Transcranial Magnetic Stimulation combined with electromyography and electroencephalography as a diagnostic and prognostic tool in Juvenile Myoclonus Epilepsy.

Juvenile Myoclonic Epilepsy (JME) is one of the most common forms of
generalised epilepsy in children and young adults. It is characterised by
myoclonus, generalised seizures and an increased vulnerability to psychiatric
complaints. Although seizure freedom is achieved in most with anti-epileptic
drugs (AED) after several trials, more than 10% of patients continue to have
seizures.
Increased cortical excitability has emerged as a general feature of epilepsy
that is also present in JME. Cortical excitability can be measured safely and
non-invasively with Transcranial Magnetic Stimulation (TMS). Previous research
with TMS in people with JME and other types of epilepsy has shown that AED
lowers cortical excitability. Substantial decrease after initiation of AED
treatment positively correlates with seizure reduction on group level.
Currently, AED treatment initiation is based on the clinical experience of the
treating physician. There are indications that early effective AED treatment is
of great importance, as this influences the prognosis. Cortical excitability
changes upon AED treatment may help guide rational selection of the appropriate
drug and dosage for an individual person. If this is proven feasible, TMS may
revolutionise epilepsy treatment, as it will offer a means to measure and
predict treatment effectiveness, which is as of yet impossible.
The cause of psychiatric vulnerability in people with JME is incompletely
understood. It is plausible that pathologic changes in cortical excitability,
especially in the frontal cortex, underlie this characteristic of the disease.
Altered cortical excitability may also alter functional connectivity in people
with JME compared to healthy controls. New techniques such as TMS-EEG, offer
the opportunity to investigate these changes.

Addition 17-6-2015
It has long been known that there is a bidirectional association between
epilepsy and migraine. However, it is unclear what the pathophysiological basis
of this association is. It is possible that this has to do with altered
cortical excitability. In migraine, cortical excitability was so far not
assessed using TMS-EEG.

The aim of the proposed research is twofold:
1) To investigate whether TMS can help guide individual AED treatment to
improve response.
a. in people with first seizures
b. in people who (temporarely) want to lower or stop medication
2) To investigate cortical excitability changes with TMS-EEG to shed light on
the relation between cortical excitability and psychological disturbances in
JME patients.

Controlled observational study

Participants with JME will come 2 to 7 times for measurements that will take
between 80 and 150 minutes.

Healthy participants will be asked to come twice, with a year in between. The
measurement sessions will take about 120 minutes.

Participants will be asked to fill in a screening list before participation,
which consists of questions on medical and neurological history, including
symptoms that could be indicative of migraine, family history of migraine and
epilepsy, use of medication and lifestyle.

Prior to each measuring session participants will be asked whether they are
pregnant and about their lifestyle in the hours preceding the measurements.

After each session, participants will be asked to rate their comfort/discomfort
during the measurents (TMS and EMG).

A neuropsychological evaluation will be carried out twice. This will include
the Strooptest, Trail making test, Word fluency test, Digit span and a
impulsiveness rating scale. During the first and last session, people with
epilepsy will be asked to fill in the Quolie-89, to evaluate any changes in
quality of life.

All participants with epilepsy will be asked to keep a seizure diary.

All participants will be asked to abstain from drinking alcohol and using drugs
in the 24 hrs preceding the sessions, not to smoke in 12 hours preceding the
sessions and not to drink coffee in the 6 hours preceding the sessions.

Nerve conductionstudies can lead to local discomfort, but carries no known
long-term risks.

A blooddrop test is the least invasive way to obtain blood for pharmacologic
evaluations. Aside from local discomfort, no risks are associated.

Electromyography can lead to slight discomfort during the procedure.
Infrequently, the needle can cause a muscle hemohrrage. This carries no
long-term risks.

TMS can lead to slight discomfort during the evaluation, and some subjects
report local pain on the scalp that is not severe and only lasts while the
experiment lasts. In rare cases, syncope has been reported. Very rarely, a
seizure may be triggered by TMS. The risk amongst people with epilepsy is
0-3.6%. Most seizures during TMS were reported in people with refractory
temporal lobe epilepsy who were undergoing pre-surgical evaluation and in whom
anti-epileptic drugs were tapered. This type of epilepsy is different from JME.
It is more difficult to treat, and the setting is very different as a
pre-surgical evaluation is aimed at triggering seizures. We expect, based on
literature, that the probability of a TMS-triggered seizure in people with JME
is well below 3.6%, and nil in healthy controls.