Lehner v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 08-554V

Filed: July 22, 2015

For Publication

****************************

RICK LEHNER and *

SHELLEY LEHNER, as parents and *

natural guardians, on behalf of their * Influenza [“Flu”] Vaccination; Autism

minor daughter, C.L., * Spectrum Disorder [“ASD”];

* Autoimmune Encephalopathy; Voltage

Petitioners, * Gated Potassium Channel [“VGKC”]

v. * Antibodies; Treating Physicians;

* Expert Qualifications; Causation;

SECRETARY OF HEALTH * Motion to Exclude Expert as

AND HUMAN SERVICES, * Duplicative.

*

Respondent. *

****************************

Sheila A. Bjorklund, Esq., Lommen Abdo Law Firm, Minneapolis, MN, for petitioners.

Traci R. Patton, Esq., U.S. Department of Justice, Washington, DC, for respondent.

DECISION AND RULING1

Vowell, Chief Special Master:

On August 1, 2008, Rick and Shelley Lehner [“petitioners”] filed a petition for

compensation under the National Vaccine Injury Compensation Program, 42 U.S.C.

§300aa-10, et seq.2 [the “Vaccine Act” or “Program”], on behalf of their minor daughter,

C.L.

1

Because this decision contains a reasoned explanation for my action in this case, it will be posted on the

United States Court of Federal Claims’ website, in accordance with the E-Government Act of 2002, Pub.

L. No. 107-347, 116 Stat. 2899, 2913 (Dec. 17, 2002). Each party has 14 days within which to request

redaction “of any information furnished by that party: (1) that is a trade secret or commercial or financial in

substance and is privileged or confidential; or (2) that includes medical files or similar files, the disclosure

of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b). Otherwise, the

entire decision will be available to the public.

2

National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755. Hereinafter, for

ease of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. §

300aa (2012).

Petitioners initially claimed that thimerosal in C.L.’s childhood vaccines caused

their daughter’s autism spectrum disorder [“ASD”].3 Petition, filed Aug. 1, 2008, at 2. In

2011, they amended their claim to allege that their daughter sustained an autoimmune

encephalopathy as the result of an influenza vaccine received in November 2005.

Petitioners’ Amended Petition, filed Feb. 22, 2011, at 3.

In order to prevail under the Program, petitioners must prove either that C.L.

sustained a “Table” injury4 or that a vaccine listed on the Table was the actual cause of

an injury (an “off-Table” injury). Because C.L.’s alleged injury is not a Table injury for

the influenza vaccine, petitioners must produce preponderant evidence that the

influenza vaccine was substantially responsible for C.L.’s injury. After considering the

record as a whole,5 I hold that petitioners have failed to establish their entitlement to

compensation.

I. Procedural History.

A. Omnibus Autism Proceeding.

When petitioners filed their original petition, they requested to be included in the

Omnibus Autism Proceeding [“OAP”].6 Petition at 2. The OAP was created to resolve

3

“Autism Spectrum Disorder” or “ASD” is an umbrella term for certain developmental disorders, including

autism (also referred to as autistic disorder), pervasive developmental disorder-not otherwise specified

[“PDD-NOS”], and Asperger’s Disorder. See R. Luyster, et al., Language Assessment and Development

in Toddlers with Autism Spectrum Disorders, J. AUTISM DEV. DISORD., 38: 1426-38 (2008), filed as Res.

Ex. DD [hereinafter “Luyster, Res. Ex. DD”], at 1426.

4

A “Table” injury is an injury listed on the Vaccine Injury Table [“Table”], 42 C.F.R. § 100.3 (2011),

corresponding to the vaccine received within the time frame specified.

5

See § 13(a): “Compensation shall be awarded . . . if the special master or court finds on the record as a

whole–(A) that the petitioner has demonstrated by a preponderance of the evidence the matters required

in the petition by section 300aa-11(c)(1);” see also § 13(b)(1) (indicating that the court or special master

shall consider the entire record in determining if petitioner is entitled to compensation).

6

By opting into the OAP, petitioners alleged that:

[a]s a direct result of one or more vaccinations covered under the National Vaccine Injury

Compensation Program, the vaccinee in question has developed a neurodevelopmental

disorder, consisting of an Autism Spectrum Disorder [“ASD”] or a similar disorder. This

disorder was caused by a measles-mumps-rubella (MMR) vaccination; by the

“thimerosal” ingredient in certain Diphtheria-Tetanus-Pertussis (DTP), Diphtheria-

Tetanus-acellular Pertussis (DTaP), Hepatitis B, and H[a]emophilus Influenza[e] Type B

(HIB) vaccinations; or by some combination of the two.

In re: Claims for Vaccine Injuries Resulting in Autism Spectrum Disorder or a Similar Neurodevelopmental

Disorder, Various Petitioners v. Sec’y, HHS, Autism General Order #1, 2002 WL 31696785, at *2 (Fed.

Cl. Spec. Mstr. July 3, 2002).

2

what ultimately totaled about 5,700 petitions alleging that vaccines or the thimerosal

preservative contained in some vaccines caused autism spectrum disorders. In an

omnibus proceeding, cases presenting similar theories of injury are grouped together in

a manner similar to class action litigation. Test cases are selected in which to present

the common question of vaccine causation, but unlike class action litigation, the parties,

other than those in the test cases themselves, are not bound by the results. Instead,

omnibus proceedings develop evidence on the issue of vaccine causation, and that

evidence is available to resolve the remaining omnibus cases. In the OAP, the

selection of test cases was made by the Petitioners’ Steering Committee, a group of

lawyers representing OAP petitioners. Three OAP test cases were selected for each of

the two theories of vaccine causation advanced by the petitioners’ bar. Hearings were

conducted in 2007 and 2008 and decisions denying compensation issued in 2009 and

2010.7 The decisions in the Theory 1 test cases (which advanced the theory that the

MMR vaccine, either alone or in concert with thimerosal-containing vaccines, caused

autism) were appealed; the decisions in the Theory 2 test cases (which advanced the

theory that thimerosal-containing vaccines caused autism) were not appealed.8

C.L.’s case was filed after the hearings in the test cases began, but before the

decisions were issued. Thus, unlike the early OAP petitioners, petitioners were required

to produce medical records in order to position C.L.’s case for resolution after the

special masters’ decisions were issued in the test cases and appellate review

concluded. Petitioners’ Exhibits [“Pet. Exs.”] 1 through 8 were filed on October 21,

2008.

When the final appellate decision in the OAP test cases was issued in August

9

2010, the court began the process of notifying petitioners in the approximately 4,800

remaining OAP cases of the results and asking them how they intended to proceed.10

7

The Theory 1 test cases are Cedillo v. Sec’y, HHS, No. 98-916V, 2009 WL 331968 (Fed. Cl. Spec. Mstr.

Feb. 12, 2009), aff’d, 89 Fed. Cl. 158 (2009), aff’d, 617 F.3d 1328 (Fed. Cir. 2010); Hazlehurst v. Sec’y,

HHS, No. 03-654V, 2009 WL 332306 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d, 88 Fed. Cl. 473 (2009),

aff’d, 604 F.3d 1343 (Fed. Cir. 2010); Snyder v. Sec’y, HHS, No. 01-162V, 2009 WL 332044 (Fed. Cl.

Spec. Mstr. Feb. 12, 2009), aff’d, 88 Fed. Cl. 706 (2009). Petitioners in Snyder did not appeal the

decision of the U.S. Court of Federal Claims. The Theory 2 test cases are Dwyer v. Sec’y, HHS, No. 03-

1202V, 2010 WL 892250 (Fed. Cl. Spec. Mstr. Mar. 12, 2010); King v. Sec’y, HHS, No. 03-584V, 2010

WL 892296 (Fed. Cl. Spec. Mstr. Mar. 12, 2010); Mead v. Sec’y, HHS, No. 03-215V, 2010 WL 892248

(Fed. Cl. Spec. Mstr. Mar. 12, 2010). The petitioners in each of the three Theory 2 test cases chose not to

appeal.

8

A more detailed explanation of the creation of the OAP and the effects of opting into it can be found in

Dwyer, No. 03-1202V, 2010 WL 892250, at *3.

9

Cedillo, 617 F.3d 1328.

10

The vast majority of these petitioners either voluntarily dismissed their cases or failed to respond,

eventually resulting in dismissals for failure to prosecute. Petitioners’ case is one of approximately 70

ASD cases currently proceeding to a decision on one of several alternative theories of causation.

3

B. Procedural History Post-Test Cases.

On February 22, 2011, petitioners asked that their petition be removed from the

OAP,11 and filed an amended petition alleging that the influenza vaccine that C.L.

received on November 25, 2005, “substantially contributed to her development of

clinically significant levels of VGKC-ABs [voltage-gated potassium channel antibodies12],

leading to an autoimmune encephalopathy with resultant injury to brain cells and

developmental regression.” Amended Petition [“Am. Petition”] at 3. The amended

petition was accompanied by an expert report from Dr. Richard Frye (Pet. Ex. 10)

setting forth this new theory.

Between February 22, 2011, when petitioners filed their amended petition, and

October 8, 2013, when I issued the pre-hearing order, petitioners filed both new and

updated medical records. During the same time period, the parties filed multiple expert

reports, as well as extensive medical literature.

Respondent initially filed an expert report from Dr. Mark Gorman in response to

Dr. Frye’s report. Respondent’s Exhibit [“Res. Ex.”] A, filed Apr. 26, 2011. Thereafter,

on October 19, 2011, petitioners filed a status report informing the court that Dr. Frye

would not be able to testify on petitioners’ behalf.13 On April 2, 2012, after being

afforded additional time to locate a new expert, petitioners filed the report of Dr. Yuval

Shafrir. Pet. Ex. 11. A supplemental report from Dr. Shafrir was filed on August 15,

11

The special master initially assigned to this case granted petitioners’ motion on February 25, 2011.

12

Neurons in the central and peripheral nervous systems use proteins to communicate (signal) within and

between cells. Voltage-gated potassium channels [“VGKC”] are cell membrane proteins that allow

potassium ions to cross the cell membrane, generating electrical signals. The “gates” open and close

based on changes in the cell membrane. In the central nervous system, these neuronal voltage-gated

potassium channel proteins play an important role in axonal conduction and synaptic transmission.

Autoantibodies, which were once thought to be targeted against the VGKC, have been reported to play a

role in some types of neurological illnesses in children and adults. R. Dhamija, et al., Neuronal Voltage-

Gated Potassium Channel Complex Autoimmunity in Children, PEDIATR. NEUROL., 44(4): 275-81 (2011),

filed as Pet. Ex. 11c and as Res. Ex. N [hereinafter “Dhamija, Pet. Ex. 11c”]. “Autoantibodies against the

voltage-gated potassium channel (VGKC) complex measured by radioimmunoprecipitation have been

reported in a broad spectrum of immunotherapy-responsive neurological illnesses in children and adults.”

R. Patterson, et al., Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex

antibodies: experience from a tertiary referral centre, J. NEUROL. NEUROSURG. PSYCHIATRY, published

online June 11, 2013, filed as Res. Ex. CC [hereinafter “Patterson, Res. Ex. CC”], at 1. Recently, “it has

become clear that VGKC antibodies are not directed against the VGKC itself, but against other cell

surface antigens that form part of the VGKC complex.” Id. As one of C.L.’s treating physicians, Dr.

Deborah Renaud, explained to C.L.’s family, “[i]t is presumed that the antibodies against the potassium

channels caused them to malfunction and, therefore, the electrical current in the neurons which are the

electrical cells of the brain [are] impaired.” Pet. Ex. 9, p. 7

13

Doctor Frye’s inability to testify in Program cases was due to changed employment. See Order, issued

Sept. 19, 2011.

4

2012. Pet. Ex. 16. Petitioners also filed a letter from Angela Vincent, Ph.D., to

petitioners’ counsel. Pet. Ex. 21.

Following the filing of Dr. Gorman’s initial report, respondent filed two

supplemental expert reports from Dr. Gorman (Res. Ex. I, filed July 16, 2012; Res. Ex.

W, filed Jan. 2, 2013) and two expert reports from Dr. Joseph Dalmau (Res. Ex. J, filed

Nov. 14, 2012; Res. Ex. AA, filed Aug. 23, 2013).

Prior to the two-day entitlement hearing on January 27-28, 2014, the parties filed

pre-hearing briefs and a joint statement of facts not in dispute. Petitioners also filed a

supplemental expert report from Dr. Shafrir (Pet. Ex. 23, filed Dec. 11, 2013), and

shortly before the hearing, an affidavit from Mr. Lehner, and photographs and videos of

C.L. Petitioners appeared at the hearing via video teleconference. The three expert

witnesses appeared in person.

Post-hearing, petitioners filed supplemental medical records as well as additional

video and photographs of C.L., pursuant to my order. Petitioners also filed a written

motion to exclude Dr. Gorman’s testimony, which supplemented and explained the oral

motion to exclude that petitioners’ counsel made during the hearing. Respondent filed a

response to the motion to exclude on April 7, 2014, to which petitioners filed a reply on

April 10, 2014.

This case presents diagnostic and causation issues, complicated by a change in

the scientific and medical understanding of the role of voltage-gated potassium channel

autoantibodies in autoimmune encephalitis that occurred around the time Dr. Frye

authored his initial expert report in this case. The issues to be resolved include whether

C.L. experienced encephalitis after her influenza vaccination, whether the vaccination

played any role in her development of the antibodies found years later, and whether

these antibodies played any role in her developmental regression. Ultimately, the issue

is whether petitioners have demonstrated by preponderant evidence that the influenza

vaccine caused the developmental regression which was diagnosed as an autism

symptom by several treating specialists, and which was later characterized as

autoimmune encephalitis or autoimmune encephalopathy by Dr. Frye and some of

C.L.’s treating physicians.

II. Legal Standards Applying to Off-Table Causation Claims.

When petitioners allege an off-Table injury, eligibility for compensation is

established when, by a preponderance of the evidence, petitioners demonstrate that the

vaccinee received, in the United States, a vaccine appearing on the Table and

sustained an illness, disability, injury, or condition caused by the vaccine or experienced

a significant aggravation of a preexisting condition. They must also demonstrate that

5

the condition has persisted for more than six months.14 Vaccine Act litigation rarely

concerns whether the vaccine appears on the Table, the geographical location of

administration, or whether the symptoms have persisted for the requisite time. Rather,

in the very small minority of Vaccine Act cases that proceed to a hearing, the most

common issue to be resolved by the special master is whether the injury alleged was

caused by the vaccine.

To establish legal causation in an off-Table case, Vaccine Act petitioners must

establish by preponderant evidence: (1) a reliable medical theory causally connecting

the vaccination and the injury; (2) a logical sequence of cause and effect showing that

the vaccination was the reason for the injury; and (3) a proximate temporal relationship

between vaccination and injury. Althen v. Sec’y, HHS, 418 F.3d 1274, 1278 (Fed. Cir.

2005); see de Bazan v. Sec’y, HHS, 539 F.3d 1347, 1351-52 (Fed. Cir. 2008); Caves v.

Sec’y, HHS, 100 Fed. Cl. 119, 132 (2011), aff’d per curiam, 463 Fed. Appx. 932 (Fed.

Cir. 2012) (specifying that each Althen factor must be established by preponderant

evidence). The applicable level of proof is the “traditional tort standard of ‘preponderant

evidence.’” Moberly v. Sec’y, HHS, 592 F.3d 1315, 1322 (Fed. Cir. 2010) (citing de

Bazan, 539 F.3d at 1351; Pafford v. Sec’y, HHS, 451 F.3d 1352, 1355 (Fed. Cir. 2006);

Capizzano v. Sec’y, HHS, 440 F.3d 1317, 1320 (Fed. Cir. 2006); Althen, 418 F.3d at

1278). Although special masters are not bound by the formal rules of evidence

generally applicable in federal courts, they are required to find evidence reliable before

they may consider it. Knudsen v. Sec’y, HHS, 35 F.3d 543, 548-49 (Fed. Cir. 1994)

(Petitioner has the burden to present a reliable and reputable medical theory, which

must be “legally probable, not medically or scientifically certain.”); Daubert v. Merrell

Dow Pharmaceuticals, 509 U.S. 579, 590 (1993) (holding that scientific evidence and

expert opinions must be reliable to be admissible). The preponderance standard

“requires the trier of fact to believe that the existence of a fact is more probable than its

nonexistence.” In re Winship, 397 U.S. 358, 371 (1970) (Harlan, J., concurring)

(internal quotation and citation omitted).

Another formulation of the causation requirement in off-Table cases is the “Can it

cause?” and “Did it cause?” inquiries used in toxic tort litigation. These queries are also

referred to as issues of general and specific causation. Prong 1 of Althen has been

characterized as an alternative formulation of the “Can it cause?” or general causation

query. Prong 2 of Althen, the requirement for a logical sequence of cause and effect

between the vaccine and the injury, has been characterized as addressing the “Did it

cause?” or specific causation query. See Pafford v. Sec’y, HHS, No. 01-165V, 2004 WL

1717359, at *4 (Fed. Cl. Spec. Mstr. July 16, 2004), aff’d, 64 Fed. Cl. 19 (2005), aff’d,

451 F.3d 1352 (2006). Prong 3 of Althen, the requirement that the injury sustained

occur within a medically appropriate interval after vaccination, is subsumed into the

14

Section 13(a)(1)(A). This section provides that petitioner must demonstrate “by a preponderance of the

evidence the matters required in the petition by section 300aa–11(c)(1) . . . .” Section 11(c)(1) contains

the factors listed above, along with others not relevant to this case.

6

other inquiries. Even if a particular vaccine has been causally associated with an injury,

petitioner must still establish facts and circumstances that make it more likely than not

that this vaccine caused the particular injury. Timing may be one of those

circumstances.

Whether a case is analyzed under Althen or the “Can it cause?” formulation,

petitioners are not required to establish identification and proof of specific biological

mechanisms, as “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.” Althen, 418 F.3d at 1280. Petitioners need not show that the

vaccination was the sole cause, or even the predominant cause, of the injury or

condition; showing that the vaccination was a “substantial factor”15 in causing the

condition, and was a “but for” cause, are sufficient for recovery. Shyface v. Sec’y, HHS,

165 F.3d 1344, 1352 (Fed. Cir. 1999); see also Pafford, 451 F.3d at 1355 (petitioners

must establish that a vaccination was a substantial factor and that harm would not have

occurred in the absence of vaccination). Petitioners cannot be required to show

“epidemiologic studies, rechallenge, the presence of pathological markers or genetic

disposition, or general acceptance in the scientific or medical communities to establish a

logical sequence of cause and effect” (Capizzano, 440 F.3d at 1325), but the special

master may certainly consider such evidence when filed. Andreu v. Sec’y, HHS, 569

F.3d 1367, 1379 (Fed. Cir. 2009) (Special masters may consider medical literature and

epidemiological evidence, when it is submitted, in “reaching an informed judgment as to

whether a particular vaccine likely caused a particular injury.”). Causation is determined

on a case by case basis, with “no hard and fast per se scientific or medical rules.”

Knudsen, 35 F.3d at 548 (Fed. Cir. 1994). Close calls regarding causation must be

resolved in favor of petitioners. Althen, 418 F.3d at 1280; but see Knudsen, 35 F.3d at

550 (when evidence is in equipoise, the party with the burden of proof fails to meet that

burden).

In Vaccine Act cases, special masters are frequently confronted by expert

witnesses with diametrically opposing positions on causation. When experts disagree,

many factors influence a fact-finder to accept some testimony and reject other contrary

testimony. As the Federal Circuit noted, “[a]ssessments as to the reliability of expert

testimony often turn on credibility determinations, particularly in cases . . . where there

is little supporting evidence for the expert’s opinion.” Moberly, 592 F.3d at 1325-26.

Objective factors, including the qualifications, training, and experience of the expert

witnesses; the extent to which their proffered opinions are supported by reliable medical

research and other testimony; and the factual basis for their opinions are all significant

15

The Restatement (Third) of Torts has eliminated “substantial factor” in the factual cause analysis. § 26

cmt. j (2010). Because the Federal Circuit has held that the causation analysis in the Restatement

(Second) of Torts applies to off-Table Vaccine Act cases (see Walther v. Sec’y, HHS, 485 F.3d 1146,

1151 (Fed. Cir. 2007); Shyface, 165 F.3d at 1352), this change does not affect the determination of legal

cause in Vaccine Act cases: whether the vaccination is a “substantial factor” is still a consideration in

determining whether it is the legal cause of an injury.

7

factors in determining what testimony to credit and what to reject. Lalonde v. Sec’y,

HHS, 746 F.3d 1334, 1340 (Fed. Cir. 2014) (noting that “as the finder of fact, the special

master was responsible for assessing the reliability of [the expert’s] testimony by looking

for reliable medical or scientific support” (citing Moberly, 592 F.3d at 1324-25)).

Congress contemplated that special masters would weigh and evaluate opposing

expert opinions in determining whether petitioners have met their burden of proof.

Congress clearly specified petitioners’ burden of proof in off-Table cases as the

preponderance of the evidence standard. It directed special masters to consider the

evidence as a whole, but stated that special masters are not bound by any particular

piece of evidence contained in the record.16 In weighing and evaluating expert opinions

in Vaccine Act cases, the same factors the Supreme Court has considered important in

determining their admissibility provide the weights and counterweights. See Kumho

Tire Co. v. Carmichael, 526 U.S. 137, 149-50 (1999); Terran v. Sec’y, HHS, 195 F.3d

1302, 1316 (Fed. Cir. 1999). As the Supreme Court has noted, a trial court is not

required to accept the ipse dixit of any expert’s medical or scientific opinion because the

“court may conclude that there is simply too great an analytical gap between the data

and the opinion proffered.” Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997).

Although special masters are not bound by the formal rules of evidence generally

applicable in federal courts, the Federal Rules of Evidence and cases interpreting them

can guide special masters in their decisions. Daubert, which interpreted Rule 702 of the

Federal Rules of Evidence, provides a useful framework for evaluating scientific

evidence in Program cases. Terran, 195 F.3d at 1316 (concluding that it was

reasonable for the special master to use Daubert to evaluate the reliability of an expert’s

testimony); Cedillo v. Sec’y, HHS, 617 F.3d 1328, 1339 (Fed. Cir. 2010) (noting that

special masters are to consider all relevant and reliable evidence filed in a case and

may use Daubert factors in their evaluation of expert testimony); Davis v. Sec’y, HHS,

94 Fed. Cl. 53, 67 (2010) (describing the Daubert factors as an “acceptable evidentiary-

gauging tool with respect to persuasiveness of expert testimony already admitted . . . by

special masters in vaccine cases”); see also Snyder, 88 Fed. Cl. at 718 (quoting Ryman

v. Sec’y, HHS, 65 Fed. Cl. 35, 40-41 (2005) (special masters perform gatekeeping

function when determining “whether a particular petitioner’s expert medical testimony

supporting biological probability may be admitted or credited or otherwise relied upon”

and as a “trier-of-fact [a special master] may properly consider the credibility and

applicability of medical theories”)). The special master’s use of the Daubert factors to

evaluate the reliability of expert opinions in Vaccine Act cases has been cited with

approval by the Federal Circuit more recently in Andreu, 569 F.3d at 1379 and Moberly,

16

See § 13(a)(1)(A) (preponderance standard); § 13(a)(1) (“Compensation shall be awarded . . . if the

special master or court finds on the record as a whole . . . .” ); § 13(b)(1) (indicating that the court or

special master shall consider the entire record in determining if petitioner is entitled to compensation and

special master is not bound by any “diagnosis, conclusion, judgment, test result, report, or summary”

contained in the record).

8

592 F.3d at 1324. See also Vaughan v. Sec’y, HHS, 107 Fed. Cl. 212, 222 (2012)

(“The Federal Circuit has repeatedly stated that the Special Master may refer to Daubert

to assess reliability of expert testimony in vaccine cases.”). Special masters decide

questions of credibility, plausibility, probability, and reliability, and ultimately determine

to which side the balance of the evidence is tipped. See Pafford, 451 F.3d at 1359.

Bearing all these legal standards in mind, I now turn to the evidence presented in

this case.

III. Medical History.

Most of C.L.’s medical history is not in dispute.17 Although C.L. experienced a

loss of skills at some point between an early intervention evaluation in September 2005

and an evaluation by a neurologist in February 2006, more precise dating is difficult.

Given the wide disparity in reports concerning when she began losing skills, it is unlikely

that the loss of skills was sudden or abrupt. C.L.’s autism diagnosis is not seriously

disputed; she met the diagnostic criteria on two different tests performed by different

specialists in the spring and summer of 2006. Petitioners acknowledge the diagnosis,

but claim that it is the result of an autoimmune encephalopathy as evidenced by the

presence of voltage-gated potassium channel autoantibodies. Whether C.L. showed

improvement in behavior and skills as the result of treatment for an autoimmune

encephalopathy is a matter upon which the parties disagree. Petitioners contend that

any improvement is evidence that the antibodies were responsible (or a marker) for

autoimmune encephalitis and thus evidence that she had encephalitis, not autism per

se. The ultimate basis for their claim for compensation is that the influenza vaccination

triggered an autoimmune condition, a claim that respondent vigorously contests.

I set forth most of C.L.’s history prior to the vaccination in a summarized fashion

while examining therapy records, contemporaneous medical records, and histories

provided to specialists surrounding the regression/loss of skills in more detail. The

records pertaining to her diagnosis and treatment for the VGKC antibodies are also set

forth at greater length.

A. C.L.’s Early Medical History.

C.L. and her fraternal twin sister were born prematurely in late July 2003. There

were initial concerns about C.L.’s oxygen levels after birth and her newborn metabolic

screening test results, resulting in a week in a special care nursery on oxygen, tube

17

The parties identified the following issues as disputed (1) “the extent of C.L.’s pre-existing

developmental delay;” (2) “[t]he onset of C.L.’s neurological condition;” and (3) “[t]he cause of C.L.’s

neurological condition.” Joint Pre-hearing Submission Identifying Issues, filed Jan. 7, 2014, at 1.

9

feedings, and antibiotics before being discharged to home.18 C.L. developed on the

slower side of normal in her first 14 months of life. Pet. Exs. 7, p. 8; 4, p. 50; 13, p. 2; 3,

p. 8; 9, p. 2. She experienced colic, gastroesophageal reflux [“GER”], formula

intolerance, and bronchitis in her first three months of life. Pet. Ex. 3, pp. 10-13.

However, petitioners testified that there were no concerns regarding C.L.’s development

during her first year.19 Transcript [“Tr.”] at 10, 105.

Between October 2003 and October 2004, C.L. was seen for routine illnesses

and received the standard childhood vaccinations, including an influenza vaccination in

October 2004, without any apparent ill effects. Pet. Ex. 3, p. 2; see generally Pet. Ex. 3,

pp. 14-31.

B. Concerns about Developmental Delay.

On October 27, 2004, C.L. was seen for her 15 month well child checkup. She

was described as a “picky eater” and was still taking formula. Pet. Ex. 3, p. 32. The

medical record reflected that problems or concerns about C.L.’s behavior were

discussed, specifically noting a “? [question of] mild GM [Gross Motor] delay – just

starting to walk beyond a few steps.” Id. The examining physician noted a “[p]lan” to

“watch [C.L.’s] GM closely.” Id. Mrs. Lehner testified that “there was really no concern”

at this time and the physician “just wanted to keep an eye on [C.L.] to make sure she

kept progressing in her gross motor skills” and after that C.L. “started walking . . . and

there were no issues at all.” Tr. at 12. In an August 2008 letter to petitioners, C.L.’s

pediatrician, Dr. Judith Snook, noted that C.L. was not using “mama” or “dada”

specifically at this checkup. Pet. Ex. 8, p. 1.20

Behavior concerns were also raised at C.L.’s 18 month well child checkup on

January 27, 2005. Pet. Exs. 3, p. 36; 8, p. 1. This time the pediatrician noted a few

specific problems, including difficulty in getting C.L. to go to sleep and that she was a

dramatic child prone to temper tantrums. Id. However, developmental issues were not

specifically identified as a concern. Id. Her vocabulary contained at least three words,

and the pediatrician and Mrs. Lehner estimated that C.L. had more than 10 words. Id.

She scribbled and used a spoon. Id. Mrs. Lehner testified that C.L. was, and still is, a

“very energetic, very strong-willed child” and that “there were no concerns as far as

18

These facts are derived from histories in C.L.’s treatment records. Neither Mrs. Lehner’s labor and

delivery records nor C.L.’s medical records from her stay in the Special Care Unit following birth were filed

by petitioner. See Res. Pre-hearing Br. at 2, n.1.

19

As C.L.’s primary caretaker, Mrs. Lehner provided testimony that was much more detailed than Mr.

Lehner’s. Accordingly, as petitioners testified consistently with one another, I have focused on Mrs.

Lehner’s testimony.

20

This letter was dated August 4, 2008, three days after the original petition was filed in this case. The

first line of the letter indicated that the letter was intended as a summary of how concerns with C.L.’s

development became apparent, and was prepared at petitioners’ request. Pet. Ex. 8, p. 1.

10

behavior issues” at C.L.’s 18 month well child checkup. Tr. at 13. She was seen again

in February 2005 for an upper respiratory infection [“URI”]. Pet. Ex. 3, p. 37.

C.L. was evaluated again about a month later, this time specifically for

“behavioral concerns,” including temper tantrums that lasted more than one hour,

excessive crying, extreme clinginess, insensitivity “to temperature, sound, touch,” and

restricted food choices. Pet. Ex. 3, p. 38. She was described as an “emotional child.”

Id. Although she slept “ok” and usually took a one hour nap, she was not well-rested.

Id. Appropriate responses to these behaviors were discussed, including recommended

reading about the “strong willed child.” Id. This visit is not mentioned in Dr. Snook’s

August 2008 letter. Pet. Ex. 8, p. 1. Mrs. Lehner testified that the causes of these

behavioral concerns were the URIs that C.L. suffered between October 2004 and

February 2005.21 Tr. at 14. However, no illnesses (other than a pustule on C.L.’s heel)

were listed as concerns on this visit. Pet. Ex. 3, p. 38. Mrs. Lehner testified to her

belief that the physician simply thought C.L. was “a very strong-willed child”, and that

“there were no concerns about her behavior.” Tr. at 14.

At her two year well child checkup on August 9, 2005, C.L. was diagnosed with a

mild language delay. Pet. Ex. 3, p. 41. Doctor Snook, the same physician who saw

C.L. at her 18 month well child visit and who had evaluated the behavioral concerns in

February 2005, again noted behavioral concerns, including occasional temper tantrums.

Id.; Pet. Ex. 8, p.1. She noted that C.L. had less than 20 words, spoke no sentences,

and babble[d]“a lot.” Id. C.L. could not name pictures. Pet. Ex. 8, p. 1. Doctor Snook

also recorded that C.L. had mild constipation and was a picky eater. Pet. Exs. 3, p. 41;

8, p. 1. She referred C.L. for a speech and language evaluation. Id.

Mrs. Lehner testified that when C.L. was two years old, she spoke about 20

words, was walking and running, had no eating concerns, and was a very social child

who used eye contact, words, and gestures to communicate. Tr. at 15-17. Mrs. Lehner

recalled that Dr. Snook had some concerns at this visit because C.L. “was not yet

making full sentences” and suggested that she be evaluated through the school system

where C.L.’s twin sister was receiving speech and physical therapy.22 Tr. at 17-18. Mr.

Lehner testified that he had no concerns about C.L.’s language development at this

time, noting she was clearly “outpacing” her twin sister. Tr. at 107.

21

C.L.’s pediatric records document three visits during this time period for URI symptoms. Pet. Ex. 3, pp.

31, 33, 37.

22

Mrs. Lehner reported that C.L.’s twin had developmental delay as well, and received early intervention

services due to motor and speech delays. Pet. Ex. 9, p. 233. C.L.’s twin sister had a history of significant

delays earlier than C.L. and had features of pervasive developmental disorder [“PDD.”]. Pet. Ex. 7, p. 8.

11

C. Initial Developmental Evaluation.

C.L.’s speech and language evaluation was conducted by the Shakopee Public

Schools in September 2005, with a written report issued on October 12, 2005. Pet. Ex.

5, p. 2. During the evaluation, Mrs. Lehner stated that the reason for the referral was

concern by C.L.’s pediatrician that she was not putting two words together. Id.

C.L. was evaluated using several diagnostic tests, including the Bayley Scales of

Infant Development [“BSID”] and three types of language tests. Pet. Ex. 5, pp. 2-4.

She was classified as “mildly delayed” in cognitive development (id., p. 2), but was

significantly delayed in language (id., p. 4).23 During the in-home evaluation, C.L.

laughed and vocalized, but did not spontaneously use words during play. Id., p. 3. The

only recognizable words uttered during the visit were “mommy” and “bye.” Id. These

observations contrasted somewhat with C.L.’s scores on the Preschool Language

Scale, which showed her expressive and receptive language to be in the low average

range. Id. The most concerning language delay was observed in the evaluation of her

spontaneous language sample. C.L. made 20 “utterances,” only 10 of which were

understood as words; the other 10 were scored as babbling. A child of C.L.’s age

should have been able to make 50 utterances. The only items C.L. could name during

one test were “dog,” “boat,” “apple,” and “eye.” The evaluator commented that C.L.’s

expressive vocabulary was “significantly delayed.” Id., p. 4.

Mrs. Lehner’s impression of C.L.’s performance during this evaluation was that

she was found to be “right on track” in her mental abilities, to have “normal” gross motor

skills (“running, jumping, climbing”) (something not formally evaluated during this

testing), and a “mild language delay.” Tr. at 19-20. She testified that at the time of this

evaluation, C.L. was “using words constantly,” “cleaning up [her] articulation,” and

pairing words “with eye contact, gesturing, [and] pointing.” Id. at 20. This testimony

contrasts with what Mrs. Lehner reported at the time of the evaluation, which was that

C.L. had “about 20 words, and [was] not saying two or more words together in a

phrase.” Pet. Ex. 5, p. 2. Additionally, on a form completed by Ms. Lehner prior to the

evaluation that asked her to list any concerns she had about C.L., Mrs. Lehner wrote

that C.L. “tries to communicate but babbles instead of using words.” Id., p. 9.

C.L. was found eligible for special education services as a child with a language

disorder. Pet. Ex. 5, p. 5. She received a weekly home visit and was eligible to attend

a weekly toddler group and a parent and child group. Id., p. 12. Records of individual

23

During testimony, Dr. Shafrir asserted that C.L.’s language delay was “mild.” Tr. at 143, 145, 208-13.

Although C .L. scored in the low average range on the Preschool Language Scale-4 test, she qualified for

speech and language services because her expressive vocabulary was 2.6 standard deviations below the

norm, and her spontaneous language was 3.0 deviations below the norm. Pet. Ex. 5, p. 5. On the

expressive vocabulary test, she scored below the first percentile. Id., p. 4. Taken together, the language

tests establish that C.L.’s expressive language was significantly delayed.

12

therapy sessions were not filed, but C.L.’s six-month review by the school district was

filed and is discussed in more detail in Part D. 2, below.

D. Allegedly Causal Vaccination and Subsequent Development.

1. Vaccination.

C.L. received an influenza vaccination on November 25, 2005. Pet. Ex. 3, p. 2.

Since no office visit notes were prepared for this visit, it is likely that C.L. was not

otherwise examined or treated that day. Mrs. Lehner testified that C.L. had an

immediate reaction to this vaccination,24 developing a low grade fever and becoming

cranky and irritable. Tr. at 23. Mrs. Lehner indicated that she had been warned that

this type of reaction was a normal side effect of vaccination and she treated C.L. with

Advil for several days, as instructed at her vaccination appointment. Tr. at 23-24. No

subsequent contemporaneous medical record reported any reaction.

2. Post Vaccination Development.

Petitioners claim that C.L. experienced a dramatic developmental regression

after her influenza vaccination. Tr. at 24. However, the formal assessments of her

development during that period do not reflect a sudden regression, but rather a gradual

loss of skills and abilities. Indeed, it was not until February 13-14, 2006, that her

parents became concerned enough about the loss of vocabulary and other symptoms to

request an urgent neurology consultation. Although it is clear that C.L. experienced a

plateau (if not a regression) in her language skills and a significant loss of social and

cognitive abilities between September 2005 and December 2006 (compare Pet. Ex. 5,

pp. 2-5 (initial evaluation) with pp. 22-35 (reevaluation)), the contemporaneous medical

and therapy records do not show a sudden regression on the heels of—or even within a

month of—her influenza vaccination.

Mrs. Lehner testified that over the course of the month following her influenza

vaccination, C.L.’s behavior became much worse, she became withdrawn, and she

began “the rocking, the humming, . . .finger-flicking . . . she kind of went into her own

world.” Tr. at 24.

However, on December 19, 2005, during a speech and language pathology

evaluation at St. Francis Capable Kids [“St. Francis”], C.L.’s parents recounted that they

had become concerned about her speech and language development six months earlier

when she was not gaining new words, was unable to combine words, and most of her

24

In responding to a question from her attorney that contained an incorrect date for this vaccination,

Mrs. Lehner implied that the vaccination occurred on November 21, 2005. Tr. at 23. C..L. received her

vaccination on November 25, 2005.

13

sounds came out as “da-da.” Pet. Ex. 14, p. 2.25 At this evaluation, Mrs. Lehner

reported that C.L. was currently in good physical health, but “has difficulty with her sleep

and has feeding issues.” Id. The background information reflected that C.L.’s

“developmental pattern consists of an overall delay.” Id. Mrs. Lehner also reported that

C.L. communicated largely through gestures and that she and her husband were able to

understand her speech only about 10% of the time. Id. C.L. was frustrated when she

was not understood. Id. None of these concerns were noted as sudden or recent.

The evaluation included the Rosetti Infant-Toddler Language Scale, which

included an assessment of preverbal and verbal areas of communication and

interaction, based on direct observation or elicitation of a behavior or caregiver report.

Pet. Ex. 14, p. 3. C.L.’s pragmatic language skills evaluation reflected that she did not

vocalize to call others, respond to other children’s vocalizations, or attend to her name.

Id. Overall, C.L. showed mastery of language skills primarily at the level of a six to nine

month infant (except for gestures, in which she scored at the 12-15 month level), with

scattered skill mastery from the 15-27 month level. Id. The evaluator concluded that

C.L. had significant delays in expressive and receptive language, and delays in

pragmatic and play skills. Id. Cognitive development was not evaluated. Id., p. 5.

There were no references in the several pages of observations to C.L. rocking,

humming, finger-flicking, or being disengaged from others. The evaluation apparently

included some assessments of her interaction with other children, but it is unclear

whether these were observations by the speech and language pathologist or based on

parental report. Pet. Ex. 14, pp. 3-5. The therapist noted that her play was appropriate

and that C.L. initiated eye contact. Id., p. 6.

C.L. saw Dr. Snook again on December 22, 2005, for concerns about “sleep

problems” and “feeding issues,” some of the same concerns raised at the St. Francis

evaluation three days earlier. Pet. Ex. 3, p. 42. No reactions to or concerns about the

influenza vaccination were reported. This pediatric record reflected that C.L. was

receiving Pediasure to supplement her diet and that she refused many solids. Id. It

noted that she put her hands in her mouth “a lot.” Id. A referral to St. Francis for

feeding issues was discussed at this visit. Id.; Pet. Ex. 8, p. 2. She slept about 10-11

hours per night but would not nap. Id.26 When placed in her crib to nap, she cried and

jumped but refused to sleep. Id. In the evening, she would cry for a minute and then

fall asleep. Id. In her August 2008 letter, Dr. Snook interpreted the next part of the note

as stating that C.L. was awakening “3-4 times at night.” Pet. Ex. 8, p. 2. She would

then cry for 30-90 minutes before returning to sleep. Pet. Ex. 3, p. 42. Neither the

25

Mrs. Lehner testified that the statement that their concerns arose “six months ago [June 2005]” is

inaccurate and that the evaluator must have “rounded up” because the first time she became concerned

about C.L.’s speech was at her two year well child check with Dr. Snook in August of 2005. Tr. at 26-27.

26

In the August 2008 letter, Dr. Snook phrased this as C.L. “stay[ed] in bed for 10 to 11 hours at night,

but was not sleeping very well.” Pet. Ex. 8, p. 2.

14

sleep nor the eating issues were precisely new; both had been reported at various times

during sick and well child visits. See, e.g., Pet. Ex. 3, pp. 32, 36, 38. However, Dr.

Snook thought the sleep problems were a significant departure from C.L.’s previous

sleep patterns (Pet. Ex. 8, p. 2), a point echoed by Mrs. Lehner in her testimony. Tr. at

25.

C.L. had her first speech therapy session at St. Francis on January 4, 2006.

Pet. Ex. 14, p. 7. She put her fingers in her mouth upon entering the session, a

mannerism C.L. reportedly employed when unsure of her environment. Id. She

warmed to the therapist quickly and imitated the words “up,” “baba” for bubbles, and

called her mother by name to get her attention. Id. Eye contact was sporadic but

purposeful. Id. No concerns regarding recent regression or loss of words were noted.

At the next therapy session on January 18, C.L. vocalized two syllables for

“cracker” and “bubbles” and made eye contact with the therapist about 20% of the time.

Pet. Ex. 14, p. 1. She was frequently frustrated, however, with attempts to relate

pictures to the actual item. Id.

On January 20, 2006, Dr. Snook saw C.L. for a URI and her ongoing feeding

problems and referred her to a gastroenterologist. Pet. Exs. 3, p. 43; 8, p. 2. Again, no

concerns regarding regression were noted in the record.

On January 24, 2006, C.L. returned to St. Francis for an occupational therapy

(“OT”) evaluation regarding her feeding issues. Pet. Ex. 14, pp. 9-15. She reportedly

responded “fairly well to all activities presented, but . . . did become agitated at times”

and kept her blanket close throughout most of the session as a self-soothing

mechanism. Id., p. 11. Mrs. Lehner reported that C.L. had a sinus infection and was on

antibiotics, but indicated that C.L.’s behavior during the evaluation was typical of what

she saw at home. Id. Mrs. Lehner shared that she was concerned about the

“significant limitations” in what food C.L. was willing to eat and the poor volume of food

she consumed. Id. The evaluator, occupational therapist Margaret Taylor, found that

C.L. displayed “emerging imitation skills, comprehension of simple one-step directions,

and positive response to routine.” Id., p. 12. However, she also found that C.L. had

“substantial delays in sensory processing skills, oral[-]motor strength and coordination

and decreased muscle tone,” which impacted “her nutritional well-being and overall

health.” Id.

Ms. Taylor concluded that “these delays can, in part, be attributed to [C.L.’s] birth

history and her developmental delays following a period of reportedly normal

development until 2 years of age.” Pet. Ex. 14, p. 12. Doctor Snook’s concern about

C.L.’s gross motor development at 15 months of age was not mentioned. Mrs. Lehner

reported that C.L. “met most of her developmental milestones late” and exhibited “signs

of regression in terms of her communication development at the same time she started

having feeding difficulties around two years of age.” Id., p. 13. Individual feeding

15

therapy was recommended on a weekly basis, as were changes to home feeding

routines. Id., pp. 14-15.

At C.L.’s February 1, 2006 speech session at St. Francis, she did not make eye

contact with her mom, but did hand her bubbles upon request. Pet. Ex. 14, p. 16. She

used the word “no” twice, but did not say “hi” or “bye,” words she had previously used.

Id. She was still having trouble using the picture exchange system (abbreviated as

“PECS” in the therapy records). Id.; see also Pet. Ex. 4, p. 69 (explaining PECS).

At the February 8, 2006 speech session, Mrs. Lehner reported that C.L. was

“doing more lining up of items at home.” Pet. Ex. 14, p. 17. C.L. smiled at and made

eye contact with the therapist during a game, and used the words “bubble” and “quack.”

Id. During her feeding therapy session, which she tolerated for only about 15 minutes,

she made poor eye contact. Id., p. 18. Her response to bath time had reportedly

improved, but she had decreased tolerance for changes in her routine. Id.

Mrs. Lehner’s testimony about the period between the Christmas holiday of 2005

and February 2006 was that C.L. became “a completely different child.” Tr. at 30. The

changes included a loss of previously acquired words, episodes of staring into space,

and repetitive behaviors, such as rocking, humming, and finger flicking. Tr. at 30. Mrs.

Lehner testified that she was troubled by these changes and contacted Dr. Snook in

February 2006 for a consultation. Tr. at 31-32. There is no record reflecting an office

visit, but the telephone records for the pediatric practice reflect that Mrs. Lehner

communicated with the pediatric practice on February 13 and 14, 2006, to voice

concern about C.L.’s “loss of milestones, loss of words.” Pet. Ex. 3, p. 109; see also

Pet. Ex. 8, p. 2 (noting that “therapists had similar concerns” about loss of words, not

talking much, waving or pointing). C.L. was referred to a specific neurologist, Dr. Steve

Janousek, at petitioners’ request for a “sooner appointment.” Id.; Pet. Ex. 7, p. 2.

Apparently, petitioners were already familiar with Dr. Janousek, possibly because C.L.’s

twin had seen him. See Pet. Ex. 7, p. 2.

C.L. demonstrated the use of two signs in lieu of words at the speech therapy

session on February 15, 2006. Pet. Ex. 17, p. 20. She paid attention to the therapist

during the feeding session, and imitated gestures. Id. She vocalized during feeding,

but without any apparent meaning. Id. She used “mommy” once. She would not

imitate new words. Id. She made eye contact during a game, and said “hi” three times.

Id. The therapist noted that C.L.’s attention was better at this session, but reported that

she had staring episodes that were unaffected by calling her name or moving into her

space. Pet. Ex. 17, p. 20. The therapy note indicated that C.L. was going to have a

neurological checkup, as recommended by her physician. Id.

On February 22, 2006, C.L. saw Dr. Janousek for developmental delay and “a

new regression of skills.” Pet. Ex. 7, pp. 2, 8. Petitioners completed a checklist at the

time of the appointment, which included a developmental history. Pet. Ex. 7, pp. 3-6.

16

They reported that C.L. said her first word with meaning and without prompting between

12-16 months of age, but was still not putting two words together. Pet. Ex. 7, p. 4. She

“sometimes” had problems making or maintaining eye contact, difficulty with change or

transitions, and “school problems.” Pet. Ex. 7, p. 4. Presumably the latter reference

was to the speech or occupational therapy C.L. was receiving. They also noted that

C.L. had “always” had problems with outbursts in response to frustration and tended to

be isolated in play. Id. Additionally, they indicated that there had been a worsening of

motor or intellectual skill. Id.

The chart notes from this visit reflected that C.L.” has had a concerning degree of

developmental regression.” Id., p. 8. By history, she had “mild delays” in her

development, but otherwise was doing well. Id. The primary focus had been on C.L.’s

twin sister, who reportedly had significant delays and “some PDD [pervasive

developmental disorder] features.” Id. Doctor Janousek recorded that “[o]ver the last

several months, [C.L.] stopped talking,” developed poor eye contact, exhibited

outbursts, and became more isolated in her play, whereas she was previously reported

to be very social.” Id. No significant decline in motor function was noted. Id.

In comparing Dr. Janousek’s notes to those of the speech therapist at St.

Francis, the reference to C.L. having stopped talking was not completely accurate, as

the therapy records did reflect the use of words. The few words recorded in the

January-February 2006 therapy sessions did not add up to the 20 words C.L. had (as

reported by Mrs. Lehner) during the September 2005 school system evaluation,

indicating a possible loss of language. C.L.’s eye contact was diminished as compared

to the September evaluation as well. The temper tantrums, reported as “outbursts” in

Dr. Janousek’s records, were not new; they had been a subject of concern since C.L.’s

15 month checkup. And, C.L.’s parents had reported the day of Dr. Janousek’s

evaluation that C.L. had “always” engaged in isolated play. The only new symptom

reported to Dr. Janousek was the staring spells, and those were first noted by the

therapist two days after the requested referral to a neurologist.

On neurological examination, C.L. was described as alert, avoidant of eye

contact, exhibiting “significant tactile defensiveness,” and nonverbal. Pet. Ex. 7, p. 8.

Her motor examination and reflexes were normal and she was not ataxic. Id. Doctor

Janousek diagnosed regression, and ordered an MRI,27 EEG,28 genetic testing, blood

tests for lactate, pyruvate, and ammonia, and urine amino and organic acid testing,

tests typically performed to assess the possibility of a mitochondrial disorder. Id., pp. 9-

12. The EEG was performed the same day as the initial visit to Dr. Janousek and,

27

Magnetic resonance imaging (MRI) is “a method of visualizing soft tissues of the body.” DORLAND’S

ILLUSTRATED MEDICAL DICTIONARY (31st ed. 2007) [“DORLAND’S”] at 928.

28

An electroencephalogram (EEG) records the electrical activity of brain cells and is typically performed

“to identify and evaluate patients with seizures.” K. Pagona & T. Pagona, MOSBY’S MANUAL OF

DIAGNOSTIC AND LABORATORY TESTS (4th ed. 2009) [“MOSBY’S LABS”] at 573.

17

although the testing was terminated early, the results were read as normal. Id., p. 10.

Serum lactate and pyruvate levels were normal and the ammonia level was very slightly

below the reference range. Id., pp. 13-14. Urine amino acids were assessed as

essentially normal, as were the urine organic acids. Genetic testing ruled out Fragile X

and Rett syndromes.29 Id., p. 24. The MRI was normal as well. Id., p. 27. Doctor

Janousek diagnosed C.L. with “encephalopathy, other.” Id., p. 23.

According to Mrs. Lehner’s testimony, Dr. Janousek “agreed that [C.L.] exhibited

autistic features,” but he “could not officially diagnose her.”30 Tr. at 33. Mrs. Lehner

further testified that Dr. Janousek felt C.L.’s regression was more pronounced than was

typical and that she exhibited developmental delay.31 Id.

On April 11, 2006, C.L. was reevaluated by the Shakopee Public Schools to

determine her progress in achieving the goals set in October 2005 after the September

evaluation. Since C.L. failed to meet any of the goals set to improve her speech and

language, these goals were adjusted downward. Pet. Ex. 5, p. 20. In view of her

problems with social interaction, goals regarding joint activities were set, to include

increasing eye contact, verbalizing and gesturing greetings, and engaging in joint

activity with another person for short periods of time. Id., p. 18. C.L.’s vocabulary

continued to be limited to about 20 words—the same level reflected in the October 2005

report.32 Id., p. 20.

C.L. was seen by her pediatrician, Dr. Snook, on April 25, 2006, to clear her for

anesthesia for the MRI. Doctor Snook noted that C.L. was experiencing a regression of

skills to include social skills, language, and eye contact. Pet. Ex. 3, p. 45. She also

29

The test interpretation contained a note that reflected an “understanding that this individual has clinical

features that are consistent with a diagnosis of Rett syndrome” and that the “negative results neither

confirm nor rule out the diagnosis of Rett syndrome.” Pet. Ex. 4, p. 15. Rett syndrome is an autism

spectrum disorder that has a known genetic cause. Snyder, 2009 WL 332044, *31, 36, 48. Symptoms

include loss of language and motor skills, as well as some characteristic stereotypic movements

(handwringing). Id. at *36, 42. Other than the complete or near complete lack of language, C.L. did not

present with symptoms indicative of Rett syndrome. Thus, this disclaimer on the laboratory report may

have been standard language and not specific to C.L.’s case.

30

In August 2006, Mrs. Lehner also reported to a developmental pediatrician that Dr. Janousek told her

that C.L. exhibited “autistic features.” Pet. Ex. 9, p. 232.

31

Doctor Janousek’s records did indicate that C.L.’s regression was more pronounced than would be

expected in a typical autism case, but this was at a follow-up visit in May 2006, not at the initial visit. See

Pet. Ex. 7, p. 29.

32

The record indicates “October 2006.” Clearly this was an error, given that Pet. Ex. 5, p. 2 reflects that

the initial evaluation took place in September 2005 and the report was dated in October 2005. Based on

the many concerns about loss of language reflected in other reports and the few words reported by C.L.’s

teachers at St. Francis and in the school system evaluation, it is unlikely that C.L. still had the 20 word

vocabulary reported here.

18

indicated that C.L. had no intelligible words and repetitively placed her hand in front of

her face. Id.

Doctor Janousek evaluated C.L. again on May 30, 2006, and noted that despite

“[e]xtensive evaluation . . . no definable reason for [C.L.’s] developmental regression”

had been found. Id., p. 29. Doctor Janousek described C.L. as having “typical features

of autism” but “a more pronounced developmental regression than one would expect,

given an autism spectrum diagnosis.”33 Id., p. 29. Doctor Janousek also indicated that

C.L. had experienced no further regression in her developmental skills, was alert during

her examination, exhibited some tactile defensiveness, and made some eye contact,

although no language was heard. Id.

3. Formal Autism Diagnosis.

In June of 2006, a psychological evaluation was conducted at Children’s

Hospitals and Clinics of Minnesota. The evaluation was at the request of Drs. Snook

and Janousek “due to concerns regarding the possibility of an autism spectrum

disorder.” Pet. Ex. 4, p. 50. C.L.’s parents reported that their concerns regarding her

language began when she turned two and was not yet putting two words together. Id.

They reported that C.L. began to lose skills (particularly social skills) at two and one-half

years of age (which would have been in late January 2006), and developed feeding

problems in January 2006. Id. Her social functioning had “greatly decreased” as well.

Id. She had difficulty getting to sleep and would often scream for over an hour when put

to bed. Id. Newer symptoms included a loss of interest in others, often seeming to be

in her own world, not acknowledging the presence of others, and the emergence of

repetitive, self-stimulatory behaviors. Pet. Ex. 4, p. 50. C.L. no longer allowed others to

read to her and appeared to resent others imposing themselves on her. Id. She was

described as seldom happy and typically irritable. She reportedly laughed for no

reason. Id.

During testing, C.L. wandered around the room, calmed herself by lying on the

floor with a blanket over her head, made minimal eye contact, banged toys just to hear

a repetitive noise, displayed minimal pointing, and used some single words mixed with

33

Three articles filed by respondent suggest that C.L.’s “pronounced developmental regression” was not

unusual for a child with an autism diagnosis. See S. Rogers, Developmental Regression in Autism

Spectrum Disorders, MENTAL RETARDATION & DEVELOP. DISAB. RESEARCH REV, 10: 139-43 (2004), filed as

Res. Ex. S [hereinafter “Rogers, Res. Ex. S”], at 140 (reporting that a clear developmental loss of

previously acquired skills is well-documented as one of the patterns of regression in ASD); C. Lord, et al.,

Regression and word loss in autistic spectrum disorders, J. CHILD PSYCH. & PSYCHIAT., 45(5): 936-55

(2004), filed as Res. Ex. R [hereinafter “Lord, Res. Ex. R”], at 946 (reviewing literature on loss of words

and noting that almost all children who experienced a loss of words also experienced a loss of social

skills); R. Landa, Diagnosis of autism spectrum disorders in the first 3 years of life, NATURE CLINICAL

PRACTICE NEUROL., 4(3): 138-47 (2008), filed as Res. Ex. EE [“Landa, Res. Ex. EE”], at 141 (observing

that retrospective reviews found regression in 10-50% of those with an ASD diagnosis).

19

gibberish. Pet. Ex. 4, p. 51. She also engaged in visual stimulation by waving her hand

in front of her eyes. Id. Mrs. Lehner testified that C.L.’s abilities at the time of this

testing “were pretty much the same as they were right after she regressed.” Tr. at 36.

C.L. spoke a few words but most vocalizations were just sounds. Id.

Her cognitive skills had improved since the initial administration of the BSID; she

was now functioning at the developmental age of 23 months, but the improvement had

not kept pace with her age. Pet. Ex. 4, p. 51. Because she was older (35 months of

age), her cognitive score dropped from 80 to 52.34 Id. Her score of 41 on the Childhood

Autism Rating Scale [“CARS”] fell within the autistic range. Id., p. 52.

After a thorough evaluation,35 Dr. (Ph.D.) Mary Zielinksi diagnosed C.L. with

significantly delayed cognitive skills, scattered skill development, and significantly

delayed adaptive skills, particularly in language, social functioning, and interaction.

These difficulties resulted in a diagnosis of “pervasive developmental disorder (a.k.a.

autism spectrum disorder).” Pet. Ex. 4, pp. 52, 63.

4. Subsequent Evaluations.

Robert Voight, M.D., performed a developmental pediatric assessment of C.L. at

the Mayo Clinic on August 10, 2006. Pet. Ex. 9, p. 231. By report, C.L. began waving

“bye-bye” at just over one year of age, but then stopped and currently used the gesture

only with prompting.36 Id. She began using “mama” and “dada” at 12-18 months of age

specifically to refer to her parents and had never lost this skill.37 Id. By two years of

age, she used between 20-25 words, but at the time of the assessment, she used only

two or three words spontaneously. Id. Her pediatrician first became concerned about

34

Doctor Shafrir described this decline in the cognitive score on the BSID when compared to C.L.’s score

on the first administration of the BSID as a “profound regression” adding that “you can’t have a better

example of regression.” Tr. at 150. Rather than showing a loss of skills—the usual definition of

regression in the context of ASD—the test components showed that C.L. had acquired skills as she aged,

but not at the rate expected for a typically developing child. Doctor Shafrir did not comment on the third

administration of the BSID in which C.L.’s cognitive abilities were scored as 90, within the normal range.

Pet. Exs. 9, p. 232; 5, p. 24. In a re-evaluation by Shakopee Public Schools on December 5, 2006, the

evaluator commented on these discrepant scores by noting that C.L.’s symptoms could be highly

variable. Pet. Ex. 5, p. 24. Doctor Renaud, who first treated C.L. for the VGKC antibodies discovered in

2008 commented that C.L. had good days and bad days as well. Pet. Ex. 9, p. 3.

35

The evaluation included interviews with petitioners, C.L.’s speech pathologist, the evaluations for

speech and occupational therapy performed by St. Francis staff and the school district (all discussed

supra), and the test results from these evaluations as well as administration of additional tests, including

the CARS. Pet. Ex. 4, p. 51.

36

Mrs. Lehner did not indicate when C.L. lost this skill.

37

Doctor Snook’s letter suggests that C.L. began using these words with specificity between 15-18

months of age. Pet. Ex. 8, p. 1.

20

her development when she was two years old but not yet combining words. Id., p. 232.

C.L. learned to indicate body parts before the age of two and never lost this skill. Id., p.

231. She was able to follow single-step commands without gestures, but had never

mastered two-step commands. Id. Her language acquisition stopped between the ages

of 24 and 30 months of age. Mrs. Lehner indicated that she first became concerned

about C.L.’s social and behavioral interactions when C.L. was around the age of two

and one-half.38 Id., pp. 231-32. Sometime thereafter, C.L began engaging in

stereotypic behavior and repetitive running in circles. Id., p. 232.

Prior to Dr. Voigt’s assessment, C.L. was tested on August 4, 2006, by a child

psychologist at the Mayo Clinic. Pet. Ex. 9, p. 232. One of the tests performed was the

BSID, the same test performed by the school system in September 2005, and by Dr.

Zielinksi at Children’s Hospitals and Clinics of Minnesota in June 2006. C.L.’s cognitive

function score on the September 2005 test was 80 (with 100 being average and a

standard deviation of 15). See Pet. Ex. 5, p. 2. Her score in June 2006 was 52. See

Pet. Ex. 4, p. 51. In the August testing, her cognitive functioning score had risen to 90,

placing her within the average range, but she scored well below the norm in social-

emotional and adaptive functioning. Pet. Ex. 9, p. 232. Testing specific for ASD was

performed using the Autism Diagnostic Observation Schedule [“ADOS”]. C.L.’s

communication score was 5, exceeding the autism cutoff of 4, and her ADOS social

interaction score was 14, exceeding the cutoff of 7. Id. Her overall score of 19

significantly exceeded the autism cutoff of 12. Id.

At this visit, Dr. Voigt diagnosed C.L. with autism. Pet. Ex. 9, pp. 234-36. He

noted concerns about regression in speech and language development at two years of

age, with “persistent discrepant and disproportionate delays in her speech and

language development relative to her nonverbal, visual problem solving and gross

motor development over time.” Id., p. 234. He also diagnosed her with developmental

dysphasia/communication disorder. Id., pp. 236-37.

She was seen again at the developmental pediatric clinic at Children’s Hospitals

and Clinics of Minnesota on August 15, 2006 “to discuss medical and development[al]

issues related to autism.” Pet. Ex. 4, p. 60. By history, C.L. was colicky and irritable as

an infant, in contrast with her twin sister, who was described as “laid back.” Id. C.L.

had early problems with reflux, and was reported to be a “high need” infant who had

tantrums with little provocation. Id. Mrs. Lehner reported that C.L. walked at 15 months

of age, began combining words at two years of age,39 and had adequate social skills.

Id. Mrs. Lehner indicated that she and her husband began to be concerned in

December (referring to December 2005). Id. C.L.’s language was described as “mainly

38

C.L. would have been two and one-half years old in late December 2005.

39

Once again, Mrs. Lehner’s recall was imprecise, as, at two years of age, C.L. was referred to early

intervention services precisely because she was not combining words.

21

gibberish and squeals.” Id. She had a couple of words and would say “no.” Id. She

was reported to understand what was said to her. Id. Mrs. Lehner also described

repetitive behaviors, including running in clockwise circles and putting her hand over her

right eye. Id. Additionally, C.L. occasionally walked on tiptoes, enjoyed tactile

simulation,40 and had difficulty with sitting and having a book read to her. Id.

On examination, C.L.’s height and weight were both reported as greater than the

50th percentile, and she was observed to have coarse facial features and mildly

flattened affect. Pet. Ex. 4, p. 61. She did not seek assistance, but engaged in self-

directed activities. Id. She spun a puzzle, ran back and forth, put her right hand to her

face at times, and had some high pitched vocalizations. Id. Although she had a stable

walk, she could not jump on command or throw or catch a ball. Id. She was able to

point at pictures in a book and stack six blocks, but could not identify colors or count.

Id. Mrs. Lehner asked for and received information about supplements and other

supports.41 Id.; see also id., p. 83.

Prior to this appointment, C.L.’s early childhood special education teacher

completed a questionnaire about C.L.’s abilities and performance to be used during the

August 15 evaluation. Pet. Ex. 4, p. 68. She identified C.L.’s ability to pick up on ideas

presented and to follow a schedule as strengths, but found her cognitive,

communication, and social skills, along with her sleep and feeding problems, to be

areas of concern. Id., p. 69. She described C.L. as withdrawing from other children and

adults. Id., p. 70. Goals for C.L.’s new IEP were to include increasing her

communication (through pictures, words, or signs), social interaction, and problem

solving (cognitive) skills, as well as working on sensory integration. Id. In response to a

question about progress, she noted that C.L. had begun using PECS. Id. Also, C.L.

was sharing eye contact and laughter when she enjoyed an activity. Id. The teacher

wrote that beginning in April, she had begun thinking that C.L. needed much more time

in therapy as well as more peer involvement time. Id. She noted that she had

suspected for some time that C.L. might have ASD, as C.L. exhibited many ASD

characteristics. Id., p. 71.

The parent questionnaire completed for this evaluation reflected that C.L.’s

parents first became concerned about her lack of verbal and social skills, lack of eye

contact, and poor eating and sleeping when C.L. was about 27 months of age. Pet. Ex.

4, p. 72. C.L. was 27 months of age in October 2006, around the same time the school

system completed C.L.’s initial evaluation. On the form, C.L.’s parents noted a loss of

40

Based on reports of tactile defensiveness, this likely referred to C.L.’s desire to touch different textured

items, such as books with a tactile focus, rather than a desire to be touched, tickled, or otherwise

stimulated by the touch of others. Pet. Ex. 5, p 26 (Shakopee Public Schools’ Evaluation of December 5,

2006, showed C.L. to be seeking books with tactile themes).

41

Doctor Voigt had cautioned against the use of alternative treatments for autism, including dietary

supplements. See Pet. Ex. 9, p. 236.

22

verbal and social skills, and described her as withdrawn, easily frustrated, and prone to

temper tantrums. Id., pp. 76-77. They reported that the regression had occurred about

six to seven months prior to this visit. Id., p. 77. This would place the onset of

regression in the January-February 2006 time frame (assuming the form, which is

undated, was completed in late July or early August in preparation for the August 15

appointment).

Doctor Snook saw C.L. for her three year well child visit on August 18, 2006, and

reported that she had been diagnosed with autism, but was “sleeping better, [had] fewer

tantrums, [and] less extreme behavior.” Pet. Ex. 3, p. 47.

C.L.’s occupational therapist at St. Francis reported on October 18, 2006, that

C.L. demonstrated “increased participation, cooperati[on], tolerance, and independence

with activities,” as well as “increased eye contact.” Pet. Ex. 14, p. 115.

A reevaluation of C.L. by the Shakopee school system took place on December

5, 2006. Her special education teacher reported that she had limited vocabulary, with

three words used spontaneously, but not consistently or frequently. Pet. Ex. 5, p. 22.

She was beginning to use the picture exchange system, but was not imitating words.

Id. Any eye contact was fleeting. Id., p. 23. She played by herself in the classroom

and did not show any awareness of her twin sister there. Id. She did not use toys

functionally and did not demonstrate any pretend play. Id. Mrs. Lehner shared that C.L.

“appeared to regress in her skills approximately around December of 2005.” Id., p. 23.

She and Mr. Lehner noted the loss of social and verbal skills. Id.

Prior to this evaluation, C.L. was retested with many of the same testing

instruments used in September 2005. Although the school system did not re-administer

the BSID, the evaluators compared C.L.’s initial September 2005 score with the June

2006 test performed by Minneapolis Children’s Hospital (scored as 52) and the August

2006 test performed at the Mayo Clinic (scored as 90). Pet. Ex. 5, p. 24. The

evaluation team noted the “great variability or inconsistency” in these test scores. Id.

Her teacher commented that it was difficult to assess C.L.’s cognitive skills because of

her communication delays. Id. She was unable to perform most tasks on the Hawaii

Early Learning Profile at the 36 month level. Id. Her receptive vocabulary was scored

at 80, with 100 being the mean score and a standard deviation of 15, placing her in the

9th percentile. Id., p. 25. Her expressive vocabulary was not scored, as she did not

identify any pictures. Id. In summarizing C.L.’s speech and language, the evaluators

noted that she had decreased eye contact, no verbal communication in the classroom

setting, was avoidant of physical proximity to other children and adults, and had

difficulty initiating or responding to joint attention and reciprocal social communication.

Id., p. 26.

C.L. was observed by an ASD consultant for the school district as part of the

evaluation. Pet. Ex. 5, pp. 31-33. The observations were scored against a school

23

system checklist for ASD eligibility, and C.L. was found eligible for special education

services as a student with ASD and also required occupational and speech therapy.

Id., p. 33.

Doctor Janousek evaluated C.L. again on January 23, 2007 and found that she

had “made slow gains in development” since her last appointment in May 2006,

including “some gains in eye contact and language development.” Pet. Ex. 7, p. 36.

Mrs. Lehner testified that C.L. began to receive ABA therapy in January 2007, after an

extended time on the Minnesota Autism Center’s waiting list. Tr. at 37-38. The therapy

was recommended by Dr. Janousek. Tr. at 35.

C.L. continued to be seen by Metropolitan Pediatric Specialists throughout 2007

and 2008 for various routine illnesses, including URIs, chronic cough, rhinitis,

constipation, and thrush. See generally Pet. Ex. 3, pp. 53-70. She was also seen at the

University of Minnesota Children’s Hospital-Fairview in 2007-08 for a variety of testing

and treatment, mostly related to potential allergies. See generally, Pet. Ex. 6, pp. 1-87.

Doctor Janousek examined C.L. on September 26, 2008 and found that, while

she “has received ABA therapy and is making some progress, . . . she continues to

have profound neurodevelopmental deficiency.” Pet. Ex. 7, p 51. Doctor Janousek

found that C.L. “continued to exhibit autistic features,” had experienced a “pronounced

neurodevelopmental regression at one point,” and “has a twin who also has autistic

features, but is higher functioning.” Id. He referred C.L. for an evaluation with Dr.

Renaud at the Mayo Clinic, as Mrs. Lehner sought further evaluation into the cause of

C.L.’s developmental regression. Id. Precisely why he selected Dr. Renaud was not

clearly stated in the record of his referral but, as discussed below in Part E, Dr. Renaud

was engaged in research into voltage-gated potassium channels and autoimmune

encephalopathy, and Dr. Janousek may have been aware of this research.

E. Voltage-Gated Potassium Channel Antibodies: Testing and Treatment.

1. Background Information.

According to respondent’s expert, Dr. Dalmau, autoimmune encephalitis—C.L.’s

appropriate diagnosis, according to petitioners—was discovered in 2005-07. Tr. at 297;

see also J. Dalmau, et al., Clinical experience and laboratory investigations in patients

with anti-NMDAR encephalitis, LANCET NEUROL. 10: 63-74 (2011), filed as Pet. Ex. 16b

[hereinafter “Dalmau, Pet. Ex. 16b”] (explaining how various forms of autoimmune

encephalitis came to be recognized as diagnostic entities); M. Gable, et al., The

Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That

of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis

Project, CLINICAL INFECTIOUS DISEASES, 54(7): 899-904 (2012), filed as Pet. Ex. 16a

[hereinafter “Gable, Pet. Ex. 16a”], at 899 (discussing a novel form of autoimmune

24

encephalitis first reported in 2007 (anti-NDMAR encephalitis)).42 In another article, Dr.

Dalmau was credited with being the first to describe limbic encephalitis associated with

anti-NMDAR antibodies. See T. Hung, et al., Anti-N-Methyl-D-Aspartate Receptor

Encephalitis, PEDIATR. AND NEONATOL., 52: 361-64 (2011), filed as Pet. Ex. 16c

[hereinafter “Hung, Pet. Ex. 16c”], at 361.

The discovery that some previously idiopathic forms of encephalitis were

attributable to autoantibodies produced as the result of tumors (paraneoplastic

syndromes) or from unknown causes generated considerable research.43 Doctor

Angela Vincent’s laboratory in England, the Mayo Clinic in Minnesota, and Dr. Dalmau

were major contributors to the growing body of information filed as exhibits in this

case.44 The idea that autoantibodies could be responsible for otherwise idiopathic forms

of encephalitis began to encompass other newly identified antibodies in the absence of

tumors. According to Dr. Dalmau, voltage-gated potassium channel antibodies were so

named in a study performed about 16 years prior to the hearing. Tr. at 301. They

eventually became suspects as causal of some forms of encephalitis, based in part on

work done at the Mayo Clinic.45

In 2001-07, the Mayo Clinic’s Neuroimmunology Laboratory began widespread

autoantibody screening of patients suspected of having an autoimmune neurological

disorder, as a part of a prospective clinical study. See Tan, et al., Clinical spectrum of

voltage-gated potassium channel autoimmunity, NEUROL., 70(20): 1883-90 (2008), filed

as Pet. Ex. 10i [hereinafter “Tan, Pet. Ex. 10i], at 2.46 Out of more than 130,000 serum

42

Doctor Dalmau was a co-author of this study, which reported findings of the California Encephalitis

Project, an entity established to study encephalitis and its causes. Anti-NDMAR encephalitis was first

reported in 2007 and later discovered to be “a significant cause of encephalitis in certain age groups.”

Gable, Pet. Ex. 16a at 899-900.

43

Doctor Gorman’s testimony reflected that body of research has continued to grow. He testified that

since July 16, 2012, around the time he authored his second report in this case, about 50 new journal

articles on voltage-gated potassium channel antibody encephalitis had been published. Tr. at 469.

44

Of the medical journal articles filed as exhibits, Dr. Vincent was a contributor or senior researcher on at

least nine articles; Drs. Renaud and McKeon (both of whom treated C.L.) on at least three articles, and

Dr. Dalmau a contributor to or senior researcher on at least eight articles. Doctor Vincent is not a

practicing physician. However, she is a well-known researcher in the field of autoimmune

neuroimmunology who has published with Dr. Dalmau. Tr. at 382, 448.

45

As discussed in more detail later in this decision, Dr. Dalmau testified at some length that only certain

subtypes of the so-called VGKC antibodies, with antibodies against specific proteins, are pathogenic or

disease-causing, and that limbic encephalitis, which had been attributed to VGKC antibodies was actually

caused by other autoantigens. See generally, Tr. 300-20; Pet. Ex. J at 7-9 (Dr. Dalmau’s expert report);

Dalmau, Pet. Ex. 16b, at 63 (noting that leucine-rich, glioma-inactivated 1 (LGI1) is a synaptic antibody

“which is the main autoantigen of limbic encephalitis previously attributed to voltage-gated potassium

channels”).

46

Ordinarily, I cite to the page numbers of the article itself, rather than the page numbers assigned by the

party filing the medical journal article, in order to allow those reading the decision who do not have access

25

samples, 80 patients (with a median age of 65) were found to have VGKC

autoantibodies. Additional information for 72 of the 80 patients was obtained. Sixty of

the patients had diagnoses which included inflammatory or neurodegenerative

disorders, Creutzfeldt-Jakob disease [“CJD”],47 recurrent transient amnesia, and several

other psychiatric disorders. Id., p. 5. Cognitive impairment was the most common

neurological complaint. Id., p. 6.

Doctors Renaud and McKeon, two of C.L.’s treaters, were co-authors of an

article discussing documentation of VGKC antibodies in children. C.L. was one of the

12 children discussed in the article as positive for the VGKC antibodies. C.L. was

Patient No. 11 in the report. Tr. at 398-99; Dhamija, Pet. Ex. 11c. This article is

discussed in more detail in Section V.B.1.b.(2)(b), below.

2. Referral to Mayo Clinic Child and Adolescent Neurology.

Mrs. Lehner testified that Dr. Janousek referred C.L. to Dr. Renaud at the Mayo

Clinic because her regression was “more pronounced than a typical autistic regression.”

Tr. at 40. Doctor Renaud, a pediatric neurologist, examined C.L. on October 20, 2008.

She found C.L. to be “a 5-year-old girl with a history of normal early development and

subsequent regression with a diagnosis of autism.” Pet. Ex. 9, p. 4. Doctor Renaud

noted that Mrs. Lehner “feels that the regression followed an influenza vaccine.” Id.

Doctor Renaud ordered a number of laboratory tests as part of her evaluation. Id., pp.

4-5. She diagnosed C.L. with “[d]evelopmental regression with autistic features” and

“[p]ossible coarsening of the features, rule out storage disorder.” Id., p. 1.

The history of onset of C.L.’s regression reported at this visit was somewhat

different from the histories appearing in more contemporaneous records and histories

provided by Mrs. Lehner at around the time of the autism diagnosis. Mrs. Lehner

reported that after the influenza vaccination in November 2005, C.L. developed self-

stimulatory behaviors in December, including rocking her body and humming—reported

behaviors that do not appear in any of the therapy or medical records from December

2005 or January 2006. Pet. Ex. 9, p. 2. Decreased eye contact and flicking her fingers

in front of her eyes were also reported as occurring prior to the loss of words. Id. At the

December 2005 St. Francis evaluation, the therapist noted that C.L. initiated eye

contact, but one can infer some loss of eye contact from contemporaneous therapy

records from January and February 2006. Pet. Ex. 14, pp. 1, 6-7, 16. The finger

flicking was not reported during this time. Some stereotypic behaviors were reported,

including placing her hand in front of her face (April 2006) (Pet. Ex. 3, p. 45) and putting

to the exhibits to follow the citations. The copy of the article filed does not contain page numbers integral

to the article. Therefore, for this exhibit, citations are made to the exhibit page numbers assigned by

petitioners, which are found at the bottom of each page.

47

A variant of CJD is caused by the same agent that causes bovine spongiform encephalopathy or “mad

cow disease.” DORLAND’S at 538, 622.

26

her hands in her mouth (December 2005) (Pet. Ex. 3, p. 42). Mrs. Lehner indicated at

the St. Francis evaluation that C.L. put her hands in her mouth when she was unsure of

her environment, suggesting that this mannerism was not of recent origin. Pet. Ex. 14,

p. 7. Waving her hand or fingers in front of her eyes was not reported until June 2006.

Pet. Ex. 4, p. 51. Although Mrs. Lehner did not provide Dr. Renaud a specific time

period for when the loss of social skills and affectionate behavior were first observed,

the contemporaneous records indicate that a regression of C.L.’s social skills was first

reported in February 2006. Pet. Ex. 7, p. 8.

Mrs. Lehner also reported at Dr. Renaud’s evaluation that C.L. then had

approximately 50 words or approximations of words, but rarely combined two words.

Pet. Ex. 9, p. 3. She could follow simple one-step commands. Id. C.L. had bad and

good days, but had no new regressions. Id. She learned slowly and made gains, but

the gap between C.L. and her peers was widening. Id. Intelligence testing in January

2008 had placed her IQ at 70. Pet. Ex. 9, p. 3.

Other reported symptoms included flicking her hands,48 humming, galloping, and

teeth grinding. Pet. Ex. 9, p. 3. She reportedly had “hypotonia since the regression,”

fell asleep well, was rested in the morning, and did not nap. Id. The number of

nighttime awakenings had improved in the past six months. Id.

On examination, C.L. was noted to be “mildly coarse-appearing,” with acne,

bilateral ear pits, slightly coarse facial features, bushy eyebrows, coarse thin hair, mild

hypotonia with good strength and symmetric deep tendon reflexes. Pet. Ex. 9, p. 4.

Doctor Renaud noted that Mrs. Lehner “felt that the regression occurred following a flu

vaccination” and had brought with her to the appointment “a number of items from the

internet” regarding autism and developmental regression, which Dr. Renaud reviewed

with the family. Id.

Doctor Renaud proposed a battery of tests. Because C.L.’s regression was

described as “sudden,” a “paraneoplastic antibody panel” was ordered “to ensure that

there are no antibodies against the brain which could represent a treatable autoimmune

disorder.” Pet. Ex. 9, p. 5. This panel encompassed the testing for VGKC antibodies to

determine if C.L. had experienced autoimmune encephalitis.49

48

This appears to be the first report of C.L. “flicking” her hands, but this does not seem to be materially

different from the “finger flicking” previously reported. Such stereotypic mannerisms are common in

children diagnosed with ASD. See Landa, Res. Ex. EE at 138, 141 (discussing stereotypical behavior in

ASD).

49

The test results appear at Pet. Ex. 9, pp. 9-16. As Dr. Renaud did not comment on any of the results

other than the VGKC antibodies, presumably none of the testing raised any diagnostic concerns.

27

3. Diagnosis of VGKC Antibodies and Possible Autoimmune Encephalitis.

On November 17, 2008, Dr. Renaud saw C.L. for a follow-up visit after C.L.’s

laboratory tests indicated in October 2008 that C.L. had an abnormal level of “antibodies

to neuronal voltage-gaited potassium channels.” Pet. Ex. 9, p. 7. Prior to this visit, C.L.

had been placed on prednisolone to suppress any ongoing immune response. Pet. Ex.

9, p. 7. Increased appetite and thirst along with flushed cheeks were reported. Id.

There had been no dramatic changes in C.L.’s behavior while on this steroid, but C.L.

may have had an increase in eye contact, both as reported by C.L.’s parents and as

observed by Dr. Renaud. Id.

During the visit, Dr. Renaud “discussed the function of potassium channels” in

detail with petitioners. Pet. Ex. 9, p 7. She noted that “it is unclear at this time whether

this is the cause of her developmental regression and autism,” but as the antibodies are

“a potentially treatable cause of deterioration, we will treat this as an autoimmune

disorder.” Id. Although no significant change in C.L. was seen with the 18 days of

prednisolone treatment, Dr. Renaud indicated that, in view of the three years since

C.L.’s deterioration, a response to treatment might not be seen for “several months.” Id.

Her plan was to continue with prednisolone50 to suppress “the ongoing immune

response” and intravenous immunoglobulin [“IVIG”] to “hopefully remove the

antibodies.” Id., pp. 7-8. She revised her diagnosis of C.L. to include neuronal voltage-

gated potassium channel antibodies with possible autoimmune encephalopathy, in

addition to the global developmental delay and autistic features in her earlier

diagnosis.51 Id., p. 8

4. Treatment for VGKC Antibodies and Response.

a. Petitioners’ Assertions.

From October 2008 through the time of the hearing, C.L. was treated, more or

less continuously, for presumed autoimmune encephalopathy or encephalitis, based on

the presence of high levels of VGKC antibodies.52 Mrs. Lehner testified that C.L.

50

The text of Dr. Renaud’s notes in the Impression/Report/Plan section indicated in one sentence that

C.L. was taking prednisolone, and in a later sentence that she was taking prednisone. The “Current

Medications” section indicated that she was taking prednisolone. Pet. Ex. 9, p.7. A telephone message

from Mrs. Lehner to Dr. Renaud on November 25, 2008, reflected that C.L. had been on prednisone for a

month or so, and was reporting side effects. However, her medication listing referred to prednisolone.

51

In February 2009, Dr. Renaud changed C.L.’s diagnosis from possible to probable autoimmune

encephalopathy, with the global developmental delay and “autistic features” diagnoses unchanged. Pet.

Ex. 9, p. 26

52

It does not appear that C.L. received any treatment for her VGKC antibodies between April 2010 and

November 2011. Pet. Exs. 6, p.128 (noting last rituximab treatment in April 2010); 9, pp. 118-19

(resuming treatment in late November 2011).

28

exhibited “gains” while on treatment, but suffered some side effects. Tr. at 43-44. By

2010, C.L. was making “slow and steady gains,” but was still globally developmentally

delayed. Tr. at 46. Mrs. Lehner testified that in the fall of 2011 she began to see

improvement in C.L.’s “attending” (i.e., ability to pay attention and observe her

environment and imitate others) after C.L. resumed treatment with Dr. Renaud (which

occurred in September 2011, Pet. Ex. 9, p. 81) and started a higher dose of the steroid

prednisolone. Tr. at 48. C.L. made further improvements in her behavior after the

dosage was increased in March 2012. Tr. at 48-49. Mrs. Lehner testified that at the

time of the hearing [January 28, 2014], C.L. was able to make requests with eye

contact, label things, seek out affection without prompting, read words, write letters, and

respond to two step commands. Tr. at 53-55. She conceded that C.L. was still not able

to read sentences and that her articulation needed to be “clean[ed] up.” Tr. at 54. Mrs.

Lehner testified that C.L. received special services in an autism classroom and ABA

therapy at home on a part-time basis during the school year and full-time during the

summer. Tr. at 54-56. A more objective assessment of C.L.’s level of performance is

found in C.L.’s school records during 2009-11 and December 2012-March 2013, see

generally Pet. Ex. 5, pp. 45-266, portions of which are discussed in subsections b and f,

below.

b. Initial Treatment at Mayo Clinic and Response.

C.L.’s initial treatment, from October 2008 through June 2009, was provided by

Dr. Renaud. C.L. was treated with a steroid (prednisolone) and an immune suppressant

drug (CellCept)53 to suppress production of the VGKC antibodies, and with intravenous

immunoglobulin [“IVIG”] therapy to remove the antibodies from her system. Steroid

therapy began in late October 2008, but due to side effects reported by her parents,54

she was weaned off prednisolone beginning in January 2009. See Pet. Ex. 9, pp. 7

(beginning treatment), 22 (discussion about discontinuation of prednisolone due to side

effects and lack of any significant improvement). In February 2009, CellCept was

substituted, initially at a low dose (id., p. 26), but when the dose was substantially

increased in April 2009 (id., p. 36), severe side effects ensued55 and she was abruptly

53

“Mycophenolate (CellCept) is used with other medications to help prevent transplant organ rejection

(attack of the transplanted organ by the immune system of the person receiving the organ) in people who

have received kidney, heart, and liver transplants. . . . It works by weakening the body's immune system

so it will not attack and reject the transplanted organ.” U.S. National Library of Medicine, MedlinePlus,

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601081.html (last visited July 9, 2015).

54

Mrs. Lehner reported that C.L. experienced sleep disturbances, became very clingy, and made a new

noise when crying or shouting. Pet. Ex. 9, p. 19. She was advised that prednisolone is known to often

cause behavioral disturbances and restless sleep, but IVIG was unlikely to cause such side effects. A

reduction in the dose of prednisolone was suggested. Id. The family temporarily reduced the dose, but

observed no changes in her behaviors. Id., p. 20.

55

See Pet. Ex. 9, pp. 39, 41-43 (telephone calls and office visits reporting significant side effects,

including incontinence and a facial rash from CellCept). Doctor Renaud consulted a rheumatologist who

recommended stopping the treatment, as incontinence was a recognized side effect of CellCept. Id., p.

29

taken off the drug (id., pp. 39, 41-43). IVIG therapy began in November 2009, initially

on a monthly basis, but when therapy with CellCept ended, the IVIG schedule was

increased to every two weeks beginning in April 2009. Id., pp. 35-36.

In mid-April 2009, C.L.’s parents indicated that they were not sure if they wanted

to continue with the treatment for the VGKC antibodies, including IVIG and medications.

Pet. Ex. 9, p. 42. However, at a visit near the end of April 2009, they agreed to try three

more IVIG infusions at two week intervals. Id., p. 46. On July 2, 2009, C.L.’s parents

notified Dr. Renaud that they were stopping IVIG therapy. Id., p. 61.56

During her treatment, C.L.’s blood was drawn regularly to measure the levels of

VGKC antibodies in her system. Antibody levels fluctuated over the course of

treatment, but remained persistently abnormal. Pet. Ex. 9, p. 106.

Doctor Renaud’s treatment records, including parental reports and her own

observations, reflect overall improvement in C.L.’s behavior and symptoms; however,

the improvements did not appear to correspond to the varying antibody levels measured

throughout her treatment.57 Although parental reports at most of the appointments

42. The incontinence improved when CellCept was stopped, but some problems persisted as of April 29,

2009. Id., p. 45.

56

C.L.’s parents thought the IVIG treatment might be causing some side effects as well. In February

2009, Mrs. Lehner called Dr. Renaud’s office to report that C.L. was being very clingy and more irritable.

Pet. Ex. 9, p. 27. This behavior persisted through March 5, 2009. Id., pp. 29, 32 (telephone calls

concerning behaviors they thought might be related to IVIG treatment). However, it appears that the lack

of any real improvement may have contributed to this decision. See id., pp. 58-59 (Mr. Lehner’s

assessment of C.L.’s progress after being out of the country for a period of time).

57

A normal potassium channel antibody level is less than 0.02 according to the Mayo Clinic’s laboratory

reports. See, e.g., Pet. Ex. 9, p. 106. C.L.’s antibody levels fluctuated over time, as did her behavior and

skills; however, there was no consistent correlation between low antibody levels and improved behavior

or, conversely, between high antibody levels and poor behavior or loss of skills. On January 8, 2009

C.L.’s antibodies had dropped to 0.78 (down from 1.69 on November 18, 2008), but there was no

significant change in her behavior reported at her January 7, 2009 doctor visit. Pet. Ex. 9, pp. 22-23,106.

Improvement was reported at the February 18 visit, although C.L.’s antibodies had risen to 0.94 as

measured on February 19, 2009. Pet. Ex. 9, pp. 26, 106. On April 15, 2009, C.L.’s antibodies were 1.74

and Mrs. Lehner reported that she thought C.L. was regressing (although this regression was attributed to

C.L.’s use of CellCept). Pet. Ex. 9, pp. 39-42, 106. On May 14, 2009, C.L.’s antibodies measured 1.18

and she was reported to be doing well and talking more. Pet. Ex. 9, pp. 50, 106. On August 26, 2009,

C.L.’s VGKC antibody level was up to 1.82 after not having IVIG for two months and she was reported to

have greater understanding and to be more focused. Pet. Ex. 9, pp. 63,106. On February 18, 2012,

C.L.’s VGKC antibodies measured 0.92, up from 0.31 on January 21, 2012, and C.L. was reported to

have experienced some gains at her March 7, 2012 doctor’s visit. Pet. Ex. 9, pp. 127-28. On July 26,

2012, C.L.’s antibodies were measured at 0.56, slightly up from 0.44 on May 17, 2012, and she was

reported to be “having some tantrums and aggressive behavior” although her “skills, language, and

cognitive abilities” remained stable. Pet. Ex. 9, pp. 183, 141.

30

included some area in which C.L. had improved,58 other evidence suggests that the

improvements may not have been as substantial as reported. At the end of June 2009,

just prior to the July 2, 2009 decision to stop IVIG treatment, Mr. Lehner was out of the

country for a period of time, which was variously reported as three weeks and three

months. Upon his return, he commented that he thought C.L. was vocalizing more, but

had not noticed any other specific changes. Pet. Ex. 9, p. 58. Her eye contact with

family members was described as “reasonable.” Id.

In March 2009, C.L. received an assessment of her progress by a psychologist.

See Pet. Ex. 5, p. 78. Her scores on the Vineland Adaptive Behavior Scale were largely

in the 1st percentile or below, and her score on the ADOS was again in the autistic

range. Id.

Additionally, C.L.’s school records from the period of March through November

2009 (including a classroom observation and two IEP reviews) do not reflect the

increased vocabulary and significantly improved eye contact reported at the monthly

visits to Dr. Renaud. See Pet. Ex. 5, pp. 45-49 (classroom observations in March 2009

noting C.L.’s use of two-word phrases only when motivated and prompted; C.L.’s need

for prompting to produce 20 different two-word requests within three hours; her making

eye contact only with a familiar person; her non-responsiveness to questions; and her

need for an assistive device to make “I want” requests); pp. 55, 57 (observations on her

April 2009 IEP which noted that she was not spontaneously putting words together in a

sentence); pp. 57-59 (observations for IEP progress in June and November 2009); p. 61

(noting at April 2009 meeting to develop IEP for the following school year that C.L.’s

58

C.L. was reported in February 2009 as improving in vocabulary, using two-word phrases, and having

slightly improved eye contact; however, when frustrated she ground her teeth, gagged herself, and

banged her head. Pet. Ex. 9, p. 25. Shortly after the February IVIG treatment, Mrs. Lehner reported her

as very clingy and more irritable. Id., p. 27. In March 2009, she was reported as acquiring a few new

words and having reasonable eye contact, but continued to have behavioral problems. Id., pp. 30-31. In

early April 2009, Mrs. Lehner reported that C.L. was combining words, making requests, and interacting

more, but continued to have stereotypical behavior and had begun gagging herself. At a visit on April 15,

2009, though, Mrs. Lehner reported that C.L.’s behaviors had “not improved at all” and she felt that “in

general she was regressing.” Id., p. 39. She was concerned that the school would not permit C.L. to

return the following school year, due to her behavior problems. She reported that C.L.’s vocabulary had

remained stable while off the prednisolone. Doctor Renaud commented that C.L. did not use any words

during this visit. Id., p. 41. At a visit on April 29, 2009 (when C.L. was off prednisolone and CellCept, and

had not received IVIG since April 1, 2009 (see Pet. Ex. 9, pp. 94,101)), she was reported to be using two-

to three-word phrases, seeking out more social interaction, and was more content at school. Id., p. 45. In

mid-May 2009, C.L.‘s family thought her communication and interaction had improved since the last IVIG

dose. Doctor Renaud noted that C.L. greeted her and answered a few questions with single words. Id.,

p. 53. She assessed C.L. with incremental improvements after each IVIG infusion on the two-week

interval schedule. At the end of June 2009, C.L. was reported to be calmer, with improved

understanding, but still galloping and humming. Id., p. 58. At the end of August 2009, two months after

the last IVIG treatment, C.L. was described as more focused, with better understanding. A recent EEG

was described as normal, and C.L. had not had any regressions since stopping treatment. Id., pp. 63-64,

67 (phone call reflecting that C.L. had an EEG, not an MRI as reported at the August 26 visit).

31

progress had been “limited” and that she had struggled with irritability and behavioral

problems in the past few months); p. 63 (evaluation from summer session reflecting that

she could say familiar words in a song, would say her own name when asked, followed

one-step directions, and played alongside peers without interaction); p. 65 (October

2009 IEP report reflecting that she could use one-word phrases, needed frequent

prompting, and was using PECS at home to make “I want” requests).

C.L. was retested to confirm her continued need for special education services in

December 2009 (a state-mandated requirement). While she had gained skills since the

initial testing in September 2005 (performed by the school system) and June 2006

(testing outside the school system), she again scored as severely impaired—frequently

in the 1st percentile ranking or below. Pet. Ex. 5, pp. 70-72. Her parents reported their

primary concerns were her autism diagnosis and her lack of communication and peer

interactions. Id., p. 70. C.L. was also retested for an autism spectrum disorder. The

cut-off score for an autism diagnosis was 85 or higher; C.L. was scored over 100 in

separate evaluations by her parents, kindergarten teacher, and special education

teacher. Id., p. 74.

During the same time frame when C.L. received VGKC antibody treatments from

Dr. Renaud, she was also receiving ABA therapy at the Lovaas Institute and speech

and occupational therapy through the school system. Pet. Ex. 17, pp. 22-23 (Lovaas

history of services received by C.L. from 2005-10). Consequently, it is difficult to

attribute C.L.’s improvement, if any, to the specific therapies prescribed by Dr. Renaud.

What is clear is that there was not a dramatic or significant improvement in C.L.’s

functioning. This is especially evident when considering that her April 2009 IEP goals

were continued at the June and November 2009 progress reviews, rather than marked

as achieved. See Pet. Ex 5, pp. 56-60.

c. Switch in Therapies and Providers.

On August 26, 2009, C.L. saw Dr. Renaud again. She had received her last IVIG

treatment on June 24, 2009. Pet. Ex. 9, pp. 63-64. She was reported to be more vocal

and having better understanding since the June visit. Off therapy, her antibody level as

measured on this visit had risen to 1.82. Id., p. 66. In a sample taken in October 2009,

C.L.’s antibody level again rose, this time to 2.17. Id., pp. 67-68.

C.L. saw Dr. Renaud and Dr. Ann Reed, a rheumatologist, on November 3, 2009.

C.L. had been ill about a month earlier and had eye surgery about two weeks prior to

the visit. Pet. Ex. 9, p. 72. Her parents reported regression in C.L.’s communication

and behavior over the prior four to six weeks. Id. Doctor Reed recorded that since July,

C.L. had more aggressive behavior, screaming, and bedwetting. Id., p. 69. I note that

this appears to contradict the reports of her behavior at the August visit to Dr. Renaud.

On examination by Dr. Reed, C.L. was interactive but distractible. Id., p. 70. The side

32

effects and potential benefits of rituximab59 were discussed. Id. In discussions with Dr.

Renaud, the family expressed concern about her deterioration, and Dr. Renaud

attributed it to withdrawal of treatment. Id., p. 73.

In December 2009, Mrs. Lehner requested that C.L.’s treatment records from

Mayo be sent to the University of Minnesota, Fairview. Pet. Ex. 9, p. 75. In February

2010, C.L. had her first appointment at the pediatric rheumatology clinic there. The

reason for the appointment was described as to obtain a second opinion regarding

C.L.’s VGKC autoantibodies. Pet. Ex. 6, p. 89. Doctor Binstadt reviewed C.L.’s records

with petitioners, noting that her “primary symptoms are developmental delay on the

autism spectrum.” Id. C.L.’s parents reported to Dr. Binstadt that C.L. had been “doing

well” until she was found to have speech delay in October of 2005. Id. They described

a loss of words and the onset of self-stimulatory behaviors as beginning two weeks after

her November 2005 influenza vaccination. Id.

Doctor Binstadt referenced the Tan article, Pet. Ex. 10i, for the work done by the

Mayo group on VGKC antibodies, the link of such antibodies to neurological disorders in

adults, and the success in treating patients by immunosuppressive therapy. Pet. Ex. 6,

p. 89. He summarized C.L.’s treatment by Dr. Renaud. Id.

After discussion of the risks and potential benefits, Dr. Binstadt and petitioners

elected to treat C.L. with rituximab. Pet. Ex. 6, pp. 90-91, 96-97, 119. No evidence of

improvement in C.L.’s condition was observed after she received two rituximab

treatments and treatment was discontinued in April 2010, notwithstanding Dr. Binstadt’s

view that it was likely too early to see a benefit. Id., p.128. Her VGKC antibodies,

which were measured at 1.68 prior to receiving the first treatment (id., p. 98), rose

between the first and second treatments to 1.89 (id., p. 119); and were 2.69 after the

second treatment (id., p. 130). Doctor Binstadt did not know what clinical significance

the increase in VGKC antibodies might have. Id. (“Whether there is any clinically

significant difference between these two values is not known, to my understanding.”).

d. Involvement with Dr. Vincent.

Petitioners’ Ex. 20 contains a series of email messages from Dr. Vincent to Mrs.

Lehner, C.L.’s maternal grandfather, or to Dr. Binstadt. Although the exhibit does not

contain their messages to Dr. Vincent, the one-sided messages give a fairly clear

59

Rituximab (trade name Rituxan) was described by Dr. Bryce Binstadt, a physician who later prescribed

it as a treatment, as a monoclonal antibody that acted as a B-cell depletion therapy. Pet. Ex. 6, p. 90. He

explained that it “works by depleting the CD20-expressing B cells, the precursor cells to antibody-

producing plasma cells” and is “well tolerated and leads to improvement in patients with autoantibody

mediated disorders.” Id.

33

picture of what transpired in their correspondence between March 2011 and December

2012.60

C.L.’s grandfather, who attended many of C.L.’s appointments with Dr. Renaud,

somehow learned of Dr. Vincent’s work on VGKC antibodies. He wrote Dr. Vincent

about C.L.’s history and treatment. On March 22, 2011, Dr. Vincent responded,

commenting on several aspects of C.L.’s recent treatment and testing. Pet. Ex. 20, pp.

2-3. She stated that it was not unusual for antibody levels to vary and speculated that

the variations could be due to the possible presence of two specific proteins, LGI1 and

CASPR2.61 Id., p. 3. She offered to test a sample of C.L.’s serum for these specific

antibodies and the “proteins they are against – eg. caspr2 or lgi1 [sic].” Id. She

indicated that what had been reported to her about C.L.’s clinical course was “difficult to

understand well,” but that “rituximab may take some time to work.” Id.

Throughout the correspondence, Dr. Vincent expressed excitement at finding a

possible connection between VGKC antibodies and autism. She mentioned an

unpublished study she had conducted looking for CASPR 2 antibodies in children with

autism but the wording suggested that she had been unable to find the antibodies. Pet.

Ex. 20, p. 3. She also mentioned her research into maternal antibodies and autism. Id.

Doctor Vincent’s email messages to Dr. Binstadt concerned the testing of C.L.’s

serum for antibodies. Pet. Ex. 20, pp. 4-5. When C.L.’s serum sample was finally

obtained, shipped and tested in May 2011, she tested negative for CASPR2 and LGI1

antibodies, but positive (at a level of 0.91) for VGKC antibodies. Pet. Ex. 20, pp. 14-17.

Doctor Vincent then suggested she continue to study C.L.’s “serum to try to determine

the exact target of her antibodies.” Id., p. 19. She suggested testing C.L.’s serum on

cultured brain cells to see where there might be binding of the antibodies present. Id.,

pp. 19-21, 23. The email messages do not indicate whether this testing was ever

performed.

Doctor Vincent’s opinions on the significance of the antibodies present in C.L. are

discussed in Section V.B.1.b.(1)(c), below.

e. Return to Treatment at Mayo.

C.L. resumed treatment with Dr. Renaud in September 2011. Pet. Ex. 9, p. 81.

Doctor Renaud noted that C.L.’s VGKC antibody level increased during her treatment

by Dr. Binstadt, but that the level had declined to 1.30 in November 2010, some four

60

One additional message, which is undated, appears at Pet. Ex. 20, p. 24, after the last dated message

from December 31, 2012. Id., p. 23.

61

These are the two antibodies found in the VGKC complex that have specific pathogenic associations.

See, e.g., Tr. at 416-17; Pet. Ex. 21, p. 1.

34

months after rituximab treatment ended.62 Pet. Ex. 9, p. 81. She also noted that there

had been no obvious regression of skills. Id. Although C.L. was not communicating

much verbally, she was using single words to label things, was beginning to use an iPad

as an assistive communication device, seemed to understand more than she could say,

followed two step commands, and had occasional two word combinations. Id. Her

words, however, were “often approximations.” Id. Additionally, she noted that C.L.’s

eye contact had improved “over time despite not receiving ABA therapy since

September 2010.” Id. The foregoing suggests that the reports provided of C.L.’s

functioning during Dr. Renaud’s earlier treatment were either somewhat inflated or C.L.

had indeed lost some skills. Given that this description of C.L.’s level of functioning was

more consistent with what was recorded in her school records, the “improvements”

noted earlier may not have been accurate. Compare id. with descriptions in n.58,

supra. Although Dr. Renaud assessed C.L. as not having regressed since her last

evaluation in November 2009, C.L.’s family felt that she had “not made two years of

progress” in that time. Pet. Ex. 9, p. 82.

Doctor Renaud recommended intermittent pulse IV methylprednisolone, rather

than the oral prednisolone C.L. had received in 2008. Pet. Ex. 9, p. 82. She also

suggested pairing this therapy with another drug, Imuran.63 Interestingly, Dr. Renaud

recorded C.L.’s diagnoses as global developmental delay with autistic features and

neuronal voltage-gated potassium channel antibodies, but, in contrast to her earlier

diagnoses, did not record either a possible or probable autoimmune encephalopathy as

a diagnosis. Id.

The family apparently agreed with the recommendation to treat C.L. with IV

steroids monthly, as she received her first infusion in late November 2011. Pet. Ex. 9,

pp. 118-19. Her antibody level was measured at 1.0 prior to beginning the infusion,

which was slightly higher than the level in September 2011, when she returned to Dr.

Renaud’s practice. Id., p. 119. No side effects were reported. Doctor Renaud also

noted that ABA therapy had resumed full-time in September. Id. Her antibody levels

declined to 0.69 on December 5, 2011. Id., p. 121. The antibody levels were even

lower at the time of the second infusion on December 23, 2011, down to 0.42, and lower

still, to 0.31, after a subsequent infusion. Id., pp. 124-25.

At a February 2012 visit with Dr. Renaud, Mrs. Lehner reported that C.L. had

experienced gains since resuming steroid therapy, including improvement in eye

contact, responsiveness to her name, imitation of vocalizations, and spontaneous

vocalizations. Pet. Ex. 9, p. 127. Although it was not a huge gain, she indicated that

there had been some benefit and none of the sleep problems and aggression seen

during the earlier oral steroid therapy. Id. On examination, Dr. Renaud observed good

62

The level had further declined as of the date of this appointment. The sample drawn on September 14,

2011, was reported as 0.83. Pet. Ex. 9, p. 90.

63

It does not appear that this additional medication was ever added to C.L.’s treatment regimen.

35

eye contact, the use of some single words, and that C.L. was calmer than on previous

visits. Id. C.L.’s most recent antibody level showed some rebound, going up to 0.92,

but the increase in antibodies was not accompanied by any clinical deterioration. Id., p.

128. Doctor Renaud opted to increase the dose of oral steroid and to infuse every two

weeks for five infusions. Id.

C. L.’s antibody level was down to 0.48 in the April 2012 blood draw. Pet. Ex. 9,

p. 151. C.L. was next seen by Dr. Renaud on May 24, 2012. Id., p. 154. C.L. was

reported as agitated for about a day after the infusion of the increased dose. Id. The

skills reported were similar to those at previous visits, but C.L. was saying things when

prompted, rather than initiating the use of words. Id. Mrs. Lehner described C.L. as

“less settled” over the past week and reported that she was having trouble falling

asleep. Id. C.L.’s grandfather raised questions about the effectiveness of plasma

exchange as a possible treatment; Dr. Renaud reviewed the papers he had found and

noted that this treatment had been used in limbic encephalitis, a more acute illness than

C.L. demonstrated.64 Id., p. 155.

Behavioral concerns resurfaced at the July 2012 visit to Dr. Renaud. C.L.’s

skills, language and cognitive abilities were described as stable, and she had not

received any steroid infusions since May 2012. Pet. Ex. 9, p. 183. However, she was

having tantrums and aggressive behavior, was scratching, and was described as “quite

emotional.” Pet. Ex. 9, p. 183. She was gagging herself to the point of vomiting, had

stopped eating solid food, and was taking more than two hours to fall asleep, after

which she would awaken during the night and not return to sleep. Id. After a review of

past and proposed treatments, Dr. Renaud suggested that C.L. see one of the clinic’s

neuroimmunologists. The family agreed, and Dr. Renaud arranged an appointment on

July 31. Id., pp. 183-84.

The reports of gains from the IV steroid treatment were undercut by other

evaluations of C.L.’s condition. A May 30, 2012 reassessment by the Minnesota Autism

Center indicated that C.L.’s “Full Scale IQ” score was 40, which was in the “mentally

deficient range,” and was certainly not improved over prior scores. Pet. Ex. 13, p. 31.

Additionally, C.L.’s CARS score remained in the “severely autistic” category.” Pet. Ex.

13, p. 33.

f. Evaluation at the Autoimmune Neurology Clinic.

64

Doctor Vincent had mentioned plasma exchange as a possible treatment in July 2011. Pet. Ex. 20, p.

20.

36

C.L. saw Drs. Andrew McKeon65 and Stacey Clardy in the Autoimmune

Neurology Clinic on July 31, 2012. Doctor Clardy reviewed the medical history provided

by C.L.’s mother and grandfather, which repeated the claim that C.L. lost milestones

and had a complete change in personality and behavior within a few weeks of her

influenza vaccination. Pet. Ex. 9, p. 189. They reported that her language had stayed

stable with about 50 words or word approximations, that she could follow some simple

two-step commands, and that she had no major regressions or dramatic improvements

since 2005, but was gaining skills at school. Id. Doctor Clardy characterized the oral

steroid treatment as producing “questionable minor improvement in language use, but

with intolerable behavioral side-effects.” Id., p. 190. She saw no “appreciable benefit”

from IVIG; no apparent benefit and some side effects from CellCept; and no significant

improvement but no side effects from the IV steroid treatment. Id. She described C.L.

as a “unique case.” Id., p. 191. She noted that the “phenotype of VGKC-antibodies in

the pediatric population is not fully characterized,” and that the few case reports

available described many manifestations.66 Id. Doctor Clardy indicated that, at this

point, it was impossible to know if C.L. had experienced autoimmune encephalitis when

she was two, whether some of her symptoms represented sequelae of that condition, or

whether the VGKC antibodies were related to her autism. Id. She commented that an

individual may have persistent antibodies without clinical symptoms. Id. Although

C.L.’s parents had focused on antibody levels in deciding whether treatment was

effective (see, e.g., Pet. Ex. 9, p. 150 (telephone message that parents did not feel

comfortable in scheduling an IV steroid infusion without knowing the antibody levels)),

Dr. Clardy recommended focusing on clinical improvement, as difficult as it might be to

objectively assess, as antibody levels “have been known to persist in patients with

clinical remission of symptoms.” Id., pp. 191. She noted that there had been

questionable improvements in the past on language, but no family member had ever

seen an improvement in social skills or cognitive function. Id., p. 192.

Doctor McKeon’s own consultation notes repeated the history of a regression

after an influenza vaccination, with the development one month later of self-stimulatory

behavior, rocking, humming, and decreased visual contact. Pet. Ex. 9, pp. 193-94.

C.L.’s grandfather reported that before the vaccination, C.L. was bright and interactive,

but a month afterwards, she would just sit in a corner and refuse to make eye contact.

He also reported that she stopped talking and was less affectionate. Id., p. 193. Doctor

McKeon observed C.L. to run around the room, making some eye contact, but she did

65

Doctor McKeon is a respected adult neurologist with a focus on autoimmune encephalopathy and has

collaborated in research with Dr. Dalmau. Tr. at 382.

66

Dhamija, Pet. Ex. 11c, reported on 12 pediatric cases of VGKC antibodies (including C.L.’s). Eleven of

the patients were seen at the Mayo Clinic. Dhamija, Pet. Ex. 11c at 278. Their symptoms varied widely,

ranging from motor tics and episodic flushing to cerebellar ataxia and limbic encephalitis. Id. at 276.

There were no symptoms common to a majority of the patients. The wide variety of symptoms reported in

this article in connection with the presence of VGKC antibodies mirrors Dr. Dalmau’s observations,

discussed in Section V.B.1.b.(2)(b), below.

37

not have the social or language skills of child of her age. Id. Consistent with the

observations of several other physicians, Dr. McKeon noted some coarse facial

features.67 Id., p. 194.

Based on the reports of “the rapid onset” of C.L.’s regression, Dr. McKeon opined

that “she may have had an unusual manifestation of an autoimmune encephalitis at that

time.” Pet. Ex. 9, p. 194. As an alternative, he hypothesized that “the potassium

channel autoantibodies, though present, are not related to her developmental

problems.” Id. He cautioned that even if she had experienced autoimmune

encephalitis, the “window” for successful treatment of the condition may have passed.”

Id.

Both physicians recommended a full dose trial of IV steroids with Dr. Renaud, but

indicated that treatment should be discontinued if no clinical improvement was

observed. Pet. Ex. 9, pp. 192, 194.

Thereafter, C.L. continued to receive immunotherapy treatments from Dr.

Renaud, who increased her dosage of steroids in September 2012. See generally Pet.

Ex. 9, pp. 200-06. In December of 2012, C.L.’s mother reported that C.L. was having

behavioral side effects as a result of the steroids, including “trying to injure herself and

others, [and] trying to kick the car door.” Id., p. 217.

Subsequently, some improvements in behavior and skills were noted. C.L.

continued to receive ABA therapy, and her family and the ABA therapist felt she had

made significant progress. Pet. Ex. 9, pp. 221, 247 (as reported to Dr. Renaud during

C.L.’s January and April 2013 appointments). Mrs. Lehner testified that they saw “the

biggest gains” in C.L.’s behavior with the increased steroid dose. Tr. at 53. During

C.L.’s January and April 2013 appointments with Dr. Renaud, C.L.’s family reported

improvements in both her behavior and skills. See Ex. 9, pp. 119, 127, 154, 221, 247.

C.L.’s antibody levels remained above normal, and continued to fluctuate. Id., pp. 222,

227, 238, 248. In January 2013, C.L.’s parents elected to reenroll her in public school,

rather than continue home school plus full time ABA therapy. Pet. Ex. 5, p. 201.

However, notwithstanding these noted improvements, C.L. continued to qualify for

“special education services as a student with Autism Spectrum Disorder.” Pet Ex. 5, p.

214.

As part of reenrolling in public school, C.L. was reevaluated for special education

services. While C.L.’s eye contact and joint attention were improved, her

communication skills were poor. She did not engage in age appropriate play, did not

interact with her peers, preferred repetitive and self-stimulatory behavior, exhibited a

67

In addition to the other observations of coarse features mentioned above, Dr. Deborah Freese, a

pediatric gastroenterologist, saw C.L. in June of 2012 and observed her to be “mildly dysmorphic with

frontal bossing and a large head size.” Pet. Ex. 9, p. 181.

38

low frustration tolerance, and sought sensory input by putting things in her mouth, and

smelling and touching them. Pet Ex. 5, p. 206. C.L.’s most recently filed IEP indicated

that she continued to have needs in the areas of social interaction, behavioral

regulation, communication, functional skills as well as academic skills. Pet Ex. 5, pp.

227-35.

g. Seizure Disorder Diagnosis.

At the end of April 2013, C.L. was found unconscious on the playground. School

personnel presumed she had hit her head. Pet. Exs. 22, p. 1; 3, p. 131. About a week

later, on May 3, 2013, C.L. suffered a seizure witnessed by her father. Pet. Exs. 22, p.

1; 3, p. 13168; 9, pp. 251, 254. On May 14, 2013, C.L. was seen by Dr. Chadwick, a

pediatric neurologist, for an evaluation of her seizures. She was diagnosed with

complex partial epilepsy in addition to autism.69 Pet. Ex. 22, pp. 1-3. C.L. experienced

another seizure several days later and was prescribed Trileptal, with good results in

seizure control. Id., p. 7. However, C.L. was experiencing “anger, aggression, and

agitation issues” with some recent improvement. Id. As of February 2014, C.L.

continued to receive Trileptal, and IV steroid infusions. Pet. Ex. 9, p. 266. A gain of

skills was also reported. Id.

5. Other conditions.

C.L.’s medical records also document treatment for a number of minor childhood

illnesses and other conditions, including surgery for “lazy eye,” evaluation, biopsies, and

treatment for gastroesophageal reflux, some alternative tests and treatments for ASD,

and many school and therapy records. See generally Pet. Exs. 3-6; 13-14; 17; 19.

Although I have reviewed these exhibits as a part of the “record as a whole” (see §

13(a)), and some are mentioned in passing in the medical records summary above, they

are not discussed further in this decision, as they are not relevant to the issues

presented in this case.

68

The history reflected in this record is that Dr. Donald Chadwick witnessed her May 3 seizure; however,

based on Dr. Chadwick’s records, the history of a witnessed seizure should reflect that C.L.’s father, not

Dr. Chadwick, witnessed it.

69

Doctor Shafrir testified that many individuals with autism eventually develop seizure disorders. Tr. at

131. He also testified that the majority of autistic children will develop seizures by the time they reach

their 18th birthday. Tr. at 255. See also Snyder, 2009 WL 332044, at *32 (“About 20–30% of children

with ASD have or will develop epilepsy over the course of their lives, often beginning during

adolescence.”).

39

IV. Experts, Opinions, Diagnoses, and Motion to Exclude.

A. Expert Qualifications.

1. Doctor Frye.

Doctor Frye’s curriculum vitae [“C.V.”] was not filed in this case, making it difficult

to assess his qualifications to offer an expert opinion on autoimmune encephalitis and

the role of VGKC antibodies in the condition, much less on whether such a condition

would present with symptoms warranting an autism diagnosis. However, I am familiar

with Dr. Frye in general, as he has testified as a pediatric neurologist specializing in the

treatment of children with neurodevelopmental disorders in other Vaccine Program

cases. See Paluck v. Sec'y, HHS, 786 F.3d 1373 (Fed. Cir. 2015); Bast v. Sec’y, HHS,

2012 WL 6858040, at *3 (Fed. Cl. Spec. Mstr. Dec. 20, 2012).

At the time Dr. Frye wrote his expert report in this case he was an Assistant

Professor of Pediatrics and Neurology at the University of Texas Health Science Center.

Pet. Ex. 10 at 3.

2. Doctor Shafrir.

Doctor Shafrir is board certified in neurology, with special qualifications in child

neurology and clinical neurophysiology. Pet. Ex. 11a at 2; Tr. at 128. After his

residency training, Dr. Shafrir completed a fellowship in pediatric neurophysiology and

epileptology at Miami Children’s Hospital. Pet. Ex. 11a at 1; Tr. at 128.

He is primarily a clinician, and is currently in private practice in Baltimore, MD,

where he sees patients five days a week. Tr. at 130; Pet. Ex. 11a at 3. He also

teaches residents at Sinai Hospital, and is an Assistant Professor at the University of

Maryland School of Medicine. Tr. at 128-29; Pet. Ex. 11a at 3. Doctor Shafrir has an

interest in autism spectrum disorders and currently sees approximately 200 ASD

patients, but he has no specialized training in the diagnosis, management, or treatment

of ASD. Tr. at 130-31, 203. He explained that he did not see most of his ASD patients

actively, because there was very little that he could do for them by way of treatment. Tr.

at 130-31. Most of his ASD patients had already been evaluated or tested for ASD by

the time he saw them. Tr. at 132. He did not appear to place much value on ASD

diagnostic criteria (Tr. at 134-35, 206-07), and indicated that he did not order many tests

to try to determine if there was a cause for the disorder in individual patients (Tr. at 136-

37).

40

He has treated approximately three patients in his career with autoimmune

encephalitis. Tr. at 139. He has not conducted any research in ASD,70 autoimmune

encephalopathies, or voltage-gated antibodies. Tr. at 203-04. He has no expertise in

autoimmunity in particular or immunology in general. He has never treated a patient

with VGKC antibodies, although he had “seen two patients” with NMDAR encephalitis.

Tr. at 208, 227. However, he claimed, based on his reading of published medical

literature, that he was an expert on “how different antibodies can cause autoimmune

encephalopathy.” Tr. at 217. In one of many tangential answers to relatively

straightforward questions, Dr. Shafrir testified that his “life is dedicated to autism.” Tr. at

148.

3. Doctor Angela Vincent.

Petitioners filed a June 4, 2013 email message from Dr. Vincent to their attorney,

Ms. Sheila Bjorkland, as Pet. Ex. 21, as well as the email correspondence from Dr.

Vincent, as Pet. Ex. 20. Although petitioner’s counsel characterized Dr. Vincent’s June

4, 2013 letter as an “Expert Report,” the letter is better characterized as a medical

record describing testing and a commentary on the significance of the results. A C.V.

for Dr. Vincent was not included; however, I note that she co-authored a number of the

medical journal articles that were filed as exhibits by both parties.

In the June 4, 2013 message, Dr. Vincent noted that she is a clinical

immunologist with 35 years of experience researching diseases of the nervous system

caused by autoantibodies to membrane receptors, ion channels, or related proteins.

Pet. Ex. 21, p. 1. Her group of researchers made some early discoveries in antibodies

thought to be involved with neurological symptoms, including the first description of the

potassium channel antibodies in 1995, and developed the first test for the antibodies.

Id. Her laboratory tests over 50,000 samples per year. Id. Doctor Dalmau testified that

Dr. Vincent is a leading contributor to the field of autoimmune neurology with whom he

has published but, to his knowledge, she is not a medical doctor and does not see

patients. Tr. at 379-80, 448.

Based on the information provided, she clearly possessed the qualifications to

test C.L.’s blood for the presence of VGKC autoantibodies and to opine on the

significance of the results. She did not offer an opinion on the role of the influenza

vaccination in causing the antibodies.

70

Doctor Shafrir has published an abstract on Landau-Kleffner Syndrome. Tr. at 204. Landau-Kleffner

Syndrome is an acquired epileptic aphasia presenting in childhood and is a condition that frequently

resembles autism spectrum disorders. See DORLAND’S at 1861.

41

4. Doctor Dalmau.

Doctor Dalmau is a world-class expert in the areas of autoimmune

encephalopathy and encephalitis and voltage-gated potassium channel antibodies. He

is a neurologist with specialties in neuroimmunology and neuro-oncology. Tr. at 293-97.

He also has a Ph.D. in immunology and cancer-associated immunology.71 Tr. at 293.

After his residency training in Spain, Dr. Dalmau completed a fellowship in neurology at

New York Hospital, Cornell University, and a fellowship in medical oncology at Memorial

Hospital for Cancer and Allied Diseases in New York, NY. Res. Ex. K at 1.

At the time of the hearing, Dr. Dalmau served as the director of laboratories

involving neuro-oncology and neuroimmunology at the University of Barcelona in Spain.

He also serves on the faculty of the University of Pennsylvania in Philadelphia and the

University of Barcelona in Spain. Res. Ex. LL at 2; Tr. at 293-94. He has been a

reviewer for over 25 medical journals and sat on the editorial board of four neurology

journals. Res. Ex. LL at 6.

Doctor Dalmau is an award-winning researcher in the field of neuroimmunology

and at the time of the hearing, was a consultant in neuroimmunology for the National

Institutes of Health [“NIH”]. Tr. at 294-95; Res. Ex. LL at 3. The current focus of Dr.

Dalmau’s research is on three aspects of autoimmune encephalitis: studying known

disorders; identifying new disorders, antibodies, and target antigens; and studying

mechanistically how antibodies act on the brain. Tr. at 298-99. He is the primary author

of or a primary contributor to approximately 270 published articles, of which nearly 95%

deal with autoimmune disorders. Tr. at 299. The articles published most recently have

largely dealt with autoimmune encephalopathies and encephalitis. Id.

His clinical practice involves many patients with autoimmune encephalitis,

predominantly referral patients seeking confirmation of an immune-mediated disorder

diagnosis. Tr. at 297-98. Twenty percent of these patients are children, all of whom

have autoimmune neurological conditions. Id. Based on these credentials, Dr. Dalmau

was offered as an expert in neuroimmunology with special expertise in autoimmune

encephalopathy and autoimmune encephalitis without objection. Tr. at 299-300. The

hearing in this case was the first time he has testified. Tr. at 300.

5. Doctor Gorman.

Doctor Gorman is a board-certified neurologist, with special qualifications in child

neurology. He specializes in pediatric neuroimmunology. Res. Ex. MM at 10, 16; Tr. at

454-55, 485. After his residency, Dr. Gorman completed a fellowship in child neurology

and multiple sclerosis. Res. Ex. MM at 1-2.

71

Because Dr. Dalmau completed his residency in Spain, he is not eligible for board certification in the

United States. Tr. at 292.

42

At the time of the hearing, Dr. Gorman was the director of the pediatric multiple

sclerosis program, the neuroimmunology program, and the inpatient neurology service

at Boston Children’s Hospital. Res. Ex. MM at 2-3. He was an assistant professor at

Harvard Medical School and taught at Boston Children’s Hospital. Id. at 2; Tr. at 455.

His clinical practice was limited to pediatric neuroimmunology patients, whom he saw

one full day a week, with the remainder of his time involving a research practice in

multiple sclerosis, and in other aspects of neuroimmunology distinct from multiple

sclerosis. Tr. at 456-57. He has numerous peer reviewed publications and has served

as a reviewer for several medical journals. Tr. at 457; Res. Ex. MM at 4, 12-14. Doctor

Gorman saw ASD patients in the context of providing autoimmunity consultations and

as part of his in-patient attending responsibilities; but he did not represent himself as

having any special expertise in ASD. Tr. at 495.

B. Petitioners’ Motion to Exclude Dr. Gorman’s Testimony.

Prior to discussing the expert opinions on diagnosis and causation, I first deal

with petitioners’ mid-hearing motion to exclude Dr. Gorman’s testimony as cumulative.

The issue was first raised by oral motion at the hearing on January 28, 2014. Tr. at

451-53. Given that nothing precluded petitioners from raising the issue in a pre-hearing

status conference or by written motion prior to the hearing, and the fact that Dr. Gorman

was present and prepared to testify, I elected to hear his testimony and decide later

whether to consider it in making my decision. Id.

In the post-hearing order, I directed petitioners to file a written motion

summarizing their arguments for excluding Dr. Gorman’s testimony. Order, issued Jan.

30, 2014. Petitioners filed their Motion to Exclude [“Pet. Motion”] on March 10, 2014;

respondent filed a Response to Petitioners’ Motion [“Res. Response”] on April 7, 2014;

and petitioners filed a Reply to Respondent’s Response [“Pet. Reply”] on April 10, 2014.

Petitioners argued that Dr. Gorman’s testimony should be excluded as violating

the “rules of fundamental fairness” because: (1) Dr. Gorman conceded he would defer

to Dr. Dalmau’s expertise72 regarding VGKC encephalopathy, and thus any testimony by

Dr. Gorman regarding autoimmune encephalopathy and VGKC antibodies would be

cumulative and duplicative; (2) Dr. Gorman’s testimony regarding the onset and

causation of ASD was beyond his expertise; and (3) his testimony on ASD was beyond

the scope of his expert reports and “amounted to trial by ambush.” See generally Pet.

Motion. Despite my instructions that petitioners provide specific objections, Tr. at 475,

72

It is unsurprising that Dr. Gorman would defer to Dr. Dalmau’s expertise regarding VGKC antibodies

and autoimmune encephalopathy, as few experts anywhere in the world possess Dr. Dalmau’s

knowledge. That does not automatically make Dr. Gorman’s testimony cumulative. I note that the motion

to exclude was made prior to hearing his testimony. Thus, petitioners were only assuming that the

testimony would be cumulative. Further, as discussed above in the post-hearing brief on the matter,

petitioners failed to cite any specific examples of cumulative testimony offered by Dr. Gorman.

43

petitioners failed to cite any specific examples of cumulative testimony offered by Dr.

Gorman. Rather, petitioners asserted that as Dr. Gorman deferred to Dr. Dalmau’s

expertise “it is a matter of simple logic than any testimony he offered regarding VGKC

antibodies and [C.L.’s] situation was merely cumulative.” Pet. Reply at 1. Petitioners

argued Dr. Gorman’s testimony on VGKC antibodies “was anecdotal of his own

experience and not specific to C.L.’s situation.” Id. at 1-2. I disagree with all of

petitioners’ arguments.

At the hearing Dr. Gorman testified consistent with his revised opinion73 that C.L.

did not have an autoimmune encephalopathy, let alone one related to VGKC antibodies.

Consistent with his initial opinion in this claim, he testified that the vaccination was not

responsible for the antibodies and that C.L. evidenced significant developmental delay

prior to her influenza vaccination. He also testified about C.L.’s autism spectrum

disorder diagnosis and his disagreements with some of Dr. Shafrir’s testimony about

ASD.

The Vaccine Act vests the special master with the authority to determine the

weight to be afforded evidence, while requiring the special master to consider the entire

record. §§ 13(a)(1), 13(b)(1). The statute further provides that the rules established to

73

Doctor Gorman initially agreed with Dr. Frye that C.L. suffered an autoimmune encephalopathy related

to VGKC antibodies, but he also opined at the same time that her condition was not caused or

exacerbated by her influenza vaccination. Res. Ex. A at 2-5. His opinion was that C.L. suffered

“significant developmental delay” prior to her November 25, 2005 influenza vaccine, that the extent of that

delay was underestimated, and that if the VGKC antibodies played any role in her condition, they were

likely present before the vaccination. Id. at 4. He clearly disagreed with Dr. Frye’s “sweeping general

statements about purported links between various vaccinations and lupus, Guillain Barré syndrome, and

autoimmune thrombocytopenia,” as well as “potential mechanisms of autoimmunity,” which Dr. Gorman

did not find relevant to C.L.’s case. Id. He pointed specifically to the “lack of scientific evidence” linking

influenza vaccine to VGKC antibody disorders. Id. at 5. After Dr. Dalmau submitted his opinion in this

case explaining that recent research had established that only certain types of VGKC antibodies

appeared to play a causal role in autoimmune encephalitis, Dr. Gorman changed his initial opinion that

C.L. suffered an autoimmune encephalopathy. Res. Ex. W. After considering the opinion and evidence

submitted by Dr. Dalmau, reviewing additional medical literature, and having recently evaluated a patient

with elevated VGKC antibodies himself, Dr. Gorman indicated that he was in agreement with Dr. Dalmau

that C.L. “did not have an autoimmune encephalopathy related to VGKC complex antibodies.” Res. Ex.

W at 1. I note that it appears that Dr. Gorman and Dr. Frye had previously collaborated on a publication,

which perhaps explains why he was willing to accept Dr. Frye’s opinion on the presence of an

autoimmune encephalopathy, but disagreed with his conclusions on the role of the vaccine in triggering it,

as the latter was a matter in which Dr. Gorman had expertise. See Res. Ex. B at 7 (“Clinical

Communications” category on Dr. Gorman’s C.V. reflecting a publication with “R. Frye”); see also id. at 7-

8 (“Original Articles” category, reflecting publications on the role of vaccines and infections in neurological

demyelinating disorders (references 4, 5, and 12)). At the hearing, Dr. Gorman summarized the reasons

for his changed opinion as including information from Dr. Dalmau about the technical limitations of the

radioimmunoassay testing performed on C.L.; the lack of any control establishing the normal range for

such antibodies by the Mayo Clinic; the testing by Dr. Vincent for the pathogenic antibodies, which was

negative; the rapidly expanding volume of scientific literature about VGKC antibodies; and his personal

experience with two patients and Mayo Clinic testing results. Tr. at 467-72.

44

govern Vaccine Act proceedings should “include flexible and informal standards for

admissibility of evidence.” § 12(d)(2)(b). Vaccine Rule 8(b)(1), which controls the

admission of evidence, including expert testimony, in cases filed in the Vaccine

Program, indicates that “[i]n receiving evidence, the special master will not be bound by

common law or statutory rules of evidence but must consider all relevant and reliable

evidence governed by principles of fundamental fairness to both parties.” Petitioners in

general often benefit from this approach, as Daubert and its progeny are rarely used to

exclude witnesses; instead, the Daubert factors are used to weigh and evaluate expert

testimony.74

Doctor Gorman, unlike Dr. Dalmau, is a board certified pediatric neurologist who

specializes in pediatric neuroimmunology. As such, Dr. Gorman is clearly qualified to

testify and opine in the areas of pediatric neurology and immunology, which encompass

the topics of ASD, autoimmune encephalopathy, and VGKC antibodies.75 As to his

supposed lack of qualifications to opine on ASD, Dr. Gorman has the same general

qualifications as Dr. Shafrir, another pediatric neurologist. I note that at least two of the

physicians who treated C.L. were pediatric neurologists (Drs. Renaud and Chadwick)

and Dr. Janousek was identified as a neurologist. Although Dr. Shafrir saw children

with ASD, he did not appear to have any special qualifications, apart from his training as

a pediatric neurologist, to do so, and Dr. Gorman saw children with ASD as a part of his

pediatric neuroimmunology practice. Thus, Dr. Gorman was at least as qualified on the

topic of ASD as Dr. Shafrir, and more qualified than Dr. Shafrir on the immunological

and autoimmune aspects of the causation theory petitioners chose to present.

The fact that Dr. Gorman conceded the expertise of Dr. Dalmau, who, according

to petitioners’ own expert, is a “pioneer in this field [having] essentially discover[ed] the

74

For example, much of the evidence pertaining to the causation theories presented in the OAP test

cases and considered by the special masters was excluded, based on its lack of reliability, by the state

and federal judges in the autism cases litigated outside the Vaccine Program. See Blackwell v. Wyeth,

408 Md. 575, 971 A.2d 235 (2009); Doe v. Ortho-Clinical Diagnostics, Inc., 440 F. Supp. 2d 465

(M.D.N.C. 2006); Redfoot v. B.F. Ascher & Co., No. C 05-2045 PJH, 2007 WL 1593239 (N.D. Cal. June

1, 2007).

75

I note that some of the medical journal articles filed addressed VGKC antibodies in adults, while others

focused on the antibodies in children. For example, the following articles focus on children: Dhamija, Pet.

Ex. 11c; Y. Hacohen, et al., Paediatric autoimmune encephalopathies: clinical features, laboratory

investigations and outcomes in patients with or without antibodies to known central nervous system

autoantigens, J. NEUROL. NEUROSURG. PSYCHIATRY, 84: 748-55 (2013), filed as Pet. Ex. 23a [hereinafter

“Hacohen, Pet. Ex. 23a”]; and J. Suleiman, et al., VGKC antibodies in pediatric encephalitis presenting

with status epilepticus, NEUROLOGY, 76: 1252-55 (2011), filed as Pet. Ex. 23b [hereinafter “Suleiman, Pet.,

Ex. 23b”]. These articles focus on adults: J. Lilleker et al., VGKC complex antibodies in epilepsy:

Diagnostic yield and therapeutic implications, SEIZURE, 22:776-79 (2013), filed as Pet. Ex. 23d

[hereinafter “Lilleker, Pet. Ex. 23d”]; S. Wong, et al., An effective immunotherapy regimen for VGKC

antibody-positive limbic encephalitis, J. NEUROL., NEUROSURG. & PSYCHIATRY 81: 1167-69 (2010), filed as

Res. Ex. F [hereinafter “Wong, Res. Ex. F”]; E. Lancaster, et al., Investigations of Caspr2, an Autoantigen

of Encephalitis and Neuromyotonia, ANN. NEUROL., 69: 303-11 (2011), filed as Res. Ex. Q [hereinafter,

“Lancaster, Res. Ex. Q].

45

entity of autoimmune encephalitis” does not render Dr. Gorman unqualified to testify.

Pet. Ex. 16 at 1; see also Tr. at 139, 520 (acknowledging Dr. Dalmau’s expertise and

qualifications). Nor does the fact that Dr. Gorman’s testimony overlapped to some

degree with Dr. Dalmau’s testimony make Dr. Gorman’s testimony inadmissible. While

a special master might chose to preclude a party from offering the opinions of two

medical experts within the same field, nothing in the Vaccine Rules or the Act itself

requires one to do so. Moreover, while Dr. Dalmau has specialized in the area of

autoimmune encephalopathy and encephalitis and, in particular, the VGKC antibodies

at issue in this case, he primarily treats adults; whereas Dr. Gorman specializes in

pediatric neuroimmunology and has published on the role of vaccines and infections.

See Section IV. A.; n.72, supra. Thus, they bring some differences in background to

their understanding of the causation issues in question.

Petitioners had ample opportunity to move to exclude Dr. Gorman’s testimony

prior to the hearing, rather than blindsiding respondent, not to mention the special

master, with the issue for the first time at hearing.

Petitioners’ argument that Dr. Gorman’s changed opinion should preclude his

testimony was, essentially, unsupported by law or practice. In more than nine years as

a special master, I have seen many experts modify their opinions under a variety of

circumstances, and in particular, many petitioners’ experts change their theories in mid-

hearing.76 Doctor Gorman’s changed opinion is certainly a matter to be considered in

determining how much weight to give to his opinions,77 but to preclude him from

testifying because he had changed his opinion is simply not warranted.

I conclude that Dr. Gorman should not have been precluded from testimony

based on his changed opinion in this matter, nor on his concession of Dr. Dalmau’s

superior knowledge regarding autoimmune encephalopathy and encephalitis and VGKC

76

To some degree, Dr. Shafrir did so in this case, acknowledging at the end of the hearing that Dr.

Dalmau’s explanations had changed his opinion and conceding that C.L. did not have the pathogenic

antibodies associated with autoimmune encephalitis. See Section V.B.1. b, below.

77

A trier of fact might well question the expertise and reliability of an expert who does such an about-face

on a diagnostic issue, but Dr. Gorman’s candid acknowledgment that he was wrong speaks volumes

about his honesty and credibility. The causes of autoimmune encephalitis are a “cutting edge” area of

medical and scientific research, about which Drs. Frye, Gorman, and Shafrir were all simply wrong

because new evidence became available between the filing of this claim and the hearing. I suspect that

even Dr. Dalmau might have expressed some agreement with Dr. Frye about a connection between

VGKC antibodies and autoimmune encephalitis at a point before Dr. Dalmau became suspicious about

the wide variety of symptoms attributed to VGKC antibodies, and before he completed his more recent

research identifying only certain VGKC antibodies as causal of autoimmune encephalitis—antibodies not

present in C.L. I have excluded consideration of experts’ testimony based on matters that reflected on

their credibility, see, e.g., Raymo v. Sec'y, HHS, No. 11-0654V, 2014 WL 1092274, at *16 (Fed. Cl. Spec.

Mstr. Feb. 24, 2014), but see no basis here to exclude categorically all of Dr. Gorman’s testimony. I

found his willingness to admit an error refreshing.

46

antibodies, although they are factors to be considered in the weight accorded to his

testimony. I add that Dr. Dalmau’s testimony did not require buttressing by Dr. Gorman.

As to Dr. Gorman’s testimony regarding ASDs in general, and C.L.’s ASD

diagnosis in particular, I find his testimony permissible. As I pointed out at the hearing,

Dr. Gorman has opined consistently that C.L.’s neurological injury pre-dated her

November 25, 2005 vaccination. Tr. at 453 (citing Res. Ex. A); see also Res. Reply at 5

(“Dr. Gorman has consistently stated that [C.L.’s] well-documented early developmental

delays mark the onset of her neurologic condition and that her influenza vaccination

played no role.” (citing Res. Ex. A; Res. Ex. I at 3; Res. Ex W; Tr. at 462-66, 480, 500,

511-12)). Further, the medical records are replete with references to C.L.’s ASD

diagnosis, and Dr. Shafrir discussed ASD in his testimony. Thus, petitioners cannot

claim to be surprised regarding Dr. Gorman’s thoughts about C.L.’s ASD diagnosis and

symptoms.

It was not fundamentally unfair to hear this testimony. To the contrary, the rules

of fundamental fairness require that respondent be allowed to respond to the evidence

offered by petitioners and, as a pediatric neurologist, Dr. Gorman was qualified to offer

testimony in counterpoint to that of Dr. Shafrir on ASD.

Finally, while I am overruling petitioners’ objections, my ultimate findings in this

case would be unchanged even were I to exclude Dr. Gorman’s testimony. In

particular, the testimony he offered on ASD was encompassed in the medical journal

articles that Dr. Dalmau referenced in his expert reports.

C. Diagnoses.

C.L. has received two diagnoses relevant to the issue of causation. Her ASD

diagnosis is not in dispute, but the parties are in disagreement about whether C.L. truly

experienced autoimmune encephalopathy or encephalitis78 and, if so, whether that

condition is responsible for the symptoms resulting in the ASD diagnosis.

When the injury or diagnosis itself is disputed, and “the proposed injuries differ

significantly in their pathology,” the special master may “first find which of [the]

diagnoses was best supported by the evidence presented in the record before applying

the Althen test so that the special master could subsequently determine causation

relative to the injury.” Broekelschen v. Sec'y, HHS., 618 F.3d 1339, 1346 (Fed. Cir.

2010).

78

The medical records establish that C.L. received a diagnosis of probable autoimmune encephalitis

during the first round of treatment with Dr. Renaud. However, this diagnosis did not appear in Dr.

Renaud’s later records, although she continued to treat C.L. for the condition. The fact that C.L. has

VGKC antibodies is not in dispute.

47

1. Autism Spectrum Disorder.79

a. Diagnostic Criteria and Characteristics.

The terms “autism spectrum disorder,” “autistic disorder,” or “autism” refer to a

class of neurodevelopmental disorders marked by “qualitative impairments in the

development of social and communication skills, often accompanied by stereotyped and

restricted patterns of interests and behavior.” Landa, Res. Ex. EE, at 138. Symptoms

of the onset of the disorder must occur before the child is three years old. Id.

Parents of children diagnosed with ASD often report that they first became

concerned about some aspect of their child’s behavior at about 18 months of age.

Landa, Res. Ex. EE, at 139. However, concerns may arise at other points during the

first year of life. Id. Eighty percent of parents of children subsequently diagnosed with

ASD have observed abnormal behaviors in their child by two years of age, typically

involving speech and language development and, less frequently, involving social, play,

sensory, motor, or medical problems, or problems relating to eating, sleeping, and

behavior. Id. at 139-40.

Regression or loss of skills is reported in a substantial minority of children with

ASD. Loss of language skills or vocabulary is often observed in these children,

although social skills loss is seen as well. Lord, Res. Ex. R, at 936; Rogers, Res. Ex. S,

at 141 (loss of eye contact described in 90% of children with regression as well as loss

of social interests). More than 90% of children with regression had only single-word

speech prior to the loss of vocabulary; only 3% had developed phrase speech prior to

their regression. Rogers, Res. Ex. S, at 141. C.L. had only single words, and not many

of them, at the time of her regression.

Rogers described three different patterns of autism onset: (1) developmental

concerns present from birth, with parents reporting atypical behaviors across the first

year of life; (2) early milestone achievement followed by a developmental plateau,

where the children fail to develop the social and communicative skills that differentiate

children with ASD from those with typical development; and (3) a clear developmental

loss of previously-demonstrated skills—a regression. Rogers, Res. Ex. S at 140.

Further study of children who present with regression has demonstrated that “a very

79

This subsection discusses the diagnostic criteria in effect at the time of C.L.’s initial diagnosis, the

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [“DSM-IV-TR”]. The

DSM-IV-TR has since been replaced by the DSM-5. The symptoms recognized by the medical

community at large as those of an ASD have not changed, but the criteria for diagnosis have been

refined, and the distinctions drawn in the DSM-IV among the diagnoses of autistic disorder, PDD-NOS,

and Asperger’s disorder have been eliminated. See American Psychiatric Association, Autism Spectrum

Disorder Fact Sheet,

http://www.dsm5.org/Documents/Autism%20Spectrum%20Disorder%20Fact%20Sheet.pdf (highlighting

the differences between DSM-IV and DSM-V) (last visited July 15, 2015).

48

small proportion of children with autism exhibit a period of truly typical (“normal”)

development; only approximately 15% of children who later lose ski

This text is long and has been trimmed here. Open the source document for the complete record.