Paired pulse TMS-EEG in epilepsy: improving the evaluation of therapeutic efficacy

Epilepsy is one of the most common neurological disorders. Due to an increased
cortical excitability of the brain of epilepsy patients, epileptic seizures can
occur. Once the diagnosis of epilepsy is confirmed, in most patients
anti-epileptic drugs (AEDs) are prescribed. These AEDs should reduce the number
and/or severity of the epileptic seizures. Because, absence or re-occurrence of
seizures after prescribing medication is the only indication to assess whether
therapy is successful or not, evaluation of therapeutic efficacy is often
time-consuming.

Transcranial magnetic stimulation (TMS) in combination with EEG makes it
possible to stimulate the brain by applying magnetic pulses, while
simultaneously measuring the response of the brain to the applied pulse. In
this way TMS provides the opportunity to assess cortical excitability.

The combination of paired pulse TMS-EEG makes it hopefully possible to evaluate
the therapeutic efficacy of prescribed AEDs faster and more reliable.

The primary objective of this study is to evaluate differences in motor evoked
potential (MEP) and TMS evoked potential (TEP) to paired pulse TMS between
epilepsy patients with a successful response to AEDs and those who do not
(refractory patients).

Secondary objectives are
1) To evaluate differences in MEP and TEP to paired pulse TMS in epilepsy
patients with different types of epilepsy or using different types of AEDs
2) To explore (additional) signal analysis techniques for characterising the
MEP and TEP to paired pulse TMS

Interventional study at the Clinical Neurophysiology and Neurology departments
of the Medisch Spectrum Twente.

All patients will undergo 3 to 4 paired pulse TMS sessions, over a period of
one year. The first TMS session will take place while the patient is still drug
naïve, the second session 8 to 12 weeks after starting with AEDs, and the final
session 1 year after starting with AEDs. Optionally, an additional fourth TMS
session will take place, in case a second AED is prescribed (8-12 weeks after
starting the second AED).

Paired pulse TMS is a non-invasive, safe and painless technique.

For each TMS session: Applying the EEG cap and EMG electrodes takes ~15
minutes, locating the motor hot spot and determining the rMT ~10 minutes for
each side, and the TMS session ~45 minutes. A total of 600 paired pulses and
~100 single pulses are applied. During the TMS session subjects will be seated
in a comfortable chair.

The EEG and EMG measurements, and listening to the noise sounds, will only
produce minor discomfort and do not have associated risks. Paired pulse TMS is
generally well tolerated and considered to be non-invasive, safe, and painless.

Possible side-effects and risks include: hearing problems, syncope, headache,
local pain, discomfort or seizures.
Overall, the risk of this study is low.

The subjects will have no benefit from participating in this study.