CHRISTIAN J. MORAN, Special Master.
Charlene Ellis is the mother of X.G., a boy with multiple health problems, which began before his birth.
Ms. Ellis does not claim that any vaccine caused X.G.'s delayed development. Rather, Ms. Ellis alleges that a set of vaccinations, most notably the diphtheria-tetanus-acellular pertussis (DTaP) vaccination, caused him to suffer a seizure disorder. Ms. Ellis's claim is grounded in the (undisputed) temporal sequence that the DTaP vaccination occurred one day before X.G.'s first seizure. To assist her in prosecuting her claim, Ms. Ellis retained a pediatric neurologist, Marcel Kinsbourne.
The Secretary does not agree that the DTaP vaccination affected X.G. adversely. For his part, the Secretary relies upon a practicing pediatric neurologist, Elaine Wirrell. Dr. Wirrell opines that either the CMV infection or the genetic mutation could have caused (and mostly likely did cause) X.G.'s seizure disorder. Dr. Wirrell further disputes the theory of causation.
The parties agreed to submit this matter on the papers. The better evidence is consistent with the Secretary's position. The Secretary has established that either the CMV infection or the genetic mutation was the likely cause of X.G.'s seizure disorder. This finding is consistent with the medical literature and consistent with the opinion of Dr. Wirrell. Dr. Wirrell is more qualified than Dr. Kinsbourne. Her reports are comprehensive, address points in depth, and are supported by medical literature. In contrast, Dr. Kinsbourne's reports overlook or skirt around issues and contain opinions not consistent with medical literature. Thus, the undersigned credits Dr. Wirrell's opinion rather than Dr. Kinsbourne's opinion. To the limited extent that the treating doctors have expressed opinions about the cause of X.G.'s problems, they align with Dr. Wirrell. Finally, Ms. Ellis has not established, on a more-likely-than-not basis, that the vaccination either caused or significantly aggravated X.G.'s seizure disorder.
X.G.'s very early medical history is reviewed in some detail because, as one of his doctors later said, his "prenatal and perinatal courses were complicated." Exhibit 45 at 76.
On January 6, 2010, Ms. Ellis went to an office of Planned Parenthood, seeking a pregnancy test. She reported that her last menstrual period was on November 9, 2009. Exhibit 1 at 12. (These dates help estimate stages of fetal development.) The pregnancy test was positive for the child Ms. Ellis would name X.G.
At conception, X.G. had a mutation in a gene known as MED13L and a mutation in a gene known as LMNA. Exhibit 58 at 11, 23.
When the genetic testing was done in 2016, Ms. Ellis was tested, but X.G.'s father was not. The genetic testing on Ms. Ellis revealed that she did not have the MED13L mutation. The absence of genetic testing for X.G.'s father meant that Ambry Genetics could not determine whether X.G.'s "alteration occurred in a de novo fashion." Exhibit 58 at 14.
X.G.'s genotype was heterozygous, meaning he had different alleles. Exhibit 58 at 11;
Ambry Genetics classified X.G.'s genetic mutation as a "variant of uncertain significance." "Overall, the evidence suggests that the identified MED13L alteration is possibly the cause of the patient's clinical symptoms." Exhibit 58 at 11. The Ambry Genetics report references 11 articles about the MED13L gene.
After referencing some of these articles, Dr. Kinsbourne opined that "The likelihood of a child with a MED13L variant having seizures without further provocation is somewhat elevated relative to the general population, but is far from meeting the more-likely-than-not standard." Exhibit 59 at 2. Dr. Wirrell, however, took a different view. She stated "the literature provides supportive evidence that MED13L is in fact an independent risk factor for epilepsy." Exhibit KK at 1.
Based upon some of the material that Ambry Genetics cited, the Genetic and Rare Disease Information Center of the National Institutes of Health stated: "Other features of MED13L haploinsufficiency syndrome include . . . recurrent seizures (epilepsy)." Court Exhibit 1001.
Notwithstanding this genetic mutation, Ms. Ellis's pregnancy appeared to continue normally for a while.
CMV infections are either asymptomatic or symptomatic with approximately 90 percent deemed asymptomatic. Exhibit C (
The severity of an in utero CMV infection depends upon many factors, including the time the virus is acquired. Exhibit G (Vlatka Mejaški Bošnjak et al.,
Although the experts did not explain how the brain develops in utero as well as they could have, the referenced articles provide helpful background information. "Three distinct but overlapping processes are involved in the development of the cerebral cortex, namely neuronal and later, glial proliferation, neuronal migration and cortical organization." Exhibit 50 (Renzo Guerrini et al.,
A symptomatic congenital CMV infection can cause various consequences.
Migration disorders are associated with epilepsy. In one study, 19 patients had a migration disorder from a CMV infection and six of them suffered from epilepsy. Exhibit 35 (Yasuhiro Suzuki et al.,
On the other hand, a study of 14 patients with symptomatic congenital cytomegalovirus infection found "no correlation between migration disorders . . . and epilepsy." Exhibit J (Renzo Manara et al.,
Microcephaly, in turn, is associated with epilepsy. For example, Manara and others, who had found no correlation between migration disorders in epilepsy, concluded that "microcephaly is the most specific predictor for severe neurological sequelae." Exhibit J (Manara) at 963. They explained that microcephaly "can be considered an indirect sign of severe nervous tissue loss resulting from an early damage to the germinal matrix, which is known to be selectively vulnerable to CMV infection."
Data about CMV infections and seizure disorders are found in at least two studies. Dr. Kinsbourne pointed to Boppana. Exhibit 20 at 1. In Boppana, of 105 patients with symptomatic congenital CMV infection, 7 (or approximately 7 percent) had seizures. Exhibit 21 (Boppana) at 95 (table 2). An increased frequency of seizures was reported by Alarcon and group. Exhibit I at 830. There, 8 of 23 (or 34 percent) children born with symptomatic congenital CMV infection had seizures.
As previously noted, the May 28, 2010 ultrasound showed a slightly small fetus. The next ultrasound, which was performed on July 30, 2010, also showed a small fetus. Exhibit 2.2 at 38-39 / pdf 3-4;
The delivery summary records that X.G. was born on August 3, 2010. Exhibit 2.1 at 16. Due in part to deep decelerations, Ms. Ellis underwent an emergency Caesarean-section. Exhibit 3.3 at 126-27 / pdf 27-28. In the report from the operation, the doctor commented that there was a "true knot" in X.G.'s umbilical cord.
X.G.'s Apgar scores were 9 and 9. Exhibit 2.1 at 16. His birth weight was 2,435 grams (5 pounds 6 ounces). His length was 19 inches and his head circumference was 30 centimeters. Exhibit 4.1 at 4. The neonatologist ordered a series of tests. Exhibit 4.1 at 6. As Dr. Wirrell outlines, many tests turned out normal.
However, one test showed abnormal results. X.G.'s urine tested positive for CMV infection. Exhibit 4.1 at 26. Again, because the CMV infection is so significant, it bears repeating that the experts agree that X.G. had a CMV infection in utero. Exhibit 20 at 1.
Because of X.G.'s intrauterine growth retardation, he was sent for an ultrasound of his head. The impression was "mild hydrocephalus." Exhibit 4.2 at 41 pdf 6. Hydrocephalus is "a condition marked by dilation of the cerebral ventricles."
In light of the detection of CMV, at discharge Ms. Ellis was directed to follow up with a pediatric neurologist and a pediatric ophthalmologist. Exhibit 4.1 at 5.
Before continuing to the remainder of X.G.'s medical history, it should be emphasized that X.G. was born with the two conditions that Dr. Wirrell identifies as the likely causes of his seizure disorder: a genetic mutation and a congenital CMV infection. When Dr. Kinsbourne wrote his first report, doctors did not know about the genetic mutation. Yet, at the time of Dr. Kinsbourne's first report, doctors had identified the X.G.'s in utero CMV infection. Without identifying the in utero CMV infection as the cause of X.G.'s problems, Dr. Kinsbourne still recognized that X.G. had problems before the vaccination. He wrote: "X.G. sustained severe prenatal cortical damage, which led to deranged development of cortex and secondary microcephaly." Exhibit 18 at 2. The unfortunate nature of this "severe prenatal cortical damage" became apparent in the ensuing months.
On September 29, 2010, the Suffolk County Department of Health Services administered a set of vaccinations to X.G. Exhibit 14 at 52, 64 (vaccination chart). The handwritten notes suggest that this visit was relatively routine. Although the doctors ordered a repeat of the New York State newborn screen, the results were normal.
X.G. saw pediatric neurologists on October 28, 2010. One pediatric neurologist was a fellow, Julia Holtmann, and the other was the chief of pediatric neurology, Joseph Maytal. Dr. Holtmann, who primarily authored the report, described some parts of X.G.'s history including his premature birth. Dr. Holtmann stated the reason for the visit was the ultrasound, performed when X.G. was two-days old. Dr. Holtmann's report does not mention CMV. For X.G.'s history in the approximately three months since his birth, Dr. Holtmann recorded that he "has been well. He feeds well. He appears to hear and see well." Exhibit 7 at 1. In the neurologic examination, Dr. Holtmann stated that X.G. "makes good eye contact. He tracks 90 degrees. . . . He turns his head when his name is being called."
X.G. returned to his pediatrician at Suffolk County on December 20, 2010. He was given a second set of vaccines. Exhibit 14 at 52, 64. The handwritten notes from this appointment are not easily read.
The next medical record suggests that the pediatrician (Dr. Malki) referred X.G. to a pediatric neurologist due to "intermittent arching of back" and, apparently, was requesting early intervention. Exhibit 7 at 11. This appointment took place at Schneider Children's Hospital, part of the North Shore-Long Island Jewish Health System on January 6, 2011. The pediatric neurologists noted that X.G. had a history of intrauterine growth retardation and germinal matrix hemorrhages with hydrocephalus. They did not mention CMV in their note. The examination appears basically normal, except the motor exam says mild increased tone. They recommended early intervention and follow up in two months.
The record appears not to contain any report of a follow up appointment with Dr. Holtmann, Dr. Maytal, who saw X.G. on October 28, 2010, or the pediatric neurologists from Schneider Children's Hospital. Instead, the next visit appears to be a visit for routine care at Suffolk County on April 8, 2011.
In this appointment, Ms. Ellis provided a history in which she described X.G. as "grasping, holding toys, throwing toys."
On the next day, April 9, 2011, an ambulance brought X.G. to the emergency department of Good Samaritan Hospital. His parents reported that except for receiving vaccinations yesterday, he was otherwise in good health. He came to the emergency department because "His eyes rolled back and he was shaking." Exhibit 5.2 at 152 / pdf 65. X.G. did not vomit, did not have a fever, and did not have a runny nose.
In the hospital, another doctor (Oleg Goloubenko) obtained a slightly different history. Dr. Goloubenko's history begins with the vaccinations from a day earlier. He records that some vaccines were given for a third time and that for the first two doses, X.G. developed "low-grade fever." Exhibit 5.2 at 148 / pdf 61.
Dr. Goloubenko recorded that X.G. was apparently in good health this morning. Then, in the afternoon, he became less active and smiled less. While in a car going shopping, "all of a sudden, he developed jerking movements in his upper and lower extremities, whole body associated with rigidity and eyes and head deviation to the right." "Convulsions lasted for two minutes and then stopped on [their] own."
In the emergency department, X.G. had a second episode and was given Ativan. Then, Dr. Goloubenko was present for a third episode, lasting 15-20 seconds.
One of the tests was a CT of the brain without contrast. The interpreting radiologist, Wan Kim, found "a diffuse mild dilation of the ventricles as well as a widened subarachnoid space as well as prominent sulci." Dr. Kim continued: "It could be physiological at this age group with underdeveloped CSF resorption function of the granulation. But, it appears to be unusually more prominent." Exhibit 5.2 at 143/pdf 56.
On April 10, 2011, Mikhail Mirer, who is identified as a pediatric neurologist, consulted. Dr. Mirer stated that X.G.'s past medical history included birth at 34 weeks of gestational age, hydrocephalus, and a sonogram. Dr. Mirer also records that X.G. "was followed by [a] neurologist every two months since birth. As per mother there were no major concerns except the history of hydrocephalus. Child was not recently sick." Exhibit 5.2 at 166/pdf 79.
The MRI without contrast took place on April 10, 2011 and indicates that X.G.'s history included hydrocephalus. The radiologist's impression was that the MRI showed abnormalities. Specifically, "Lateral ventricular prominence out of proportion to the adjacent sulci, particularly at the temporal horns. This can reflect a degree of hydrocephalus although there is no current evidence of transependymal flow CSF to suggest an acute process. Findings may also potentially represent anatomic variation." Exhibit 5.2 at 145/pdf 58.
According to a record from April 22, 2011, X.G. was discharged on April 11, 2011. His parents were instructed to give him phenobarbital four times per day and to follow up with Dr. Mirer. Exhibit 5.1 at 3.
A handwritten note from Suffolk County Department of Health Services indicated that Ms. Ellis was having difficulty scheduling the follow up appointment with a neurologist. It appears that some doctors were not in her insurance company's list of providers. Exhibit 14 at 58.
These obstacles did not completely defeat X.G.'s parents in their pursuit of medical care for their child. On April 20, 2011, X.G. was seen by a pediatrician for Suffolk County. The chief complaint states: eight-month old male "seen [at] Good Sam. Hospital 4/9/11 for seizures. Here for [follow up] and lab work." The current medications included phenobarbital 1 tsp. 2x daily. The doctor's notes, which are again difficult to read, indicate that X.G. had had "no further seizures." The doctor also indicates that X.G. has an appointment with a pediatric neurologist on May 26, 2011, and the pediatrician wanted the results of laboratory studies to be faxed to Dr. Mirer. Exhibit 14 at 57. Although blood was drawn during the appointment on April 20, 2011 (
Later, on April 20, 2011, at approximately 10:30 PM, Ms. Ellis brought X.G. to the Emergency Department at Southside Hospital. She informed the triage nurse that X.G. has been "having seizure activity every hour, lasting approx. 1 min and then gradually lasting longer, since 430 pm." Exhibit 15 at 45. The triage nurse also reported a "similar episode last week, went to good sam given phenobarbital rx."
A doctor at Good Samaritan Hospital, Mercy Drew, saw him and dictated a report at 4:50 AM on April 21, 2011. The history that Dr. Drew obtained was slightly different from the report given in the emergency department with respect to the events on April 20, 2011.
Exhibit 5.1 at 28.
For X.G.'s history a few weeks earlier, Dr. Drew's history is again a little different. Dr. Drew accurately records that X.G. was "first admitted to Good Samaritan PICU on the 9th of April 2011." She also states that he had "CT scan, MRI, and EEG done which revealed hydrocephalus."
In the PICU, someone completed a "growth and development assessment." The form contains three columns, with one column containing various milestones. Each milestone is associated with two boxes that could be checked, one for "exam" and the other for "history." The person who filled out the form placed an X in the history box for every milestone through 6-9 months. There are no X's in the "exam" column. Exhibit 5.1 at 14.
Later on April 21, 2011, Dr. Mirer saw X.G. again. Dr. Mirer commented that: "Parents were given direct instructions about the dosage and the schedule of the medication, however, the parents decided to stop the medication because child remained seizure-free. On admission, the phenobarbital level was 6 which is below therapeutic."
X.G. underwent another CT scan of his brain on April 22, 2011. The interpreting radiologist, Dr. Kim, found no significant change from the CT scan on April 9, 2011.
Later on April 22, 2011, X.G. was discharged. The discharge summary emphasized that Dr. Mirer "feels this is a compliance issue and the patient needs to take his phenobarbital twice a day on a daily basis without missing a dose. The patient also needs to follow up with a neurologist either himself or other neurologist at LIJ."
On April 28, 2011, X.G. saw a pediatrician from Suffolk County. X.G.'s mother and father told Dr. Rodriguez that X.G. has a history of seizures and hydrocephalus. Under development, Dr. Rodriguez has noted that by history, he is "not sitting by himself." Exhibit 9 at 6. Dr. Rodriguez's plan was for X.G. to follow up with the service from Good Samaritan Hospital.
On May 5, 2011, X.G. returned to Schneider Children's Hospital of the North Shore-Long Island Jewish Health System, where he had been seen on January 6, 2011. The interval history indicates that X.G. has had "2 seizures since last visit. [First] one was April 9, [second] one week later" and contains an accurate recitation about details. For development, the person obtaining the history recorded that X.G. "can roll, tracks, hears, can pull to sit but not sit up [with] support." For the neurological examination, the doctor indicated that X.G. had increased "tone throughout, moves [extremities] spont[aneously]." The pediatric neurologists recommended screening for hearing problems, an ophthalmologic examination, and a routine EEG. Exhibit 7 at 10.
The EEG took place on May 23, 2011, and appears to have lasted for approximately 20 minutes. The doctors who interpreted the EEG, Dr. Maytal and Dr. Patricia Krief, stated that the EEG showed spikes, indicating "the presence of a potentially epileptogenic focus over the left central head region." Exhibit 7 at 17-18.
In the Suffolk County records, there is a page titled "Pediatric Problem List." It contains four entries with the most recent being May 17, 2011. There, someone has written: "[history of] seizure 4/9/11. [Follow up] Ped. Neurology. No flu shot. [History of] seizures." Exhibit 14 at 66.
On June 24, 2011, Ms. Ellis brought X.G. to the Southside Hospital Emergency Department because X.G. "had 3 seizures today." Exhibit 15 at 31. Ms. Ellis informed the doctor that X.G. takes phenobarbital for his seizures and "she is compliant."
At the Cohen Children's Medical Center, X.G. was examined by one doctor upon admission. Exhibit 16.1 at 8. It also appears that an EEG was performed on June 24, 2011, although an actual record from the EEG is not readily apparent.
A pediatric neurologist (Dr. Malbari) consulted. Her notes states: "Phenobarbital level found to be subtherapeutic. [Patient] now [status post] bolus and increase of phenobarbital dose. . . . [Patient] doing well, will [discharge] home after wife gets out of work. [Follow up] in clinic."
This follow-up appointment took place with Dr. Malbari at Cohen Children's Medical Center. For history, Dr. Malbari mentions that X.G. had "microcephaly, epilepsy, IUGR? [intrauterine growth restriction], urine CMV (+)." He has been doing better after the dose of phenobarbital was increased. For development, X.G. babbles and rolls over, but he cannot sit without support. Exhibit 7 at 8.
After the July 2011 visit at Cohen's Children's Medical Center, the routine medical records generally contribute relatively little information about the cause of X.G.'s seizures. Thus, although all the medical records have been reviewed, the remaining discussion omits some of them and summarizes others more briefly.
The seizure in June 2011 was X.G.'s last until April 2012, when he was being weaned from phenobarbital and was starting Keppra.
On September 21, 2012, X.G. underwent an MRI of the brain without contrast at the North Shore-Long Island Jewish Health System. The radiologists listed X.G.'s history as a "2-year-old with seizures and microcephaly" and they did not have access to any previous MRIs. The MRI revealed: "A wide spread neuronal migration anomaly involv[ing] both cerebral hemispheres, with multiple areas of cortical thickening/cortical dysplasia, undersulcation, and blurring of the gray matter white matter junction." Exhibit 8 at 1. Because this MRI showed "neuronal migration," Dr. Wirrell and Dr. Harum discussed its significance extensively.
X.G. continued to experience seizures periodically. He had one on November 18, 2012 (exhibit 15 at 2), and another on January 10, 2013 (exhibit 10 at 8).
On April 16, 2013, X.G. had his first visit at the office of his new pediatricians, Weill Cornell Physicians. The first doctor to see him was Matthew Marks. Dr. Marks began his notes by stating that X.G.'s care was being transferred from Mid-Suffolk pediatrics, where he was last seen at 2 years old.
Dr. Marks's referral for an orthopedic consultation was to the Hospital for Special Surgery, which took place on May 9, 2013. Dr. Venu Nemani from the spina bifida and pediatric orthopedic clinic of the Hospital for Special Surgery saw him. The reason for the consultation was developmental delay and not walking. The history that Dr. Nemani obtained states that X.G.'s "birth history included an anoxic brain injury when the umbilical cord was found to be in a knot." Exhibit 13 at 6.
After the visit at the Hospital for Special Care, X.G. returned to Weill Cornell on May 24, 2013.
On August 9, 2013, X.G. returned to Weill Cornell. He saw a pediatrician and had lab work done. Exhibit 45 at 17, 21-25. On October 22, 2013, Dr. Marks saw X.G. again. Dr. Marks noted that X.G.'s immunizations were not up to date and that Ms. Ellis thought the immunizations precipitated his first seizure. Exhibit 45 at 26-30. In another visit on January 29, 2014, the doctor noted that Ms. Ellis was refusing more immunizations.
On March 21, 2014, Matthew McCarthy, a pediatrician at Weill Cornell, saw X.G. Dr. McCarthy referred the family to pediatric genetics and ordered an EEG.
A four-year old checkup took place on September 2, 2014, with Denver Brown, a pediatrician. Dr. Brown noted that Ms. Ellis did not show up for the EEG, which had been ordered in March, and that the referral for genetics was still outstanding. In X.G.'s history, Dr. Brown stated that he had a seizure about one month ago. Dr. Brown administered another dose of the DTaP and IPV vaccines and again referred X.G. to neurology and genetics. Exhibit 45 at 42-48.
A continuous video EEG from October 31, 2014, was abnormal.
In March 2015, Ms. Ellis was working with a school to develop an Individualized Education Plan for X.G. in kindergarten. At this time, his developmental age was approximately 18 months. His seizures were "fairly well controlled on Keppra." Exhibit 45 at 60-64 (record from Jennifer Cross, pediatrician with specialty in child development).
It appears that Dr. Cross again referred X.G. for genetic testing because on May 24, 2016, Lilian Cohen, a medical geneticist at Weill Cornell, examined X.G. at Dr. Cross's request. Dr. Cohen recommended whole exome sequencing. Exhibit 58 at 29-33. Ms. Ellis consented to this genetic testing on June 15, 2016.
Ambry Genetics issued its report identifying the alteration in the MED13L and LMNA genes on September 6, 2016. Exhibit 58 at 11, 23. X.G. was approximately 6 years old when these genetic mutations, which were present in him since conception, were discovered.
On March 24, 2017, a 32-minute video EEG was abnormal. The EEG showed abundant epileptiform discharges. Exhibit 45 at 83-84. On the day of the video EEG, another pediatric neurologist, Eric James Mallack, saw X.G. for his seizures. Dr. Mallack recorded that the "last seizure [was] 3 weeks ago, 4 months ago was last seizure prior to that." Dr. Mallack also stated that X.G. was diagnosed with MED13L syndrome based upon the Ambry testing.
The records from March 24, 2017, are the most recent medical records filed.
Through her attorney, Ms. Ellis filed her petition on May 17, 2013. The relatively skeletal petition alleges that the April 8, 2011 vaccinations caused or significantly aggravated X.G.'s seizure disorder and developmental delays. Ms. Ellis periodically filed medical records until November 4, 2013, when she filed her statement of completion.
The Secretary reviewed this material in his report filed pursuant to Vaccine Rule 4, on November 22, 2013. The Secretary's summary of medical records noted that X.G. was born with microcephaly, suffered from intrauterine growth retardation, and tested positive for CMV. Resp't's Rep. at 2. The Secretary also identified medical records in which doctors were concerned about X.G.'s development before he was vaccinated. Resp't's Rep. at 3-4 (citing Dr. Holtmann's October 28, 2010 record, the December 20, 2010 pediatrician's record, the January 16, 2011 referral to early intervention, and the April 8, 2011 diagnosis of developmental delay). Ultimately, the Secretary recommended against compensation, because Ms. Ellis did not meet her burden of proof. In particular, Ms. Ellis had not presented a report from a treating doctor who opined that a vaccination harmed X.G. and had not presented an opinion from a specially retained expert on the same subject. Resp't's Rep. at 11-14. Moreover, the Secretary identified the congenital CMV infection as an alternative explanation for X.G.'s developmental delays and seizures.
In the ensuing status conference, the parties discussed the issues in the case including whether Ms. Ellis would proceed on a significant aggravation theory. Ms. Ellis requested 75 days to produce an expert report because of the complicated issues.
Ms. Ellis filed the first report from Dr. Kinsbourne on May 12, 2014. Exhibit 18. This report is relatively brief, approximately 3 ½ pages long. Dr. Kinsbourne did not discuss the CMV infection. Dr. Kinsbourne also omitted any discussion of the medical records in which a doctor expressed concerns about X.G.'s development from October 20, 2010 through April 8, 2011. Dr. Kinsbourne opined that the acellular pertussis vaccination significantly aggravated X.G.'s pre-existing condition and caused him to suffer a severe refractory seizure disorder. Exhibit 18 at 4.
Ms. Ellis was instructed to obtain a supplemental expert report from Dr. Kinsbourne. Based upon
Ms. Ellis responded by filing a 1 ½ page report from Dr. Kinsbourne. Dr. Kinsbourne stated that X.G.'s "brain injuries are consistent" with congenital CMV infections. With respect to the question of how X.G. would have developed but-for the vaccinations, Dr. Kinsbourne stated: "we cannot know whether X.G. would have joined the minority of affected children who become epileptic had he not receive DTaP vaccination that ushered in his seizure disorder." Exhibit 20 at 1.
Ms. Ellis was again instructed to obtain a supplemental report. Dr. Kinsbourne was expected to provide an opinion that differentiated disabilities due to the congenital CMV infection from injuries induced by the vaccination. Order, issued June 25, 2014.
This process took a relatively lengthy amount of time. On September 3, 2014, Ms. Ellis's attorney represented that he was attempting to retain a specialist in pediatric infectious diseases with knowledge about CMV infections, Karen Harum. Mr. Gage represented that although Dr. Harum has good qualifications as a medical doctor, she did not have much experience as an expert in the Vaccine Program. To guide Dr. Harum and any other experts, the undersigned proposed a set of instructions. Order, issued February 3, 2015. On March 6, 2015, Ms. Ellis represented that Dr. Harum will opine about CMV exposure and Dr. Kinsbourne will address how the acellular pertussis vaccine can cause an encephalopathy — a neurologic topic.
Ms. Ellis filed the first report from Dr. Harum on May 1, 2015. Primarily because X.G. had an eight-month history of "mostly normal" development, Dr. Harum expected that X.G. would have had a much better outcome. Exhibit 30 at 3-4.
Ms. Ellis also filed a supplemental report from Dr. Kinsbourne that more directly addressed the elements of a significant aggravation claim. Exhibit 38. In response to all these reports, the Secretary filed a single report from Dr. Wirrell. Exhibit D. Dr. Wirrell's first report was approximately 12 ½ pages. Her recitation of facts from the medical records was both detailed and accurate.
Dr. Wirrell's opinion was that X.G.'s congenital CMV infection caused a malformation of cortical development, which made the risk of developing epilepsy very likely (over 80-90 percent). Exhibit D at 13. In addition, Dr. Wirrell challenged many assertions made by Dr. Kinsbourne and Dr. Harum.
Dr. Wirrell brings out that an infant's brain is poorly myelinated. Myelination is a process that is most pronounced in the first 2-3 years of life. Until myelination become sufficiently advanced, infants and toddlers cannot accomplish complex motor coordination such as walking and talking. Therefore, impairments in an infant's brain may not become apparent for several months or even 1-2 years. Exhibit D at 12.
The myelination process is one reason why Dr. Wirrell disagrees with Dr. Harum's assertion that X.G. was "nearly normal" at 8 months of age. In addition, in Dr. Wirrell's view, the "medical records provided contradict this statement, as there are several references to developmental delay, as well as the findings of jitteriness, increased tone, and tendency to arch his back, which are in keeping with early signs of motor delay." Exhibit D at 12.
Dr. Wirrell also addressed the temporal sequence in which X.G.'s first seizure closely followed his vaccinations. "[I]n children like X.G., with an underlying predisposition to epilepsy due to a severe brain malformation, intercurrent illness, fever or other psychological or physiological stressors may lower the seizure threshold, unmasking epilepsy. However, such illnesses or stressors are NOT the cause of the epilepsy, but simply lower the seizure threshold such that epilepsy is unmasked." Exhibit D at 12.
Dr. Wirrell's report provoked additional questions for Dr. Harum and Dr. Kinsbourne.
Dr. Harum answered the questions asked in the September 11, 2015 order in a report dated November 5, 2015. Dr. Harum addressed how the process of myelination affects MRI imaging. She stated:
Exhibit 39 at 1-2. Dr. Harum's reference to seeing the MRI images started the parties on a relatively unproductive detour.
In a November 12, 2015 status report, Ms. Ellis contended that a "`battle ground' in this case is what the MRI's do, or do not, show." Thus, Ms. Ellis planned to obtain the MRI images, to transmit them to a pediatric neuroradiologist at Stanford University (Dr. Barnes), and to obtain a report from him. Ms. Ellis further proposed that after Dr. Barnes wrote a report, Dr. Kinsbourne would answer the questions posed in the September 11, 2015 order. Then, Dr. Wirrell would respond. Ms. Ellis further offered that all these steps could fit within the schedule leading to a hearing on March 8-9, 2016.
These plans, however, went awry. By January 6, 2016, Mr. Gage had obtained the MRI images from the April 10, 2011 MRI at Good Samaritan Hospital. Exhibit 5.2 at pdf 58. However, Mr. Gage was having difficulty obtaining images for the September 22, 2012 MRI from North Shore-Long Island Jewish Health System. Exhibit 8 at 2. Without the images, Dr. Barnes could not write his report. Thus, the schedule for the March 8-9, 2016 hearing was cancelled. Order, issued Jan. 7, 2016.
After more complications in obtaining the images from the 2012 MRI, Mr. Gage received them and sent them to Dr. Barnes. Dr. Barnes eventually told Dr. Kinsbourne that X.G. "had polymicrogyria, which is diffuse throughout both cerebral hemispheres." Exhibit 43 (report from Dr. Kinsbourne). Dr. Barnes also told Dr. Kinsbourne that he (Dr. Barnes) was overcommitted and could not write a report.
In an August 30, 2016 status conference, the parties discussed the information that Dr. Barnes had provided via Dr. Kinsbourne. Dr. Barnes did not add meaningful information to the point Dr. Harum had raised in her November 5, 2015 report. There, Dr. Harum said that the migrational abnormality apparent on the 2012 MRI was not that significant in part because it was not apparent on the 2010 MRI. Exhibit 39 at 1. About ten months later, Dr. Barnes had not commented about any differences between the two MRIs, or, more precisely, Dr. Kinsbourne did not have any comment from Dr. Barnes in Dr. Kinsbourne's report.
Although Ms. Ellis decided not to obtain a report from a neuroradiologist, the Secretary wanted to give his expert, Dr. Wirrell, a chance to review the MRI images. She provided her opinion in a report filed as exhibit V on September 6, 2016.
Dr. Wirrell begins with a review of the more recent MRI, which was conducted on September 21, 2012. Dr. Wirrell interprets the MRI images as showing that X.G. has "diffuse polymicrogyria, maximal in the perisylvian regions, diffuse white matter loss, ventriculomegaly, and cerebral atrophy, all of which would be consistent with a CMV infection in the late second trimester." Exhibit V at 2.
Dr. Wirrell then reviews the earlier MRI, which was taken when X.G. was eight-months old on April 10, 2011. Dr. Wirrell explains developmental features of children, particularly children under one year of age, make obtaining clear information about brain disease difficult. Exhibit V at 2.
Dr. Wirrell further explains that "it is my opinion that the diffuse malformation of cortical development, along with associated white matter changes and cerebral atrophy, resulting from CMV infection in the late second semester, are the cause of [X.G.'s] epilepsy and developmental delay. These changes clearly predate his immunization."
Dr. Wirrell also repeated her previously expressed opinion about the temporal relationship between the vaccination and the seizures. "In children who are predisposed to epilepsy as a result of a severe structural brain abnormality, concurrent physiologic stressors, such as illness, fever, sleep deprivation or vaccination could
After the parties informally communicated mutually convenient dates for a hearing on August 23-24, 2017, the undersigned issued an order for that event. The order also required Ms. Ellis to submit updated medical records, Ms. Ellis to file a pre-hearing brief, and the Secretary to file a pre-hearing brief. Orders, issued Sept. 21, 2016, Oct. 28, 2016. On November 14, 2016, a status conference was held to discuss the content expected in the forthcoming briefs.
After the reminders about the need to file updated medical records, Ms. Ellis filed records from the Hospital for Special Surgery and Weill Cornell (exhibits 44-45) on April 21, 2017. Collectively, these medical records provide information about X.G. from May 2013 through March 2017.
Also, on April 21, 2017, Ms. Ellis filed her prehearing brief and supplemental reports from Dr. Harum (exhibit 46) and from Dr. Kinsbourne (exhibit 47). Dr. Harum's report is simplistic, consisting of three paragraphs. In the first paragraph, she discusses X.G.'s condition at the age of eight months, before he started to have seizures. In the second paragraph, she describes X.G.'s condition at the age of five years when he had "spastic tetraplegic cerebral palsy and an ongoing variety of seizures on Keppra." Exhibit 46 at 1. In its entirety, the final paragraph reads: "I conclude that X.G.'s condition is significantly worsened by the onset of seizures both in the short-term and in the long term."
Dr. Kinsbourne's April 21, 2017 report was partially in response to the September 10, 2015 order. In answering a question about whether the initial set of seizures caused any lasting damage, Dr. Kinsbourne also responded to Dr. Wirrell's opinion about a lower seizure threshold. Dr. Kinsbourne opined that: "It was the lowering of the seizure threshold that did the lasting damage." Dr. Kinsbourne explained: "It did so by setting in motion a sequence of events that resulted in severe epilepsy and severe mental retardation. `Unmasking a predisposition' amounts to a two-hit process. Susceptibility is provoked into clinical reality by risk factor, the vaccinations. Both of the `hits,' susceptibility and risk factor, are causal." Exhibit 47 at 3. Like Dr. Harum, Dr. Kinsbourne did not discuss the detection of the MED13L gene mutation.
The Secretary filed a response from Dr. Wirrell only one week later. Dr. Wirrell summarized the information from the updated medical records in exhibits 44 and 45. Exhibit AA at 1-2. Unlike Dr. Harum and Dr. Kinsbourne, Dr. Wirrell discussed the MED13L gene mutation. She stated that the patients with a mutation in their MED13L gene have an increased risk for epilepsy. Therefore, X.G. "has both congenital CMV with diffuse cortical malformations . . . and . . . MED13L syndrome which is unrelated to the congenital CMV. Both of these conditions contribute to his significant neurodevelopmental disabilities." Exhibit AA at 2.
On June 30, 2017, Ms. Ellis filed another report from Dr. Kinsbourne. He stated MED13L syndrome "is characterized by developmental delay independent of delay caused by CMV." Exhibit 57. Because X.G. has two independent factors associated with developmental delay, Dr. Kinsbourne could no longer attribute the developmental delay to vaccination. But, Dr. Kinsbourne asserted that "The MED13L syndrome does not feature epilepsy as one of its manifestations. Therefore I continue to adhere to the opinion that . . . X.G.'s seizure disorder was caused by the DTaP vaccination."
Ms. Ellis filed a motion for a ruling on the record. She stated that she "will no longer be pursuing a claim for developmental delay." She asserted that "Petitioner has submitted all the evidence that petitioner believes the special master needs to issue a ruling in this case on the issue of the introduction of seizures." She requested that the special master allow the parties to submit briefs and to cancel the hearing scheduled for August 2017. Pet'r's Mot., filed July 5, 2017.
This motion was denied without prejudice. The undersigned noted that although Ms. Ellis had requested authority to issue a subpoena to obtain the genetic testing from Ambry Genetics, Ms. Ellis had not filed any reports from Ambry Genetics. In addition, the undersigned filed an excerpt from the website of the National Institutes of Health about MED13L syndrome. According to the Genetic and Rare Diseases Information Center, "other features of MED13L haploinsufficiency syndrome include . . . recurrent seizures (epilepsy)." Exhibit 1001 at 1. This information from the National Institutes of Health seemed inconsistent with Dr. Kinsbourne's assertion that "The MED13L syndrome does not feature epilepsy as one of its manifestations." Exhibit 57. Finally, the undersigned suggested that the parties may want to retain experts in the field of genetics. This suggestion was more directed to Ms. Ellis because "[i]n the undersigned's experience, Dr. Kinsbourne's credentials in the field of genetics are not particularly strong.
On the day that the undersigned expressed interest in reviewing the report of genetic testing from Ambry Genetics, Ms. Ellis filed the report as Exhibit 58. As discussed extensively above, the testing by Ambry Genetics is the foundation for the finding that X.G. suffers from a MED13L gene mutation.
Once Ms. Ellis filed the genetic testing from Ambry Genetics, Dr. Wirrell promptly presented a report on the MED13L gene. After citing articles, Dr. Wirrell asserted "the literature provides supportive evidence that MED13L is in fact an independent risk factor for epilepsy. While I believe that the diffuse cortical malformation places [X.G.] at [the] highest risk of seizures, the MED13L mutation further leads to a lowering of the seizure threshold, making it very likely that [X.G.] would have developed epilepsy, regardless of any vaccination." Exhibit KK (report filed July 19, 2017) at 1-2.
On August 1, 2017, a status conference was held to discuss the parties' plans for resolving the case. Ms. Ellis declared that she wanted to proceed with the theory that the vaccines contributed to X.G.'s seizures but she did not anticipate getting a geneticist. The parties agreed that after a time for submitting briefs, the case could be submitted on the papers. Thus the hearing scheduled for August 23-24, 2017 was canceled. Order, issued Aug. 2, 2017.
Dr. Kinsbourne addressed the MED13L mutation for a second time in a report dated August 10, 2017. Although Dr. Kinsbourne had earlier declared that "the MED13L syndrome does
Dr. Wirrell generally disagreed with Dr. Kinsbourne. Exhibit MM. This report appeared to complete the parties' submission of evidence.
The parties then submitted a series of briefs. Ms. Ellis filed an initial brief, dated November 22, 2017, and a reply brief, dated February 5, 2018. The Secretary filed one brief on December 23, 2017.
After the case became ready for adjudication, the undersigned realized that Dr. Kinsbourne had not properly cited an article that apparently showed that from a group of 35 children with an MED13L mutation, six children had seizures.
A petitioner is required to establish her case by a preponderance of the evidence. 42 U.S.C. § 300aa-13(1)(a). The preponderance of the evidence standard requires a "trier of fact to believe that the existence of a fact is more probable than its nonexistence before [he] may find in favor of the party who has the burden to persuade the judge of the fact's existence."
Distinguishing between "preponderant evidence" and "medical certainty" is important because a special master should not impose an evidentiary burden that is too high.
As confirmed in
Four overlapping reasons indicate that Ms. Ellis is not entitled to compensation. The foundational reason is that Dr. Wirrell has persuasively explained that either the in utero CMV infection or the genetic mutation — two factors that are independent from the vaccination — are likely causes of X.G.'s seizure disorder. This reason, in turn, is based upon the subsidiary determination that Dr. Wirrell has much more experience treating children who are like X.G. This background makes her opinions more credible than Dr. Kinsbourne. Next, the weight of opinions from treating doctors align with Dr. Wirrell's opinion. Finally, Ms. Ellis has not established that the vaccinations either caused X.G.'s seizure disorder or significantly aggravated his pre-existing conditions.
When petitioners establish the
Here, the Secretary has identified two factors that are likely to have caused X.G.'s seizure disorder: the congenital CMV infection and the genetic mutation. These factors are both independent of each other and independent of the vaccination.
As discussed above, the CMV infection probably caused two different consequences for X.G.: a migration disorder (more specifically bilateral perisylvian polymicrogyria) and microcephaly. Dr. Wirrell submitted articles showing that both a migration disorder and microcephaly are associated with epilepsy. Based upon these studies and her own work, Dr. Wirrell estimated X.G.'s likelihood of developing seizures solely based on the infection at more than 80 percent. Exhibit D at 13, exhibit AA at 4. Ms. Ellis did not effectively undermine Dr. Wirrell's opinion.
The 2008 Leventer article discussed eight types of malformations of cortical development, including polymicrogyria and tuberous sclerosis.
Dr. Wirrell answered this argument by relying upon the 2010 Leventer article that Ms. Ellis had actually filed as exhibit 54. Exhibit AA at 4. Unlike the 2008 Leventer article, which was about different types of cortical malformations, the 2010 Leventer article was about the specific type of cortical malformation affecting X.G. — polymicrogyria. Within the types of polymicrogyria, the relevant one is bilateral perisylvian polymicrogyria because that is the subtype X.G. has. Leventer and colleagues found that "bilateral perisylvian polymicrogyria had a significantly lower age at seizure onset than unilateral perisylvian polymicrogyria (median age of onset 12 months versus 99 months)." Exhibit 54 (Leventer) at 1424. A median age of onset of 12 months is much closer to X.G.'s actual onset (8 months) and effectively refutes Dr. Kinsbourne's assertion that X.G.'s onset was "far earlier" than expected.
In addition to the consequences of the CMV infection, Dr. Wirrell also proposed that the MED13L mutation could be the cause for X.G.'s seizures. However, in her view, the cortical malformation presented a larger risk than the genetic mutation. Exhibit MM.
Overall, the evidence that an MED13L mutation can cause seizures was persuasive. In other words, the Secretary met his burden of establishing, on a more-likely-than-not basis, that MED13L mutations can cause seizures.
Relying upon Dr. Wirrell and various articles, the Secretary argued that a mutation in the MED13L gene can cause seizures. Resp't's Resp., filed Dec. 23, 2017, at 10. In response, Ms. Ellis did not challenge that the MED13L mutation can cause seizures. Rather, as discussed in more detail below, Ms. Ellis's argument is that the interval between the vaccination and the onset of seizures (approximately one day) necessarily implicates the vaccination as contributing to the seizures.
Ms. Ellis's brief's apparent acquiescence to the point that a mutation in the MED13L gene can cause seizures is consistent with the final position of her expert. In Dr. Kinsbourne's last report, he opined "epileptic activity may occur but is not among the core attributes of disorders associated with MED13L variants. The likelihood of a child with a MED13L variant having seizures without further provocation is somewhat elevated relative to the general population." Exhibit 59 at 2.
Taken with the opinions of Dr. Wirrell, Dr. Kinsbourne's acknowledgment that "epileptic activity may occur . . . with MED13L variants" means that a preponderance of evidence supports a finding that MED13L variants can cause seizures. Nevertheless, it is important to recognize that the evidence does not point in one direction.
The undersigned's experience in hearing other cases involving genetic mutations (
The unanswered questions make the Secretary's case with respect to the genetic mutation less strong than the evidence presented in a case involving a mutation in a different gene, known as SCN1A. There, the Secretary presented the opinion of a board-certified geneticist and the undersigned characterized "the evidence about the causal role of the mutation" as "clear and convincing."
Of course, X.G.'s case is different from
In an attempt to counter this finding, Ms. Ellis argued that Dr. Wirrell "has admitted that the April 8, 2011 vaccinations caused the onset of X.G.'s seizures." Pet'r's Pre-Hear'g Br., filed Apr. 23, 2017, at 14;
Dr. Wirrell actually said the following:
Exhibit D at 12.
Dr. Wirrell expressed a similar opinion in her second report:
Exhibit V at 4.
Dr. Wirrell's distinction between a vaccination unmasking a structural malformation, which leads to an initial seizure, and a vaccination being the cause of a seizure disorder has been endorsed by persuasive Vaccine Program precedent (although other cases have rejected that distinction). Ms. Ellis also did not note the language distinction of a vaccination
In one case, a girl received a set of vaccines, including the DTaP vaccine, at four months and suffered a seizure within seven hours.
While the SCN1A cases were decided relatively recently, an early case in the Vaccine Program also demonstrates that in appropriate cases, special masters have found genetic disorders caused a seizure disorder. Matthew Jordan was born prematurely and suffered from multiple problems, including microcephaly and kidney problems.
Matthew's parents brought a claim in the Vaccine Program, alleging that the DPT vaccination caused him to suffer a residual seizure disorder, which was, at that time, listed on the Vaccine Table. The Secretary attempted to rebut the presumption of causation by establishing a factor unrelated to the DPT vaccination, namely the genetic disorder, caused Matthew's seizure disorder. To meet his burden of proof, the Secretary presented opinions from a board-certified pediatric neurologist, Ihor Rak, and a board-certified geneticist, Leslie Raffel. They generally opined that the DPT vaccination did not cause Matthew's seizure disorder. In a passage foreshadowing Dr. Wirrell's opinion in the present case, the special master summarized the geneticist's testimony:
To counter the Secretary's evidence, Matthew's parents relied upon Dr. Kinsbourne. Much like the present case, Dr. Kinsbourne acknowledged that "a neuromigrational disorder raises the risks of seizures beyond the general population."
On a motion for review, the Court ruled that the special master's analysis was not arbitrary. Substantial evidence, including the disparity in the experience of the testifying experts, supported the findings.
The reasoning in
Federal Circuit precedent also undermines the reasoning in another case in which the special master rejected the Secretary's unmasking theory. The parents of Camille Priest alleged that a DPT vaccination caused their daughter to suffer injuries listed on the Vaccine Table: encephalopathy, residual seizure disorder, and hypotensive-hyporesponsive shock collapse.
Against Dr. Wirrell's opinion, Dr. Kinsbourne seems to demand proof at a level of scientific certainty.
By now, there should be no question that special masters may consider the qualifications and experience of the experts appearing before them.
It should also be apparent by now that Dr. Kinsbourne's experience is lacking. Although Dr. Kinsbourne greatly contributed to the field of pediatric neurology, his advancements stopped in 1991, when he stopped practicing pediatric neurology.
The concerns about Dr. Kinsbourne's lack of current practice in pediatric neurology are neither novel nor, according to appellate authorities, arbitrary. In 2000, — nearly 20 years ago — a special master explained that she could not rely upon Dr. Kinsbourne because, in part, he "has had no clinical experience in
The undersigned found that Dr. Kinsbourne's lack of current experience was a factor weighing against his opinion in a case in which the child-vaccinee was found to have an underlying genetic mutation. Snyder, 2011 WL 3022544, at *5-6, *21-22. When the Federal Circuit reinstated that decision, it ruled that the special master did not err in concluding that the Secretary's experts were better qualified than Dr. Kinsbourne.
So, too, in this case, Dr. Wirrell's qualifications in pediatric neurology are superior to Dr. Kinsbourne's qualifications.
Dr. Wirrell has also written articles and books on the topic of seizures in infants and children. One notable example is that Dr. Wirrell "co-authored the chapter of Epilepsies in Infancy for the most recent version of
Thus, by background alone, Dr. Wirrell is better qualified to discuss the etiology of X.G.'s seizure problem. But, even within the confines of this case, Dr. Wirrell's opinions are more credible.
Problems with Dr. Kinsbourne's reports started in his initial report, which omitted any discussion of the CMV infection, despite his awareness that the CMV infection was an issue. The Secretary's review of the medical records identified the CMV infection and proposed the congenital CMV infection "was responsible for . . . [X.G.'s] development of seizures starting on April 9, 2011." Resp't's Rep. at 12-13. Later, the Secretary asserted that the congenital CMV infection "provides an alternate explanation for the onset of his seizures."
However, Dr. Kinsbourne's recitation of facts involving X.G.'s birth was relatively short (two paragraphs) and did not mention the CMV infection at all. Dr. Kinsbourne opined: "The medical records do not offer any evidence for alternative causation of the seizures." Exhibit 18 at 4. Dr. Kinsbourne's statement, especially after the Secretary had already identified the CMV infection as an "alternate explanation," strains credulity.
Dr. Kinsbourne's second report acknowledges that X.G.'s "prenatal injury was most likely due to a congenital cytomegalovirus (CMV) infection." Exhibit 20 at 1. To discuss symptomatic CMV infections, Dr. Kinsbourne presented one article, exhibit 21 (Boppana). Boppana showed that children with symptomatic CMV infections suffer seizures at a rate "well above population expectations." Exhibit 20 (Dr. Kinsbourne's report) at 1. This information further undermines Dr. Kinsbourne's earlier assertion that there was no alternative explanation for the seizures.
Dr. Kinsbourne's analysis of the significance of the MED13L gene was similar. After information about the mutation was first presented in this case, Dr. Kinsbourne stated, without citing any authority, that the "MED13L syndrome does not feature epilepsy as one of its manifestations." Exhibit 57. The basis for this statement is not at all clear, as it is not consistent with material present in the case at the time when Dr. Kinsbourne offered this statement. The report from Ambry Genetics about X.G. states: "Other features reported in a subset of patients [with MED13L alterations] include . . . epilepsy." Exhibit 58 at 13.
After Dr. Wirrell identified articles linking the mutation to children with epilepsy (exhibit KK), Dr. Kinsbourne took a more nuanced view. He stated "epileptic activity may occur but is not among the core attributes of disorders associated with MED13L variants." Exhibit 59 at 2. The term "core attributes" makes Dr. Kinsbourne's opinion more accurate than his initial statement, which suggested that the MED13L syndrome was not associated with epilepsy at all.
Finally, Dr. Kinsbourne seemed to ignore X.G.'s migrational disorder. To review, the first MRI from April 20, 2011, was done when he was relatively young (less than one year old) and when his brain was still myelinating. This MRI showed some abnormal features. Exhibit 5.2 at 145 / pdf 58. The second MRI from September 21, 2012, showed a "wide spread neuronal migration anomaly." Exhibit 8 at 1.
Dr. Kinsbourne appears not to have attributed any significance to the migrational disorder. It is true that Dr. Kinsbourne's first report mentions both MRIs (exhibit 18 at 1-2) and his second report acknowledges that X.G.'s prenatal brain injury caused "widespread cortical dysplasia" (exhibit 20 at 1). However, Dr. Kinsbourne's initial reports contain no discussion of the significance of the malformation of X.G.'s brain. From reading Dr. Kinsbourne's first two reports, it appears that this deviation in brain structure was no more than an incidental finding, unrelated to seizures.
Dr. Wirrell's view was different. She opined that X.G.'s structural abnormalities were relevant to his seizures. Citing four studies as examples, Dr. Wirrell offered: "Several studies have shown that neuroimaging abnormalities are highly correlated with development of epilepsy in children with congenital CMV." Exhibit D at 9. Later, Dr. Wirrell emphasized: "The vast majority of children with a diffuse, bilateral malformation of cortical development, most probably caused by symptomatic congenital CMV, would be expected to develop . . . epilepsy, which would have a high risk of being medically intractable."
When Dr. Kinsbourne was ordered to address the studies connecting brain structural anomalies to epilepsy, the discordant approaches of Dr. Kinsbourne versus Dr. Wirrell were illuminated. Dr. Kinsbourne explained that in his earlier reports, he "was referring to the larger group of children with congenital [CMV], most of whom do not have cortical malformations. Dr. Wirrell referred specifically to those who did have such malformations." Exhibit 47 at 1. What Dr. Kinsbourne did not explain was why he chose to base his opinion upon children who were noticeably different from X.G. — children who did not have a cortical malformation. Thus, Dr. Kinsbourne has constructed an "apples to oranges" analysis, and Dr. Wirrell has constructed an "apples to apples" analysis.
Dr. Wirrell's analysis of the significance of X.G.'s MRIs is much more persuasive than Dr. Kinsbourne's skirting of the issue. In connection with the MRIs, it is worth noting that Dr. Kinsbourne never directly challenged Dr. Wirrell's interpretation of them.
Overall, because of the undersigned's awareness of Dr. Kinsbourne's lack of clinical practice, especially with respect to treating children with genetic disorders causing seizures, the undersigned suggested that Ms. Ellis should consider obtaining a report from a pediatric geneticist. A person with expertise in pediatric genetics could have helped Ms. Ellis. However, Ms. Ellis chose to stay with Dr. Kinsbourne. Order, issued July 11, 2017. Now, having chosen to rest her case with Dr. Kinsbourne, Ms. Ellis is left with an expert who has not practiced in more than two decades and who did not credibly grapple with the complex issues in X.G.'s case.
In short, Ms. Ellis has failed to present a persuasive case due, in part, to the relative weakness of her expert.
Special masters should consider opinions treating doctors express.
Here, overall, the treating doctors tended not to blame the vaccination for X.G.'s seizures. Admittedly, relatively few treating doctors created medical records in which the doctors discussed the cause of X.G.'s seizures. But, most of their statements and their actions seem to suggest that the treating doctors thought that the vaccination did not harm him.
In early June 2012, X.G. had a seizure when his phenobarbital level was low. Exhibit 16.2 at 86 / pdf 34. Within a few days, Ms. Ellis and X.G.'s father brought X.G. to Mid-Suffolk Pediatrics to catch up on vaccines. In this context, the doctor recorded that X.G. had had a seizure the past weekend. The doctor also described X.G. as "well appearing." The doctor ordered an additional dose of Pentacel and a dose of the varicella vaccine.
As previously mentioned, after Ms. Ellis moved, she transferred X.G.'s care to Weill Cornell.
Dr. Kearney's colleagues at Weill Cornell continued to suggest that X.G. receive updated vaccinations.
Ms. Ellis's resistance to authorizing more flu vaccines continued on September 2, 2014, when she brought X.G. for a four-year old checkup. The pediatrician, Denver Brown, wanted X.G. to receive more vaccines but Ms. Ellis refused the flu vaccine. Dr. Brown ordered and Ms. Ellis accepted a dose of Kinrix, which combines the DTaP and IPV vaccines. Exhibit 45 at 47-48.
The final record from a treating doctor relevant to the causation inquiry came after Ambry Genetics conducted genetic testing. On March 24, 2017, a pediatric neurologist, Eric James Mallack, stated that based upon whole-exome sequencing, X.G. was recently diagnosed "with MED13L Syndrome." Exhibit 45 at 82.
Dr. Mallack's report seems consistent with Dr. Wirrell's opinion that X.G.'s genetic mutation has affected him detrimentally just as Dr. Kearney's May 24, 2013 report about X.G.'s CMV infection is consistent with Dr. Wirrell's opinion. In contrast, Ms. Ellis has not identified any treating doctors — not even the author of the May 17, 2011 note — who linked X.G.'s seizures to the vaccination.
The pediatricians' actions shed some light on their thinking. The pediatricians often recommended that X.G. receive more vaccinations. On two occasions, doctors gave X.G. another dose of the DTaP vaccine. Exhibit 14 at 8 (June 8, 2012) and exhibit 45 at 48 (Sept. 2, 2014). After encountering the supposedly inciting substance again, X.G. did not have a seizure immediately. Following the June 2012 DTaP vaccination, X.G. had another seizure about three months later. Exhibit 15 at 14. Similarly, after the September 2014 DTaP vaccination, X.G. had another seizure about one month later. Exhibit 45 at 49. Dr. Wirrell commented: "X.G. received a subsequent dose of acellular pertussis vaccine with no exacerbation of seizures or other symptoms." Exhibit AA at 5. Dr. Kinsbourne did not address this point. The lack of adverse response upon rechallenge tends to suggest that the DTaP did not cause the seizures.
Consequently, the medical records are against a finding that the vaccination contributed to X.G.'s seizure disorder. They more support a finding that either the in utero infection or the genetic mutation caused X.G.'s seizure disorder.
A finding that X.G.'s genetic mutation and his in utero CMV infection are likely causes of his seizure disorder necessarily implies that the vaccination did not cause his seizure disorder.
Preliminarily, setting out Ms. Ellis's claim is important. As just explained, she claims that the vaccination contributed to her son's "seizure disorder." "Seizure disorder" is different from the April 9, 2011 seizure. "Seizure disorder," in this context, means the series of seizures that X.G. has experienced intermittently after April 9, 2011.
A claim that the DTaP vaccination caused the April 9, 2011 seizure alone is pointless. If Ms. Ellis's claim the vaccine-induced injury terminated with the conclusion of the April 9, 2011 seizure, then she could not receive compensation. To qualify for compensation, Ms. Ellis must establish that the vaccination-caused injury lasted for more than six months. 42 U.S.C. § 300aa-11(c)(1)(D)(i);
To establish the necessary six months of harm, Ms. Ellis attempts to argue that the April 9, 2011 seizure caused lasting consequences. Citing two relatively old articles, Dr. Kinsbourne opines "`seizures beget seizures.'" Exhibit 59 at 2 (citing exhibit 61 (Kang Chen et al.,
The consequence, if any, of X.G.'s April 9, 2011 seizure is critical to Ms. Ellis's claim that "the vaccines X.G. received on April 8, 2011 caused his seizure disorder." Pet'r's Mot., filed Nov. 22, 2017, at 2. The stronger and more persuasive evidence shows that X.G.'s on-going seizure disorder stems from either his genetic mutation or his in utero CMV infection.
Alternatively, Ms. Ellis presents the theory that the DTaP vaccination significantly aggravated his preexisting condition. Ms. Ellis elaborates: "the vaccinations triggered any pre-existing latency to become patent. The onset of seizures at such a young age is unquestionably a significant aggravation in X.G.'s condition." Pet'r's Mot., filed Nov. 22, 2017, at 3;
In evaluating a claim that a vaccine significantly aggravated a pre-existing disorder, special masters should consider the natural course of the underlying condition.
Preponderant evidence does not support Ms. Ellis's case because Dr. Kinsbourne did not offer a persuasive opinion about how X.G. would have fared in absence of the vaccination.
Consistent with Dr. Kinsbourne's report, Ms. Ellis argues that (1) the vaccination caused X.G. to suffer his initial seizure earlier than he would have but for the vaccination, and (2) the earlier onset of seizures means a worse outcome. For the first proposition, Ms. Ellis and Dr. Kinsbourne relied primarily upon a 2008 article by Leventer, which indicated that the onset of seizures is often in the second decade. Pet'r's Br. filed Nov. 22, 2017, at 5; exhibit 47 (Dr. Kinsbourne's report) at 2. However, as explained above, the 2008 Leventer article provides an inapt basis for comparison to X.G. as this article studies children with many types of migration disorders. In contrast, the precise migration disorder that X.G. has (bilateral perisylvian polymicrogyria) was studied in the 2010 Leventer article. Exhibit 54. Thus, the 2010 Leventer article serves as a more accurate basis for comparison and that article indicates that median age of onset of seizures in children with bilateral perisylvian polymicrogyria is 12 months.
Moreover, bilateral perisylvian polymicrogyria is not X.G.'s only problem. He also suffered from microcephaly and a genetic mutation, both of which are associated with seizures. Consequently, the evidence does not weigh in favor of a finding that X.G. had his first seizure sooner than he would have had absent the vaccination. This finding, in turn, means that evaluating Ms. Ellis's second point — the earlier onset of seizures means a worse outcome — is not required.
In contrast, Dr. Wirrell provided opinions that a natural consequence of an in utero CMV infections is a seizure disorder. She also opined that a MED13L mutation can cause seizures. On both points, Dr. Wirrell cited literature that supported her opinions.
It may be the case that the April 8, 2011 DTaP vaccination contributed to X.G.'s April 9, 2011 seizure. In one sense, X.G.'s condition on April 10, 2011, the day after the seizure, was worse than X.G.'s condition on April 7, 2011, the day before the vaccination. X.G. went from a boy who had never experienced a seizure to a boy who had experienced a seizure. However, in another sense, X.G.'s condition did not change. X.G. had been born with microencephaly, a migration disorder, and a genetic mutation. Ms. Ellis has not presented any evidence that the vaccine altered these physical traits. His development is consistent with the outcomes expected from these conditions.
The short interval between the vaccination and the onset of X.G.'s seizure disorder, by itself, could suggest that the vaccination caused the seizure disorder. But "temporal association is not sufficient, however, to establish causation in fact."
Despite Ms. Ellis's sympathetic status as a mother of a disabled child, she is not entitled to compensation through the Vaccine Program. The evidence shows that the DTaP vaccine did not contribute to X.G.'s outcome.
The Clerk's Office is instructed to enter judgment in accord with this decision.
As to the timing of the CMV infection, there is no overt disagreement between the experts. As stated in the text, Dr. Wirrell places the CMV infection before the 28-week ultrasound. Although Dr. Kinsbourne wrote reports after this report from Dr. Wirrell, he did not propose a different date of infection or otherwise challenge Dr. Wirrell's opinion on this point.
Moreover, multiple doctors characterized X.G. as microcephalic. Exhibit 7 at 15, exhibit 8 at 1, exhibit 45 at 9.
