11
SELECTED REPORTED CASES: 2013
I.D. v. Secretary of Health and Human Services, Respondent
Summary: In this decision the government has agreed to compensate the victim, identified as I.D., with $1,076,412.15 and an unspecified amount to fund an annuity after a Hepatitis B vaccination caused chronic fatigue syndrome (CFS).
Compensated Vaccine Injury: Chronic Fatigue Syndrome
Chronic fatigue syndrome, or CFS, is a debilitating and complex disorder characterized by profound fatigue that is not improved by bed rest and that may be worsened by physical or mental activity. Symptoms affect several body systems and may include weakness, muscle pain, impaired memory and/or mental concentration, and insomnia, which can result in reduced participation in daily activities.
Damages; decision based on proffer; Hepatitis B vaccine; chronic fatigue syndrome.
Case No. 04-1593V
Date Filed: April 26, 2013
I.D. v. Secretary of Health and Human Services, Respondent
DECISION AWARDING DAMAGES
The Honorable Susan G. Braden
Special Master Christian J. Moran
On October 25, 2004, I.D.’s parents filed a petition on I.D.’s behalf seeking compensation under the National Vaccine Injury Compensation Program, 42 U.S.C. §§ 300aa-1 et seq., alleging that a dose of the Hepatitis B vaccination caused I.D. to develop chronic fatigue syndrome. On April 22, 2011, the United States Court of Federal Claims determined that I.D. is entitled to compensation under the Vaccine Act. On April 19, 2013, the undersigned issued a ruling regarding damages.
On April 26, 2013, respondent filed a Status Report on Award of Compensation, to which petitioner agrees. This status report is construed as a Proffer on Award of Compensation. Based upon the record as a whole, the special master finds the proffer reasonable and that petitioner is entitled to an award as stated in therein. Pursuant to the attached proffer, the court awards petitioner:
1. A lump sum payment of $1,076,412.15 representing compensation for life care expenses expected to be incurred during the first year after judgment ($40,357.92), lost future earnings ($838,566.45), pain and suffering ($194,580.48), and past un-reimbursable expenses ($2,907.30), in the form of a check payable to petitioner; and
2. An amount sufficient to purchase an annuity contract, subject to the conditions described in the attached Proffer (attached as Appendix A), that will provide payments for the life care items contained in the life care plan, as illustrated by the proffer’s chart, paid to the life insurance company from which the annuity will be purchased. Compensation for Year Two (beginning on the first anniversary of the date of judgment) and all subsequent years shall be provided through respondent’s purchase of an annuity, which annuity shall make payments directly to petitioner, only so long as petitioner is alive at the time a particular payment is due. At the Secretary’s sole discretion, the periodic payments may be provided to petitioner in monthly, quarterly, annual, or other installments. The “annual amounts” set forth in the proffer’s chart describe only the total yearly sum to be paid to petitioner and do not require that the payment be made in one annual installment.
IT IS SO ORDERED
Clifton Haigler and Charity Haigler, legal representatives of a minor child, Thomas Thurlow Haigler, v. Secretary of the Department of Health and Human Services
Summary: In this case decision, issued after a hearing, Special Master Dorsey rules that a varicella vaccination caused a child to suffer encephalitis, resulting in permanent brain damage.
Compensated Vaccine Injury: Encephalitis
Encephalitis is inflammation and swelling of the brain, most often due to infections.
Case No: 11-508V
Date Filed: August 9, 2011
Clifton Haigler and Charity Haigler, legal representatives of a minor child, Thomas Thurlow Haigler, v. Secretary of the Department of Health and Human Services
Dorsey, Special Master
On August 9, 2011, Clifton and Charity Haigler filed a petition for compensation under the National Vaccine Injury Compensation program, as the legal representatives of their son, Thomas Thurlow Haigler, in which they alleged that a varicella vaccination that Thomas received on October 2, 2008, caused him to suffer encephalitis. Petitioners further alleged that the vaccination “caused permanent brain damage and will continue to block [Thomas’s] mental development.”
FACTS
Thomas was born on September 18, 2006, in Stanly County, North Carolina. There were no observed physical abnormalities. Thomas’s Apgar scores were 8 and 9, at 1 and 5 minutes, respectively. The results of the North Carolina State newborn screening blood tests were normal.
Over the next year, Thomas had a number of childhood illnesses, but was otherwise considered “normal,” “alert [and] active,” and “well developed.” At his 10 and 12 month well-child visits, Thomas’s developmental milestones were assessed by use of the “Ages & Stages Questionnaires” (“ASQ”). Thomas’s communication, gross and fine motor skills, problem solving and personal social skills were noted to be normal. Thomas’s hearing and vision were also noted to be normal.
On November 13, 2007, Thomas presented to his pediatrician with complaints of “tugging” his ears, nasal draining, and a cough. The assessment was bilateral otitis media, resolving. At this visit, Thomas received a number of vaccinations including the mumps-measles-rubella (“MMR”) and Varivax vaccines. At his 18-month check-up, on April 24, 2008, Thomas’s physical exam was normal except for slight edema of his nose. Thomas was noted to be healthy, and his 18-month ASQ reflected normal development.
On October 2, 2008, Thomas, age two, received a second full dose of the Varivax vaccine at the Stanly County Health Department. Approximately two weeks later, on October 16, 2008, Thomas was brought to his pediatrician by his mother, with complaints of fever, cough, runny nose, mouth lesions and mouth pain, decreased appetite, and an episode of shaking for approximately 10 minutes. While in the pediatrician’s office, Thomas began having tonic/clonic seizures. Initially, his temperature was 100.9ºF auxiliary, but it increased to 104.4ºF. Thomas continued having seizures and EMS was called.
Thomas was taken from the pediatrician’s office by ambulance to the Stanly Regional Emergency Department. On arrival at 1:39 P.M., Thomas was having a seizure and was unresponsive. Thomas was noted to be listless, post-ictal and unresponsive. At 3:39 P.M., he was in severe respiratory distress with rhonchi and wheezing. Thomas was intubated. Thomas was diagnosed as having status epilepticus, seizure disorder, fever, bacteremia, and pneumonitis.
At approximately 3:45 P.M., Thomas was taken by air transport from the Stanly Regional Emergency Room to the Carolinas Medical Center Pediatric Intensive Care Unit (“PICU”).
On his first night in the PICU, October 16, 2008, Thomas had questionable seizure activity of symmetric, rhythmic jerking of his legs and smacking of his lips. An electroencephalogram (“EEG”) was conducted on October 17, 2008, and revealed right frontal epileptiform activity. The laboratory studies were significant for elevated liver function levels, and a diagnosis of hepatitis was made.
On October 16, 2008, an initial assessment performed in the PICU revealed that Thomas had multiple ulcers on his lips with dried blood. These were also described as “several labial [mouth] ulcers.” On October 18, 2008, Dr. Ahmed documented two lesions on Thomas’s lips and three “crusted vesicular lesions.” On October 19, 2008, the medical records state that Thomas’s lip lesions and left auricle (ear) blisters had resolved. In the neurologist’s progress note dated October 21, 2008, an erythematous skin rash was documented. The neurologist noted, “Question whether drug eruption or part of underlying possible infectious process.”
From October 17 to 18, 2008, Thomas’s neurological examinations were abnormal, and he was unresponsive. On October 18, 2008, Dr. Amina Ahmed diagnosed Thomas with meningoencephalitis and hepatitis. Tests for herpes simplex virus, enterovirus, Rocky Mountain Spotted Fever, Bartonella, cytomegalovirus, Toxoplasma, Epstein-Barr Virus, lymphocytic choriomeningitis virus and Arbovirus were negative. Additionally, bacterial and viral cultures of Thomas’s blood, urine and stool were negative. There is no documentation which establishes that any of the health care providers who were treating Thomas at the time were aware that he had received the varicella vaccine two weeks prior.
On October 19, 2008, Thomas again experienced jerking of his legs and smacking of his lips. A video EEG showed suppression consistent with diffuse encephalopathy of a nonspecific nature. A repeat CT scan showed progressive loss of gray-white matter differentiation. While in the PICU, Thomas experienced episodes of teeth grinding, moaning, posturing and hypertonicity. He was intubated from October 21 to 24, 2008, due to a decline in his neurological status. An EEG performed on October 22, 2008, showed diffuse disorganization, suppression and slow brain waves, but no epileptic activity.
On October 28, 2008, Thomas was diagnosed with meningoencephalitis of unclear etiology. On October 31, 2008, the PICU attending physician diagnosed Thomas with an altered mental status secondary to a “viral meningoencephalitis.” On November 2, 2008, Thomas was noted to be “neurologically devastated, likely secondary to viral meningoencephalitis.”
Thomas was discharged from the Carolinas Medical Center on November 5, 2008. His discharge diagnoses included meningoencephalitis, new onset of seizures, and hepatitis. Thomas was transferred to a rehabilitation facility for physical therapy, occupational and speech therapy.
On April 17, 2009, Ms. Haigler called Thomas’s pediatrician Dr. Linda Lawrence to report that Thomas had received a vaccine on October 2, 2008, and then had “an episode” on October 16, 2008, where he “broke out in blisters around his mouth and ears.” Ms. Haigler asked if the varicella vaccine could have caused her son’s encephalitis. She further stated that “her family physician told her that the varicella vaccine probably could have caused encephalitis.” Dr. Lawrence reviewed Thomas’s vaccine history, and noted that the vaccine given to him on October 2, 2008, was not his first varicella vaccine. Dr. Lawrence, or someone in her office, documented that the “medical opinion was that vaccine did not cause encephalitis.”
Petitioners subsequently sought a second opinion regarding the cause of and treatment for Thomas’s seizures. On April 23, 2009, Thomas was seen by Dr. Jean-Ronel Corbier, a neurologist, at his Northeast Pediatric Neurology office. Dr. Corbier diagnosed Thomas with encephalitis, encephalopathy and partial complex seizures. Dr. Corbier subsequently reviewed Thomas’s medical records and ordered and reviewed his diagnostic studies.
On September 28, 2009, Dr. Corbier noted that a brain MRI performed on Thomas on August 21, 2009, showed global atrophy, and that an EEG performed on the same day showed “diffuse epileptiform discharges and slowing” compatibility with a “diffuse underlying encephalopathy.” On November 9, 2009, Dr. Corbier interpreted a 24-hour video EEG performed of Thomas as showing “frequent, multifocal and generalized epileptiform discharges that at times were almost continuous.” In February 2010, Thomas was diagnosed with cortical blindness.
Based on the most recent medical records from 2010, Thomas continues to have seizures, has a gastrostomy tube for nutrition, has limited motor function, and is non-verbal.
On April 1, 2013, the parties filed a joint stipulation of undisputed facts. Among other things, “[t]he parties agree that Thomas received his first varicella vaccine on November 13, 2007, and a second dose . . . on October 2, 2008.” They also agree that “Thomas suffered from encephalitis and that his parents first sought medical treatment for this condition on October 16, 2008.” Varicella, commonly known as chickenpox, is a member of the herpes virus family, and is caused by the varicella zoster virus (“VZV”). Potential complications of a VZV infection include neurologic complications, including encephalitis and meningitis.
To receive compensation under the Program, petitioners must prove . . . that Thomas suffered an injury that was actually caused by the varicella vaccine.
PETITIONERS’ EXPERT, DR. CORBIER
Dr. Corbier became Thomas’s treating pediatric neurologist in April of 2009.
Dr. Corbier opined that Thomas’s October 2, 2008 varicella vaccination caused him to develop meningoencephalitis, which resulted in prolonged seizures, “global developmental delay, hypoxic ischemic encephalopathy, and very refractory epilepsy.” Dr. Corbier considers all of these injuries to be part of a more generalized seizure disorder. Dr. Corbier describes Thomas’s current condition as “a severe, ongoing seizure disorder . . . along with severe neurological regression . . . which persists till this day.”
Dr. Corbier testified as follows:
While the research has shown that while rare, it’s not a common occurrence at all, but while rare, in certain cases vaccination, including in kids with varicella, can lead to devastating neurological complications, including meningoencephalitis . . . So based on all of this information, my conclusion has been and still continues to be that the varicella vaccine much more likely than not contributed to Thomas Haigler’s devastating change as far as meningoencephalitis, hypoxic ischemic encephalopathy, and the devastation that we see today.
MEDICAL LITERATURE
Dr. Corbier cites several studies which support his opinion that individuals may develop an infection after a varicella vaccination, which can lead to the development of meningoencephalitis and resulting neurological complications, including seizures.
Dr. Corbier cited the Chouliaras article, a case report of “an immunocompetent 3½ year old girl who developed encephalitis and herpes zoster opthalmieus 20 months after her immunization with varicella zoster virus vaccine.” The authors concluded that the “[VZV] vaccine strain may cause encephalitis in children even in the absence of underlying immunodeficiency.”
Dr. Corbier also referenced the Iyer article, where the authors described a case of “vaccine associated aseptic meningitis after herpes zoster in a previously healthy child.” The authors noted that “serious adverse events have occasionally been reported with vaccine-strain varicella-zoster virus,” and that the “varicella zoster virus has increasingly been implicated in central nervous system (‘CNS’) infections in immunocompetent individuals as well.”
Dr. Corbier also referenced the Chaves article*. The authors of this article found that 5% of documented adverse events associated with the varicella vaccine were “serious.” These adverse events included meningitis, fever, encephalopathy, and seizures.
Finally, Dr. Corbier referenced the Koskiniemi collaborative study, which found that the “[v]aricella-zoster virus . . . was the main agent associated with encephalitis,” in a study of “3231 patients with acute central nervous system . . . symptoms of suspected viral origin.” The authors found that “VZV seems to have achieved a major role in viral infections of [the central nervous system].”
RESPONDENT’S EXPERT, DR. HOLMES
Dr. Gregory Holmes, also a pediatric neurologist, testified on behalf of respondent.
Dr. Holmes estimated that he has treated five to seven patients for varicella encephalitis, and has seen “a lot of post-infectious varicella problems.” None of the patients, however, had developed varicella encephalitis secondary to a vaccine.
Dr. Holmes asserted that Thomas’s vaccination did not cause his injuries, although he agreed that the varicella vaccine can cause neurologic injuries, including those from which Thomas suffers. Dr. Holmes agrees with Dr. Corbier that medical reports have documented a causal relationship between the varicella vaccine and encephalitis.
He testified that the varicella vaccine contains a live virus that “could invade the central nervous system” and cause encephalitis. Although he considered it “[e]xtremely rare . . . in people that are not immunocompromised,” Dr. Holmes agreed that the varicella vaccine can cause an individual to develop both encephalitis and an encephalopathy through a direct or primary varicella infection.
PETITIONERS’ EXPERT, DR. CORBIER
Dr. Corbier opines that there is a logical sequence of cause and effect between Thomas’s vaccination and his encephalitis. First, Dr. Corbier states that Thomas exhibited signs and symptoms of an infectious process shortly after his second varicella vaccination on October 2, 2008, including blisters, fever, and seizures. Dr. Corbier testified that:
Well, the logical sequence is that a young child is given a live attenuated vaccine. The vaccine is shown under—based on the information that we have in rare cases to in some patients lead to certain neurological complications. We know that Thomas was given two doses [of the varicella vaccine] that were fairly close together and . . . two weeks later he developed blisters and other changes to suggest that perhaps he developed complications from the varicella vaccine. So I believe there is a logical sequence there of events.
Dr. Corbier also based his causation opinion on the fact that Thomas had “an extensive workup which included lumbar puncture, neuroimaging, and various labs, was diagnosed with meningoencephalitis . . . and had evidence of hepatitis,” and that there was no other viral explanation found for his illness.” Various viruses were ruled out during Thomas’s hospitalization, including HSV, EBV, LMCV, adenoviruses, Bartonella, and Arbovirus. There is no evidence to suggest that Thomas was exposed to any virus other than the VZV within a medically appropriate time frame.
Lastly, Dr. Corbier considered the time frame within which Thomas’s injuries manifested after his vaccination as strong support for his opinion that they are vaccine-related. Thomas rapidly became more ill and “quickly went on to develop severe epilepsy and global devastation.” Based on the timeline, Dr. Corbier opined that Thomas’s clinical course provided circumstantial evidence of a “clear-cut event” of vaccine-induced harm.
EVALUATION OF THE EVIDENCE
Dr. Corbier’s opinion regarding causation is straightforward. After receiving the varicella vaccine, with a live attenuated virus, Thomas developed a varicella infection, either through direct infection or reactivation, which caused encephalitis. He then developed severe epilepsy and global neurological devastation.
It is uncontested that Thomas was exposed to varicella through the vaccination, and the treating physicians and experts agree that his encephalitis is most likely due to a viral infection. As discussed, Thomas’s clinical course was consistent with viral encephalitis, and there is no evidence of exposure to any other virus that would have caused it. The most likely viruses were tested for and ruled out, except that no specific testing was performed for the VZV. The only known virus to which Thomas was exposed was the VZV contained in his subject vaccination.
All of these factual findings provide sufficient circumstantial evidence for the undersigned to conclude that Thomas’s subject vaccine more likely than not caused his encephalitis and resultant injuries.
CONCLUSION
For the reasons discussed above, the undersigned finds that petitioners are entitled to compensation because they have provided sufficient circumstantial evidence that preponderates in their favor.
IT IS SO ORDERED.
Katea D. Stitt, as Personal Representative of the Estate of Pamela Wanga Stitt, Petitioner v. Secretary of the Department of Health and Human Services, Respondent
Summary: In this case decision, Special Master Zane rules after a hearing that the petitioner died as a result of vaccine induced Guillain-Barré syndrome (“GBS”).
Compensated Vaccine Injury: Guillain-Barré Syndrome (“GBS”) Leading to Death
Guillain-Barré syndrome is a disorder in which the body’s immune system attacks part of the peripheral nervous system. The first symptoms of this disorder include varying degrees of weakness or tingling sensations in the legs. In many instances, the weakness and abnormal sensations spread to the arms and upper body. These symptoms can increase in intensity until the muscles cannot be used at all and the patient is almost totally paralyzed. In these cases, the disorder is life-threatening and is considered a medical emergency. The patient is often put on a ventilator to assist with breathing. Most patients, however, recover from even the most severe cases of Guillain-Barré syndrome (GBS), although some continue to have some degree of weakness. Guillain-Barré syndrome is rare.
Case No: 09-653V
Date Filed: May 31, 2013
Katea D. Stitt, as Personal Representative of the Estate of Pamela Wanga Stitt, Petitioner v. Secretary of the Department of Health and Human Services, Respondent
Case No: 09-653V
Date Filed: May 31, 2013
RULING ON ENTITLEMENT
Special Master Zane
This matter is before the undersigned on the issue of entitlement following a hearing. Petitioner, Katea D. Stitt (“Petitioner”), as the personal representative of the estate of her mother, Pamela Wanga Stitt (“Mrs. Stitt”), filed this petition alleging that the trivalent influenza (“flu”) vaccination Mrs. Stitt received on September 25, 2008, caused Mrs. Stitt to develop Guillain-Barré Syndrome (“GBS”), which then caused her death. Petitioner seeks compensation pursuant to the National Childhood Vaccine Injury Act.
Petitioner contends that the evidence shows that it is more probable than not that the flu vaccine was a substantial factor in causing Mrs. Stitt’s GBS and subsequent death. Petitioner relies on molecular mimicry as the medical theory that causally connects the flu vaccine to GBS. Petitioner argues that Mrs. Stitt’s clinical picture and the results of diagnostic tests demonstrate a logical sequence of cause and effect showing the flu vaccine caused Mrs. Stitt’s GBS. Finally, Petitioner maintains that the 5½ weeks between the vaccine and Mrs. Stitt’s hospitalization are within the standard, medically acceptable time frame of six weeks between infection and onset of symptoms. Petitioner argues that she has satisfied her burden and shown by preponderant evidence that the flu vaccine caused her GBS, which, in turn, caused her death.
Respondent argues that Petitioner has not satisfied her burden of proof. Although Respondent acknowledges that Mrs. Stitt’s GBS was one of the causes of her death, Respondent claims that Petitioner has failed to satisfy her burden of showing the flu vaccine caused Mrs. Stitt’s GBS. Respondent contends that Petitioner’s presentation of molecular mimicry as a theory is inadequate because Petitioner has failed to identify a specific protein in the peripheral myelin as being similar to the antigen in the flu vaccine as evidence that molecular mimicry could occur. Respondent also contends that because Petitioner could not point to any direct evidence that would specifically identify the vaccine as the cause, Petitioner did not present sufficient evidence to show a logical sequence of cause and effect. Respondent further claims that Petitioner also failed to show a logical sequence because epidemiological evidence indicates that in a majority of GBS cases, the cause is an infection. As a result, Respondent claims that the cause of Mrs. Stitt’s GBS is more likely to be something other than the vaccine. Thus, according to Respondent, Petitioner fails to present sufficient evidence that the vaccine was a substantial factor in causing Mrs. Stitt’s GBS and subsequent death.
For the reasons set forth below, upon review of the record as a whole, the undersigned concludes that Petitioner has satisfied her burden. She has shown by preponderant evidence that the vaccine was a substantial factor in bringing about Mrs. Stitt’s GBS. And Mrs. Stitt’s GBS was a substantial factor in bringing about her death. Petitioner is entitled to compensation.
FACTS
The facts as evidenced by the records and testimony are as follows:
Mrs. Stitt received an influenza (“flu”) vaccination on September 25, 2008, at her local Safeway store. She was 74. At that time, Mrs. Stitt’s medical condition was generally healthy, although she did have hypertension. Mrs. Stitt’s medical history indicated that she had had gallbladder surgery and intermittent lower back pain over the last few years. Mrs. Stitt had also had some specific orthopedic issues, i.e., rotator cuff problems and a twisted ankle. Approximately a week after she received the flu vaccine, on October 2, 2008, Mrs. Stitt went to her orthopedist, Dr. Moskovitz, for a follow-up on her right knee and left shoulder pain (Rotator Cuff Syndrome). At that time, Mrs. Stitt mentioned a new complaint, i.e., stiffness and pain in both her hands and in her fingers, with the symptoms being greater in her right versus her left hand and fingers.
On October 30, 2008, Mrs. Stitt visited her primary care physician/internist, Dr. George Graves, for a follow-up on her hypertension. Mrs. Stitt reiterated the complaint she had made to her orthopedist of tingling in her hand up to her elbow for the past month. She denied complaints of chest pain, shortness of breath, and cough. There was no indication of any complaints of stomach problems, nausea, diarrhea or vomiting.
A few days later, on November 3, 2008, Mrs. Stitt telephoned her doctor complaining of tingling in her hands and feet. Later that same day, Mrs. Stitt was admitted to Sibley Hospital due to leg weakness. At the time of her admission, Mrs. Stitt told the admitting personnel that she had had leg weakness since the morning, that her knees buckled twice, and that she experienced shortness of breath and polyuria.
Upon admission, Dr. Mahgoub, a neurologist, provided a consult. He specifically noted that Mrs. Stitt had received a flu vaccine four weeks before admission and that the differential diagnosis, which included GBS, was well described. Having noted the receipt of the flu vaccine and possible GBS diagnosis, Dr. Mahgoub noted that the Centers for Disease Control (“CDC”) and Food and Drug Administration (“FDA”) had not issued an alert in connection with the flu vaccine. Nonetheless, Dr. Mahgoub made a note to contact the CDC out of concern regarding the vaccine being a possible cause. Mrs. Stitt’s laboratory tests showed an elevated glucose level and elevated liver enzymes with otherwise normal results. Mrs. Stitt continued to experience leg weakness, as well as weakness in her arms.
On November 6, 2008, the results from an electrodiagnostic study confirmed that Mrs. Stitt’s presentation was consistent with GBS. Mrs. Stitt was treated with a two-day course of IVIG. Because she developed shallow breathing and an increased respiratory rate on that day, Mrs. Stitt was intubated. Within a day, Mrs. Stitt developed what was diagnosed as staphylococcus pneumonia. She was treated with antibiotics. Mrs. Stitt also developed a fever and an elevated white blood cell count.
Beginning November 10, 2008, Mrs. Stitt’s strength in her extremities began to return and her breathing improved. However, it was also determined that Mrs. Stitt had developed hemolytic anemia due to her IVIG treatment. As a result, her IVIG treatment was stopped after just two courses.
By November 12, 2008, Mrs. Stitt’s pneumonia had resolved. Later that day, Mrs. Stitt was removed from the ventilator. Mrs. Stitt was noted to be “doing quite well” and to have a good voice. On November 13, 2008, Mrs. Stitt was again noted to be “doing well,” “breathing easily,” and “swallowing without difficulty,” and her pneumonia had resolved. Plans were made to transfer Mrs. Stitt to the National Rehabilitation Hospital.
On November 14, 2008, Mrs. Stitt was discharged from Sibley Hospital to the National Rehabilitation Hospital. The discharge summary indicated that Mrs. Stitt was diagnosed with, inter alia, GBS. The doctors told Petitioner that Mrs. Stitt’s GBS was caused either by the flu vaccine or some other unidentified infection.
On November 16, 2008, while at the National Rehabilitation Hospital, Mrs. Stitt experienced severe respiratory distress and was transported to Washington Hospital Center. Mrs. Stitt was intubated. A chest X-ray revealed bibasal infiltrates and an echocardiography demonstrated a nearly collapsed ventricle suggestive of hypovolemia (defined as an abnormally decreased volume of circulating blood in the body; the most common cause is hemorrhage). An evaluation for cardiac arrest revealed that Ms. Stitt had a cardiomyopathy (a general diagnostic term designating primary noninflammatory disease of the heart muscle, often of obscure or unknown etiology).
On the following day, November 17, 2008, Mrs. Stitt’s EKG tests revealed changes in her ST-elevation and increased enzymes. She received cardiac catherization, which revealed non-obstructive coronary artery disease, elevated right heart filling pressures, and takotsubo with severe liver dysfunction. Mrs. Stitt’s lab results revealed no abnormalities in her stool cultures.
Mrs. Stitt was placed on a ventilator, and on November 18, 2008, she suffered hypoxic respiratory failure while on the ventilator. Mrs. Stitt was determined to have takotsubo syndrome with functional obstruction of liver outflow. There was no change in Mrs. Stitt’s status the next day, November 19, 2008. Later on November 19, 2008, Mrs. Stitt began to experience worsening hypotension due to sepsis versus takotsubo cardiomyopathy. Mrs. Stitt’s mental status worsened and her family decided that she should not be resuscitated. Ms. Stitt died on November 20, 2008. Her causes of death were listed as: (A) Cardiogenic shock; (B) Cardiomyopathy; (C) GBS; and (D) Pneumonia. An autopsy was performed on January 12, 2009. The autopsy report listed the causes of death as, inter alia, (1) Septic shock with respiratory failure (clinical) and (2) GBS (clinical).
The parties stipulated that Mrs. Stitt had been diagnosed with GBS at the time of her discharge from Sibley Hospital to the National Rehabilitation Hospital. The parties also stipulated that the medical records listed GBS as a cause of her death. Finally, the parties stipulated that the autopsy report identified GBS as one of the causes of Mrs. Stitt’s death.
DISCUSSION
A. Petitioner Has Presented Sufficient Proof of a Medical Theory Causally Connecting the Flu Vaccine to Mrs. Stitt’s GBS, Satisfying Althen’s Prong One.
B. Petitioner Has Provided Sufficient Evidence Which Demonstrates a Logical Sequence of Cause and Effect Showing the Vaccine Was a Substantial Factor Leading to Mrs. Stitt’s GBS, Satisfying Althen’s Prong Two.
C. Petitioner Has Shown That Mrs. Stitt’s GBS Occurred Within a Medically Acceptable Time Frame, Thereby, Satisfying Althen’s Prong Three.
CONCLUSION
For the reasons stated above, the evidence presented demonstrates that the flu vaccine Mrs. Stitt received was a substantial factor in causing Mrs. Stitt’s GBS. And, her GBS was a substantial factor in causing her death. Petitioner has established entitlement to compensation under the Vaccine Act.
IT IS SO ORDERED.
Walter Ray Graves, and Lisa Graves as Representatives of the Estate of Hayley Nicole Graves, Deceased, v. Secretary of the Department of Health and Human Services
Summary: In this case, Merow, Senior Judge Merow rules, upon review after a hearing that the Prevnar vaccine caused the victim’s seizures and eventual death.
Compensated Vaccine Injury: Status Epilepticus, Leading to Death
PREVNAR
Case No: 02-0211V
Date Filed: February 25, 2013
Walter Ray Graves, and Lisa Graves as Representatives of the Estate of Hayley Nicole Graves, Deceased, v. Secretary of the Department of Health and Human Services
Merow, Senior Judge
Following the death of their infant daughter Hayley, petitioners Walter and Lisa Graves allege that a Prevnar vaccination on August 8, 2000, caused the onset of Hayley’s seizures two days later. She was hospitalized immediately and continually thereafter for twenty-nine days, primarily in pediatric intensive care. Despite a battery of tests, treatment and examination by specialists, Hayley’s seizures were unremitting and she died on September 24, 2000. Her death certificate documents the immediate cause of death as “[s]tatus epilepticus,” and an underlying cause as “[i]ntractable seizures.” Neither Hayley nor her family had a prior history of seizures.
FACTS
Hayley Graves was born on November 4, 1999 in Ft. Worth, Texas. At her well-baby check-up when she was five months old no physical abnormalities were noted. She had attained all developmental milestones.
At that August 8, 2000 appointment, at approximately 11:15 a.m., Hayley received a Hepatitis B and her second Prevnar vaccination.
According to the affidavit of Hayley’s mother, Lisa Graves, filed with the Petition in this matter, the remainder of August 8, 2000, Hayley acted normally. On August 9, 2000, she was restless and stayed awake until about 10:30 or 11:00 p.m. Early on the morning of August 10, 2000, Hayley woke up about 6:45 a.m. and, according to the affidavit: “she did not appear right. The left side of her body was moving and it would not stop. We called the doctor’s office and waited for a return call; however, at 7:15 a.m. when we still had not heard back from the doctor’s office, we left for Cook’s Children[s] Medical Center.”
Hayley was admitted and transferred to the pediatric intensive care unit (“PICU”) under the care of Dr. Brian Ryals, a pediatric neurologist. An EEG showed “ongoing electrical seizure activity emanating from right central brain regions.” An MRI and CT scan were normal. Because barbiturate doses were prescribed, she was intubated, ventilated, and an arterial line was placed. She was continuously monitored and received regular doses of anticonvulsant medication, but her seizures did not stop.
Hayley remained in intensive care until transferred to a “regular” room for about five days until noon on August 29, 2000, when she was airlifted to the Hermann Hospital Epileptic Center in Houston, Texas for evaluation and treatment by Dr. James W. Wheless, Chief of Pediatric Neurology at the University of Tennessee College of Medicine, who later testified in these proceedings that Prevnar could and did cause her seizures and did so within a medically appropriate time.
For twenty-six days at Hermann Hospital, Hayley was evaluated by several specialists; multiple attempts were made to control her seizures without success. Tragically, her seizures which started the early morning of August 10, 2000, never stopped and Hayley died in the pediatric intensive care unit of the Hermann Hospital on September 24, 2000.
Hayley’s death certificate recorded her cause of death as “[s]tatus epilepticus,” caused by “[i]ntractable seizures.” An autopsy performed on September 29, 2000, concluded that Hayley “died as a result of hypoxic encephalopathy which reportedly occurred following a seizure which developed following a meningitis [sic] vaccine.”
PROCEDURAL BACKGROUND
Dr. Wheless was concerned that the Prevnar vaccination was the cause for Hayley’s death and he referred petitioners to the office of Richard Gage. (Tr. 272- 74.) Petitioners filed a petition for vaccine injury compensation on September 16, 2002, alleging that Hayley suffered seizures and death as a result of receiving Prevnar and Hepatitis B vaccinations on August 8, 2000.
On December 26, 2007, petitioners filed a report from Hayley’s treating pediatric neurologist and pediatric epilepsy specialist, Dr. James W. Wheless. Dr. Wheless opined:
Prevnar vaccine is known to cause seizures, both afebrile and febrile (without and with a fever) and these can be serious, and potentially even lead to death. It is my medical opinion that Hayley’s vaccine was associated with the onset of her seizures, which proved to be intractable and her acute encephalopathy, which then progressed to chronic encephalopathy accompanied by an intractable seizure disorder, and ultimately this was fatal and responsible for her death. An extensive evaluation was performed, including obtaining her brain post-mortem, and after examining this no other cause could be found. It is established that Prevnar vaccine can contribute to this type of injury. Prevnar is established as causing this type of injury and, in this case, it is also my belief that the vaccine did cause this injury.
It is my opinion, based on a reasonable degree of medical probability, that the Prevnar vaccination, which Hayley Graves received when she was nine months old, caused her severe refractory seizure disorder that caused her death. This is a causation-in-fact opinion and is based on my role as her treating physician and as an expert in the field of pediatric epilepsy.
Giving appropriate credit to the opinion of Dr. Wheless, the treating pediatric neurologist, and given the absence of any other reason for the sudden onset of Hayley’s intractable seizures which, despite her continuous specialized hospitalization, litany of tests and treatments and examination by specialists did not stop, the preponderant credible evidence bar of causation was met.
CONCLUSION
For the reasons stated herein, the court concludes that on the record as a whole, petitioners presented sufficient evidence to meet the Vaccine Act’s preponderant standard for causation of the biological plausibility of the Prevnar vaccine triggering the onset of seizures, as well as increased duration and intractability of seizures, supported by reliable medical literature and expert testimony including that of Dr. Wheless, Hayley’s treating physician.
The record evidence established a medical theory causally connecting the Prevnar vaccination with the instigation as well as the duration and intractability of the seizures which resulted in Hayley’s death. A logical sequence of cause and effect was established that the Prevnar vaccine did cause the instigation of Hayley’s seizures and the increased duration and intractability within an appropriate time frame.
Accordingly, the court determines that entitlement has been proven.
IT IS SO ORDERED.
Michael Stephen Saw, Petitioner v. Secretary of the Department of Health and Human Services, Respondent
Summary: In this decision following a hearing, Chief Special Master Patricia E. Campbell-Smith rules that the victim suffered a small nerve fiber neuropathy as a result of a hepatitis B vaccine.
Compensated Vaccine Injury: Small Nerve Fiber Neuropathy
Small Nerve Fiber Neuropathy; Finding of Entitlement to Compensation
Case No: 01-0707V
Date Filed: May 24, 2013
Michael Stephen Saw, Petitioner v. Secretary of the Department of Health and Human Services, Respondent
RULING ON ENTITLEMENT
Patricia E. Campbell-Smith
Chief Special Master
This case is before the undersigned on remand. The issue before the undersigned is whether the Hepatitis B vaccines that petitioner, Michael Shaw, received on May 5, 1999, and June 11, 1999, caused him to suffer a small nerve fiber neuropathy. The undersigned finds, by a preponderance of the evidence, that petitioner’s vaccinations caused his injury.
In so finding, the undersigned notes that this ruling represents a “close call” and should accordingly be resolved in favor of petitioner.
PROCEDURAL HISTORY
On December 20, 2001, petitioner filed a petition pursuant to the National Injury Compensation Program (Vaccine Program or Program), wherein he alleged that his Hepatitis B vaccinations caused him to suffer a neuropathy. Thereafter, petitioner submitted an expert report opining that he either suffered the condition of transverse myelitis (“TM”) or of chronic inflammatory demyelinating polyneuropathy (“CIDP”) as a result of his vaccinations.
An evidentiary hearing was convened on March 12, 2008, to elicit the testimony of Sherri Tenpenny, D.O., an osteopathic physician, on behalf of petitioner, and Thomas Leist, M.D., a neurologist, on behalf of respondent. In a decision filed August 31, 2009, the undersigned found that petitioner failed to demonstrate entitlement to compensation. Specifically, the undersigned found that petitioner did not suffer from either of the conditions TM or CIDP as his expert, Dr. Tenpenny, had asserted in her theory of vaccine-related causation. Accordingly, the undersigned found that petitioner failed to establish a logical sequence of cause and effect as then presented, and denied compensation. Pivotal to the undersigned’s finding of no entitlement in Shaw I was the finding, after a careful review, that to the extent petitioner’s injury was a neurologic one, petitioner’s medical records indicated that the more likely consensus diagnosis was a small fiber neuropathy. But, as Dr. Leist testified at the March 12, 2008 hearing, “small nerve fibers lack the myelin sheaths that would be harmed by the [petitioner’s] proposed demyelination process.” Petitioner did not rebut this testimony. Thus, relying on the unrefuted testimony of Dr. Leist, the undersigned found that petitioner’s proposed theory of causation, demyelination, failed when applied to The National Vaccine Injury Compensation Program is set forth in Part 2 of the National Childhood Vaccine Injury Act of 1986.
On September 21, 2009, petitioner filed a Motion for Reconsideration of Shaw I, asserting that the undersigned’s Decision was not in accordance with the law and seeking to introduce evidence, previously available but not filed, that small nerve fibers “may well” be myelinated. The undersigned denied the Motion for Reconsideration explaining that the evidence concerning small fibers was available to the petitioner two years prior to the filing of the expert report by Dr. Tenpenny and at the time of the hearing. The undersigned observed that the inability of petitioner to rebut the testimony of Dr. Leist was attributable “directly to Dr. Tenpenny’s acknowledged lack of expertise in neurological matters.” Moreover, the undersigned noted that the newly presented information regarding myelinated small nerve fibers was not persuasive “in the absence of any evidence presented by petitioner regarding how this evidence supports the theory of causation proposed by petitioner in this case for the specific injuries of TM and CIDP that Dr. Tenpenny’s opinion contemplated.”
Petitioner moved the United States Court of Federal Claims to review the undersigned’s decision. Motion for Review filed September 30, 2009. On review, the court determined that the Shaw I decision—was “thorough and well reasoned”—in finding that petitioner neither suffered TM or CIDP, but rather a small fiber neuropathy. The reviewing judge upheld the undersigned’s finding that the unrebutted testimony at hearing established that “Mr. Shaw’s medical theory, demyelination, was incapable of causing small fiber neuropathy.” However, the court concluded that “in light of the purposes and structure of the Vaccine Act, we find it in the interest of justice for the [undersigned] to consider the effect of the newly offered evidence.” The court left to the discretion of the undersigned the decision whether to re-open the record beyond allowing consideration of the new evidence and permitting respondent’s expert Dr. Leist an opportunity to comment on that evidence.
On remand and after consultation with the parties, the undersigned afforded petitioner an opportunity to retain an expert in neurology to explain how the newly offered evidence supported petitioner’s theory of the case. Respondent’s expert, Dr. Leist, also was offered an opportunity to address the newly presented evidence. Order filed March 12, 2010. Petitioner ultimately offered the opinion of Thomas Morgan, M.D., a neurologist, in support of his vaccine claim. Respondent again offered the neurologic expertise of Dr. Leist, who challenged petitioner’s newly asserted theory of causation.
Another expert hearing was conducted on July 28, 2010 in Washington, D.C. The undersigned sought the testimony of Drs. Morgan and Leist on the issue of whether or not petitioner developed a small fiber neuropathy as a result of his Hepatitis B vaccine series. On remand, Mr. Shaw continued to rely on a theory of causation in fact. In support of his claim, he has filed: (1) an affidavit, (2) medical records, (3) the medical opinion of Dr. Morgan, (4) supporting medical literature, and (5) post-hearing briefs. Respondent offered: (1) the expert opinion of Dr. Leist, (2) a number of medical articles, and (3) a post-hearing memorandum to rebut petitioner’s claim.
FACTS
The facts set forth below are largely derived from the undersigned’s recitation of the acts in Shaw I. In general, the parties do not dispute the facts of this case, but rather the medical and legal conclusions to be drawn from them. As directed by the Vaccine Act, the undersigned has carefully considered, in addition to all other relevant medical and scientific evidence contained in the record, the diagnoses, conclusions, and medical judgments contained in the record regarding the nature, causation and aggravation of petitioner’s condition as well as the results of diagnostic tests contained in the record. Declining to review here the entirety of petitioner’s voluminous medical records, the undersigned focuses on the records upon which the parties have relied most heavily.
Petitioner was born on June 15, 1959. His medical history is most notable for a couple of concussive head injuries, a cracked pelvis, a chipped tailbone, a fractured nose, and broken hands and feet. Prior to receiving the vaccinations at issue in this case, petitioner traveled extensively in his professional capacity as the corporate general manager for a large, multi-national trading firm. He had responsibilities for approximately 30 offices throughout the Asian Pacific region. Recreationally, Mr. Shaw enjoyed extreme sports activities, including motor cross riding, mountain biking, roller-blading, hang gliding, parachuting, rafting and mountain climbing. He also enjoyed golf, tennis, skiing, softball and basketball.
In anticipation of scheduled business travel and as part of an employment-related immunization program, Mr. Shaw received his first Hepatitis B vaccination on May 5, 1999. He did not recall experiencing any effects after that vaccination. The next month, on June 11, 1999, he received his second Hepatitis B vaccination and a polio vaccination. The medical records indicate that on June 21, 1999, 10 days after receiving the Hepatitis B vaccination of interest, petitioner visited his primary care physician, John Roberts, M.D., of Blackhawk Medical Group, complaining of recurring numbness in his right leg below the knee. Petitioner reported that the numbness had begun on June 17, 1999, four days prior to his visit to Dr. Roberts and six days after he had received his second Hepatitis B vaccine. The numbness was “now progressing to a throbbing pain.” Dr. Roberts noted a patient history of trauma associated with his motor cross riding. Dr. Roberts diagnosed petitioner with lumbar strain and nerve compression. Dr. Roberts prescribed prednisone and urged petitioner to obtain x-rays and magnetic resonance image (MRI) of his back.
Petitioner began an international business trip on June 23, 1999. In his affidavit, prepared on October 17, 2006, he recalled that: By the time I reached my first stop in England, both my feet [and] legs were affected. During business meetings in India, I began to experience tremors in my limbs, cognitive memory/speech problems, and coordination difficulties. Prior to returning home from the two-week trip, my arms were also affected. The symptoms now included not only numbness and tingling but also sharp, shooting, burning, and throbbing pain. I managed to complete the trip in defiance of significant pain. Once home, the pain continued. I experienced numbness in both of my hands and legs and had spasms in my back.
Petitioner underwent imaging of his spine on July 6, 1999. The MRI of his cervical spine produced an impression of early disc degeneration without extrusion. The MRI of his lumbar spine was normal.
On July 9, 1999, three days after his spinal MRIs, petitioner returned to his primary care provider. He complained of flu-like symptoms and of continued numbness in his right leg. Although the office notes reflect a history of numbness in petitioner left leg and hands, only a general time frame of symptom onset is specified (petitioner reporting, during a visit to his primary care physician on October 27, 1999, that his numbness had progressed to all of his extremities in late June). The diagnostic impression at the July 9, 1999 visit was sinusitis and strain in the lumbar and cervical regions of the spine. The examining physician prescribed Lorabid and Xanax and ordered physical therapy.
Treatment Sought During the First Six Months after the Hepatitis B Vaccination Five weeks later, on August 18, 1999, petitioner visited Samuel Jorgenson, M.D., an orthopedist. Petitioner reported a two-month history of right foot pain and intermittent numbness and tingling in his arms, hands, and feet. Petitioner also reported that he did not continue to take the Xanax he had been prescribed because it caused drowsiness. Dr. Jorgenson’s physical examination revealed a decreased sensation to sharp pin prick in petitioner’s right foot when compared with his left one. It was the orthopedist’s assessment that petitioner had a possible entrapment neuropathy in his lower right extremity. Lorabid is an antibiotic indicated for the treatment of mild to moderate infections.
Dr. Jorgenson referred petitioner for an electromyogram that was conducted on September 2, 1999. The electromyogram (or EMG) revealed no evidence of acute or chronic lumbosacral radiculopathy, plexopathy or peripheral neuropathy. Petitioner had described symptoms of progressive burning pain and intermittent numbness from his foot to his ankle that, at times, emanated to his knee. The physician interpreting the EMG results noted that the patient was most likely exhibiting very early symptoms of idiopathic peripheral neuropathy and recommended a trial of Neurontin to reduce the burning parasthesias.
Approximately two months later, on November 9, 1999, petitioner saw Janet Lin, a neurologist, on referral from Dr. Roberts, his primary care physician. Dr. Lin noted that petitioner’s neurologic exam was normal except for some minimal sensory abnormalities in his hands and feet. Although petitioner reported feeling fatigued, there was no evidence of muscle weakness. Dr. Lin believed that petitioner was suffering a post-inflammatory neuropathy related to immunizations. During her examination nearly five months after petitioner received the subject vaccination, Dr. Lin surmised that the culprit might be the Hepatitis B immunization that petitioner received because petitioner had received all the other immunizations previously.
Treatment Sought Over the Next Two Years
Petitioner sought treatment from a variety of specialists over the next two years. An electromyogram (or EMG) is a test that is used to record the electrical activity of muscles. When muscles are active, they produce an electrical current. This current is usually proportional to the level of the muscle activity. . . . EMGs can be used to detect abnormal electrical activity of muscle that can occur in many diseases and conditions, including . . . inflammation of muscles, pinched nerves, [and] peripheral nerve damage (damage to nerves in the arms and legs).
On referral from his primary care doctor, petitioner consulted on February 28, 2000 with Benedict Villanueva, M.D., an infectious disease specialist. As reflected in the notes from the consultation, Dr. Roberts had referred petitioner to Dr. Villanueva for an evaluation of whether his symptoms of diffuse sensory neuropathy were a possible post vaccine adverse reaction. The particular vaccine under examination was the polio vaccine—not the Hepatitis B vaccine—that petitioner had received in June 1999. Dr. Villanueva noted that petitioner had a normal EMG, a basically normal MRI of his cervical and lumbar area and, with the exception of a slightly elevated protein level, a normal spinal tap. In Dr. Villanueva’s assessment, among the possible etiologies for petitioner’s subjective diffuse sensory polyneuropathy would be a rare/remote adverse reaction to the polio vaccine. But, Dr. Villanueva observed, such reactions occur within a few weeks after immunization and, to his knowledge, do not last for several months after the inoculation.
Approximately one month later, petitioner underwent further neurologic examination by Catherine Lomen-Hoerth, M.D., at the University of California in San Francisco. He returned to Dr. Lomen-Hoerth on May 10, 2000, for a follow-up of continuing pain and numbness. Dr. Lomen-Hoerth noted that petitioner’s discomfort had progressed and was worse than when she had examined him for the first time one month earlier. It was Dr. Lomen-Hoerth’s impression that petitioner had a progressive small fiber neuropathy rather than a static neuropathy related to his vaccinations last summer.
On referral from his neurologist Dr. Lomen-Hoerth, petitioner saw David Martin, M.D., a rheumatologist, on July 31, 2000. The purpose of the referral was to evaluate petitioner’s severe fatigue, weight loss, intermittent burning rash on both arms and joint pain. It was Dr. Martin’s impression that extensive laboratory work and physical examination failed to produce any clear evidence of connective tissue disease. In his view, petitioner suffered from an idiopathic syndrome associated with chronic fatigue and . . . possibly related to a vaccine exposure or possibly a toxin. Dr. Martin suspected that petitioner’s condition had an underlying psychiatric component with possible depression.
On referral from Dr. Lomen-Hoerth, petitioner was examined by Nicholas Maragakis, M.D., a neurologist at John Hopkins Hospital on August 21, 2000, for evaluation of a possible small fiber neuropathy. Dr. Maragakis spinal tap or cerebrospinal fluid (CSF) examination that yields an elevated protein level may be indicative of an underlying infectious or inflammatory process. Noted that petitioner’s “exam [was] normal, with the exception of some mild decreased pinprick sensation in the hands and feet, which is often typical for a small fiber neuropathy. Of note, quantitative sensory testing at an outside hospital was essentially normal. I think this most likely represents some form of small fiber neuropathy.” In an addendum to his August 21, 2000 report, Dr. Maragakis noted that petitioner’s skin biopsy “demonstrated a normal range of epidermal nerve fiber density;” however, he found the biopsy was “suggestive of early nerve fiber degeneration” and that a later biopsy “may be useful.”
Over four months later, on January 3, 2001, petitioner presented to the emergency room acting strange and confused and complaining of worsening pain in his extremities. The admission notes indicate that petitioner has a neuropathic condition that has waxed and waned, but is slowly progressive. The admission notes also indicated that petitioner had experienced some changes in mental status, including poor memory, decreased alertness, and diminished concentration. The diagnosis on discharge was acute severe exacerbation of chronic neuropathy pain.
On May 8, 2001, petitioner saw Rex Chiu, M.D., an internist at Stanford Hospital and Clinics, on referral from Dr. Lomen-Hoerth. Dr. Chiu noted that petitioner experienced an onset of numbness and tingling in his left toe six days after receiving a polio vaccination and a Hepatitis B vaccination in anticipation of business travel to India. Petitioner’s developing symptoms produced a concern for a post-inflammatory reaction to the immunizations, but a trial course of prednisone provided no relief. Following a series of visits to diverse medical specialists, the consensus diagnosis appears to be small fiber neuropathy. Dr. Chiu wrote that because petitioner’s neurologic changes seem to have arisen after his immunization in 1999, there is question as to whether there is some type of autoimmune or other reaction to this vaccination, which may now be worsening in a progressive fashion. Dr. Chiu noted: The patient is Hepatitis B negative, referring to the lack of Hepatitis B antibodies that might be expected to appear. Dr. Chiu planned to refer petitioner for further neurologic and rheumatologic examination at Stanford.
On referral from Dr. Chiu, Yuen So, M.D., a neurologist at Stanford, examined petitioner on July 12, 2001. Dr. So noted that petitioner had seen a number of neurologists over a two-year period. Dr. So further noted that the most disabling feature of petitioner’s illness was his diffuse pain. Based on a physical examination of petitioner and a review of petitioner’s laboratory test results, Dr. So wrote: It is conceivable that [petitioner] had an acute, predominantly sensory polyneuropathy back in 1999. But without the records of petitioner’s medical evaluation during that time period, Dr. So found it difficult to ascribe petitioner’s complaint of progressive symptoms since 1999 to the received vaccinations. Disturbing to Dr. So about petitioner’s condition was the a very diverse nature of petitioner’s symptoms.
Also disturbing to Dr. So was the lack of objective evidence of neuropathic abnormality in a patient who has had ongoing disease for a course of two years. Contrary to normal expectations for a patient suspected of having a prior acute neuropathy, petitioner did not demonstrate a slow and steady course of improvement. Dr. So described the case as a very difficult one to diagnose and to treat.
In September 2001, petitioner and his wife moved from northern California to Delaware. Approximately two months later, on November 8, 2001, petitioner visited Gail Berkenblit, M.D., an internist at Johns Hopkins, for ongoing chronic pain. Dr. Berkenblit conducted a physical examination and reviewed the records that petitioner presented regarding his extensive laboratory work. Dr. Berkenblit took an extensive patient history and noted that petitioner’s evaluations have been essentially normal, including his autonomic function testing. Petitioner’s initial diagnosis was a possible post inflammatory neuropathy. Subsequently, petitioner received evaluations for a possible small fiber neuropathy. Repeated testing, however, had not disclosed any definite evidence of a small fiber neuropathy. Rather, swelling noticed in the distal leg sites during a neurologic examination at Johns Hopkins by Dr. Nicholas Maragakis was suggestive of early possible nerve fiber degeneration. During the office visit, Dr. Berkenblit addressed concerns expressed by petitioner and his wife that petitioner’s symptoms resulted from his Hepatitis B vaccination. Dr. Berkenblit observed that there is no clear link between Hepatitis B vaccination and progressive neuropathic pain, but noted that if petitioner did develop symptoms of a sensory neuropathy as a consequence of the vaccine, it would most likely be as an autoimmune type mechanism and not a vaccine contamination issue as petitioner’s wife speculated.
Petitioner filed his vaccine claim on December 20, 2001.
On January 15, 2002, a second skin biopsy was taken from several different places on petitioner’s leg. The test result again showed a normal range of epidermal nerve fiber density, offering “no definitive evidence” of a small fiber neuropathy and “no clear progression compared to the August 2000 biopsies.”
Three weeks later, on February 7, 2002, petitioner visited Lee Dresser, M.D., a neurologist, for an evaluation. Dr. Dresser noted that previous evaluations by neurologists included an assumption that petitioner had developed a sensory neuropathy as a response to his vaccination but that diagnosis was modified as extensive testing has returned negative results. It was Dr. Dresser’s impression that petitioner suffers from diffuse dysesthetic pain following remote vaccinations. Of interest to Dr. Dresser was the finding of a mild elevation of petitioner’s spinal fluid protein following petitioner’s extensive and otherwise unremarkable testing. Dr. Dresser observed that petitioner’s symptoms were essentially 100% subjective with no significant objective findings on . . . testing or examination. Dr. Dresser found petitioner’s case to be a very complicated one.
Opinions of Possible Vaccine-Related Causation
To assist petitioner with his pending vaccine claim, Dr. Roberts, the primary care physician who examined petitioner when his symptoms first began in 1999, wrote a letter dated February 13, 2002. Dr. Roberts stated that petitioner had no significant neurologic symptoms prior to the petitioner’s receipt of the Hepatitis B vaccination and that petitioner began to develop neurologic complaints shortly after his immunization. Id. It was Dr. Roberts’ belief that the temporal relationship between the received vaccination and the onset of petitioner’s symptoms strongly correlated with the hypothesis that the symptoms were caused by the vaccination. Thereafter, other treating doctors offered views about what may have caused petitioner’s symptoms.
On January 21, 2003, Robert Allen, M.D., an evaluator retained by the defense in connection with the worker’s compensation claim filed by petitioner, examined petitioner.
Dr. Allen observed that petitioner’s neurologic evaluations (including biopsies) have not documented any progressive neurologic disease. In Dr. Allen’s opinion, petitioner’s clinical history and physical examination, together with the extensive objective work-up, suggested a diagnosis of fibromyalgia. He explained that the diagnosis of fibromyalgia involves the presence of widespread musculoskeletal pain, as well as multiple tender points . . . that occur both above and below the waist. He stated that the etiology of his fibromyalgia remains unclear and may have developed as a result of the June 1999 vaccinations. But, Dr. Allen acknowledged, such causation is impossible to confirm or deny. Dr. Allen was one of two evaluators to diagnose petitioner with fibromyalgia, a diagnosis that is disputed by petitioner’s treating physicians. The diagnosis of fibromyalgia was first considered by the defense evaluator, Dr. Robert Allen. Another defense evaluator, Dr. Charles Skomer, diagnosed a chronic pain condition but allowed that petitioner’s symptoms were possibly consistent with a finding of fibromyalgia. But, there is no evidence in either the multiple neurologic or rheumatologic evaluations contained in petitioner’s medical records.
On April 29, 2003, Harold Buttram, M.D., an internist with Woodlands Healing Research Center, examined petitioner. Dr. Buttram noted that petitioner had become ill following chelation efforts to eliminate mercury, and subsequent testing indicated that mercury toxicity was not an issue for petitioner. Dr. Buttram further noted that Dr. Tenpenny, the treating physician who testified at the first hearing on petitioner’s behalf, had directed petitioner’s mercury detoxicification process. Aware that petitioner’s vaccine claim was pending, Dr. Buttram wrote: “For the records, it is my opinion that the patient’s peripheral neuropathy is directly related to (was caused by) a series of two Hepatitis B vaccines.” Noting that petitioner Aha[d] been diagnosed by neurologists as having chronic neuropathic pain, Dr. Buttram prepared an opinion letter dated June 6, 2003, stating that he agreed with the diagnosis of the neurologists and reiterating that petitioner’s condition was caused by a series of Hepatitis B vaccines.
On November 4, 2004, petitioner was given a diagnosis of “vaccine-induced neuroimmune dysfunction” by Vincent Natali, M.D., a general practitioner. Thereafter, on December 23, 2004, David Waldman, M.D., another physician, issued an extensive report concerning petitioner’s disability status. Dr. Waldman’s report was informed by his review of petitioner’s medical records, his review of medical literature, and a physical examination of petitioner.
Contained in Dr. Waldman’s report was a detailed, chronological summary of petitioner’s medical evaluations and laboratory results. Also contained in Dr. Waldman’s report was a summary of medical articles that he had reviewed, in connection with his evaluation of petitioner, concerning complications from the Hepatitis B vaccination. Dr. Waldman concluded there is no evidence within the records submitted that, prior to 6/11/99, Mr. Shaw had any neurological injury and was not able to function. . . . After the vaccinations of 6/11/99, Mr. Shaw began a very complex medical history, resulting in a chronic pain disorder syndrome. . . . Mr. Shaw has a problem with pain medicine addiction, which he did not have prior to his industrial injury. As stated within his multiple medical records, as a consequence of his work related chronic pain disorder, he has developed a drug dependence. . . . There is no evidence in review of the medical records that Mr. Shaw has a fibromyalgia syndrome. . . . Rather, Mr. Shaw has developed a chronic neuropathic pain syndrome. Although the exact etiology has not been determined, based on the review of the medical records and medical literature, it is with medical probability that this syndrome was a consequence of the vaccinations received on 6/11/99. This opinion that this syndrome occurred post vaccination has also been supported by multiple clinical evaluators . . . including Dr. Janet Lin and Dr. [Catherine] Lomen-Hoerth [two neurologists] at UCSF Medical Center. This has also been supported by recent evaluations which Mr. Shaw has sought to obtain relief from his pain syndrome . . . with multiple sequela, including drug dependence, and these conditions are industrial in nature.
Pamela P. Palmer, M.D., an anesthesiologist at the UCSF Medical Center’s Pain Management Center, examined petitioner nearly nine months later on September 20, 2005. Dr. Palmer assessed petitioner as “a 46 year-old gentleman with six years of diffuse pain after vaccination, consistent with a diffuse small fiber neuropathy.”
Four months later, on January 30, 2006, petitioner was evaluated by Phyllis A. Cullen, M.D., an anesthesiologist and pain specialist with the Chico Pain Clinic in Chico, California. Dr. Cullen reported petitioner’s history as that of “a 46 year old man who suffered an intense reaction to a Hepatitis B vaccine in 1999, developing a small fiber neuropathy.” Dr. Cullen’s impression after examining petitioner was that he had a “small fiber neuropathy.”
Thereafter, Robert E. Sullivan, M.D., who prescribed petitioner’s medicinal cannabis, found on February 13, 2007, that petitioner’s “chronic polyneuropathy persists, secondary to a Hepatitis B adverse reaction.”
Petitioner testified at the 2008 hearing for his vaccine claim that he continued to experience fluctuating levels of pain. His pain is best managed by the opiate therapy he has been prescribed. A neuropsychologic evaluation was subsequently conducted by Alfred L. Scopp, Ph.D., at the request of petitioner’s disability attorney. In a lengthy report dated June 25, 2008, Dr. Scopp concluded that petitioner suffered from a “progressive peripheral neuropathy subsequent to Hepatitis B inoculation.”
On August 7, 2008, petitioner was seen by Oscar N. Abeliuk, M.D., a neurologist for a comprehensive neurologic consultation in connection with his disability claim. Dr. Abeliuk prepared a lengthy report, in which he determined that petitioner suffered from a “decreased perception of pinprick and light touch in a symmetrical distribution in the upper and lower extremities distally, suggestive of long-term polyneuropathy (in this case, small fiber type).” Dr. Abeliuk offered as a diagnosis, “chronic debilitating polyneuropathy, well documented by multiple tests. Doctor Lomen-Hoerth has determined the presence of small fiber polyneuropathy affecting the upper and lower extremities, as documented by a skin biopsy at Johns Hopkins, with disturbing skin sensations.”
On May 18, 2009, petitioner was seen by Joel M. Rothfeld, Ph.D, M.D., for a neurologic consultation. In Dr. Rothfeld’s assessment, petitioner has a “history of distal small fiber neuropathy with chronic pain refractory to multiple medication therapies.” Dr. Rothfeld found that petitioner’s “neurolgical exam revealed alodynic response to sensory testing distal lower extremities consistent with small fiber neuropathy neuropathic pain.”
Petitioner appears to have remained under the care of his primary treating neurologist, Dr. Catherine Lomen-Hoerth. Dr. Lomen-Hoerth found after her examination of petitioner on August 26, 2009, that clinically [petitioner] appears to have a progressive small fiber neuropathy, with documentation on skin biopsy suggestive of an early small fiber neuropathy. These type of neuropathies typically have normal nerve conduction studies and normal neuroimaging, as was the case with Mr. Shaw. . . . He is unable to work due to an inability to stand or sit for any period of time and has an inability to type well due to numbness and pain.
In a letter dated November 14, 2009 to Cigna Disability Claims department, Dr. Pamela P. Palmer, the anesthesiologist who continued to treat petitioner for pain, noted that he suffers from “a clearly diagnosed small-fiber neuropathy” and urged that his disability benefits be reinstated. Likewise, his primary care physician, Katherine Julian, M.D., wrote a letter requesting reinstatement of petitioner’s disability benefits. Dr. Julian explained that “it is unclear as to the . . . etiology of his neuropathy, though specialists believe the cause is likely due to a vaccine he received in the late 1990’s. . . . However, he has been evaluated by neurology, and standard office-based nerve testing does reveal neuropathy.”
APPLICABLE LEGAL STANDARDS
The Vaccine Act provides two separate methods by which to obtain Program compensation: (1) Vaccine Injury Table (Table) claims; and (2) causation in fact (off-Table) claims. When asserting a Table claim, a claimant is afforded a presumption of causation if he shows that he received a vaccine listed on the Table and suffered an injury listed on the Table within the prescribed time period. If unable to establish a Table claim, the claimant must show that his injury was caused in fact by the vaccine he received.
The Vaccine Act provides for the compensation of any illness, disability, injury, or condition not set forth in the Vaccine Injury Table but which was caused by a vaccine covered under the Program. The Act does not require a petitioner bringing a non-Table claim to categorize the suffered injury. Rather, a petitioner is required only to show that the vaccine in question caused injury-regardless of the ultimate diagnosis. When, as in this case, the conditions at issue present with many of the same symptoms—but the underlying causes and required treatments are different—and when, as in this case, the evidence for causation depends on the particular diagnosis of petitioner’s condition, a special master may consider whether the record supports the diagnosis proposed by petitioner. A petitioner may prove entitlement to Program compensation of an off-Table case by satisfying the three-part test set forth by the Federal Circuit in Althen v. Secretary of Health & Human Services. Concisely stated, a claimant’s burden is to show by preponderant evidence that the vaccination brought about [his] 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. If a claimant satisfies this burden, he is entitled to recover unless the government shows, also by a preponderance of evidence, that the injury was in fact caused by factors unrelated to the vaccine. To prevail, a claimant’s theory of causation must be supported by a reputable medical or scientific explanation. A claimant need not produce medical literature or epidemiologic evidence in support of his theory causation, but if such evidence is submitted, a special master may consider the scientific soundness of that evidence in reaching an informed judgment as to whether a particular vaccination more likely than not caused a particular injury.
While Althen contemplates that the provided support for a claimant’s theory of causation is based on a reputable medical or scientific explanation, that support need not rise to the level of medical or scientific certainty for a petitioner to prevail on a vaccine claim. In Andreu, the Federal Circuit made clear that submitted medical literature and epidemiologic evidence must be viewed, however, not through the lens of the laboratorian, but instead from the vantage point of the Vaccine Act’s preponderant evidence standard: “The standard of proof required by the [Vaccine] Act is simple preponderance of evidence; not scientific certainty. . . . [I]t is not plaintiff’s burden to disprove every possible ground of causation suggested by defendant nor must the findings of the court meet the standards of the laboratorian.”
When reviewing offered scientific evidence, a special master must take into account that a finding of causation in the medical community may require a much higher level of certainty than that required by the Vaccine Act to establish a prima facie case. Also reiterated in Andreu is the importance in vaccine cases of considering medical opinions contained in the records or presented at hearing testimony. Such opinions, explained the Circuit Court, can be quite probative since 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. However, consistent with the Vaccine Act, a special master is not bound by any diagnosis, conclusion, judgment, test result, report, or summary contained in the record. A special master must consider the entire record and the course of the subject injury when evaluating the weight to be afforded to any offered diagnosis, conclusion, judgment, test result, report, or summary contained in the record.
ANALYSIS
Opinion of Petitioner’s Expert Witness, Dr. Morgan
In support of his vaccine claim, on remand, Mr. Shaw relies on the opinions of the treating physicians contained in his filed medical records, as well as the offered expert report and remand hearing testimony of Dr. Morgan. Having obtained a medical degree from Meharry Medical College in 1970, Dr. Morgan is board-certified by the American Board of Psychiatry and Neurology, as well as by the American Board of Independent Medical Examiners. Dr. Morgan is a practicing neurologist, whose focus is neurologic injury and disability. Dr. Morgan is also an Assistant Professor at Brown University, School of Medicine in the Department of Clinical Neuroscience.
It is Dr. Morgan’s opinion, based on the evaluations of petitioner’s treating physicians, the medical records, the medical literature, as well as his own expertise, that Mr. Shaw suffers from a small fiber neuropathy. It is the further position of Dr. Morgan that petitioner’s injury resulted from a demyelination of his peripheral nerves through the biological mechanism of molecular mimicry caused by the Hepatitis B vaccines he received. This theory of causation contemplates that the administered “vaccine stimulates the host’s immune system to react to the Hepatitis B antigen and cross react with the myelinated nerve fibers of the host. This mistaken attack by the body’s own immune system is secondary to the similarity between the foreign Hepatitis B antigen and the myelin component in the host.” In sum, Dr. Morgan posits that the Hepatitis B vaccine can cause demyelination of the peripheral nerves, id., and a finding that petitioner suffers from “a small fiber neuropathy causally related to a post-vaccinal immune mediated peripheral nerve disorder,” is supported by the “time of symptom onset.”
Opinion of Respondent’s Expert Witness, Dr. Leist
To address the opinion offered by Dr. Morgan, respondent offered the opinion and testimony of Dr. Leist, who serves as Chief of the Division of Neuroimmunology and Director of the Comprehensive Multiple Sclerosis (MS) Center at Thomas Jefferson University in Philadelphia, Pennsylvania. Possessing a doctorate in biochemistry from the University of Zurich in 1985 and a medical degree from the University of Miami in 1993, Dr. Leist augmented his studies by pursuing postgraduate training in the areas of pathology, microbiology, immunology and neurology. Board-certified by the American Board of Psychiatry and Neurology and describing himself as a bench-trained immunologist with strong interests in general immunology and viral immunology, he has focused, through his training, on diseases that are immunologic in nature and affect the nervous system.
Dr. Leist takes issue with Dr. Morgan’s opinion. Dr. Leist notes as an initial matter, that Mr. Shaw has had two skin biopsies performed to evaluate whether he has a small fiber neuropathy. In both instances, the biopsies exhibited “normal epidermal nerve fiber density”—a result that did not support a finding that petitioner suffer from a small fiber neuropathy. Leist further notes that neither the MRIs or the electrophysiologic studies that were performed for Mr. Shaw, after the vaccinations at issue, showed evidence of a demyelinating or inflammatory process in the peripheral or central nervous system. Additional evidence that in Dr. Leist’s view diminishes the likelihood that petitioner’s injury is vaccine-related is the negative result of the test conducted for antibodies against the Hepatitis B vaccine on September 26, 2001.That negative finding, according to Dr. Leist, indicates that petitioner’s Hepatitis B vaccination did not result in the type of T-cell response necessary to precipitate demyelination.
Evaluating Whether Petitioner Suffers a Small Fiber Neuropathy
Among the issues to be resolved is whether petitioner suffers from a small fiber neuropathy. For the reasons discussed below the undersigned is persuaded that petitioner more likely than not suffers from a small fiber neuropathy. At hearing, petitioner’s expert, Dr. Morgan, provided the following background information concerning small fiber neuropathy. He explained that a small fiber neuropathy is a syndrome that “primarily involves the sensory nerves.” He elaborated that a “hallmark” of this condition are both “positive” and “negative” symptoms. Id. Positive symptoms are sharp pains and involve the myelinated Alpha Delta fibers; in contrast, negative symptoms are numbness and involve the unmyelinated C fibers. He testified that “small nerve fibers are nerves that are made up of both unmyelinated fibers, called C fibers; and . . . myelinated fibers called Alpha Delta fibers” which are “thinly myelinated.” The medical records indicate that Mr. Shaw began to experience both the positive symptom of “pins and needles” and the negative symptom of “some numbness,” approximately six days after his June 11, 1999 Hepatitis B immunization—as reported to his treating physician (noting that his numbness began on June 17, 1999, four days prior to his visit to Dr. Roberts and six days after he received his second Hepatitis B vaccine, and that numbness was “progressing to a throbbing pain”).
Petitioner experienced the symptoms in his hands and feet (“glove and stocking”). According to Dr. Morgan, the numbness in all four limbs reported to petitioner’s orthopedic surgeon was a negative symptom involving the unmyelinated C fibers. Contrastingly, the reported “shooting pain in the limbs with throbbing” was a positive symptom implicating the myelinated fibers.” Dr. Morgan’s testimony explaining the symptoms of small nerve fiber dysfunction was consistent with petitioner’s filed medical literature.
Petitioner’s Laboratory Tests: Dr. Morgan addressed petitioner’s various medical tests and the test results, asserting that they supported or, at least, did not contradict a diagnosis of small fiber neuropathy. Referring to petitioner’s skin biopsies, Dr. Morgan explained that petitioner’s early test results showed a “normal range of epidermal nerve fiber density,” but when considered with his other skin biopsy results, revealed abnormality. Dr. Morgan testified that petitioner’s treater, Dr. Maragakis, determined from petitioner’s first skin biopsy that the “nerve swellings . . . could be the beginning of a nerve degeneration” (addendum to August 21, 2000 report of Dr. Maragakis discussing the results of petitioner’s first skin biopsy). Because petitioner’s symptoms did not improve, but progressively worsened after that biopsy, Dr. Lomen-Hoerth, petitioner’s treating neurologist, recommended repeating the skin biopsy. The second skin biopsy was taken from several different places on petitioner’s leg, including she proximal thigh, his distal thigh, and his distal leg. The test result again showed a normal range of epidermal nerve fiber density offering “no definitive skin biopsy is considered the best method for diagnosing a small fiber neuropathy.” A skin biopsy will report an abnormal result in 67% of small fiber neuropathy cases. Dr. Morgan testified, however, that the result was “not normal” at the proximal thigh location because petitioner’s “nerve fiber distribution was borderline” normal with a patchy distribution and that some of the examined fibers were “fragmented and contained small swellings.” Similarly at the distal leg the nerve fiber “distribution again is patchy.” In Dr. Morgan’s opinion, this “patchy” distribution of nerve fiber cells is consistent with a small fiber neuropathy. Dr. Morgan also addressed the findings of petitioner’s EMG and nerve conduction exams which were documented as normal. Dr. Morgan explained that an abnormal EMG requires “some involvement of the . . . ventral nerve root,” but because small fiber neuropathy “doesn’t involve the ventral nerve root that supplies motor fibers,” an EMG would not show abnormality.
Dr. Morgan also discussed petitioner’s conduction study. Dr. Morgan offered that: Sensory nerve conduction, which is a little more sensitive than motor nerve . . . measures more . . . heavily myelinated fibers. And if that process is spared, you won’t see abnormalities on the nerve conduction and the nerve conduction velocities will be normal, particularly the sensory nerve conductions. And so . . . the nerve conduction study just further supports that this petitioner’s injury involves . . . small fibers, both myelinated and unmyelinated. Dr. Morgan further offered that small fiber sensory neuropathy does not involve sufficient heavily myelinated fibers to “create abnormalities in the nerve conduction testing.” He added that “if there is too much involvement of the heavily myelinated fibers,” the condition no longer falls within small fiber neuropathy category.” Petitioner’s treating neurologist, Dr. Lomen-Hoerth, commented, in her notes that petitioner’s “normal nerve conduction” studies “do not exclude a small fiber neuropathy.” The electromyographer, Dr. James Wei, who reviewed the nerve conduction studies agreed with Dr. Lomen-Hoerth.
The filed medical literature confirms the difficulty described by Dr. Morgan in diagnosing a small fiber neuropathy. As observed in the 2002 Lacomis article, small-fiber neuropathy is a “commonly encountered disorder” that is “frustrating to clinicians because of difficulties in proving the diagnosis and in treatment.” Consistent with Dr. Morgan’s testimony, Lacomis observed that to the extent routine nerve conduction studies assess large-fiber function, they are generally normal.” Lacomis also states that although “heart variability can be assessed on some EMG equipment . . . it is likely that the subtle abnormalities associated with most small-fiber neuropathies will not be detected.”
Respondent’s expert Dr. Leist is not persuaded that petitioner suffers from a small fiber neuropathy. In his view, petitioner’s test results—particularly the skin biopsies—provide evidence that “weighs against” a small fiber neuropathy diagnosis. Dr. Leist opines, “I would expect that if somebody has progressive symptoms over a period of time, that there would be evidence of a progressive underlying dysfunction. . . . would I expect . . . an objectifiable finding of, for example, nerve loss over the one and a half or two years between the two skin biopsies? Yes, I would expect this. The fact that it’s not there, I would consider as less usual. . . .The fact that it doesn’t show abnormality clearly doesn’t support a finding of small fiber neuropathy.”
The Opinions of Petitioner’s Treating Doctors: Dr. Morgan also relied on the opinions of petitioner’s treating physicians who variously considered a small fiber neuropathy diagnosis. Petitioner’s doctors recorded different impressions about the precise nature of his injury. What is consistently reported, however, is a condition involving a progressive and chronic pain syndrome. After a careful review of petitioner’s records and the expert testimony, the undersigned is persuaded that it is more likely than not that petitioner suffers from a small fiber neuropathy. Interpretation of the EMG results in September of 1999: The patient is most likely exhibiting very early symptoms of idiopathic peripheral neuropathy. Dr. Lin indicating that petitioner was suffering a post-inflammatory neuropathy related to immunizations. Dr. Villanueva discussing petitioner’s subjective diffuse sensory polyneuropathy. Dr. Lomen-Hoerth’s impression in May of 2000 that petitioner had a progressive small fiber neuropathy. Dr. Maragakis’s view that “this most likely represents some form of small fiber neuropathy.” Dr. So opining in July 2001: It is conceivable that petitioner had an acute, predominantly sensory polyneuropathy back in 1999. Dr. Waldman finding in December 2004 that “Mr. Shaw has developed a chronic neuropathic pain syndrome.” Dr. Cullen’s reported patient’s history as that of “a 46 year old man who suffered an intense reaction to a Hepatitis B vaccine in 1999, developing a small fiber neuropathy.” Dr. Palmer describing petitioner as “a 46 year-old gentleman with six years of diffuse pain after vaccination, consistent with a diffuse small fiber neuropathy.” Dr. Robert Sullivan finding in February 2007 that petitioner’s “chronic polyneuropathy persists.” Dr. Alfred Scopp indicating that petitioner has an Axis III diagnosis of peripheral neuropathy.” Dr. Oscar Abeliuk found petitioner’s condition to be “suggestive of long-term polyneuropathy (in this case, small fiber type).” Dr. Rothfeld’s assessment that petitioner has a “history of and current neurologic responses consistent with small fiber neuropathy with chronic pain.” Petitioner’s primary treating neurologist, Dr. Lomen-Hoerth, finding again in August 2009 that “clinically petitioner appears to have a progressive small fiber neuropathy, with documentation on skin biopsy suggestive of an early small fiber neuropathy.” In November of 2009, Dr. Palmer, who treated petitioner for pain, noting that he suffers from “a clearly diagnosed small-fiber neuropathy.”
It is true—as respondent points out, see Respondent’s Post-Hearing Brief on Remand filed November 17, 2010, that many of petitioner’s treating physicians did not make a definitive diagnosis of small fiber neuropathy. But, it is this diagnosis that his various treaters and evaluations most frequently considered based chiefly on petitioner’s neurologic responses. Recognizing that the “objective” tests and studies do not clearly demonstrate or negate a diagnosis of small fiber neuropathy, the undersigned is persuaded that petitioner’s clinical presentation (as reflected in the medical records), the opinions of petitioner’s treating physicians, the expert opinion of Dr. Morgan and the cited medical literature adequately support such a finding. While the undersigned cannot find with medical certainty that petitioner suffers from a small fiber neuropathy, the undersigned does find that more likely than not petitioner is afflicted with this condition, and the undersigned is mindful that “the standard of proof required by the Vaccine Act is simple preponderance of evidence; not scientific certainty.” The undersigned notes that Dr. Maragakis later indicated that he could not “make a diagnosis of peripheral neuropathy based on any of the based on any of the studies” performed.
Evaluating Petitioner’s Claim under the Althen Prongs
As stated earlier, petitioner must prove causation by showing: (1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing the vaccination was the reason for the injury; and (3) a proximate temporal relationship between the vaccination and the injury. The undersigned addresses each of the prongs of the Althen standard in turn. For ease of discussion, the undersigned addresses the first and the third prongs of the Althen before turning to the second prong.
Petitioner’s Offered Medical Theory: Petitioner must offer a medical theory causally connecting the vaccination and the injury. As discussed above, Dr. Morgan opined in his written report that petitioner’s small fiber neuropathy resulted from his Hepatitis B vaccine causing a demyelination of his peripheral nerves through a biological mechanism of molecular mimicry. This theory contemplates that the “vaccine stimulates the host[’s] immune system to react to the Hepatitis B antigen and cross react with the myelinated nerve fibers of the host. . . . This mistaken attack by the body’s own immune system is secondary to the similarity between the foreign Hepatitis B antigen and the myelin component in the host.”
At hearing, Dr. Morgan explained his theory of molecular mimicry as follows: It starts at the dorsal root ganglion and that ganglion has unmyelinated, myelinated, heavily myelinated fibers. There is an antigen antibody reaction that occurs there, disrupts the myelin and is reflected in the peripheral nerve and small fibers, specifically involving both the alpha thinly myelinated fibers and the unmyelinated C fibers. And that is caused by an immune mechanism which is the antigen from the vaccine that looks at the normal self myelin, cross reacts with it, and causes this initial inflammatory reaction. And which then leads to the gradual demyelination affecting the nerve roots, which then account for the person’s—for Mr. Shaw’s—symptoms. Dr. Morgan pointed to Petitioner’s Trial Exhibit Number 5 to further describe this mechanism: And so you could see where if someone got an inflammatory demyelinative reaction, how the secondary effects would affect both . . . the unmyelinated fiber, which is the C fiber, which is what we see with small fiber neuropathy; but it also affects the thinly myelinated fiber, which also is part of small fiber neuropathy. And there’s some suggestion that it actually affects some of even the heavier myelinated fibers but not much. If it does, then it becomes no longer a small fiber neuropathy. . . . So it’s a complex understanding of it, but I think it explains why these things aren’t just black and white . . . it’s not one root, one root and everything is nicely fit. That’s why these syndromes are called syndromes. And they overlap.
Dr. Morgan testified that inflammatory cells have likewise been observed, from autopsy slides, in the dorsal root ganglion of patients with Guillain-Barré syndrome. Dr. Morgan offered evidence supporting petitioner’s theory, that molecular mimicry can cause “a post-vaccinal type of neuropathy,” in the form of medical literature. Specifically, the Lacomis article notes that “in some patients with idiopathic small-fiber neuropathy, an inflammatory autoimmune basis has been hypothesized, and circumstantial evidence is available.” Lacomis goes on to discuss this evidence, concluding: “Thus, there is evidence that suggests, but does not prove, that infections or autoimmune processes may cause small-fiber neuropathy. Unfortunately, there are no good laboratory markers of this autoimmune process.”
But, Dr. Leist took issue with the lack of evidence that the Hepatitis B vaccination can harm unmyelinated C fibers, and was not persuaded by Dr. Morgan’s explanation that the unmyelinated C fibers experience secondary effects or bystander effects from the post vaccinal inflammatory demyelinative reaction. At the first hearing in this case, Dr. Leist conceded that it is “potentially possible” that the Hepatitis B vaccine can cause auto-immune reactions. In making this statement, Dr. Leist indicated that he was relying upon “the opinion of the Institute of Medicine (IOM), which says it’s possible to put a mechanism together by which Hepatitis B could cause an immune mediated injury.” Notwithstanding this statement by the IOM, Dr. Leist found in this case there is not “a reputable theory by which one could explain a small fiber neuropathy, a theory that is accepted . . . it’s not accepted with respect to the Hepatitis B vaccine.”
Reviewing the evidence on balance, the undersigned finds preponderant evidence of a “medical theory causally connecting the vaccination and the injury.” To be sure, such evidence in this case is not scientifically certain—as respondent points out—the medical literature does not specifically link the Hepatitis B vaccination or any vaccination to the injury of small fiber neuropathy. However, petitioner has provided a sound “medical or scientific explanation that pertains specifically to the petitioner’s case . . . that is ‘legally probably,’ even if not medically or scientifically certain.”
The undersigned will next examine the third prong of the Althen test—the temporal relationship between Mr. Shaw’s vaccination and his injury—as this evidence is pivotal to the undersigned’s analysis of the second Althen prong.
The Temporal Relationship between the Vaccination and the Injury: Petitioner must show more than a proximate temporal relationship between the vaccination and the injury to satisfy the burden of showing actual causation.
The contemporaneous medical records indicate that petitioner’s symptoms began six days after the receipt of his second Hepatitis B vaccination. Dr. Morgan testified that six days is appropriate for onset of an immune related disorder. Respondent’s expert, Dr. Leist, agreed that the “temporal relationship between the administration of the vaccine and the onset of symptoms was appropriate. It is within a period of time that would be acceptable . . . for an immune response to appear at all.” Because symptoms of petitioner’s injury occurred within an appropriate medical time frame for an immune-mediated injury, petitioner has satisfied the third prong of the Althen standard.
The undersigned turns now to address petitioner’s proposed sequence of cause and effect.
The Sequence of Cause and Effect: The Federal Circuit has observed that an offered medical theory is persuasive when accompanied by proof of a logical sequence of cause and effect showing that the vaccination was the reason for the injury, the logical sequence being supported by reputable medical or scientific explanation, i.e., evidence in the form of scientific studies or expert medical testimony. The Federal Circuit has found the opinions of treating physicians to be particularly probative in evaluating the second prong of Althen, particularly “if a claimant satisfies the first and third prongs of the Althen standard” as “treating physicians are likely to be in the best position to determine whether a logical sequence of cause and effect shows that the vaccination was the reason for the injury.”
As discussed above, Mr. Shaw has satisfied the first and third prongs of the Althen standard. In considering whether Mr. Shaw has demonstrated a logical sequence of cause and effect, the undersigned turns to the opinions of his treating physicians. As an initial matter, the undersigned notes that it is undisputed that the “leading cause” of small fiber neuropathy is idiopathic—it cannot be identified. However, progress is being made toward identifying potential causes of small fiber neuropathy, to include the possibility of infections or autoimmune causes.
Petitioner has been evaluated and/or treated by a substantial number of physicians since his symptoms began in 1999. A remarkable number, although not all, of these treating doctors have either postulated or ascribed vaccine causation to his injury. Particularly persuasive to the undersigned was the opinion of vaccine-related causation expressed by petitioner’s treating neurologists. Dr. Lin, an examining neurologist, recorded that petitioner was suffering a post-inflammatory neuropathy related to immunizations. It was Dr. Lomen-Hoerth’s, Mr. Shaw’s primary neurologist, early impression that petitioner had a progressive small fiber neuropathy rather than a static neuropathy related to his vaccinations. A consulting neurologist, Dr. Dresser recorded his impression in 2002 that petitioner suffers from diffuse dysesthetic pain following remote vaccinations. Dr. Martin, a rheumatologist, indicated that petitioner suffered from an idiopathic syndrome associated with chronic fatigue and . . . is possibly related to a vaccine exposure or possibly a toxin. Dr. Chiu, an internist, observed that because petitioner’s neurologic changes seem to have arisen after his immunization in 1999, there is a question as to whether there is some type of autoimmune or other reaction to this vaccination.” Dr. Berkenblit, an internist, maintained that while there is no clear link between Hepatitis B vaccination and progressive neuropathic pain, if Mr. Shaw did develop symptoms of a sensory neuropathy as a consequence of the vaccine, it would most likely be an autoimmune type mechanism. Dr. Roberts, petitioner’s primary care physician, wrote a letter in 2002 indicating his belief that the temporal relationship between the received vaccination and the onset of petitioner’s symptoms strongly correlated with the hypothesis that the symptoms were caused by the vaccination. Dr. Allen, who evaluated petitioner in connection with his worker’s compensation claim, believed that petitioner’s injury “may have developed as a result of the June 1999 vaccinations.” Dr. Buttram, an internist, maintained the opinion that Mr. Shaw’s “peripheral neuropathy is directly related to (was caused by) a series of two Hepatitis B vaccines. “Vaccine-induced neuroimmune dysfunction” was the diagnosis of Dr. Natali, a general practitioner. Dr. Cullen, an anesthesiologist, described petitioner in 2006 as “a 46-year-old man who suffered an intense adverse reaction to a Hepatitis B vaccine in 1999, developing a small fiber neuropathy.” Dr. Palmer, another anesthesiologist, assessed petitioner as “a 46-year-old gentleman with six years of diffuse pain after vaccination, consistent with a diffuse small-fiber neuropathy. . . .” Dr. Sullivan found in February 2007 that petitioner’s “chronic polyneuropathy persists, secondary to a Hepatitis B adverse reaction.” In a report following a neuropsychological evaluation conducted at the request of petitioner’s disability attorney, Dr. Scopp concluded that petitioner suffered from a “progressive peripheral neuropathy subsequent to Hepatitis B inoculation.” Requesting reinstatement of petitioner’s disability benefits, Dr. Julian, a primary care physician, wrote, “Specialists believe the cause of petitioner’s neuropathy is likely due to a vaccine he received in the late 1990’s.”
Respondent points out that some of petitioner’s treaters subsequently modified their early opinions of vaccine causation or failed to ascribe his injury to vaccine-related causation. For example, Dr. Chiu noted the temporal relationship to the vaccine, but did not opine as to causation. Dr. Villanueva doubted vaccine causation, and Dr. Lin later altered her initial diagnosis of vaccine-related post inflammatory neuropathy. The undersigned takes note of these observations; but the record indicates that a number of the petitioner’s treating physicians postulated that petitioner’s condition was vaccine-mediated, informed—in part—by the temporal relationship between Mr. Shaw’s vaccinations and the onset of his injury.
Respondent further argues that Dr. Morgan’s theory of a post-vaccine immune response causing a demyelinating injury must fail because the evidence does not support a finding that Mr. Shaw experienced an immune response to his vaccination. Respondent bases this assertion on the finding that petitioner’s September 26, 2001 antibody testing was negative for IgG antibodies, the class of antibodies that assist in fighting against infection. Dr. Leist testified that while IgM antibodies initially mount a response to vaccination (or any other presented antigen), these antibodies are normally converted to IgG antibodies starting at day seven or eight. It was Dr. Allen’s view that petitioner was suffering from fibromyalgia.
However, on cross-examination, Dr. Leist conceded that IgM antibodies may “play a role” in demyelinating disorders that petitioner may have had a significant IgM response that never converted to an IgG response, and that petitioner was never tested for IgM antibodies. However, Dr. Leist maintained that while these were “theoretical” possibilities, he found them to be “exceedingly improbable.”
On balance, the undersigned is persuaded that petitioner has demonstrated a logical sequence of cause and effect. Petitioner has presented sound scientific testimony from a medical expert, well qualified in the field of neurology, that offers a cogent explanation of how petitioner’s Hepatitis B vaccination more likely than not caused him to develop a small fiber neuropathy by way of molecular mimicry. Petitioner has presented uncontested evidence of a proximate temporal relationship between the vaccination and the injury. And, finally, a number of petitioner’s treating physicians attributed Mr. Shaw’s injury to the Hepatitis B vaccines he received.
CONCLUSION
As discussed above, the undersigned finds that petitioner has established by preponderant evidence in this close case that his Hepatitis B vaccination was the legal cause of his small fiber neuropathy. The undersigned further finds that there is not a preponderance of the evidence that the legal cause of Mr. Shaw’s injury was due to factors unrelated to his Hepatitis B vaccination. Accordingly, the undersigned finds Mr. Shaw is entitled to compensation under the Vaccine Act. A separate damages order will issue.
IT IS SO ORDERED.
Anita Roberts and Gary Roberts, Co-petitioners, as Next Friends, Parents acting on behalf of Amber D. Roberts their minor child, Petitioners v. Secretary of Health and Human Services, Respondent
Summary: In this decision following a hearing, Special Master Zane rules that the victim suffered transverse myelitis after receiving a tetanus-diptheria-acellular pertussis vaccine.
Compensated Vaccine Injury: Transverse Myelitis
According to the National Institute of Neurological Disorders and Stroke, transverse myelitis is a neurological disorder caused by inflammation across both sides of one level, or segment, of the spinal cord. The term myelitis refers to inflammation of the spinal cord; transverse simply describes the position of the inflammation, that is, across the width of the spinal cord. Attacks of inflammation can damage or destroy myelin, the fatty insulating substance that covers nerve cell fibers. This damage causes nervous system scars that interrupt communications between the nerves in the spinal cord and the rest of the body.
Symptoms of transverse myelitis include a loss of spinal cord function over several hours to several weeks. What usually begins as a sudden onset of lower back pain, muscle weakness, or abnormal sensations in the toes and feet can rapidly progress to more severe symptoms, including paralysis, urinary retention, and loss of bowel control. Although some patients recover from transverse myelitis with minor or no residual problems, others suffer permanent impairments that affect their ability to perform ordinary tasks of daily living. Most patients will have only one episode of transverse myelitis; a small percentage may have a recurrence.
The segment of the spinal cord at which the damage occurs determines which parts of the body are affected. Nerves in the cervical (neck) region control signals to the neck, arms, hands, and muscles of breathing (the diaphragm). Nerves in the thoracic (upper back) region relay signals to the torso and some parts of the arms. Nerves at the lumbar (mid-back) level control signals to the hips and legs. Finally, sacral nerves, located within the lowest segment of the spinal cord, relay signals to the groin, toes, and some parts of the legs. Damage at one segment will affect function at that segment and segments below it. In patients with transverse myelitis, demyelination usually occurs at the thoracic level, causing problems with leg movement and bowel and bladder control, which require signals from the lower segments of the spinal cord.
Transverse myelitis occurs in adults and children, in both genders, and in all races. No familial predisposition is apparent. A peak in incidence rates (the number of new cases per year) appears to occur between 10 and 19 years and 30 and 39 years. Although only a few studies have examined incidence rates, it is estimated that about 1,400 new cases of transverse myelitis are diagnosed each year in the United States, and approximately 33,000 Americans have some type of disability resulting from the disorder.
Researchers are uncertain of the exact causes of transverse myelitis. The inflammation that causes such extensive damage to nerve fibers of the spinal cord may result from viral infections or abnormal immune reactions. Transverse myelitis also may occur as a complication of syphilis, measles, Lyme disease, and some vaccinations, including those for chickenpox and rabies. Cases in which a cause cannot be identified are called idiopathic.
Transverse myelitis often develops following viral infections. Infectious agents suspected of causing transverse myelitis include varicella zoster (the virus that causes chickenpox and shingles), herpes simplex, cytomegalovirus, Epstein-Barr, influenza, echovirus, human immunodeficiency virus (HIV), hepatitis A, and rubella. Bacterial skin infections, middle-ear infections (otitis media), and Mycoplasma pneumoniae (bacterial pneumonia) have also been associated with the condition.
In post-infectious cases of transverse myelitis, immune system mechanisms, rather than active viral or bacterial infections, appear to play an important role in causing damage to spinal nerves. Although researchers have not yet identified the precise mechanisms of spinal cord injury in these cases, stimulation of the immune system in response to infection indicates that an autoimmune reaction may be responsible. In autoimmune diseases, the immune system, which normally protects the body from foreign organisms, mistakenly attacks the body’s own tissue, causing inflammation and, in some cases, damage to myelin within the spinal cord.
Because some affected individuals also have autoimmune diseases such as systemic lupus erythematosus, Sjogren’s syndrome, and sarcoidosis, some scientists suggest that transverse myelitis may also be an autoimmune disorder. In addition, some cancers may trigger an abnormal immune response that may lead to transverse myelitis.
In some people, transverse myeltis represents the first symptom of an underlying demyelinating disease of the central nervous system such as multiple sclerosis (MS) or neuromyelitis optica (NMO). A form of transverse myelitis known as “partial” myelitis—because it affects only a portion of the cross-sectional area of the spinal cord—is more characteristic of MS. Neuromyelitis optica typically causes both transverse myelitis and optic neuritis (inflammation of the optic nerve that results in visual loss), but not necessarily at the same time. All patients with transverse myelitis should be evaluated for MS or NMO because patients with these diagnoses may require different treatments, especially therapies to prevent future attacks.
Transverse myelitis may be either acute (developing over hours to several days) or subacute (usually developing over 1 to 4 weeks). Initial symptoms usually include localized lower back pain, sudden paresthesias (abnormal sensations such as burning, tickling, pricking, or tingling) in the legs, sensory loss, and paraparesis (partial paralysis of the legs). Paraparesis may progress to paraplegia (paralysis of the legs and lower part of the trunk). Urinary bladder and bowel dysfunction is common. Many patients also report experiencing muscle spasms, a general feeling of discomfort, headache, fever, and loss of appetite. Depending on which segment of the spinal cord is involved, some patients may experience respiratory problems as well.
From this wide array of symptoms, four classic features of transverse myelitis emerge: (1) weakness of the legs and arms, (2) pain, (3) sensory alteration, and (4) bowel and bladder dysfunction. Most patients will experience weakness of varying degrees in their legs; some also experience it in their arms. Initially, people with transverse myelitis may notice that they are stumbling or dragging one foot or that their legs seem heavier than normal. Coordination of hand and arm movements, as well as arm and hand strength may also be compromised. Progression of the disease leads to full paralysis of the legs, requiring the patient to use a wheelchair.
Pain is the primary presenting symptom of transverse myelitis in approximately one-third to one-half of all patients. The pain may be localized in the lower back or may consist of sharp, shooting sensations that radiate down the legs or arms or around the torso.
Patients who experience sensory disturbances often use terms such as numbness, tingling, coldness, or burning to describe their symptoms. Up to 80 percent of those with transverse myelitis report areas of heightened sensitivity to touch, such that clothing or a light touch with a finger causes significant discomfort or pain (a condition called allodynia). Many also experience heightened sensitivity to changes in temperature or to extreme heat or cold.
Bladder and bowel problems may involve increased frequency of the urge to urinate or have bowel movements, incontinence, difficulty voiding, the sensation of incomplete evacuation, and constipation. Over the course of the disease, the majority of people with transverse myelitis will experience one or several of these symptoms.
Entitlement; tetanus-diptheria-accellular pertussis vaccination (“Tdap”); transverse myelitis (“TM”); oligoclonal banding; infarction; fibrocartilaginous embolism (“FCE”)
Case No: 09-427V
Date Filed: August 29, 2013
Anita Roberts and Gary Roberts, Co-petitioners, as Next Friends, Parents acting on behalf of Amber D. Roberts their minor child, Petitioners v. Secretary of Health and Human Services, Respondent
RULING
Special Master Zane
Petitioners, Anita Roberts and Gary Roberts (“Petitioners”), on behalf of their daughter, Amber Roberts (“A.R.”), filed a petition alleging that the tetanus-diptheria-acellular pertussisvaccine (“Tdap”) caused A.R. to suffer transverse myelitis. Petitioners seek compensation pursuant to the National Childhood Vaccine Injury Act. As explained below, upon consideration of the record as a whole, the special master concludes that Petitioners have satisfied their burden of showing by preponderant evidence that the vaccine was a substantial factor in causing A.R.’s autoimmune problem, transverse myelitis (“TM”). As explained below, there is ample evidence to satisfy Althen’s Prong 1. Petitioners rely on the well-recognized theory of molecular mimicry as the plausible medical theory that explains how the vaccine could have caused A.R.’s injuries. And, there is no dispute regarding Althen’s Prong 3. The parties’ experts agree that the time between vaccination and onset, approximately four weeks, is a medically appropriate temporal relationship.
The parties’ primary disagreement relates to Althen Prong 2 and whether Petitioners made a sufficient showing that there was a logical sequence of cause and effect between the vaccine and A.R.’s injuries. With regard to this issue, both parties have presented detailed evidence regarding the proper diagnosis of A.R.’s injury, the permanent paralysis of her lower extremities, and whether it was due to an inflammation caused by an autoimmune response, TM, or was the result of an infarction, embolism or FCE. As set forth below, the record, in particular, the clinical evidence and the results of the objective diagnostic tests with supporting medical literature in the record, sufficiently supports Petitioners’ claim as to Althen’s Prong 2. As such, Petitioners have satisfied all three Althen Prongs and have satisfied their burden.
FACTS
A.R. was born on July 2, 1995. P’s Ex. 1. During the first 11 years of her life A.R. was generally healthy. On July 06, 2006, A.R. visited her pediatrician for a sixth grade check-up. Although she complained of back pain at that time, the records noted she was generally healthy. She received a Tdap vaccine. After receiving the vaccine, A.R. noticed a knot under the skin where she received the shot and her skin was slightly swollen. About a week after receiving the vaccine, A.R. felt her feet tingled a bit while she was riding in her father’s truck. The tingling was not like the sensation of her legs falling asleep, which she had experienced before. Petitioner reported sitting in the back of her father’s truck with her legs crossed for 30 to 45 minutes prior to feeling the tingling in her legs. Petitioner also reported never experiencing this type of tingling before.
On August 4, 2006, A.R. went to the county fair with her mother, brother, and some of her brother’s friends. While at the fair, A.R. rode some rides, denied having any back or hip pain. Her mother said A.R. did not tell her about any pains. The next morning A.R.’s mother recalled A.R. complaining of a slight back ache. At some point on August 5, 2006, A.R. went to the bathroom. On the way to the bathroom, her feet felt a little heavy although she was still able to walk to the bathroom. In addition, she had some slight incontinence. A.R. sat down on the toilet and her legs got heavy and she could not get back up. She fell to the bathroom floor. She still had some feeling in her legs but then it started to go away and eventually she felt nothing. Her mother and brother helped her up, and they went to the hospital.
At the hospital, the initial impression was an acute onset of being unable to feel or move her legs. The notes from A.R’s neurologic exam recorded A.R. as having “abnormal proprioception of the right and left lower extremities.” The symptoms were consistent with a central lesion leading to a sensory defect affecting both sides of the body. An x-ray of the thoracic spine was taken, which showed no evidence of an acute fracture. The primary diagnosis was acute paraplegia. A.R. was transferred by ambulance to the Cincinnati Children’s Hospital. The impression recorded at the time A.R. presented at the emergency department of Cincinnati Children’s Hospital was acute onset lower extremity paralysis, afebrile, and without any previous illness. Magnetic Resonance Imaging (“MRI”) of A.R.’s cervical spine and a lumbar puncture were performed. Cerebral spinal fluid (“CSF”) results indicated a protein of 60 and red blood cell count of 8. It was noted that although the CSF study was considered normal, it was to be repeated because it was still very early after presentation. The initial MRI report noted “mild central cord high T2 signal from T10 to the conus.” The impression was that this might represent myelitis, viral infection, or less likely cord ischemia or Guillain-Barré. Additionally, disc desiccation was observed at L2/L3, L3/L4, L4/L5, and L5/S1 and there was no evidence of cord compression. A subsequent addendum note in the report observed an abnormal T2 signal within the cord appeared to extend to the T7 level, although axial T2-weighted images demonstrated motion artifact. A.R. was admitted to the hospital in stable condition with an ER diagnosis of paraplegia.
The hospital admission records reflect in the medical history that A.R. complained of bilateral hip pain the night of the fair. A.R. disputed this, testifying that the source of this statement was her father who had not been at home with her to have any knowledge of that.
On August 6, 2006, the attending physician noted the MRI findings with the T2 signal on at least the T10-T12 segments. P’s Ex. 11 a 146. He also noted bilateral flaccid paralysis of the lower extremities. His impression was that A.R. had transverse myelitis. On August 10, 2006, repeat CSF studies were performed. The repeat studies showed a white blood cell count of six [reference range: 0-4] and CSF protein at 58 mg/dL [reference range: 12-60 mg/dL]. Testing of the CSF obtained during the lumbar puncture on August 10, 2006, revealed oligoclonal bands, with the bands also present in A.R.’s serum sample, which had not been present previously. Additionally, the IgG levels had increased from the levels of August 6, 2006.
A.R.’s condition did not improve, and she subsequently began intravenous gamma globulin treatment on August 11, 2006, followed by a prednisone taper treatment started on August 12, 2006. A.R.’s condition, however, still did not change. On August 14, 2006, it was noted that A.R. had “slightly improved sensation” and she was transferred to the inpatient rehabilitation floor with a formal diagnosis of transverse myelitis. Over the next month, A.R. received occupational, recreational, and physical therapy. A.R.’s condition, however, did not improve further, and she was discharged on September 15, 2006.
After the discharge, A.R. was seen by pediatric neurologist, Lois Krousgrill, for a follow up on September 27, 2006. Dr. Krousgrill noted that A.R. had no recovery from motor or sensory function. Dr. Krousgrill’s impression was idiopathic TM.
A second MRI was performed on November 1, 2006 which showed a subtle hyperintense T2 signal “centrally within the cord at the T6-T7 level.” The report continued: “Hyperintense T2 signal to a greater degree is noted with the cord from the T8-T9 level to the L1 level.” The radiologist noted that the signal at the T8-T9 level “likely represents myelomalacia.” “Significant atrophy” from T8-T9 to the tip of the conus was also observed. In addition, the image was remarkable for mild disc desiccation from L2-3 to L5-S1 level, as well as subtle disc bulges at L2-L3, L3-L4, and L4-L5.
A.R. was readmitted to Cincinnati Children’s hospital for initial plasmapheresis treatments on October 30, 2006 and November 2, 2006. She received further plasmapheresis treatments three times per week over the next two weeks. Unfortunately, Amber did not improve upon the treatment and no marked recovery was observed. Despite treatment and therapy, A.R. continued to have a neurogenic bladder/bowel, period decubitis ulcers, multiple UTIs, incontinence, vaginal candidiasis, joint contractures, and constipation since the onset of the acute paralysis symptom. At the time of hearing, A.R. was in 11th grade, was still in a wheelchair and could not stand or walk. There were ten treatments originally scheduled, but the ninth and tenth were abandoned when A.R. had no recovery after the first eight treatments.
PROCEDURAL HISTORY
On July 1, 2009, Petitioners, Gary Roberts and Anita Roberts filed a petition for compensation under the National Vaccine Injury Act if 1986 on behalf of her daughter, A.R. Petitioners alleged that A.R. suffered from TM as a result of her receipt of a Tdap vaccine on July 06, 2006. Subsequently, the parties filed expert reports. On October 14, 2010, pursuant to order of the previously assigned Special Master, supplemental expert reports were filed.
On March 26 and 27, 2012, an entitlement hearing was held in Cincinnati, OH. One of the petitioners, Anita Roberts, and A.R. testified. Three expert witnesses testified on behalf of Petitioners. First, Dr. Lois Krousgrill, a neurologist, who had examined A.R. at and near the time of the onset of A.R.’s injuries, testified. She opined that A.R. had TM, not an embolism or infarction or fibrocartilaginous embolism (“FCE”) based on her clinical picture and the results of diagnostic tests. She further testified that she believed there was a relationship between the vaccine and A.R.’s TM. Second, Dr. Sidney Houff, a neurologist, testified. Dr. Houff opined that A.R. had suffered from an autoimmune reaction to the vaccine she received which caused her to have transverse myelitis. Third and finally, Dr. Mary Edwards-Brown, a neuroradiologist, testified that this was an unusual case of TM. She further concluded that the TM was due to the vaccine.
Two experts testified on behalf of Respondent. First, Dr. John Sladky, a neurologist, testified. He opined that he believed that A.R.’s clinical features were more indicative of a spinal cord infarction, an embolism or FCE than TM, an inflammatory condition. He further opined that even if A.R. had TM, he did not think there was enough evidence to conclude the vaccine caused it. Second, Dr. Louis Vezina, a neuroradiologist, testified. Dr. Vezina opined that based on the imaging studies, the findings were consistent with those of a lower spinal cord infarction; embolism and FCE are described in various places in the record and the terms are used interchangeably. In essence, they refer to an event that abruptly stops the blood flow to the spinal cord, i.e., a stroke in the spinal cord. Infarction is a blood clot in the spine; an embolism was described as a blockage that caused a cut off of blood flow down the spine. Transverse myelitis (TM) is an acute “inflammatory” disorder of the spinal cord resulting in bilateral motor, sensory, and sphincter deficits below the level of the lesion.
APPLICABLE LEGAL STANDARDS
The Vaccine Act provides two means of recovery: Table claims and off-Table claims. In an off-Table, or causation-in-fact, case, such as this one, a petitioner must prove actual causation by a preponderance of the evidence. To prove actual causation, a petitioner 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.” Causation is determined on a case-by-case basis. A petitioner satisfies this burden if he or she provides: (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 proximate temporal relationship between vaccination and injury. A petitioner must satisfy the three Althen prongs by preponderant evidence. This preponderant-evidence standard “simply requires the trier of fact to believe that the existence of a fact is more probable than its nonexistence” (noting the standard requires that a petitioner demonstrate the existence of the element is “more probable than not”). Evidence used to satisfy one of the Althen prongs can overlap and be used to satisfy another prong. There are no “hard and fast per se scientific or medical rules” for finding causation under the Vaccine Act. The Vaccine Act does provide that a claimant may satisfy the preponderant evidence standard by producing “medical records or a medical opinion.” A petitioner must provide a reputable medical or scientific explanation that pertains specifically to the petitioner’s case. However, the explanation need only be “legally probable, not medically or scientifically certain.” Along these lines, a special master may not require “epidemiologic studies . . . or general acceptance in the scientific or medical communities. . . .” At the same time, special masters are “entitled to require some indicia of reliability to support the assertion of the expert witness.” In determining reliability, in a Table case, unlike the present case, a claimant who shows that he or she received a vaccination listed in the Vaccine Injury Table, 42 U.S.C. § 300aa–14, and suffered an injury listed in the Table within a prescribed period is afforded a presumption of causation.
When a party relies upon expert testimony, that testimony must have a reliable scientific basis. Although a party need not produce medical literature to establish causation, where such evidence is submitted, the special master can consider it in reaching an informed judgment as to whether a particular vaccination likely caused a particular injury. Causation can be supported by a treating physician’s opinion that a vaccination was causally linked to the vaccinee’s injury if the special master finds the opinion to be both reliable and persuasive. At the same time, in cases in which a petitioner relies upon expert testimony to prove causation, the expert testimony must rest upon an objective and reliable scientific basis and must prove causation to a degree of legal certainty, but not to a medical or scientific certainty.” A petitioner must provide a reputable medical or scientific explanation that pertains specifically to the petitioner’s case, although the explanation need only be legally probable, not medically or scientifically certain.” Although a petitioner may rely solely on expert testimony, “an expert opinion is no better than the soundness of the reasons supporting it.” Therefore, a special master does not need to credit “expert opinion testimony that is connected to the existing data or methodology ‘only by the ipse dixit of the expert,’ or where ‘there is simply too great an analytical gap between the data and the opinion proffered.’ With regard to alternative causes, the respondent bears the burden of proving by preponderant evidence that an alternative cause, or factor unrelated, was the sole cause of the injury. But, neither 42 U.S.C. § 300aa-13 nor the decisions limit what evidence the special master may consider in deciding whether a prima facie case has been established. As a result, the government may also present and the special master may consider evidence of alternative causes on the issue of the adequacy of the petitioner’s evidence regarding the petitioner’s case-in-chief. In this regard, there are two particular points that the decisions make clear. First, a special master may not require the petitioner to shoulder the burden of eliminating all possible alternative causes in order to establish a prima facie case. Second, a special master may find that a factor other than a vaccine caused the injury in question only if that finding is supported by a preponderance of the evidence. The petitioner does not bear the burden of eliminating alternative independent potential causes, and the respondent has the burden of proving an alternative cause as the sole, unrelated factor that caused the injury by a preponderance of evidence. It is established that a special master is entitled to, and should, consider the record as a whole in determining causation. In considering the record, the Vaccine Act does not contemplate full blown tort litigation. A petitioner may use circumstantial evidence to prove the case, and “close calls” regarding causation must be resolved in favor of the petitioner. Indeed, “the purpose of the Vaccine Act’s preponderance standard is to allow the finding of causation in a field bereft of complete and direct proof of how vaccines affect the human body.”
DISCUSSION
Having considered the record as a whole and discussed below, the special master concludes that Petitioners have satisfied their burden of establishing by preponderant evidence that they are entitled to compensation.
Petitioners Have Presented a Plausible Medical Theory, Molecular Mimicry, Along With Supporting Literature That the Vaccine Can Cause A.R.’s Injuries, Thereby Satisfying Althen Prong
Petitioners have satisfied Althen’s Prong 1 by presenting a plausible medical theory. In support of Prong 1, Petitioners’ expert, Dr. Houff, described the process of molecular mimicry as a mechanism whereby the vaccine could cause an autoimmune response that could result in TM, what he had concluded A.R. experienced. This was also discussed in the article submitted, Transverse Myelitis and Vaccines: A Multi-analysis. Petitioners also submitted a number of other articles from various medical journals. The medical literature submitted provided further support that it has been recognized that Tdap could cause TM. Those articles are evidence supportive of Petitioners’ theory.
Respondent’s expert, Dr. Sladky, did not deny that vaccines might cause autoimmune responses such as TM. In commenting on Petitioners’ theory, without providing any particular reasoning, Dr. Sladky merely said, in a conclusory fashion, that he was not sure there was sufficient evidence on which to base Petitioners’ conclusion regarding a theory.
Respondent’s expert did admit that Petitioners had certainly submitted literature in support of their theory. Dr. Sladky expressed that the articles were not that persuasive because they showed the rarity of TM post-vaccine. Nonetheless, Dr. Sladky admitted that there were case reports that supported the theory of TM as a complication of vaccinations, including Tdap. For purposes of the Vaccine Program, Petitioners are not required to establish that there is epidemiological evidence to support their theory.
Rather, the Vaccine Program acknowledges the rarity of vaccine-caused injuries, and, nonetheless, recognizes that compensation for such injuries is appropriate. The purpose of the Vaccine Act’s preponderance standard is to allow the finding of causation in a field bereft of complete and direct proof of how vaccines affect the human body, explaining that “to require identification and proof of specific biological mechanisms would be inconsistent with the purpose and nature of the vaccine compensation program.”
Considering the evidence with these standards in mind, Petitioners have presented sufficient evidence to demonstrate a plausible medical theory by which the vaccine could have caused the condition with which Petitioners claim A.R. suffers, TM. Petitioners have satisfied Althen’s Prong 1.
Petitioners Have Presented Preponderant Evidence That There Is a Logical Sequence of Cause and Effect Between the Vaccine and A.R.’s Injuries By Showing That A.R.’s Injuries Were Caused by an Autoimmune Response and Not an Embolism and That the Vaccine Was a Substantial Factor in Causing the Injury
Petitioners claimed that A.R. suffered from transverse myelitis, an inflammatory demylinating condition in the central nervous system that was caused by an autoimmune response. Respondent, on the other hand, while not claiming to present an alternative cause or factor unrelated as a defense, nonetheless, argued that there was evidence that A.R.’s injury was more likely caused by an embolism obstructing blood from flowing down the spine. As such, according to Respondent, Petitioners had not satisfied their burden as to Prong 2.
The record demonstrates that there was evidence that A.R.’s clinical picture along with the diagnostic tests support that A.R.’s injuries were caused by an inflammation of the central nervous system that was caused by an autoimmune response. The record also demonstrates that there is preponderant evidence that the vaccine caused that injury.
Petitioners Have Shown by Preponderant Evidence That A.R. Experienced an Autoimmune Response Petitioners have presented sufficient evidence that A.R.’s symptoms were caused by an autoimmune response. First, Dr. Krousgrill, one of A.R.’s treating physicians, concluded that A.R. had TM, a condition caused by an autoimmune response. In reaching her conclusion, Dr. Krousgrill relied on her examination of A.R., her review of medical records and her medical knowledge. One factor that Dr. Krousgrill considered was the progression of A.R.’s symptoms. Dr. Krousgrill noted that A.R.’s symptoms began with A.R. experiencing tingling in her legs shortly after receipt of the vaccination. The tingling in her legs was different than that she had experienced in the past. And, A.R. had also explained that for several hours before she went to the bathroom on August 5, 2006, A.R. had experienced tingling. This indicated that the onset was not the abrupt onset that occurred over a matter of minutes, a conclusion upon which Respondent’s experts had relied in formulating their opinions. Instead, it was consistent with an autoimmune response, TM. Dr. Krousgrill also looked at the temporal relation and the MRI findings that indicated a focal inflammatory process in the central portion of the cord that involved the entire cord. In addition, although the CSF proteins were steadily high between the first and second lumbar punctures, the fact is that A.R. did not have many white blood counts. Finally, the appearance of oligoclonal bands in the central nervous system indicated an active infection or inflammation. The location of the lesion and broad extent of it shown on the MRI findings indicated that it was more likely this was a transverse process.
Dr. Houff testified that he concluded that A.R. suffered an autoimmune response. He based his conclusion on A.R.’s picture as a whole, i.e., the clinical picture, the exam, the radiology, her spinal fluid and all the studies. In particular, the signal on the MRI findings from that indicated a widespread effect, from T-2 through T-7, the evidence of oligoclonal banding after the second tap, the elevated complement, her high level of C-1 inhibitor, and the emergency room finding some sensation above the knee but no sensation below the knees and a mild sensation above the knees to T-12 and her poor rectal tone and incontinence all indicated that A.R. experienced a progressive, autoimmune response. Additionally, Dr. Houff explained that A.R. met four of the criteria for TM as established by the Transverse Myelitis Working Group. The four “inflammation” criteria that were present included abnormal godlinlim enhancement of the spinal cord, “a CSF pleocytosis,” and “elevated CSF IgG index.” Id. at 4. Those inflammatory markers within the spinal cord are critical factors to distinguish TM, a type of inflammatory myelopathy, from other noninflammatory myelopathy, like “ischemia, radiation, epidural lipomatosis or fibrocartilagenous embolism.”
Petitioners’ evidence shows that the presence of the majority of the criteria as well as the results of the independent evaluations support Petitioner’s request. There is ample evidence to support Petitioners.
Respondent’s Argument That the Cause of A.R.’s Injuries Is Likely an Embolism, Infarction or FCE Versus TM Is Unreliable and Unsupported by the Facts. Respondent’s claims that there is evidence that A.R.’s injuries are more likely caused by an embolism are unsupported by the objective clinical and diagnostic evidence, and her expert’s conclusions are unreliable. Whereas both of Petitioners’ expert neurologists, Dr. Krousgill and Dr. Houff, presented logically reliable testimony, Respondent’s expert’s, Dr. Sladky’s, testimony did not present the same level of reliability.
First, Dr. Sladky admitted that the theory that this is an infarction cannot necessarily be shown. For instance, he admitted there was no evidence as to how an infarct might have happened because there is no evidence of any trauma. In part his conclusion is simply based on the fact that he “doesn’t think that TM would behave in the fashion it did. And, he admitted that there was no evidence of severe back pain, something indicative of FCE. And, the objective evidence indicated that A.R.’s conditions are unlikely due to an embolism. As Dr. Brown explained, based on the view of the MRI, this was not an infarction because there is not a focal lesion that one would expect to see in an infarction. Rather, the lesion is quite widespread, consistent with an autoimmune response. And, the injury about which Respondent theorizes is also inconsistent with the anatomy of the blood supply to the spinal cord. For this theory to actually occur this disk material would have had to enter one of the lumbar arterials and somehow communicated with a vessel coming off the aorta, but that’s not the way the arterial anatomy works. One has a small artery at each lumbar vertebral level supplying a small amount of the blood supply to the cauda equine, and there’s not even a spinal cord at that level, but just nerve roots. One can somehow have an embolism in one artery and have it somehow get to another part of the spinal cord. That’s not the way the arterial anatomy is constructed.
Dr. Krousgrill testified that it was significant that the entire cord was affected and that indicated this was TM versus an embolism. The two primary avenues for circulation to the cord are the anterior spinal artery. It would be unusual to have an ischemia in all 3 vessels simultaneously all at the same level. Unlike A.R.’s situation, when a spinal artery is involved it is typically an anterior or lateral cord syndrome with mild or mixed sensory results. The clinical progression is not consistent with an infarction or embolism.
Additionally, Dr. Brown also reiterated that which Petitioners’ other experts, Dr. Krousgrill and Dr. Houff, had already stated in connection with their conclusions of the lumbar punctures or spinal taps performed on August 6 as compared to those performed on August 10. It was significant that in the first tap there was not evidence of oligoclonal banding, whereas in the section one there was, because an inflammatory response in the spinal cord does not look full blown immediately. It takes some time.
This objective, diagnostic evidence shows that there is a lack of support for Respondent’s claimed cause and support for Petitioners’ claim that A.R. experienced an autoimmune response. Second, Respondent’s expert, Dr. Sladky, acknowledged that there was a basis for a conclusion that A.R. had an autoimmune response. He admitted that some of the accepted criteria for TM were definitely present. He also admitted that there is respected literature that includes TM as a complication of vaccinations, including Tdap vaccinations. And he admitted that oligoclonal bands are indicative of an immune response. In fact, Dr. Sladky’s explanation for the oligoclonal bands being in the serum and spinal fluid is not logical in light of the facts. He testified that the presence of oligoclonal banding in serum and the spinal fluid even if it was infarction could be explained because IgG was produced originally in the serum as a result of immunization and was leaked into the spinal fluid through broken blood barrier resulting from infarction. But, Dr. Vezina disagreed that the banding would appear just in the course after a vaccine, saying it was clearly an abnormal response. Finally, a last factor in considering the reliability of his testimony that the special master must consider is the information that was revealed relative to Dr. Sladky’s status at the time of his work on this case and testimony. In May 2013, it was revealed that Dr. Sladky’s medical license had agreed not to practice medicine from August 2008 to March 2009 and then had agreed to a suspension of his license that lasted from June 2009 to March 2010. At that time his license was restored on a probationary basis, the probation finally terminating on July 2011. At the time he submitted his expert reports in this case, he was on probation. And, in discussing his qualifications at the hearing, no mention was made of these circumstances and such information was glossed over. In fact, in his testimony, Dr. Sladky said he was the Chief of the Pediatric Dept. at Emory University until 2009. But, given that he was not practicing medicine after August 2008, it is questionable whether that could be the case. Certainly, this leads the special master to pause when weighing the experts’ opinions. For all the foregoing reasons, the special master does not find Dr. Sladky’s testimony as reliable and persuasive as the testimony of Dr. Houff and Dr. Krousgill.
Dr. Vezina, Respondent’s neuroradiologist, admitted in his testimony that although he thought TM was less likely, based on the MRI findings, A.R.’s injuries could be either spinal cord infarction or TM. He also testified that with regard to an infarction there would have to be some sort of trauma. He deferred to the neurologist on this but admitted that he needed more information before he could state that such trauma had occurred. He also acknowledged that A.R. had four of the recognized diagnostic criteria for TM, i.e., (1) development of sensory, motor, or autonomic dysfunction attributable to the spinal cord; (2) bilateral signs and/or symptoms; (3) clearly defined sensory level (assumes we have this but doesn’t have the medical records); (4) inflammation within the spinal cord demonstrated by CSF, or elevated IgG indexed. Dr. Vezina also testified that he had no direct evidence to prove that that Amber suffered an infarct from FCE. Finally, Dr. Vezina admitted that this was a close call and “it’s not a clear vascular thing” because it’s a focal lesion and on the whole cord. In many ways, Dr. Vezina’s testimony was consistent with Dr. Brown’s testimony as well as Petitioners’ other experts. He acknowledged that there was clearly clinical and diagnostic evidence that A.R. suffered from TM. As he stated this is a close call. In the Vaccine Program, Petitioners are accorded the benefit of close calls.
There Is Preponderant Evidence Showing the Vaccine to Be a Substantial Factor in Causing the Autoimmune Response
There is also preponderant evidence that the Tdap vaccine was a substantial factor in causing A.R.’s TM. Dr. Krousgrill, the treating physician, concluded that having looked at a number of potential etiologies, the vaccine was significant. Admittedly, she could not make this a definitive diagnosis based upon a standard of reasonable degree of medical certainty, but she certainly believed there was a relationship between the vaccine and A.R.’s TM. (treating physicians’ opinions should be considered). Dr. Houff also explained that in this case he felt there was enough data to conclude within a reasonable degree of medical probability that the vaccine caused A.R.’s injuries. In so doing, he explained that it’s very hard to conclude that vaccines cause injuries. He acknowledged the importance of vaccines. At the same time, based on his assessment of the clinical picture in this case, including (1) the progression of her illness, (2) the temporal association, and (3) the lack of indication of another infection, the data was enough to conclude that the vaccine caused A.R. an aberrant immune response that attacked her nervous system, her spinal cord. And, Dr. Brown also discussed how she had concluded that the vaccine caused A.R.’s injuries. She relied on the classic appearance of TM on the imaging study, the time frame and A.R.’s history up to that point.
Respondent’s expert, Dr. Sladky, did not definitively rule out the vaccine as a cause. Instead, in his expert report he simply stated he did not think Dr. Houff provided a compelling argument to support this position. Weighing the testimony as presented, the special master finds that Petitioners’ experts were more persuasive. They explained logically and methodically their reasoning for concluding the vaccine was a substantial factor. At the same time, they did not overstate their positions, instead acknowledging that it would be difficult, if not impossible, to prove the vaccine was the cause as a matter of medical certainty. On the other hand, Respondent’s expert primarily presented a conclusory statement that he did not believe Petitioners had satisfied their burden. In addition to that, the special master must also look at the cumulative evidence on all three prongs in that evidence that satisfies Prongs 1 and 3 can overlap and be used to satisfy Prong 2. Here, there is sufficient evidence to satisfy Prong 1.
There is no question that Prong 3 has been satisfied. The treating physician, Dr. Krousgrill, having considered the clinical picture of A.R. at or near the time of the onset of symptoms, looked for other potential causes and considered them but found none. Tr. at 8-9. Similarly, with regard to temporal relationship, there is not much question that it is satisfied. That evidence also overlaps and supports the evidence in the record relating to Prong 2. In sum, Petitioners have presented sufficient proof to demonstrate satisfy their burden as to Prong 2. In particular, the MRI at the time of the onset of A.R.’s condition indicated a lesion with the entire spinal cord being involved, which is consistent with inflammation versus embolism. Additionally, the presence of oligoclonal banding, which was not present initially, and the fact that the CSF protein levels increased, are indicators that the cause was an immune mediated process, which would eliminate FCE as a potential cause. The fact that A.R. reported having heaviness in her legs for some time and even up to hours before her trip to the bathroom when she was unable to move and still had some feeling for a period afterwards indicates that this was not an abrupt onset as Respondent contends and upon which her expert bases his conclusions. And Petitioners have also presented preponderant evidence that the Tdap vaccine A.R. received was a substantial factor in causing that autoimmune response. Petitioners’ experts carefully examined the record for other possible explanations, [and] researched the medical literature.
In weighing the Petitioners’ experts versus Respondent’s experts, the special master concludes that Petitioners’ experts’ opinions are more reliable. In particular, A.R.’s treating physician, Dr. Krousgrill, testified for Petitioners that she had concluded A.R. had TM. Dr. Houff gave a reasoned explanation that A.R. had TM and that the vaccine caused it. On the other hand, Dr. Sladky, Respondent’s expert, admitted that embolisms were more rare than TM.
Respondent’s claims that the evidence of inflammation was unlikely does not seem consistent with the appearance of oligoclonal bands. Dr. Vezina said that the appearance of banding would not occur merely because someone had a vaccine. Rather, it was clearly an abnormal response.
Considering the supporting literature, the strong evidence of the temporal relation, the evidence of an autoimmune response and lack of any other possible etiology, there is sufficient evidence to show a logical sequence of cause and effect. Petitioners have satisfied Althen’s Prong 2.
There Is No Dispute as to Althen Prong 3
Finally, that there is a medically appropriate temporal relationship is not disputed. The parties agreed that the time frame between the receipt of the vaccine on July 6, 2006 and the onset of the injuries on August 5, 2006, is medically appropriate.
CONCLUSION
Upon review of the evidence and an assessment of the reliability of the opinions of the various expert witnesses, the special master concludes that Petitioners have established by preponderant evidence that they are entitled to compensation. The matter shall now proceed to consideration of damages.
IT IS SO ORDERED.
Doug Paluck and Rhonda Paluck, as parents and natural guardians on behalf of their minor son, Karl Paluck, Petitioners v. Secretary of Health and Human Services, Respondent
Summary: In this case, Judge Lettow rules on appeal after a hearing that a Special Master erred in earlier decisions and that the victim’s pre-existing underlying mitochondrial disease or dysfunction was aggravated by administration of MMR, varicella, and Prevnar vaccines.
Compensated Vaccine Injury: Aggravation of a Pre-existing Mitochondrial Defect Leading to Neurologic Injury
Vaccine case; petitioners’ challenge to a special master’s decision on remand; off-Table claim stemming from neurological damage allegedly caused or aggravated by administration of MMR, varicella, and Prevnar vaccines to a child with a genetic mitochondrial defect; claim asserting an aggravation of a pre-existing condition; Loving causation framework; entitlement; remand
Case No: 07-889V
Date Filed: October 29, 2013
Doug Paluck and Rhonda Paluck, as parents and natural guardians on behalf of their minor son, Karl Paluck, Petitioners v. Secretary of Health and Human Services, Respondent
OPINION AND ORDER
Charles F. Lettow, Judge
Petitioners, Rhonda and Doug Paluck, on behalf of their son Karl Paluck, seek review of a decision on remand by a special master dated May 10, 2013, denying them compensation under the National Childhood Vaccine Injury Act of 1986. Petitioners filed in accord with the Rules of the Court of Federal Claims. This opinion and order will remain sealed for fourteen days, within which time the parties may propose redactions.
Their claim on December 21, 2007, alleging that Karl’s receipt of the measles-mumps-rubella (“MMR”), varicella, and Prevnar vaccines on January 19, 2005 caused him either to develop an impairment or to exacerbate a preexisting condition, resulting in severe neurological damage. The Secretary of Health and Human Services acknowledges Karl’s injury but contends that its cause is unrelated to the vaccines. Petitioners’ claim is an off-Table injury claim, requiring proof of causation in fact by a preponderance of the evidence. The special master assigned to the case initially denied petitioners’ claim for compensation on December 14, 2011, finding that the Palucks failed to meet the three-part causation test established in Althen. In response to a motion by petitioners for review, this court rendered a decision on April 18, 2012, vacating the special master’s findings under all three Althen prongs and remanding the case to the special master, while “making no affirmative findings of its own.” In its decision ordering remand, the court directed the special master and the parties first to reassess whether petitioners’ claim was a significant-aggravation claim that had to be analyzed under the six-part test explicated in Loving v. Secretary of Dep’t of Health & Human Servs., which the special master had not applied. The Loving test combines the three causation factors from Althen with three additional factors that consider a claimant’s health before and after the vaccination. The court also directed the special master to reconsider the record as a whole before making new findings regarding causation in fact.
In the remanded proceedings before the special master, no new evidence was submitted by either party. Supplemental briefing regarding Karl’s developmental delays before and after the vaccine was completed by September 19, 2012. The statutory period for decision after the remand expired without a resolution, and on January 30, 2013, petitioners again moved for review by this court because of the delay. On May 3, 2013, the court denied the motion, but directed the special master to issue a decision within 120 days. The special master issued a decision a week thereafter, on May 10, 2013, again denying petitioners’ claim.
Petitioners renewed their motion for review of the special master’s decision by this court, contending that the special master’s findings of fact and conclusions of law are arbitrary and capricious, an abuse of discretion, and not in accord with the law. The Palucks ask this court to make its own findings of fact and issue a decision on entitlement in their favor.
The government argues that the special master’s decision was premised on adequate findings of fact and conclusions of law and should be left undisturbed. The Palucks’ motion for review, filed June 10, 2013, has been fully briefed, and a hearing was held on September 18, 2013.
FACTS
Karl Paluck currently suffers from an unspecified mitochondrial disorder that was most likely present at birth. At the time of the vaccinations, that disorder had not been detected. After the vaccinations, Karl became severely disabled, but the parties disagree as to the cause.
Karl was born on January 15, 2004 and showed no apparent signs of disability from birth through about the first eight months of life. A concern about developmental delay was first recorded on September 27, 2004 by Ms. Heather Ernst during developmental screening at Karl’s daycare provider, as part of the North Dakota Right Track Program. She observed delays in his gross and fine motor skills and referred him to an infant development service, K.I.D.S. K.I.D.S. evaluated Karl on October 21, 2004. The evaluation examined areas of fine motor skills, gross motor skills, speech and language skills, cognition, and adaptive behavior. Four test protocols were used: Bayley Scales of Infant Development (“Bayley Scales”), PDMS-2 Developmental Motor Scales—gross and fine motor scales (“PDMS-2”), Preschool Language Scale-3 (“PLS-3”), and Vineland Adaptive Behavior Scales (“Vineland”).
The Bayley Scales protocol is generally used to test a child’s cognitive skills (i.e., ability to remember, problem solve, use and understand language, and identify early number concepts). Karl scored “within normal limits” and was found to have an 11% delay.
Testing with PDMS-2’s gross motor scales evaluated Karl’s ability to use his large muscles, and testing with PDMS-2’s fine motor scales evaluated Karl’s ability to use his small muscles. Karl showed significant delay in his gross motor skills: 44% delay in stationary skills (i.e., head and trunk control, sitting), 67% delay in locomotion skills (i.e., rolling/crawling and object manipulation), and 67% delay in reflexes (i.e., ability to stay upright.
The special master wrongly attributed the referral to K.I.D.S. as having been prompted by a visit to Karl’s pediatrician, Dr. Stephen McDonough, as a result of an examination at eight months. In actuality, Karl was not examined at eight months of age by Dr. McDonough. Rather, he was examined at four months, six months, and one year by Dr. McDonough. Overall, he ranked in the first percentile for gross motor skills. He showed less delay in his fine motor skills: 11% delay in grasping and 22% delay in visual motor integration (i.e., hand-eye control), ranking in the eighth percentile. Karl could roll over, but he could not sit without support or crawl. He could not lift his legs off of the floor while lying on his back. He was, however, using a “wide variety” of fine motor skills. The evaluators could not determine with certainty the reason for his gross motor delays, but ultimately believed that low muscle tone was the underlying cause of Karl’s inability to sit and crawl. The evaluators believed that Karl presented with elevated tone in his legs because he was using them to compensate for the instability he felt in his arms and trunk. PLS-3 was employed to evaluate Karl’s ability to use and understand language. Karl showed moderate delays: 33% delay in auditory comprehension and 22% delay in expressive communication, ranking in the 32nd percentile. He was able to combine sounds and produce four different consonant sounds, but he was not imitating others’ sounds or responding to “no, no, Karl.” Lastly, the Vineland protocol tested Karl’s ability to care for his needs. It looked to his communication skills, daily living skills, socialization, and motor skills. Overall, Karl was evaluated as 14% delayed. He was 22% behind in communication skills, 11% behind in daily living skills, 0% behind in socialization skills, and 33% behind in motor skills, ranking in the thirtieth percentile overall. Ultimately, K.I.D.S. determined that Karl presented a “mixed picture” and recommended that he “receive infant development services from the K.I.D.S. program targeting his speech/language, gross motor, and the delays in fine motor related to low muscle tone.”
Both parties’ experts agreed that the K.I.D.S. evaluation was “good and extensive,” but they disagreed as to the significance of the findings relative to Karl’s neurological health. At the time Karl underwent his first evaluation for his developmental delays, he was experiencing recurrent bouts of otitis media and rashes that were later identified as erythema multiforme. The erythema multiforme was first noticed on October 14. Tone is a measurement of the muscles’ ability to maintain the body in proper posture in different positions, such as sitting, standing, or being held. Normal tone means the muscles are maintaining the body in proper posture. Low tone means the muscles do not sufficiently function to maintain the body in proper posture. Otitis media is “inflammation of the middle ear,” commonly known as an ear infection. Biopsy results from December 28, 2004 confirmed that the rash was consistent with erythema multiforme. Erythema multiforme, which has rash-like symptoms, is “either of two conditions characterized by sudden eruption of erythematous papules, some of which evolve into target 2004, a week before the K.I.D.S. testing. Thereafter, the record is replete with visits and telephone calls to the Dickinson Clinic between October 2004 and January 2005 regarding Karl’s otitis media and erythema multiforme, documenting no fewer than eleven visits and telephone calls during those few months. Dr. Robert Snodgrass, respondent’s expert, sees significance in Karl’s erythema multiforme, not because children with rashes are rare, but because erythema multiforme is relatively uncommon. It is a hypersensitivity reaction, and in Karl’s case, it persisted for months.
Moreover, both Dr. Snodgrass and Dr. Richard Frye, petitioners’ expert, testified that it is evidence of immune activation. It suggests that Karl was under some immune stress in the months leading up to the vaccinations on January 19, 2005. Notably, the erythema multiforme improved after a physician, Dr. Amy Oksa, prescribed Orapred, an immune suppressant drug, but recurred when Karl stopped taking it. Most of Karl’s medical record in November and December 2004 centers on treating Karl’s otitis media and erythema multiforme. On December 27, 2004, Karl saw Dr. McDonough for an ear check. The record of the visit states that Karl’s recent medical history, as reported by his parents, was “positive for a fever.” At that time, Dr. McDonough also lesions consisting of a central papule surrounded by a discolored ring or rings. Both represent reactions of the skin and mucous membranes to factors such as viral skin infections . . . agents (including drugs) that are ingested or irritate the skin; [or] malignancy.”
For its arguments, the government relies upon the testimony and reports submitted to the special master by its expert, Dr. Robert Snodgrass. Dr. Snodgrass is a professor of pediatrics and neurology at the University of California, Los Angeles School of Medicine. He received a bachelor’s degree in social relations from Harvard College and an M.D., magna cum laude, from Harvard Medical School. Dr. Snodgrass is board-certified in neurology, with special competence in child neurology. He has written dozens of articles and has held professorships at medical institutions associated with Harvard University, Cambridge University, the University of Southern California, Stanford University, the University of Mississippi, and the University of California, Los Angeles.
To support their contentions, the Palucks rely upon the testimony and reports submitted to the special master by their expert, Dr. Richard Frye. Dr. Frye is an assistant professor of pediatrics and neurology at the University of Texas Houston Health Science Center. He received a bachelor’s degree in psychobiology from C.W. Post of Long Island University, a master’s degree in biomedical science/biostatistics from Drexel University, and both a Ph.D. in physiology and biophysics and an M.D. from Georgetown University. Dr. Frye is board-certified in general pediatrics and in neurology with special competence in child neurology. He has published numerous articles and has held residencies or professorships affiliated with Harvard University, Boston University, the University of Miami, the University of Florida, and the University of Texas.
On January 6, 2005, the daycare noted that the K.I.D.S. Program worked with Karl for thirty minutes, that Karl cried during “tummy time,” and that he seemed very tired that day. The next day, the daycare recorded that he was “crabby” in the afternoon. There are no other daycare notes describing Karl before the vaccinations.
On January 19, 2005, Karl saw Dr. McDonough for his one year well-child checkup. Dr. McDonough administered DENVER II, a common developmental screening test. The evaluation is recorded on a standardized form on which the doctor notes whether a child “passes” or “fails” certain developmental skills appropriate for his or her chronological age. On January 19, Karl passed “imitate activities,” “play ball with examiner,” “indicate wants,” “bang 2 cubes held by hands,” “thumb finger grasp,” “jabber,” say “dada/mama specific,” say “single syllables,” “pull to stand,” and “stand holding on.” Karl failed “get to sitting,” “stand 2 [seconds],” “stand alone,” say “one word,” “wave bye-bye,” and “play pat a cake.”
Dr. Frye testified that Dr. McDonough incorrectly scored the DENVER II screening for some skills. Petitioners provided a standard DENVER II chart, which shows that there is a shaded box behind each skill listed on the form. Dr. Frye explained that only when that shaded box ends before reaching the child’s chronological age should the child be considered to have “failed” the skill. The shaded box indicates what percentage of children have developed a skill at a certain chronological age. For example, the skill of saying “one word” is accompanied by a shaded box that extends from about ten months to fifteen months. Only when a child turns 15 months and still cannot speak one word, should a child be noted as having “failed” the skill. Thus, according to Dr. Frye’s testimony, Karl’s only true failed skills should have been “get to sitting,” “stand 2 [seconds],” and “play pat-a-cake.” Dr. Frye also noted that some of the skills Karl passed were fairly advanced for his age, such as “imitate activities,” which less than 75% of children can do at that age. Dr. Frye testified that Karl showed less of a delay at twelve months than he did at nine months. He estimated that Karl was about four or five months delayed in October based on the results of the K.I.D.S. evaluation, and about three months delayed in January based on the DENVER II evaluation.
At this same appointment, Dr. McDonough made additional findings regarding Karl. On a chart labeled “physical examination,” Dr. McDonough marked the category “neuromuscular” as abnormal, noting “muscle tone ↑ . . . upper . . . extremities . . . beats clonus [right ankle].” Dr. McDonough checked the category “hips” as normal and wrote next to it some word or words followed by “ROM,” meaning range of motion. Dr. McDonough also wrote on the same chart that Karl “doesn’t hold cup well,” circled the word “babbles,” and next to “1-3 words,” he wrote “no words.” He also circled the word “crawl” and wrote next to it “4 point” (i.e., hands and knees). Finally, at this same appointment, Karl was given the MMR, varicella, and Prevnar vaccines.
Within two days of receiving the vaccinations, Karl showed signs of irritability, fever, and fatigue. His daycare recorded that he had a temperature of 101.5 degrees on January 21, 2005, and recorded a temperature of 101.3 degrees seven days later on January 28, 2005. Dr. Frye and Dr. Snodgrass disagree over whether the vaccinations caused Karl’s subsequent and persistent fever. The daycare records in the two weeks following the vaccination reveal that Karl was often fussy, did not eat or nap well, and was tired. The only positive note occurred on February 3, 2005, when the daycare recorded that “Shiela from the K.I.D.S. [text missing].” There is some confusion over precisely what Dr. McDonough wrote on the “neuromuscular” line of the chart. Dr. Snodgrass testified as follows on cross-examination:
Q. If you look at that handwritten note of Dr. McDonough, he’s noting muscle tone increase positive upper. He doesn’t say upper and lower, does he?
A. I think he does. It’s kind of hard to read. Now I wouldn’t criticize anybody who has trouble reading it, but if you look along that line it says muscle tone and there’s an arrow pointing up and a plus. Then it says upper and then you go down to the next line and you see L-O-W-E-R. To the left of the L-O-W-E-R is something that I think is an ampersand sign, meaning upper and lower, and then I think you can clearly read extremities after you see lower.
Frye maintained in testimony that the writing preceding “ROM” is the word “full,” meaning Karl’s hips showed a full range of motion. In contrast, Dr. Snodgrass stated that the writing preceding “ROM” indicated decreased range of motion. The word could also possibly be “good.” Based on other medical records, Dr. McDonough’s notation likely does not mean that Karl could successfully complete full cross-crawl movements.
On February 8, 2005, the daycare noted that Karl was trying to crawl by “pulling his body.” On February 7, 2005, the Palucks first took Karl to a chiropractor to address his problems sitting, crawling, and walking. On February 9, 2005, the chiropractor recorded some abnormalities with Karl’s hips on cross crawl. Karl’s chiropractic record contains an entry for February 11, 2005 in which is written the word “spastic.” There is significant disagreement between the parties over whether the chiropractic records suggest decline or improvement through February and March 2005. The subjective assessments noted in later entries are variable:
• February 14—“better mood,”
• February 16—“less rigid—more comfortable on all 4s”
• February 18—“less rigid—‘happier’”
• February 20—“stiff Mid + T—‘happy—moving around—til last nite & today’”
• February 21—“Mid T tite & SOP—irritable”
• February 24—“Spastic Mid T’s & ↓ Ts”
• March 1—“No BM yesterday”
• March 4—“BMs better—less fussy”
• March 8—“less hypertonicity—[illegible] ↑ on all fours/BMs more regular”
• March 10—“Not sleeping last night/2AM-5AM/irritable/good day yesterday”
• March 17—“Upper [illegible] skin blotches—back pain.” On this day the chiropractor also noted, “palpation of spine [painful] baby cries loud when touched.”
• March 27—“rigid lower extreme. Palp. [illegible]—‘doing well ‘til yesterday’ ‘took a few crawl steps’”
• March 30 (record of a phone conversation)—“Phone convers. w/ Brenda [Erie] SCSS Re. poss. abuse alleg. I responded—No—discussed poss. Adverse Rx/vaccine, CP [cerebral palsy], Cerebellar Tumor.”
Although these entries are variable, they do not show any significant improvement. Many of the comments in the records are written in quotes or describe Karl’s behavior outside his appointment, suggesting that they are descriptions of his mood and behavior at home, given to the chiropractor by the Karl’s parents. For example, February 18: “happier,” February 20: “happy,” March 27: “doing well ‘til yesterday,” “took a few crawl steps,” April 2: “good mood this week” “seeing improvement.” A telephone conversation record with Dr. McDonough’s office dated March 22, 2005 documents the Palucks’ report that Karl had “some brief crawling” and is “babbling more,” but is “not sitting on his own,” “leans to one side.”
On January 19, 2005, Dr. McDonough had referred Karl to physical and occupational therapy. Dr. Frye described spasticity as “being the extreme for increased tone.”
Dr. Snodgrass found that the notations of Karl’s “brief crawling” and “babbling more” were signs of progress since Karl’s December 27, 2004, visit with Dr. McDonough. This conclusion by the government’s expert was contrary to that reached contemporaneously by Karl’s treating physician, Dr. McDonough, who noted on the same telephone record that he would make a referral to Dr. Siriwan Kriengkrairut, a pediatric neurologist. On March 24, 2005, Dr. McDonough wrote the consultation request, citing Karl’s “gross motor delay, global developmental delay, and hypertonicity” as the reasons. Global developmental delay is broader than isolated gross motor delay. “Global developmental delay is when you’re affected in several areas.” (Frye). Dr. McDonough wrote that he “would appreciate [Dr. Kreingkrairut’s] evaluation and medical investigations into the etiology of [Karl’s] developmental delay and hypertonicity.”
In mid to late March, Karl developed a cold. On March 28, 2005, he saw Dr. Gary Peterson at the Dickinson Clinic for “four days of [a] wheezy cough” and a “runny nose for two weeks.” The doctor noted early bilateral otitis media and bronchiolitis. He provided a SVN (nebulizer) treatment in the office and also prescribed one for use at home. He noted that Mrs. Paluck preferred “no antibiotics be written as yet since he has had the trouble with erythema multiforme in the past.”
By mid-April, Karl’s health was significantly worse than it was in January 2005. He continued to suffer from recurrences of otitis media. Karl saw Dr. McDonough on April 13, 2005 for a Pre-Anesthesia Evaluation for a magnetic resonance imaging (“MRI”) test that was to be performed on Karl. He noted “global developmental delay,” including problems with “speech and fine and gross motor development.” Dr. McDonough also wrote that Karl’s “hips are tight with decreased hip flexion to about 70 degrees bilaterally with increased [a word appears to be absent, probably “tone”] in the lower extremities. This is a change of hip movement over the last couple of months.” Karl had not had any evidence of erythema within the past three weeks.
The neurologist, Dr. Kriengkrairut, examined Karl on April 19, 2005. She documented a brief history of the onset of Karl’s problems. “According to the father since [the onset of erythema multiforme in October 2004] the child has regressed. . . . In December of 2004 his condition got worse. His hands and feet were swelled up. He was given medications. This has markedly improved from a month ago when he seemed back to his normal. Father reported that since he has been improving with the skin lesions, he also made progress in terms of development, but overall he is still behind.” Following the physical examination, she reported “truncal hypotonia with marked spasticity of the extremities. The baby has tendency to do cortical thumb bilaterally, worse on the right compared to the left. . . . Baby does not babble. . . . Delayed development as well as hypotonia of the extremities may be secondary to central nervous system pathology.” Overall, she labeled Karl as having “global delayed development.”
Dr. Frye testified that this report by Dr. Kriengrairut suggests a substantial neurological regression in Karl since January 2005. Dr. Snodgrass disagreed that the problems observed by Dr. Kriengkrairut differed substantially from the problems observed by Dr. McDonough in January.
A chiropractic record entry from April 25, 2005, reports decreased range of motion. Dr. McDonough saw Karl the next day, on April 26, 2005, and wrote that Karl “rolls over but does not sit without support. He does not crawl and does not say any words. . . . Hips are tight on range of motion.” Dr. McDonough again described Karl as suffering from global developmental delay.
Dr. Kriengkrairut had recommended an MRI of Karl’s brain, which was performed on April 27, 2005. The results were initially interpreted as normal, but a reexamination of the results from April 2005 following a more apparently abnormal MRI in July 2005 discerned evidence of a then-existing brain abnormality—thinning of the corporal callosum. The parties’ experts disagreed as to when the thinning most likely began. Dr. Frye opined that it occurred “recent to the MRI, after January 2005” (Frye), whereas Dr. Snodgrass testified that he has “seen similar scans in people who had prenatal infections.”
Karl declined further in the ensuing months. While the special master found isolated instances of slight improvement, these events contrasted with a general trend of deterioration from April 2005 to July 2005. On May 4, 2005, Karl was evaluated by a speech therapist, Ms. Trisha Getz. At that time, Karl had fewer language skills than he had in October 2004, and his total language score was in the first percentile (Frye). In October 2004, he could produce at least four consonant sounds, but by May 2005, he could no longer produce any consonant sounds, although he could still produce a couple vowel sounds. By May, Karl’s only gesture was reaching for objects. Ms. Getz noted, “Karl’s parents report he had an MRI last week, which has ‘wiped him out’ and they report a decrease in many skills since undergoing the anesthesia. . . . Mom reports he has had a decrease in speech production in the last few months.” Her reports through September 8, 2005 indicate little to no improvement. (“very little progress” and “no goals met”). Karl continued to be unable to approximate sounds or produce any consonants.
Karl suffered a seizure on July 12, 2005, followed by additional seizures over the next two days. Dr. McDonough examined Karl on July 16, 2005 and assessed him as having “global developmental delay with seizure disorder, possible deteriorating neurologic status in that he is unable to do some things that he was able to do previously.” On July 19, 2005, Karl was admitted to Children’s Hospital in St. Paul, Minnesota by Dr. Michael Frost. While there, MRI results showed furthering thinning of the corporal callosum, strongly suggesting that Karl was suffering from neurodegeneration. On October 27, 2005, Karl had another MRI, which showed no significant change in Karl’s brain since the July 2005 MRI. “The progression of signal changes between [4/27/05 and 7/22/05] may have represented evolution of one toxic/metabolic or hypotoxic ischemic event.”
Since July 2005, Karl has lived in a state of severe neurological disability. Earlier in 2013, he was in dire health. “There is a ‘do not resuscitate order now in place’ for him, and ‘he is bedridden or wheelchair-ridden, has a tracheotomy tube, and is on a ventilator to breathe for him.’”
PRIOR DECISIONS
Paluck I
The Palucks filed their petition for compensation on December 21, 2007, alleging that Karl “sustained a permanent injury to his brain and central nervous system as a result of receipt of his childhood vaccines . . . [and] that the exposure to childhood vaccines caused and/or aggravated a mitochondrial disorder in Karl.” Three hearings in the case were held over the course of 2010. At the hearings, the parties disagreed as to whether Karl’s vaccines caused or aggravated his neurodegenerative course. Dr. Frye testified that the vaccines either caused Karl’s injury, or aggravated his condition, according to the following theory:
[V]accines, by intention, activate the immune system; this in turn leads to the development of potentially toxic elements within the body, namely reactive oxygen species (ROS) and reactive nitrogen species (RNS); ROS and RNS are usually balanced under normal conditions by the (antioxidant) systems of the body; however, if certain parts of the body, namely the mitochondria, are not working properly, more toxic elements will be produced and will be unchecked by antioxidants, resulting in oxidative stress, leading to a cascade of intracellular events leading to apoptosis or cellular death. Brain cells are more vulnerable to this process and with death of brain cells, neurodegeneration and developmental regression are likely.
Applying the theory to Karl’s case, Dr. Frye testified that Karl had an underlying mitochondrial disorder that prevented him from coping with the oxidative stress of the vaccines. This led to “decompensation” within his cells and eventually cellular death, resulting in neurodegeneration.
Dr. Snodgrass disagreed, testifying that “there are problems with [Dr. Frye’s] theory in general and there are problems with its specific application to the case of Karl Paluck.” He criticized Dr. Frye’s theory generally on the ground of lack of published peer-reviewed literature demonstrating that vaccines cause oxidative stress in humans, although he acknowledged supporting animal-model data. In his view also, Karl’s medical history did not support the idea that vaccines caused or aggravated his condition. Dr. Snodgrass stated that Karl manifested developmental delays before his vaccinations on January 19, 2005. Dr. Snodgrass additionally stated that between January and April 2005, Karl’s condition fluctuated, but did not worsen, as would be expected had the vaccines caused Karl’s injury.
The special master issued a decision denying compensation on December 14, 2011, concluding that petitioners had failed to prove by a preponderance of the evidence that the vaccines administered to Karl on January 19, 2005 caused his injury or significantly aggravated a preexisting condition. In so holding, the special master applied the three-prong causation framework set out in Althen, which requires a petitioner to show by preponderant evidence that the vaccination brought about [the] injury by providing: (1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of a proximate temporal relationship between vaccination and injury.
The special master found that the Palucks had failed to carry their burden as to any of the three prongs.
Regarding Althen’s first prong, the special master was not convinced by the evidence presented that vaccines produce oxidative stress generally or oxidative damage particularly in persons with mitochondrial disorders. Regarding Althen’s second prong, the special master found that Karl’s history did not demonstrate a logical sequence of cause and effect between the vaccinations and Karl’s injury. According to the special master, Dr. Frye’s theory required that Karl’s medical history evidence a continuous downward trajectory, which “did not match what actually happened to Karl.” Instead, the special master credited Dr. Snodgrass’s testimony that Karl’s development fluctuated between September 2004 and April 2005, with Karl actually improving between the time of his January 2005 vaccinations and late March 2005. Regarding Althen’s third prong, the special master concluded that oxidative damage would have occurred in Karl within fourteen days, and that Karl’s immediate post-vaccination symptoms—fever, irritability, and, according to his chiropractor, spasticity and hypertonicity—did not evidence such damage. Finding that Karl did not manifest further neurological regression until April 2005, the special master determined that Karl’s injury fell outside the medically acceptable timeframe for vaccine injury.
Paluck II
Petitioners filed a motion for review of the special master’s decision in Paluck I on January 13, 2012, arguing that the special master’s conclusions on all three Althen prongs were “arbitrary and capricious, an abuse of discretion, or not otherwise in accord with the law.” The government urged affirmance.
Oral argument was held on March 21, 2012. On April 18, 2012, this court vacated the special master’s findings of fact and conclusions of law, and remanded the case to the special master for further proceedings. The court expressly did not make any affirmative findings of fact of its own. The court reviewed the special master’s determinations of law de novo, and his findings of fact for clear error.
First, the court directed the special master to reconsider whether petitioners’ claim should be analyzed as a significant aggravation claim or a new injury claim. The special master had analyzed it using the standards applicable to a new injury claim without discussion of whether those standards were most appropriate.
Second, the court addressed the special master’s findings under each of the three Althen prongs. Regarding Althen’s first prong, a medical theory causally connecting the vaccination and the injury, the court held that the special master required a higher level of proof, i.e., a higher level of scientific certainty, than is demanded by the Vaccine Act. The Vaccine Act does not require that “evidence be medically or scientifically certain.” To support his theory, Dr. Frye relied on a peer-reviewed study published in a well-respected medical journal, various studies showing oxidative stress in animals as a result of vaccines, and a case study. While the special master correctly determined that none of the evidence was definitive proof of the medical validity of Dr. Frye’s theory, it was arbitrary and capricious for him to discard it as completely as he did. The court also noted that Dr. Snodgrass did not dispute the reputability of the theory but only noted the dearth of human studies establishing it as fact. The court vacated the special master’s finding that petitioners failed to show by a preponderance of the evidence that vaccines can cause oxidative stress and that children with mitochondrial disorders are particularly vulnerable to oxidative stress and directed the special master to reconsider the evidence in the record under the correct legal standard. The court also vacated the special master’s finding under Althen’s second prong that petitioners failed to demonstrate, by a preponderance of the evidence, a logical sequence of cause and effect showing that the vaccinations caused Karl’s injury. The special master had given considerable weight to unexplained notations throughout the record that Karl was progressing in his ability to prepare to crawl through the months of February, March, and April, which was something he could not do at the critical appointment on January 19, 2005 with Dr. McDonough, when he was vaccinated. Karl was never formally evaluated as being able to crawl. At most, there was evidence that he was making some preparatory crawl motions at times. Similarly, the special master concluded that notations of babbling suggested development throughout the same months, despite evidence that Karl actually lost language abilities. Moreover, the court opined that the special master failed fully to consider the chiropractor’s records from February and March and Dr. McDonough’s referral to a pediatric neurologist in March. The court held that the special master’s finding that Karl’s efforts to crawl and babbling signaled improvement, therefore negating a logical sequence of cause and effect between Karl’s vaccines and injury, should be vacated due to a failure to consider all of the salient evidence.
Lastly, the court vacated the special master’s finding regarding Althen’s third prong, a proximate temporal relationship between the vaccination and injury. According to the special master, the medical literature suggested that the medically acceptable interval between vaccination and the onset of symptoms of neurological injury would be two weeks. The court rejected this conclusion. Given the medical literature relied upon by Dr. Frye, including a case study demonstrating neurodegeneration occurring post-vaccination over a period of several months and a published study showing neurodegeneration occurring following infection in patients with mitochondrial disorders over a period extending to nineteen days, it was arbitrary and capricious for the special master to set a “hard and fast limit of two weeks.” The court also held that the special master’s finding that Karl did not manifest any symptoms of neurologic injury within a medically acceptable interval after the vaccination was arbitrary and capricious because it failed to consider the record as a whole.
Paluck IV
Before deciding the case on remand, the special master requested supplemental briefing and any additional evidence from the parties regarding the classification of Karl’s injury as a new injury or a significant aggravation claim. If the claim were found to be a significant aggravation claim, then the Loving factors would apply, which combine the three Althen causation factors with three additional factors that inquire into the claimant’s condition before and after the vaccination. Both parties submitted supplemental briefs, but neither submitted additional evidence. The special master determined that Karl’s claim is one of significant aggravation and must be analyzed under the six Loving factors because Karl’s developmental delays in the autumn of 2005 strongly suggested pre-existing problems with his central nervous system.
The first prong of Loving requires addressing Karl’s condition prior to vaccination. The parties agreed that Karl’s mitochondrial defect was likely affecting his health before the vaccinations. The parties disagreed over the extent of delay in Karl’s language skills and the cause of Karl’s gross motor delays. The special master found that the “preponderant weight of the evidence favors finding that Karl’s language development was delayed prior to his vaccination.” He also found that Karl’s gross motor delays and language delays, in existence before the vaccinations, were caused by abnormalities in his central nervous system. He further determined that Karl’s gross motor skill delays had worsened between December 27, 2004 and January 19, 2005.
The second prong concerns Karl’s condition following the vaccination. The special master extensively summarized Karl’s records in the months following the vaccination. He looked to Karl’s daycare records, Karl’s chiropractic record, Dr. McDonough’s referral to the pediatric neurologist, Dr. Kriengkrairut’s neurological exam, Karl’s MRI in April 2005, Karl’s speech therapy records, the seizures and hospitalization in July 2005, and Karl’s other medical visits and mitochondrial testing.
The third prong of Loving asks whether Karl’s current condition constitutes a significant aggravation of his condition prior to the vaccine. Without elaboration, the special master found that “by virtually any metric, Karl was worse” after receiving the vaccines.
The fourth prong of Loving, which correlates to the first prong of Althen, addresses whether there is a medical theory causally connecting the worsened condition to the vaccine. In response to this court’s opinion in Paluck II, “both parties essentially agreed that the Palucks’ evidence met the standard for medical plausibility as defined by the court.” The special master accepted this apparent concession by the government without discussion, noting only that this concession does not lessen the petitioners’ burden of proof under Loving prongs five and six.
The fifth prong of Loving requires petitioners to establish, by a preponderance of the evidence, a logical sequence of cause and effect showing that the vaccination significantly aggravated Karl’s condition. The special master determined that Dr. Frye’s theory “was predicated on a downhill trajectory.” Thus, the special master looked for evidence that Karl’s health declined without any improvement from one day to the next following the vaccinations on January 19, 2005. In accordance with this court’s order on remand, the special master considered in detail “Karl’s chiropractic records, Karl’s treating doctors’ statements regarding the cause of Karl’s decline, and Dr. McDonough’s referral to a pediatric neurologist.” In considering the chiropractor’s notations from February and March, the special master found that it was “difficult to glean much significance from them.” Ultimately, he found that the evidence of decline was too variable to suggest a linear decline, as he considered Dr. Frye’s theory to require.
The final prong of Loving requires the special master to determine a medically acceptable temporal relationship between the vaccine and the significant aggravation and then determine whether the claimant’s injuries occurred within that time frame. Upon reconsideration of an article by Dr. Joseph L. Edmonds, the special master lengthened the medically acceptable temporal interval from two weeks, which he had specified in Paluck I, to three weeks. Accordingly, the special master looked for evidence of neurodegeneration, defined as the loss of a skill, within three weeks following January 19, 2005, which extended to February 10, 2005. Karl’s daycare records and chiropractic records were the only records contemporaneously created during that period. The special master was persuaded by the government’s expert that Karl’s fevers and irritability in the ten days following the vaccinations did not constitute encephalopathy, as Dr. Frye had opined. Additionally, the special master was unconvinced by Dr. Frye’s testimony that the chiropractor’s notation describing Karl as “spastic” on February 11, 2005 was evidence of “a very severe neurological event suggesting a very rapid change in his central nervous system.”
The special master posited three reasons for not relying on the chiropractor’s notation: in his view, (1) spasticity is closely related to hypertonia, which Dr. McDonough noticed on January 19, 2005, (2) chiropractors are not sufficiently well trained to recognize clinical spasticity in infants, and (3) the variability of the chiropractor’s records rendered them unreliable. The special master also placed emphasis on the fact that Karl did not appear to stay home from daycare in February, nor did he see doctors with the same frequency he had in December, although he saw the chiropractor frequently.
Overall, the special master concluded that Karl had not been as sick in February as he was in December. The special master concluded that the petitioners could not show by a preponderance of the evidence that Karl manifested evidence of neurological degeneration within the three-week “bound of the appropriate temporal limit.”
Based upon a failure of proof respecting the fifth and sixth prongs of Loving, the special master denied entitlement to compensation.
STANDARDS FOR REVIEW
Under the Vaccine Act, the court may “set aside any findings of fact or conclusions of law of the special master found to be arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law and issue its own findings of fact and conclusions of law.” The special master’s determinations of law are reviewed de novo. The special master’s findings of fact are reviewed for clear error. “We uphold the special master’s findings of fact unless they are arbitrary or capricious” (citing Capizzano v. Secretary of Health & Human Servs.).
Under Vaccine Rule 8(b) (1), the special master must “consider all relevant and reliable evidence.” Vaccine Rule 8(b) (1); see also 42 U.S.C. § 300aa-13(b) (1) “The special master or court shall consider the entire record and the cause of the injury, disability, illness, or condition until the date of the judgment of the special master or court.” A special master’s findings regarding the probative value of the evidence and the credibility of witnesses will not be disturbed so long as they are “supported by substantial evidence.” Doe v. Secretary of Health & Human Servs. (citing Whitecotton).
As this court stated previously, a deferential standard of review “is not a rubber stamp.” The special master must “consider the relevant evidence of record, draw plausible inferences and articulate a rational basis for the decision.” And, while the special master need not address every snippet of evidence adduced in the case, he cannot dismiss so much contrary evidence that it appears that he “simply failed to consider genuinely the evidentiary record before him” (Campbell v. Secretary of Health & Human Servs.).
ANALYSIS
There is no dispute that Karl’s claim involves an “off-Table” injury, i.e., an injury or aggravated condition that is not listed on the Vaccine Injury Table set out at 42 U.S.C. § 300aa-14(a). Accordingly, petitioners must prove causation in fact. The special master concluded that petitioners’ claim is most appropriately analyzed as a significant-aggravation claim governed by the Loving factors. Petitioners continue to contest classification of the claim as a significant-aggravation claim rather than a new-injury claim, notwithstanding the circumstance that the special master found that the factors related specifically to significant aggravation had been satisfied. Petitioners also contest the special master’s conclusions primarily respecting Loving prongs five and six, i.e., logical sequence of cause and effect and medically acceptable temporal interval, respectively. The government urges affirmance of the special master’s findings.
New Injury or Significant Aggravation
The Vaccine Act defines “significant aggravation” as “any change for the worse in a preexisting condition which results in markedly greater disability, pain, or illness accompanied by substantial deterioration of health.” After giving the parties an opportunity to file supplemental briefs and giving them an opportunity to present more evidence, the special master concluded that the preponderance of the evidence weighed in favor of finding that petitioners’ claim should be analyzed as a significant-aggravation claim. Petitioners maintain that Karl’s neurodegeneration constitutes a new injury, distinct from any delays he might have been experiencing in the months before the vaccination. The government avers that Karl’s neurodegeneration can only be properly analyzed as a significant-aggravation claim because he already showed signs of developmental delay before the vaccination. Whether petitioners’ claim should be classified as a new injury or significant-aggravation claim rests on the “the precise definition of Karl’s injury, which is a precondition to identifying the timing of its symptoms” and “whether indicia of Karl’s neurodegeneration followed the typical course of a person that suffers from his type of mitochondrial defect.” In its remand opinion, this court sought elucidation of whether developmental delays were the best indicator of neurological injury in someone with a mitochondrial defect. The special master, on remand, specifically asked the parties to address Karl’s “neurological, not mitochondrial, symptoms” before the vaccination.
The government responded that “one cannot separate ‘mitochondrial symptoms’ from the symptoms related to mitochondrial disorder-affected organs, including the central nervous system.”
Petitioners, however, pointed to pieces of evidence in the record to show that Karl first exhibited neurological symptoms after the vaccinations, including the chiropractor’s records from February and March 2005, the K.I.D.S. evaluation, the April 2005 MRI, and the April 2005 neurological assessment.
The experts disagree about the significance each of these pieces of evidence.
Petitioners emphasized the October 2004 K.I.D.S. evaluation which found “Karl’s brain to be functioning within normal limits” and attributed Karl’s gross motor delay to low muscle tone. Dr. Frye testified that the K.I.D.S. evaluation was significant because it showed that Karl’s cognitive abilities were unimpaired in October 2004. In his view, the concern was Karl’s low muscle tone, not his central nervous system. He further explained that this low muscle tone was most likely due to Karl’s then-undiagnosed mitochondrial disorder. Dr. Frye testified that although Karl’s language skills were below average according to the PLS-3 test, the delay was minimal. His combined standard score for the PLS-3 was 96, and Dr. Frye testified that the average is 100. “Ninety-six is very close to 100 on these scales.” According to Dr. Frye, “Karl’s delays were most prominently gross motor delays, maybe a little bit of fine motor delays, but cognition, language was absolutely normal . . . His ability to make language sounds and to interact with others, to be attentive to what was going on in the room, this was all very important and shows that his brain and cognition were working.”
Dr. Snodgrass disagreed without elaboration. He opined that describing Karl as “right at the average” was not accurate and that the K.I.D.S. evaluation did not show Karl’s cognition and language as “absolutely normal,” as Dr. Frye described.
In turning to the chiropractor’s notation of spasticity in February 2005, the cortical thumbing noted in April 2005, and the MRI results from April 2005, the experts disagreed over the significance of all three of these. In short, Dr. Frye found all three to be evidence of sudden neurological regression after the vaccinations, and Dr. Snodgrass found them to be either a continuation of the same problems that existed before the vaccinations or insignificant.
The experts disputed the value of the chiropractic records in determining Karl’s neurological state in February and March. In particular, they disagreed over the significance of the chiropractor’s notation of “spastic” on February 11, 2005. Dr. Frye testified that the chiropractor’s finding of spasticity “suggests a very severe neurological event, and that suggests . . . that there was very rapid change in his central nervous system.” Dr. Snodgrass saw no special significance in that record, testifying that “they [the chiropractic clinic] often say spastic, stiff, et cetera. So they are reporting on the same general phenomenon which first became evident to Dr. McDonough in January . . . I think that a chiropractor would have some idea of what spastic means, but not necessarily the same that a physician would. And I think when you’re talking about a 13- or 14-month-old child, I don’t think chiropractors are in a position to make any nuanced statements about them. . . . I don’t believe they are trained to evaluate infants.”
The experts also disputed the importance of Dr. Kriengkrairut’s finding of cortical thumbing in April 2005. Dr. Frye called it a “significant sign of advanced upper motor neuron lesions and something that you don’t see with just some type of change in tone or even mild spasticity; that is a very significant finding.” He considered that the cortical thumbing, in addition to being a sign of neurological change, demonstrated an impairment occurring since December 2004, when Karl was able to open his hands and grab wrapping paper at Christmas (Frye). Dr. Snodgrass disagreed that the problems observed by Dr. Kriengkrairut differed substantially from the problems observed by Dr. McDonough in January 2005. “The function recorded in January by Dr. McDonough is the same function that was recorded by Dr. Kriengkrairut in April and by Dr. McDonough when he again saw Karl in April.” Dr. Snodgrass testified that cortical thumbing is not a significant finding and is not one he would have expected Dr. McDonough, a pediatrician, to note. Upon further questioning by the special master, Dr. Snodgrass stated that thumbing is abnormal in a one-year-old, but in the context of also seeing increased tone, it is insignificant. He further stated that the thumbing was not necessarily “cortical,” and thus was not necessarily representative of a brain abnormality.
Lastly, regarding the April 2005 MRI, Dr. Snodgrass and Dr. Frye both concede that it showed evidence of thinning of the corporal callosum, but Dr. Snodgrass testified that that thinning could have been present since birth, whereas Dr. Frye testified that it most likely occurred close in time to the MRI, after the January 2005 vaccinations.
Whether Karl’s severe neurodegeneration would have eventually resulted from his mitochondrial defect without the vaccinations posed a vexing issue. The government and petitioners appear to agree that mitochondrial disorders are “a heterogeneous group of disorders characterized by impaired energy production due to genetically based oxidative phosphorylation dysfunction.” They also agree that manifestations of mitochondrial diseases are variable. The government maintains that “the aggravation of symptoms as Karl aged stemmed from the natural progression of the disease.”
The special master asked Dr. Frye what he would think if a hypothetical child, with Karl’s same genetic makeup and medical history, experienced the same neurodegeneration as Karl, without having received any vaccinations. Dr. Frye responded that he would immediately look for some other trigger, such as a bad infection or a bad viral illness because it would be very puzzling to see such a regression with no identifiable cause.
Dr. Snodgrass stated that “mitochrondrial problems are heterogeneous. . . . They vary enormously.”
The evidentiary record is bereft of any basis for a natural progression of a mitochrondrial condition to the severely debilitating point Karl experienced. The special master acknowledged that it was possible that Karl’s gross motor delays were purely related to low muscle tone and not his central nervous system, but he believed three reasons supported finding that Karl had preexisting neurodegeneration allegedly significantly aggravated by the vaccines. First, it is generally accepted that there is a connection between muscle tone and the nervous system. Second, Karl showed delay in his expressive language according to the K.I.D.S. evaluation in October 2004. Third, the special master pointed to the Palucks’ Amended Petition, filed October 17, 2008, stating that they allege that the vaccines “caused a ‘significant aggravation’ of Karl’s underlying mitochondrial disorder, leading to . . . subsequent neurodevelopmental regression.”
The special master’s reasoning in finding evident neurodegeneration prior to the vaccinations is partially but not fully supported by the record. The parties accepted that the central nervous system helps maintain muscle tone, but the experts did not agree that low muscle tone is necessarily a result of a problem in the central nervous system. Dr. Frye testified that Karl’s gross motor delays were attributable to “problems with muscle development, and energy that the muscle needs, because of his [then-undiagnosed] mitochondrial disorder.” This testimony is corroborated by the contemporaneous finding by the K.I.D.S. evaluators that Karl’s delays were likely a result of low muscle tone. It is also corroborated by the fact that Dr. McDonough did not recommend that Karl see a neurologist until late March. If low muscle tone was necessarily caused by a problem in the central nervous system, that would have been evidence that the K.I.D.S. evaluators and Dr. McDonough should have been and actually were concerned about neurological causes from October 2004 onwards. Contrastingly, Dr. Snodgrass nonetheless opined that Karl’s gross motor delays and observed low muscle tone were secondary to undiagnosed problems in his central nervous system. Although Dr. Snodgrass’s opinion is plausible, it is supported by the contemporaneous medical records only insofar as Dr. McDonough’s examination of Karl on January 19, 2005 indicated “two beats clonus [right ankle].”
The special master’s emphasis on Karl’s language delay as evidence of pre-vaccination neurodegeneration is minimally supported by the record. There is evidence of delay, but the delay is moderate at most. Petitioners assert there was absolutely no cognitive or language delay. Karl tested within normal limits on the Bayley Scales and tested slightly below average on the PLS-3 scales. Karl was, however, referred to speech therapy by the K.I.D.S. program evaluators. There is room for debate over whether Karl’s language skills were actually “delayed,” and the special master could have reasonably concluded that being below average, even just slightly, constitutes delay, but to label that delay as evidence of then-existing problems in the central nervous system stretches inference from the evidence too far. In stating that “expressive language tends, at least in the absence of other identified causes, to be considered a Central Nervous System problem,” the special master only cites Dr. Snodgrass’s testimony that “alludes” to such a connection between expressive language and CNS. Any cognitive and language delays that Karl had were mild prior to the vaccination and were not of strong concern. To find that these delays definitively represented a “CNS problem” is not supported by substantial evidence.
The special master commented that “special masters ‘can always rule on a factual issue no matter how scanty the evidence is,’” but that recitation is not a license to ignore the record. In this instance, substantial contemporaneous medical records exist. The four-month and six-month evaluations by Dr. McDonough, the records of illness with otitis media and erytherma multiforme, and especially the K.I.D.S. evaluative results provide significant information about Karl’s condition pre-vaccination. These records suggest that no one believed or even suspected Karl’s problems were neurological in nature until after the vaccinations. The special master is not free to decide otherwise in the face of this evidence.
Despite these flaws, the special master’s conclusion that petitioners’ claim is one of significant aggravation and not new injury will not be disturbed. It is evident that Karl faced a multitude of setbacks in the fall. He was not a completely healthy child when he received the vaccinations. He had an undiagnosed mitochondrial disorder that was causing developmental delays in some areas, and he was experiencing repeated stresses to his immune system in the form of persistent otitis media and erythema multiforme. Given this, the ankle clonus might, but does not necessarily, represent neurological injury. On cross-examination, Dr. Snodgrass explained that a severely agitated child “who is screaming his head off” might have clonus. Petitioners’ counsel asked Dr. Snodgrass whether two beats of clonus is “mild clonus.” Dr. Snodgrass replied, “I think that depends on the circumstance. I think the basic issue is it’s clonus, which was not present before.” Upon further questioning, Dr. Snodgrass responded, “Well, it’s—two beats of clonus is less than say five. But it’s still not normal.”
Evidence that Karl’s immune system was not functioning optimally, the court concurs that petitioners’ claim is more appropriately analyzed as one of significant aggravation. It is not necessary to find with specificity that Karl’s gross motor delays were neurological rather than musculoskeletal in nature prior to the vaccinations. If Karl’s problems prior to the vaccinations on January 19, 2005, were neurological, the impairment was small and not evident to the treating physicians. Given petitioners’ claim that the vaccine overwhelmed Karl’s immune system, causing cell death, it is enough to find that Karl’s body was under immune stress in the months leading up to the vaccinations and that his underlying mitochondrial defect made his body less able to respond to immune stressors. Thus, petitioners’ claim is properly analyzed as one of significant aggravation and not new injury.
Loving Factors
After determining that petitioners’ claim is more properly analyzed as a significant aggravation claim, the special master applied the Loving test. The court concurs that the Loving test applies and requires preponderant proof of: (1) the person’s condition prior to administration of the vaccine, (2) the person’s current condition (or the condition following the vaccination if that is also pertinent), (3) whether the person’s current condition constitutes a ‘significant aggravation’ of the person’s condition prior to vaccination, (4) a medical theory causally connecting such a significantly worsened condition to the vaccination, (5) a logical sequence of cause and effect showing that the vaccination was the reason for the significant aggravation, and (6) a showing of a proximate temporal relationship between the vaccination and the significant aggravation.
Loving Prong 1—Condition Prior to the Vaccinations: The special master found that “overall, by January 19, 2005, Karl had problems in his CNS. His pediatrician diagnosed him with gross motor delays, which had worsened in the preceding three weeks. Karl was also having problems with his language. Finally, Karl was recovering from the most recent episode of erythema multiforme.”
Petitioners contest the special master’s findings regarding Karl’s condition before the vaccinations as arbitrary and capricious and not in accord with the law. First, they challenge the special master’s interpretation of Dr. Snodgrass’s testimony as meaning that the erythema multiforme was another possible cause of the neurodegeneration. Second, they dispute the special master’s finding that Karl had expressive language delay that, “in the absence of other identified causes, is to be considered a CNS problem.” Third, petitioners question the special master’s finding that Karl’s developmental delays worsened between December 2004 and January 2005, contending that the special master ignored Dr. Frye’s testimony to the contrary.
The government asserts that the special master’s conclusions of fact, including his conclusion that Karl’s delays prior to January 2005 represented a problem with his central nervous system, are supported by appropriate evidence.
The special master recounted the evidentiary record in his analysis of Karl’s condition prior to the vaccinations. He considered both the contemporaneous medical records and the expert testimony regarding Karl’s recurrent erythema multiforme, finding that it was evidence of chronic activation of Karl’s immune system.
The dispute over whether Karl’s language abilities were delayed poses a different type of issue. As discussed supra, reasonable minds could differ over whether Karl could or should be classified as having had a speech delay before the vaccinations. Consequently, the special master could properly conclude that Karl had speech delays. On the other hand, there is no evidence that those speech delays were necessarily a result of neurological problems. As discussed supra regarding the propriety of a significant-aggravation analysis, the contemporaneous records do not suggest that Karl’s treating physicians and therapists believed that any extant pre-vaccination speech delay was neurological in nature.
Regarding Karl’s gross motor delays, the special master found that they represented problems in his central nervous system before the January 19, 2005 vaccinations. In support, the special master compares Dr. McDonough’s findings in December 2004, that Karl had normal muscle tone and no ankle clonus, to his findings in January 2005, that Karl had increased tone and two beats of clonus in his right ankle. This evidence supports the special master’s conclusion that Karl’s physical condition had worsened between December 2004 and January 2005. A report by the same doctor that Karl went from normal muscle tone to increased muscle tone and from no ankle clonus to two beats of ankle clonus is compelling. Again, however, the special master’s conclusion that this worsening is necessarily a result of problems with Karl’s central nervous system steps beyond the inferences that can permissibly be drawn from the medical evidence. Although Karl’s medical problems make this case a significant-aggravation claim rather than a new-injury claim, there is very little direct evidence.
The special master questioned whether the erytherma multiforme could have caused Karl’s eventual neurodegeneration but determined that “resolution of this question is not necessary because . . . Karl did not significantly decline in the weeks immediately following January 19, 2005, when he both received a set of vaccinations and suffered another bout of erythema multiforme.” This latter observation foreshadows the special master’s analysis of Loving prong six, addressed.
December 27, 2004, Dr. McDonough saw Karl when his parents brought him into the clinic for otitis media and possible erythema multiforme. Under “Developmental History” Dr. McDonough recorded, possibly based upon discussion with Karl’s parents that “he has several words that he says.” On January 19, 2005, however, he recorded that Karl had no words, except for “mama” and “dada.” No other evidence suggests that Karl ever had any words beyond “mama” and “dada,” and, as such, the descriptive statement in Dr. McDonough’s report of December 27, 2004 is uncorroborated that Karl’s condition before the vaccinations had a neurological foundation. Certainly his treating medical providers did not think it was neurological at the time. Thus, the evidence shows that Karl had gross motor delays and speech delays, but it does not support finding that those delays were caused by a significant impairment of his central nervous system. If his central nervous system was adversely affected, any such disability was not a major one.
Loving Prong 2—Condition Following the Vaccinations: Loving prong two inquiries into the claimant’s current condition or condition following the vaccinations. As the special master noted, because Karl’s current condition is not at issue, the focus turns to his condition in the six months following receipt of the vaccines. Two days after the vaccinations, Karl’s daycare recorded that he had a temperature of 101.5 degrees. For the next week, Karl reportedly acted tired and fussy. On January 28, nine days after the vaccinations, Karl still had a fever of 101.3, as recorded by his daycare. The experts disagree as to the cause of the fever. Dr. Frye testified that the fever was a symptom of immune activation caused by the vaccinations on January 19, 2005. Dr. Frye also opined that Karl’s symptoms in late January and early February indicated the first signs of the biological processes that eventually led to Karl’s neurological regression (describing Karl’s post-vaccination symptoms as manifesting encephalopathy). Dr. Snodgrass disagreed, stating that the fever on January 21 manifested too quickly to be attributed to the vaccines, that the continued fever on January 28 was more likely due to an outbreak of Karl’s erythema multiforme, and that the fevers in any event were not related to Karl’s neurological decline. Karl’s daycare records, which extend through February 8th, largely describe him as being tired, irritable, and fussy. Karl’s chiropractic records, which begin on February 7, 2005, describe Karl as “irritable” on February 9th and then “spastic” on February 11, 2005. The next three visits suggest some slight progress, but the chiropractor’s assessment of Karl’s condition remained the same. The following visits noted increased stiffening and spasticity, with the assessment of Karl’s condition remaining the same. The first visits of March again indicated some slight progress, but the remaining three visits in March showed a decline and decreased range of motion. In April, Karl’s condition continued to be variable. The K.I.D.S. evaluation pointed specifically to low muscle tone, and Dr. McDonough did not refer Karl to a neurologist until late March 2005, two months after the vaccination, following reports that Karl was deteriorating further. Dr. Snodgrass testified that the MMR vaccine introduces a virus into the body that grows with time. Those viruses “will present a larger stimulus at seven to ten days than they do on day 1, 2, or 3.” This is unlike a killed bacteria vaccine, which does not multiply in the body and causes reactions more quickly. Karl’s daycare noted the reappearance of spots on his arms and legs on January 31, 2005. The chiropractor’s records document a decline, albeit not a linear one. The observation by the chiropractor that he was “spastic” is significant. That Karl was a little less spastic or stiff some days than others does not mean that Karl’s condition improved beyond his initial appointments in early February. This is consistent with Dr. Frye’s theory that Karl was likely experiencing changes at the cellular level that would take time to appear at the clinical observation level. Moreover, there was a phone conversation between Brenda Erie of Stark County Social Services and the chiropractor on March 30, 2005, reproduced below, where the chiropractor discussed possible causes for Karl’s condition, including abuse, adverse reaction to medication or a vaccine, cerebral palsy, or a cerebellar tumor: The special master read this record as indicating that “the chiropractor answered ‘No’” to the possibility that an adverse reaction to the vaccination might have caused Karl’s deteriorating condition. In the hearing held by the court on September 18, 2013, the government acknowledged that the special master misread this record. The chiropractor said “No” to child abuse allegations, not to the possibility of an adverse reaction to a medication, cerebral palsy, or a cerebellar tumor.
On March 24, 2005, Dr. McDonough referred Karl to a neurologist. This occurred two days after a phone call between Dr. McDonough and the Palucks, during which the Palucks reported that Karl had some brief crawling, was not sitting on his own, leans to one side, is babbling more, and has an intermittent rash. This is the first time in the record that anyone recommended Karl see a neurologist. At that point, Dr. McDonough could not have thought Karl had improved since the January vaccinations.
On March 28, 2005, Karl had a bout of otitis media and bronchiolitis, documented by Dr. Gary Peterson. A week later, Karl’s symptoms were improving in that regard and the doctor recommended weaning him off the nebulizer that he had been using to treat the bronchiolitis. On April 13, Karl saw Dr. McDonough for a pre-anesthesia appointment in preparation for his planned MRI. At that point, Dr. McDonough noted “increased tone in the upper and lower extremities,” no clonus, “decreased hip flexion to about 70 degrees bilaterally,” no speech, and “global developmental delay with resolving otitis media.” Dr. McDonough described the decreased hip flexion as “a change in hip movement over the last couple months.” He also documented his hope that “the parents would agree to evaluation for congenital infections, metabolic disorders, and other tests requested by Dr. Kriengkrairut for his global developmental delay.”
Dr. Frye testified that this examination represented a neurological decline in Karl “because now he has increased tone in the upper and lower extremities, so—and he says, ‘Global developmental delay with resolving otitis media.’ So here his concerns are that his neurological exam has gotten worse” since January 2005. Dr. Frye further opined that Dr. McDonough’s suspicion of a metabolic disorder was consistent with a finding of increased tone. Increased tone suggested damage to the cortex of the brain, which can be seen in white-matter abnormalities in an MRI.
Dr. Snodgrass disagreed that the examination on April 13th evidenced significant change, stating that while the hip flexion is more severely limited, it was present in January in any case.
On April 19, 2005, Karl saw the pediatric neurologist, Dr. Kriengkrairut. She reported “truncal hypotonia with marked spasticity of the extremities. The baby has tendency to do cortical thumb bilaterally, worse on the right compared to the left. . . . Baby does not babble. . . . Delayed development as well as hypotonia of the extremities may be secondary to central nervous system pathology.”
Dr. Frye testified that this report by Dr. Kriengkrairut suggests substantial worsening in Karl. “This is a third medical provider talking about spasticity, not just some subtle increases in tone. She actually says on the motor exam ‘marked spasticity.’ This is very, very different than just a subtle change in tone.” Dr. Frye also explained that hypotonia, cortical thumbing, and cessation of babbling all represent neurological regression. Dr. Snodgrass disagreed. He considered that Dr. Kriengkrairut’s exam revealed no new neurological problems in Karl. In his view, cortical thumbing was not a significant finding. He also stated that the thumbing was not necessarily “cortical” and thus was not necessarily representative of a brain abnormality. Dr. Snodgrass’s critical commentary on Dr. Kriengkrairut’s findings appears to have had two objectives, first, to suggest that Karl’s neurological condition in April 2005 was not substantially different from his condition before the vaccinations, and, second, to suggest that Karl’s neurological condition was not deteriorating. Both implications have no support in the contemporaneous medical records. Karl’s pediatrician, Dr. McDonough, in March had referred Karl to Dr. Kriengkrairut for a detailed neurological examination because of perceived neurological abnormalities. Dr. Kriengkrairut found multiple indicia of “central nervous system pathology.” What Dr. McDonough had suspected was in fact borne out by Dr. Kriengkrairut. The spasticity first observed by the chiropractor in early mid-February, shortly after the vaccinations, was still evident, along with other neurological abnormalities. By April, Karl was regressing markedly.
In summary, the court finds that Karl had significant signs of neurodegeneration by the end of April, as evidenced by the marked spasticity, cortical thumbing, and lack of babbling observed by Dr. Kriengkrairut, the decreased hip flexion and “global developmental delay” noted by Dr. McDonough, and the belatedly diagnosed abnormal MRI exam from April 27, 2005.
In May 2005, Karl saw a speech therapist. Karl made no progress throughout May regarding his speech, and the therapist’s records show that Karl had lost skills since October 2004. He could no longer produce consonant sounds, but continued to be able to reach for desired toys. Karl’s evaluation in September 2005 stated, “No goals met.”
On July 12, 2005, Karl experienced his first seizure. Upon discharge from the Med Center One Hospital in Bismarck, Dr. McDonough noted that he had “global developmental delay with seizure disorder, possible deteriorating neurologic status in that he is unable to do some things that he was able to do previously.” On July 19, 2005, Karl saw Dr. Michael Frost at St. Paul Children’s Hospital in Minnesota. His medical history from that appointment notes that Karl “has been receiving therapies with some intermittent decreased tone but overall he is declining in all areas.” It also notes that by fourteen months, i.e, March 15, 2005, Karl showed no signs of significant developmental progress. Dr. Frost noted that Karl was being admitted for a determination of what the etiology might be for his deteriorating neurological status. Dr. Frost believed, after a second MRI in July, that Karl was experiencing neurodegeneration. A third MRI performed in October 2005 showed that the thinning of Karl’s corporal callosum had stabilized, suggesting that there may have been a toxic or metabolic event he experienced that had also stabilized. In short, Karl’s condition following the vaccinations reflected marked neurodegeneration.
Loving Prong 3—Whether the post-vaccination condition constitutes a significant aggravation of the pre-vaccination condition: By October 2005, Karl had “no purposeful movements. He had increased tone throughout and increased deep tendon reflexes throughout with multiple beats of clonus at the ankles.” He had no specific smiling or distinctive eye contact. This condition starkly contrasts to the previously “very happy” child, that was “aware and tuned into faces” and who “enjoyed interactive play.” The special master properly concluded that substantial evidence showed that Karl was indisputably worse in the months following his vaccination. The parties do not dispute this finding, and the court concurs that substantial evidence supports the special master’s conclusion.
Loving Prong 4 (Althen Prong 1)—Whether there is a medical theory causally connecting the significantly worsened condition to the vaccination: The special master found that petitioners satisfied their burden of proof as to Loving prong four (Althern prong one), i.e., in showing that a medical theory causally connected Karl’s worsened condition to the vaccination. The special master succinctly stated that “in briefing after the court’s Opinion and Order, the parties essentially agreed that the Palucks’ evidence met the standard as defined by the court.” In that connection, the special master quoted the government’s interpretation of Paluck II as having “hamstrung the special master from denying compensation under prong one of Althen.”
On this second review, the government contends that the court in Paluck II “inappropriately relaxed the Vaccine Act’s requirements.” Respondent’s opinion (referring to the court’s observation in Paluck II), is “that Dr. Frye’s theory is, while not scientifically certain, under active, continuing scientific investigation by a range of researchers, showing that it is sufficiently worthy and reliable to merit that extensive scientific injury.” The government’s criticism is misplaced. The Federal Circuit has repeatedly emphasized that preponderant proof of causation does not require scientific certainty, but rather a showing that the vaccine more likely than not caused the injury.
“While this case involves . . . a sequence hitherto unproven in medicine, the purpose of the Vaccine Act’s preponderance standard is to allow the finding of causation in a field bereft of complete and direct proof of how vaccines affect the human body. A petitioner must provide a reputable medical or scientific explanation that pertains specifically to the petitioner’s case, although the explanation need only be ‘legally probable, not medically or scientifically certain.’” “Requiring ‘epidemiologic studies . . . or general acceptance in the scientific or medical communities . . . impermissibly raises a claimant’s burden under the Vaccine Act.’” Even so, the preponderance standard for causation is not to be confused with a standard requiring only “possible” or “plausible” causation.
Mitochondrial disorders are only incompletely understood in biomedical science, although basic mechanisms are known. Those with normally functioning mitochondria have better antioxidant defenses that allow them to “convert . . . reactive oxygen species to harmless compounds.” This is because mitochondria are responsible for the creation of the energy-carrying molecule, adenosine triphosphate (“ATP”), which is required for the synthesis of the primary antioxidant, glutathione. Contrastingly, defective mitochondria can have an opposite effect, themselves producing abnormally high amounts of reactive oxygen species, which can cause damage. Thus, people with mitochondrial defects are more vulnerable to oxidative stress.
Dr. Snodgrass did not disagree with the basic premises behind Dr. Frye’s theory, but he disagreed that there was evidence, i.e., published peer-reviewed studies, that normal vaccines given to humans cause oxidative stress. “I would say that if you have a mitochondrial abnormality, your ability to recover from excessive reactive oxygen species or reactive nitrogen species may be less.” Vaccines can affect children with mitochondrial disorders. Dr. Snodgrass stated that of his about twenty patients with a mitochondrial disorder, none of them have worsened with immunization, but he admitted that because mitochondrial disorders are heterogeneous, it is difficult to predict how the same stressor would affect different people. On cross-examination, Dr. Snodgrass conceded that, in theory, Karl’s otitis media, erythema multiforme, and the vaccines administered in January 2005 could have “all worked together and been a substantial factor in bringing about his neurodegeneration.” He maintained, however, that that the theoretical postulate was not established in this case because Karl did not get worse in January and February after the immunizations. Nonetheless, whether Karl got worse in January and February after the vaccinations does not relate to the legal acceptability of Dr. Frye’s theory under Loving prong four, but instead bears on Loving prongs five and six, i.e., the logical sequence of cause and effect and a medically acceptable approximate temporal relationship.
Contrary to the government’s reading of this court’s articulation of a standard for Loving prong four (Althen prong one) in Paluck II, it is not solely because a theory is under active scientific investigation that it is reputable, worthy, and reliable. The court instead was stating that the special master could not wholly discount animal studies showing oxidative stress resulting from vaccinations plus ongoing, continuing scientific investigation into whether humans also can experience similar oxidative stress resulting from vaccinations. Nor could the special master discredit a peer-reviewed study that suggested oxidative stress in humans resulted from receipt of the flu vaccine, solely because the researcher used a different biomarker than he did in a prior study. (Michael Phillips et al., Effect of Influenza Vaccination on Oxidative Stress Products in Breath, J. Breath Research, June 2010). The court was not relaxing the standard for reliability, but rather was applying the pertinent and appropriate standard where research was underway testing reputable theories that were supported by basic knowledge.
Loving Prong 5 (Althen Prong 2)—Whether there is a logical sequence of cause and effect showing that the vaccination caused the significant aggravation: Accepting Dr. Frye’s theory of causation that vaccines can activate an overwhelming immune response in children with mitochondrial defects and lead to neurodegeneration, the next inquiry is whether, in Karl’s particular case, that process occurred. Similar to the level of proof required in establishing a medical theory, the sequence of cause and effect must be “logical and legally probable, not medically or scientifically certain.”
Petitioners contend that the special master put aside expert testimony and contemporaneous medical records in favor of drawing his own medical conclusions from the evidence. Specifically, petitioners challenge his reading of the chiropractic records, Dr. McDonough’s referral to the neurologist in March 2005, and testimony regarding the various MRIs.
First, the special master determined that Dr. Frye’s theory requires a linear, downward decline without any periodic improvements. Both the government and the special master cite this court’s opinion in Paluck II for the proposition that this court approved of the special master’s prior conclusion that “petitioners’ medical theory predicted a steady, downward decline in health after vaccination.” The court did not disturb the finding that Dr. Frye’s theory was predicated on a downhill trajectory.” The citation provided by both the respondent and the special master misapprehends the court’s prior action. This court did not address the special master’s determination in Paluck I that Karl’s regression could only fit Dr. Frye’s theory if Karl experienced a “continuous downward slope” of injury. The decision to require a linear, downward slope is unfounded in the testimony. The special master in Paluck I interpreted Dr. Frye’s phrase that “Karl’s progress looked like it was just a progressive hill downward for about six months,” to mean “a continuous downward slope.” The special master maintained this interpretation in Paluck IV (“the special master again concludes that Karl’s deterioration was non-linear”). Dr. Frye, however, never suggested that a child experiencing neurodegeneration could not have periods of remission or improvement. His use of the word “progressive” does not mean a continuous linear decline. As a general matter, when used in describing a disease, progressive means “increasing in extent or severity.” Merriam-Webster’s Tenth Collegiate Dictionary 932 (1998); see also New Oxford American Dictionary 1396 (2010) (“(of a disease or ailment) increasing in severity or extent”). This standard medical usage allows for a non-linear decline. To fall within Dr. Frye’s theory and the applicable medical literature, it is sufficient if Karl’s medical records show a decline in condition over time, notwithstanding periods of remission or modest improvement.
Second, the special master considered the chiropractic records and statements by his treating physicians regarding Karl’s decline. In the remand, the court ordered the special master to reconsider the importance of these particular pieces of the record, in conjunction with other pieces of the record. Accordingly, this court will consider the entire record in determining whether petitioners have met their burden of proof under Loving prong five.
Karl had a fever on January 21, 2005, two days after the vaccinations that continued to be evident on January 28, 2005, nine days after the vaccinations. Daycare notes from the intervening days consistently show that Karl was tired, irritable, and not eating well. According to Dr. Frye, these are all systemic signs of being sick, that is, signs of immune activation. Dr. Frye testified that a fever any time within two weeks of a vaccination could reasonably be attributed to the vaccination.
Dr. Snodgrass disagreed that Karl’s fever could have been caused by the vaccines. He explained that the MMR and varicella vaccines do cause fever in some children, but fever would not usually appear until the seventh or eighth day. On cross-examination, petitioners’ counsel asked Dr. Snodgrass whether he was familiar with the packaging insert accompanying the Prevnar vaccine, which states that “15% of children who receive PCV-7 report fever of greater than 38 degrees centigrade within two days following vaccination.” He responded that he was, but that the packaging insert does not truly prove causation as a scientific matter. He referred to a study about the MMR vaccine, one of the other vaccines Karl received, which took 500 sets of identical twins, giving one twin the vaccine and the other a placebo. In his view, this type of study better proves that a vaccine causes fevers. In short, Dr. Snodgrass again looked for medical certainty where none is required. It is sufficiently logical that Karl had a reaction to the Prevnar vaccine, manifesting as a fever within two days. He additionally did not explain why the fever on day nine could not be attributed to the vaccinations, stating only that Karl’s fevers could have been due to an outbreak of his erythema multiforme, which reappeared on January 31st. He testified further that fever is very common among children in daycare and may not specifically indicate oxidative stress. Similarly, in his view, while irritability might be an indication of something serious, it is not specific.
Several points of common ground exist. A fever is usually a symptom of immune activation; that much was acknowledged by both experts. And, the daycare records contemporaneously documented that Karl had lethargy and irritability along with the fever in the days following the vaccinations. While fever, lethargy, and irritability might possibly have been caused by something besides the vaccinations, sufficient evidence exists to indicate that they were in fact caused by the vaccinations. That at least one of the five vaccines that Karl received, or a combination thereof, caused him to have a fever due to immune activation is logical and legally probable. A prima facie case to that effect was established. Accordingly, the burden shifted to the respondent to show another, alternative, cause. That shifted burden was not met, nor did the respondent attempt to meet it.
Dr. Frye’s theory postulates that immune activation can cause the development of potentially toxic reactive oxygen species and reactive nitrogen species that, if left unchecked by the body’s antioxidants, can lead to oxidative stress and cell death. Thus, one would look for evidence of whether Karl experienced cell death. In this case, petitioners contend that Karl’s neurodegeneration is evidence of brain cell death.
Karl’s health deteriorated in February 2005. The chiropractor noted he was spastic on February 11, 2005. As detailed previously, Karl’s later chiropractic records reflect varying levels of rigidity and tone. Regardless of whether Karl had days in the subsequent weeks where he was more or less rigid, Karl never appeared to improve above his initial assessment, and he was still reported as spastic in April by the pediatric neurologist, Dr. Kriengkrairut. Upon questioning by the special master regarding the chiropractic treatment Karl received, Dr. Frye testified that spasticity can be improved by “pulling the muscles and loosening the muscles so that they have full range of motion.” This does not solve the upper neuron problem causing the spasticity, but it can mitigate the symptoms. “By manipulating the muscles you’re resetting the feedback mechanism that sets the tone of the muscles. . . . When neurons from the brain aren’t there the feedback loop becomes or is set too high and the muscles have too much tone. . . . By using physical therapy we start to stretch out the muscles and that can try to reset the feedback loop that we have in the muscles.” That Karl’s tone fluctuated while he was seeing the chiropractor and the K.I.D.S. therapists would be expected.
In asserting that Karl did not decline between January and February, Dr. Snodgrass stated that “the single most important thing is that we had a lot of calls and doctor visits in November and December. If Karl had a precipitous decline in January and February, these parents who seem to be responsible parents would have been calling and visiting the doctor, that’s number one.” Dr. Snodgrass’s inference and the special master’s reliance on it are not supported by substantial evidence. Karl’s parents actually were taking him frequently to a medical provider, i.e., the chiropractor. They took him to the chiropractor nine times in a three week period in February alone, apparently believing that Karl had a pinched nerve preventing his development. Dr. Snodgrass can disagree with their course of action, implicitly being critical of treatment by a chiropractor rather than a physician, but his testimony implying that the Palucks thought medical treatment unnecessary for Karl is not supported by evidence.
Contrary to the special master’s conclusion, the fact that Karl had few visible signs of injury other than fever immediately following the vaccinations is in keeping with Dr. Frye’s theory (“part of the Althen prong 2 analysis may consider whether the expert’s ‘theory accounted for the vaccinee’s injury’” (quoting Hibbard v. Secretary of Health & Human Servs.). Dr. Frye testified that changes at the cellular level would occur first and would take time to become clinically visible. That the MRI from April 2005 was initially interpreted as normal and only later reinterpreted as abnormal upon re-examination in July 2005 suggests that the changes were indeed small at first, but they had been initiated. Because the changes were likely occurring at a cellular level at first, Karl was probably worsening in February and March even if it was not linearly progressive. The rate at which that process would occur would depend on the type and severity of the person’s mitochondrial disorder. As an example, Dr. Frye pointed to the Hannah Poling case study (referring to R. Ex. 21q, Jon S. Poling, Richard E. Frye, John Shoffner & Andrew W. Zimmerman, Developmental Regression and Mitochondrial Dysfunction in a Child with Autism, 21 J. Child Neurology 170 (2006)). Hannah was a developmentally normal nineteen-month-old girl who, within 48 hours of receiving several vaccinations, developed a high fever, inconsolable crying, irritability, and lethargy, and refused to walk. Four days later, she could not walk up stairs. She had a low-grade intermittent fever during the next twelve days. She continued to decline over the next three months, developing autistic behaviors and losing all speech. Previously she had been able to say at least twenty words. It was later discovered that she had a mitochondrial disorder. In 2006, at the time of publication of the case study, Hannah was six and had greatly improved in her language functions and sociability, although she still exhibited mild autism. This case study did not prove causation with any medical certainty, but it hypothesized that “if mitochondrial dysfunction is present at the time of infections and immunizations in young children, the added oxidative stresses from immune activation on cellular energy metabolism are likely to be especially critical for the central nervous system, which is highly dependent on mitochondrial function.” Dr. Frye pointed to similarities between Hannah and Karl. First, they have similar mitochondrial abnormalities. Both received MMR and varicella vaccinations, developed a fever around 48 hours later, became noticeably irritable, and eventually experienced neurological regression. Hannah’s decline occurred more quickly in some ways, but her regression, like Karl’s, appeared to continue over a number of months. Her appetite remained poor for six months, but she began saying a few words again about four months after the vaccinations. In contrast, Karl has experienced complete neurodegeneration and is not expected to improve. Dr. Frye opined that Karl’s pre-existing chronic immune activation may have impaired his ability to recover as Hannah did.
Dr. Frye also pointed to a peer-reviewed article by Dr. John Shoffner and others. The researchers found in a retrospective study that autistic regression occurred twice as often in a subset of autistic children with mitochondrial disorders after a fever than it did in the general population of autistic children (referring to John Shoffner et al., Fever Plus Mitochondrial Diseases Could Be Risk Factors for Autistic Regression, 25 J. Child Neurology, 2010). Approximately 25% of children with autism will experience autistic regression before the age of three. The researchers defined autistic regression to mean “a loss of developmental skills that included speech, receptive skills, eye contact, and social interests in individuals.” A relationship between fever and regression was defined as “regression beginning within two weeks of a febrile episode without the suggestion of infection, meningitis, or encephalitis.” In the study, 60.7% of the children experienced autistic regression, which was a “statistically significant increase” over the estimated 25% reported in the general autistic population. A high percentage, 70.6%, of those who experienced autistic regression did so following a fever. In 33.3% of those who experienced autistic regression following fever, the fever was associated with response to a vaccination. The specific vaccine schedule leading to fever in the subjects was not available. The study acknowledged that “due to the complexities in mitochondrial disease pathogenesis, oxidative phosphorylation enzyme defects are highly variable even among groups of individuals who harbor identical mutations.” According to Dr. Frye, this study, combined with the Poling case study, strongly suggested that vaccinations in children with mitochondrial diseases can cause fever followed by regressive loss of skills.
Dr. Snodgrass cited a number of differences between Karl’s case and Hannah’s case. First, Hannah’s clinical worsening was much more dramatic than Karl’s. She refused to walk within 48 hours of receiving the vaccination, a more notable loss of skill than anything Karl experienced. Second, there is no evidence that Karl suffered encephalopathy, and it was agreed that Hannah did. “In Karl’s case we really don’t see that. In this retrospective study, researchers examined the charts of 28 children who they knew to have autism and mitochondrial disease. They used the charts to determine whether the children experienced fever followed by autistic regression.
(Phosphorylation is defined as “the metabolic process of introducing a phosphate group into an organic molecule.” Oxidative phosphorylation, specifically, is defined as “the formation of high energy phosphate bonds by phosphorylation of ADP to ATP coupled to the transfer of electrons from reduced coenzymes (NADH or FADH2) to molecular oxygen via the electron transport chain. . . . Three molecules of ATP per NADH and two per FADH2 are produced as a result of a proton gradient created across the mitochondrial inner membrane by the electron transport chain.” Thus, “oxidative phosphorylation enzyme defects” can be understood as defects in ATP production.)
“Yes, he was irritable. Irritability is not encephalopathy. He was not kept home from day care, he was not taken to the doctor. So we do not see evidence that Karl had encephalopathy.” As for Dr. Frye’s reliance on the Shoffner paper, Dr. Snodgrass criticized its simplicity, questioning how researchers could have known that any particular fever that a child experienced caused the regression.
Dr. Snodgrass’s critiques might provide valid points of departure for further scientific study in this area of medicine, but they do not negate the evidentiary value provided by the Poling case report or the Shoffner study. Dr. Snodgrass and Dr. Frye agreed that case studies do not prove causation. But Dr. Frye correctly pointed out that “that’s where science starts is with case reports.” Dr. Frye testified that this particular area of medicine is “emerging and evolving.” Mitochondrial diseases themselves are difficult to identify, and their courses of progression are not easily predicted. The effect of fevers on those with a mitochondrial disorder is even more difficult to assess. The Poling case report and the Shoffner study nonetheless provide indicia for this case.
In considering the opinions of Karl’s treating doctors as to the cause of Karl’s decline, the special master considered the chiropractor’s opinion, Dr. McDonough’s referral to the neurologist, and the MRI reports. First, as discussed supra, the special master’s statement that the chiropractor did not believe Karl had an adverse reaction to a vaccine simply misread a handwritten entry in the medical record. Rather, the chiropractor believed it was possible Karl had an adverse reaction to a vaccine. Second, in reviewing Dr. McDonough’s referral to Dr. Kriengkrairut, the pediatric neurologist, the special master inquired into Dr. McDonough’s motivations. Aside from desiring more complete testing of Karl’s neurological system, the special master opined that Dr. McDonough made the referral because he was “frustrated the Palucks were not following his recommendations for physical therapy, occupational therapy, and a stimulation program for Karl.” The special master criticized petitioners for not raising the argument that Dr. McDonough made the referral because he believed Karl was getting worse. The special master apparently ignored Dr. Frye’s testimony on direct examination that the referral is “the first indication that we have that the pediatrician is now concerned to such a level that Karl needs to see a neurologist.” There simply is no evidentiary support for the special master’s hypothesis that Dr. McDonough made the referral out of frustration with the Palucks. Third, regarding the MRI reports, the special master concluded that “the Palucks have not established that Dr. Frye’s conclusion that Karl’s corpus callosum started to thin after the vaccination is more likely than Dr. Snodgrass’s conclusion that the corpus callosum could have been thin before the vaccination.” Accordingly, the special master used his finding that Karl had problems in his central nervous system before the vaccination as the tie breaker to determine that the thinning occurred before the vaccinations. This court has overturned the special master’s finding that Karl definitively had neurological problems before. Evidence of causation need not be proven to a medical certainty; it need only be “logical and legally probable.” The subtlety of the thinning in April, and the clarity of the thinning in July, suggests that the thinning had only begun in April or shortly before then. Petitioners have presented sufficient evidence to show that Karl regressed after receiving the vaccines, and they have provided medical records and medical literature to establish, by a preponderance of the evidence, that Karl’s pre-existing medical problems were significantly aggravated by the vaccinations. Karl had a fever shortly after receiving the vaccinations, was described as “spastic” for the first time on February 11, was referred to a neurologist in March, and by April had a negative neurological evaluation and an abnormal MRI. Petitioners presented a peer-reviewed study showing increased regression in children with mitochondrial diseases following fever. They also presented a case study demonstrating that a young girl with an underlying mitochondrial disorder lost previously developed skills over the course of months after experiencing a fever within 48 hours of vaccinations. Petitioners have carried their burden of proof on this prong.
Loving Prong 6 (Althen Prong 3)—Whether a medically acceptable proximate temporal relationship exists between the vaccination and the significant aggravation: The final prong of the Loving analysis requires the court to determine the time frame for which it is medically acceptable to infer causation and whether the onset of the claimant’s injury occurred within that time frame.
Petitioners contend that the special master ignored the record in concluding that Karl exhibited no evidence of neurodegeneration within an acceptable time frame. Specifically, they argue that he ignored Dr. Frye’s testimony that evidence of neurodegeneration occurred within a medically acceptable time.
Respondent maintains that the special master carefully considered all of the evidence and found respondent’s expert more persuasive than petitioners’, an approach and result that is well within the special master’s role as a finder of fact.
In Paluck IV, the special master found that the medically acceptable temporal interval is three weeks. He based this determination largely on an article by Dr. Edmonds entitled The Otolaryngological Manifestations of Mitochondrial Disease and the Risk of Neurodegeneration with Infection. The Edmonds article collected information about 40 patients with mitochondrial diseases. Of these forty patients, eighteen experienced neurodegenerative events. Intercurrent infection was recognized as a precipitant of neurodegenerative events in thirteen of these eighteen patients. The article graphically depicts the timing of the onset of neurodegenerative events after the onset of infection as ranging until nineteen days after infection. While the Edmonds article looked for neurodegeneration after infection, not reaction to a vaccination, both experts agree that it provides a reasonable guideline for neurodegeneration following immune activation.
The special master also relied on the Shoffner study, which found that a relationship between fever and autistic regression existed, but this reliance is somewhat misplaced because the Shoffner study defined a relationship between fever and regression as occurring within two weeks, excluding later sequela. Therefore, by definition, the study could not have found a relationship between fever and regression more attenuated than two weeks. Thus, while the Shoffner article supports a statement that autistic regression following fever can occur within two weeks, it cannot equally support a statement that autistic regression following fever must occur within two weeks. The special master also relied on the Hannah Poling case study, noting that she had a fever within 48 hours, could not climb the stairs within seven days, and developed a rash within two weeks.
The Edmonds article is the most enlightening regarding an acceptable medical time frame for the onset of neurodegenerative events following immune system activation. The Edmonds article, however, acknowledges the severe dearth of medical literature in this area: “Because of the relative novelty of mitochondrial disorders, no reports in the literature have quantified the risk for neurodegenerative events triggered by infections in patients with mitochondrial disease.” Dr. Bob Naviaux, Co-Director of the Mitochondrial and Metabolic Disease Center at the University of California, San Diego, expressed a similar sentiment in commenting on the Shoffner study—“Commentary on John Shoffner et al., Fever Plus Mitochondrial Disease Could Be Risk Factors for Autistic Regression, published in J. Child Neurology (2010).” According to Dr. Naviaux, the temporal relationship between the triggering event and neurodegeneration is unsettled. There appears to be a more rapid “flare” response and a more delayed “fade” response. He credited the Shoffner study with providing a touchstone for new questions, such as “which kinds of mitochondrial defects lead to rapid, high-grade fevers in response to infection or vaccination” and “which defects lead to a failed fever response, or to a low-grade fever, or to a reduced immune response to vaccination?”
Dr. Frye accepted the premises of these articles, testifying that the temporal link requires much further study. He did testify, however, that an adverse reaction to a vaccine is likely to appear within a week of receiving it. He further stated that the adverse reaction can peak several days after the vaccination, and then “lead to . . . metabolic decompensation, which is an ongoing process . . . that will continue until it burns itself out,” if it is not interrupted. Dr. Snodgrass and Dr. Frye disagree whether Karl’s first fever, within two days of the vaccination, could have been caused by the vaccination, but they apparently agree that any fever around one week following Karl’s vaccinations could have been caused by the vaccines. Thus, at least Karl’s continuing fever is safely within any type of medically accepted time frame for Karl’s injury.
The special master appeared determined to establish a definitive bound for neurodegeneration, but the court disagrees that such a bound can be sharply delineated in this specific area. Neither the medical literature nor the expert testimony stated with any certainty when neurodegeneration can be expected to begin in all cases. Dr. Snodgrass based his testimony that a change would have to begin “within a few weeks” on the Edmonds article. As previously discussed, the Edmonds article is the first of its kind and cannot be read to suggest a definitive temporal interval for neurodegeneration in response to all triggering events for any type of mitochondrial disorder. In response to questioning from the special master, Dr. Frye testified that the timing for neurodegenerative changes to appear clinically in a child would depend on the severity and type of mitochondrial disorder. This is consistent with Dr. Naviaux’s commentary on the Shoffner study.
In this instance, Dr. Frye pinpointed the chiropractor’s notation that Karl was “spastic” on February 11, 2005 as an identifiable neurodegenerative event. To Dr. Frye, the neurodegenerative process must have begun by then. This event occurred within the general time frame suggested by both the special master and Dr. Snodgrass. (“The change should come within a few weeks.”) Starting with this chiropractic notation, the record shows Karl experienced a general decline. His chiropractic assessment remained the same throughout all of February, even if the subjective descriptions of Karl’s day-to-day behaviors varied. Karl was losing language throughout this period, and by late March, Dr. McDonough saw a need for him to be evaluated by a neurologist.
In conclusion, setting a hard and fast time frame in an uncertain area undergoing sustained scientific investigation is contrary to the precepts governing the Vaccine Act. Karl had a fever within 48 hours of the vaccinations, accompanied by a week of lethargy, irritability, more fever, and disrupted sleeping and eating cycles. This prompt reaction is consistent with an adverse immune reaction to the vaccines. An observation of spasticity followed within a time that all agreed would have been appropriate for a neurodegenerative event. Karl experienced total decline within six months, and he did not continue to develop in any way after the vaccinations. These facts combined with his febrile reaction to the vaccine show, by a preponderance of the evidence, that Karl’s existing medical setbacks were significantly aggravated by his receipt of the vaccinations within a medically acceptable time.
CONCLUSION
For the reasons stated, the Palucks’ motion for review is GRANTED, the special master’s decision of May 10, 2013 denying compensation is VACATED, and the court acts in accord with 42 U.S.C. § 300aa-12(e)(2)(B) to find that petitioners have satisfied each of the six Loving elements and are entitled to compensation under the Act. The case is remanded to the special master to determine compensation.
IT IS SO ORDERED.
* Sandra S. Chaves et al., “Safety of Varicella Vaccine after Licensure in the United States: Experience from Reports to the Vaccine Adverse Event Reporting System, 1995-2005,” 197 J. Infectious Diseases S170 (2008)