In addition to the oscillatory brain activity, the nonoscillatory (scale-free) components of the background electroencephalogram (EEG) may provide further information about the complexity of the underlying neuronal network. As epilepsy is considered a network disease, such scale-free metrics might help to delineate the epileptic network. Here, we performed an analysis of the sleep oscillatory (spindle, slow wave, and rhythmic spectral power) and nonoscillatory (H exponent) intracranial EEG using multiple interictal features to estimate whether and how they deviate from normalcy in 38 adults with drug-resistant epilepsy.
Methods
To quantify intracranial EEG abnormalities within and outside the seizure onset areas, patients' values were adjusted based on normative maps derived from the open-access Montreal Neurological Institute open iEEG Atlas. In a subset of 29 patients who underwent resective surgery, we estimated the predictive value of these features to identify the epileptogenic zone in those with a good postsurgical outcome.
Results
We found that distinct sleep oscillatory and nonoscillatory metrics behave differently across the epileptic network, with the strongest differences observed for (1) a reduction in spindle activity (spindle rates and rhythmic sigma power in the 10–16 Hz band), (2) a higher rhythmic gamma power (30–80 Hz), and (3) a higher H exponent (steeper 1/f slope). As expected, epileptic spikes were also highest in the seizure onset areas. Furthermore, in surgical patients, the H exponent achieved the highest performance (balanced accuracy of .76) for classifying resected versus nonresected channels in good outcome patients.
Significance
This work suggests that nonoscillatory components of the intracranial EEG signal could serve as promising interictal sleep candidates of epileptogenicity in patients with drug-resistant epilepsy. Our findings further advance the understanding of epilepsy as a disease, whereby absence or loss of sleep physiology may provide information complementary to pathological epileptic processes.
{"title":"Oscillatory and nonoscillatory sleep electroencephalographic biomarkers of the epileptic network","authors":"Véronique Latreille, Justin Corbin-Lapointe, Laure Peter-Derex, John Thomas, Jean-Marc Lina, Birgit Frauscher","doi":"10.1111/epi.18088","DOIUrl":"10.1111/epi.18088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In addition to the oscillatory brain activity, the nonoscillatory (scale-free) components of the background electroencephalogram (EEG) may provide further information about the complexity of the underlying neuronal network. As epilepsy is considered a network disease, such scale-free metrics might help to delineate the epileptic network. Here, we performed an analysis of the sleep oscillatory (spindle, slow wave, and rhythmic spectral power) and nonoscillatory (<i>H</i> exponent) intracranial EEG using multiple interictal features to estimate whether and how they deviate from normalcy in 38 adults with drug-resistant epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To quantify intracranial EEG abnormalities within and outside the seizure onset areas, patients' values were adjusted based on normative maps derived from the open-access Montreal Neurological Institute open iEEG Atlas. In a subset of 29 patients who underwent resective surgery, we estimated the predictive value of these features to identify the epileptogenic zone in those with a good postsurgical outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that distinct sleep oscillatory and nonoscillatory metrics behave differently across the epileptic network, with the strongest differences observed for (1) a reduction in spindle activity (spindle rates and rhythmic sigma power in the 10–16 Hz band), (2) a higher rhythmic gamma power (30–80 Hz), and (3) a higher <i>H</i> exponent (steeper 1/<i>f</i> slope). As expected, epileptic spikes were also highest in the seizure onset areas. Furthermore, in surgical patients, the <i>H</i> exponent achieved the highest performance (balanced accuracy of .76) for classifying resected versus nonresected channels in good outcome patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This work suggests that nonoscillatory components of the intracranial EEG signal could serve as promising interictal sleep candidates of epileptogenicity in patients with drug-resistant epilepsy. Our findings further advance the understanding of epilepsy as a disease, whereby absence or loss of sleep physiology may provide information complementary to pathological epileptic processes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"3038-3051"},"PeriodicalIF":6.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meir Bialer, Svein I. Johannessen, Matthias J. Koepp, Emilio Perucca, Piero Perucca, Torbjörn Tomson, H. Steve White
The 17th Eilat Conference on New Antiepileptic Drugs and Devices took place in Madrid, Spain on May 5–8, 2024. As usual, the core part of the conference consisted of presentations on investigational drugs at various stages of development for epilepsy-related indications. Summaries of information on compounds in preclinical or early clinical development are included in an accompanying publication (Part I). In this article, we provide summaries for five compounds in more advanced clinical development, i.e. compounds for which some information on antiseizure activity in individuals with epilepsy is available. These investigational treatments include azetukalner (XEN1101), a potent, KV7.2/7.3-specific potassium channel opener in development for the treatment of focal seizures, generalized tonic–clonic seizures, and major depressive disorder; bexicaserin (LP352), a selective 5-HT2C receptor superagonist in development for the treatment of seizures associated with developmental and epileptic encephalopathies; radiprodil, a selective negative allosteric modulator of NR2B subunit-containing N-methyl-D-aspartate glutamate receptors, in development for the treatment of seizures and behavior manifestations associated with disorders caused by gain-of-function mutations in the GRIN1, −2A, -2B, or -2D genes; soticlestat (TAK-935), a selective inhibitor of cholesterol 24-hydroxylase in development for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome; and STK-001, an antisense oligonucleotide designed to upregulate Nav1.1 protein expression and improve outcomes in individuals with Dravet syndrome. The diversity in mechanisms of action of these agents illustrates different approaches being pursued in the discovery of novel treatments for seizures and epilepsy. For two of the compounds discussed in this report (azetukalner and soticlestat), clinical evidence of efficacy has already been obtained in a randomized placebo-controlled adjunctive-therapy trial. For the other compounds, adequately powered placebo-controlled efficacy trials have not been completed to date.
{"title":"Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development","authors":"Meir Bialer, Svein I. Johannessen, Matthias J. Koepp, Emilio Perucca, Piero Perucca, Torbjörn Tomson, H. Steve White","doi":"10.1111/epi.18075","DOIUrl":"10.1111/epi.18075","url":null,"abstract":"<p>The 17th Eilat Conference on New Antiepileptic Drugs and Devices took place in Madrid, Spain on May 5–8, 2024. As usual, the core part of the conference consisted of presentations on investigational drugs at various stages of development for epilepsy-related indications. Summaries of information on compounds in preclinical or early clinical development are included in an accompanying publication (Part I). In this article, we provide summaries for five compounds in more advanced clinical development, i.e. compounds for which some information on antiseizure activity in individuals with epilepsy is available. These investigational treatments include azetukalner (XEN1101), a potent, K<sub>V</sub>7.2/7.3-specific potassium channel opener in development for the treatment of focal seizures, generalized tonic–clonic seizures, and major depressive disorder; bexicaserin (LP352), a selective 5-HT<sub>2C</sub> receptor superagonist in development for the treatment of seizures associated with developmental and epileptic encephalopathies; radiprodil, a selective negative allosteric modulator of NR2B subunit-containing N-methyl-D-aspartate glutamate receptors, in development for the treatment of seizures and behavior manifestations associated with disorders caused by gain-of-function mutations in the <i>GRIN1</i>, <i>−2A</i>, <i>-2B</i>, or <i>-2D</i> genes; soticlestat (TAK-935), a selective inhibitor of cholesterol 24-hydroxylase in development for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome; and STK-001, an antisense oligonucleotide designed to upregulate Na<sub>v</sub>1.1 protein expression and improve outcomes in individuals with Dravet syndrome. The diversity in mechanisms of action of these agents illustrates different approaches being pursued in the discovery of novel treatments for seizures and epilepsy. For two of the compounds discussed in this report (azetukalner and soticlestat), clinical evidence of efficacy has already been obtained in a randomized placebo-controlled adjunctive-therapy trial. For the other compounds, adequately powered placebo-controlled efficacy trials have not been completed to date.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"2858-2882"},"PeriodicalIF":6.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Sun, Meng-Yun Ku, Chih-Ching Liu, Li-Nien Chien
Objective
Among motor vehicle crashes (MVCs), little is known about whether the characteristics and collision features involving drivers with epilepsy differ from those involving drivers without any history of epilepsy. We assessed MVC features and the effect of epilepsy diagnosis on the risk of severe crash-related injuries among drivers.
Methods
A total of 33 174 MVC events among people with epilepsy (PWE) and 663 480 MVC events of age- and sex-matched non-PWE (1:20) were selected. Crash-related features that involved drivers with and without epilepsy were compared, including driver eligibility, medical history of comorbidities and medications, road and environmental conditions, and accident causes. Cox and logistic regression analyses were used to examine the risks of fatality and severe injury among drivers with and without epilepsy.
Results
PWE involved in MVCs were more likely to have lower socioeconomic status, comorbidities, scooter drivers without a qualified driver's license, driving under the influence of alcohol, and be involved in single-vehicle accidents than non-PWE. Drivers with epilepsy also had a higher risk of fatality within 30 days of MVC, with an adjusted hazard ratio (aHR) of 1.37 (95% confidence interval [CI], 1.20–1.57) and a higher risk of hospital admission within 3 days after MVC (aHR, 1.33; 95% CI, 1.29–1.38) compared to that of non-PWE.
Significance
The characteristics of MVCs of drivers with epilepsy were distinct from those of non-affected drivers. And higher fatality and injury rates were observed among drivers with epilepsy, which should be considered in further policymaking regarding safe driving of PWE.
{"title":"Characteristics of motor vehicle crashes and fatality risk among drivers with epilepsy","authors":"Yu Sun, Meng-Yun Ku, Chih-Ching Liu, Li-Nien Chien","doi":"10.1111/epi.18097","DOIUrl":"10.1111/epi.18097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Among motor vehicle crashes (MVCs), little is known about whether the characteristics and collision features involving drivers with epilepsy differ from those involving drivers without any history of epilepsy. We assessed MVC features and the effect of epilepsy diagnosis on the risk of severe crash-related injuries among drivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 33 174 MVC events among people with epilepsy (PWE) and 663 480 MVC events of age- and sex-matched non-PWE (1:20) were selected. Crash-related features that involved drivers with and without epilepsy were compared, including driver eligibility, medical history of comorbidities and medications, road and environmental conditions, and accident causes. Cox and logistic regression analyses were used to examine the risks of fatality and severe injury among drivers with and without epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PWE involved in MVCs were more likely to have lower socioeconomic status, comorbidities, scooter drivers without a qualified driver's license, driving under the influence of alcohol, and be involved in single-vehicle accidents than non-PWE. Drivers with epilepsy also had a higher risk of fatality within 30 days of MVC, with an adjusted hazard ratio (aHR) of 1.37 (95% confidence interval [CI], 1.20–1.57) and a higher risk of hospital admission within 3 days after MVC (aHR, 1.33; 95% CI, 1.29–1.38) compared to that of non-PWE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>The characteristics of MVCs of drivers with epilepsy were distinct from those of non-affected drivers. And higher fatality and injury rates were observed among drivers with epilepsy, which should be considered in further policymaking regarding safe driving of PWE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"2984-2994"},"PeriodicalIF":6.6,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian Ervin, Christina Kargol, Anna W. Byars, Jason Buroker, Leonid Rozhkov, Jesse Skoch, Francesco T. Mangano, Hansel M. Greiner, Paul S. Horn, Katherine Holland, Ravindra Arya
Objective
We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high-gamma power modulations (HGM) during a visual naming task, although these sites were found language-negative on standard-of-care electrical stimulation mapping (ESM).
Methods
In drug-resistant epilepsy patients who underwent resection/ablation after stereo-electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1-year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming-related HGM. The analyses were adjusted for 1-year seizure freedom, operated hemispheres, and the volumes of surgical lesions.
Results
In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [β] = −.10), working memory (β = −.10), VLI (β = −.14), and letter–word identification (LWI; β = −.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (β = −.31), story memory immediate (β = −.27), verbal learning recognition (β = −.18), LWI (β = −.16), spelling (β = −.49), and passage comprehension (β = −.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere.
Significance
HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits.
{"title":"High-gamma modulation language mapping and cognitive outcomes after epilepsy surgery","authors":"Brian Ervin, Christina Kargol, Anna W. Byars, Jason Buroker, Leonid Rozhkov, Jesse Skoch, Francesco T. Mangano, Hansel M. Greiner, Paul S. Horn, Katherine Holland, Ravindra Arya","doi":"10.1111/epi.18096","DOIUrl":"10.1111/epi.18096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high-gamma power modulations (HGM) during a visual naming task, although these sites were found language-negative on standard-of-care electrical stimulation mapping (ESM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In drug-resistant epilepsy patients who underwent resection/ablation after stereo-electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1-year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming-related HGM. The analyses were adjusted for 1-year seizure freedom, operated hemispheres, and the volumes of surgical lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [<i>β</i>] = −.10), working memory (<i>β</i> = −.10), VLI (<i>β</i> = −.14), and letter–word identification (LWI; <i>β</i> = −.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (<i>β</i> = −.31), story memory immediate (<i>β</i> = −.27), verbal learning recognition (<i>β</i> = −.18), LWI (<i>β</i> = −.16), spelling (<i>β</i> = −.49), and passage comprehension (<i>β</i> = −.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"3052-3063"},"PeriodicalIF":6.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauri Rekola, Maria Peltola, Jukka Vanhanen, Juha Wilenius, Eeva-Liisa Metsähonkala, Leena Kämppi, Leena Lauronen, Päivi Nevalainen
Objective
This study was undertaken to investigate the potential of interictal electroencephalographic (EEG) findings and electrically stimulated seizures during stereo-EEG (SEEG) as surrogate markers for the spontaneous seizure onset zone (spSOZ). We hypothesized that combining the localizing information of these markers would allow clinically meaningful estimation of the spSOZ.
Methods
We included all patients (n = 63) who underwent SEEG between January 2013 and March 2020 at Helsinki University Hospital and had spontaneous seizures during the recording. We scored spikes, gamma activity, and background abnormality on each channel visually during a 12-h epoch containing waking state and sleep. Based on semiology, we classified stimulated seizures as typical or atypical/unclassifiable and estimated the stimulated SOZ (stimSOZ) for typical seizures. To assess which markers increased the odds of channel inclusion in the spSOZ, we fitted mixed effects logistic regression models.
Results
A combined regression model including the stimSOZ and interictal markers scored during sleep performed better in estimating which channels were part of the spSOZ than models based on stimSOZ (p < .001) or interictal markers (p < .001) alone. Of the individual markers, the effect sizes were greatest for inclusion of a channel in the stimSOZ (odds ratio [OR] = 60, 95% confidence interval [CI] = 37–97, p < .001) and for continuous (OR = 25, 95% CI = 12–55, p < .001) and subcontinuous (OR = 36, 95% CI = 21–64, p < .001) interictal spiking. At the individual level, the model's accuracy to predict spSOZ inclusion varied markedly (median accuracy = 85.7, range = 54.4–100), which was not explained by etiology (p > .05).
Significance
Compared to either marker alone, combining visually rated interictal SEEG markers and stimulated seizures improved prediction of which SEEG channels belonged to the spSOZ. Inclusion in the stimSOZ and continuous or subcontinuous spikes increased the odds of spSOZ inclusion the most. Future studies should investigate whether suboptimal sampling of the true epileptogenic zone can explain the model's poor performance in certain patients.
{"title":"Combined value of interictal markers and stimulated seizures to estimate the seizure onset zone in stereoelectroencephalography","authors":"Lauri Rekola, Maria Peltola, Jukka Vanhanen, Juha Wilenius, Eeva-Liisa Metsähonkala, Leena Kämppi, Leena Lauronen, Päivi Nevalainen","doi":"10.1111/epi.18083","DOIUrl":"10.1111/epi.18083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study was undertaken to investigate the potential of interictal electroencephalographic (EEG) findings and electrically stimulated seizures during stereo-EEG (SEEG) as surrogate markers for the spontaneous seizure onset zone (spSOZ). We hypothesized that combining the localizing information of these markers would allow clinically meaningful estimation of the spSOZ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included all patients (<i>n</i> = 63) who underwent SEEG between January 2013 and March 2020 at Helsinki University Hospital and had spontaneous seizures during the recording. We scored spikes, gamma activity, and background abnormality on each channel visually during a 12-h epoch containing waking state and sleep. Based on semiology, we classified stimulated seizures as typical or atypical/unclassifiable and estimated the stimulated SOZ (stimSOZ) for typical seizures. To assess which markers increased the odds of channel inclusion in the spSOZ, we fitted mixed effects logistic regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A combined regression model including the stimSOZ and interictal markers scored during sleep performed better in estimating which channels were part of the spSOZ than models based on stimSOZ (<i>p</i> < .001) or interictal markers (<i>p</i> < .001) alone. Of the individual markers, the effect sizes were greatest for inclusion of a channel in the stimSOZ (odds ratio [OR] = 60, 95% confidence interval [CI] = 37–97, <i>p</i> < .001) and for continuous (OR = 25, 95% CI = 12–55, <i>p</i> < .001) and subcontinuous (OR = 36, 95% CI = 21–64, <i>p</i> < .001) interictal spiking. At the individual level, the model's accuracy to predict spSOZ inclusion varied markedly (median accuracy = 85.7, range = 54.4–100), which was not explained by etiology (<i>p</i> > .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Compared to either marker alone, combining visually rated interictal SEEG markers and stimulated seizures improved prediction of which SEEG channels belonged to the spSOZ. Inclusion in the stimSOZ and continuous or subcontinuous spikes increased the odds of spSOZ inclusion the most. Future studies should investigate whether suboptimal sampling of the true epileptogenic zone can explain the model's poor performance in certain patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"2946-2958"},"PeriodicalIF":6.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dana Ayoub, Fatima Jaafar, Amal Al-Hajje, Pascale Salameh, Jeremy Jost, Ghassan Hmaimess, Jaafar Wazne, Zein Ismail-Fawaz, Sandra Sabbagh, Farid Boumediene, Ahmad Beydoun
Objective
Previous studies assessing factors associated with drug-resistant epilepsy (DRE) were constrained by their amalgamation of all epilepsy syndromes in their analyses and the absence of uniform criteria for defining DRE. Our objective was to identify predictors of DRE among the four primary childhood epilepsy syndrome groups within a cohort of children with new onset seizures, using the International League Against Epilepsy (ILAE) definition of DRE and the recent classification of epilepsies.
Methods
This is a prospective study of 676 children with new onset seizures initiated on antiseizure medication. Patients were monitored for the occurrence of DRE according to the ILAE criteria and were categorized into one of four epilepsy groups: self-limited focal epilepsies (SeLFEs), genetic generalized epilepsies (GGEs), developmental epileptic encephalopathies (DEEs), and focal epilepsies. Cox regression analysis was performed to identify predictors of DRE within each epilepsy group.
Results
Overall, 29.3% of children were classified as having DRE, with the highest incidence observed among children diagnosed with DEEs (77.7%), followed by focal epilepsies (31.5%). Across the entire cohort, predictors of DRE included the presence of an epileptogenic lesion, a higher pretreatment number of seizures, experiencing multiple seizure types, presence and severity of intellectual and developmental delay, myoclonus, and younger age at epilepsy onset. Within the GGEs, only a younger age at seizure onset and experiencing multiple seizure types predicted DRE. Among focal epilepsies, predictors of DRE included the presence of an epileptogenic lesion, experiencing multiple seizure types, and having a greater number of pretreatment seizures. Within the DEEs, predictors of DRE were the occurrence of tonic seizures. Predictors of DRE within SeLFEs could not be identified.
Significance
This study indicates that different epilepsy syndromes are associated with distinct predictors of drug resistance. Anticipation of drug resistance within various groups is feasible using accessible clinical variables throughout the disease course.
研究目的以往评估耐药性癫痫（DRE）相关因素的研究受到了限制，因为它们在分析中合并了所有癫痫综合征，而且缺乏定义 DRE 的统一标准。我们的目标是采用国际抗癫痫联盟（ILAE）对 DRE 的定义和最新的癫痫分类，在新发癫痫儿童队列中确定四个主要儿童癫痫综合征组中 DRE 的预测因素：这是一项前瞻性研究，研究对象是 676 名开始服用抗癫痫药物的新发癫痫发作儿童。根据ILAE标准监测患者是否出现DRE，并将其分为四类癫痫：自限性局灶性癫痫（SeLFEs）、遗传性全身性癫痫（GGEs）、发育性癫痫性脑病（DEEs）和局灶性癫痫。对每个癫痫组别进行了Cox回归分析，以确定DRE的预测因素：总体而言，29.3%的儿童被归类为患有DRE，其中诊断为DEEs的儿童发病率最高（77.7%），其次是局灶性癫痫（31.5%）。在整个队列中，预测 DRE 的因素包括存在致痫病灶、治疗前癫痫发作次数较多、经历多种癫痫发作类型、存在智力和发育迟缓及其严重程度、肌阵挛以及癫痫发病年龄较小。在普通癫痫患者中，只有发病年龄较小和经历多种癫痫发作类型才能预测 DRE。在局灶性癫痫中，预测 DRE 的因素包括存在致痫病灶、经历多种发作类型以及治疗前发作次数较多。在DEEs中，强直性发作是DRE的预测因素。在 SeLFEs 中，无法确定 DRE 的预测因素：这项研究表明，不同的癫痫综合征与不同的耐药性预测因素有关。利用整个病程中可获得的临床变量来预测不同群体的耐药性是可行的。
{"title":"Predictors of drug-resistant epilepsy in childhood epilepsy syndromes: A subgroup analysis from a prospective cohort study","authors":"Dana Ayoub, Fatima Jaafar, Amal Al-Hajje, Pascale Salameh, Jeremy Jost, Ghassan Hmaimess, Jaafar Wazne, Zein Ismail-Fawaz, Sandra Sabbagh, Farid Boumediene, Ahmad Beydoun","doi":"10.1111/epi.18100","DOIUrl":"10.1111/epi.18100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Previous studies assessing factors associated with drug-resistant epilepsy (DRE) were constrained by their amalgamation of all epilepsy syndromes in their analyses and the absence of uniform criteria for defining DRE. Our objective was to identify predictors of DRE among the four primary childhood epilepsy syndrome groups within a cohort of children with new onset seizures, using the International League Against Epilepsy (ILAE) definition of DRE and the recent classification of epilepsies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a prospective study of 676 children with new onset seizures initiated on antiseizure medication. Patients were monitored for the occurrence of DRE according to the ILAE criteria and were categorized into one of four epilepsy groups: self-limited focal epilepsies (SeLFEs), genetic generalized epilepsies (GGEs), developmental epileptic encephalopathies (DEEs), and focal epilepsies. Cox regression analysis was performed to identify predictors of DRE within each epilepsy group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 29.3% of children were classified as having DRE, with the highest incidence observed among children diagnosed with DEEs (77.7%), followed by focal epilepsies (31.5%). Across the entire cohort, predictors of DRE included the presence of an epileptogenic lesion, a higher pretreatment number of seizures, experiencing multiple seizure types, presence and severity of intellectual and developmental delay, myoclonus, and younger age at epilepsy onset. Within the GGEs, only a younger age at seizure onset and experiencing multiple seizure types predicted DRE. Among focal epilepsies, predictors of DRE included the presence of an epileptogenic lesion, experiencing multiple seizure types, and having a greater number of pretreatment seizures. Within the DEEs, predictors of DRE were the occurrence of tonic seizures. Predictors of DRE within SeLFEs could not be identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This study indicates that different epilepsy syndromes are associated with distinct predictors of drug resistance. Anticipation of drug resistance within various groups is feasible using accessible clinical variables throughout the disease course.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"2995-3009"},"PeriodicalIF":6.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongbin Wang, Zhen Qiao, Kun Luan, Wei Xiang, Xiuying Chang, Yanru Zhang, Ningning Wei, KeWei Wang
Objective
Pharmacological activation of neuronal Kv7 channels by the antiepileptic drug retigabine (RTG; ezogabine) has been proven effective in treating partial epilepsy. However, RTG was withdrawn from the market due to the toxicity caused by its phenazinium dimer metabolites, leading to peripheral skin discoloration and retinal abnormalities. To address the undesirable metabolic properties of RTG and prevent the formation of phenazinium dimers, we made chemical modifications to RTG, resulting in a new RTG derivative, 1025c, N,N′-{4-[(4-fluorobenzyl) (prop-2-yn-1-yl)amino]-1,2-phenylene}bis(3,3-dimethylbutanamide).
Methods
Whole-cell recordings were used to evaluate Kv7 channel openers. Site-directed mutagenesis and molecular docking were adopted to investigate the molecular mechanism underlying 1025c and Kv7.2 interactions. Mouse seizure models of maximal electroshock (MES), subcutaneous pentylenetetrazol (scPTZ), and PTZ-induced kindling were utilized to test compound antiepileptic activity.
Results
The novel compound 1025c selectively activates whole-cell Kv7.2/7.3 currents in a concentration-dependent manner, with half-maximal effective concentration of .91 ± .17 μmol·L−1. The 1025c compound also causes a leftward shift in Kv7.2/7.3 current activation toward a more hyperpolarized membrane potential, with a shift of the half voltage of maximal activation (ΔV1/2) of −18.6 ± 3.0 mV. Intraperitoneal administration of 1025c demonstrates dose-dependent antiseizure activities in assays of MES, scPTZ, and PTZ-induced kindling models. Moreover, through site-directed mutagenesis combined with molecular docking, a key residue Trp236 has been identified as critical for 1025c-mediated activation of Kv7.2 channels. Photostability experiments further reveal that 1025c is more photostable than RTG and is unable to dimerize.
Significance
Our findings demonstrate that 1025c exhibits potent and selective activation of neuronal Kv7 channels without being metabolized to phenazinium dimers, suggesting its developmental potential as an antiseizure agent for therapy.
{"title":"Identification of a new retigabine derivative with improved photostability for selective activation of neuronal Kv7 channels and antiseizure activity","authors":"Hongbin Wang, Zhen Qiao, Kun Luan, Wei Xiang, Xiuying Chang, Yanru Zhang, Ningning Wei, KeWei Wang","doi":"10.1111/epi.18092","DOIUrl":"10.1111/epi.18092","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Pharmacological activation of neuronal Kv7 channels by the antiepileptic drug retigabine (RTG; ezogabine) has been proven effective in treating partial epilepsy. However, RTG was withdrawn from the market due to the toxicity caused by its phenazinium dimer metabolites, leading to peripheral skin discoloration and retinal abnormalities. To address the undesirable metabolic properties of RTG and prevent the formation of phenazinium dimers, we made chemical modifications to RTG, resulting in a new RTG derivative, 1025c, <i>N,N′</i>-{4-[(4-fluorobenzyl) (prop-2-yn-1-yl)amino]-1,2-phenylene}bis(3,3-dimethylbutanamide).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-cell recordings were used to evaluate Kv7 channel openers. Site-directed mutagenesis and molecular docking were adopted to investigate the molecular mechanism underlying 1025c and Kv7.2 interactions. Mouse seizure models of maximal electroshock (MES), subcutaneous pentylenetetrazol (scPTZ), and PTZ-induced kindling were utilized to test compound antiepileptic activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The novel compound 1025c selectively activates whole-cell Kv7.2/7.3 currents in a concentration-dependent manner, with half-maximal effective concentration of .91 ± .17 μmol·L<sup>−1</sup>. The 1025c compound also causes a leftward shift in Kv7.2/7.3 current activation toward a more hyperpolarized membrane potential, with a shift of the half voltage of maximal activation (ΔV<sub>1/2</sub>) of −18.6 ± 3.0 mV. Intraperitoneal administration of 1025c demonstrates dose-dependent antiseizure activities in assays of MES, scPTZ, and PTZ-induced kindling models. Moreover, through site-directed mutagenesis combined with molecular docking, a key residue Trp236 has been identified as critical for 1025c-mediated activation of Kv7.2 channels. Photostability experiments further reveal that 1025c is more photostable than RTG and is unable to dimerize.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Our findings demonstrate that 1025c exhibits potent and selective activation of neuronal Kv7 channels without being metabolized to phenazinium dimers, suggesting its developmental potential as an antiseizure agent for therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"2923-2934"},"PeriodicalIF":6.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Mansilla, Jesper Tveit, Harald Aurlien, Tamir Avigdor, Victoria Ros-Castello, Alyssa Ho, Chifaou Abdallah, Jean Gotman, Sándor Beniczky, Birgit Frauscher
Objective
The automated interpretation of clinical electroencephalograms (EEGs) using artificial intelligence (AI) holds the potential to bridge the treatment gap in resource-limited settings and reduce the workload at specialized centers. However, to facilitate broad clinical implementation, it is essential to establish generalizability across diverse patient populations and equipment. We assessed whether SCORE-AI demonstrates diagnostic accuracy comparable to that of experts when applied to a geographically different patient population, recorded with distinct EEG equipment and technical settings.
Methods
We assessed the diagnostic accuracy of a “fixed-and-frozen” AI model, using an independent dataset and external gold standard, and benchmarked it against three experts blinded to all other data. The dataset comprised 50% normal and 50% abnormal routine EEGs, equally distributed among the four major classes of EEG abnormalities (focal epileptiform, generalized epileptiform, focal nonepileptiform, and diffuse nonepileptiform). To assess diagnostic accuracy, we computed sensitivity, specificity, and accuracy of the AI model and the experts against the external gold standard.
Results
We analyzed EEGs from 104 patients (64 females, median age = 38.6 [range = 16–91] years). SCORE-AI performed equally well compared to the experts, with an overall accuracy of 92% (95% confidence interval [CI] = 90%–94%) versus 94% (95% CI = 92%–96%). There was no significant difference between SCORE-AI and the experts for any metric or category. SCORE-AI performed well independently of the vigilance state (false classification during awake: 5/41 [12.2%], false classification during sleep: 2/11 [18.2%]; p = .63) and normal variants (false classification in presence of normal variants: 4/14 [28.6%], false classification in absence of normal variants: 3/38 [7.9%]; p = .07).
Significance
SCORE-AI achieved diagnostic performance equal to human experts in an EEG dataset independent of the development dataset, in a geographically distinct patient population, recorded with different equipment and technical settings than the development dataset.
{"title":"Generalizability of electroencephalographic interpretation using artificial intelligence: An external validation study","authors":"Daniel Mansilla, Jesper Tveit, Harald Aurlien, Tamir Avigdor, Victoria Ros-Castello, Alyssa Ho, Chifaou Abdallah, Jean Gotman, Sándor Beniczky, Birgit Frauscher","doi":"10.1111/epi.18082","DOIUrl":"10.1111/epi.18082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The automated interpretation of clinical electroencephalograms (EEGs) using artificial intelligence (AI) holds the potential to bridge the treatment gap in resource-limited settings and reduce the workload at specialized centers. However, to facilitate broad clinical implementation, it is essential to establish generalizability across diverse patient populations and equipment. We assessed whether SCORE-AI demonstrates diagnostic accuracy comparable to that of experts when applied to a geographically different patient population, recorded with distinct EEG equipment and technical settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed the diagnostic accuracy of a “fixed-and-frozen” AI model, using an independent dataset and external gold standard, and benchmarked it against three experts blinded to all other data. The dataset comprised 50% normal and 50% abnormal routine EEGs, equally distributed among the four major classes of EEG abnormalities (focal epileptiform, generalized epileptiform, focal nonepileptiform, and diffuse nonepileptiform). To assess diagnostic accuracy, we computed sensitivity, specificity, and accuracy of the AI model and the experts against the external gold standard.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analyzed EEGs from 104 patients (64 females, median age = 38.6 [range = 16–91] years). SCORE-AI performed equally well compared to the experts, with an overall accuracy of 92% (95% confidence interval [CI] = 90%–94%) versus 94% (95% CI = 92%–96%). There was no significant difference between SCORE-AI and the experts for any metric or category. SCORE-AI performed well independently of the vigilance state (false classification during awake: 5/41 [12.2%], false classification during sleep: 2/11 [18.2%]; <i>p</i> = .63) and normal variants (false classification in presence of normal variants: 4/14 [28.6%], false classification in absence of normal variants: 3/38 [7.9%]; <i>p</i> = .07).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>SCORE-AI achieved diagnostic performance equal to human experts in an EEG dataset independent of the development dataset, in a geographically distinct patient population, recorded with different equipment and technical settings than the development dataset.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"3028-3037"},"PeriodicalIF":6.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roberta Roberti, Giovanni Assenza, Francesca Bisulli, Giovanni Boero, Laura Canafoglia, Valentina Chiesa, Carlo Di Bonaventura, Giancarlo Di Gennaro, Maurizio Elia, Edoardo Ferlazzo, Alfonso Giordano, Angela La Neve, Claudio Liguori, Stefano Meletti, Francesca Felicia Operto, Nicola Pietrafusa, Monica Puligheddu, Patrizia Pulitano, Eleonora Rosati, Ilaria Sammarra, Elena Tartara, Giampaolo Vatti, Flavio Villani, CNB EAP Italy Study Group, Emilio Russo, Simona Lattanzi
Objective
This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy.
Methods
This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses.
Results
A total of 236 subjects with a median age of 38 (Q1–Q3 = 27–49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q1–Q3 = 2.50–4.47) at baseline to 2.50 (Q1–Q3 = 1.67–3.50) at 12 months (p < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel.
Significance
Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.
{"title":"Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program","authors":"Roberta Roberti, Giovanni Assenza, Francesca Bisulli, Giovanni Boero, Laura Canafoglia, Valentina Chiesa, Carlo Di Bonaventura, Giancarlo Di Gennaro, Maurizio Elia, Edoardo Ferlazzo, Alfonso Giordano, Angela La Neve, Claudio Liguori, Stefano Meletti, Francesca Felicia Operto, Nicola Pietrafusa, Monica Puligheddu, Patrizia Pulitano, Eleonora Rosati, Ilaria Sammarra, Elena Tartara, Giampaolo Vatti, Flavio Villani, CNB EAP Italy Study Group, Emilio Russo, Simona Lattanzi","doi":"10.1111/epi.18091","DOIUrl":"10.1111/epi.18091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 236 subjects with a median age of 38 (Q<sub>1</sub>–Q<sub>3</sub> = 27–49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q<sub>1</sub>–Q<sub>3</sub> = 2.50–4.47) at baseline to 2.50 (Q<sub>1</sub>–Q<sub>3</sub> = 1.67–3.50) at 12 months (<i>p</i> < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"2909-2922"},"PeriodicalIF":6.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gregory A. Worrell, Jie Cui, Filip Mivalt, Vaclav Kremen
{"title":"Letter regarding “Modification of brain conductivity in human focal epilepsy: A model-based estimation from stereoelectroencephalography” by Lagarde et al","authors":"Gregory A. Worrell, Jie Cui, Filip Mivalt, Vaclav Kremen","doi":"10.1111/epi.18093","DOIUrl":"10.1111/epi.18093","url":null,"abstract":"","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"3115-3116"},"PeriodicalIF":6.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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