Proof of Principle for a Diagnostic Blood Test of Recurrent Seizures
Conditions: Epilepsy
Sponsor: Cognizance Biomarkers, LLC

 
 
 
 
 
Cognizance Biomarkers, LLC 
3160 Chestnut St 
Suite 200 
Philadelphia, PA 19104-2853 
 
 
Biomarker Protocol:  
Proof of Principle for a Diagnostic Blood Test of Recurrent Seizures 
 
Study Center: 
University of Pennsylvania 
 
 
Initial version Date: March 26, 2013 
Amendment 1: April 7, 2014 
Amendment 2: August 31, 2014 
Amendment 3: October 19, 2014 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This document contains confidential information; any disclosure without the consent of Cognizance Biomarkers, LLC 
is prohibited except as required under applicable laws or regulations. 

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Cognizance Biomarkers, LLC 
CARPE: Epilepsy Biomarker 
Confidential 
Protocol Version 1 
 
 
Contents 
1 
BACKGROUND & RATIONALE ......................................................................................................... 3 
2 
STUDY DESIGN ................................................................................................................................... 4 
3 
SUBJECT SELECTION, ENROLLMENT, & WITHDRAW .................................................................. 5 
3.1 
VULNERABLE POPULATIONS ........................................................................................................... 5 
3.2 
INCLUSION CRITERIA ...................................................................................................................... 5 
3.2.1 
Research Subjects .................................................................................................................. 5 
3.2.2 
Control Subjects ...................................................................................................................... 6 
3.3 
EXCLUSION CRITERIA ..................................................................................................................... 6 
3.3.1 
Research Subjects .................................................................................................................. 6 
3.3.2 
Control Subjects ...................................................................................................................... 6 
3.4 
RECRUITMENT ............................................................................................................................... 6 
3.5 
INFORMED CONSENT ...................................................................................................................... 7 
3.6 
WITHDRAW .................................................................................................................................... 7 
4 
RISK ANALYSIS .................................................................................................................................. 7 
5 
SAFETY AND ADVERSE EVENTS ..................................................................................................... 8 
5.1 
DEFINITIONS .................................................................................................................................. 8 
5.2 
RECORDING AND REPORTING ADVERSE EVENTS ............................................................................. 8 
5.3 
MEDICAL MONITORING ................................................................................................................... 9 
6 
DATA HANDLING ................................................................................................................................ 9 
6.1 
RESEARCH SUBJECTS .................................................................................................................... 9 
6.2 
CONTROL SUBJECTS ...................................................................................................................... 9 
7 
DATA ANALYSIS ................................................................................................................................ 9 
7.1 
SAMPLE SIZE DETERMINATION ........................................................................................................ 9 
7.2 
STATISTICAL METHODS .................................................................................................................. 9 
8 
SAMPLE COLLECTION .................................................................................................................... 10 
9 
SAMPLE PROCESSING AND STORAGE ........................................................................................ 11 
9.1 
DURATION OF STORAGE ............................................................................................................... 11 
9.2 
VIAL LABELING ............................................................................................................................. 11 
9.3 
SAMPLE PREPARATION ................................................................................................................. 11 
10 
PRIVACY AND CONFIDENTIALITY ................................................................................................. 11 
10.1 
STUDY SAMPLES .......................................................................................................................... 11 
10.2 
MEDICAL INFORMATION ................................................................................................................ 11 
11 
REFERENCES ................................................................................................................................... 11 
 
 
 
 
 
 

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CARPE: Epilepsy Biomarker 
Confidential 
Protocol Version 1 
 
 
 
1 
Background & Rationale 
The CDC estimates that approximately 10% of the US population will experience a seizure and 3% will be 
diagnosed with recurrent seizures (epilepsy) before age 80. Unfortunately, diagnosing epilepsy is often a 
long, costly, and challenging process involving a combination of a physician’s clinical impression, 
electroencephalogram (EEG), magnetic resonance imaging (MRI) and, where available, a multiday 
inpatient test that combines closed circuit TV and EEG (CCTV/ EEG monitoring). Due to both the high 
cost and complexity of diagnosis, approximately 30% of patients who are treated by a neurologist for 
epilepsy are actually experiencing events from other causes, such as syncope, transient ischemic attack, 
or psychiatric disorder.1 A rapid, cost-effective, and accurate blood test for epilepsy would allow clinicians 
to prescribe treatment quickly for patients who test positive and to redirect the workup on patients who 
test negative. While there have been many previous efforts to find such a blood test, including tests of 
hormone concentrations such as prolactin and tests of brain tissue breakdown such as neuron specific 
enolase, 2, 3 these have not had a high enough sensitivity or specificity for epilepsy to be of clinical value.  
 
Recent studies have established that brain inflammation is a prevalent etiological process factor in focal 
epilepsies, and may contribute to seizure generation.4  Levels of pro-inflammatory cytokines are 
increased in epilepsy surgical pathology specimens, which likely elevate levels of excitatory 
neurotransmitters and impair neuronal inhibition, increasing the likelihood of seizures.5 Further, blocking 
this inflammation reduces or prevents seizures in preclinical models.6  
 
Consistent with this research, investigators at the University of Pennsylvania have identified a potential 
diagnostic blood test for epilepsy called the CNS-specific Assay for Recurrent Paroxysmal Events 
(CARPE), which is defined as the ratio of the plasma concentrations of two lymphocytic regulatory 
proteins: TARC and sICAM5. The CNS-specific component of this test is the soluble fraction of 
Intracellular Adhesion Molecule 5 (sICAM5), a protein that likely originates in the CNS. Preliminary data 
show that anti-inflammatory sICAM5 concentrations are consistently low in epilepsy patients. The second 
component of the test is Thymus and Activation Regulated Chemokine (TARC or CCL17), a lymphocyte 
chemoattractor that in preliminary data was present in consistently high concentrations in epilepsy 
patients. In contrast with the T-cell inhibitory function of sICAM5, TARC binds specifically to CCR4 
receptors on T-cells and induced chemotaxis in T-cell lines. TARC is known to be principally expressed 
peripherally in blood mononuclear cells and the thymus.7, 8 The origin of the high concentrations of TARC 
found in patients with seizures is not known and could arise either systemically or within the central 
nervous system. Nonetheless, TARC concentrations are high in patients with seizures, consistent with a 
pro-inflammatory process. 
 
The present study is designed to establish the accuracy of CARPE as a diagnostic tool for epilepsy in an 
outpatient neurology clinic, the population that would most immediately benefit from such a test. 
Exploratory goals include determining whether additional cytokines and chemokines may enhance 
CARPE’s accuracy, determining whether levels of sICAM5 or other cytokines or chemokines predict or 
confirm subjects’ responses to antiepileptic drugs (AEDs), and determining the degree to which CARPE’s 
accuracy is temporally related to seizures or seizure-like events. 
 
 

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CARPE: Epilepsy Biomarker 
Confidential 
Protocol Version 1 
2 
Study Design 
Specific Aim 1: To establish the accuracy of the CARPE blood test for determining the presence of 
epilepsy, and in doing so, establish the threshold for diagnosis 
a. Hypothesis: CARPE will accurately identify greater than 70% of patients as epileptic 
b. Method 1a: Enroll a total of 240 Research Subjects aged 12 and older who have been referred to 
the University of Pennsylvania’s Penn Epilepsy Center for diagnostic evaluation and have a 
subsequent workup at Penn or an outside site that includes an EEG. All subjects will be asked to 
provide a single sample of blood for CARPE testing and allow the study team to review their 
medical records and collect information about their epilepsy diagnosis. Subjects who enroll and 
do not give a blood sample and have an EEG that is available for study review will be replaced  
Analyzed subjects’ clinically indicated work-up must include an EEG, and additional diagnostic 
tests will be at the discretion of the subjects’ physicians. After six months of clinical care, an 
independent panel of three epileptologists will review the subjects’ medicals records and 
determine each subject’s diagnosis. The study team will compare the panel’s diagnoses with the 
CARPE results  
c. Method 1b: Collect up to two 5ml tubes of blood via a single venipuncture from a maximum of 240 
individuals aged 18 and over who accompany patients to their Penn Epilepsy Center 
appointments as true controls. To be eligible, Control Subjects must confirm that they have not 
been diagnosed with epilepsy and that they are not taking any medications used to treat epilepsy, 
and they will be asked to sign a separate Informed Consent Form. As explained in the ICF, the 
study team will not collect any PHI from Control Subjects; information collected will be limited to 
the following data points at the time of consent: age, gender, presence of an epilepsy diagnosis, 
and whether they are taking any medications used to treat epilepsy (potential subjects will be 
provided with a comprehensive list with brand and generic medication names to review). 
 
Specific Aim 2: As an exploratory endpoint, we will determine whether additional cytokines and 
chemokines may enhance the accuracy of the CARPE  
 
Specific Aim 3: As an exploratory endpoint, we will determine whether CARPE’s diagnostic accuracy is 
temporally related to time of last seizure 
a. Hypothesis: CARPE’s accuracy decreases as more time elapses between the seizure or seizure-
like event and sample collection 
b. Method: Collect postictal blood samples from Research Subjects aged 12 and older who have 
been referred to the University of Pennsylvania for continuous video EEG (cVEEG) monitoring. 
Subjects will be asked to provide a single sample of blood for CARPE testing per day and up to 
one additional blood sample per day (12:00am-11:59pm) if the subject experiences a seizure or 
seizure-like event while undergoing cVEEG. 
We will use clinical determination as the gold standard for classifying the event.  
 
Specific Aim 4: As an exploratory endpoint, we will determine whether levels of sICAM5 or other cytokines 
or chemokines predict or confirm AED efficacy  

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a. Hypothesis: CARPE levels will distinguish Research Subjects who achieve seizure freedom, 
defined seizure freedom since treatment change 
b. Method: Research Subjects who join the study will have the option of providing a sample of blood 
for research at any regularly scheduled clinic visit that takes place during the 12 months after 
enrollment 
 
 
 
3 
Subject Selection, Enrollment, & Withdraw 
3.1 
Vulnerable Populations 
Fetuses, neonates, and prisoners are not eligible to participate. Pregnant women will not be targeted but 
will not be excluded, provided that they have not given, and are not expected to give, blood for any other 
reason within one week of the study. Children under 12 are excluded; children aged 12-17 must provide 
assent if they are mentally capable of doing so, and must also have a caregiver provide Informed 
Consent on their behalf. 
 
Potential Control Subjects must be able to provide consent on their own behalf. Research Subjects who 
are unable to consent for themselves, including those who are institutionalized, are eligible provided that 
they do not express any objections and a Legally Authorized Representative (LAR) signs Informed 
Consent on their behalf. Inclusion of individuals who are unable to provide informed consent is based on 
the principle of beneficence: approximately 25% of epilepsy patients fall into this category, and they are 
well-represented in the group that may ultimately benefit from this test. In all cases, every effort will be 
made to inform both the potential subject and the healthcare representative of the study and the 
associated risks and benefits.   
 
Any member of the following classes, who is reasonably available, may act as a subject’s healthcare 
representative (in descending order of priority): 
• 
Spouse (unless an action for divorce is pending)  
• 
Adult child (18 years or older) 
• 
Parent 
• 
Adult sibling 
• 
Adult grandchild  
• 
Other adult who has knowledge of the patient’s preferences and values, including but not limited 
to religious and moral beliefs, who assess how the patient would make decisions 
 
3.2 
Inclusion Criteria 
3.2.1 Research Subjects 
• 
Aged 12 and older 
• 
Evaluation in at least one of the following settings: 
o 
Newly referred to the University of Pennsylvania’s Penn Epilepsy Center. These patients may not 
have completed any diagnostic evaluation at Penn, other than an initial physician consultation, 

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Protocol Version 1 
prior to enrollment and must agree to allow the study team to collect records regarding their 
diagnostic evaluations (including EEG). Diagnostic evaluations may take place at Penn or outside 
sites 
o 
All patients who are admitted to the University of Pennsylvania for cVEEG monitoring 
3.2.2 Control Subjects 
• 
Aged 18 and older 
• 
Provide verbal confirmation that they do not experience seizures or suspected seizures of any 
type (a single instance of febrile seizure prior to age 2 is allowed) 
• 
Provide verbal confirmation that they have not taken any medications used to treat seizures for a 
minimum of two months prior to providing a blood sample 
• 
Able to provide Informed Consent 
 
 
3.3 
Exclusion Criteria 
3.3.1 Research Subjects 
 
• 
Patients who, in the opinion of the investigator or the patient’s neurologist, are unable to give 
Informed Consent due to mental impairment or any other reason AND do not have a LAR who can 
give Informed Consent on their behalf. Patients aged 12-17 (inclusive) must provide assent if they are 
mentally capable of doing so, and must also have a caregiver who provides Informed Consent on 
their behalf 
• 
Patients who, in the opinion of their neurologist at the University of Pennsylvania, are not good 
candidates for donating blood for any reason 
3.3.2 Control Subjects 
• 
Younger than 18 
• 
Experience seizures or suspected seizures of any type (a single instance of febrile seizure prior 
to age 2 is allowed) 
• 
Treatment with an anti-seizure medication within two months prior to providing a blood sample 
• 
Unable to provide Informed Consent 
 
3.4 
Recruitment  
Before the research begins, the Principal Investigator will present this study to the University of 
Pennsylvania’s Neurology Department’s Patient-Oriented Research Committee.   
 
The study team will also present the study to the attending epileptologists, resident physicians, fellows, 
and nurse practitioners at the Penn Epilepsy Center and ask for their advance permission to contact their 
new patients in the outpatient clinic, and their patients who are admitted to HUP for cVEEG monitoring. 
Physicians who object to the study for any reason may elect not to allow their patients to participate. 
Physicians and nurse practitioners may also elect to contact the study team to prohibit them from inviting 
individual patients to join for any reason, or to prohibit enrolled subjects from giving blood. All Research 
Subjects who join the study at their first outpatient visit may provide a blood sample in support of Specific 
Aim 1, regardless of when the blood draw occurs – at their first visit or at a later visit – since they will have 
been prospectively identified and enrolled as part of a true cohort. 
 

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CARPE: Epilepsy Biomarker 
Confidential 
Protocol Version 1 
In the interest of enrolling a true cohort and in consideration of the low-risk nature of this study, in the 
absence of an attending physician’s objection, the study team may approach all potentially eligibly 
patients (provided that the physician has previously approved the study as described above). 
 
The study team will review clinic lists and identify patients who are attending new outpatient visits at the 
Penn Epilepsy Center or are being admitted for cVEEG monitoring. A member of the study team may 
approach and consent any potential subject in the outpatient setting at any point during their visit. The 
study team may approach any potential subject who has been admitted for cVEEG monitoring at any 
point after his her or admission. 
 
The study team will invite adults who accompany Research Subjects to participate as Control Subjects as 
time permits until a maximum of 240 Control Subjects have provided a single blood sample. 
3.5 
Informed Consent 
No blood sample or medical information may be collected prior to or in absence of a subject or subject’s 
LAR giving Informed Consent. 
 
To begin the informed consent process, an appropriately trained member of the study team, such as the 
Principal Investigator, Sub-Investigator, Study Coordinator, or Research Assistant, will approach potential 
subjects in a private area and explain the overall study and the consent document using language that 
the individual can easily understand. The study team will make every effort to complete the informed 
consent process in a private room, but when space constraints render this impossible and potential 
subjects do not object, the study team may complete the informed consent process in a semi-private 
alcove space in the outpatient clinic normally. When all of the potential subject’s questions have been 
answered to his or her satisfaction, he or she will be invited to sign the Informed Consent form. All 
subjects will receive a copy of the signed document.  Original signed Informed Consent forms will be kept 
in the study files, in a locked office at the Penn Epilepsy Center. This process applies to both Research 
and Control Subjects. 
 
3.6 
Withdraw 
If a Research or Control subject informs the research team either by phone or mail of his or her desire to 
withdraw from the study and the subject’s sample or samples have not already been used for research, 
that subject’s samples will be destroyed as outlined in the Informed Consent form.  This decision will not 
affect results from research already preformed on the subject’s samples, but no additional tests will be 
carried out and the study team will not access his or her medical record after notification of withdraw. 
 
 
4 
Risk Analysis 
An appropriately trained individual will draw a single sample of approximately 5ml of blood by 
venipuncture no more than twice per day. Risks of venipuncture include discomfort, bruising, dizziness, 
and rarely fainting and infection. 
 
The greatest risk associated with this study is the release of health records.  In addition to following all 
HIPAA guidelines, the study team will take extensive steps to minimize this risk, as described below in 
Section 9, “Sample Processing and Storage,” and Section 10, “Privacy and Confidentiality.” 
 

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Protocol Version 1 
 
5 
Safety and Adverse Events 
All adverse events will be collected and reported in accordance with International Conference on 
Harmonization and Good Clinical Practice Guidelines.  
5.1 
Definitions 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study. A preexisting condition should only be considered an AE if it increases in 
frequency or intensity during the study. 
 
Serious Adverse Event 
A serious adverse event (SAE) is an AE that results in any of the following outcomes:  
• Death 
• Life-threatening 
• Hospitalization or prolongation of hospitalization 
• Congenital anomaly or birth defect 
• Persistent or significant disability or incapacity 
• Important medical event (in the investigator’s judgment, the event jeopardizes the subject’s health, 
or required intervention to prevent another serious outcome listed above) 
 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency  (i.e. not described in study-related documents) 
• Related or possibly related to participation in the research (i.e. there is a reasonable possibility that 
the  research procedures may have caused the incident experience, or outcome) 
• Places subjects or others at greater risk of physical, psychological, economic, or social harm 
 
5.2 
Recording and Reporting Adverse Events 
Because this is not an interventional study, AE recording and reporting will be limited to AEs that may be 
related to study procedures (i.e., blood draws). All AEs that occur from the time that subjects sign 
informed consent through their completion of the research blood draws will be collected and reported. 
 
Study staff must actively seek information about adverse events and unanticipated problems involving 
risk to subjects or others. Adverse events must be recorded in the case report form (CRF).   
 
The clinical course of each AE must be followed until resolution, stabilization, or the investigator’s 
determination that study participation did not cause the AE. SAEs that are ongoing at the end of the study 
must be followed through final outcome. Any SAE that occurs after a research blood draw and is 
considered to be possibly related to the study should be recorded and reported immediately. 
 
All SAEs must be reported to Cognizance Biomarkers as soon as possible, but no later 24 hours after the 
study staff becomes aware of the event. The event should be reported using Cognizance Biomarkers’ 
SAE report form, and include all readily available information. Follow-up reports must be issued as new 

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CARPE: Epilepsy Biomarker 
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Protocol Version 1 
information about the SAE becomes available. Additionally, study staff must follow institutional 
requirements for reporting AEs, SAEs, and unanticipated problems involving risks to subjects and others. 
 
5.3 
Medical Monitoring 
Cognizance Biomarkers will monitor the study progress on-site at periodic intervals throughout the study.  
This will include careful assessment and appropriate reporting of adverse events as noted above. 
 
 
6 
Data Handling 
6.1 
Research Subjects 
Source documentation of subjects’ medical history, clinical epilepsy diagnostic procedures, and epilepsy 
medications will remain in subjects’ medical charts. Signed Informed Consent/ HIPPA forms will be stored 
in separate study binders. The only study procedures associated with this research are blood draws; all 
other data used for the study will be extracted from subjects’ medical records and recorded on the CRFs. 
6.2 
Control Subjects 
Data will be limited to the following, and will be self-reported at the time of Consent: 
• 
Gender 
• 
Age 
• 
Confirmation that they do not experience seizure or suspected seizures 
• 
Confirmation that they are not being treated with anti-seizure medications for any condition 
 
All data will be stored in study binders, separate from signed Informed Consent/ HIPPA forms.  
 
 
7 
Data Analysis 
7.1 
Sample Size Determination 
Enrollment will continue until 240 outpatients have joined the study, provided a single blood sample, and 
undergone an EEG that is accessible to the study team. Subjects who either do not provide a blood 
sample or do not undergo an EEG will be replaced.  
 
This sample size is based on the need for 68 subjects per group and reflects the expectation that within 
six months of initial presentation, 50% will be diagnosed with epilepsy, 30% will be diagnosed with non-
epileptic events, and 20% will have an unknown diagnosis. 
 
Control samples will be used as needed to further validate the CARPE test. 
 
 
7.2 
Statistical Methods 
The goals of the study are to determine whether the CARPE value can be used effectively and accurately 
to diagnose patients with epilepsy, and to establish the threshold for diagnosis. The CARPE AUC from 

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CARPE: Epilepsy Biomarker 
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Protocol Version 1 
the ROC curve of our pilot data was 1.0 and the sICAM5 AUC was 0.87. For a conservative estimate, the 
sample size will be estimated based on the sICAM5 AUC, which is the lower value.  
  
 
Accuracy: To determine the accuracy of the test, we will construct ROC curves for sensitivity and 
specificity of CARPE by varying the threshold value for classifying epilepsy patients. The gold standard 
for constructing the ROC curve will be the diagnosis as determined by the panel of three independent 
epileptologists. The aim of this part of the study is to construct a reliable ROC curve. It is likely that the 
gold standard panel will not come to a conclusive diagnosis approximately 20% of the time, and these 
unknowns will not be included in the ROC determination. We will consider a conclusive diagnosis to be 
agreement between at least two of the three epileptologists that the subject is epileptic or non-epileptic at 
the time of evaluation. We use the AUC of the ROC curve as a global measure of the effectiveness of 
these measurements. To this end, we assume that the prevalence rate is 50% for epilepsy among all the 
study subjects. Moreover, we assume that the CARPE and sICAM5 measures are normally distributed for 
both epilepsy and non-epilepsy subjects.  
  
 
With an Alpha of 0.05 and a Beta of 0.2, comparing the AUC of 0.87 to the null hypothesis value of 0.7, 
the minimal required sample size per group is 68. The smaller group in this study will be subjects who 
have the diagnosis of non-epileptic attacks, which will likely represent 30% of the whole group. This 
justifies the sample size n=240 as adequate for the study. The determination of success will be based on 
this analysis. 
 
 
Threshold: The second analysis will establish the threshold values to be used for the expected 
subsequent study.  The goal is to choose the threshold value of CARPE for identifying epilepsy subjects 
with specificity of 0.8 and sensitivity of 0.8. For this analysis the entire study group will be analyzed. The 
panel of epileptologists will provide their best estimate of likely epileptic or likely non-epileptic events for 
this analysis (agreement among two members of the panel will be sufficient).   
 
Our gold standard comparator in for this study is the panel of three independent epileptologists rather 
than EEG alone due to the fact that EEG’s sensitivity for detecting epilepsy is only 50%.9,10 It is 
understood that CARPE must significantly exceed this in order to be considered a useful diagnostic test. 
 
 
8 
Sample Collection 
• 
Outpatient Research and Control Subjects will be asked to provide up to two 5ml tubes of blood  
via venipuncture for research at enrollment. It will not be considered a violation if the Control 
Subject gives less than two tubes of blood (i.e., if he or she gives one tube or less, or if the 
phlebotomist is unable to obtain any amount of blood).  
• 
Subjects who undergo cVEEG monitoring at HUP will be asked to provide no more than two 5ml 
sample of blood via venipuncture per day (12am-11:59pm) for research.    
• 
All Research Subjects will have the option of providing an additional single 5ml sample of blood 
via venipuncture for research at any regularly scheduled clinic visit that takes place within 12 
months of enrollment (Control Subjects will only be asked to give blood at the time of enrollment.) 
 
All samples will be collected at the Hospital of the University of Pennsylvania’s Department of Neurology.  
 
All blood draws are optional, and it will not be considered a protocol deviation of a blood draw is missed 
for any reason (including subject preference).   

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9 
Sample Processing and Storage 
9.1 
Duration of Storage 
Cognizance Biomarkers will store subjects’ samples for approximately five years; this will allow ample 
time for batch processing and re-testing as necessary. We will destroy all samples that have not been 
processed after five years. 
 
9.2 
Vial Labeling 
All samples collected for research will be de-identified and labeled with the date, protocol number, and a 
numerical or alphanumerical code. The samples will not include any subject identifiers.   
 
9.3 
Sample Preparation 
As soon as possible after it is drawn, plasma will be isolated from whole blood and stored at -80oC. The 
plasma will be assayed using academic or commercial testing. 
 
10 Privacy and Confidentiality 
10.1 Study Samples 
Only personnel authorized by the University of Pennsylvania’s IRB and Cognizance Biomarkers will have 
direct access to the study samples and documents. Samples will be labeled with only the following 
information: date of collection, protocol number, and numerical or alphanumerical ID. Control Samples will 
be designated as such with the letter “C.” Any subsequent vials used during research will also be free 
from personally identifying information and may only include, at most, the information listed above. 
 
10.2 Medical Information 
All records pertaining to the identity of participants in the Research Repository will be maintained as 
private and confidential.  Data will be labeled with the Subject ID (001, 002, etc) and protocol number 
only.   
 
 
11 References 
 
1. 
Benbadis SR, Allen Hauser W. An estimate of the prevalence of psychogenic non-epileptic 
seizures. Seizure. Jun 2000;9(4):280-281. 
2. 
Collins WC, Lanigan O, Callaghan N. Plasma prolactin concentrations following epileptic and 
pseudoseizures. J Neurol Neurosurg Psychiatry. Jun 1983;46(6):505-508. 
3. 
Lee SY, Choi YC, Kim JH, Kim WJ. Serum neuron-specific enolase level as a biomarker in 
differential diagnosis of seizure and syncope. J Neurol. Oct 2010;257(10):1708-1712. 

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4.  
Maroso M, Balosso S, Ravizza T, et al. Toll-like receptor 4 and high-mobility group box-1 are 
involved in ictogenesis and can be targeted to reduce seizures. Nat Med. Apr 2010;16(4):413-
419. 
5. 
Ortinski PI, Dong J, Mungenast A, et al. Selective induction of astrocytic gliosis generates deficits 
in neuronal inhibition. Nat Neurosci. May;13(5):584-591. 
6. 
Vezzani A, Balosso S, Maroso M, Zardoni D, Noe F, Ravizza T. ICE/caspase 1 inhibitors and IL-
1beta receptor antagonists as potential therapeutics in epilepsy. Curr Opin Investig Drugs. Jan 
2010;11(1):43-50. 
7. 
Imai T, Baba M, Nishimura M, Kakizaki M, Takagi S, Yoshie O. The T cell-directed CC chemokine 
TARC is a highly specific biological ligand for CC chemokine receptor 4. J Biol Chem. Jun 6 
1997;272(23):15036-15042. 
8. 
Imai T, Yoshida T, Baba M, Nishimura M, Kakizaki M, Yoshie O. Molecular cloning of a novel T 
cell-directed CC chemokine expressed in thymus by signal sequence trap using Epstein-Barr 
virus vector. J Biol Chem. Aug 30 1996;271(35):21514-21521. 
9. 
Salinsky M, Kanter R, Dasheiff RM. Effectiveness of multiple EEGs in supporting the diagnosis of 
epilepsy: an operational curve. Epilepsia. Jul-Aug 1987;28(4):331-334. 
10. 
King MA, Newton MR, Jackson GD, Fitt GJ, Mitchell LA, Silvapulle MJ, Berkovic SF. Epileptology 
of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance 
imaging study of 300 consecutive patients. Lancet. Sep 26 1998;352(9133):1007-1011.