VICP Registry Case Source Bundle Canonical URL: https://vicp-registry.org/case/USCOURTS-cofc-1_15-vv-00972 Package ID: USCOURTS-cofc-1_15-vv-00972 Petitioner: Paul Mondello Filed: 2015-09-03 Decided: 2018-04-16 Vaccine: hepatitis A Vaccination date: 2013-11-15 Condition: seizure disorder Outcome: compensated Award amount USD: 50995 AI-assisted case summary: Paul Mondello, born October 2, 1943, received a Twinrix hepatitis A and B vaccine on November 15, 2013. He subsequently developed a seizure disorder. The initial petition was dismissed by the Special Master for lack of evidence of causation. The petitioner appealed, and the Court of Federal Claims reversed, finding that there was at least some evidence suggesting a theory of causation and that the Special Master had erred in assigning the burden of disproving alternative causes to the petitioner. The case was remanded for further proceedings. On remand, the Special Master heard testimony from Mr. Mondello and his treating neurologist, Dr. Suzanne Bourque. Dr. Bourque opined that the vaccine, in combination with Mr. Mondello's comorbidities and the subsequent administration of cyproheptadine, contributed to his seizures. Respondent presented an expert, Dr. Thomas Leist, who disagreed, attributing the seizures solely to cyproheptadine and finding no evidence of a vaccine reaction or aseptic meningitis. After considering the evidence, including testimony and expert reports, Special Master Mindy Michaels Roth found that Mr. Mondello was entitled to compensation, satisfying the Althen prongs for causation. The parties subsequently reached a stipulation for damages, and on April 16, 2018, the court awarded Mr. Mondello $50,995.29 in compensation. Petitioner was represented by Verne E. Paradie, Jr., and respondent was represented by Darryl R. Wishard. The Special Master was Mindy Michaels Roth. Theory of causation field: Paul Mondello, born 10/02/1943, received a Hepatitis A vaccine on 11/15/2013. He developed a seizure disorder. The Special Master initially dismissed the claim for lack of causation. The Court of Federal Claims reversed, remanding for further proceedings. On remand, petitioner's treating neurologist, Dr. Suzanne Bourque, testified that the Hepatitis A vaccine, in combination with Mr. Mondello's comorbidities (including prior head injury, alcoholism, and chronic pain) and the subsequent administration of cyproheptadine, lowered his seizure threshold and triggered the seizures. Dr. Bourque suspected aseptic meningitis as a possible vaccine reaction, evidenced by elevated CSF protein, headache, nausea, and vomiting. Respondent's expert, Dr. Thomas Leist, opined that cyproheptadine was the sole cause of the seizures and that there was no evidence of a vaccine reaction or aseptic meningitis. Dr. Leist attributed Mr. Mondello's symptoms in the week following vaccination to his comorbidities. Special Master Mindy Michaels Roth found Dr. Bourque's opinion more compelling, concluding that the Hepatitis A vaccine, in combination with comorbidities and cyproheptadine, caused the seizures, satisfying the Althen prongs. Petitioner was awarded $50,995.29 in a lump sum. Attorneys for petitioner were Verne E. Paradie, Jr., and for respondent was Darryl R. Wishard. Decision date: 04/16/2018. Public staged source text: ================================================================================ DOCUMENT 1: USCOURTS-cofc-1_15-vv-00972-0 Date issued/filed: 2017-05-22 Pages: 14 Docket text: JUDGE VACCINE REPORTED OPINION re: 44 Order on Motion for Review, Judge Vaccine Reported Opinion Signed by Senior Judge Eric G. Bruggink. (jpk1) Copy to parties. Modified on 6/23/2017 - minor typographical change made to PDF (jt1). -------------------------------------------------------------------------------- Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 1 of 14 In the United States Court of Federal Claims No. 15-972V (Originally filed: May 1, 2017) (Re-filed: May 22, 2017)1 * * * * * * * * * * * * * * * * * * * * * * PAUL MONDELLO, Petitioner, National Childhood v. Vaccine Injury Act; Hepatitis A Vaccine; SECRETARY OF THE Seizure Disorder; Motion DEPARTMENT OF HEALTH AND for Review; Causation. HUMAN SERVICES, Respondent. * * * * * * * * * * * * * * * * * * * * * * Verne E. Paradie, Jr., Lewiston, ME, for petitioner. Darryl R. Wishard, Senior Trial Attorney in the Torts Branch of the Civil Division, Department of Justice, Washington, DC, with whom are, Benjamin C. Mizer, Assistant Attorney General, C. Salvatore D’Alessio, Director, Catherine E. Reeves, Deputy Director, for respondent. OPINION BRUGGINK, Judge. This is a case brought under the National Childhood Vaccine Injury Act for compensation for injuries allegedly sustained after the administration of a hepatitis A vaccination received by petitioner, Paul Mondello, on November 1 Publication of this opinion was deferred pending the parties’ review for redaction of protected information. See Rules of the Court of Federal Claims, App. B, Rule 18(b). Neither party submitted proposed redactions. Accordingly, the opinion appears below in full. Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 2 of 14 15, 2013.2 The petition alleges that the vaccine caused him to develop a seizure disorder and related neurological symptoms and deficits. The Special Master dismissed the petition for lack of evidence of causation. Petitioner has appealed that decision in a motion for review to this court. The motion is fully briefed, and oral argument is deemed unnecessary. Because there was some evidence evincing a theory of causation, we reverse the Special Master’s decision and remand for further proceedings consistent with this opinion. BACKGROUND I. Factual History Petitioner was born on October 2, 1943. He served in the Vietnam War and was honorably discharged after receiving a severe blow to the head and crush injuries to his knees and back. Afterwards, he was treated at Togus Veterans Administration Hospital (“Togus”) for hypertension, post-traumatic stress disorder (“PTSD”), osteoarthritis, hearing loss, gastroesophageal reflux disorder, migraines, abnormal glucose, chronic back pain, and chronic hepatitis. Petitioner’s medical history included Agent Orange exposure, traumatic brain injury, crush injuries to the knees and back, and Stevens- Johnson syndrome from taking hydrochlorothiazide. Petitioner was admitted to a rehabilitation program at Togus for alcohol and daily cannabis dependence in October 2013. He also regularly used benzodiazepine to treat panic attacks and anxiety, but reported having discontinued its use during this time period. He was also prescribed cyproheptadine, an antihistamine, for his PTSD-related symptoms during this admission at Togus.3 2 Petitioner was administered a Twinrix hepatitis A and B vaccination, but most of petitioner’s records refer only to hepatitis A vaccination as the cause of his seizure disorder. 3 Cyproheptadine is an anti-histamine used to relieve allergy symptoms such as sneezing, itching, watery eyes, runny nose, and other symptoms of allergies. It is also used to treat nightmares in those suffering from symptoms of PTSD. Its side affects are reported as including dizziness, blurred vision, fatigue, and palpitations. Overdosage can result in hallucinations, convulsions, and central nervous system (“CNS”) depression. It is thought to have additive effects with (continued...) 2 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 3 of 14 On November 15, 2013, petitioner visited Togus for a follow up to his rehabilitation. Records from that visit noted that he reported not having had alcohol for 36 days and that his medications included cyproheptadine. It was during this visit when petitioner received a Twinrix hepatitis A and B vaccine. A week later, on November 22, 2013, petitioner was admitted to St. Joseph’s Hospital during an episode of active seizures and an altered state of consciousness. He was actively seizing upon arrival at the hospital. His wife reported that he had not been feeling well since receiving the Twinrix vaccination and that he suffered from nausea, vomiting, and poor appetite. She also stated that petitioner had taken cyproheptadine for the first time at around 4:00 pm that day because he was experiencing tremors, anxiety, and chest palpitations. She recalled that he became confused shortly thereafter and began hallucinating and talking about flashes of light at approximately 5:00 pm, which was about the time petitioner had the seizures. Upon arrival at the hospital, petitioner had a Glasgow Coma Scale (“CGS”) score of 7; he was intubated and administered diazepam.4 He underwent a CT scan of his head, which was normal. He tested positive for benzodiazepines and marijuana. Petitioner was then transferred to the emergency department at Eastern Main Medical Center (“EMMC”) with an assessment of “generalized status epilepticus of unknown cause,”and noting that petitioner was a longstanding alcoholic but had been sober for 46 days, with no prior history of seizures. Mondello v. Sec’y of HHS, No. 15-972V, Slip. Op. at 3 n.4. (Fed. Cl. Spec. Mstr. Nov. 15, 2016) (quoting Pet.’s Ex. 1 at 31). At EMMC, petitioner underwent a battery of diagnostic tests. An EEG showed “diffuse right-sided slowing,” “transient periodic right lateralized discharges involving frontal area,” and “intermittent spikes throughout the record involving right frontal area.” Id. (quoting Pet.’s Ex. 5 at 1394). An MRI revealed “no acute or malignant intracranial process,” with “moderate burden 3(...continued) alcohol and other CNS depressants. Mondello v. Sec’y of HHS, No. 15-972V, Slip. Op. at 3 n.4. (Fed. Cl. Spec. Mstr. Nov. 15, 2016) (unpublished order dismissing petition). 4 GCS is used to measure the severity of an acute brain injury, where a score of 3 is the most severe and a score of 15 is the least severe. 3 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 4 of 14 of white matter signal changes” and “mild diffuse cerebral volume loss.” Id. (quoting Pet. Ex. 5 at 1400). Treating physicians were uncertain of the clinical significance of these results. While at EMMC, petitioner was treated by a neurologist, Dr. Bourque. She ordered a lumbar puncture of Mr. Mondello because of the possibility that he may have had an aseptic meningitis related to the vaccination. The lab test was negative for meningitis. Dr. Bourque prescribed Keppra, an anti-seizure medication, and petitioner was discharged from EMMC on November 27, 2013, with a diagnosis of new-onset seizure, with delirium and hyponatremia.5 The discharge summary reflected no specific cause but noted that his condition was consistent with alcohol withdrawal and the possibility of benzodiazepine withdrawal. The summary also reported that the hepatitis A vaccine’s effects, along with other medications and health problems were all of note as well as possibly having a causal link. Through December 2013, petitioner received physical therapy at home. On January 9, 2014, he sought care at Mayo Practice Associates (“Mayo”) after complaining of left trapezius strain and knee pain. The Mayo record listed cyproheptadine as one of his allergies, with a reaction of seizures and confusion. On January 30, 2014, petitioner met with Dr. Bourque for a follow-up visit. Her notes from that occasion record that she had initially treated him at EMMC on November 2013 for a new onset of seizures. Those notes further reflected that he had been administered a hepatitis A vaccine one week prior to his hospitalization and that he reported experiencing nausea, vomiting, headache, and chills during the intervening week. Further stated was that, on the day of hospitalization, he took four milligrams of cyproheptadine for the first time in his life. His wife informed doctors that within 20-30 minutes of taking cyproheptadine, he started experiencing visual hallucinations. She then left the room to call 911, and when she came back, found him seizing. Dr. Bourque’s notes also record that petitioner had not suffered any further severe headaches, seizures, fevers, or lateral weakness since his discharge from EEMC, and had done well on Keppra. Overall, his mental 5 Hyponatremia is a condition when the level of sodium in the blood becomes abnormally low, which can cause nausea, vomiting, headache, confusion, fatigue, muscle weakness, and seizures. 4 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 5 of 14 status had returned close to baseline, although his wife stated that he occasionally had episodes during which his ability to give directions seemed impaired. Dr. Bourque suggested that he see a neuropsychologist for a baseline assessment of cognitive strengths and weaknesses. On April 7, 2014, petitioner again saw Dr. Bourque for another follow- up appointment. Dr. Bourque again recorded petitioner’s history regarding the administration of the vaccine, subsequent illness, and presentation at the hospital for seizures a week later. Notes from the April 7 visit indicate that Mr. Mondello had not experienced any more seizures nor spells of confusion, but had started drinking again intermittently. These notes also reflect that petitioner was again tested with an EEG on February 24, 2014, which returned normal results. During this visit, Dr. Bourque also discussed with petitioner tapering off Keppra. She warned, however, that there was a potential for recurrent seizures. She also mentioned the possibility of switching from Keppra to Trileptal, but Mr. Mondello was not interested in pursuing any of these options because it would have meant that he would have had to stop driving for three to six months, and he had been tolerating Keppra better. Almost a year later, on March 20, 2015, petitioner was treated by Dr. Bourque for a possible seizure despite the anticonvulsants after petitioner had, of his own initiative, reduced his Keppra dosage by a quarter for two days. He reported returning to the full dose during the weekend prior to this visit, but that on the following Tuesday he experienced an unusual 30-second episode of facial distortion and general unresponsiveness without limb shaking, automatisms, or lip smacking. In her records, Dr. Bourque again noted the history of hepatitis A vaccine a week prior to the initial 2013 seizures and the first dose of cyproheptadine shortly before the seizure onset. She advised that petitioner return to his regular Keppra dosage and that they would discuss tapering off it again later that fall. Petitioner’s next visit to Dr. Bourque was on October 2, 2015. He had suffered no further seizures after the March 20, 2015 appointment. Dr. Bourque noted that: [p]etitioner continues to have a history of hospitalization with what was suspected to be possibly a provoked seizure in 2013, but with an abnormal EEG at that time. When he tried taking himself off Keppra earlier this year, he had what was an atypical spell that may have represented a seizure, so we will continue on 5 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 6 of 14 Keppra. Pet’s Ex. 7 at 1451. On March 18, 2016, petitioner returned for his final visit to Dr. Bourque regarding his seizures. Petitioner reported to Dr. Bourque that, although he had not experienced any further seizures, he was experiencing some cognitive difficulties. The doctor’s notes again recited his history beginning with the 2013 hepatitis vaccine and subsequent hospitalization. These notes included the opinion that the 2013 seizures were the result of a combination of petitioner’s being unwell from the hepatitis A vaccine and having taken cyproheptadine. Her diagnosis for petitioner’s cognitive trouble was that it was likely the result of a combination of his previous head injuries, alcoholism, chronic pain, and untreated psychiatric illness. Petitioner was discharged from neurological care on this date. II. Procedural History On September 3, 2015, petitioner timely filed a petition for compensation under the National Childhood Vaccine Injury Act, 42 U.S.C. §§ 300aa-1 to-34 (2012) (“Vaccine Act”). He eventually, after twice supplementing, filed all of his relevant medical records. Respondent subsequently filed a report, as required by Vaccine Rule 4(c)(1), recommending against compensation. Respondent argued that petitioner had failed to satisfy the causation standard articulated in Althen v. Sec’y of HHS., 418 F.3d 1274, 1278 (Fed. Cir. 2005), and further avered that “the more likely cause of petitioner’s seizure onset was the resultant side effect of his first dose of cyproheptadine.” Resp’t Rule 4(c) Report at 6. The Special Master reviewed the petitioner’s records and ordered him to file an expert report because his records did not provide a medical theory causally connecting the vaccine at issue with petitioner’s injury. Mondello v. Sec’y of HHS, No. 15-972V (Fed. Cl. Spec. Mstr. May 19, 2016). Petitioner instead informed the court that he had filed all of his relevant medical records and would not be filing an expert report. Then, on August 1, 2016, petitioner filed a 10-page motion asking for a decision on the merits based on the record as it was, or, in the alterative, for an evidentiary hearing. In his motion for a ruling on the record, petitioner relied most on Dr. Bourque’s treatment records, arguing that they contained the doctor’s opinion 6 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 7 of 14 that the vaccination was a substantial factor in bringing about his seizure disorder. Petitioner acknowledged that he had not submitted an expert opinion as to “the exact biological mechanism” causing his illness but argued that none was necessary given the temporal relationship between the onset of symptoms after the vaccination, medical literature in the record, and Dr. Bourque’s “opinion that the vaccination was a contributing factor to Mr. Mondello’s condition.” Pet.’s Mot. for Ruling on the R. 4. He further argued that requiring proof of a specific biological mechanism was inconsistent with the purpose of the Act and imposed an impermissibly high evidentiary standard on claimants. After confirming that petitioner understood the ramifications of a ruling on the record as opposed to a dismissal decision, the Special Master issued a decision on November 15, 2016, dismissing the petition because petitioner “failed to produce preponderant evidence that the hepatitis A vaccination [was] responsible for his condition.” Mondello, Slip. Op. at 9. The Special Master reviewed Dr. Bourque’s records but disagreed with petitioner as to their contents. She found that they did not offer any specific causative theory of how Mr. Mondello’s seizures were caused by the vaccine and that the doctor did not otherwise opine that the seizure would not have occurred in the absence of the vaccination. Id. at 8. The Special Master stated that the medical records were only a detailed recitation of the facts related to petitioner’s hospitalization and his symptoms since November 2013. She further found that petitioner’s list of other morbidities, along with his first dose of cyproheptadine, undermined the allegation that the hepatitis A vaccine was more likely than not the cause of, or a substantial factor in causing, the seizure disorder. Without a sufficient medical opinion on causality or other plausible medical theory in support of his claim, the Special Master held that she was constrained by the case law to dismiss the petition for lack of evidence of causation. Petitioner filed a motion for review of this decision on December 14, 2016, and respondent filed a response to the motion on January 11, 2017. DISCUSSION In his motion for review, petitioner asserts that the Special Master erred in ignoring the opinion of the treating physician and should not have penalized petitioner for not hiring an expert to opine on causation. Petitioner argues that Dr. Bourque’s records contained an opinion that the hepatitis vaccination was a substantial causative factor in the seizures that he suffered. That Dr. Bourque did not posit a theory of the precise biological mechanism that caused the 7 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 8 of 14 vaccine to injure plaintiff is not dispositive, according to petitioner, particularly given her more general opinion that it was a co-factor in causing the injury and the medical literature that he argues provides an etiological link between the vaccine and the seizures suffered. By emphasizing the fact that petitioner did not submit an outside expert opinion and by not taking account of the relevant medical and scientific literature, the Special Master impermissibly raised petitioner’s burden of providing a medical theory beyond that of biological plausibility–all that is required by the Vaccine Act–argues petitioner. As to a temporal link between the vaccine and the injury, petitioner contends that his medical records show that he became ill immediately after being vaccinated and that he remained so until he was hospitalized with the seizures. The cyproheptadine posited as a cause by the government is a red herring because he was already sick before taking it; he asserts that he would not have taken it had he not been ill for a whole week following the vaccination. The government responds that the Special Master appropriately considered all the evidence and followed applicable legal precedent in determining that petitioner failed to meet his burden of proving causation. Respondent agrees with the Special Master that Dr. Bourque’s records do not contain any specific medical theory regarding how the hepatitis A vaccine could cause the seizures, which is insufficient to meet the standard of proof, it argues. Respondent also offers petitioner’s other medical and substance abuse problems as factors undermining his claim that the vaccine was “more likely than not” the cause of his seizure onset. Respondent further contends that petitioner misinterprets the law regarding the significance of the opinions of treating physicians, especially when, as in this case, they do not posit an actual theory of biological causality or unequivocally state that the cause of the injury was the vaccine. Finally, in response to petitioner’s point that the Special Master ignored his medical literature aimed at the first prong–a medical theory of causation–the government argues that the special masters are not required to discuss every piece of evidence present in the record as long as the decision is clear that they have considered all of the parties’ evidence and arguments. I. Jurisdiction And Standard Of Review We have jurisdiction pursuant to 42 U.S.C. § 300aa-12 to hear appeals 8 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 9 of 14 of decisions by the Office of Special Masters granting or denying compensation. In reviewing a decision rendered by a Special Master, we may: (1) uphold the findings of fact and conclusions of law; (2) set aside any of the findings of fact or conclusions of law “found to be arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law;” or (3) remand the petition to the special master for further action in accordance with the court’s direction. 42 U.S.C. § 300aa-12(e)(2)(A)-(C). In deciding a motion for review, we do not “re-weigh the factual evidence, or . . . assess whether the special master correctly evaluated the evidence” nor do we “examine the probative value of the evidence or the credibility of the witnesses. These are all areas within the purview of the fact finder.” Lampe v. Sec’y of HHS, 219 F.3d 1357, 1360 (Fed. Cir. 2000). This means that if the Special Master has considered the relevant evidence of the record, drawn plausible inferences, and articulated a rational basis for the decision, the court reviewing the Special Master’s decision is compelled to uphold the findings as neither arbitrary nor capricious. Cedillo v. Sec’y of HHS, 617 F.3d 1328, 1338 (Fed. Cir. 2010). To receive compensation for a vaccine related injury under the Vaccine Act, the petitioner bears the burden of proving by a preponderance of the evidence the elements required to entitle him or her to relief, which are listed in 42 U.S.C. § 300aa-11(c)(1). For an “off table” injury case, as here, the petitioner has the burden to prove that the vaccine “caused” the illness, disability, injury, or condition. Id. § 300aa-11(c)(1)(C)(ii)(I). This mean that a petitioner must show by preponderant evidence both that the vaccination was a “substantial factor” in causing the illness, disability, injury, or condition and that the harm would not have occurred in the absence of the vaccination. Shyface v. Sec’y of HHS, 165 F.3d 1344, 1352 (Fed. Cir. 1999). In order to establish that the vaccine was a substantial factor in causing the injury, petitioner must show: (1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a proximate temporal relationship between the vaccination and injury. Althen, 418 F.3d at 1278. The same evidence may be used to establish multiple of the Althen prongs. Capizzano v. Sec’y of HHS, 418 F.3d 1317, 1326 (Fed. Cir. 2006). The first prong of the Althen test focuses on whether the vaccine in question can cause the type of injury alleged. Pafford v. Sec’y of HHS, 451 F.3d 1352, 1356 (Fed. Cir. 2006). This inquiry allows medical opinion as 9 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 10 of 14 proof, even without scientific studies in medical literature providing “objective confirmation” of medical plausibility. Althen, 418 F.3d at 1279. The second prong is concerned with whether the vaccine did cause petitioner’s injury, which involves the presentation of a “reputable medical or scientific explanation.” Id. It, like the first prong, however, does not require proof of a “specific biological mechanism[].” Capizzano, 440 F.3d at 1325 (citing Knudsen, 35 F.3d at 549). Circumstantial evidence may also be cited to meet the test. Id. (citing Althen, 418 F.3d at 1280). Finally, the third prong demands a showing that the injury’s onset occurred “within a time frame for which, given the medical understanding of the disorder’s etiology, it is medically acceptable to infer causation-in-fact.”De Bazan v. Sec’y of HHS, 539 F.3d 1347, 1352 (Fed. Cir. 2008). If the petitioner can meet the causation standard, he has established a prima facie case, and the burden shifts to the government to prove “[by] a preponderance of the evidence that the [petitioner’s injury] is due to factors unrelated to the administration of the vaccine described in the petition.” 42 U.S.C. § 300aa-13(a)(1)(B). Walther v. Sec’y of HHS, 485 F.3d 1146, 1151 (Fed. Cir. 2007). II. Dr. Bourque’s Medical Records Offer An Opinion Of A Causal Link Between The Hepatitis A Vaccine And Petitioner’s Seizure Disorder The Vaccine Act requires petitioners to provide, at a minimum, proof in the form of medical records or by medical opinion. 42 U.S.C. § 300aa- 13(a)(1) (requiring proof of causation “by medical records or by medical opinion). Medical records “warrant consideration as trustworthy evidence” because these records are “generally contemporaneous to the medical events,” and “accuracy has an extra premium.” Cucuras v. Sec’y of HHS, 993 F.2d 1525, 1528 (Fed. Cir. 1993). The medical records and opinions of treating physicians are “quite probative” because “treating physicians are likely to be in the best position to determine whether a logical sequence of cause and effect show[s] that the vaccination was the reason for the injury. Capizzano, 440 F.3d at 1326. Here, the Special Master considered the records of Dr. Bourque but found them “not [to] offer any opinions regarding causation between Mr. Mondello’s receipt of the hepatitis A vaccine and the onset of seizures.” Mondello, Slip. Op. at 7. She found that the doctor’s records provided only a history of events prior to and post-vaccination. Thus, petitioner’s choice not 10 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 11 of 14 to provide an expert opinion causally linking the vaccine to the seizures or other symptoms suffered by petitioner was fatal to his claim. “Ultimately, petitioner has failed to provide either a sufficient medical opinion or plausible medical theory in support of his claim that the hepatitis vaccine caused or significantly contributed to his seizures.” Id. at 8. Further, the Special Master decided that the petitioner’s prior medical history (“co-morbidities”), the fact that he took the particular antihistamine just prior to the onset of seizures, and his record of having used CNS depressants contemporaneous with the antihistamine undermined any evidence suggesting a “more likely than not” link between the vaccine and the injuries suffered by petitioner. Id. We cannot go so far. Most of what is contained in Dr. Bourque’s notes and records is, as stated by the Special Master, a recitation of Mr. Mondello’s medical history, centering on his 2013 seizure episode. It is of note, however, that in each record of treatment, Dr. Bourque is careful to continue to point out the close temporal relationship between the administration of the Twinrix vaccine and the onset of seizures. Also of importance to her is the fact that petitioner was sick almost immediately after the vaccination, even prior to taking the cyproheptadine. Most important, however, is the record from petitioner’s final visit to Dr. Bourque in March 2016. It states, “Impression and Plan: Mr. Mondello continues to have a history of hospitalization in November 2013 for suspected provoked seizure, which was likely a combination of being unwell from a hepatitis A vaccine and the compilation of cyproheptadine . . . .” Pet.’s Ex. 9 at 1486. That is an opinion regarding causation. As stated in several of Dr. Bourque’s notes from earlier visits, she viewed the seizure episode in 2013 as provoked, i.e., not caused by an already existing medical condition suffered by petitioner. Her notes from petitioner’s final visit indicate her opinion that the provocation for the seizure was a combination of the illness suffered as a result of the vaccine and cyproheptadine. We make no judgment regarding its weight or sufficiency to meet petitioner’s burden under the Vaccine Act, but we cannot agree that Dr. Bourque provided no opinion regarding medical causation of the seizure episode. Further, there are other pieces of evidence submitted by petitioner that arguably lend some support to his claim. He submitted two pieces of medical literature along with Vaccine Information Sheets and a Twinrix package insert in support of his motion for a decision on the record. The first is a study entitled “A case-control study of serious autoimmune adverse events following hepatitis B immunization” by David and Mark Geier. In it, the authors reported that they found an increased incidence of serious autoimmune disorders 11 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 12 of 14 following administration of the hepatitis B vaccine to adults as compared to a control group administered only a tetanus vaccine between the years of 1990- 2004. Pet.’s Ex. 13. The second study presented by petitioner is entitled “Population-Level Evidence for an Autoimmune Etiology of Epilepsy” by Mei-Sing Ong, et al. Pet’s Ex. 14. This study found an increased risk of epilepsy, a seizure disorder, among non-elderly patients with autoimmune diseases. Petitioner suggests that these two studies, read together, provide evidence of a biological causation between the hepatitis vaccine and the seizures experienced by plaintiff. Further, the vaccine information sheets and Twinrix package insert are cited by petitioner to support the idea that the illness he experienced during the week after the vaccination but before the seizure is consistent with the frequent side effects listed for the vaccine that he was administered. Although the Federal Circuit makes clear that claimant need not produce medical literature or epidemiological evidence to establish causation under the Vaccine Act, where such evidence is submitted, the Special Master can consider it to determine whether a vaccine in question did in fact cause a particular injury. See Althen, 418 F.3d at 1280; see also Capizzano, 440 F.3d 1317 at 1324. Petitioner, however, must provide a reputable medical or scientific explanation that pertains specifically to the petitioner’s case, although the explanation need only be “legally probable, not medically or scientifically certain.” Knudsen v. Sec’y of HHS, 35 F.3d 543, 548-49 (Fed. Cir. 1994). Here, petitioner submitted two pieces of medical literature. The first found an increased incidence of serious autoimmune adverse effects of hepatitis B vaccination. Pet.’s Ex. 13 (David A. & Mark R. Geier, A Case- Control Study of Serious Autoimmune Adverse Events Following Hepatitis B Immunization, Autoimmunity, June 2005, at 295). The other evaluated how the risk of serious seizure disorders increases in patients with autoimmune disease. “[S]pecific autoimmune causes, typically associated with autoantibodies, have been increasingly identified in a subset of previously idiopathic seizure disorders. In some of these situations, seizures are associated with other nerologic manifestation; in others, they are the only sign of neurologic autoimmunity.” Pet.’s Ex. 14 (Mai-Sing Ong, Isaac S. Kohane, Tianxi Cai, Mark P. Gorman, Kenneth D. Mandl, Population-Level Evidence for an Autoimmune Etiology of Epilepsy, JAMA Neurology, 2014, at 569.). This evidence does not appear to have been considered in the decision below. 12 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 13 of 14 Respondent cites to Snyder v. Sec’y of HHS, 36 Fed. Cl. 461, 466 (1996) and Murphy v. Sec’y of HHS, 23 Cl. Ct. 726, 734 n.8 (1991), for the proposition that a special master need not discuss every piece of evidence in the record so long as her decision makes clear that she fully considered petitioner’s relevant evidence and arguments. The government argues that nothing cited by petitioner provides a reputable medical theory of vaccine causation, either alone or when considered with Dr. Bourque’s medical records, and thus the Special Master did not err by not specifically calling this fact out in her decision. We cannot say on review whether this evidence ought to have changed the Special Master’s decision nor do we make an attempt to consider whether it is sufficient to provide some proof of etiology. It may well be that expert testimony would be necessary to elucidate the question of whether these studies lend any support to petitioner’s claim. We also cannot say, however, that, on their face, they are irrelevant to petitioner’s claim for compensation. Nor can we say that we are confident that the Special Master considered them before rejecting the petition as insufficiently positing a theory of causation. III. Possible Legal Error Assigning Burden to Petitioner to Eliminate Alternative Causes Finally, the Special Master concluded that the petitioner’s co- morbidities and the coincidence of other substances in his blood prior to the seizure episode, when viewed along with the lack of a medical theory of causation, made it impossible for petitioner to show that the hepatitis vaccination is “more likely than not” the cause of, or a substantial factor in causing, the seizures that occurred on November 22, 2013. Mondello, Slip Op. at 8. Although it is not clear precisely what weight she was assigning petitioner’s other medical problems and the relationship between the other substances and the seizures, those were cited as factors in denying petitioner’s claim. The Vaccine Act provides that, when there are multiple independent potential causes, and petitioner has met his burden on causation, the Secretary then has the burden to prove, also by preponderance of evidence, that the vaccination in question did not cause the harm or the injury was in fact caused by factors unrelated to the vaccine. Walther, 485 F.3d at 1151. Here, Dr. Bourque opined that it was likely a combination of the vaccine-caused illness and the cyproheptadine that provoked petitioner’s seizures. The Act only 13 Case 1:15-vv-00972-EGB Document 46 Filed 05/22/17 Page 14 of 14 requires a showing of “but for” causation and that the vaccine was a “substantial factor,” not that the vaccine was the only cause. Thus the coincidence of another potential causal agent is not fatal to a claim under the Act. If petitioner meets its burden on causation, then it is the government’s burden to prove that some other cause is to blame, not petitioner’s to disprove it. To the extent the Special Master assigned the burden of eliminating alternative independent potential causes to petitioner, we conclude that she erred. CONCLUSION Because the record contains at least some evidence suggesting a theory of causation, we find that the Special Master erred in her conclusion that petitioner’s claim had to be dismissed for not providing any evidence of a theory of causation. Further, to the extent that petitioner was assigned the burden of disproving alternate causes, that was error. We make no findings regarding the sufficiency of Dr. Bourque’s opinion nor the medical literature submitted. That is left to the Special Master on remand. Accordingly, the following is ordered: 1. Petitioner’s motion for review of the Special Master’s November 15, 2016 decision is granted. 2. This case is hereby remanded to the Special Master for further proceedings consistent with this opinion. s/Eric G. Bruggink ERIC G. BRUGGINK Senior Judge 14 ================================================================================ DOCUMENT 2: USCOURTS-cofc-1_15-vv-00972-1 Date issued/filed: 2018-02-20 Pages: 23 Docket text: PUBLIC ORDER/RULING (Originally filed: 1/24/2018) regarding 74 Ruling on Entitlement. Signed by Special Master Mindy Michaels Roth. (mw) Service on parties made. -------------------------------------------------------------------------------- Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 1 of 23 In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS No. 15-972V Filed: January 24, 2018 * * * * * * * * * * * * * * * * * * * * * PAUL MONDELLO, * To Be Published * Petitioner, * v. * Ruling on Entitlement on * Remand; Vaccine Act SECRETARY OF HEALTH * Entitlement; Hepatitis A AND HUMAN SERVICES, * Vaccine; Aseptic Meningitis; * Seizures. Respondent. * * * * * * * * * * * * * * * * * * * * * * Verne E. Paradie, Jr., Paradie Sherman, et al., Lewiston, ME, for petitioner. Darryl Wishard, U.S. Department of Justice, Washington, DC, for respondent. RULING ON ENTITLEMENT ON REMAND1 Roth, Special Master: On September 30, 2015, Paul Mondello (“petitioner” or “Mr. Mondello”) timely filed a petition for compensation under the National Vaccine Injury Compensation Program, 42 U.S.C. § 300aa-10, et seq.2 (“Vaccine Act” or “Program”). The petition alleges that Mr. Mondello suffers from a seizure disorder caused by the hepatitis A vaccination he received on November 15, 2013. Petition at ¶¶ 2, 15. The petition further alleges that Mr. Mondello’s injuries persisted for more than six months. Id. at ¶ 12. Petitioner’s claim was denied by the undersigned after petitioner filed a Motion for Ruling on the Record. Mondello v. Sec’y of HHS, No. 15-972V (Fed. Cl. Spec Mstr. Nov. 15, 2016). Petitioner filed a Motion for Review and the Court of Federal Claims remanded the decision, ordering reconsideration of the evidence. Mondello v. Sec’y of HHS, 132 Fed. Cl. 316 (2017). 1 Because this published ruling contains a reasoned explanation for the action in this case, I intend to post this decision on the United States Court of Federal Claims' website, in accordance with the E-Government Act of 2002, Pub. L. No. 107-347, § 205, 116 Stat. 2899, 2913 (codified as amended at 44 U.S.C. § 3501 note (2006)). In accordance with Vaccine Rule 18(b), a party has 14 days to identify and move to delete medical or other information that satisfies the criteria in § 300aa-12(d)(4)(B). Further, consistent with the rule requirement, a motion for redaction must include a proposed redacted decision. If, upon review, I agree that the identified material fits within the requirements of that provision, I will delete such material from public access. 2 National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755 (1986). Hereinafter, for ease of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa (2012). Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 2 of 23 In accordance with the Court of Federal Claims’ order, the undersigned has reviewed all of the evidence after remand. The Motion for Ruling on the Record was filed on an underdeveloped record; therefore, the undersigned heard testimony from the petitioner and his treating neurologist. Respondent filed an expert report in response to the oral opinions of petitioner’s neurologist, Dr. Bourque. Now that petitioner’s record is more developed, he has provided preponderant evidence that supports the Althen prongs. Therefore, petitioner is entitled to compensation. I. Procedural History A. Office of Special Masters The petition was filed on November 3, 2015. ECF No. 1. The medical record was completed on December 26, 2015. ECF No. 19. On January 11, 2016, respondent filed his Rule 4(c) report recommending against compensation. Resp. Rpt., ECF No. 20. In his report, respondent stated that petitioner had failed to satisfy the causation standards for an off-Table case as articulated in Althen v. Sec’y of Health and Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005). Respondent stated that “the more likely cause of petitioner’s seizure onset was the resultant side effect of his first dose of cyproheptadine.” Resp. Rpt. at 6. This case was initially assigned to Special Master Hamilton-Fieldman, but reassigned to me on January 14, 2016. ECF No. 21. Following a status conference on January 28, 2016, petitioner was ordered to retain an expert. Scheduling Order, ECF No. 23. On April 17, 2016, petitioner filed medical records from Dr. Bourque, petitioner’s treating neurologist, as Pet. Ex. 9, along with a status report (“Pet. S.R.”), in which petitioner stated that “Dr. Bourque’s latest record and opinions establish that the vaccination was a substantial factor in bringing about his current condition.” Pet. S.R., ECF No. 26, at 1. A status conference was held on May 19, 2016, to discuss petitioner’s need for an expert report which complied with “the Althen criteria required to prove causation in the program.” Scheduling Order, ECF No. 27, at 1. On July 18, 2016, petitioner filed a status report stating “he does not intend on submitting an expert report and instead, anticipates filing a Motion for Ruling on the Record.” Pet. S.R., ECF No. 31, at 1. On August 1, 2016, petitioner filed a motion for a ruling on the record along with the Twinrix (Hepatitis A/B) package insert, vaccine information sheets for Hepatitis A and B vaccines, and two articles of medical literature.3 Pet. Ex. 10-14, ECF No. 32. At a status conference on September 22, 2016, petitioner’s counsel confirmed that petitioner “requested a ruling on the record as opposed to a dismissal decision.” Scheduling Order, ECF No. 33, at 1. The undersigned issued a Ruling on the Record on November 15, 2016, denying entitlement to compensation and dismissing the petition. Decision, ECF No. 34. B. Court of Federal Claims Petitioner filed a Motion for Review on December 14, 2016. ECF No. 40. Petitioner 3 Though the records indicate that petitioner received a Twinrix (hepatitis A and B) vaccine, according to the petition, petitioner alleges injuries only as a result of the hepatitis A vaccine and the petition was not amended to allege otherwise. See Petition at ¶¶ 2, 15. 2 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 3 of 23 submitted that, while he did not proffer an expert opinion providing a biological mechanism, the combination of Dr. Bourque’s opinion and the medical literature filed was sufficient to establish a prima facie case under Althen. Id. at 5. Respondent filed a response on January 11, 2017, maintaining that petitioner failed to proffer a medical theory of causation which complied with the Althen criteria. ECF No. 42. On May 1, 2017, the Court granted petitioner’s motion for review, finding that petitioner had proffered “at least some evidence suggesting a theory of causation,” that the undersigned erred in assigning to petitioner the burden of disproving alternate causes and that it appeared the submitted literature was not considered. This matter was remanded to the undersigned for further proceedings. Mondello v. Sec’y of Health & Human Servs., 132 Fed. Cl. 316 (2017). C. Office of Special Masters on Remand A status conference was held on May 9, 2017; the undersigned suggested hearing testimony from petitioner as well as his treating physician, Dr. Bourque. Scheduling Order, ECF No. 45. Petitioner’s counsel advised that Dr. Bourque was no longer petitioner’s treating physician and may be difficult to contact. The undersigned informed the parties that, in order to allow time to further develop the record, petitioner should file a Motion to Stay the Proceedings. Petitioner filed a Motion to Stay Proceedings on June 12, 2017, and a 30 day stay was granted. Motion, ECF No. 47; Order, ECF No. 48. On June 22, 2017, petitioner filed a status report advising the Court that Dr. Bourque had moved her practice from Maine to San Rafael, California; petitioner had reached out to Dr. Bourque but had not yet received a response. Pet. S.R., ECF No. 49. Petitioner was ordered to file a status report by July 6, 2017, indicating petitioner’s availability to testify at a fact hearing. Petitioner filed two status reports on July 5, 2017, stating that petitioner was available to give testimony via video conference on July 12 and 13, 2017, and advising that petitioner would be submitting an affidavit from Dr. Bourque “regarding her conclusions and opinions on the cause and mechanism of Petitioner’s medical condition.” ECF Nos. 50, 51. Petitioner was ordered to file a status report by July 17, 2017, suggesting dates in August of 2017 on which both petitioner and Dr. Bourque would be available to testify. Non-PDF Order, issued July 5, 2017. On July 17, 2017, petitioner requested an extension of time until July 31, 2017 to file his status report. ECF No. 52. Petitioner filed a status report on July 31, 2017, stating that petitioner would be available to give testimony in late August, and advising that, while petitioner expected to file an affidavit from Dr. Bourque, it may be necessary to issue a subpoena in order obtain Dr. Bourque’s testimony. ECF No. 53. Petitioner was ordered to file an affidavit from Dr. Bourque by August 14, 2017, as well as a status report indicating both petitioner’s and respondent’s availability for a hearing on either August 29 or August 30, 2017. Scheduling Order ECF No. 54. Petitioner was also ordered to file a motion to further stay proceedings. Id. On August 14, petitioner filed an affidavit from Dr. Bourque and a status report advising that petitioner’s counsel was available for a fact hearing on August 22, 28, 30, and 31. ECF Nos. 55, 56. Petitioner also filed a Motion to Stay Proceedings, 3 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 4 of 23 requesting a 150 day stay. ECF No. 57. The undersigned granted petitioner’s motion in part for a stay of 60 days. ECF No. 58. Hearings were held via video conference on August 28, 2017 and September 7, 2017 for the testimony of petitioner and Dr. Bourque, respectively. See Prehearing Order, ECF Nos. 59-60. On October 3, 2017, respondent filed an expert report from a neurologist, Dr. Leist. Pet. Ex. E-J, ECF No. 68. That same day, I issued an order stating that on September 7, 2017, Dr. Bourque testified that petitioner suffered from aseptic meningitis as a result of his hepatitis vaccine, which lowered his seizure threshold and was one of several contributing factors to his development of seizures following his ingestion of cyproheptadine eight days after the vaccination. Scheduling Order at 1, ECF No. 69. The order further stated that respondent’s expert, Dr. Leist, opined that there was no evidence in the medical records that petitioner suffered from aseptic meningitis following the hepatitis vaccine. Petitioner was ordered to file medical literature in support of Dr. Bourque’s opinions showing (1) a connection between the hepatitis vaccine and aseptic meningitis; (2) a connection between aseptic meningitis and seizures; and (3) a connection between the hepatitis vaccine and seizures. Id. On November 14, 2017, petitioner filed a status report stating that he had no further evidence to offer and requesting the opportunity to cross-examine respondent’s expert. Pet. S.R., ECF No. 70. During a status conference held on November 15, 2017, respondent objected to petitioner’s request to cross-examine Dr. Leist and referred to a discussion on the record following Dr. Bourque’s testimony in September, in which petitioner mentioned only reserving his right to have Dr. Bourque respond to Dr. Leist in a written submission. Scheduling Order at 1, ECF No. 71. I agreed that petitioner had reserved his right to have Dr. Bourque respond to Dr. Leist’s report, but noted that petitioner’s counsel would be allowed to cross-examine Dr. Leist if he felt that it was necessary to ensure that the record was complete. Id. Petitioner’s counsel stated that he considered the record to be well-developed, and asked for time to reconsider his request to cross- examine Dr. Leist. Id. On November 16, 2017, petitioner filed a status report withdrawing his request to cross-examine Dr. Leist, indicating that he no longer felt it was necessary. Pet. S.R. at 1, ECF No. 73. Dr. Bourque did not respond to Dr. Leist’s report or opinions. This matter is now ripe for decision. II. Relevant Medical History and Petitioner’s Testimony Petitioner provided testimony via videoconference on August 28, 2017. At the time of his testimony, he was very confused. Since his vaccination, petitioner has been diagnosed with stage IV metastatic prostate cancer. Tr. 6. At the time of his testimony, he had just concluded radiation treatment. Tr. 6-8. He often conflated what he claimed to be complaints following the vaccination with those associated with his cancer. For example, when his counsel asked him if he was sick part of the week, or the whole week after receipt of his vaccination, petitioner responded, “It was horrible. It was horrible. I was awake, I hurt, I can’t describe how I felt. There’s no way to describe how it feels. It hurts – I didn’t know I had the bone cancer for years, and that’s why it got advanced, and that’s why it hurts so bad. Everything hurts. And I just had the thing last – shot yesterday – yesterday or the day before yesterday and I’m still trying to recover from the shots.” Tr. 15. 4 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 5 of 23 Petitioner was referring to his last cancer treatment received the day before his testimony. Petitioner’s counsel did an admirable job trying to keep petitioner focused and on point. A. Petitioner’s Health Prior to the Hepatitis Vaccination Petitioner was born on October 2, 1943. Pet. Ex. 3 at 218. Petitioner served in the Vietnam War; he was honorably discharged after receiving a severe blow to the head and crush injuries to his knees and back. Pet. Ex. 2 at 80, 83. Petitioner received his primary care at Togus Veterans Administration Hospital (“Togus”). He was treated for hypertension, Post-Traumatic Stress Disorder (“PTSD”), osteoarthritis, hearing loss, gastroesophageal reflux disorder (“GERD”), migraines, abnormal glucose, chronic back pain, and chronic hepatitis C. Id. at 99-100. His past medical history also included Agent Orange exposure, alcohol dependence, Stevens-Johnson syndrome after taking hydrochlorothiazide,4 hyponatremia,5 and an allergy to sulfa drugs. Id. at 83, 155; Pet. Ex. 3 at 304, 308; Tr. 30-32, 45. On November 22, 2012, one year prior to his alleged vaccine related injuries, petitioner presented to the emergency room with nausea, vomiting, fever and headache as a result of hyponatremia. See generally Pet. Ex. 5. Petitioner returned two or three days later due to continued headache. He had apparently fallen and hit his head. A head CT was performed and was normal. Id. Just prior to the receipt of the vaccine alleged herein, petitioner was admitted to Togus’ inpatient rehabilitation program for alcohol and cannabis dependence following 15 years of a fifth of whiskey a day. Pet. Ex. 2 at 79. Petitioner had a certificate for medical marijuana and ate a brownie at night to help him sleep. Id. at 118. Petitioner regularly used benzodiazepine to treat panic attacks and anxiety but claimed to have discontinued its use prior to his vaccination. Id. at 111, 117. On November 15, 2013, petitioner presented for follow-up at Togus. Pet. Ex. 2 at 99. He was noted to be without alcohol for 36 days. Id. During that visit, he received a Twinrix hepatitis A and B vaccine. Id. at 102. Petitioner alleges that only the hepatitis A vaccine caused him to develop seizures. Pet. at ¶¶3, 15. At hearing, petitioner stated that he did not recall the nurse who administered the vaccine informing him that he could develop fever, chills, or muscle aches after the vaccine. Tr. 33-34. 4 Petitioner had Stevens – Johnson Syndrome from hydrochlorothiazide, which treats water retention. Stevens- Johnson Syndrome is a reaction to medications or injection, with a red-purplish rash that spreads and blisters. It requires emergency medical attention, usually hospitalization, and permanent avoidance of the medication. Stevens- Johnson syndrome, MAYO CLINIC (Apr. 22, 2014), http://www.mayoclinic.org/diseases-conditions/stevens-johnson- syndrome/basics/definition/con-20029623 (LAST VISITED OCT. 31, 2016). 5 Hyponatremia is a condition that occurs when the level of sodium in the blood becomes abnormally low. Hyponatremia can cause nausea, vomiting, headache, confusion, fatigue, muscle weakness, and seizures. Hyponatremia, MAYO CLINIC (May 28, 2014), http://wwwmayoclinic.org/diseases- conditions/hyponatremia/basics/symptoms/con-20031445 (LAST VISITED NOV. 2, 2016). Petitioner had been diagnosed with hyponatremia a year prior to the administration of his hepatitis vaccine, during his hospital visit on November 22, 2012. See generally Pet. Ex. 5. 5 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 6 of 23 B. Petitioner’s Health after the Hepatitis Vaccination and Testimony Petitioner testified that as soon as he received the vaccine, he immediately felt sick; his headache was “screaming.” He had no idea how he drove home. He admitted to having headaches since Vietnam, but this one was worse, but he didn’t say anything to anyone at Togus. Tr. 11; 39. According to the petitioner, Togus is over a two-hour drive, or 250 miles, from his home, and though he put his home address into the GPS, he got lost several times and drove past his own house. Tr. 11. By the time he got home, he had a fever, headache, nausea, and vomiting. Tr. 39- 40. He has not “eaten right” since receiving the hepatitis vaccine. Tr. 13. Petitioner stated that in the week following the vaccination, he suffered from vomiting, fatigue, headaches, and could not stay awake. He also had a high fever. Tr. 13, 16-17. Petitioner testified that other than his usual medications, he did not take anything for the vomiting, headache, or fever that week. Tr. 49-50. Petitioner did recall his wife making him a protein drink during the week after the vaccination. Tr. 52. According to petitioner the headache, fever, nausea, and vomiting persisted until his wife called an ambulance to take him to the hospital. Tr. 14. Petitioner testified that his wife called the doctor at Togus twice to report petitioner’s symptoms and left messages, but the doctor did not call back. Tr. 40. He later stated that his wife called the doctor in Newport, not Togus, but he couldn’t remember her name.6 Tr. 49. Petitioner was reminded by counsel that his wife had to call an ambulance after he took cyproheptadine.7 Tr. 18. According to the petitioner, he was given cyproheptadine for pain and he took it for the first time four or five days after the vaccination because he was in severe pain, his headache was “so bad,” and he was “sick as a dog.” Tr. 19, 52. He later conceded that the pain he was referring to after the vaccination was probably from the cancer, not the vaccination, admitting that he has had pain from the cancer way before he received the vaccination. Tr. 27, 44. Petitioner stated that after he took the cyproheptadine, he began seeing flashing lights as well as “little tiny red bugs.” Tr. 18. His wife became scared and called an ambulance when she found him in a La- Z-Boy recliner, seizing. Tr. 18, 20. According to the petitioner, he was shaking so much that the EMTs could not administer the propofol. Tr. 20. Petitioner stated that his wife was told he stopped breathing at least three times. Tr. 20. 6 Petitioner has not produced any medical records or telephone records to confirm that any phone calls were made to any doctor the week following the vaccination. Petitioner’s wife did not testify at hearing, though she was present outside of the hearing room during petitioner’s testimony. The undersigned asked both counsel if either wanted testimony from Mrs. Mondello after petitioner had finished testifying, but both counsel stated that they did not. 7 Cyproheptadine is an antihistamine used to relieve allergy symptoms such as sneezing, itching, watery eyes, runny nose, and other symptoms of allergies. Cyproheptadine, University of Michigan Health System (Dec. 3, 2013), http://www.uofmhealth.org/health-library/d00790a1 (last visited Nov. 1, 2016). Side effects of cyproheptadine include sedation, dizziness, urticaria, blurred vision, palpitations, and fatigue; overdosage may produce hallucinations, CNS depression, and convulsions. Cyproheptadine may have “additive effects” with alcohol and other CNS depressants, like sedatives or antianxiety agents. Cyproheptadine is contraindicated for “elderly, debilitated” patients. Cyproheptadine Hydrochloride Tablets – Drug Summary, PDRnet, http://www.pdrnet/drug- summary/Cyproheptadine-Hydrochloride-Tablets-cyproheptadine-hydrochloride-1549 (last visited Nov. 1, 2016). 6 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 7 of 23 When asked what medications he was taking at the time of the seizure, petitioner could not recall, but stated that his wife gives him his medications. Tr. 40-41. When asked about gabapentin,8 petitioner responded he believed he took it to help with his memory, and to help him eat. Tr. 42. Petitioner indicated that he used medical marijuana, but denied that he used it at the time he received the vaccine. Tr. 47-48. Upon his arrival to St. Joseph’s Hospital on November 22, 2013, it was noted, “Patient was last known well (about 1 hour PTA). (pt’s wife at bedside and reports that pt. recently had a hepatitis A vaccination given to him on Friday and has not been feeling well since. Nausea/vomiting and poor apetite. (sic) Per pt’s wife at approx. 5 pm today he began to hallucinate (visual)).” Pet. Ex. 1 at 7. Petitioner’s wife also reported that petitioner had taken cyproheptadine for the first time at around 4 p.m.; he became confused shortly thereafter and began hallucinating and talking about flashes of light. Pet. Ex. 3 at 296. Petitioner then had a seizure and his wife called an ambulance. Id. Petitioner’s Glasgow Score (GCS)9 upon arrival was 7; he was intubated and administered Valium. Pet. Ex. 1 at 8, 21. A head CT was normal. Id. at 25. A urine test was positive for benzodiazepines and marijuana, with elevated glucose, trace blood, and protein. Id. at 26-27. Petitioner was then transferred to the emergency department at Eastern Maine Medical Center (“EMMC”) with an assessment of “generalized status epilepticus of unknown cause.” Id. at 31. It was noted that petitioner was a longstanding alcoholic but had been sober for 46 days, and had no prior history of seizures. Id. at 7, 22. While at EMMC, petitioner underwent testing, including a chest x-ray, EEG, and head MRI without contrast. Pet. Ex. 5 at 1393-99. The chest x-ray revealed that petitioner’s heart was “mildly enlarged.” Id. at 1396. Petitioner’s EEG reflected “diffuse right-sided slowing,” “transient periodic right lateralized discharges involving frontal area,” and “intermittent spikes throughout the record involving right frontal area.” Id. at 1394. Petitioner’s MRI of the head showed “no acute or malignant intracranial process,” with “moderate burden of white matter signal changes” and “mild diffuse cerebral volume loss.” Id. at 1400. The general impression of the MRI was a finding of uncertain clinical significance. Id. Petitioner came under the care of Dr. Bourque, a neurologist. Dr. Bourque ordered a lumbar puncture to rule out herpes simplex virus encephalitis “or other bacterial meningitis.” Pet. Ex. 7 at 1435. Dr. Bourque noted a concern that petitioner “may have an aseptic meningitis related to the vaccination.” Id. Petitioner’s labs were negative for cryptococcus and herpes simplex virus. Pet. Ex. 3 at 290. His lumbar puncture showed a “modest elevation in cerebrospinal fluid protein.” Id. at 289. Dr. Bourque prescribed 500 mg of Keppra twice a day for seizures. Pet. Ex. 7 at 1435. 8 Gabapentin is an anticonvulsant used to treat refractory focal seizures, neuropathic pain, and migraines. Common side effects include dizziness, ataxia, sedation, fatigue, and nystagmus. See Dorland’s Illustrated Medical Dictionary 753 (Saunders eds., 32nd ed. 2012); see also Pediatric Neurology: Principles & Practice 962-63, 1197, 2378 (Swaiman, Ashwal, & Ferriero eds., 4th ed. 2006). 9 “GCS” is the abbreviation for “Glasgow Coma Scale.” The Glasgow Coma Scale is the most common scoring system used to gauge the severity of an acute brain injury, with a score of “3” as the most severe and a score of “15” as the least severe, or normal. What Is the Glasgow Coma Scale?, BRAINLINE.ORG, http://www.brainline.org/content/2010/10/what-is-the-glasgow-coma-scalehtml (LAST VISITED NOV. 1, 2016). 7 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 8 of 23 Petitioner was discharged from EMMC on November 27, 2013, with a diagnosis of “new- onset seizure,” delirium and hyponatremia. Pet. Ex. 3 at 285. Petitioner’s discharge summary stated: “[at] the time of this dictation, there is no specific etiology assigned to this patient’s symptoms. Certainly his general condition was consistent with alcohol withdrawal although the patient and multiple family members state that there has been on (sic) use of alcohol in the past six weeks. One must also consider the possibility of withdrawal from benzodiazepines, the effects of the hepatitis A vaccine that he received a few days prior, withdrawal from other medications, side effects of other medications, and a multitude of other metabolic derangements. In addition, the patient’s history of a traumatic brain injury in Vietnam may put him at increased risk for development of a seizure disorder. Despite the lack of a specific diagnosis, the patient’s general condition has improved remarkably. He is now essentially at his baseline.” Id. at 290. Petitioner received physical therapy at home through December 2013. See generally Pet. Ex. 4. Petitioner next presented to Mayo Practice Associates (“Mayo”) on January 9, 2014, complaining of left trapezius strain and knee pain. Pet. Ex. 8 at 1475. Petitioner’s records list “cyproheptadine HCl” as one of his allergies, with a reaction of “seizures, confusion.” Id. at 1476. Petitioner returned to Mayo on January 23, 2014, for a follow-up of palpitations. Id. at 1477. The assessment was that he had an elevated prostate-specific antigen, palpitations, and benign localized prostatic hyperplasia. Id. at 1479. On January 30, 2014, petitioner presented to Dr. Bourque for a follow-up. Pet. Ex. 7 at 1421. Dr. Bourque noted that she had initially met petitioner at the hospital on November 23, 2013 when he presented with a new onset of seizures. Id. Her notes for that date state: “At the time of the hospitalization, he had had a hepatitis A vaccination 1 week prior, and for that week had had nausea, vomiting, headache, and chills. He had been tremulous and just generally not feeling well. On the day of presentation, he took for the first time ever cyproheptadine 4 mg, and he had never taken this medication before. His wife states that within 20-30 minutes he started having visual hallucinations, and she went to call 911 and when she came back, she found him seizing.” Id. “He has not had any further severe headaches that occurred the week of presentation. He also has not had any fevers or lateralized weakness. There have been no seizures.” Id. Following her examination, Dr. Bourque documented “Impression and Plan: [Petitioner] presented to hospital in November 2013 one week following hepatitis A vaccination and was found to have altered mental status following intake of cyproheptadine and subsequent recurrent seizures. He has done well post discharge on Keppra in terms of no further seizures. Overall, his mental status has returned close to baseline according to the family, although his wife states 8 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 9 of 23 he has occasional episodes where his ability to give directions seems impaired.” Id. at 1422. Dr. Bourque suggested he be seen by neuropsychology to get a baseline and assess cognitive strengths and weaknesses. Id. On February 24, 2014, a repeat EEG was performed which was normal. Prior findings seen during his hospitalization had resolved. Pet. Ex. 7 at 1430. On April 7, 2014, petitioner returned to Dr. Bourque for follow up of seizures. Dr. Bourque noted: “He has been on Keppra ever since the episode, which occurred during a week when he had had the hepatitis A vaccine and was not feeling well and was subsequently given 4 mg of cyproheptadine and shortly after developed visual hallucinations and seizures. He has continued on the (sic) Keppra and has not had any further seizures.” Pet. Ex. 7 at 1429. He had gone back to drinking alcohol but stopped again a week and a half ago. Id. He started driving with no issues and there has been no further “confusion spells.” Id. A repeat EEG performed on February 24, 2014 was normal and the prior findings seen during the hospitalization had resolved. Id. at 1430. Following examination, Dr. Bourque reported: “Impression and Plan: [Petitioner] had presented to hospital on November 2013 one week after a hepatitis A vaccination and developed hallucinations and seizures shortly after taking cyproheptadine. He has had no further seizures. His EEG is now normal. I did discuss with [petitioner] and his wife today that in light of the provoked nature of his seizures and the normal EEG, we could consider tapering off the Keppra, although there is potential for recurrent seizures. He is not interested in pursuing this option as it would mean stopping driving for 6 months. We also discussed the possibility of switching Keppra to Trileptal, however, he finds he is tolerating it better and is not interested in not driving for 3 months during the switch.” Id. Petitioner next presented to Dr. Bourque nearly a year later on March 20, 2015 for possible “breakthrough seizure.” Pet. Ex. 7 at 1426. Petitioner testified that he had tried to wean himself off Keppra without consulting a doctor; he became sick immediately. Tr. 22-23. He stated that after he started slurring his words and his speech was garbled, he started retaking Keppra. Tr. 23. Dr. Bourque noted that petitioner “had hepatitis A vaccine and was given 4 mg of cyproheptadine. He had an abnormal EEG at that time and was started on Keppra. We continued the Keppra as we did not know if he would have any further predisposition to seizures, and he did not want to go with driving cessation and his wife was worried about another seizure.” Id. Dr. Bourque advised that he should remain on the full dose and she would see him in the fall to discuss tapering. Id. at 1427. Petitioner returned to Dr. Bourque on October 2, 2015 for follow up. Pet. Ex. 7 at 1450. He had no further seizures. Under “Impression and Plan,” Dr. Bourque noted that petitioner “continues to have a history of hospitalization with what was suspected to be possible be (sic) a provoked seizure in 2013, with an abnormal EEG at that time. When he tried taking himself off Keppra earlier this year, he had what was an atypical spell that may have represented a seizure so we will continue the Keppra.” Id. at 1451. 9 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 10 of 23 On March 18, 2016, petitioner returned to Dr. Bourque for a follow up. Pet. Ex. 9 at 1485. He was again noted to have had a seizure in November of 2013 after he had “a hepatitis vaccine and had been feeling unwell and was given cyproheptadine.” Id. Since an “unusual episode” when he tried to wean off Keppra, he has had no further seizures. Id. “He does find that overall he is not very good in familiar places and finding his way. He also finds it difficult to do things that he previously did for years. He does continue to have intermittent lapses in his alcoholism.” Id. After her examination, Dr. Bourque noted “Impression and Plan: [petitioner] continues to have a history of hospitalization in November 2013 for suspected provoked seizure, which was likely a combination of being unwell from a hepatitis A vaccine and the compilation of cyproheptadine….He has some various cognitive complaints, which are likely multifactorial in light of his prior head injuries, alcoholism, chronic pain and untreated psychiatric illness.…He does continue on thiamine.” Id. at 1486. He was discharged from neurological care on that date. Id. Petitioner testified that, in the summer of either 2016 or 2017, his Keppra was increased after his wife accidentally slammed the trunk lid on his head, causing him to have a seizure the next day. Tr. 24. Petitioner is being treated for Stage IV metastatic prostate cancer. Tr. 6. III. Expert Opinions and Literature The petitioner relied upon his treating neurologist, Dr. Suzanne Bourque, to support his claim that the seizures he suffered were caused by the hepatitis A vaccine he received. Dr. Bourque is a neurologist with a specialty in neuromuscular disease. Tr. 60; Pet. Ex. 15. She earned her medical degree from the University of British Columbia, Vancouver, in 2006 and completed a residency in neurology in 2011, followed by a one-year fellowship in neuromuscular disease. Tr. 60-61; Pet. Ex. 15. Dr. Bourque practiced at EMMC until April of 2016. Tr. 61. She now works for Kaiser Permanente in San Rafael, California. Tr. 60. In response to Dr. Bourque’s testimony and the literature submitted by petitioner, respondent submitted an expert report from Dr. Thomas Leist. Dr. Leist has a Ph.D. in biochemistry from the University of Zurich and a medical degree from the University of Miami. Resp. Ex. F at 1. He completed his residency in neurology at Cornell Medical Center. Id. Since 2000, Dr. Leist has been a professor of neurology at Thomas Jefferson University, where he is also the director of Hospital-based Neurology Infusion Services. Id. Dr. Leist did not testify. Dr. Bourque based her theory upon her experience as a neurologist, petitioner’s clinical presentation, and elevated proteins present in the petitioner’s cerebrospinal fluid (“CSF”). Her theory was that petitioner developed aseptic meningitis10 following receipt of the hepatitis A 10 Aseptic meningitis describes any clinical syndrome characterized by meningeal inflammation not caused by an identifiable pathogen in the CSF. Allan R. Tunkel et al., Acute Meningitis, 1 MANDELL, DOUGLAS, AND BENNETT’S PRINCIPLES AND PRACTICES OF INFECTIOUS DISEASES 1189 (7th ed. 2010), hereinafter “Infectious Diseases.” Common symptoms in adults with aseptic meningitis include headache, photophobia, stiff neck, rash, diarrhea, cough, upper respiratory symptoms, anorexia, and vomiting. Id. at 1204-05. 10 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 11 of 23 vaccine, which lowered his seizure threshold to the extent that introducing cyproheptadine to his already-primed system caused him to have a seizure. Tr. 77. Dr. Bourque explained that viral illness or vaccination can cause the tissues covering the brain and spinal cord to become inflamed, leading to aseptic meningitis.11 Tr. 74, 82; Pet. Ex. 16 at 2. According to Dr. Bourque, “meningitis” is the general term for inflammation of the meninges and brain. When no bacteria is present, it is called “aseptic.” Tr. 83. According to Dr. Bourque, there is no test for aseptic meningitis, but symptoms of fever and elevated protein are an indication of the disease. Tr. 83. Petitioner’s history of nausea, vomiting, and worsened headaches after the hepatitis vaccine made her suspect aseptic meningitis. Tr. 67-68; Pet. Ex. 16 at 2; Pet. Ex. 3 at 307. She therefore ordered a lumbar puncture to rule out herpes simplex virus encephalitis and aseptic meningitis. Pet. Ex. 16 at 2. The test results were negative for a viral infection. Dr. Bourque admitted that sometimes CSF proteins are elevated for no reason.12 Pet. Ex. 16 at 2; Tr. 101-02, 119-20. Dr. Leist dismissed Dr. Bourque’s theory of aseptic meningitis, stating that petitioner’s medical records did not support the diagnosis. Resp. Ex. E at 6. According to Dr. Leist, petitioner’s diagnostic work up showed a white cell count of less than 1, red cell count of 3, glucose of 82 and protein of 88. Pet. Ex. 3 at 1279; Tr. 141. When aseptic meningitis is present, the white cell count is elevated; petitioner’s white cell count was not elevated. Resp. Ex. E at 6; see also Resp. Ex. G13 at 1. Dr. Leist further stated that petitioner’s elevated CSF protein was a normal increase typically seen after seizures. Resp. Ex. E at 7; Resp. Ex. I14 at 1, 3. Dr. Leist also stated that petitioner’s medical history of lower back injury or his later diagnosis of stage IV prostate cancer could have been responsible for the elevated CSF protein level.15 Resp. Ex. E at 7. 11 Noninfectious etiologies of aseptic meningitis include, but are not limited to, certain drugs, vaccines, systemic illness, and medical procedures. Infectious Diseases at 1190. 12 “CSF pleocytosis is almost always presents” in aseptic meningitis. The total CSF cell count is usually 100 to 1000 cell/mm3. However, “elevated CSF protein and decreased CSF glucose concentrations, if present, are usually mild….” Infectious Diseases at 1207. 13 Barbara Negrini et al., Cerebrospinal Fluid Findings in Aseptic Versus Bacterial Meningitis, PEDIATRICS, 105(2): 316-19 (2000), filed as Resp. Ex. G. In this study, cases of aseptic meningitis were defined as having at least 20 white blood cells/mm3. This study was done on children and the authors noted that the data was difficult to interpret because many of the patients received antibiotics prior to the lumbar puncture. Petitioner was given acyclovir on November 24, 2013, due to Dr. Bourque’s concern for viral infection, but discontinued after the lumbar puncture results were available. Pet. Ex. 3 at 959. 14 Vaso Zisimopoulou et al., Cerebrospinal fluid analysis after unprovoked first seizure, FUNCT NEUROL, 31(2): 101-07 (2016), filed as Resp. Ex. I. This study was on males with an average age of 36. The results showed that CSF protein was higher than normal after an unprovoked seizure, and implied a disruption of the blood-brain barrier in patients with unprovoked seizures. Abnormal protein levels showed significant positive correlation with male gender and older age. It was noted that “Lumbar degenerative changes and/or stenosis found in older patients can potentially confound the correlation of age with CSF protein elevation.” Id. at 3. Petitioner had chronic back pain. Pet. Ex. 2 at 99-100. 15 Petitioner refused a referral for a prostate biopsy for elevated prostate-specific antigen (PSA) during a visit to Mayo Practice Associates on January 23, 2014. Pet. Ex. 8 at 1479; Resp. Ex. E at 4. 11 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 12 of 23 Dr. Leist submitted that the Institute of Medicine reviewed the adverse events following hepatitis A and B vaccination, and aseptic meningitis is not listed as an adverse event for either vaccine. Resp. Ex. E at 6. The IOM Report states that three publications reported encephalitis or encephalopathy after hepatitis B vaccine, but did not provide any support for a connection other than temporal relationship. Id. at 6-7; Resp. Ex. H.16 Dr. Bourque further opined that seizure activity can manifest itself after anything that lowers the seizure threshold, such as a prior head injury. Tr. 68, 70, 74. She explained that petitioner had a “provoked” seizure because he seized after a triggering event, like the use of a medication, noting that unlike unprovoked seizures, someone suffering from a provoked seizure is less likely to have another seizure. Tr. 77-78. When petitioner came under her care, she researched the role of the hepatitis vaccine to determine a cause for his seizures. She could not recall if she found anything about hepatitis vaccine specifically, versus vaccinations in general. Tr. 105, 120. She did not research the medically appropriate time period for a vaccine to cause seizures, nor did she know whether hepatitis A vaccine can cause seizures. Tr. 105-06, 120. She also looked up cyproheptadine to determine whether it was a potential cause for petitioner’s seizures and found that seizures were a potential side effect of the medication. Tr. 65- 66; 117-18; see Resp. Ex. C,17 Resp. Ex. D.18 Dr. Bourque agreed that the cyproheptadine could have been responsible for petitioner’s abnormal EEG while hospitalized, but did not believe that it would have caused petitioner’s elevated CSF protein. Tr. 118-20. According to Dr. Bourque “…anything in theory could have triggered this.” Tr. 95, 98- 102. “That’s the hard thing with seizures, it’s always kind of estimating the potential contributors and what their susceptibility is and it’s hard to be definitive.” Tr. 118. Dr. Bourque opined that a combination of petitioner’s prior traumatic brain injury, his recent sobriety after a long history of alcoholism, and the hepatitis vaccine contributed to his lowered seizure threshold. Tr. 131-32. The cyproheptadine was the “trigger” for petitioner’s seizures, based on timing, and had a major role. Tr. 85, 132. Dr. Leist agreed that the cyproheptadine taken by the petitioner was the “provoking agent” of petitioner’s seizures. Resp. Ex. E at 6. Dr. Leist submitted that animal models show that administering cyproheptadine made it easier to induce seizures, increase the severity of seizures, and reduce the efficacy of anti-epileptic medications. Resp. Ex. E at 6; Resp. Ex. C.19 16 K. Stratton, et al., ADVERSE EVENTS OF VACCINES: EVIDENCE AND CAUSALITY (2012) at 421-38, filed as Resp. Ex. H. 17 Damanpreet Singh and Rajesh Kumar Goel, Proconvulsant potential of cyproheptadine in experimental animal models, FUNDAM CLIN PHARMACOL, 24: 451-55(2010) (Noting that cyproheptadine is frequently prescribed as an appetite stimulant, and found that cyproheptadine reduces seizure threshold and decreases the efficacy of clinically used anti-epileptic drugs), filed as Resp. Ex. C. 18 Luke Shankar et al., Cyproheptadine induced seizures, MED RES CHRON, 2(1) 41-43 (2015) (concluding that cyproheptadine reduces seizure threshold, increases the severity of seizures, and decreases the efficacy of clinically used anti-epileptic drugs), filed as Resp. Ex. D. 19 Supra, n.17. 12 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 13 of 23 Dr. Leist added that petitioner’s other health issues were more likely to blame for his feeling ill in the week prior to the seizure. Dr. Leist stated that though petitioner’s wife had reported that he had experienced nausea, vomiting and poor appetite following the hepatitis vaccine, he had similar gastrointestinal complaints a year earlier associated with hyponatremia and had been hyponatremic on October 10 and 15 of 2013 during his alcohol rehabilitation. Resp. Ex. E at 7; Pet. Ex. 2 at 65. Dr. Leist added that petitioner was discharged from alcohol rehabilitation with a new prescription for Venlafaxine, which may have been responsible for his not feeling well and has been associated with hyponatremia in the elderly with symptoms of headache, difficulty concentrating, memory impairment, confusion, weakness and unsteadiness which may lead to falls. Seizures are also associated with the medication. Resp. Ex. E at 7-8; Resp. Ex. J.20 Dr. Leist concluded that there was no evidence in the record that petitioner suffered from aseptic meningitis on November 22, 2013, or that petitioner had any adverse reaction to the hepatitis vaccine he received. Dr. Leist concluded that the cyproheptadine was the cause of Mr. Mondello’s seizures and that the hepatitis vaccine had no role. Resp. Ex. E at 8. In support of his petition, petitioner submitted a vaccine information sheet for hepatitis A; a vaccine information sheet for hepatitis B; the package insert for Twinrix vaccine, an article titled “A case-control study of serious autoimmune adverse events following hepatitis B immunization” by David and Mark Geier;21 and an article titled “Population-Level Evidence for an Autoimmune Etiology of Epilepsy” by Mei-Sing Ong et al.22 Pet. Ex. 10-14. None of the literature submitted addressed hepatitis A vaccine and/or aseptic meningitis.23 The vaccine information sheets submitted by petitioner list the benefits of receiving the hepatitis vaccine, the complications that receiving hepatitis A or B vaccine can cause, and the risks of reaction from the vaccinations which include soreness or redness where the shot was given, low-grade fever, headache and tiredness which could last one to two days, feeling faint, shoulder pain, or an allergic reaction which could happen within minutes to a few hours after vaccination. See generally Pet. Ex. 10-11. Petitioner submitted the package insert for Twinrix which lists “convulsions” among the events that have suspected causal connection to the components of Twinrix. Pet. Ex. 12 at 7. The package insert contains the following: “These events are reported voluntarily from a population of uncertain size, [so] it is not possible to reliably estimate their frequency or establish a causal relationship to product exposure.” Id. at 6. Special masters have found that vaccine package inserts are not probative of causation. See H.L. v Sec’y of Health & Human Servs, No. 10-197V, 2016 WL 3751848, at *13 (Fed. Cir. 2017); Sullivan v. Sec’y of Health & Human Servs., No 10-398, 20 Effexor (venlafaxine hydrochloride) prescribing information, Wyeth Pharmaceuticals, Inc., filed as Resp. Ex. J. 21 David A. Geier and Mark R. Geier, A case-control study of serious autoimmune adverse events following hepatitis B immunization, AUTOIMMUNITY, 38(4): 295-301 (2005), filed as Pet. Ex. 13. 22 Mei-Sing Ong et al., Population-Level Evidence for an Autoimmune Etiology of Epilepsy, JAMA NEUROL, 71(5): 569-74 (2014), filed as Pet. Ex. 14. 23 Dr. Bourque did not provide any literature in support of her opinions in this matter, despite an opportunity to do so. See Scheduling Order, ECF No. 69. 13 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 14 of 23 2015 WL 1404957, at *20 (Fed. Cl. Spec. Mstr. Feb 13, 2015)(“[s]tatements contained in vaccine inserts do not constitute reliable proof of causation, and cannot be deemed admissions that vaccines in question have the capacity to harm a particular petitioner in a specific manner”); see also Werderitsh v. Sec’y of Health & Human Servs., No. 99-319V, 2005 WL 3320041, at *8 (Fed. Cl. Spec. Mstr. Nov. 10, 2005)(quoting CFR § 600.80 as saying “A report or information submitted by licensed manufacturer…does not necessarily reflect a conclusion by the licensed manufacturer or FDA that the report or information constitutes an admission that the biological product caused or contributed to an adverse effect.”). Petitioner submitted a 2005 case study by Dr. Mark Geier and Mr. David Geier24 titled “A case-control study of serious autoimmune adverse events following hepatitis B immunization.” The study relied upon data from the Vaccine Adverse Events Reporting (VAERS) database and discussed the increase of autoimmune diseases following hepatitis B vaccine.25 Dr. Leist pointed out that VAERS is a passive reporting system which collects data on adverse events associated with vaccinations for signal finding purposes. Pet. Ex. 13; Resp. Ex. E at 5. He explained that VAERS provides neither conclusions regarding causation nor data on incidence. See Manville v. Sec’y of Health & Human Servs., 63 Fed. Cl. 482, 494 (2004) (finding that the special master did not err in dismissing “any significant value” of VAERS reports proffered by petitioner where the special master “noted that a VAERS report can be filed by anyone, thereby bringing into question the quantity and quality of the information gathered…”). The article provided no evidence for any association between Hepatitis A/B vaccination and seizure disorder. Id. It is notable that studies by David and Mark Geier have been routinely discredited in this program due to Dr. Mark Geier not being qualified to opine on issues of neurology, immunology, or rheumatology.26 The Ong article, “Population-Level Evidence for an Autoimmune Etiology of Epilepsy,” submitted by petitioner, examined “the relationship between epilepsy and 12 autoimmune 24 David A. Geier is not a doctor. He has not earned any advanced medical or scientific degrees. Riggins v. Sec’y of Health & Human Servs., No. 99-382V, 2009 WL 3319818, at *6-7 (Fed. Cl. Spec. Mstr. June 15, 2009). The State of Maryland revoked Mark Geier’s license to practice medicine in 2012. Hooker v. Sec’y of Health & Human Servs., No. 02-472V2016 WL 3456435, at *30-31 (Fed. Cl. Spec. Mstr. May 19, 2016). 25 Pet. Ex. 13, supra n.21. 26 See Doe/78 v. Sec’y of Health & Human Servs., 2010 WL 3154546 (Fed. Cl. Spec. Mstr. Jul. 26, 2010) (finding the published medical research of Dr. Mark Geier and his son to be unreliable. (Fn. 16)); Pafford, 451 F.3d 1352 (concluding that the special master was justified in rejecting the testimony of Dr. Mark Geier based on the insufficiency of Dr. Geier’s credentials); Raj v. Sec’y of Health & Human Servs., No. 96-294V, 2001WL 963984 (Fed. Cl. Spec. Mstr. Jun. 14, 2001)(criticizing Dr. Mark Geier as poorly qualified to opine on neurologic issues and finding his testimony to be “quite unpersuasive.”); Haim v. Sec’y of Health & Human Servs., No. 90-1031V, 1993 WL 346392 (Fed. Cl. Spec. Mstr. Aug. 27, 1993) (holding that the testimony of Dr. Mark Geier did not meet the level of evidentiary reliability required by Daubert, because it was not based upon scientific validity, valid methodology, peer review or testing, and more than minimal support within the scientific community.); Marascalco v. Sec’y of Health & Human Servs., No. 90-1571V, 1993 WL 277095 (Fed. Cl. Spec. Mstr. Jul. 9, 1993)(according no weight to Dr. Geier’s testimony and finding his affidavit to be “seriously intellectually dishonest” and “an egregious example of blatant, result-oriented testimony” which “undermines wholly his credibility as a witness.”); Ormechea v. Sec’y of Health & Human Servs., No. 90-1683V, 1992 WL 151816 (Fed. Cl. Spec. Mstr. Jun. 10, 1992)(finding that, “[b]ecause Dr. [Mark] Geier has made a profession of testifying in matters to which his professional background (obstetrics, genetics) is unrelated, his testimony is of little value to the court.”). 14 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 15 of 23 diseases: type I diabetes mellitus, psoriasis, rheumatoid arthritis, Grave’s disease, Hashimoto thyroiditis, Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjogren syndrome, myasthenia gravis and celiac disease.” Pet. Ex. 14 at 1.27 Dr. Leist pointed out that the study was of children under the age of 18 and nonelderly adults under the age of 65. Resp. Ex. E at 5. Petitioner was 70 years of age at the time of his seizure, with well documented risk factors for seizures. Id. Dr. Bourque confirmed that petitioner did not have an autoimmune disease. Tr. 128. In order for an article to be relevant to petitioner’s claim, petitioner must offer some connection between the disease discussed in the article, the vaccine and petitioner’s claimed injury. See H.L., 2016 WL 3751848, at *14, n. 20 (Fed. Cir. 2017)(“Establishing a theory that a vaccine can cause injury “X” is not the same as proving that it can cause injury “Y,” absent some evidence showing that injuries X and Y share sufficient commonality.”). IV. Legal Framework The Vaccine Act provides two avenues for petitioners to receive compensation. First, a petitioner may demonstrate a “Table” injury—i.e., an injury listed on the Vaccine Injury Table that occurred within the provided time period. § 11(c)(1)(C)(i). “In such a case, causation is presumed.” Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006); see § 13(a)(1)(B). Second, where the alleged injury is not listed on the Vaccine Injury Table, a petitioner may demonstrate an “off-Table” injury, which requires that the petitioner “prove by a preponderance of the evidence that the vaccine at issue caused the injury.” Capizzano, 440 F.3d at 1320; see § 11(c)(1)(C)(ii). A petitioner need not show that the vaccination was the sole cause, or even the predominant cause, of the alleged injury; showing that the vaccination was a “substantial factor” and a “but for” cause of the injury is sufficient for recovery. Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006); Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352 (Fed. Cir. 1999).28 Once a petitioner has proven causation by preponderant evidence, “the burden then shifts to the respondent to show by a preponderance of the evidence that the injury is due to factors unrelated to the administration of the vaccine.” Deribeaux ex rel. Deribeaux v. Sec’y of Health & Human Servs., 717 F.3d 1363, 1367 (Fed. Cir. 2013) (citing § 13(a)(1)(B)). The process for making factual determinations in Vaccine Program cases begins with analyzing the medical records, which are required to be filed with the petition. § 11(c)(2). Medical records created contemporaneously with the events they describe are presumed to be accurate and “complete” such that they present all relevant information on a patient’s health problems. Cucuras v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993). In making contemporaneous reports, “accuracy has an extra premium” given that the “proper treatment hang[s] in the balance.” Id. Contemporaneous medical records that are clear, consistent, and complete warrant substantial weight “as trustworthy evidence.” Id. Indeed, “where later testimony 27 Supra, n.22. 28 The Vaccine Act also requires petitioners to show by preponderant evidence that the “residual effects or complications” of the alleged vaccine-related injury lasted for more than six months. § 11(c)(1)(D)(i). It is undisputed that this six-month requirement is satisfied in this case. 15 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 16 of 23 conflicts with earlier contemporaneous documents, courts generally give the contemporaneous documentation more weight.” Campbell ex rel. Campbell v. Sec’y of Health & Human Servs., 69 Fed. Cl. 775, 779 (2006); see United States v. U.S. Gypsum Co., 333 U.S. 364, 396 (1948). But petitioners can support their claim with oral testimony if it is credible and consistent with the medical records. See, e.g., Stevenson ex rel. Stevenson v. Sec’y of Health & Human Servs., No. 90- 2127V, 1994 WL 808592, at *7 (Fed. Cl. Spec. Mstr. June 27, 1994) (crediting the testimony of a fact witness whose “memory was sound” and “recollections were consistent with the other factual evidence”). In short, “the record as a whole” must be considered. § 13(a). Furthermore, establishing a sound and reliable medical theory connecting the vaccine to the injury often requires a petitioner to present expert testimony in support of his or her claim. Lampe v. Sec’y of Health & Human Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). The Supreme Court’s opinion in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993), requires that courts determine the reliability of an expert opinion before it may be considered as evidence. “In short, the requirement that an expert’s testimony pertain to ‘scientific knowledge’ establishes a standard of evidentiary reliability.” Id. at 590 (citation omitted). Thus, for Vaccine Act claims, a “special master is entitled to require some indicia of reliability to support the assertion of the expert witness.” Moberly ex rel. Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1324 (Fed. Cir. 2010). The Daubert factors are used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec’y of Health & Human Servs., 94 Fed. Cl. 53, 66-67 (2010) (“…uniquely in this Circuit, the Daubert factors have been employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness of expert testimony already admitted…”). Where both sides offer expert testimony, a special master’s decision may be “based on the credibility of the experts and the relative persuasiveness of their competing theories.” Broekelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing Lampe, 219 F.3d at 1362). And nothing requires the acceptance of an expert’s conclusion “connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too great an analytical gap between the data and the opinion proffered.” Snyder ex rel. Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 743 (2009) (quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)). Because petitioner did not allege an injury listed on the Vaccine Injury Table, his claim is classified as “off-Table.” As noted above, for petitioner to prevail on an “off-Table” claim, he must show by preponderant evidence that his injury resulted from the vaccination at issue. Capizzano, 440 F.3d at 1320. Doing so shifts the burden to respondent to show that the injury was caused by factors unrelated to the vaccinations. Deribeaux, 717 F.3d at 1367. To prove causation, petitioner must satisfy the three-pronged test established in Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274 (Fed. Cir. 2005). Althen requires that petitioner show by preponderant evidence that the vaccination received caused the injury “by providing: (1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of a proximate temporal relationship between vaccination and injury.” Id. at 1278. Together, these prongs must show “that the vaccine was ‘not only a but-for cause of the injury but also a substantial factor in bringing about the injury.’” Stone v. Sec’y of Health & Human Servs., 676 F.3d 1373, 1379 (Fed. Cir. 2012) (quoting Shyface, 165 F.3d at 1352-53). Causation is determined on a case- by-case basis, with “no hard and fast per se scientific or medical rules.” Knudsen v. Sec’y of Health 16 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 17 of 23 & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). The petitioner is not required to identify “specific biological mechanisms” to establish causation, nor is he required to present “epidemiologic studies, rechallenge, the presence of pathological markers or genetic disposition, or general acceptance in the scientific or medical communities.” Capizzano, 440 F.3d at 1325 (quoting Althen, 418 F.3d at 1280). “[C]lose calls regarding causation are resolved in favor of injured claimants.” Althen, 418 F.3d at 1280. In essence, the special master is looking for a medical explanation of a logical sequence of cause and effect (Althen, 418 F.3d at 1278; Grant, 956 F.2d at 1148), and medical probability rather than certainty (Knudsen, 35 F.3d at 543, 548-49). Medical probability has been explained as biologic credibility rather than specification of an exact biologic mechanism. As the Federal Circuit stated in Knudsen: Furthermore, to require identification and proof of specific biological mechanisms would be inconsistent with the purpose and nature of the vaccine compensation program. The Vaccine Act does not contemplate full blown tort litigation in the Court of Federal Claims. The Vaccine Act established a federal “compensation program” under which awards are to be “made to vaccine-injured persons quickly, easily, and with certainty and generosity.” House Report 99-908, supra, at 3, 1986 U.S.C.C.A.N. at 6344. The Court of Federal Claims is therefore not to be seen as a vehicle for ascertaining precisely how and why DTP and other vaccines sometimes destroy the health and lives of certain children while safely immunizing most others. 35 F.3d at 549. As for epidemiological support for causation, the Federal Circuit in Knudsen, 35 F.3d at 551, ruled for petitioners even when epidemiological evidence directly opposed causation from DPT vaccine. The case concerned the cause of a baby’s encephalopathy after a vaccination. Respondent provided evidence that more encephalopathies are caused by viruses than by vaccines, convincing the special master to rule against petitioners. However, the Federal Circuit thought the epidemiologic evidence should not bar petitioners from prevailing. Even though epidemiological evidence supported respondent’s defense in Knudsen that viruses were more likely to cause encephalopathy than vaccinations, the Federal Circuit held that that fact alone was not an impediment to recovery of damages. In Knudsen, the Federal Circuit stated: The bare statistical fact that there are more reported cases of viral encephalopathies than there are reported cases of DTP encephalopathies is not evidence that in a particular case an encephalopathy following a DTP vaccination was in fact caused by a viral infection present in the child and not caused by the DTP vaccine. 35 F.3d at 550. 17 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 18 of 23 The special masters “are entitled–indeed, expected–to make determinations as to the reliability of the evidence presented to them and, if appropriate, as to the credibility of the persons presenting that evidence.” Moberly, 592 F.3d at 1325. The Federal Circuit also stated that petitioner does not need epidemiological support in order to prevail and does not have the burden of proving a specific biological mechanism. Id. In Althen and Capizzano, the Federal Circuit stated that petitioner does not need to file supportive medical literature to prevail. V. Discussion Respondent defends this case by submitting that there is a lack of support in the medical records for Dr. Bourque’s theory of aseptic meningitis. Respondent did not address Dr. Bourque’s opinions regarding petitioner’s lowered seizure threshold resulting from the hepatitis vaccine and other co morbidities, causing the cyproheptadine to trigger his seizures. Respondent states that the cyproheptadine petitioner took was the sole cause of petitioner’s seizures, and petitioner’s co- morbidities were the cause of him not feeling well in the week after the hepatitis vaccine. The Federal Circuit rejected respondent’s sole cause defense in Knudsen, where respondent’s expert stated that “the only single thing that could explain all of [the baby’s] symptoms, encephalitic and non-encephalitic, was a systemic viral infection.” 35 F.3d. at 550. The Federal Circuit in Knudsen decided that the baby’s rhinorrhea was due to a virus, but her encephalopathy was due to her DPT vaccination. Id. Dr. Bourque stated that when she first saw petitioner, he was already intubated and sedated, and unable to give a history. Tr. 63-64. It was her understanding at that time that petitioner had received a vaccination about a week before and had been feeling unwell for several days, with trembling, headaches, nausea, vomiting, and chills. According to the medical records she had, petitioner’s headache was worse that week; she knew little more than that. Tr. 68; Pet. Ex. 3 at 307. She was unclear about the details, but believed he went to his health care provider during that week, who prescribed cyproheptadine; within 20 to 30 minutes of taking the cyproheptadine, petitioner started hallucinating, then seizing. Tr. 64-65, 92. Dr. Bourque explained that infection can cause seizures; petitioner’s EEG results resembled those of patients with herpes simplex virus, which was why she ordered the lumbar puncture. Tr. 74. When petitioner tested negative for viral infection, Dr. Bourque became concerned that “he had some kind of aseptic meningitis from the vaccination, and that superimposed with the cyproheptadine had predisposed him to have seizures at presentation.” Tr. 67, 77. According to Dr. Bourque, vaccinations are one of many etiologies listed for aseptic meningitis; symptoms of fever and elevated protein are an indication of the disease. Tr. 83. She explained that viral illness or vaccination can cause the tissues covering the brain and spinal cord to become inflamed, leading to aseptic meningitis. Tr. 74, 82; Pet. Ex. 16 at 2. Petitioner’s history of nausea, vomiting, and worsened headaches after the hepatitis vaccine raised a concern for aseptic meningitis. Tr. 67-68; Pet. Ex. 16 at 2; Pet. Ex. 3 at 307. Once the tests ruled out viral infection, but showed elevated CSF protein, it was suggestive of aseptic meningitis. Pet. Ex. 16 at 2; Tr. 101-02, 119-20. 18 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 19 of 23 Petitioner’s discharge summary did not mention aseptic meningitis.29 In Dr. Bourque’s opinion, that was “because it’s – I guess we can’t say for certain what – you know, there’s no test for aseptic meningitis, rarely protein can be elevated for an unclear reason, but in the context of that picture in the acute setting that’s what I suspected…aseptic meningitis is something that is a one-time event and resolves,30 so it wasn’t felt to be an ongoing relevant issue….” Tr. 102. Dr. Leist disagreed that petitioner had aseptic meninigitis, pointing out that despite petitioner’s testimony that he suffered from headaches, nausea, vomiting, and fever immediately after receiving the vaccination on November 15, 2013, there was no medical record of anaphylaxis. He further noted that petitioner was able to drive two hours home, and though petitioner states that he got lost, that could be attributed to his other preexisting cognitive issues. Resp. Ex. E at 7; Tr. 11. Dr. Bourque agreed that petitioner’s claim of developing severe headache, nausea, chills, lack of appetite, and shakiness immediately after receiving the hepatitis vaccine was unusual. Tr. 129. Dr. Leist added that petitioner had prior episodes of nausea, vomiting, and poor appetite, which were associated with hyponatremia, and that petitioner’s alcohol rehabilitation records a month prior to his vaccination in October of 2013 noted that he had hyponatremia.31 Id.; Pet. Ex. 2 at 65. Dr. Bourque agreed that hyponatremia can cause these symptoms and seizures; however, she did not believe that hyponatremia contributed to petitioner’s seizure, as his electrolyte panel at EMMC was normal. Tr. 127-28, 131. Dr. Leist countered that petitioner’s sodium levels may have been higher due to I.V. fluids.32 Id. Dr. Leist further proposed that petitioner was prescribed Venlafaxine (Effexor) upon discharge from rehabilitation, which is known to affect appetite and cause weight loss; it has also been associated with seizures. Resp. Ex. E at 7-8; Pet. Ex. 2 at 25; Resp. Ex. J.33 Patients with liver disease metabolize venlafaxine more slowly, increasing the half-life of the medication. Resp. Ex. E at 8. Petitioner had hepatitis C as well as alcohol dependence. Pet. Ex. 2 at 99-100; Pet. Ex. 3 at 304, 308. However, Dr. Leist admitted that he did not know if petitioner was taking the venlafaxine at the time. Dr. Bourque explained that petitioner had a provoked seizure, which occurs in the context of an event or a medication that triggers it. Tr. 77-78. She explained the EEG findings stating that petitioner had “tonic-clonic” seizures, meaning that the seizure activity involved the whole brain. 29 Dr. Bourque did not write petitioner’s discharge summary. While Dr. Bourque was consulted for her opinion as a neurologist, petitioner’s care was coordinated by the hospitalist, Dr. Allen; he wrote the discharge summary. Pet. Ex. 290-91. 30 Treatment of aseptic meningitis is largely supportive. Recovery is usually complete, without neurologic sequelae. Infectious Diseases at 1215. 31 Supra, n.5. 32 Petitioner’s hospital discharge summary at the time of this event lists hyponatremia as one of his conditions. Pet. Ex. 3 at 285. 33 Supra, n.20. 19 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 20 of 23 Tr. 69. She explained that “diffuse right sided slowing,” meant slowing of the brain waves on the right side, which is a nonspecific finding. Tr. 71; Pet. Ex. 8 at 1437. According to Dr. Bourque, anything can cause slowing, including infection, structural abnormality, low sugar, and migraines. “Slowing does not tell a lot.” Tr. 72-73, 75. EEG findings need to be taken as a whole and not read in parts, explaining that the rest of the findings along with the slowing, “transient periodic right lateralized discharges involving the frontal lobe” and “intermittent spikes,” suggested that “there is excess irritability of the brain that is likely predisposing to seizure.” Tr. 73. According to Dr. Bourque, the EEG results were “compatible with a focus involving the right frontal area, [and] the diffuse slowing may have been related to postictal phenomenon or lesion state,” meaning that there was some irritability, either due to the seizure or an underlying brain lesion. Tr. 75. She agreed that petitioner’s abnormal EEG could have been the result of the cyproheptadine. Tr. 118-19. She added that since petitioner’s MRI was unremarkable, there were no tumors or structural abnormalities. Tr. 76. Dr. Leist pointed out that petitioner’s EEGs taken before the seizure (November 20, 2008) and four months after the seizure (February 24, 2014) were both normal. Resp. Ex. E at 6; Pet. Ex. 7 at 1430. Dr. Leist agreed that the EEGs during the hospital admission of November 22, 2013, following the seizures, were abnormal, indicating that the EEG abnormalities were transient and directly related to the seizure presentation on November 22, 2013 from taking the cyproheptadine. Resp. Ex. E at 6; Pet. Ex. 5 at 1394. When questioned about the discharge summary which stated “There is no specific etiology sign (sic) to the patient’s symptoms, ” Dr. Bourque stated, “ I think that was accurate from their perspective that there was no – we couldn’t prove exactly what had been the exact cause of his problems.” Tr. 93-94; Pet. Ex. 3 at 290. The discharge note further stated that petitioner’s alcohol withdrawal, hepatitis A vaccine, withdrawal from other medications, side effects of other medications, and a multitude of other “metabolic derangements” should be considered in determining the cause of petitioner’s seizure. Dr. Bourque agreed “it’s just a catch-all phrase that anything in theory could have triggered this.” Tr. 94-95. Dr. Bourque stated petitioner’s presenting complaints of not feeling well during the week prior and following the hepatitis vaccine, along with the elevated CSF protein level suggested to her that petitioner was experiencing irritation in his brain. Then the cyproheptadine was introduced, triggering the seizure. According to Dr. Bourque, how each factor contributed to the seizures, she did not know, only that it was a combination of petitioner’s prior head injury, long term alcoholism, and hepatitis A vaccination that could lower his seizure threshold, and the contribution of the cyproheptadine was needed at that time for the seizure to occur. Based on the timing, the cyproheptadine played a major role, and with seizures, it is all about threshold. If petitioner had been at a different threshold when he took it, he may not have seized. “That’s the issue with seizures and that’s why it’s hard to say with any certainty the contributors.” Tr. 85-86, 131-32. While Dr. Bourque agreed that petitioner’s abnormal brain activity seen on the EEG could have been a side effect of the cyproheptadine alone, she would not agree that cyproheptadine was the only cause of petitioner’s seizures, referring to the elevated CSF protein which led her to suspect aseptic meningitis. Tr. 100-02, 118-19, 121. 20 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 21 of 23 Dr. Leist submitted that, although petitioner reportedly did not feel well in the week following his vaccination, there is no record that he suffered from changes in awareness, alertness, perception, or cognition from his usual baseline until around 4:30 pm on November 22, 2013, shortly after he took cyproheptadine for the first time. Resp. Ex. E at 7; Pet. Ex. 7 at 1435; Tr. 77. In Dr. Leist’s opinion, the cyproheptadine was the “provoking agent” of petitioner’s seizures. Resp. Ex. E at 6. Dr. Leist disregarded petitioner’s testimony that he had vomiting, fatigue, headaches, high fever, and could not stay awake in the week following the hepatitis vaccine. Tr. 13, 15-17. Dr. Bourque and Dr. Leist agreed that the cyproheptadine provoked petitioner’s seizures. Dr. Bourque opined that she suspected aseptic meningitis caused by petitioner’s receipt of the hepatitis vaccine and reported fever, severe headaches, and vomiting thereafter, but she considered that all of petitioner’s co-morbidities in combination with the hepatitis vaccine lowered petitioner’s seizure threshold so that introducing the cyproheptadine to an already primed system resulted in the development of seizures. While Dr. Leist disagreed and explained why he believed that petitioner did not have aseptic meningitis, he never addressed Dr. Bourque’s theory of lowered seizure threshold. He opined that the cyproheptadine alone was the cause of petitioner’s seizures. Dr. Leist attributed all of petitioner’s complaints in the days following the hepatitis vaccine to his various co-morbidities, concluding that the hepatitis vaccine had nothing to do it. Dr. Leist even described the effects of venlafaxine as responsible for petitioner’s not feeling well, a medication prescribed to petitioner when he was discharged from alcohol rehabilitation, without any proof that petitioner had ever taken the medication. Dr. Bourque’s opinion is more compelling and persuasive in this case. In further support of her opinions in this case, Dr. Bourque explained her office records and its wording in detail. In her first follow up visit with petitioner on January 30, 2014, Dr. Bourque noted under “Impression and plan” that “[petitioner] presented to the hospital in November 2013 one week following hepatitis A vaccination and was found to have altered mental status following intake of cyproheptadine and subsequent recurrent seizures….” Pet. Ex. 7 at 1422-23. Dr. Bourque explained that the cyproheptadine was closer in time to his seizures and was a contributor, but she did not know whether petitioner would have had a seizure if he had been feeling well prior to taking the cyproheptadine. Tr. 99-100. Dr. Bourque explained, though she did not explicitly write that she believed that the combination of the hepatitis vaccine and cyproheptadine led to petitioner’s seizures, “that was my implication.” Tr. 103. Dr. Bourque was then asked about the visit on April 7, 2014, Pet. Ex. 7 at 1429-31, in which she wrote “had presented to the hospital on November 2013 one week after hepatitis A vaccination and developed hallucinations and seizures shortly after taking cyproheptadine.” Tr. 104. She stated that she did not explicitly state that the combination of the two things led to the seizures but “to me I did there…it’s sort of the facts that occurred around his seizures, as I would view it.” Tr. 104. The next visit discussed was on March 20, 2015, in which Dr. Bourque wrote, “[Petitioner] had a history of hospitalization with what was suspected to possibly have been a provoked seizure 21 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 22 of 23 in 2013.” Pet. Ex. 7 at 1427. Dr. Bourque explained that she used the word “possibly” because provoked seizures have a much lower risk of recurrence and a lower need for continued use of anti-seizure medicine. Tr. 80, 108. However, petitioner described an incident following his attempt to wean himself off Keppra in which he may or may not have had a breakthrough seizure. Tr. 78- 79. According to Dr. Bourque, this incident was unclear and she was not convinced that it was a breakthrough seizure, but petitioner and his wife became nervous and so she continued Keppra. Tr. 80-81; 108. Dr. Bourque further explained that another reason for keeping petitioner on Keppra was in part because, in the State of Maine, you cannot drive for six months after tapering off anti- seizure medication. Tr. 80. In her October 2, 2015 office note, Dr. Bourque again referred to petitioner’s seizure as “possibly” provoked. Pet. Ex. 7 at 1451. Dr. Bourque stated that it was seven months later and since she was still unclear of what to make of the “breakthrough” seizure, “[I]t became unclear to me definitively at that point what we were dealing with.” Tr. 109-10. In his final visit on March 18, 2016, Dr. Bourque noted, “[Petitioner] continues to have a history of hospitalization in November 2013 for suspected provoked seizures which was likely a combination of being unwell from hepatitis A vaccine and the compilation of cyproheptadine.” Pet Ex. 9 at 1486; Tr. 111. Dr. Bourque agreed that this was the first time that she noted in the record that petitioner was unwell following the hepatitis A vaccine. Tr. 111-12. She stated that she meant “combination,” not “compilation.” Tr. 111. It was also pointed out to Dr. Bourque that this record was the first time she stated that petitioner’s suspected provoked seizures were likely a combination of being unwell from hepatitis A vaccine and receipt of cyproheptadine. In response, Dr. Bourque testified: “Yeah, I guess my – my other—impressions were explaining – I outlined what had occurred without being able to say for sure, but just outlining the facts of what had happened. And here I put that I suspected it was provoked by those two causes. I feel like that’s what I alluded to the whole time.” Tr. 111-13. Finally, according to Dr. Bourque, the medically appropriate time period for the onset of seizures from aseptic meningitis varies based on the individual and other factors. Tr. 128. Dr. Leist did not address the timing issue. Neither expert disputes that petitioner suffered from a host of co-existing conditions at the time he received the hepatitis vaccine. Neither disputes that petitioner suffered seizures following his taking the cyproheptadine. They disagree, however, as to what may have caused petitioner’s nausea, severe headache, fever and vomiting in the week following the hepatitis vaccine and whether petitioner suffered from aseptic meningitis during that week. They also disagree as to whether the cyproheptadine was the sole cause of petitioner’s seizures. Upon learning of all of petitioner’s co-morbidities during the hearing in which she gave testimony, Dr. Bourque was adamant that all of petitioner’s co-morbidities in combination with the hepatitis vaccine served to lower petitioner’s seizure threshold so that his taking cyproheptadine triggered the onset of seizures. Dr. Leist did not discuss the lowering of the seizure threshold, but concluded that the cyproheptadine was the sole cause of the seizures. I must analyze this case in terms of Shyface v. Sec’y of Health & Human Services, in which Cheyenne Shyface was vaccinated with whole-cell DPT at the time he was beginning an E. coli 22 Case 1:15-vv-00972-EGB Document 76 Filed 02/20/18 Page 23 of 23 infection. Both the DPT and the E. coli infection could and did cause fever, which rose to 110 degrees, resulting in his death four days later. 165 F.3d. at 1345. Respondent defended the case and argued that the E. coli infection was the cause of the baby’s fever and death. Testimony from Cheyenne’s treating physician was that both the vaccine and the infection were equally responsible for his fever and death. The Federal Circuit held that each of the two factors, the vaccine and the infection, was a substantial factor in causing the baby’s very high fever and death and but for the vaccination, the baby would not have had the high fever and would not have died. The Federal Circuit ruled in favor of petitioners even though petitioners did not prove that DPT vaccine was the only or predominant cause of death. Id. at 1353. Here, petitioner’s treating physicians in the hospital included the hepatitis vaccine as a contributing factor to the cause of his seizures, and petitioner’s treating neurologist testified to it. The Federal Circuit’s direction in Capizzano, 440 F.3d at 1326, is for special masters to consider seriously the opinions of the vaccinee’s treating doctors consistent with 42 U.S.C. § 300aa- 13(b)(1)(A) and (B), directing the special masters to consider the entire record, including the diagnoses and medical judgments of doctors. Thus, the undersigned must conclude that the opinion of petitioner's treating physicians that the combination of the hepatitis vaccine, co-morbidities and cyproheptadine were all factors in petitioner’s development of seizures is determinative of the outcome of this case. The undersigned finds that petitioner has satisfied the three prongs of Althen: (1) vaccines, which include hepatitis vaccines, can cause aseptic meningitis indicated by elevated proteins in the CSF, and causing headache, nausea, vomiting, and fever, and either alone or in combination with other co-morbidities can also reduce seizure threshold resulting in seizure activity if faced with a trigger, in this case, cyproheptadine; (2) the hepatitis vaccine did cause aseptic meningitis or irritation to petitioner’s brain resulting in fever, vomiting, more severe headache and sleepiness and in combination with his co-morbidities lowered his seizure threshold resulting in his seizures after taking cyproheptadine; and (3) petitioner’s onset of headache, nausea, vomiting, fever in the days immediately following his hepatitis vaccine was appropriate in timing and indicative of aseptic meningitis or irritation to his brain, which acting in combination with his co morbidities lowered his seizure threshold so that he seized within an hour of taking cyproheptadine within the week following the hepatitis vaccine. VI. Conclusion The undersigned finds in favor of entitlement. This case shall proceed in damages. IT IS SO ORDERED. s/Mindy Michaels Roth Mindy Michaels Roth Special Master 23 ================================================================================ DOCUMENT 3: USCOURTS-cofc-1_15-vv-00972-2 Date issued/filed: 2018-04-16 Pages: 4 Docket text: PUBLIC DECISION (Originally filed: 3/20/2018) regarding 78 DECISION Stipulation/Proffer. Signed by Special Master Mindy Michaels Roth. (mw) Service on parties made. -------------------------------------------------------------------------------- Case 1:15-vv-00972-EGB Document 86 Filed 04/16/18 Page 1 of 4 In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS (Filed: March 20, 2018) No. 15-972V * * * * * * * * * * * * * PAUL MONDELLO, * UNPUBLISHED * Petitioner, * Decision Awarding Damages; * Proffer; Hepatitis A Vaccine; v. * Seizures * SECRETARY OF HEALTH * AND HUMAN SERVICES, * * Respondent. * * * * * * * * * * * * * * * Verne E. Paradie, Jr., Esq., Paradie, Sherman et al., Lewiston, ME, for petitioner. Darryl Wishard, Esq., US Department of Justice, Washington, DC, for respondent. DECISION AWARDING DAMAGES1 Roth, Special Master: On September 3, 2015, Paul Mondello [“Mr. Mondello” or “petitioner”] filed a petition for compensation under the National Vaccine Injury Compensation Program.2 Petitioner alleges that he suffered from seizures after receiving a hepatitis A vaccine on November 15, 2013. See Petition at ¶¶2, 4, 15, ECF No. 1. On January 24, 2018, the undersigned issued a ruling on entitlement, finding that petitioner was entitled to compensation. See Ruling on Entitlement, ECF No. 74. 1 Because this unpublished decision contains a reasoned explanation for the action in this case, I intend to post this decision on the United States Court of Federal Claims' website, in accordance with the E-Government Act of 2002, Pub. L. No. 107-347, § 205, 116 Stat. 2899, 2913 (codified as amended at 44 U.S.C. § 3501 note (2012)). In accordance with Vaccine Rule 18(b), a party has 14 days to identify and move to delete medical or other information, that satisfies the criteria in 42 U.S.C. § 300aa-12(d)(4)(B). Further, consistent with the rule requirement, a motion for redaction must include a proposed redacted decision. If, upon review, I agree that the identified material fits within the requirements of that provision, I will delete such material from public access. 2 National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755. Hereinafter, for ease of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa (2012). 1 Case 1:15-vv-00972-EGB Document 86 Filed 04/16/18 Page 2 of 4 Respondent filed a proffer on March 20, 2018, agreeing to issue the following payment: A lump sum of $50,995.29 in the form of a check payable to petitioner, Paul Mondello. This amount represents compensation for all damages that would be available under § 300aa-15(a). I adopt respondent’s proffer attached hereto, and award compensation in the amount and on the terms set forth therein. The clerk of the court is directed to enter judgment in accordance with this decision.3 IT IS SO ORDERED. s/ Mindy Michaels Roth Mindy Michaels Roth Special Master 3 Pursuant to Vaccine Rule 11(a), entry of judgment can be expedited by each party filing a notice renouncing the right to seek review. 2 Case 1:15-vv-00972-EGB Document 86 Filed 04/16/18 Page 3 of 4 IN THE UNITED STATES COURT OF FEDERAL CLAIMS OFFICE OF SPECIAL MASTERS ___________________________________ ) PAUL MONDELLO, ) ) Petitioner, ) No. 15-972V ECF ) v. ) Special Master Roth ) SECRETARY OF HEALTH ) AND HUMAN SERVICES, ) ) Respondent. ) ___________________________________ ) PROFFER ON AWARD OF COMPENSATION1 I. Procedural History On September 3, 2015, Paul Mondello (“petitioner”) filed a petition for compensation under the National Childhood Vaccine Injury Act of 1986, as amended, 42 U.S.C. §§ 300aa-1 et seq. (“Vaccine Act”). Petitioner alleges that, as a result of receipt of the Hepatitis A (“Hep A”) vaccine on November 15, 2013, he suffered from seizures. The petition alleges a claim based on causation-in-fact. On January 11, 2016, respondent filed his Vaccine Rule 4(c) report, denying that entitlement to compensation was appropriate in this case. On January 24, 2018, the Special Master issued a ruling on entitlement, finding that petitioner was entitled to compensation. II. Items of Compensation Petitioner has alleged entitlement to the following elements of compensation: past and future pain and suffering, and past unreimbursed expenses. Based upon the evidence of record, respondent proffers that petitioner should be awarded $50,995.29, which represents all elements 1 This Proffer does not include attorneys’ fees and costs, which the parties intend to address after the Damages Decision is issued. Case 1:15-vv-00972-EGB Document 86 Filed 04/16/18 Page 4 of 4 of compensation to which petitioner would be entitled under 42 U.S.C. § 300aa-15(a). Petitioner agrees. III. Form of the Award Respondent recommends that the compensation provided to petitioner should be made through a lump sum payment of $50,995.29, in the form of a check payable to petitioner.2 Petitioner agrees. Respectfully submitted, CHAD A. READLER Acting Assistant Attorney General C. SALVATORE D’ALESSIO Acting Director Torts Branch, Civil Division CATHARINE E. REEVES Deputy Director Torts Branch, Civil Division ALEXIS B. BABCOCK Assistant Director Torts Branch, Civil Division /s/Darryl R. Wishard DARRYL R. WISHARD Senior Trial Attorney Torts Branch, Civil Division U. S. Department of Justice P.O. Box l46, Benjamin Franklin Station Washington, D.C. 20044-0146 Direct dial: (202) 616-4357 Dated: March 20, 2018 Fax: (202) 616-4310 2 Should petitioner die prior to entry of judgment, respondent would oppose any award for future medical expenses, future lost earnings, and future pain and suffering, and the parties reserve the right to move the Court for appropriate relief. 2