Cortical Excitability in Cryptogenic Localization‐Related Epilepsy: Interictal Transcranial Magnetic Stimulation Studies

Abstract

Summary:Purpose: To assess whether single-and pairedpulse transcranial magnetic stimulation (TMS) can measure the interictal brain excitability of medicated patients with cryptogenic localization related epilepsy (CLE). Changes in the balance between excitation and inhibition are the core phenomena in focal epileptogenesis. TMS can assess this balance in the primary motor cortex.Methods: We selected 18 patients with CLE and similar clinical features in whom we located the epileptogenic area reliably, with 11 age-and sex-matched healthy controls. For both motor cortices, we determined the threshold to TMS, the duration of the cortical silent period, and the corticocortical inhibition and facilitation curve.Results: TMS was safe. The more antiepileptic drugs (AEDs) taken by the patients, the higher their threshold to TMS. The silent period duration failed to show significant changes. On paired TMS, a cluster analysis identified a homogeneous subgroup of patients (n = 7) who showed a significantly defective corticocortical inhibition and excess facilitation. With respect to the epileptogenic area, the phenomenon was bilateral in four of these patients, ipsilateral in two, and contralateral in one. The phenomenon was independent of AEDs and many other clinical variables. However, this patient group had a higher seizure frequency and a higher proportion of electroencephalograms (EEGs) showing interictal generalized epileptic discharges than the rest of the patients.Conclusion: Paired TMS provided a valuable pathophysiologic insight into the interictal excitatory state of the cortex in CLE. This method can potentially supply useful prognostic clinical information.

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

“…The enhanced responses to electrical stimulation in epileptogenic cortex were taken as indication of an increased excitability of neural tissue in these areas. Similarly, studies using TMS consistently reported a hyperexcitability in focal epilepsies (7)(8)(9)(10). Consequently, changes in excitability have been helpful in identifying the seizure focus before resective surgery.…”

A facilitation tool: transcranial magnetic stimulation in epilepsy research

“…The altered balance between excitation and inhibition in neural membranes is the core factor to transit to the ictal state in the epileptogenic region (17). Synaptic inhibition in the brain is mediated by GABA receptors, which are divided into three classes: GABA A , GABA B , and GABA C .…”

“…The first two variables are mostly measured in single-pulse stimulation, while the third needs to be derived from a series of measurements fulfilled by paired-pulse TMS (17). Conventionally, MT is defined as the lowest stimulation intensity that elicits MEPs with peak-to-peak amplitude over 50 μV in the target muscle in at least 50% of successive trials (22).…”

New Perspectives in Transcranial Magnetic Stimulation: Epilepsy, Consciousness and the Perturbational Approach

“…Intracortical inhibition and facilitation are thought to reflect the excitability of separate populations of interneurons intrinsic to the cortical motor area. In fact, a reduction in cortical inhibition has been observed in different forms of epilepsy, including progressive myoclonic epilepsy [34, 35,161], juvenile myoclonic epilepsy (JME) [33,162], generalized epilepsy [163], and partial epilepsy [164,165]. All these studies have been performed in epileptic patients when awake after normal sleep.…”