Inter-session repeatability of cortical excitability measurements in patients with epilepsy
Introduction
Over the last decade transcranial magnetic stimulation (TMS) has evolved into an excellent tool that can be used to investigate the pathophysiology of various neurological disorders (Siniatchkin et al., 2007, Vucic and Kiernan, 2006) including epilepsy (Badawy et al., 2007, Hamer et al., 2005, Manganotti et al., 2000, Reutens and Berkovic, 1992, Werhahn et al., 2000, Ziemann, 2004, Ziemann et al., 1998). TMS offers the opportunity to examine both excitatory and inhibitory functions of central motor pathways providing non-invasive clinical measurements of neuronal excitability (Macdonell et al., 2002, Ziemann et al., 1998). It also has the potential of demonstrating how excitatory/inhibitory changes in cortical excitability related to epilepsy are modulated under certain conditions as well as after the commencement of anti-epileptic medication.
TMS has been shown to be safe in patients with epilepsy with a reported risk of inducing an epileptic seizure of only 0–3.6% (Schrader et al., 2004), mainly in patients with chronic and frequent seizures. Previous studies have shown that cortical excitability is increased in patients with epilepsy compared to non-epilepsy controls (Badawy et al., 2007, Hamer et al., 2005, Manganotti et al., 2000, Reutens and Berkovic, 1992, Werhahn et al., 2000, Ziemann, 2004, Ziemann et al., 1998). It is important to validate the repeatability of these findings within the same patients between different sessions before longitudinal studies investigating the change in cortical excitability under different settings are planned. There are no reports on inter-session variability in patients with epilepsy. Previous studies investigating reproducibility of motor threshold (MT), short intracortical inhibition (2–5 ms interstimulus intervals [ISIs]) and intracortical facilitation (10–16 ISIs) were only performed on healthy participants (Boroojerdi et al., 2000, Maeda et al., 2002, Mills and Nithi, 1997, Ziemann et al., 1998). Those studies report fairly stable and repeatable inter-session and inter-investigator measurements. There are no reports on inter-session variability in long intracortical inhibition (ISIs > 100 ms).
The current study was designed to investigate inter-session variability in cortical excitability measures in patients with new onset drug naive idiopathic generalized epilepsy (IGE) and focal epilepsy and non-epilepsy controls to determine the reliability of repeated measures in these cohorts.
Section snippets
Participants
Patients were recruited through the First Seizure at Austin Health in Melbourne. This is an acute referral service for patients not previously diagnosed with epilepsy who present to the hospital following a seizure. The diagnosis of epilepsy and its sub-syndrome was made by at least two experienced epileptologists who were blinded to the TMS results on the basis of the clinical history, imaging and EEG findings. Only patients with a confirmed diagnosis of epileptic seizures and a normal
Results
None of the patients included in the study suffered any seizures attributable to TMS.
The results of both hemispheres in all groups were analysed. There were no inter-hemispheric differences in IGE or non-epilepsy controls, so only the data for dominant hemisphere in these two cohorts are presented here.
Discussion
We previously reported an increase in motor cortical excitability in drug naïve patients with new onset epilepsy (Badawy et al., 2007). This increase was found in both hemispheres in patients with IGE (decreased, short and long intracortical inhibition), with no inter-hemispheric differences. In contrast, inter-hemispheric differences were found in focal epilepsy with decreased short and long intracortical inhibition confined to the hemisphere with the seizure focus, together with a higher MT
Conflict of interest statement
The authors report no conflicts of interest.
Acknowledgements
We thank Dr. Mark Newton and the neurologists in the First Seizure Clinic for their help in recruiting the patients, Dr. Sue Finch and the Statistical Consulting Centre at the University of Melbourne for statistical input, Dr. Danny Flanagan for his help, the EEG technicians at Austin Health and the participants for their time.
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