Effects of the noncompetitive AMPA receptor antagonist perampanel on thalamo-cortical excitability: A study of high-frequency oscillations in somatosensory evoked potentials. Issue 5 (May 2021)

• Record Type: Journal Article
• Authors: Lanzone, Jacopo; Boscarino, Marilisa; Ricci, Lorenzo; Insola, Angelo; Tombini, Mario; Di Lazzaro, Vincenzo; Assenza, Giovanni
• Is Part Of: Clinical neurophysiology. Volume 132:Issue 5(2021)
• Page Start: 1049
• Page End: 1056
• Publication Date: 2021-05
• Subjects: Epilepsy -- High frequency oscillations -- Somatosensory evoked potentials -- Perampanel -- Thalamus -- HFO -- SEP; Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2020.12.030
• Languages: English
• ISSNs: 1388-2457

Abstract

Highlights: Perampanel add-on affects the area of the early burst of SEP-HFOs. P24/N24 complex is increased in people with epilepsy and decreases after therapy with Perampanel. SEP-HFOs modifications suggest Perampanel acts on cortico-subcortical excitability. Abstract: Objective: We designed a longitudinal cohort study on People with Epilepsy (PwE) with the aim of assessing the effect of Perampanel (PER) on cortico-subcortical networks, as measured by high-frequency oscillations of somatosensory evoked potentials (SEP-HFOs). SEP-HFOs measure the excitability of both thalamo-cortical projections (early HFOs) and intracortical GABAergic synapses (late HFOs), thus they could be used to study the anti-glutamatergic action of PER, a selective antagonist of the AMPA receptor. Methods: 15 PwE eligible for PER add-on therapy, were enrolled prospectively. Subjects underwent SEPs recording from the dominant hand at two times: PwET0 (baseline, before PER titration) and PwET1 (therapeutic dose of 4 mg). HFOs were obtained by filtering N20 scalp response in the 400–800 Hz range. Patients were compared with a normative population of 15 healthy controls (HC) matched for age and sex. Results: We found a significant reduction of Total HFOs and mostly early HFOs area between PwET0 and PwET1 (p = 0.05 and p = 0.045 respectively) and between HC and PwET1 (p = 0.01). Furthermore, we found a significant reduction of P24/N24 Amplitude between PwET0 and HC and between PwET0 and PwET1 (p = 0.006 and p = 0.032, respectively). Conclusions: Introduction of PER as add-on therapy reduced the area of total HFOs, acting mainly on the early burst, related to thalamo-cortical pathways. Furthermore P24/N24 amplitude, which seems to reflect a form of cortico-subcortical integration, resulted increased in PwE at T0 and normalized at T1. Significance: Our findings suggest that PER acts on cortico-subcortical excitability. This could explain the broad spectrum of PER and its success in forms of epilepsy characterized by thalamo-cortical hyperexcitability.