Jacopo Lanzone1, Marilisa Boscarino2, Lorenzo Ricci2, Angelo Insola3, Mario Tombini2, Vincenzo Di Lazzaro2, Giovanni Assenza2. 1. Neurology, Neurophysiology and Neurobiology Unit, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy. Electronic address: j.lanzone@unicampus.it. 2. Neurology, Neurophysiology and Neurobiology Unit, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy. 3. Neurophysiology unit, CTO hospital, Rome, Italy.
Abstract
OBJECTIVE: Wedesignedalongitudinalcohortstudyon People with Epilepsy (PwE) with the aimofassessingthe effect of Perampanel (PER) oncortico-subcortical networks, as measured by high-frequency oscillations of somatosensory evoked potentials (SEP-HFOs). SEP-HFOs measure the excitability of both thalamo-corticalprojections(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 ofTotal 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.
OBJECTIVE: Wedesignedalongitudinalcohortstudyon People with Epilepsy (PwE) with the aimofassessingthe effect of Perampanel (PER) oncortico-subcortical networks, as measured by high-frequency oscillations of somatosensory evoked potentials (SEP-HFOs). SEP-HFOs measure the excitability of both thalamo-corticalprojections(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 ofTotal 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.
Authors: Giovanni Assenza; Cristofaro Nocerino; Mario Tombini; Giancarlo Di Gennaro; Alfredo D'Aniello; Alberto Verrotti; Alfonso Marrelli; Lorenzo Ricci; Jacopo Lanzone; Vincenzo Di Lazzaro; Leonilda Bilo; Antonietta Coppola Journal: Front Neurol Date: 2021-03-24 Impact factor: 4.003