Cortical inhibition by Retigabine. Assesment by transcranial magnetic stimulation in epilepsy patients.

Transcranial magnetic stimulation (TMS) has opened the possibility to asses
cortical excitability noninvasively, both in controls and patients. Its
application in epilepsy is a major area of research, since excitability changes
are at the heart of the disease . TMS has been used to investigate the
mechanism of action of several drugs. Sodium-channel blocking drugs elevate the
threshold, while drugs that act on GABAergic transmission improve intracortical
inhibition or prolong the silent period. In patients, TMS shortly after the
application of an antiepileptic drug can predict long-term seizure control.
Retigabine is a first-in-class antiepileptic drug that acts on potassium
channels. Indirectly, changes in GABAergic synaptic transmission contribute to
its efficacy. In-vivo studies of the physiological effect of Retigabine on
motor cortex in normal humans could deepen our understanding of mechanisms.
Our hypothesis is that Retigabine will shorten the silent period and diminish
intracortical facilitation on account of its action by potentiation of
inhibitory postsynaptic currents mediated by GABA receptors.

The study aims to answer the following questions:
1) What is the effect of Retigabine on cortical excitability measured by TMS ?
(primary).
2) To what extent are changes in excitabilty meausred with TMS related to
seizure control ? (secondary).

Observational neurophysiological/neuropharmacological study.
Patients with partial epilepsy, with or without secondary generalization that
have an indication to initiate adjuvant treatment with Retigabine. The
responsibility to start treatment remains within the responsibility of the
treating neurologist.
Doses of concurrent medication are kept constant during the study.
Patients with any implanted electronic device are excluded.
Patients with clinical or radiological evidence of major structural abnormality
of the motor cortex or the pyramidal tract are excluded.
TMS is performed before starting Retigabin, on 600 mg/day (post1), on 900/dag
(post2) or after any other different maintenance dose is reached (post3).
In each session resting motor threshold, short interval (2 and 5 ms)
intracortical inhibition, intracortical facilitation (10 and 15 ms), long
interval intracortical inhibition (250 and 300 ms) en silent period are
measured.

Magnetic stimulation is applied to the motor cortex. The motor response is
measured with surface electrodes on small hand muscles. TMS is not painful, but
feels unpleasant at high intensities. The present protocol focuses on responses
close to threshold. These intensities are well tolerated.
The total number of stimuli and their intensity and frequency is far from the
dose considered relevant for provocing seizures. A seizure that occurs
coincidentally during the measurement can not be excluded.
Blood samples will be taken for serum levels of retiabine and other drugs.