Non-invasive detection of potential epileptogenic cortical brain lesions

Epilepsy surgery is considered when patients are not responding to
anti-epileptic drug treatment. The presurgical evaluation for epilepsy surgery
is designed to locate the epileptogenic zone (the location of the epileptic
abnormality) and to determine if normal brain function will be affected
postoperatively.

If the epileptic focus is not adequately identified with noninvasive
investigations, long-term video-EEG monitoring with the use of intracranial EEG
(iEEG) may be required. iEEG requires neurosurgical placement of a grid of
electrodes in the surface of the brain. iEEG monitoring is physically and
psychologically demanding for the patient and his/her family.This procedure
carries the risk of severe complications, such as intracranial or intracerebral
haemorrhage or infection. Furthermore, placement of the electrodes can be
inaccurate and limited in scope resulting in a reduced chance to acquire the
required information.

The benefits of a non-invasive, safe and more patient-friendly technique to
determine the epileptogenic zone are manifold. It will allow for more accurate
placement of iEEG electrodes, or make invasive iEEG redundant and thus reduce
patient burden and risk of complications significantly.

1. Increase detection and localization of epileptogenic lesions using
non-invasive TMS stimulation of suspect region's

2. Decrease invasiveness and/or improve the accuracy of the presurgical
evaluation by comprehensive noninvasive testing of suspected epileptogenic
regions using TMS-EEG

Prior to admittance to the EMU for pre-surgical evaluation lasting 5 days, the
medical files of patients will be reviewed by the neurologists involved in this
study. Suspect regions will be determined using the MRI. Participants will
undergo a total of two TMS-EEG evaluation sessions of the suspect region during
their stay at the EMU: on the day of admission and one measurement in the
morning of the day where AED dose was tapered to its lowest point.

Using navigated TMS, the suspect region's are activated. The response to this
activation can be objectified using the electroencephalogram (EEG). This allows
for non-invasive determination of the epileptogenicity of the suspect region's.
After the second TMS-EEG measurement, a seizure induction protocol will be
started with the goal to evoke a seizure using TMS stimulation. This
measurement will be performed not at the point of lowest AED dose, but after an
appropriate increase in AED dosage to prevent unwanted non-habitual seizure
provocation. The protocol will be performed bed-side. The information gathered
with this research may reduce the extent or increase the accuracy of the more
invasive intracranial EEG measurements.

The TMS-EEG measurements will be performed during a patient's regular stay at
the EMU for the pre-surgical evaluation. Participation consists of two 30
minute TMS sessions. The regular duration of the registration (5 days) will not
be influenced by this research.The TMS stimulation itself can be experienced as
a small shock with an accompanying muscle twitch. The seizure induction
protocol will be given in a ramping-up manner, with continuous patient feedback
to determine comfort, tolerability, and effects of the stimulation trials.

TMS is a safe technique. The first and most significant complication of TMS in
literature is seizure induction in itself, especially when medication is being
tapered (2.8% chance with regular TMS protocols). While this could be seen as
an adverse effect, this is not the case in this pre-surgical setting where
patients are admitted especially for seizure recordings and in this proposals
case the aim of the study. To increase the chance on seizures it is common
practice to taper medication during a patient's stay at the EMU. The EMU is a
setting designed for optimal safety of patients in case of seizure events. In
the EMU setting, seizures are warranted and TMS evoked seizures may give
valuable clinical information that influences the decision-making process for
that patient.