Electrical Brain Stimulation to Reduce Epileptic Seizures
Condition: Temporal Lobe Epilepsy
MeSH terms: Epilepsy; Epilepsy, Temporal Lobe
Study type: Observational

Summary: 
      OBJECTIVES:

      About 15% of patients suffering from focal epilepsy are refractory to available
      pharmacological treatments. Until now, the only hope for such patients has been the
      development of new pharmaceutical treatments or epilepsy surgery. In case of inoperability,
      different types of invasive brain stimulation such as vagus nerve stimulation or deep brain
      stimulation or non-invasive repetitive TMS have been evaluated to determine their
      anticonvulsive potential. For rTMS, weak and short lasting seizure reduction has been
      reported in different epilepsy syndromes.

      A new, non-invasive stimulation technique, transcranial direct current stimulation (tDCS),
      was useful to modulate cortical excitability in many cortical areas (M1, visual cortex,
      frontal cortex). Cathodal tDCS, with a current of 1 mA, induced long-term depression in
      animal models and reportedly decreased the excitability of both human and animal cerebral
      cortex. In epilepsy patients suffering from a malformation of cortical development, a single
      session of cathodal tDCS helped reduce seizures briefly. The purpose of this protocol is to
      study the effects of repeated applications of tDCS on the excitability of the seizure focus
      in patients with poorly controlled pharmacologically refractory temporal lobe epilepsy.

      STUDY POPULATION:

      We plan to study 56 patients between the ages of 18 and 80 suffering from temporal lobe
      epilepsy.

      DESIGN:

      Subjects will be allocated by blocked randomization to one of two groups (parallel design).
      Group A will receive cathodal tDCS and group B will receive Sham-tDCS on five consecutive
      days. Each subject will participate in 9 sessions (1 baseline visit, 5 intervention visits, 3
      follow-up visits). The effect of the intervention relative to the sham stimulation will be
      evaluated by comparing seizure frequency and neuropsychological tests during the 8 weeks
      before and after the intervention.

      OUTCOME MEASURES:

      Primary outcome measure will be the mean seizure frequency per 4 weeks in the tDCS group as
      compared to the Sham-tDCS group. To analyze the effect of the intervention (tDCS), seizures
      will be evaluated during a 2x4 week baseline period before tDCS and 2x4 weeks after the
      intervention. Using these data we will calculate the percentage change of seizures per 4
      weeks.

      Secondary outcome measures will be the scores of the neuropsychological testing (HVLT-R,
      BVMT-R, CTMT, COWAT) and number of epileptiform discharges in the EEG. Furthermore, th...
    

Detailed description: 
      OBJECTIVES:

      About 15% of patients suffering from focal epilepsy are refractory to available
      pharmacological treatments. Until now, the only hope for such patients has been the
      development of new pharmaceutical treatments or epilepsy surgery. In case of inoperability,
      different types of invasive brain stimulation such as vagus nerve stimulation or deep brain
      stimulation or non-invasive repetitive TMS have been evaluated to determine their
      anticonvulsive potential. For rTMS, weak and short lasting seizure reduction has been
      reported in different epilepsy syndromes.

      A new, non-invasive stimulation technique, transcranial direct current stimulation (tDCS),
      was useful to modulate cortical excitability in many cortical areas (M1, visual cortex,
      frontal cortex). Cathodal tDCS, with a current of 1 mA, induced long-term depression in
      animal models and reportedly decreased the excitability of both human and animal cerebral
      cortex. In epilepsy patients suffering from a malformation of cortical development, a single
      session of cathodal tDCS applied to various cortical areas including frontal and temporal
      cortex helped reduce seizures briefly. The purpose of this protocol is to study the effects
      of repeated applications of tDCS on the excitability of the seizure focus in patients with
      poorly controlled pharmacologically refractory frontal and/or temporal lobe epilepsy.

      STUDY POPULATION:

      We plan to study 56 patients between the ages of 18 and 80 suffering from frontal and/or
      temporal lobe epilepsy.

      DESIGN:

      Subjects will be allocated by blocked randomization to one of two groups (parallel design).
      Group A will receive cathodal tDCS and group B will receive Sham-tDCS on five consecutive
      days. Each subject will participate in 9 sessions (1 baseline visit, 5 intervention visits, 3
      follow-up visits). The effect of the intervention relative to the sham stimulation will be
      evaluated by comparing seizure frequency and neuropsychological tests during the 8 weeks
      before and after the intervention.

      OUTCOME MEASURES:

      Primary outcome measure will be the mean seizure frequency per 4 weeks in the tCDS group as
      compared to the Sham-tDCS group. To analyze the effect of the intervention (tDCS), seizures
      will be evaluated during a 2x4 week baseline period before tDCS and a 2x4 weeks after the
      intervention. Using these data we will calculate the percentage change of seizures/4 weeks.

      Secondary outcome measures will be the scores of the neuropsychological testing (HVLT-R,
      BVMT-R, CTMT, COWAT) and number of epileptiform discharges in the EEG. Furthermore, the
      patients will answer several questionnaires to evaluate quality of life (QOLIE-31-P), seizure
      severity (SSQ), and mood (BDI). To better understand the mechanisms underlying the proposed
      change of seizure frequency, we will use single- and paired- pulse transcranial magnetic
      stimulation (TMS) to identify corticomotor excitability changes.
    

Keywords: Epilepsy; Temporal Lobe Epilepsy; Cortical Excitability; Transcranial Direct Current Stimulation (tDCS); Memory Testing; Seizures; Transcranial Magnetic Stimulation (TMS); Memory; Plasticity