Long-interval intracortical inhibition as biomarker for epilepsy: a transcranial magnetic stimulation study

Abstract

Cortical excitability, as measured by transcranial magnetic stimulation combined with electromyography, is a potential biomarker for the diagnosis and follow-up of epilepsy. We report on long-interval intracortical inhibition data measured in four different centres in healthy controls (n = 95), subjects with refractory genetic generalized epilepsy (n = 40) and with refractory focal epilepsy (n = 69). Long-interval intracortical inhibition was measured by applying two supra-threshold stimuli with an interstimulus interval of 50, 100, 150, 200 and 250 ms and calculating the ratio between the response to the second (test stimulus) and to the first (conditioning stimulus). In all subjects, the median response ratio showed inhibition at all interstimulus intervals. Using a mixed linear-effects model, we compared the long-interval intracortical inhibition response ratios between the different subject types. We conducted two analyses; one including data from the four centres and one excluding data from Centre 2, as the methods in this centre differed from the others. In the first analysis, we found no differences in long-interval intracortical inhibition between the different subject types. In all subjects, the response ratios at interstimulus intervals 100 and 150 ms showed significantly more inhibition than the response ratios at 50, 200 and 250 ms. Our second analysis showed a significant interaction between interstimulus interval and subject type (P = 0.0003). Post hoc testing showed significant differences between controls and refractory focal epilepsy at interstimulus intervals of 100 ms (P = 0.02) and 200 ms (P = 0.04). There were no significant differences between controls and refractory generalized epilepsy groups or between the refractory generalized and focal epilepsy groups. Our results do not support the body of previous work that suggests that long-interval intracortical inhibition is significantly reduced in refractory focal and genetic generalized epilepsy. Results from the second analysis are even in sharper contrast with previous work, showing inhibition in refractory focal epilepsy at 200 ms instead of facilitation previously reported. Methodological differences, especially shorter intervals between the pulse pairs, may have contributed to our inability to reproduce previous findings. Based on our results, we suggest that long-interval intracortical inhibition as measured by transcranial magnetic stimulation and electromyography is unlikely to have clinical use as a biomarker of epilepsy.

Lacosamide-Induced Dyskinesia in Children With Intractable Epilepsy

“…19 Impaired inhibition likely plays a role not only in a variety of pediatric movement disorders, but also in epilepsy. 20,21 While the specific effects of lacosamide on motor inhibition in children with epilepsy is unknown, lacosamide does decrease motor cortex excitability in adults. 22 Although aberrant inhibition may be associated with dyskinesias stemming from a variety of etiologies, key differences in the specific circuitry involved for a particular individual may explain how the same drug can relieve or provoke similar-appearing movements in different disease states.…”

Transcranial magnetic stimulation as a tool to understand genetic conditions associated with epilepsy

“…9 A number of studies have attempted to identify TMS-based biomarkers for diagnosis or prediction of treatment response in the epilepsies. 10,11 In general, these studies have involved relatively heterogenous patient groups, which may have contributed to the paucity of clinically adopted markers. 10,11 Studying TMS in genetically-defined patient groups may decrease inter-individual variability and increase power for detecting clinically useful signatures of pathophysiological processes yielding biomarkers for diagnosis and treatment of these conditions.…”

“…10,11 In general, these studies have involved relatively heterogenous patient groups, which may have contributed to the paucity of clinically adopted markers. 10,11 Studying TMS in genetically-defined patient groups may decrease inter-individual variability and increase power for detecting clinically useful signatures of pathophysiological processes yielding biomarkers for diagnosis and treatment of these conditions. This approach has already been employed for several genetic conditions of relevance to epilepsy, which we now review.…”

TMS-EEG: first steps towards a clinical application in epilepsy

“…Although the findings of ppTMS studies are the most consistent and promising, it should be noted that the majority of positive studies were from a single research group. Even though they have confirmed their own findings multiple times for different types of epilepsy, these results have not been reproduced by other authors (Bauer et al 2018). …”

“…Although significant differences were found for various excitability measures, with LICI as the most promising measure, TMS-EMG results have been conflicting (Bauer et al 2018;. For TMS-EEG data is limited, with only a handful studies published so far.…”