The value of simultaneous TMS-EEG recordings for diagnostic purposes in epilepsy patients

Epilepsy is one of the most common neurological diseases. The diagnosis of
epilepsy is currently based on clinical history together with EEG recordings.
However, EEG it is not very sensitive in the sense that it does not always
include epileptiform activity. Therefore, patients with unclassified spells
often undergo multiple EEG registrations before a diagnosis and treatment plan
can be made. It would be beneficial to have a method to provoke the occurrence
of epileptiform activity.
Transcranial magnetic stimulation (TMS) is a non-invasive method that can be
used to stimulate parts of the human brain. Due to recent developments, it is
now possible to record TMS and EEG simultaneously. In this way, the changes in
brain activity induced by TMS can be recorded with EEG.

To investigate whether it is possible to induce epileptiform activity with TMS.
We expect to see abnormal discharges on TMS-EEG and we expect that these
findings are of diagnostic value and will help to localize the epilepsy.

Single pulse TMS will be performed starting at an intensity of the resting
motor threshold. Stimulation will be delivered at the standard electrode
positions; F7(8), F3(4), T3(4), C3(4), T5(6), P3(4). After eight stimuli at
each position, the EEG responses are analyzed. If no response is seen, the
stimulation will be proceeded at higher intensities, in 30% increments, until a
response is visible or until the maximum output level of the TMS equipment is
reached.

Participants will not directly benefit from their participation in the study,
except for a compensatory (financial) incentive. TMS is a widely used
non-invasive brain stimulation technique, based on the principle of
electromagnetic induction. During stimulation, the participant will likely hear
the clicks of the TMS pulses and experience stimulation of nerves and muscles
of the head. The most common side effect is a light transient headache (2-4%
occurrence). A severe headache is uncommon (0.3-0.5% occurrence). In TMS
studies of patient populations (e.g. epilepsy) or those exceeding the standard
protocols (e.g. in intensity or frequency) epileptic seizures have been
reported in rare cases, most of these induced seizures can be attributed to
high-frequency stimulation. In the current study, healthy participants and
patients will be stimulated with a protocol that falls within the safety
guidelines, i.e. high-frequency stimulation is not used. A seizure that occurs
coincidentally during the measurement cannot be excluded. Although it is not
expected, in case of the (accidental) occurrence of an epileptic seizure a
neurologist/clinical neurophysiologist will always attend the TMS experiment.
So specialized care can be given.
All subjects are screened for their relevant medical history and other TMS
safety aspects (e.g. metal parts in the head). In summary, because the risk and
burden associated with participation can be considered negligible-to-minimal,
we do not expect serious adverse events during the project.