NORA BETH DORSEY, Chief Special Master.
On October 15, 2010, Kimberly Faoro and Tyson Faoro ("petitioners") filed a petition for compensation under the National Vaccine Injury Compensation Program (the "Vaccine Act" or "Program")
During the course of the proceedings, the parties discovered and do not dispute that H.E.F. was born with a mutation of her SCN1A gene and that she has a seizure disorder known as Dravet syndrome.
The parties agree and stipulate that the only issue to be resolved is "whether any of the vaccines, alone or in combination, that H.E.F received on December 28, 2007, caused or significantly aggravated H.E.F.'s condition." Joint Prehearing Submission ("Jt. Sub.") at 1.
The undersigned agrees with respondent that H.E.F.'s SCN1A gene mutation is the reason she has Dravet syndrome and associated neurological symptoms, and finds that petitioners have failed to show by a preponderance of the evidence that H.E.F.'s injuries were caused or significantly aggravated by her December 28, 2007 vaccinations. Although H.E.F.'s vaccinations may have caused a low-grade fever or otherwise triggered her first seizure, neither that initial seizure nor her vaccinations caused or significantly aggravated her Dravet syndrome and resulting neurological complications. Rather, her SCN1A genetic mutation is more likely than not the sole cause of her injuries. For that reason, the undersigned also finds by a preponderance of the evidence that respondent has provided an alternative cause of H.E.F.'s injuries, and, therefore, petitioners are not entitled to compensation.
In the discussion below, the undersigned describes the pertinent factual background, a description of the genetic mutation and information on Dravet syndrome, and a history of the procedural developments in this case. This is followed by a discussion of the applicable standards of proof for causation and significant aggravation, and an analysis of the expert testimony, arguments and evidence as presented by the parties. Finally, the undersigned discusses whether respondent presented sufficient evidence to prove alternative causation.
While the undersigned has considered all the evidence in this case and the record as a whole, the following is a brief summary of the medical records, testimony, and discussion of Dravet syndrome taken from the record in the case. This is by no means a complete recitation of all the relevant facts and evidence considered.
H.E.F. was born on August 28, 2007. Jt. Sub. at 1. She was delivered at 40 weeks gestation. Pet. Ex. 4 at 9. Her birth weight was 7 pounds 3½ ounces and her Apgar scores were nine (9) and ten (10) at one and five minutes, respectively. Pet. Ex. 4 at 9, 24. She passed her newborn hearing test and her newborn screening tests were all normal. Pet. Ex. 7 at 20, 27. H.E.F.'s neonatal course was unremarkable and she was discharged in good health on August 30, 2007. Pet. Ex. 4 at 8.
Of note, H.E.F.'s mother ("Ms. Faoro") was 27 years old at the time of delivery and H.E.F. was her fifth child. Pet. Ex. 3 at 250; Pet. Ex. 4 at 8. Ms. Faoro's past medical history was significant for migraines, hypothyroidism, and mild obesity. Pet. Ex. 3 at 246-47. During her pregnancy with H.E.F., Ms. Faoro received antibiotics for a urinary tract infection and bronchitis, and she was also treated for viral gastritis.
H.E.F. received her early pediatric care from Dr. Rebecca White at Mahaska Health Partnership. Pet. Ex. 5. On September 4, 2007, H.E.F. was treated for diarrhea and a diaper rash.
On October 2, 2007, H.E.F. was seen and treated for thrush and dermatitis. Pet. Ex. 5 at 7. On October 9, 2007, H.E.F. presented to Dr. White's office again with greenish-yellow matter in her eyes and persistent diaper rash.
On October 22, 2007, H.E.F. received her two-month vaccines — Pediarix
Approximately one week later on October 31, 2007, H.E.F. was taken again to the ED for fever and diarrhea and was diagnosed with an ear infection. Pet. Ex. 7 at 48-49. She returned to the ED the next day, November 1, 2007, with fever.
The next week, on November 6, 2007, H.E.F. was seen by Dr. White for vomiting, coughing, congestion and diarrhea. Pet. Ex. 5 at 12. H.E.F. was diagnosed with gastroenteritis and an upper respiratory infection.
On December 20, 2007, H.E.F. was seen by Dr. White for complaints of diarrhea for the past three days and vomiting. Pet. Ex. 5 at 13. She was diagnosed with gastroenteritis and thrush.
Approximately six to seven hours after receiving her vaccinations, H.E.F. began to have "shaking of her right side involving both her arm and leg" and had temporarily lost the use of her right arm. Pet. Ex. 7 at 92. H.E.F. was taken to the ED where she was seen by her pediatrician, Dr. White.
Around 2:00 a.m. on December 29, 2007, H.E.F. was taken to the ED after she had a second episode of seizure activity. Pet. Ex. 7 at 104-05. This seizure caused her left arm to curl up and shake for approximately two minutes and then go flaccid.
H.E.F.'s next seizure was associated with an illness. On January 17, 2008, H.E.F. had a seizure affecting her left extremities due to a respiratory syncytial virus ("RSV") and she was taken to the ED at Mahaska Hospital. Pet. Ex. 7 at 115. The EMS report stated that H.E.F.'s parents called EMS because H.E.F. was experiencing "involuntary muscle tremors and jerking in her left-side extremities" after which her left upper extremity was immobile.
On February 6, 2008, H.E.F. returned to Mahaska Hospital because she experienced a left-sided seizure lasting at least seven minutes. Pet. Ex. 7 at 159. She then suffered another seizure, this time a "right sided partial complex seizure, which lasted approximately eight minutes."
H.E.F. improved and did not experience another seizure until April 8, 2008, when she was taken to Mahaska Hospital by ambulance because of generalized twitching of her left extremities for 45-50 minutes. Pet. Ex. 7 at 219. H.E.F. had a fever of 102 degrees. She was treated with Valium and phenobarbital.
During the spring of 2008, H.E.F.'s parents moved from Oskaloosa, Iowa, to Ottumwa. Pet. Ex. 1 at 10. H.E.F. received continuing pediatric care from Ottumwa Pediatrics and later from All-Ages Pediatric Clinic. Pet. Ex. 1; Pet. Ex. 12; Pet. Ex. 19. On June 12, 2008, Dr. Eric L. Dodson of Ottumwa Pediatrics referred H.E.F. to the Mayo Clinic for repeated episodes of "status epilepticus." Pet. Ex. 16 at 7. She was diagnosed with "epilepsy with tendency for recurrent prolonged seizures." Pet. Ex. 16 at 9.
On June 21, 2008, Dr. Narawong contacted the Mayo Clinic and explained that H.E.F. was experiencing "unprovoked recurrent status epilepticus." Pet. Ex. 16 at 14. One month later, on July 22, 2008, H.E.F. had a seizure and was taken to Dr. Dodson who prescribed Diastat and Midazolam. Pet. Ex. 16 at 16. The next day, July 23, 2008, H.E.F. presented to the Mayo Clinic for an appointment regarding her seizures. Dr. K.C. Nickels diagnosed H.E.F. with intractable recurrent status epilepticus and noted she may have Dravet syndrome.
On November 26, 2008, H.E.F. experienced another seizure and was taken to BCH. Pet. Ex. 8 at 380, 495, 573. On January 16, 2009, H.E.F. experienced a seizure associated with a fever and an upper respiratory tract infection. Pet. Ex. 16 at 35. Her seizure was treated with Valium.
A few months later, on April 17, 2009, H.E.F. experienced a seizure during a visit to the Mayo Pediatric Neurology Clinic. Pet. Ex. 16 at 44, 52. After arriving in the ED, she had another left-sided seizure lasting approximately 20 minutes.
From summer through the winter of 2009-2010, H.E.F. continued to experience seizure activity associated with high fevers of 104 to 105 degrees. Pet. Ex. 16 at 91-92, 102. On January 7, 2010, H.E.F. suffered another seizure associated with a high fever.
A few years later, on June 2, 2012, during a visit to the Mayo Clinic, neurologist Dr. Amy M. Martyanov documented that H.E.F. was being seen in follow-up for her "Dravet's syndrome." Pet. Ex. 16 at 120. Dr. Martyanov noted that H.E.F. "has very classic Dravet's phenotype with prolonged seizures that are temperature sensitive," although at the time of her examination, H.E.F. was noted as doing well regarding her seizure control.
In April 2013, H.E.F. experienced breakthrough seizures after having no seizures since November of 2011. Pet. Ex. 16b at 3. These seizures occurred over several days and were accompanied by a fever of 104 degrees.
Kimberly Faoro is one of the petitioners and H.E.F's mother. She has seven children, and H.E.F. is the only one who has a seizure disorder. Tr. 8. Ms. Faoro's other children all have had DTaP vaccines during their first year of life and did not experience seizures after vaccination. Tr. 38. Ms. Faoro does not have Dravet syndrome or any other seizure disorder. Tr. 8-9. She did not receive her childhood vaccinations until age four. Tr. 35.
H.E.F. received her first vaccinations when she was two months old, on October 22, 2007. After the vaccinations, she vomited and had diarrhea but did not experience any seizures. Tr. 14-15. H.E.F. received her four month vaccinations on December 28, 2007. That same afternoon, H.E.F. experienced jerking of her left arm and leg. Tr. 16-18. She did not have a fever at this time. Tr. 35. H.E.F. was taken to the ED, where she did have fever. Tr. 36. She was treated and discharged. Tr. 19. The next day, December 29, 2007, H.E.F. had jerking on the opposite side of her body. Tr. 20. She was ultimately taken to BCH in Des Moines by ambulance. Tr. 21. H.E.F was noted to have esotropia,
Ms. Faoro testified that H.E.F. experienced developmental delay. As a child, H.E.F. did not roll over, crawl, or climb up furniture like her siblings. Tr. 23. At nine and one-half months, H.E.F. was referred to early childhood intervention. Tr. 25. On August 11, 2008, an evaluation was performed that showed H.E.F. had a 25% delay in her cognitive skills. Tr. 26.
Currently, H.E.F. is eight years old and is able to walk but she has problems with her balance. Tr. 27. She is able to speak in two- to three-word sentences and can eat with a fork and spoon. Tr. 28. H.E.F. still has seizures, but less frequently. She has had two seizures in the last six months. Tr. 31. She takes Depakote for her seizure disorder. Tr. 33. H.E.F. had no seizures prior to the vaccines she received at her four-month well-child visit. Tr. 14-15.
In addition to the facts set forth above, the following facts relate to H.E.F.'s SCN1A gene mutation and Dravet syndrome.
On June 12, 2008, physicians from the Mayo Clinic recommended that H.E.F. undergo genetic testing. Pet. Ex. 16 at 9. On September 5, 2008, Transgenomic Clinical Reference Laboratory reported the results of H.E.F.'s genetic tests, which revealed that she has a novel SCN1A mutation (a "variant C.2531T>G in exon 14 that encodes a stop (TGA) at codon 844").
A gene is a molecular unit of heredity. It contains DNA which is a molecule that carries most of the genetic instructions used in the development, functioning, and reproduction of all known living organisms and many viruses. Resp't Ex. C. at 5. DNA encodes a functional RNA (or protein product) through a process known as translation. Tr. 302; Resp't Ex. C. at 5. Resp't Ex. G at 6-7, 11. This process of translation from the DNA to RNA produces a specific amino acid chain which becomes an active protein and performs specific functions in the cell.
H.E.F.'s mother also underwent genetic testing and the results revealed that she has the same gene mutation as H.E.F. But Ms. Faoro is asymptomatic and shows no signs of Dravet syndrome. H.E.F.'s father and maternal grandmother were also tested and they do not have the gene mutation. Pet. Ex. 1 ¶ 113; Pet. Ex. 16 at 90; Pet. Ex. 28. To explain this phenomena, respondent proposes a theory of mosaicism (meaning the mutation is in some of the cells). Mosaicism, which is more fully discussed below, is the explanation proposed by respondent's expert for why Ms. Faoro is asymptomatic. Petitioners contend that respondent's theory that Ms. Faoro is mosaic is only speculation and has not been confirmed by any testing. Jt. Sub. at 3.
Dravet syndrome is a rare condition with an incidence of 1:40,000 children.
Dravet syndrome is also referred to as Severe Myoclonic Epilepsy of Infancy ("SMEI") and is an epilepsy syndrome that typically starts around six months of age.
The following is a brief summary of events that chronicle H.E.F.'s developmental delay. H.E.F. was born on August 28, 2007. At two weeks of age, September 4, 2007, Dr. White noted, H.E.F. "move[d] her arms and legs equally and focuse[d] on faces." Pet. Ex. 5 at 4. A few days later, on September 11, 2007, H.E.F. was noted to be "active" and "alert."
At approximately six months of age, on January 17, 2008, records from Mahaska Hospital state that H.E.F. displayed a social smile, rolled over by herself, and was babbling. Pet. Ex. 7 at 135. At approximately six and one-half months of age, on February 6, 2008, H.E.F. was noted as being active and alert and she had normal reflexes.
At ten months of age, on July 23, 2008, at a Mayo Clinic appointment, H.E.F. was "able to drink a bottle easily with either hand," track objects and faces well, and move all four extremities." Pet. Ex. 16 at 17. Dr. Katherine Nickels noted that H.E.F. was developing normally. Pet. Ex. 19 at 18. However, given H.E.F.'s symptoms and history of seizure activity, Dr. Nickels suspected that she had Dravet syndrome.
On January 9, 2009, at 16 months of age, during a visit to the Mayo Clinic, H.E.F. was noted to be "making progress" developmentally. Pet. Ex. 16 at 32. She was alert and interactive, could walk, run, crouch, use a fork and spoon, participate in pretend play and follow commands.
On November 23, 2009, at two years and three months of age, Dr. Nickels noted that H.E.F. was progressing developmentally. She responded to her name, understood "no," could easily climb, could say approximately 15 words, and was able to draw lines with a crayon. Pet. Ex. 16 at 102. On June 2, 2010, at two years and nine months of age, H.E.F. was alert and interactive, used two-word phrases, followed objects with her eyes, could reach for objects, and had "good resistive strength" and a stable gait.
H.E.F.'s diagnosis on July 11, 2013 (at almost 6 years of age) was that H.E.F. had Dravet syndrome and "developmental delay, ataxia, dysmetria, and behavioral control consistent with Dravet syndrome comorbidities." Pet. Ex. 16b at 5-6. H.E.F. was alert and interactive, had good climbing skills, clearly combined approximately four words, but again had an unstable gait.
Petitioners filed their petition on October 15, 2010. Respondent filed her report pursuant to Vaccine Rule 4(c) on March 28, 2011. Petitioners filed four expert reports from Dr. Barbara Burton and one from Dr. Marcel Kinsbourne. Respondent filed two expert reports from Dr. Rajesh Sachdeo and two from Dr. Gerald Raymond. In total, the parties filed approximately 72 medical texts and articles. The parties also filed pre-hearing briefs.
A two-day hearing was held on June 3-4, 2014. Ms. Faoro testified on the first day of the hearing, and was present during the entire hearing. Drs. Burton and Kinsbourne testified on behalf of petitioners and Drs. Sachdeo and Raymond testified on behalf of respondent.
A post-hearing status conference was held on June 26, 2014, to discuss the issue of having all of Ms. Faoro's biological children tested for the SCNIA gene mutation. With the consent and agreement of Ms. Faoro, the parties worked together to obtain familial genetic testing.
However, on August 3, 2015, respondent filed a motion for leave to file a supplemental report from Dr. Raymond and additional literature on the basis that respondent had additional relevant evidence. In the motion, respondent stated that on July 31, 2015, Dr. Raymond had learned of an SCN1A mutation database hosted by the Institute of Neurosciences, Guangzhou Medical University, in China. Dr. Raymond stated that he had not known of the database at the time of the hearing. "Upon searching this database, Dr. Raymond learned of additional evidence, including medical literature, related to the specific SCN1A mutation at issue in this case." Respondent's Motion to File Additional Evidence, Aug. 3, 2015, at 1. Petitioners objected to respondent's motion as untimely and because it was perceived as a way for respondent to introduce additional argument about the evidence which the court had not solicited.
On August 12, 2015, a status conference was held to discuss the dispute. Respondent stated that the database information was new information, available only as of 2015, and was not available to her experts at the time of the hearing in this case in June 2014. Respondent also clarified that one of the articles identified in her motion was a study conducted by the Mayo Clinic involving a patient that was later identified to be H.E.F. Petitioners confirmed that H.E.F. was the individual involved in this study. Respondent explained that the article stated that H.E.F's specific genetic mutation was classified as a disease-causing mutation, and that Dr. Raymond's supplemental report would discuss the significance of this article. After discussion, the parties agreed to work together to redact the portions of Dr. Raymond's supplemental report considered by petitioners to constitute argument, i.e., not a factual discussion of the additional evidence, and agreed to file the redacted report and medical literature, including the link to the SCN1A database referenced by Dr. Raymond. On August 13, 2015, respondent filed the redacted supplemental report of Dr. Raymond and two additional medical articles.
The Vaccine Act established the Program to compensate vaccine-related injuries and deaths. § 300aa-10(a). "Congress designed the Vaccine Program to supplement the state law civil tort system as a simple, fair and expeditious means for compensating vaccine-related injured persons. The Program was established to award `vaccine-injured persons quickly, easily, and with certainty and generosity.'"
To establish causation in fact, a petitioner must show by a preponderance of the evidence that but for the vaccination, the petitioner would not have been injured, and that the vaccination was a substantial factor in bringing about the injury.
Causation is determined on a case-by-case basis, with "no hard and fast
To receive compensation under the Program, petitioners must prove either: (1) that H.E.F. suffered a "Table Injury"—i.e., an injury listed on the Vaccine Injury Table— corresponding to a vaccine that she received, or (2) that H.E.F. suffered an injury that was actually caused by the vaccine (or vaccines) she received.
Because petitioners do not allege that H.E.F. suffered a Table injury, they must prove that a vaccine H.E.F. received caused her injury. To do so, they must establish, by preponderant evidence: (1) a medical theory causally connecting a vaccine and H.E.F.'s injury ("
Another important aspect of the causation-in-fact case law under the Vaccine Act concerns the factors that a special master should consider in evaluating the reliability of expert testimony and other scientific evidence relating to causation issues. In
The first issue presented is whether H.E.F.'s December 28, 2007 vaccinations can and did cause her injury. Jt. Sub. at 3. As an initial matter, it must be clarified that the parties do not dispute that H.E.F. was born with a mutation of her SCN1A gene and that the vaccinations at issue did not cause her gene mutation.
Under
Petitioners' theory of causation need not be medically or scientifically certain, but it must be informed by "sound and reliable medical or scientific explanation."
Dr. Marcel Kinsbourne is currently a tenured professor of clinical psychology for graduate students at The New School, University of New York. Tr. 120. He received his medical degree from Oxford University in 1955. Tr. 122. Dr. Kinsbourne then studied neurology, general pediatrics, and pediatric neurology until 1964. Pet. Ex. 31A at 1-2. Dr. Kinsbourne came to the United States in 1967 and became an Associate Professor of Pediatrics and Neurology at Duke University Medical Center in Durham, N.C.
To explain why Ms. Faoro has the same genetic mutation at H.E.F. but is asymptomatic, Dr. Kinsbourne proposes a "second hit" theory. Pet. Ex. 30 at 7. According to Dr. Kinsbourne, the SCN1A genetic mutation creates a "susceptibility" in an individual.
According to Dr. Kinsbourne, environmental triggers can include vaccines, viruses and bacterial infections. Tr. 175-76. He states that the DTaP vaccine "often causes fever and it also can cause a proinflammatory cascade that causes seizures."
According to Dr. Kinsbourne, the SCN1A genetic mutation is known to lower an infant's seizure threshold due to a fever. Tr. 143. Dr. Kinsbourne cites an article by Ceulemans et al.
Dr. Kinsbourne explains that vaccines, like infections, may "cause the release of proinflammatory cytokines, including interleukin 1 beta (IL-1β) as part of a reaction by the innate immune system." Pet. Ex. 30 at 7. Citing an article by Vezzani and Baram,
In support of his theory about potential environmental triggers, Dr. Kinsbourne cites six articles.
Dr. Kinsbourne also relies on the Sell and Menassian
In his expert report, Dr. Kinsbourne also cites the McIntosh study
Dr. Burton is a medical geneticist who currently practices at the Ann & Robert H. Lurie Children's Hospital of Chicago, which is affiliated with the Northwestern University School of Medicine. Tr. 47. She attended medical school at Northwestern University Feinberg School of Medicine, and completed a residency in pediatrics. Dr. Burton then completed a two-year fellowship in medical genetics at Children's Memorial Hospital. She is board-certified by the American Board of Pediatrics and the American Board of Medical Genetics, with subspecialties in clinical genetics and clinical biochemical genetics. Pet. Ex. 36 at 2. Dr. Burton is currently a Professor of Pediatrics at Northwestern University, a member of the Center for Genetic Medicine, and a Clinical Practice Director of the Division of Genetics at Children's Memorial Hospital. She serves as a director and consultant for a number of different clinics at Children's Memorial Hospital, including the Institute for Fetal Health, the PKU clinic, and the Marfan syndrome clinic.
In her current position, Dr. Burton provides "care to patients and families who have birth defects or genetic disorders." Tr. 48. She orders diagnostic testing, provides genetic counseling, as well as ongoing medical care and treatment to her patients with certain genetic disorders. Tr. 48. Although Dr. Burton occasionally sees patients with Dravet syndrome for genetic counseling, or evaluation and diagnosis, she does not typically provide ongoing care and treatment for these patients, as they are usually followed by a pediatric neurologist. Tr. 49.
In addition to patient care and teaching, Dr. Burton also has a number of current research grants and contracts, and she has authored books, book chapters, and hundreds of articles and abstracts.
Dr. Burton explained her view of the significance of an inherited mutation. She agrees that "specific mutations (changes) in [the SCN1A] gene are known to be associated with [Dravet syndrome], a condition that causes intractable seizures and developmental disabilities in children." Pet. Ex. 29 at 1. However, she states that "[m]ost disease-causing mutations in SCN1A that result in [Dravet syndrome] are de novo, meaning that they are not present in the parent. If a variant of unknown significance is detected in a parent who is clinically normal, it is typically concluded that the genetic change is not responsible for the patient's abnormalities and most likely represents a normal variant."
Dr. Burton disagrees with respondent's explanation of mosaicism to explain why a mother with the same mutation as her child is asymptomatic, whereas the daughter has a severe form of disease caused by the mutation. She defines mosaicism as a situation where there is "more than one population of cells, just like if you have a mosaic tile pattern on the floor where there's more than one color of tiles . . . there's more than one type of cell . . . some cells have the mutation and some don't. . . . It's a mixed population of cells." Tr. 66. While Dr. Burton agrees that mosaicism is one theory "demonstrated in some families where there's been a normal parent," she states that there can also be other explanations. Tr. 67, 70. She states that there are genetic factors or "some other environmental factors" that may explain why a parent is normal, but the child has Dravet syndrome. Tr. 75. Dr. Burton warns against speculating that a parent is mosaic without additional evidence because there are "too many exceptions in genetics." Tr. 82.
Dr. Burton concedes that she is not an expert in the area of vaccine-induced brain injury or in vaccine-gene interactions, and she clarifies that she did not "come up with the vaccine" as a cause of H.E.F.'s condition. Tr. 89, 104-06. Nonetheless, Dr. Burton testified that the theory proposed by Dr. Kinsbourne, that vaccination could be an environmental trigger for the development of Dravet syndrome in a child with an underlying genetic vulnerability, sounds "very reasonable." Tr. 89, 95. She emphasized, however, that the issue was outside the scope of her expertise. Tr. 76-77.
Dr. Sachdeo is a neurologist who specializes in epilepsy, and he treats children and adults with seizure disorders. Tr. 208. He attended medical school at the Christian Medical College in India. After moving to the United States, Dr. Sachdeo completed his residency at Loyola University Medical Center. He obtained his subspecialty training in epilepsy through a fellowship at Rush-Presbyterian St. Luke's Medical Center in Chicago. Resp't Ex. A-6 at 2. Dr. Sachdeo is currently a Clinical Professor of Neurology at UMDNJ Robert Wood Johnson Medical School in New Jersey. Resp't Ex. A at 1. He is an attending physician at a number of hospitals, including the Robert Wood Johnson University Hospital and Princeton University Medical Center.
Dr. Sachdeo disagrees with Dr. Kinsbourne's "second hit" theory, stating there is no proof that environmental factors cause Dravet syndrome. Tr. 230, 232. Likewise, he disagrees that vaccinations cause or significantly aggravate Dravet syndrome. Resp't Ex. A at 4. While Dr. Sachdeo agrees that a "vaccination might trigger earlier onset" of Dravet syndrome in children with the SCN1A mutation, he states that "there is `no evidence that vaccination before or after disease onset affects outcome'" in patients with Dravet syndrome.
Dr. Sachdeo also disagrees with Dr. Kinsbourne's theory that vaccines function like infections or that they cause a proinflammatory process that causes or contributes to Dravet syndrome. Dr. Sachdeo testified that there is no evidence that vaccinations interact with the lower seizure threshold caused by the SCN1A mutation (Pet. Ex. 30 at 7) and thus trigger the seizure disorder. Tr. 233. He states that while fever, hot baths, or infection may all initiate seizures in children with Dravet syndrome, the time or cause of the initial seizure does not impact or affect the clinical course of the disease. Tr. 234. A child may have his first seizure two months earlier, but the earlier onset does not change the ultimate clinical course or prognosis. Tr. 265. Similarly, he states that there is no difference in patients who have seizure onset associated with vaccinations as opposed to those who do not. Tr. 266. Dr. Sachdeo states that none of these conditions cause the genetic disorder or the genetic susceptibility in a child. Tr. 236.
Dr. Sachdeo also cites the McIntosh
Dr. Gerald Raymond is a pediatric neurologist who specializes in neuropathology and genetics. He attended medical school at the University of Connecticut. Resp't Ex. F at 1. After medical school, Dr. Raymond completed a residency in pediatrics and neurology.
Dr. Raymond explains that the SCN1A gene contains the recipe for the voltage-gated sodium channel, which is a series of "complex chemical reactions [that] move sodium from one side of a [cell] membrane to the other to change the polarity of the membrane." Tr. 312. The SCN1A gene, along with SCN1B gene, make up the Na
Animal models, Dr. Raymond indicated, play an important role in helping to understand the pathogenesis of Dravet syndrome. During his testimony, Dr. Raymond referenced the Oakley article
Dr. Raymond disagrees with Dr. Kinsbourne's assertion that Dravet syndrome has wide variability in genetic expression, which according to Dr. Kinsbourne explains why Ms. Faoro is asymptomatic although she carries the same genetic mutation as H.E.F. Tr. 331. Dr. Raymond explained that, generally, variations in expressivity in SCN1A have not been seen.
Dr. Raymond also disagrees with Dr. Kinsbourne's proposed theories of second hit (gene-environment) and vaccinations as similar to infections (immune-mediated response). Dr. Raymond testified that the SCN1A genetic alteration is the sole cause of H.E.F.'s Dravet syndrome and its sequela. Tr. 182; 340. The basis for Dr. Raymond's opinion is three-fold. First, current medical research and literature establishes that a "significant alteration in the [SCN1A] gene is sufficient" for the expression of Dravet syndrome. Tr. 328. Second, animal models show that if you alter or remove (knock out) one copy of the SCN1A gene, the result is Dravet syndrome (Oakley mice study discussed above). Third, the Berkovic
Dr. Raymond cites studies by Depienne,
In an article presented by respondent, the authors explained why testing for mosaicism can be difficult.
There are 1257 mutations that have been identified in the SCN1A gene.
Dr. Raymond disagrees with Drs. Kinsbourne's and Burton's assertion that a specific phenotypic expression explains why a mother is asymptomatic, but her child has a disease, although they share the same genetic mutation. Dr. Raymond explains that what was previously thought to be explained by "reduced expression and penetrance of disease-causing" genetic mutations is now explained by mosaicism. Resp't Ex. E at 1; Tr. 335. Dr. Raymond rejects the articles cited by Dr. Kinsbourne
In summary, Dr. Raymond states that mosaicism is the only explanation for the situation where a parent and child share the same SNC1A mutation (in this case, where a mutation results in a "truncation of the protein"), and the parent is asymptomatic, but the child has Dravet syndrome. Resp't Ex. E at 2.
The undersigned finds that petitioners have failed to provide preponderant evidence to support their medical theory. None of the articles cited by Dr. Kinsbourne suggest that vaccines can cause Dravet syndrome or change the clinical course of Dravet syndrome. While some studies demonstrate an association between vaccination and fever, and thus the onset of seizures in children with Dravet syndrome, the current research and medical literature establishes that vaccination does not affect the prognosis or severity of Dravet syndrome. The animal models, as presented by Dr. Raymond, provide strong evidence that Dravet syndrome will develop with or without vaccination in children with the SCNIA mutation, and truncating mutations in the SCN1A gene, like the one identified in H.E.F., are associated with a more severe prognosis. Lastly, Dr. Raymond's testimony and supportive medical literature regarding mosaicism is very persuasive. Mosaicism is the best explanation for why a parent who has the SCNIA mutation may not be symptomatic, but her child, who inherited the same mutation has the disease.
Under
Dr. Kinsbourne opines that the vaccinations that H.E.F. received on December 28, 2007, contributed to the development of her seizure disorder via the theories described above. Tr. 139; 153. He states that H.E.F.'s SCN1A mutation lowered her seizure threshold and predisposed her to having seizures. Tr. 152-153. The seizures that occurred following her receipt of vaccines on December 28, 2007, triggered the onset of her Dravet syndrome. Tr. 152. However, Dr. Kinsbourne could not say that H.E.F. would not have developed seizures had she not been vaccinated. Tr. 153. He also conceded that the vaccines H.E.F. received did not continue to cause her seizures after the onset because after that time, the vaccines "ha[d] no causal effect, in and of itself afterwards." Tr. 154. Instead, he stated that each seizure makes it more likely that there will be another seizure.
Dr. Kinsbourne testified that once H.E.F. had the initial seizure, it then became much more likely that she would have additional seizures. Tr. 172. He also opines that the vaccinations caused H.E.F. to develop a more severe form of Dravet syndrome than she would have otherwise had. Tr. 190. The basis for his opinion is that H.E.F.'s mother has the mutation but not the disease. Based on the findings published in the McIntosh article, Dr. Kinsbourne opines that the vaccine caused H.E.F. to have an earlier onset of Dravet syndrome by two months. Tr. 190. Dr. Kinsbourne cites a commentary by Dr. Elinor Ben-Menachem to support his opinion that H.E.F.'s outcome would be different but for the vaccine. Tr. 196; Pet. Ex. 30-N.
H.E.F. did have two focal
Dr. Kinsbourne concedes that he has no clinical experience in diagnosing or treating children with Dravet syndrome. He has not treated children since the SCN1A genetic mutation was discovered. Tr. 162-63.
Dr. Burton testified that the purpose of her testimony was to explain that H.E.F.'s mutation has not been established as disease-causing and thus there is insufficient evidence that it is the "sole cause" of her disease. Pet. Ex. 29A at 1 (Supplemental Expert Report of Dr. Barbara Burton). Genetic testing of H.E.F. revealed a novel variant "referred to as c.2531T>G in exon 14 of one of [her] SCN1A genes." Pet. Ex. 29 at 1. Dr. Burton emphasized that the "variant had not been reported in the literature in any other patient" and therefore, "the pathogenicity" of the mutation has not been determined.
Once novel gene variants like H.E.F.'s are detected in studies, the parents are usually tested. Tr. 114. Testing was performed on H.E.F.'s parents which revealed that H.E.F.'s mother has the same genetic mutation as her daughter. However, H.E.F. has Dravet syndrome and her mother does not. Tr. 68. Because of this, Dr. Burton opines that the genetic mutation "is not responsible for the intractable seizures and developmental disabilities observed in [H.E.F.]." Pet. Ex. 29 at 2.
Although Dr. Burton agrees that the SCN1A mutation likely contributed to H.E.F.'s Dravet syndrome, she does not believe it is the "sole cause" of the child's condition. Pet. Ex. 29A at 1. According to Dr. Burton, the only way that the genetic mutation could be the sole cause of H.E.F.'s condition is if her mother has a de novo mutation that is mosaic. Tr. 82. Dr. Burton does not, however, believe that H.E.F.'s mother is mosaic because the genetic testing that has been performed does not show evidence of mosaicism. Tr. 67-68, 114. Dr. Burton also relies on the Depienne
Dr. Burton disagrees with Dr. Raymond's explanation that H.E.F.'s gene mutation is pathogenic based on the type and location of the mutation of the gene. Resp't Ex. C at 7. Dr. Raymond explains in his expert report that H.E.F's mutation creates a stop codon, which means that the codon stops reading or transcribing the gene at a certain point, and stops formation of the protein in her DNA (also known as a truncating mutation). According to Dr. Raymond, because of this stop codon mutation, H.E.F. is more likely to have a disease-causing mutation that results in a severe dysfunction of the protein encoded by her DNA and usually results in disease.
Dr. Burton testified that expression of the gene mutation may vary based upon phenotype. Her opinion is based on results from studies
Dr. Burton also relies upon an article by Escayg and Goldin
Dr. Burton testified that if it turns out that H.E.F.'s mother is not mosaic, then the SCN1A gene mutation cannot explain H.E.F's condition. Tr. 110. That would mean H.E.F's mother would have the gene mutation in every cell in her body and is asymptomatic. Thus, the mutation alone could not be the sole cause of H.E.F.'s Dravet syndrome.
According to Dr. Burton, there is up to a 50% risk (per child) that Ms. Faoro would transmit the mutation to each of her children. Tr. 61. Thus, according to Dr. Burton, H.E.F.'s siblings are likely to have the mutation. However, the results of the children's genetic testing were all normal. Dr. Burton testified that this is either because they have not had any environmental trigger or Ms. Faoro is mosaic. Tr. 111. Dr. Burton agreed that if Ms. Faoro was mosaic, she would have a mix of cells that have the mutation and do not have the mutation, and that, probably, most of the cells in her brain do not have the mutation which is what has protected her from having any neurologic symptoms. Tr. 109. In addition, Ms. Faoro would have fewer cells in her ovary that have the gene mutation, and the risk of each of her children being born with the mutation would be less than 50%. Tr. 111.
To determine whether Ms. Faoro is mosaic, Dr. Burton testified that Ms. Faoro would have to undergo quantitative PCR and tissue biopsy testing. Tr. 108-09. If testing revealed that Ms. Faoro has the gene mutation in only a portion of her cells, it would mean that Ms. Faoro is mosaic. It would also mean that the gene mutation would not be present in many (or any) of Ms. Faoro's brain cells because she does not have an epilepsy disorder. Tr. 109. If Ms. Faoro is in fact mosaic, it also means that the gene mutation occurred the first time in her (i.e., de novo) and can be passed down to her offspring, which is what happened to H.E.F. Tr. 109. H.E.F. inherited the mutation from her mother and the mutation is contained in every cell in her body, including her brain.
Dr. Sachdeo opined that H.E.F.'s seizure disorder was a result of her Dravet syndrome, which by itself would have triggered her seizure disorder. Dr. Sachdeo stated that the vaccinations H.E.F. received had nothing to do with the development of her seizures, or the severity and outcome of her condition. Resp't Ex. A at 4-5; Tr. at 221. He testified that while the fever associated with her vaccines likely triggered the initial seizure, the vaccinations did not trigger H.E.F.'s underlying genetic disorder. Tr. 236, 284.
Dr. Sachdeo testified that H.E.F.'s clinical course was consistent with the expected course of Dravet syndrome. Tr. 227. He opined that H.E.F. began having symptoms of developmental delay at some point between 12 and 15 months, which is consistent with the clinical course of the disease. Tr. 227-228; 266. Even assuming that H.E.F. began having developmental delay at 9 ½ months of age (consistent with Ms. Faoro's testimony at the hearing), that onset too, would be consistent with the natural, clinical course of the disease. Tr. 229.
Based on his experience treating children with Dravet syndrome, Dr. Sachdeo testified that those children who respond well to medication early, tend to have a better prognosis. Tr. 265. He stated that the most important factor in determining prognosis is good seizure control through medication. Tr. 267. Based on H.E.F.'s medical records, Dr. Sachdeo testified that it took approximately a year to find medication that effectively controlled H.E.F.'s seizures. Tr. 268. Dr. Sachdeo stated that he was impressed with H.E.F.'s treatment, and he felt that she made good progress developmentally. Tr. 269. Dr. Sachdeo testified that H.E.F.'s seizures are well controlled and that her prognosis is good. Tr. 269.
Dr. Raymond testified that H.E.F.'s SCN1A gene mutation is the "sole cause" of her seizure disorder. Tr. 299; 340. Her genetic mutation is described by Dr. Raymond as a "premature Stop codon" type mutation. Tr. 302. This type of mutation affects the "function of the protein." Tr. 310. Dr. Raymond explained that 90 to 99% of truncating SCN1A mutations are associated with Dravet syndrome or other severe temperature sensitive seizure disorders. Tr. 321; 327. Moreover, H.E.F.'s specific mutation has now been "uploaded into an international SCN1A mutation database (
H.E.F.'s SCN1A gene mutation takes the amino acid sequence TTA and takes it to TGA, and that "becomes a stop, so there's no further translation of additional protein." Tr. 324. Dr. Raymond stated that this results in haploinsufficeincy
Dr. Raymond opines that the theory of mosaicism is the most logical explanation for why H.E.F. has a seizure disorder, but her mother does not. If H.E.F.'s mother is mosaic, it means that she has the SCN1A gene mutation in some, but not all of her cells. Tr. 330-31. If the percentage of abnormal cells is not highly expressed in her mother's brain, then H.E.F.'s mother is not likely to have Dravet syndrome. Tr. 331. However, H.E.F.'s mother may still pass the gene mutation to her offspring who may inherit the full-blown disordered, like H.E.F. did. H.E.F. inherited the mutation from her mother and that mutation is contained in 100% of her cells. As a result, H.E.F. has Dravet syndrome. Tr. 332.
Dr. Raymond also explained that testing to verify whether H.E.F.'s mother is mosaic is currently not commercially available. Tr. 332, 378-81. However, he stated that circumstantial evidence could be established through testing Ms. Faoro's parents or her other biological children. Tr. 384. Ms. Faoro's mother tested negative for the gene mutation. Ms. Faoro's father passed away, but Ms. Faoro testified that her father did not have a seizure disorder. Tr. 13. Without results from Ms. Faoro's father, it cannot be confirmed if Ms. Faoro is mosaic. Tr. 384. Regarding Ms. Faoro's other biological children, Dr. Raymond explains that he did not believe that any of Ms. Faoro's other children have the SCN1A genetic mutation because they do not have clinical symptoms. Tr. 365. He explained that there is a risk of between zero and 50% for each pregnancy that Ms. Faoro's child would inherit the mutation, depending on the percentage of Ms. Faoro's affected cells. Tr. 359. If all of the other children are tested and none have the SCN1A gene mutation, this would be circumstantial evidence in support of Dr. Raymond's theory that Ms. Faoro is mosaic. Tr. 385. However, if a sibling was positive for the mutation, then that would be evidence that the SCN1A mutation is not the sole cause of H.E.F.'s Dravet syndrome. Tr. 385-86.
After the hearing, the children were all tested and the results confirmed that none of them have the SCN1A gene mutation. Pet. Ex. 43. Based upon Dr. Raymond's explanation above, this is circumstantial evidence that Ms. Faoro is mosaic.
Dr. Raymond disagrees that any environmental factor was at play here. He opined that no one has identified a specific environmental factor that causes or contributes to Dravet syndrome. Tr. 372. He states that his opinion is that H.E.F.'s gene mutation is the "sole cause of her Dravet syndrome . . ." Resp't Ex. I at 1.
Petitioners have failed to prove by a preponderance of the evidence a logical sequence of cause and effect showing that the vaccines H.E.F. received caused her Dravet syndrome. First, it is undisputed that H.E.F. was born with the SCN1A gene mutation and the parties agree that her gene mutation was not caused by the vaccines. Second, H.E.F. did not sustain any permanent brain injury after her initial seizures following vaccination. The initial seizure lasted two minutes, which was followed by Todd's paralysis of her arm which resolved. H.E.F. then had a second seizure lasting two minutes, again followed by Todd's paralysis, which again resolved. After being observed in the hospital, H.E.F. was discharged home. Her diagnostic studies, including the EEG, were all normal. H.E.F.'s physical and neurological exams were normal. Dr. Kinsbourne agrees that there was no evidence of brain injury after her first two seizures.
H.E.F received her vaccines at approximately four months of age (December 28, 2007). The first medical records that describe any type of development delay appear in H.E.F.'s records on January 9, 2009, when H.E.F. was approximately 16 months of age. This was approximately one year after the vaccines at issue were administered.
Once H.E.F.'s treating physicians obtained the results of her genetic testing, they confirmed the presence of an SCN1A gene mutation and H.E.F. was diagnosed with Dravet syndrome. Once the genetic cause of H.E.F.'s illness was discovered, her diagnosis was clear. There is no indication in the record that any of H.E.F.'s treating physicians have diagnosed her with a vaccine-related injury after the results of her genetic tests were obtained and reviewed.
Petitioners' argument, that expression of the gene mutation may vary based upon phenotype, also fails. At the hearing, Dr. Burton testified that the evidence was insufficient to establish mosaicism. According to Dr. Burton, the only way that the genetic mutation could be the sole cause of H.E.F.'s condition is if her mother, Ms. Faoro, had a de novo (new) genetic mutation and was mosaic. Tr. 82, 110. Ms. Faoro's mother, H.E.F's grandmother, was tested and does not have the SCN1A gene mutation. Although Ms. Faoro's father could not be tested, Ms. Faoro testified that he did not have a seizure disorder. Tr. 13. After the hearing, testing was performed on Ms. Faoro's other biological children which revealed that none of them had the SCN1A mutation. These negative test results are strong circumstantial evidence that H.E.F.'s mother is mosaic. This strong evidence supports Dr. Raymond's theory of mosaicism. There is no basis for implicating the vaccinations as the cause in the face of this convincing evidence.
Lastly, petitioners failed to prove by preponderant evidence that Dr. Kinsbourne's theory (the vaccines affected the occurrence and severity of H.E.F.'s disease) is reliable. Dr. Kinsbourne did not provide any reliable testimony or medical literature to show that H.E.F's outcome would have been different had she not received the vaccines. The commentary cited by Dr. Kinsbourne to support his theory that the outcome of H.E.F.'s Dravet syndrome would be different, but for the vaccine, is not supported. Dr. Kinsbourne conceded that he has not treated children with Dravet syndrome. Both of respondent's experts have experience providing medical care to patients with Dravet syndrome. Respondent's experts testified that H.E.F.'s clinical course was, and continues to be, consistent with the expected course of Dravet syndrome. Respondent also provided medical literature to support her position that H.E.F.'s vaccines did not change the occurrence or severity of her clinical course of Dravet syndrome.
Under
Petitioners may meet their burden by showing: (1) when the condition for which they seek compensation first appeared after vaccination, and (2) whether the period of symptom onset is "medically acceptable to infer causation."
Dr. Kinsbourne opined that the vaccinations H.E.F. received on December 28, 2007, were a significant contributing factor to the onset of her Dravet syndrome, in part because she had her first seizure approximately seven hours after vaccination. Pet. Ex. 30 at 4, 7-8.
Dr. Kinsbourne submitted several articles in which the authors have studied the temporal relationship between vaccination and onset of the initial seizure in patients with Dravet syndrome. In the Nieto-Barrera article,
Dr. Burton stated that she is not an expert in vaccine related injuries. Tr. 76, 89. Throughout the hearing, she emphasized that she did not reach any conclusions about whether H.E.F.'s injuries were vaccine related. Tr. 90. Even so, Dr. Burton testified that based on the temporal association of H.E.F.'s seizures to her vaccinations, it was reasonable to assume that there was a causal relationship. Tr. 90.
Dr. Sachdeo stated that a temporal relationship between seizures and vaccination may exist. However, he stated that this temporal relationship does not affect the outcome in patients with Dravet syndrome. Resp't Ex. A at 5. Dr. Sachdeo estimated that 30-40% of his patients with Dravet syndrome had their first seizure within 72 hours of a vaccination. Tr. 260. He has not, however, seen any differences between his patients who have their initial seizures in temporal association with vaccines, as compared to those who do not. Tr. 264-65. The biggest factor in predicting good outcomes, according to Dr. Sachdeo, is whether a child responds well to medication early in the course of their disease. Tr. 265.
Dr. Raymond testified that following H.E.F.'s vaccination, she did experience temperature elevation followed by brief seizures. But he explained that this temporal association played "no aggravating or contributing role to her diagnosis of Dravet syndrome." Tr. 340. Dr. Raymond explained that fever, illness, and lack of sleep, are factors that may lower the seizure threshold but that these factors do not cause Dravet syndrome. Tr. 372. He stated that Dravet syndrome is caused by a genetic mutation. Tr. 339-40.
Dr. Raymond also cited the McIntosh study,
The medical records show, and all of the experts agree, that H.E.F.'s initial seizure, or seizure onset, was within 24 hours of her four month vaccinations. This proximity between vaccination and seizure onset suggests a causal relationship between the two events. But without evidence of a causal mechanism or evidence of injury, the temporal relationship is not enough.
Moreover, the McIntosh study shows that in children with Dravet syndrome, who have their initial seizures following vaccination, are no different than children who do not experience their first seizure in temporal relation with a vaccination. The clinical course and outcome are no different.
The second issue presented by the parties is whether H.E.F.'s vaccinations significantly aggravated her pre-existing injury. Jt. Prehearing Sub. at 3. The undersigned holds that it did not.
The elements of an off-Table significant aggravation case are set forth in
The first step in the
Although H.E.F. was born with the SCN1A mutation, her physical and neurological examinations were all normal prior to her December 28, 2007 vaccinations.
The second part of the
On December 28, 2007, approximately seven hours after her four month old immunizations, H.E.F. had her initial seizure which lasted about two minutes. Pet. Ex. 7 at 92. She had temporary paralysis of her right arm, but then regained full movement.
Approximately two weeks later, H.E.F. had seizure activity, this time associated with illness. Pet. Ex. 7 at 115. The seizure was described similar to her prior episodes, as "twitching of the right side which affected both the arms and legs."
In June 2008, H.E.F. was referred to the Mayo Clinic for repeat episodes of "status epilepticus." Pet. Ex. 16 at 7. She was diagnosed with "epilepsy with tendency for recurrent prolonged seizures."
Several years later, on June 2, 2012, H.E.F. during a follow-up visit to the Mayo Clinic, neurologist Dr. Amy M. Martyanov stated that H.E.F. "has very classic Dravet's phenotype with prolonged seizures that are temperature sensitive." Pet. Ex. 16 at 120.
The evidence in the record indicates that H.E.F.'s current condition is consistent with that of a child who has the SCN1A gene mutation and Dravet syndrome. Like H.E.F.'s treating neurologist, Drs. Sachdeo and Raymond (who both treat patients with Dravet syndrome) testified that H.E.F.'s clinical course is consistent with that of a child with Dravet syndrome.
The next prong of the
Based upon the facts as set forth earlier, H.E.F. had two brief seizures immediately after her December 28, 2007 vaccinations. Over time, H.E.F.'s condition deteriorated and she developed severe epilepsy and developmental delay. The undersigned must first make clear that there is no question that H.E.F.'s condition prior to and after her December 28, 2007 vaccination was worse. However, the question relevant to this prong of the
As stated above, H.E.F.'s clinical course is consistent with Dravet syndrome. Dr. Kinsbourne, however, suggests that if H.E.F. had not received the vaccines on December 28, 2007, the onset of her Dravet syndrome would have been later; or that her developmental delay may been less severe. Pet. Ex. 30 at 6. All of these arguments fail, however, because Dr. Kinsbourne concedes that there is no way to predict what H.E.F.'s outcome would have been if she had not received the vaccines. Simply stating what "may" have happened is a matter of speculation and such a statement does not provide petitioners with preponderant evidence to support their theory. Tr. 192.
Alternatively, Dr. Kinsbourne cites the McIntosh study
Petitioners have failed to show by a preponderance of the evidence that the vaccinations significantly aggravated H.E.F.'s condition. She was born with the SCN1A and her clinical course developed consistent with that condition. The undersigned finds that the vaccinations would not have changed her clinical course and thus, the vaccinations did not significantly aggravate her preexisting condition.
As set forth in section D(1) above, petitioners failed to establish by a preponderance of the evidence, a medical theory causally connecting H.E.F.'s condition, or any significant aggravation. Dr. Kinsbourne did not set forth any additional theories for petitioners' argument based on significant aggravation, apart from the theories addressed above. Therefore, petitioners failed to prove causation as to significant aggravation.
For the same reasons set forth in section D(2) above, petitioners failed to prove by preponderant evidence a logical sequence of cause and effect showing that the vaccination significantly aggravated H.E.F.'s condition.
The last element in the six-part
Again, for the same reasons set forth in section D(3), petitioners failed to prove the third prong of
Because petitioners did not meet their burden of proof on causation or significant aggravation, respondent does not have the burden of establishing a factor unrelated to the vaccination caused H.E.F.'s injuries.
Pursuant to the Vaccine Act, compensation shall be awarded where the petitioner demonstrates the requirements set forth under the Act by a preponderance of the evidence, and "there is not a preponderance of the evidence that the . . . injury . . . is due to factors unrelated to the administration of the vaccine." § 300aa-13(a)(1)(A)-(B). The Vaccine Act provides that "factors unrelated to the administration of the vaccine" are those "which are shown to have been the agent . . . principally responsible for causing the petitioner's illness, disability, injury, condition or death."
Even if petitioners had established their case by a preponderance of the evidence, their arguments fail because respondent has proven that the SCN1A mutation—a factor unrelated to the administration of the vaccines—is the agent solely responsible for causing H.E.F.'s Dravet syndrome and resultant neurological injuries.
Compensation has been denied in similar cases based upon a finding that the SCN1A mutation was a "factor unrelated to the administration of the vaccine" and the agent solely responsible for causing Dravet syndrome in a child.
In
Madison subsequently underwent genetic testing which revealed that she had a SCN1A mutation.
In
Special masters have similarly denied compensation in other SCN1A cases. The Federal Circuit's decision in
Two SCN1A cases were recently on review at the Court of Federal Claims. In both cases, the court upheld the special master's denial compensation to petitioners. In
Likewise, in
Here, respondent has put forth preponderant evidence establishing that H.E.F.'s SCN1A mutation, a factor unrelated to the administration of the vaccines, is the agent solely responsible causing her Dravet syndrome.
To prove
Respondent's expert, Dr. Raymond, explained the pathophysiology of Dravet syndrome.
Resp't Ex. C at 5.
Both parties filed medical articles and studies which establish that the international medical community generally agrees that vaccinations are not the cause of Dravet syndrome and that the SCN1A mutation is responsible for causing the disease. For example, the authors of the Brunklaus study,
Likewise, Professor Dr. Berten Ceulemans from the Department of Child Neurology at the University of Antwerp, Belgium, and her colleagues conducted a clinical study
In the McIntosh
In the Harkin article
Here, respondent has established by a preponderance of the evidence that the SCN1A mutation is the sole cause of H.E.F.'s Dravet syndrome and the resulting neurological condition.
The second prong of
H.E.F. developed Dravet syndrome as a result of her genetic mutation, not because she received vaccinations. According to Dr. Raymond, even assuming that H.E.F. had an earlier onset of her seizure disorder, this would not alter her clinical course or outcome. Tr. 328. As explained by Dr. Sachdeo, "H.E.F. . . . would have followed the same clinical course if she had not received any vaccines." Tr. 263. Dr. Raymond and Dr. Sachdeo rely on the McIntosh and Brunklaus articles, respectively, in support of their proposition.
Dr. Raymond also testified that H.E.F.'s SCN1A mutation is the "sole cause" of her seizure disorder, Dravet syndrome, developmental delay, and all of the other features of Dravet syndrome. Tr. 340. Both Dr. Raymond and Dr. Sachdeo testified that it is not necessary to invoke an environmental factor, like the vaccination, to explain H.E.F.'s condition. Tr. 161.
The last element of causation is proof of a proximate temporal relationship between the vaccination and the injury.
Petitioners frame the injury here as vaccine-caused and/or vaccine-aggravated Dravet syndrome. In reality, the only temporal relationship is between the vaccination and H.E.F.'s first two seizures. H.E.F. did not manifest the criteria for Dravet syndrome for months after her first seizure, and so there is no temporal relationship between her vaccinations and the onset of her Dravet syndrome. Moreover, H.E.F. had no brain damage after the vaccination at issue. Therefore, while H.E.F. did not have an injury that was temporally associated with the vaccination at issue, her initial seizures were, in hindsight, a suspicious sign that she might develop Dravet syndrome, or the initial manifestation of her genetic mutation. That fact alone does not establish a vaccine-related injury.
Respondent's experts, on the other hand, state that H.E.F.'s clinical course, timing of the onset of her initial seizure and overall outcome were consistent with Dravet syndrome. Therefore, the undersigned finds by a preponderance of the evidence that respondent has satisfied
For the reasons discussed above, the undersigned finds that petitioners have not established entitlement to compensation and their petition must be dismissed. In the absence of a timely filed motion for review filed pursuant to Vaccine Rule 23, the clerk is directed to enter judgment consistent with this decision.
