Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalami
Clobazam (CLB) and cenobamate (CNB) are commonly used antiseizure medications (ASMs) in the treatment of patients with drug-resistant epilepsy (DRE). However, concomitant use of these two ASMs may lead to significant treatment-related adverse events (TRAE). Furthermore, these TRAE may be exacerbated...
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Elsevier
2025-09-01
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| Series: | Epilepsy & Behavior Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589986425000590 |
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| author | Andrew Zillgitt David E Burdette Atheel Yako Revati Rashingkar Ashleigh Terrell Sydney Jacobs Michael D Staudt |
| author_facet | Andrew Zillgitt David E Burdette Atheel Yako Revati Rashingkar Ashleigh Terrell Sydney Jacobs Michael D Staudt |
| author_sort | Andrew Zillgitt |
| collection | DOAJ |
| description | Clobazam (CLB) and cenobamate (CNB) are commonly used antiseizure medications (ASMs) in the treatment of patients with drug-resistant epilepsy (DRE). However, concomitant use of these two ASMs may lead to significant treatment-related adverse events (TRAE). Furthermore, these TRAE may be exacerbated in individuals with genetic polymorphisms involving the P450 system. In patients with DRE, epilepsy surgery, including neuromodulation, may lead to improved seizure control and a reduction in systemic TRAE from ASMs. This case report describes a patient with drug-resistant idiopathic generalized epilepsy (IGE) who experienced persistent excessive somnolence correlated with elevated N-desmethylclobazam (N-CLB) levels. Pharmacogenetic testing revealed poor metabolism of CYP2C19, and N-CLB levels remained elevated and detectable for nearly one year after the discontinuation of treatment with CLB and CNB. Responsive neurostimulator (RNS) implantation within the bilateral centromedian nuclei (CMN) of the thalamus resulted in seizure freedom until N-CLB levels fell, after which there was an 83–93 % reduction in the frequency of generalized tonic-clonic seizures (GTC). |
| format | Article |
| id | doaj-art-0080263d09304d789ebcdce9e6fcf5ff |
| institution | DOAJ |
| issn | 2589-9864 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Epilepsy & Behavior Reports |
| spelling | doaj-art-0080263d09304d789ebcdce9e6fcf5ff2025-08-20T02:50:27ZengElsevierEpilepsy & Behavior Reports2589-98642025-09-013110079910.1016/j.ebr.2025.100799Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalamiAndrew Zillgitt0David E Burdette1Atheel Yako2Revati Rashingkar3Ashleigh Terrell4Sydney Jacobs5Michael D Staudt6Department of Neurology, Corewell Health William Beaumont University Hospital Adult Comprehensive Epilepsy Center, Royal Oak, MI, USA; Corresponding author.Department of Neurology, Corewell Health Butterworth Hospital Adult Comprehensive Epilepsy Center, Grand Rapids, MI, USADepartment of Neurology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USAOakland University William Beaumont School of Medicine Rochester Hills, MI, USADepartment of Neurology, Corewell Health William Beaumont University Hospital Adult Comprehensive Epilepsy Center, Royal Oak, MI, USADepartment of Neurology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USADepartment of Neurosurgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA; Department of Neurological Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USAClobazam (CLB) and cenobamate (CNB) are commonly used antiseizure medications (ASMs) in the treatment of patients with drug-resistant epilepsy (DRE). However, concomitant use of these two ASMs may lead to significant treatment-related adverse events (TRAE). Furthermore, these TRAE may be exacerbated in individuals with genetic polymorphisms involving the P450 system. In patients with DRE, epilepsy surgery, including neuromodulation, may lead to improved seizure control and a reduction in systemic TRAE from ASMs. This case report describes a patient with drug-resistant idiopathic generalized epilepsy (IGE) who experienced persistent excessive somnolence correlated with elevated N-desmethylclobazam (N-CLB) levels. Pharmacogenetic testing revealed poor metabolism of CYP2C19, and N-CLB levels remained elevated and detectable for nearly one year after the discontinuation of treatment with CLB and CNB. Responsive neurostimulator (RNS) implantation within the bilateral centromedian nuclei (CMN) of the thalamus resulted in seizure freedom until N-CLB levels fell, after which there was an 83–93 % reduction in the frequency of generalized tonic-clonic seizures (GTC).http://www.sciencedirect.com/science/article/pii/S2589986425000590ClobazamCenobamatePharmacogeneticsIdiopathic generalized epilepsyResponsive neurostimulator |
| spellingShingle | Andrew Zillgitt David E Burdette Atheel Yako Revati Rashingkar Ashleigh Terrell Sydney Jacobs Michael D Staudt Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalami Epilepsy & Behavior Reports Clobazam Cenobamate Pharmacogenetics Idiopathic generalized epilepsy Responsive neurostimulator |
| title | Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalami |
| title_full | Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalami |
| title_fullStr | Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalami |
| title_full_unstemmed | Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalami |
| title_short | Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalami |
| title_sort | synergistic seizure reduction in patient with persistently elevated n desmethylclobazam levels cyp450 genetic polymorphism and responsive neurostimulator targeting centromedian nuclei of bilateral thalami |
| topic | Clobazam Cenobamate Pharmacogenetics Idiopathic generalized epilepsy Responsive neurostimulator |
| url | http://www.sciencedirect.com/science/article/pii/S2589986425000590 |
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