demons trates that the Special Master, based on the credible evidence pr esented about the DYNC1H1 mutation, reasonably determined that L.M. was not guaranteed a mild outcome. Ra ther, her outcome, as demonstrated by the medical literature, was consistent with ch ildren who experienced infantile spasms and specifically the condition of another little girl with the same genetic mutation. Based on the foregoing, the Special Ma ster determined that the as sumption of petitioner’s experts to the effect that L.M.’s mutation would not have been as severe without the vaccination was not established. Dec. at 49-50. The Sp ecial Master’s discussion of L.M.’s condition was therefore consistent with the petitioner’s ob ligation to prove that the vaccine in fact had worsened that condition. As discussed above, the respondent is permitted to demonstrate the inadequacy of the petitioner’s evidence on a requis ite element to prove an injury claim and the Speci al Master may determine base d on his consideration of all the evidence presented that the pe titioner did not meet her burden. Stone , 676 F.3d at
1379-80. Petitioner also needed to sh ow by a preponderance of the evidence a theory causally connecting the DTaP vaccine to a significant worsening of her condition. Loving , 86 Fed. Cl. at 144 (citing Althen , 418 F.3d at 1278). The Special Master considered Dr. Boles’ opinion testimony regarding how the vaccine could impact L.M.’s mutation and found that “Dr. Boles did not persuasively explain how the vaccines32 interacted with the mutation.” Dec. at 52. The Special Master found Dr. Bole’s reliance on “personal supposition, or the general proposition that vaccination constitutes an environmental factor that can interact with genetic expression, basi ng such contentions on his own generalized observations from the tr eatment of unspecified twins,” was not a reliable theory of causation. Id. The Special Master also found that Dr. Shuman’s statements regarding the seizure-inducing potential of the DPT vaccine were not persuasive because L.M. did not receive the DP T vaccine but the different DTaP vaccine. Dec. at 54. The petitioner therefore did not have any specific evidence to explain how the DTaP vaccine that L.M. received could ha ve caused a worseni ng of her condition. The Special Master also pr operly considered if the logical sequence of events could support a finding that the DTaP vaccination caused the alleged significant aggravation of L.M.’s genetic condition. The Special Master agreed that L.M. experienced a post-vaccination fe ver and a reaction but rejected petitioner’s claim that the seizures L.M. started experiencing post -vaccination were new and the result the vaccination. The Special Master reasonably c oncluded that the record demonstrated that there was a strong “likelihood that L.M. had already experienced seizures before her February 15th ER visit[,]” and that this evidence was consistent with Dr. Zempels’ testimony as confirmed by the medical litera ture, that parents often do not recognize initial seizure activity before a more alarming incident. Dec. at 55. In this connection, it is worth noting, th at in rejecting the petitioner’s off-Table claim the Special Master explai ned that even if L.M.’s expe cted prognosis should instead be considered as a “factor un related” for which the responde nt has the burden, that he33 “would find that respondent did establish a ‘factor unrelat ed’ in the form of the relationship between the DYNC mutation and L.M’s illness.” Id . at 50-51 n.47. In reaching this conclusion, the Special Mast er relied on cases involving children with Dravet syndrome (a rare seizure disorder involving a mutation in the SCN1A gene). See id . at 29 n.35, 41-42. In the cases involvi ng Dravet syndrome, as in this case, the petitioners acknowledged that the children’ s SCN1A mutations were responsible for many of their symptoms but argued that their vaccinations had worsened their outcomes. Id. at 41-42. 16 While acknowledging that the evidence in this case was not as conclusive as the evidence involv ing the SCN1A mutations and Dravet syndrome, he concluded that in this case, as in those, the evidence established that th e genetic mutation and not the vaccination that was responsibl e for the child’s condition post-vaccination. Thus, the Special Master stated that ev en if petitioner had proven her prima facie case, he would nevertheless find that respondent establishe d “a ‘factor unrelated,’ in the form of the relationship between the [ DYNC1H1 ] mutation and L.M.’s illness. ” Dec. at 50-51, n.47. Although this court does not have to reac h whether the respondent met its burden for proving a factor unrelated, given the Special Master’s conclusions regarding the petitioner’s failure to establish a causal co nnection between L.M.’s DTaP vaccination and her condition post-vaccination to establish a significant aggravation case, it is clear from

16 To date, compensation has been denied in mo re than one dozen such cases. See Oliver , 2017 WL 747846, at *1 & n.3 (lis ting the decisions), aff’d , 133 Fed. Cl. 341 (2017), aff’d , 900 F.3d 1357 (Fed. Cir. 2018).34 the record that the Special Ma ster considered the entire re cord and reached the rational conclusion that petitioner’s had failed to establish that L.M.’s condition had worsened because of her DTaP vaccination. For th ese reasons the Special Master’s decision rejecting petitioner’s off-Table significant aggravation claim must be affirmed.
CONCLUSION Because petitioner has failed to demonstrat e that the Special Master erred in applying the law, abused his discretion or th at his findings were arbitrary or capricious the Special Master’s decision is AFFIRMED

. IT IS SO ORDERED

.

s/Nancy B. Firestone NANCY B. FIRESTONE Senior Judge