Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC
Condition: Tuberous Sclerosis Complex
MeSH terms: Tuberous Sclerosis; Epilepsy; Sclerosis
Study type: Observational

Summary: 
      To determine whether EEGs during infancy is a reliable biomarker to identify TSC patients
      that will develop infantile spasms/epilepsy in the near future and thus are appropriate
      candidates for an antiepileptogenic drug trial. Since not all patients with TSC develop
      epilepsy, it would be useful to have a biomarker that could predict those patients destined
      to have epilepsy and thus identify those TSC patients most appropriate for an
      antiepileptogenic drug trial. A recent study suggests that treating TSC patients with an
      abnormal EEG prior to onset of infantile spasms with vigabatrin may improve neurological
      outcome, but the use of EEG as a reliable biomarker of future epilepsy has not been
      rigorously validated. In this specific aim, we will test the reliability of EEG in predicting
      future development of infantile spasms or epilepsy in TSC patients during the first year of
      life.
    

Detailed description: 
      Current therapeutic approaches for epilepsy primarily represent symptomatic treatments that
      suppress seizures, but have not been demonstrated to prevent epilepsy or modify disease
      progression. In recent years, there have been tremendous interest and effort by basic
      scientists and clinicians in epilepsy in developing disease-modifying or "antiepileptogenic"
      therapies. However, these efforts are hindered by a couple significant limitations: 1)
      difficulty in identifying an appropriate high-risk patient population in which a preventative
      approach is feasible and justifiable, and 2) lack of appropriate drug targets with
      antiepileptogenic properties. Tuberous Sclerosis Complex (TSC) is one of the most common
      genetic causes of epilepsy and a subset of TSC patients may represent a rational, feasible
      population to target with an antiepileptogenic approach for several reasons. First of all,
      some patients are diagnosed with TSC at a young age before the onset of epilepsy due to
      non-neurological findings - thus, it is feasible to identify these patients and initiate a
      potential antiepileptogenic treatment at an early stage of epileptogenesis. Second, these
      patients are at high risk for developing epilepsy (~80%) in the future, including infantile
      spasms (~35%), a particularly devastating type of childhood epilepsy with a poor prognosis -
      thus, initiating a therapy with potential side effects in a pre-symptomatic stage can likely
      be justified in TSC patients. Finally, the identification of the mTOR pathway in the
      pathophysiology of TSC suggests that mTOR inhibitors could have antiepileptogenic properties
      in TSC, as already supported by pre-clinical animal studies - thus, a rational
      mechanistically-based treatment potentially already exists and can be readily tested in TSC
      patients. However, there may be significant risks and side effects of mTOR inhibitors,
      especially during early childhood, such as chronic immunosuppression and theoretical effects
      on learning, growth, and development. Thus, before initiating an antiepileptogenic drug trial
      in TSC patients, it would be beneficial to obtain further evidence to optimize the selection
      criteria and treatment paradigms to maximize efficacy and minimize side effects of mTOR
      inhibitors.

      The aim of this clinical trial is to determine whether EEGs during infancy is a reliable
      biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near
      future and thus are appropriate candidates for an antiepileptogenic drug trial.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Infants that are seizure free at the time of the study enrollment and meets genetic or
        clinical diagnostic criteria for TSC (determined as standard of care); parent/family
        guardian health status is unknown
      
Biospecimen description: 
      A single venous blood sample will be drawn from the child and parents/family guardian for
      future research studies and future genetic testing
    
Keywords: Epilepsy; TSC; Tuberous Sclerosis Complex; Infants; Seizures; Biomarkers; EEG