Role of Hormones in Susceptibility to Seizures in Women With Epilepsy
Condition: Epilepsy
MeSH terms: Epilepsy; Seizures
Study type: Observational

Summary: 
      This study will measure and compare hormone levels in women with catamenial epilepsy
      (epilepsy in which seizures are more frequent during menstrual periods), women with seizures
      not related to their menstrual cycle, and normal control subjects. It will determine whether
      there are differences among the three groups in their hormone levels or in how fast the
      levels change. It will also examine what relationship, if any, exists between hormone changes
      and seizures in women with catamenial epilepsy. The hormones under study include the gonadal
      hormones estrone, estradiol and progesterone, and the neuroactive steroids allopregnanolone,
      pregnenolone, and dehydroepiandrosterone.

      Women who meet the following criteria may be eligible for this 3-month study:

        -  Between 18 and 45 years of age, with catamenial epilepsy

        -  Between 18 and 45 years of age, with seizures, but not catamenial epilepsy

        -  Between 18 and 45 years of age, without seizures

      All participants will have a physical examination at the beginning of the study, at each
      clinic visit, and at completion or withdrawal from the study. In addition, they will undergo
      the following procedures:

      Baseline Monitoring

      For the first 2 months, all participants will keep a diary of their temperature and onset of
      menses. Women with epilepsy will also record their seizures.

      Electroencephalography (EEG)

      Healthy volunteers will have a 45-minute EEG (recording of the electrical activity of the
      brain) at the beginning of each menstrual cycle and each day during the menses. Women with
      epilepsy will have continuous EEG monitoring for 8 days, beginning 5 days before their
      menstrual period is expected. The continuous monitoring can be done on an outpatient basis,
      using a portable EEG recording device, or as an inpatient, with admission to the hospital for
      the 8 days of recording.

      Blood Sampling

      All participants will have a small blood sample (2 teaspoons) drawn once a day on days 10,
      14, 17, 19 and 21 of their menstrual cycle and three times a day on day 6 and for a period of
      8 days, starting 5 days before the expected menses and continuing for 3 days of the next
      cycle. For the days with three blood draws, a small needle that can stay in place for up to
      72 hours will be placed in the arm to avoid the discomfort of multiple needle sticks.
    

Detailed description: 
      Objectives. This is an initial pilot study to acquire information upon which a more specific,
      statistically rigorous follow-on investigation will be based. The objectives of the overall
      project are: (1) to compare the absolute levels and rates of change in levels of gonadal and
      neuroactive steroids in women with complex partial seizures and catamenial epilepsy with
      those of women with non-catamenial epilepsy and women volunteers without epilepsy, and (2) to
      determine if fluctuations in the levels of gonadal hormones (estrone, estradiol,
      progesterone) and neuroactive steroids (allopregnanolone, pregnenolone and
      dehydroepiandrosterone) correlate with seizure occurrence and the frequency of interictal
      spikes/wave discharges in women with catamenial seizure exacerbations.

      Study Populations. Group A: adult women with complex partial seizures and catamenial
      exacerbations. Group B: adult women with complex partial seizures without catamenial seizure
      exacerbations. Group C: adult female volunteers without epilepsy.

      Design. Subjects will undergo baseline monitoring of seizures and menses for two months prior
      to entry. Upon enrollment into the study, blood (10 ml) will be drawn for determinations of
      estradiol, estrone, progesterone, allopregnanolone, dehydroepiandrosterone (DHEA) and
      pregnenolone in all study populations once daily at 08:30 hr on menstrual cycle days, 10, 14,
      17, 19 and 21; and three times daily at 08:30, 13:30 and 18:00 starting 5 days before
      expected menses and continuing for a total of 8 days as well as on menstrual cycle day 6.
      During 8 days starting 5 days before expected menses interictal spike activity and seizures
      will also be monitored continuously with EEG. Comparisons of the rates of change of hormone
      levels and spike and seizure frequency will be made using the time derivatives of
      fluctuations in hormone levels or hormone level ratios. Comparisons of time series data will
      be made using nonlinear regression with an arbitrary (cubic spine) model.

      Outcome Parameters. The goal of this preliminary study is to obtain data regarding the
      fluctuation, during one menstrual cycle, of several hormones in epileptic and non-epileptic
      women of reproductive age. If the data show a relationship between (i) falling levels of
      plasma progesterone and allopregnanolone, (ii) increased levels of DHEA or pregnenolone or
      (iii) increased ratios of estrogen/progesterone, DHEA/progesterone, DHEA/allopregnanolone,
      pregnenolone/allopregnanolone and seizure manifestations and EEG documented interictal spike
      and seizure activity it would support the hypothesis that alterations in the levels of these
      steroid hormones are related to seizure exacerbations in women with catamenial epilepsy.
    

Keywords: Neurosteroids; Complex Partial Seizure; Menstrual Cycle; Allopregnanolone; Catamenial Epilepsy; Seizures; Epilepsy; Healthy Volunteer; HV; Normal Control