Clinical efficacy of low‐dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2
Abstract Familial adult myoclonus epilepsy (FAME) management relies on antiseizure medications (ASMs), which inadequately address myoclonus and cortical tremor. This study evaluates Perampanel (PER), an AMPA‐receptor antagonist, for treating FAME symptoms. Fifteen FAME2 patients participated in an o...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Epilepsia Open |
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| Online Access: | https://doi.org/10.1002/epi4.13100 |
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| author | Antonietta Coppola Claudia Cuccurullo Gianmaria Senerchia Marica Rubino Liana Veneziano Francesco Brancati Luigi Baratto Valentina Virginia Iuzzolino Leonilda Bilo Pasquale Striano Raffaele Dubbioso |
| author_facet | Antonietta Coppola Claudia Cuccurullo Gianmaria Senerchia Marica Rubino Liana Veneziano Francesco Brancati Luigi Baratto Valentina Virginia Iuzzolino Leonilda Bilo Pasquale Striano Raffaele Dubbioso |
| author_sort | Antonietta Coppola |
| collection | DOAJ |
| description | Abstract Familial adult myoclonus epilepsy (FAME) management relies on antiseizure medications (ASMs), which inadequately address myoclonus and cortical tremor. This study evaluates Perampanel (PER), an AMPA‐receptor antagonist, for treating FAME symptoms. Fifteen FAME2 patients participated in an observational prospective study. They received up to 6 mg daily of PER and underwent Unified‐Myoclonus‐Rating‐Scale (UMRS) before and after treatment. Neurophysiological evaluations, including somatosensory evoked potentials (SEPs) and transcranial magnetic stimulation (TMS), assessed PER's impact on cortical glutamatergic excitatory and GABAergic inhibitory circuits. PER treatment significantly reduced UMRS total scores (p = 0.001) and action‐myoclonus subscores (p = 0.002), irrespective of disease duration, age at onset, or testing time (p >0.05). Patients with more severe baseline myoclonus demonstrated significant improvements. Neurophysiological assessments revealed a PER‐induced decrease in sensorimotor hyperexcitability, characterized by diminished N33 amplitudes, attenuated glutamatergic facilitation, and enhanced GABAergic inhibition in the motor cortex. In conclusion, low‐dose PER is well tolerated and effective in alleviating myoclonus in FAME2 patients, supported by its modulatory effects on glutamatergic and GABAergic neuronal circuits. Plain Language Summary: This study investigated the effects of low‐dose perampanel in individuals with Familial Adult Myoclonus Epilepsy2 (FAME2), a hereditary condition characterized by epilepsy and tremors. Perampanel, an antiepileptic drug, blocks AMPA receptors in the brain, reducing excessive neural activity that causes seizures and abnormal movements. The results showed significant symptom improvement, which correlated with changes in brain activity as measured by neurophysiological tests. This study suggests that perampanel helps regulate abnormal brain signals and may help managing FAME2 symptoms. |
| format | Article |
| id | doaj-art-a87cdf2a72cc489c9b96ffe7983841c2 |
| institution | Kabale University |
| issn | 2470-9239 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj-art-a87cdf2a72cc489c9b96ffe7983841c22025-02-07T09:12:45ZengWileyEpilepsia Open2470-92392025-02-0110132132810.1002/epi4.13100Clinical efficacy of low‐dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2Antonietta Coppola0Claudia Cuccurullo1Gianmaria Senerchia2Marica Rubino3Liana Veneziano4Francesco Brancati5Luigi Baratto6Valentina Virginia Iuzzolino7Leonilda Bilo8Pasquale Striano9Raffaele Dubbioso10Department of Neuroscience Reproductive Sciences and Odontostomatology, Federico II University of Naples Naples ItalyDepartment of Neuroscience Reproductive Sciences and Odontostomatology, Federico II University of Naples Naples ItalyDepartment of Neuroscience Reproductive Sciences and Odontostomatology, Federico II University of Naples Naples ItalyDepartment of Neuroscience Reproductive Sciences and Odontostomatology, Federico II University of Naples Naples ItalyInstitute of Translational Pharmacology National Research Council Rome ItalyHuman Functional Genomics Laboratory Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Roma Rome ItalyDepartment of Neuroscience Reproductive Sciences and Odontostomatology, Federico II University of Naples Naples ItalyDepartment of Neuroscience Reproductive Sciences and Odontostomatology, Federico II University of Naples Naples ItalyDepartment of Neuroscience Reproductive Sciences and Odontostomatology, Federico II University of Naples Naples ItalyIRCCS Istituto Giannina Gaslini Genoa ItalyDepartment of Neuroscience Reproductive Sciences and Odontostomatology, Federico II University of Naples Naples ItalyAbstract Familial adult myoclonus epilepsy (FAME) management relies on antiseizure medications (ASMs), which inadequately address myoclonus and cortical tremor. This study evaluates Perampanel (PER), an AMPA‐receptor antagonist, for treating FAME symptoms. Fifteen FAME2 patients participated in an observational prospective study. They received up to 6 mg daily of PER and underwent Unified‐Myoclonus‐Rating‐Scale (UMRS) before and after treatment. Neurophysiological evaluations, including somatosensory evoked potentials (SEPs) and transcranial magnetic stimulation (TMS), assessed PER's impact on cortical glutamatergic excitatory and GABAergic inhibitory circuits. PER treatment significantly reduced UMRS total scores (p = 0.001) and action‐myoclonus subscores (p = 0.002), irrespective of disease duration, age at onset, or testing time (p >0.05). Patients with more severe baseline myoclonus demonstrated significant improvements. Neurophysiological assessments revealed a PER‐induced decrease in sensorimotor hyperexcitability, characterized by diminished N33 amplitudes, attenuated glutamatergic facilitation, and enhanced GABAergic inhibition in the motor cortex. In conclusion, low‐dose PER is well tolerated and effective in alleviating myoclonus in FAME2 patients, supported by its modulatory effects on glutamatergic and GABAergic neuronal circuits. Plain Language Summary: This study investigated the effects of low‐dose perampanel in individuals with Familial Adult Myoclonus Epilepsy2 (FAME2), a hereditary condition characterized by epilepsy and tremors. Perampanel, an antiepileptic drug, blocks AMPA receptors in the brain, reducing excessive neural activity that causes seizures and abnormal movements. The results showed significant symptom improvement, which correlated with changes in brain activity as measured by neurophysiological tests. This study suggests that perampanel helps regulate abnormal brain signals and may help managing FAME2 symptoms.https://doi.org/10.1002/epi4.13100myoclonusPerampanelsomatosensory evoked potentialstranscranial magnetic stimulation |
| spellingShingle | Antonietta Coppola Claudia Cuccurullo Gianmaria Senerchia Marica Rubino Liana Veneziano Francesco Brancati Luigi Baratto Valentina Virginia Iuzzolino Leonilda Bilo Pasquale Striano Raffaele Dubbioso Clinical efficacy of low‐dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2 Epilepsia Open myoclonus Perampanel somatosensory evoked potentials transcranial magnetic stimulation |
| title | Clinical efficacy of low‐dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2 |
| title_full | Clinical efficacy of low‐dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2 |
| title_fullStr | Clinical efficacy of low‐dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2 |
| title_full_unstemmed | Clinical efficacy of low‐dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2 |
| title_short | Clinical efficacy of low‐dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2 |
| title_sort | clinical efficacy of low dose perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2 |
| topic | myoclonus Perampanel somatosensory evoked potentials transcranial magnetic stimulation |
| url | https://doi.org/10.1002/epi4.13100 |
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