Cortical Excitability Tied to Duration and Degree of Seizure Control

brain cells neurons
brain cells neurons
This study identified a feature of the epileptic brain that evolves slowly and differs fundamentally in well-controlled and poorly controlled epilepsy.

Patients with poorly controlled and moderately controlled chronic epilepsy demonstrate differences in cortical excitability that progress over time, according to a new study published in the Annals of Clinical and Translational Neurology.

Transcranial magnetic stimulation (TMS) measures cortical excitability in patients with epilepsy and has been helpful in studies investigating antiepileptic drugs (AEDs). Previous studies demonstrated cortical excitability differences in patients with epilepsy on AEDs compared with healthy controls. TMS has also shown persistent cortical excitability in patients who are not responsive to AEDs compared with responders.  

In this study, Adam Pawley of the Department of Basic and Clinical Neuroscience at King’s College London in the United Kingdom and colleagues sought to examine the degree of cortical excitability using TMS in patients with chronic, uncontrolled epilepsy.  

The study included participants (18 years and older) from local epilepsy clinics who had epilepsy treated with AEDs. Participants were categorized into moderately controlled at 4 or less seizures per year (n=28), poorly controlled at 20 or more seizures per year (n=40), and normal controls (n=28). Exclusion criteria included contraindication to TMS, concomitant psychiatric or neurologic diagnoses, a history of nonepileptic seizures, inability to give consent or cooperate with TMS, and inability to provide a seizure diary.

Multiple TMS measurements were obtained including active motor threshold (AMT), resting motor threshold (RMT), intracortical facilitation (ICF), cortical silent period (CSP), and short-interval intracortical inhibition (SICI).  

Several potential confounders were assessed, including the participant’s age, age at diagnosis, duration of diagnosis, location of focal epilepsy, and the AEDs prescribed for the participant.

The investigators found higher RMTs and AMTs in the poorly controlled epilepsy group compared with the moderately controlled epilepsy group, which were higher than the controls’ RMTs and AMTs (P =.001 or less in all cases). Likewise, participants with poorly controlled epilepsy demonstrated lower ICF at 12 msec and 15 msec compared with controls (12 msec P =.001; 15 msec P <.001). Participants with poorly controlled epilepsy also demonstrated higher long-interval intracortical inhibition at 50 msec than the participants with moderately controlled epilepsy (P = .014). Of note, RMT and AMT increases were associated with duration of diagnosis in the group with poorly controlled epilepsy but not in the group with moderately controlled epilepsy.   

The duration of diagnosis and the AEDs prescribed did not fully explain the differences between groups.

Although imaging data were not obtained, the investigators hypothesized that in participants with poorly controlled epilepsy, the increased motor threshold with longer duration of disease may be tied to brain atrophy.

The researchers concluded that the study “identified a feature of the epileptic brain, similar across syndromes, that evolves very slowly over a timescale of years, and differs fundamentally between well-controlled and poorly controlled epilepsy.”  


Pawley AD, Chowdhury FA, Tangwiriyasakul C, et al. Cortical excitability correlates with seizure control and epilepsy duration in chronic epilepsy. Ann Clin Transl Neurol. 2017;4(2):87-97.