Abstract
Objective: Antiseizure medications (ASMs), which may influence cortical excitability, are the mainstay of epilepsy treatment. Transcranial magnetic stimulation (TMS) helps evaluate cortical excitability. We assessed changes in TMS responses using serial TMS measurements in people treated with an adjunctive noncompetitive AMPA-receptor antagonist. Methods: We included adults with refractory, active epilepsy (≥ 1 seizure/month), advised to start adjunctive treatment with the noncompetitive AMPA-receptor antagonist perampanel as outpatients. After informed consent, we performed TMS measurement at three points: baseline before starting perampanel, at around 2 months after starting (4 mg/day), and at a final/effective dose around 6 months. Dependent on seizure reduction (> 50%), participants were dichotomized into responders (Rs) and nonresponders (NRs). We compared changes in motor cortex excitability through the rMT using a linear mixed-effects model. We evaluated TMS-evoked potentials (TEPs) to single pulse and paired pulse using within-subject Monte Carlo–based permutation analysis. Results: We included 18 adults, of whom 17 (6 R, 11 NR, 1 lost to follow-up) had baseline and second-month measurements, and nine (4 R, 5 NR) had all three. In responders, motor cortex excitability, quantified by rMT, significantly increased with increasing dose. Conversely, no significant changes were seen in the NR subgroup. TEPs for the single pulse and paired pulse showed no significant clusters for any peaks between measurement and group comparisons. Interpretation: The TEPs showed no significant changes between measurements and/or groups. Motor cortex excitability quantified by rMT is a potential biomarker to track or predict treatment outcomes in people starting adjunctive perampanel for epilepsy.
| Original language | English |
|---|---|
| Pages (from-to) | 1256-1264 |
| Number of pages | 9 |
| Journal | Annals of Clinical and Translational Neurology |
| Volume | 12 |
| Issue number | 6 |
| Early online date | 17 Apr 2025 |
| DOIs | |
| Publication status | Published - Jun 2025 |
Funding
Funding: The perampanel manufacturer Eisai provided an unrestricted grant to support this study. We thank S. Shmuely, M. Demuru, E. Geertsema, and T. Punte for helping with the measurements. We want to acknowledge W. M. Stern for helping set up the measurement protocol and S. N. Kalitzin for helping with the hardware and software. J.W.S. is based at UCLH/UCL Comprehensive Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centre's funding scheme. He receives support from the Dr. Marvin Weil Epilepsy Research Fund, the Christelijke Vereniging voor de verpleging van Lijders aan Epilepsie, the UK Epilepsy Society, the National Institute of Health Research, and the Academy of Medical Sciences. R.M.H. and R.D.T. receive support from the Christelijke Vereniging voor de verpleging van Lijders aan Epilepsie. R.D.T. reports lecture and consultancy fees from Medtronic, UCB, Theravarance, Zogenix, Novartis, and Arvelle and grants from EpilepsieNL, Medtronic, Michael J Fox Foundation, NewLife Wearables, and the Netherlands Organisation for Health Research and Development (843002707). P.R.B. receives lecture fees from NovoCure and Aurikamed. J.W.S. reports personal fees from Eisai, UCB Pharma, and Angelini Pharma and grants from Angelini and UCB to his department outside the submitted work. G.H.V. reports grants from the Dutch National Epilepsy Fund and Eisai. All other authors have no disclosures to make. We thank S. Shmuely, M. Demuru, E. Geertsema, and T. Punte for helping with the measurements. We want to acknowledge W. M. Stern for helping set up the measurement protocol and S. N. Kalitzin for helping with the hardware and software. J.W.S. is based at UCLH/UCL Comprehensive Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centre's funding scheme. He receives support from the Dr. Marvin Weil Epilepsy Research Fund, the Christelijke Vereniging voor de verpleging van Lijders aan Epilepsie, the UK Epilepsy Society, the National Institute of Health Research, and the Academy of Medical Sciences. R.M.H. and R.D.T. receive support from the Christelijke Vereniging voor de verpleging van Lijders aan Epilepsie.
| Funders | Funder number |
|---|---|
| National Institute for Health and Care Research | |
| ZonMw : Dutch Organisation for Health Research and Development | 843002707 |
Keywords
- AMPA-receptor antagonist
- intracortical facilitation
- resting motor threshold
- TMS-evoked EEG potential
- transcranial magnetic stimulation
- Humans
- Middle Aged
- Male
- Evoked Potentials, Motor/drug effects
- Anticonvulsants/pharmacology
- Transcranial Magnetic Stimulation
- Young Adult
- Adult
- Nitriles
- Female
- Pyridones/pharmacology
- Drug Resistant Epilepsy/drug therapy
- Motor Cortex/drug effects
- Cortical Excitability/drug effects