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Drug resistance in idiopathic generalized epilepsies: Evidence and concepts
Joanna Gesche, Christoph P. Beier
doi : 10.1111/epi.17410
Although approximately 10%–15% of patients with idiopathic generalized epilepsy (IGE)/genetic generalized epilepsy remain drug-resistant, there is no consensus or established concept regarding the underlying mechanisms and prevalence.
Drug-resistant epilepsy and mortality�Why and when do neuromodulation and epilepsy surgery reduce overall mortality
Sylvain Rheims, Mickael R. Sperling, Philippe Ryvlin
doi : 10.1111/epi.17413
Patients with drug-resistant epilepsy have an increased mortality rate, with the majority of deaths being epilepsy related and 40% due to sudden unexpected death in epilepsy (SUDEP).
Functional neuropathology of neonatal hypoxia-ischemia by single-mouse longitudinal electroencephalography
Kevin J. Johnson, Brianna Moy, Nicholas Rensing, Alexia Robinson, Michael Ly, Ramya Chengalvala, Michael Wong, Rafael Galindo
doi : 10.1111/epi.17403
Neonatal cerebral hypoxia-ischemia (HI) results in symptomatic seizures and long-term neurodevelopmental disability. The Rice-Vannucci model of rodent neonatal HI has been used extensively to examine and translate the functional consequences of acute and chronic HI-induced encephalopathy.
Lacosamide decreases neonatal seizures without increasing apoptosis
Rachel L. Langton, Shaunik Sharma, Grant C. Tiarks, Alexander G. Bassuk, Joseph Glykys
doi : 10.1111/epi.17423
Many seizing neonates fail to respond to first-line anticonvulsant medications. Phenobarbital, an allosteric modulator of γ-aminobutyric acid type A (GABAA) receptors, has low efficacy in treating neonatal seizures and causes neuronal apoptosis.
Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods
Hatice Güler, Eda Esra Esen, Esra Balcıoğlu, Özge Göktepe, Halil Yılmaz, Arzu Hanım Yay, Mehtap Nisari, Özge Al, Sümeyye Uçar, Hilal Kübra Güçlü Ekinci, Adem Tokpınar, Seher Yılmaz
doi : 10.1111/epi.17422
This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy.
Neurobehavioral deficits and a progressive ictogenesis in the tetrodotoxin model of epileptic spasms
John T. Le, Carlos J. Ballester-Rosado, James D. Frost Jr., John W. Swann
doi : 10.1111/epi.17428
Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time.
Synergistic effects of the galanin analog 810–2 with the antiseizure medication levetiracetam in rodent seizure models
Cameron S. Metcalf, Saurabh Gagangras, Grzegorz Bulaj, H. Steve White
doi : 10.1111/epi.17420
The use of many antiseizure medications (ASMs) is limited due to pharmacoresistance and dose-limiting side effects, suggesting an unmet need for novel therapeutic approaches.
Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study
Eric Yuk Fai Wan, Vanessa Wai Sei Ng, Richard Shek-Kwan Chang, Vincent Ka Chun Yan, Celine Sze Ling Chui, Carlos King Ho Wong, Xue Li, Francisco Tsz Tsun Lai, Esther Wai Yin Chan, Ivan Fan Ngai Hung, Kui Kai Lau, Ian Chi Kei Wong
doi : 10.1111/epi.17436
The risk of seizure following BNT162b2 and CoronaVac vaccinations has been sparsely investigated. This study aimed to evaluate this association.
Early cost–utility analysis of genetically guided therapy for patients with drug-resistant epilepsy
Louisa G. Gordon, Thomas M. Elliott, Carmen Bennett, Georgina Hollway, Nicola Waddell, Lata Vadlamudi
doi : 10.1111/epi.17408
Existing gene panels were developed to understand the etiology of epilepsy, and further benefits will arise from an effective pharmacogenomics panel for personalizing therapy and achieving seizure control. Our study assessed the cost-effectiveness of a pharmacogenomics panel for patients with drug-resistant epilepsy, compared with usual care.
Gene panel to guide antiseizure medication prescribing: Does the cost justify the benefits?
Elysa Widjaja
doi : 10.1111/epi.17418
Pharmacogenomics hold the potential to identify variants associated with adverse drug reactions and treatment efficacy of anti-seizure medications.
A systems medicine strategy to predict the efficacy of drugs for monogenic epilepsies
Basel Taweel, Anthony G. Marson, Nasir Mirza
doi : 10.1111/epi.17429
Monogenic epilepsies are rare but often severe. Because of their rarity, they are neglected by traditional drug developers. Hence, many lack effective treatments.
Paroxysmal fast activity is a biomarker of treatment response in deep brain stimulation for Lennox–Gastaut syndrome
Linda J. Dalic, Aaron E. L. Warren, Chloe Spiegel, Wesley Thevathasan, Annie Roten, Kristian J. Bulluss, John S. Archer
doi : 10.1111/epi.17414
Epilepsy treatment trials typically rely on seizure diaries to determine seizure frequency, but these are time-consuming and difficult to maintain accurately.
The longitudinal effect of oxcarbazepine on thyroid function in children and adolescents with epilepsy
Hyunju Park, Jung Heo, Min-Ji Kim, Jee-Hun Lee, Min-Sun Kim, Dong-Kyu Jin, Tae Hyuk Kim, Jae Hoon Chung, Sung Yoon Cho, Sun Wook Kim
doi : 10.1111/epi.17407
Thyroid hormone abnormalities have been linked to antiseizure medications (ASMs). Oxcarbazepine is considered safer than carbamazepine because it induces the hepatic cytochrome P450 metabolic enzymes less than the carbamazepine does.
Seizure count forecasting to aid diagnostic testing in epilepsy
Emily T. Wang, Sharon Chiang, Stephen Cleboski, Vikram R. Rao, Marina Vannucci, Zulfi Haneef
doi : 10.1111/epi.17415
Epilepsy monitoring unit (EMU) admissions are critical for presurgical evaluation of drug-resistant epilepsy but may be nondiagnostic if an insufficient number of seizures are recorded.
Seizure outcome determinants in children after surgery for single unilateral lesions on magnetic resonance imaging: Role of preoperative ictal and interictal electroencephalography
Felipe Castro-Villablanca, Friederike Moeller, Suresh Pujar, Felice D'Arco, Rod C. Scott, M. Zubair Tahir, Martin Tisdall, J. Helen Cross, Christin Eltze
doi : 10.1111/epi.17425
To determine whether an ictal electroencephalographic (EEG) recording as part of presurgical evaluation of children with a demarcated single unilateral magnetic resonance imaging (MRI) lesion is indispensable for surgical decision-making, we investigated the relationship of interictal/ictal EEG and seizure semiology with seizure-free outcome.
Acute symptomatic seizures secondary to myelin oligodendrocyte glycoprotein antibody-associated disease
Mayra Montalvo, Jamal F. Khattak, Vyanka Redenbaugh, Jeffrey Britton, Cristina Valencia Sanchez, Abhigyan Datta, Jan-Mendelt Tillema, John Chen, Andrew McKeon, Sean J. Pittock, Eoin P. Flanagan, Divyanshu Dubey
doi : 10.1111/epi.17424
To report the clinical presentations and outcomes of patients with seizure and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD).
Altered cerebellar-motor loop in benign adult familial myoclonic epilepsy type 1: The structural basis of cortical tremor
Ge Wang, Yanmin Song, Jianpo Su, Zhipeng Fan, Lin Xu, Peng Fang, Chaorong Liu, Hongyu Long, Chongyu Hu, Luo Zhou, Sha Huang, Pinting Zhou, Kangrun Wang, Nan Pang, Hui Shen, Shuyu Li, Dewen Hu, Bo Xiao, Ling-Li Zeng, Lili Long
doi : 10.1111/epi.17430
Cortical tremor/myoclonus is the hallmark feature of benign adult familial myoclonic epilepsy (BAFME), the mechanism of which remains elusive. A hypothesis is that a defective control in the preexisting cerebellar-motor loop drives cortical tremor. Meanwhile, the basal ganglia system might also participate in BAFME. This study aimed to discover the structural basis of cortical tremor/myoclonus in BAFME.
Progressive slowing of clonic phase predicts postictal generalized EEG suppression
Maria Vlachou, Philippe Ryvlin, Anca Adriana Arbune, Sidsel Armand Larsen, Annette Skræp Sidaros, Melita Cacic Hribljan, Martin Fabricius, Sándor Beniczky
doi : 10.1111/epi.17434
Postictal generalized electroencephalography (EEG) suppression (PGES) is a surrogate marker of sudden unexpected death in epilepsy (SUDEP). It is still unclear which ictal phenomena lead to prolonged PGES and increased risk of SUDEP.
Corrigendum to “Brain network excitatory/inhibitory imbalance is a biomarker for drug-naive Rolandic epilepsy: A radiomics strategy�. [Epilepsia 2021, 62 (10): 2426–2438]
doi : 10.1111/epi.17443
Deficit in observational learning in experimental epilepsy
Thomas Doublet, Antoine Ghestem, Christophe Bernard
doi : 10.1111/epi.17421
Individuals use the observation of a conspecific to learn new behaviors and skills in many species. Whether observational learning is affected in epilepsy is not known.
A gain-of-function GRIA2 variant associated with neurodevelopmental delay and seizures: Functional characterization and targeted treatment
Ian D. Coombs, Julie Ziobro, Volodymyr Krotov, Taryn-Leigh Surtees, Stuart G. Cull-Candy, Mark Farrant
doi : 10.1111/epi.17419
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) are ligand-gated cationic channels formed from combinations of GluA1-4 subunits.
Successful treatment of adult Dravet syndrome patients with cenobamate
Konstantin L. Makridis, Anna-Lena Friedo, Christoph Kellinghaus, Florian-Phillip Losch, Bettina Schmitz, Christian Boßelmann, Angela M. Kaindl
doi : 10.1111/epi.17427
Dravet syndrome (DS) is a rare, drug-resistant, severe developmental and epileptic encephalopathy caused by pathogenic variants in the α subunit of the voltage-gated sodium channel gene SCN1A.
Seizures in anti-Hu–associated extra-limbic encephalitis: Characterization of a unique disease manifestation
Adrian Budhram, Manas Sharma, G. Bryan Young
doi : 10.1111/epi.17437
Anti-Hu–associated neurologic autoimmunity most often occurs in the context of small cell lung cancer and typically presents with peripheral neuropathy, cerebellar ataxia, and/or limbic encephalitis.
Drug resistance in idiopathic generalized epilepsies: Evidence and concepts
Joanna Gesche, Christoph P. Beier
doi : 10.1111/epi.17410
Although approximately 10%–15% of patients with idiopathic generalized epilepsy (IGE)/genetic generalized epilepsy remain drug-resistant, there is no consensus or established concept regarding the underlying mechanisms and prevalence.
Drug-resistant epilepsy and mortality�Why and when do neuromodulation and epilepsy surgery reduce overall mortality
Sylvain Rheims, Mickael R. Sperling, Philippe Ryvlin
doi : 10.1111/epi.17413
Patients with drug-resistant epilepsy have an increased mortality rate, with the majority of deaths being epilepsy related and 40% due to sudden unexpected death in epilepsy (SUDEP).
Functional neuropathology of neonatal hypoxia-ischemia by single-mouse longitudinal electroencephalography
Kevin J. Johnson, Brianna Moy, Nicholas Rensing, Alexia Robinson, Michael Ly, Ramya Chengalvala, Michael Wong, Rafael Galindo
doi : 10.1111/epi.17403
Neonatal cerebral hypoxia-ischemia (HI) results in symptomatic seizures and long-term neurodevelopmental disability. The Rice-Vannucci model of rodent neonatal HI has been used extensively to examine and translate the functional consequences of acute and chronic HI-induced encephalopathy.
Lacosamide decreases neonatal seizures without increasing apoptosis
Rachel L. Langton, Shaunik Sharma, Grant C. Tiarks, Alexander G. Bassuk, Joseph Glykys
doi : 10.1111/epi.17423
Many seizing neonates fail to respond to first-line anticonvulsant medications. Phenobarbital, an allosteric modulator of γ-aminobutyric acid type A (GABAA) receptors, has low efficacy in treating neonatal seizures and causes neuronal apoptosis.
Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods
Hatice Güler, Eda Esra Esen, Esra Balcıoğlu, Özge Göktepe, Halil Yılmaz, Arzu Hanım Yay, Mehtap Nisari, Özge Al, Sümeyye Uçar, Hilal Kübra Güçlü Ekinci, Adem Tokpınar, Seher Yılmaz
doi : 10.1111/epi.17422
This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy.
Neurobehavioral deficits and a progressive ictogenesis in the tetrodotoxin model of epileptic spasms
John T. Le, Carlos J. Ballester-Rosado, James D. Frost Jr., John W. Swann
doi : 10.1111/epi.17428
Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time.
Synergistic effects of the galanin analog 810–2 with the antiseizure medication levetiracetam in rodent seizure models
Cameron S. Metcalf, Saurabh Gagangras, Grzegorz Bulaj, H. Steve White
doi : 10.1111/epi.17420
The use of many antiseizure medications (ASMs) is limited due to pharmacoresistance and dose-limiting side effects, suggesting an unmet need for novel therapeutic approaches.
Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study
Eric Yuk Fai Wan, Vanessa Wai Sei Ng, Richard Shek-Kwan Chang, Vincent Ka Chun Yan, Celine Sze Ling Chui, Carlos King Ho Wong, Xue Li, Francisco Tsz Tsun Lai, Esther Wai Yin Chan, Ivan Fan Ngai Hung, Kui Kai Lau, Ian Chi Kei Wong
doi : 10.1111/epi.17436
The risk of seizure following BNT162b2 and CoronaVac vaccinations has been sparsely investigated. This study aimed to evaluate this association.
Early cost–utility analysis of genetically guided therapy for patients with drug-resistant epilepsy
Louisa G. Gordon, Thomas M. Elliott, Carmen Bennett, Georgina Hollway, Nicola Waddell, Lata Vadlamudi
doi : 10.1111/epi.17408
Existing gene panels were developed to understand the etiology of epilepsy, and further benefits will arise from an effective pharmacogenomics panel for personalizing therapy and achieving seizure control. Our study assessed the cost-effectiveness of a pharmacogenomics panel for patients with drug-resistant epilepsy, compared with usual care.
Gene panel to guide antiseizure medication prescribing: Does the cost justify the benefits?
Elysa Widjaja
doi : 10.1111/epi.17418
Pharmacogenomics hold the potential to identify variants associated with adverse drug reactions and treatment efficacy of anti-seizure medications.
A systems medicine strategy to predict the efficacy of drugs for monogenic epilepsies
Basel Taweel, Anthony G. Marson, Nasir Mirza
doi : 10.1111/epi.17429
Monogenic epilepsies are rare but often severe. Because of their rarity, they are neglected by traditional drug developers. Hence, many lack effective treatments.
Paroxysmal fast activity is a biomarker of treatment response in deep brain stimulation for Lennox–Gastaut syndrome
Linda J. Dalic, Aaron E. L. Warren, Chloe Spiegel, Wesley Thevathasan, Annie Roten, Kristian J. Bulluss, John S. Archer
doi : 10.1111/epi.17414
Epilepsy treatment trials typically rely on seizure diaries to determine seizure frequency, but these are time-consuming and difficult to maintain accurately.
The longitudinal effect of oxcarbazepine on thyroid function in children and adolescents with epilepsy
Hyunju Park, Jung Heo, Min-Ji Kim, Jee-Hun Lee, Min-Sun Kim, Dong-Kyu Jin, Tae Hyuk Kim, Jae Hoon Chung, Sung Yoon Cho, Sun Wook Kim
doi : 10.1111/epi.17407
Thyroid hormone abnormalities have been linked to antiseizure medications (ASMs). Oxcarbazepine is considered safer than carbamazepine because it induces the hepatic cytochrome P450 metabolic enzymes less than the carbamazepine does.
Seizure count forecasting to aid diagnostic testing in epilepsy
Emily T. Wang, Sharon Chiang, Stephen Cleboski, Vikram R. Rao, Marina Vannucci, Zulfi Haneef
doi : 10.1111/epi.17415
Epilepsy monitoring unit (EMU) admissions are critical for presurgical evaluation of drug-resistant epilepsy but may be nondiagnostic if an insufficient number of seizures are recorded.
Seizure outcome determinants in children after surgery for single unilateral lesions on magnetic resonance imaging: Role of preoperative ictal and interictal electroencephalography
Felipe Castro-Villablanca, Friederike Moeller, Suresh Pujar, Felice D'Arco, Rod C. Scott, M. Zubair Tahir, Martin Tisdall, J. Helen Cross, Christin Eltze
doi : 10.1111/epi.17425
To determine whether an ictal electroencephalographic (EEG) recording as part of presurgical evaluation of children with a demarcated single unilateral magnetic resonance imaging (MRI) lesion is indispensable for surgical decision-making, we investigated the relationship of interictal/ictal EEG and seizure semiology with seizure-free outcome.
Acute symptomatic seizures secondary to myelin oligodendrocyte glycoprotein antibody-associated disease
Mayra Montalvo, Jamal F. Khattak, Vyanka Redenbaugh, Jeffrey Britton, Cristina Valencia Sanchez, Abhigyan Datta, Jan-Mendelt Tillema, John Chen, Andrew McKeon, Sean J. Pittock, Eoin P. Flanagan, Divyanshu Dubey
doi : 10.1111/epi.17424
To report the clinical presentations and outcomes of patients with seizure and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD).
Altered cerebellar-motor loop in benign adult familial myoclonic epilepsy type 1: The structural basis of cortical tremor
Ge Wang, Yanmin Song, Jianpo Su, Zhipeng Fan, Lin Xu, Peng Fang, Chaorong Liu, Hongyu Long, Chongyu Hu, Luo Zhou, Sha Huang, Pinting Zhou, Kangrun Wang, Nan Pang, Hui Shen, Shuyu Li, Dewen Hu, Bo Xiao, Ling-Li Zeng, Lili Long
doi : 10.1111/epi.17430
Cortical tremor/myoclonus is the hallmark feature of benign adult familial myoclonic epilepsy (BAFME), the mechanism of which remains elusive. A hypothesis is that a defective control in the preexisting cerebellar-motor loop drives cortical tremor. Meanwhile, the basal ganglia system might also participate in BAFME. This study aimed to discover the structural basis of cortical tremor/myoclonus in BAFME.
Progressive slowing of clonic phase predicts postictal generalized EEG suppression
Maria Vlachou, Philippe Ryvlin, Anca Adriana Arbune, Sidsel Armand Larsen, Annette Skræp Sidaros, Melita Cacic Hribljan, Martin Fabricius, Sándor Beniczky
doi : 10.1111/epi.17434
Postictal generalized electroencephalography (EEG) suppression (PGES) is a surrogate marker of sudden unexpected death in epilepsy (SUDEP). It is still unclear which ictal phenomena lead to prolonged PGES and increased risk of SUDEP.
Corrigendum to “Brain network excitatory/inhibitory imbalance is a biomarker for drug-naive Rolandic epilepsy: A radiomics strategy�. [Epilepsia 2021, 62 (10): 2426–2438]
doi : 10.1111/epi.17443
Deficit in observational learning in experimental epilepsy
Thomas Doublet, Antoine Ghestem, Christophe Bernard
doi : 10.1111/epi.17421
Individuals use the observation of a conspecific to learn new behaviors and skills in many species. Whether observational learning is affected in epilepsy is not known.
A gain-of-function GRIA2 variant associated with neurodevelopmental delay and seizures: Functional characterization and targeted treatment
Ian D. Coombs, Julie Ziobro, Volodymyr Krotov, Taryn-Leigh Surtees, Stuart G. Cull-Candy, Mark Farrant
doi : 10.1111/epi.17419
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) are ligand-gated cationic channels formed from combinations of GluA1-4 subunits.
Successful treatment of adult Dravet syndrome patients with cenobamate
Konstantin L. Makridis, Anna-Lena Friedo, Christoph Kellinghaus, Florian-Phillip Losch, Bettina Schmitz, Christian Boßelmann, Angela M. Kaindl
doi : 10.1111/epi.17427
Dravet syndrome (DS) is a rare, drug-resistant, severe developmental and epileptic encephalopathy caused by pathogenic variants in the α subunit of the voltage-gated sodium channel gene SCN1A.
Seizures in anti-Hu–associated extra-limbic encephalitis: Characterization of a unique disease manifestation
Adrian Budhram, Manas Sharma, G. Bryan Young
doi : 10.1111/epi.17437
Anti-Hu–associated neurologic autoimmunity most often occurs in the context of small cell lung cancer and typically presents with peripheral neuropathy, cerebellar ataxia, and/or limbic encephalitis.
