HEP is a prospective, observational study whose primary goal is to identify clinical characteristics and bio-markers predictive of disease outcome, progression, and treatment response in participants with newly treated focal epilepsy.  The data to be collected on these participants include high-resolution clinical phenotyping (including co-morbidities) and treatment response, neuroimaging, electrophysiology, genomics and proteomics.  

A major objective of the project is to create an open data repository of clinical information and biologic samples for future studies. Participants will be enrolled over a 2 year period and follow up will continue on all participants, allowing up to 5 years (and a minimum of 3 years) of tracking. The estimated sample size is 500 participants.

The inclusion/exclusion criteria for HEP are detailed below:

Inclusion Criteria

  • Clinical seizure(s) and history consistent with focal epilepsy
  • Age ≥12 years and ≤60 years at time of seizure diagnosis
  • Age ≥12 years at time of enrollment
  • At least one confirmed spontaneous seizure in the 12 months prior to enrollment with one of the following:
    - Normal MRI with inter-ictal EEG showing focal abnormality (focal sharp waves or focal slowing)
    - Normal MRI and normal inter-ictal EEG, with clinical or electrographic seizure activity on ictal EEG
    - Focal lesion (non-progressive) on MRI with normal EEG (acceptable focal lesions include MTS, FCD, single cavernoma, and AVMs that are not of large size and lack significant amounts of hemosiderin)
    - Focal lesion (non-progressive) on MRI with focal abnormality on EEG
    - If normal EEG and normal or no MRI, a second confirmed spontaneous seizure in the 12 months prior to enrollment is required. Cases must be consistent with focal epilepsy and adjudicated by central reviewers
  • AED treatment (for seizures) instituted not more than 4 months prior to enrollment
    NOTE: Exception can be made if AED treatment was initiated more than 4 months ago, but all visit 1 activities can be completed within 5 ½ months of treatment initiation
  •  Complete AED history prior to enrollment (with approximate dates and doses) is available (exception can be made for AEDs taken for <1 week)

Exclusion Criteria

  • Idiopathic or symptomatic generalized epilepsy
  • IGE/focal epilepsy mixed syndromes
  • Any epilepsy etiology that could produce significant gliosis or brain injury and would be likely to alter biomarkers. These include:
    - Epilepsy with an etiology occurring in the previous two years that would produce significant CNS injury (e.g., traumatic brain injury that involves direct disruption of brain tissue, stroke, encephalitis).
    - History of intracranial bleeding (e.g., subarachnoid, intraparenchymal)
  • Identified genetic epilepsy syndrome
    - Focal genetic epilepsy OK to include – only one participant per family may be enrolled
  • Progressive neurological disorder (brain tumor, AD, PME, etc.)
  • Major medical co-morbidities such as renal failure requiring dialysis, metastatic cancer, HIV, or significant liver or renal disease
  • Autism Spectrum Disorder
  • Presence of moderate or greater developmental or cognitive delay prior to seizure onset (e.g., if an adolescent, not in self-contained classroom; if IQ is documented, should be > 70)
  • History of chronic drug or alcohol abuse (misuse or excessive use that interferes with activities of daily living) within the last 2 years
  • AED treatment given for non-seizure indication at or above the AED “target dose” and not stopped at least 5 AED half-lives before first seizure Seizures only during pregnancy
  • History of previous or current significant psychiatric disorder that would interfere with conduct of the study

Clinical Center Duties

  • Each Clinical Center will need to fulfill a set of specific requirements to qualify as a HEP center, including the following:
  • Ability to identify and enroll at least 10 participants per year for the first two years of the study, and to follow these participants for a minimum of three years
  • Ability to do 2-hour sleep deprived EEG (with sampling rates of 600-1000 Hz preferred)
  • Ability to meet HEP MRI protocol requirements (MRI facility capable of acquiring HEP sequences)
  • Personnel and facilities to process blood, urine and serum samples according to protocol, and store at -80ºC until time of shipment
  • Agreement to a visit-based payment model
  • On-site Wi-Fi to allow for immediate setting up of participant’s iPod
  • Computer with internet access for on-site completion of online questionnaires