Objective: Clinical investigators have hypothesized that interictal epileptiform discharges (IEDs) generated by hypothalamic hamartoma (HH) lead to cognitive dysfunction in patients with drug-resistant gelastic seizures. Herein we provide causal evidence supporting this hypothesis by demonstrating that excitatory neural bursts, when propagating from the HH to the mediodorsal thalamus during the encoding period, impair working memory.
Methods: By employing channelrhodopsin-2 photostimulation, we induced excessive neural excitation in Long-Evans rats, resembling IEDs, at the axon terminals of the lateral hypothalamus projecting toward the mediodorsal thalamus and prelimbic cortex. We recorded local field potentials (LFPs) at these sites and assessed the performance of working memory tasks with and without photostimulation. Utilizing support vector machine analysis on LFP trials under sham photostimulation, we identified the neural correlates of successful task performance. Through mixed model analyses, we evaluated the impacts of photostimulation timing and the alteration in LFP amplitude induced by photostimulation on task performance.
Results: Ten rats completed operant conditioning using a spout lever system after receiving an average of 70.7 days of training, at a rate of 135.2 trials per day. During sham photostimulation, successful trials were associated with a shorter duration of the working memory maintenance period, as well as an augmentation in the 10- to 14-Hz LFP amplitude at the mediodorsal thalamus and prelimbic cortex during the memory encoding phase. Photostimulation at the mediodorsal thalamus during encoding reduced the odds of a trial being successful by 0.19. Conversely, excessive mediodorsal thalamus LFP augmentation induced by photostimulation during encoding increased the odds of a trial being unsuccessful by 1.04.
Significance: Excessive neural excitation, specifically propagating from the lateral hypothalamus to the mediodorsal thalamus during encoding, alters physiological neural activity and transiently impairs working memory. This study clarifies the pathophysiological mechanism underlying cognitive disabilities associated with working memory impairment in HH-related epileptic encephalopathy.
{"title":"Optogenetically-induced sustained hypothalamic hyperexcitability impairs memory via thalamic spread.","authors":"Masaki Sonoda, Hisao Aimi, Keisuke Kawasaki, Haruo Toda, Shinobu Hirai, Masao Horie, Reiko Meguro, Eishi Asano, Haruo Okado, Shigeki Kameyama, Tetsuya Yamamoto, Isao Hasegawa","doi":"10.1111/epi.18321","DOIUrl":"https://doi.org/10.1111/epi.18321","url":null,"abstract":"<p><strong>Objective: </strong>Clinical investigators have hypothesized that interictal epileptiform discharges (IEDs) generated by hypothalamic hamartoma (HH) lead to cognitive dysfunction in patients with drug-resistant gelastic seizures. Herein we provide causal evidence supporting this hypothesis by demonstrating that excitatory neural bursts, when propagating from the HH to the mediodorsal thalamus during the encoding period, impair working memory.</p><p><strong>Methods: </strong>By employing channelrhodopsin-2 photostimulation, we induced excessive neural excitation in Long-Evans rats, resembling IEDs, at the axon terminals of the lateral hypothalamus projecting toward the mediodorsal thalamus and prelimbic cortex. We recorded local field potentials (LFPs) at these sites and assessed the performance of working memory tasks with and without photostimulation. Utilizing support vector machine analysis on LFP trials under sham photostimulation, we identified the neural correlates of successful task performance. Through mixed model analyses, we evaluated the impacts of photostimulation timing and the alteration in LFP amplitude induced by photostimulation on task performance.</p><p><strong>Results: </strong>Ten rats completed operant conditioning using a spout lever system after receiving an average of 70.7 days of training, at a rate of 135.2 trials per day. During sham photostimulation, successful trials were associated with a shorter duration of the working memory maintenance period, as well as an augmentation in the 10- to 14-Hz LFP amplitude at the mediodorsal thalamus and prelimbic cortex during the memory encoding phase. Photostimulation at the mediodorsal thalamus during encoding reduced the odds of a trial being successful by 0.19. Conversely, excessive mediodorsal thalamus LFP augmentation induced by photostimulation during encoding increased the odds of a trial being unsuccessful by 1.04.</p><p><strong>Significance: </strong>Excessive neural excitation, specifically propagating from the lateral hypothalamus to the mediodorsal thalamus during encoding, alters physiological neural activity and transiently impairs working memory. This study clarifies the pathophysiological mechanism underlying cognitive disabilities associated with working memory impairment in HH-related epileptic encephalopathy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604447","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}
Objective: Temporal lobe epilepsy (TLE) has been recognized as a network disorder with widespread gray matter atrophy. However, the role of connectome architecture in shaping morphological alterations and identifying atrophy epicenters remains unclear. Furthermore, individualized modeling of atrophy epicenters and their potential clinical applications have not been well established. This study aims to explore how gray matter atrophy correlates with normal connectome architecture, identify potential atrophy epicenters, and employ individualized modeling approach to evaluate the impact of different epicenter patterns on surgical outcomes in patients with TLE.
Methods: This study utilized anatomic MRI data from 126 refractory TLE patients who underwent anterior temporal lobectomy and 60 healthy controls (HCs), along with normative functional and structural connectome data, to investigate the relationship between gray matter volume (GMV) changes and functional or structural connectivity. Two models were employed to identify atrophy epicenters: a data-driven approach evaluating nodal and neighbor atrophy rankings, and a network diffusion model (NDM) simulating the spread of pathology from different seed regions. K-means clustering was applied in patient-tailored modeling to uncover distinct epicenter subtypes.
Results: Our findings indicate that the pattern of gray matter atrophy in TLE is constrained primarily by structural connectivity rather than by functional connectivity. Using the structural connectome, we pinpointed the hippocampus and adjacent temporo-limbic regions as key atrophy epicenters. The patient-tailored modeling revealed significant variability in epicenter distribution, allowing us to categorize them into two distinct subtypes. Notably, patients in subtype 2, with epicenters localized to the ipsilateral temporal pole and medial temporal lobe, exhibited significantly higher seizure-free rates compared to patients in subtype 1, whose epicenters situated in frontocentral regions.
Significance: These findings highlight the central role of structural connectivity in shaping TLE-related morphological changes. Individualized epicenter modeling may enhance surgical decisions and improve prognostic stratification in TLE management.
{"title":"Connectome architecture for gray matter atrophy and surgical outcomes in temporal lobe epilepsy.","authors":"Qiuxing Lin, Danyang Cao, Wei Li, Yingying Zhang, Yuming Li, Peiwen Liu, Xiang Huang, Kailing Huang, Qiyong Gong, Dong Zhou, Dongmei An","doi":"10.1111/epi.18343","DOIUrl":"https://doi.org/10.1111/epi.18343","url":null,"abstract":"<p><strong>Objective: </strong>Temporal lobe epilepsy (TLE) has been recognized as a network disorder with widespread gray matter atrophy. However, the role of connectome architecture in shaping morphological alterations and identifying atrophy epicenters remains unclear. Furthermore, individualized modeling of atrophy epicenters and their potential clinical applications have not been well established. This study aims to explore how gray matter atrophy correlates with normal connectome architecture, identify potential atrophy epicenters, and employ individualized modeling approach to evaluate the impact of different epicenter patterns on surgical outcomes in patients with TLE.</p><p><strong>Methods: </strong>This study utilized anatomic MRI data from 126 refractory TLE patients who underwent anterior temporal lobectomy and 60 healthy controls (HCs), along with normative functional and structural connectome data, to investigate the relationship between gray matter volume (GMV) changes and functional or structural connectivity. Two models were employed to identify atrophy epicenters: a data-driven approach evaluating nodal and neighbor atrophy rankings, and a network diffusion model (NDM) simulating the spread of pathology from different seed regions. K-means clustering was applied in patient-tailored modeling to uncover distinct epicenter subtypes.</p><p><strong>Results: </strong>Our findings indicate that the pattern of gray matter atrophy in TLE is constrained primarily by structural connectivity rather than by functional connectivity. Using the structural connectome, we pinpointed the hippocampus and adjacent temporo-limbic regions as key atrophy epicenters. The patient-tailored modeling revealed significant variability in epicenter distribution, allowing us to categorize them into two distinct subtypes. Notably, patients in subtype 2, with epicenters localized to the ipsilateral temporal pole and medial temporal lobe, exhibited significantly higher seizure-free rates compared to patients in subtype 1, whose epicenters situated in frontocentral regions.</p><p><strong>Significance: </strong>These findings highlight the central role of structural connectivity in shaping TLE-related morphological changes. Individualized epicenter modeling may enhance surgical decisions and improve prognostic stratification in TLE management.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585144","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}
Objective: The identification of epileptic lesions is crucial for improving surgical outcomes. Nevertheless, substantial focal cortical dysplasia (FCD) may be invisible on magnetic resonance imaging (MRI). We aimed to characterize the expression pattern of 18-kDa translocator protein (TSPO) in FCD and to evaluate the effectiveness of this inflammation-reflective molecular imaging technique for detecting FCD.
Methods: Patients clinically diagnosed with FCD, based on clinical features, interictal electroencephalographic (EEG) findings, and MRI characteristics, underwent positron emission tomography (PET) imaging using 18F-DPA714 and 18F-fluorodeoxyglucose (FDG) tracers. TSPO-PET activation patterns were qualitatively evaluated. Semiquantitative analysis using the Highlight Index (HI) was further performed to investigate its correlation with clinical characteristics. For patients who underwent stereo-EEG (SEEG) monitoring, the site of high-level TSPO-PET activation was compared with the seizure onset zone identified by SEEG. For patients who underwent resection surgery, the relationship between TSPO-PET uptake and histopathological findings was studied.
Results: Twenty-four patients were enrolled. Three groups were identified: MRI-positive with visible high-level TSPO-PET activation (six patients), MRI-negative with visible high-level TSPO-PET activation (thirteen patients), and MRI-positive with invisible low-level TSPO-PET activation (five patients). Regions of high-level TSPO-PET activation showed concordance with ictal discharges in five patients who underwent SEEG. Compared with FDG-PET, TSPO-PET exhibited a more prominent signal against the background (p = .0158). HI was correlated with seizure frequency (p = .0362) and the occurrence of focal to bilateral tonic-clonic seizures (p = .0294), and shorter interval between the TSPO-PET scan and the last seizure was associated with higher TSPO-PET HI (R = -.4323, p = .0349). Postoperative histopathological examination confirmed high-level TSPO-PET activation rates of 3/3 for FCD type IIb and 1/3 for FCD type IIa.
Significance: TSPO-PET activation patterns offer clinical significance for improving surgical outcomes by enhancing FCD detection during presurgical evaluation. Also, our observations offer new insights into the histopathological basis for increased TSPO uptake in humans.
{"title":"Emerging translocator protein-positron emission tomographic imaging improves detection of focal cortical dysplasia.","authors":"Zichen Qiao, Yingxue Yang, Yuanhong Chen, Linai Guo, Qing Xue, Lehong Gao, Jia Chen, Bixiao Cui, Jinghui Liu, Haoxun Yang, Xueyuan Wang, Yihe Wang, Huaqiang Zhang, Cuiping Xu, Yicong Lin, Tao Yu, Yuping Wang, Yueshan Piao, Jie Lu, Liankun Ren","doi":"10.1111/epi.18351","DOIUrl":"https://doi.org/10.1111/epi.18351","url":null,"abstract":"<p><strong>Objective: </strong>The identification of epileptic lesions is crucial for improving surgical outcomes. Nevertheless, substantial focal cortical dysplasia (FCD) may be invisible on magnetic resonance imaging (MRI). We aimed to characterize the expression pattern of 18-kDa translocator protein (TSPO) in FCD and to evaluate the effectiveness of this inflammation-reflective molecular imaging technique for detecting FCD.</p><p><strong>Methods: </strong>Patients clinically diagnosed with FCD, based on clinical features, interictal electroencephalographic (EEG) findings, and MRI characteristics, underwent positron emission tomography (PET) imaging using <sup>18</sup>F-DPA714 and <sup>18</sup>F-fluorodeoxyglucose (FDG) tracers. TSPO-PET activation patterns were qualitatively evaluated. Semiquantitative analysis using the Highlight Index (HI) was further performed to investigate its correlation with clinical characteristics. For patients who underwent stereo-EEG (SEEG) monitoring, the site of high-level TSPO-PET activation was compared with the seizure onset zone identified by SEEG. For patients who underwent resection surgery, the relationship between TSPO-PET uptake and histopathological findings was studied.</p><p><strong>Results: </strong>Twenty-four patients were enrolled. Three groups were identified: MRI-positive with visible high-level TSPO-PET activation (six patients), MRI-negative with visible high-level TSPO-PET activation (thirteen patients), and MRI-positive with invisible low-level TSPO-PET activation (five patients). Regions of high-level TSPO-PET activation showed concordance with ictal discharges in five patients who underwent SEEG. Compared with FDG-PET, TSPO-PET exhibited a more prominent signal against the background (p = .0158). HI was correlated with seizure frequency (p = .0362) and the occurrence of focal to bilateral tonic-clonic seizures (p = .0294), and shorter interval between the TSPO-PET scan and the last seizure was associated with higher TSPO-PET HI (R = -.4323, p = .0349). Postoperative histopathological examination confirmed high-level TSPO-PET activation rates of 3/3 for FCD type IIb and 1/3 for FCD type IIa.</p><p><strong>Significance: </strong>TSPO-PET activation patterns offer clinical significance for improving surgical outcomes by enhancing FCD detection during presurgical evaluation. Also, our observations offer new insights into the histopathological basis for increased TSPO uptake in humans.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585145","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}
Salvatore Citro, Sam S Javidi, Ankeeta Ankeeta, Xiaosong He, Qirui Zhang, Yolanda Kry, Michael R Sperling, Joseph I Tracy
Objective: Subjects with left temporal lobe epilepsy may either show altered hemispheric language lateralization or retain typical, left lateralization. Examining the integrity of white matter pathways involved in the adaptation or maintenance of language lateralization in these patients could have important clinical implications for preserving or potentiating compensatory language mechanisms.
Methods: We combined task functional magnetic resonance imaging and structural diffusion metrics to determine the dependency of lobe-based language laterality on white matter integrity in healthy participants and left temporal lobe epilepsy (TLE) patients. We tested for differences between individuals who expressed typical, left hemisphere laterality compared to those with atypical laterality patterns (bilateral or right hemisphere biased).
Results: A total of 41 left TLE patients and 51 sex- and age-matched healthy participants (HPs) were enrolled. In left temporal lobe epilepsy, typical patterns of frontal and temporal lateralities were less conditioned by the language-related white matter connections of the left temporal lobe. In typically organized epilepsy subjects, temporal lobe language laterality was dependent upon the structural connectivities of the left parietal lobe. Among atypically organized individuals, compared to HPs, TLE patients displayed frontal and parietal language lateralities mediated by the structural connectivities of the left parietal lobe.
Significance: Language-related left parietal lobe connections were critical both for maintaining typical left hemisphere-biased language processing in the temporal lobe and for the formation of noncanonical, potentially adaptive language processing asymmetries in the frontal and parietal lobes. Assessments of the laterality and integrity of language skills in left temporal lobe epilepsy will require modeling white matter structural influences.
{"title":"Left parietal structural connectivity mediates typical and atypical language laterality in temporal lobe epilepsy.","authors":"Salvatore Citro, Sam S Javidi, Ankeeta Ankeeta, Xiaosong He, Qirui Zhang, Yolanda Kry, Michael R Sperling, Joseph I Tracy","doi":"10.1111/epi.18298","DOIUrl":"https://doi.org/10.1111/epi.18298","url":null,"abstract":"<p><strong>Objective: </strong>Subjects with left temporal lobe epilepsy may either show altered hemispheric language lateralization or retain typical, left lateralization. Examining the integrity of white matter pathways involved in the adaptation or maintenance of language lateralization in these patients could have important clinical implications for preserving or potentiating compensatory language mechanisms.</p><p><strong>Methods: </strong>We combined task functional magnetic resonance imaging and structural diffusion metrics to determine the dependency of lobe-based language laterality on white matter integrity in healthy participants and left temporal lobe epilepsy (TLE) patients. We tested for differences between individuals who expressed typical, left hemisphere laterality compared to those with atypical laterality patterns (bilateral or right hemisphere biased).</p><p><strong>Results: </strong>A total of 41 left TLE patients and 51 sex- and age-matched healthy participants (HPs) were enrolled. In left temporal lobe epilepsy, typical patterns of frontal and temporal lateralities were less conditioned by the language-related white matter connections of the left temporal lobe. In typically organized epilepsy subjects, temporal lobe language laterality was dependent upon the structural connectivities of the left parietal lobe. Among atypically organized individuals, compared to HPs, TLE patients displayed frontal and parietal language lateralities mediated by the structural connectivities of the left parietal lobe.</p><p><strong>Significance: </strong>Language-related left parietal lobe connections were critical both for maintaining typical left hemisphere-biased language processing in the temporal lobe and for the formation of noncanonical, potentially adaptive language processing asymmetries in the frontal and parietal lobes. Assessments of the laterality and integrity of language skills in left temporal lobe epilepsy will require modeling white matter structural influences.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585147","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}
Atsuro Daida, Saarang Panchavati, Shingo Oana, Sotaro Kanai, Yipeng Zhang, Yuanyi Ding, Rajaraman R Rajsekar, Noriko Salamon, Raman Sankar, Aria Fallah, Shaun A Hussain, Vwani Roychowdhury, William Speier, Hiroki Nariai
Objective: Although the role of subcortical structures in the generation of epileptic spasms has been proposed, supporting evidence remains limited. This study aimed to provide neurophysiological evidence of thalamocortical network involvement during epileptic spasms.
Methods: We analyzed four patients (ages 2.7-16.9 years) with epileptic spasms who underwent intracranial electroencephalography (EEG) monitoring with thalamic sampling in preparation for potential neurostimulation. Epileptic spasms were initially assessed using visual inspection and time-frequency analysis. We then evaluated undirected connectivity through coherence analysis and directed connectivity using spectral Granger causality analysis between the thalamus and the seizure-onset zone, focusing on ictal connectivity changes in both slow (0.5-10 Hz) and fast (10-80 Hz) frequency bands. In addition, phase-amplitude coupling was assessed with a modulation index to examine the interaction between ictal slow and fast band activities.
Results: A total of 84 epileptic spasms were analyzed. Ictal EEG changes of slow wave complex were visually confirmed in the thalamic channels. There was an increase in signal power in both the slow and fast bands at the thalamus. Undirected (coherence) and directed (spectral Granger causality) connectivity analyses showed a significant increase in connectivity between the thalamus and seizure-onset zone in both the slow and fast bands compared to baseline. Directed connectivity in the slow bands increased equally from the thalamus to the seizure-onset zone (outflow) and vice versa (inflow). However, fast band inflow was more pronounced than outflow. The modulation index increased significantly during epileptic spasms at the thalamus. Furthermore, a higher modulation index in the cortex correlated with more pronounced clinical manifestations of epileptic spasms.
Significance: Ictal slow-wave complexes on EEG during epileptic spasms may reflect long-range thalamocortical network activation, highlighting the critical role of subcortical structures in ictogenesis and the potential treatment implications for thalamic neuromodulation.
{"title":"Evidence of thalamocortical network activation during epileptic spasms: A thalamic stereotactic EEG study.","authors":"Atsuro Daida, Saarang Panchavati, Shingo Oana, Sotaro Kanai, Yipeng Zhang, Yuanyi Ding, Rajaraman R Rajsekar, Noriko Salamon, Raman Sankar, Aria Fallah, Shaun A Hussain, Vwani Roychowdhury, William Speier, Hiroki Nariai","doi":"10.1111/epi.18349","DOIUrl":"https://doi.org/10.1111/epi.18349","url":null,"abstract":"<p><strong>Objective: </strong>Although the role of subcortical structures in the generation of epileptic spasms has been proposed, supporting evidence remains limited. This study aimed to provide neurophysiological evidence of thalamocortical network involvement during epileptic spasms.</p><p><strong>Methods: </strong>We analyzed four patients (ages 2.7-16.9 years) with epileptic spasms who underwent intracranial electroencephalography (EEG) monitoring with thalamic sampling in preparation for potential neurostimulation. Epileptic spasms were initially assessed using visual inspection and time-frequency analysis. We then evaluated undirected connectivity through coherence analysis and directed connectivity using spectral Granger causality analysis between the thalamus and the seizure-onset zone, focusing on ictal connectivity changes in both slow (0.5-10 Hz) and fast (10-80 Hz) frequency bands. In addition, phase-amplitude coupling was assessed with a modulation index to examine the interaction between ictal slow and fast band activities.</p><p><strong>Results: </strong>A total of 84 epileptic spasms were analyzed. Ictal EEG changes of slow wave complex were visually confirmed in the thalamic channels. There was an increase in signal power in both the slow and fast bands at the thalamus. Undirected (coherence) and directed (spectral Granger causality) connectivity analyses showed a significant increase in connectivity between the thalamus and seizure-onset zone in both the slow and fast bands compared to baseline. Directed connectivity in the slow bands increased equally from the thalamus to the seizure-onset zone (outflow) and vice versa (inflow). However, fast band inflow was more pronounced than outflow. The modulation index increased significantly during epileptic spasms at the thalamus. Furthermore, a higher modulation index in the cortex correlated with more pronounced clinical manifestations of epileptic spasms.</p><p><strong>Significance: </strong>Ictal slow-wave complexes on EEG during epileptic spasms may reflect long-range thalamocortical network activation, highlighting the critical role of subcortical structures in ictogenesis and the potential treatment implications for thalamic neuromodulation.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572502","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}
Colin A Ellis, Ruth Ottman, Michael P Epstein, Samuel F Berkovic, Karen L Oliver
Objective: Although previous research shows that generalized and focal epilepsies have at least some distinct genetic influences, it remains uncertain why some families manifest both types of epilepsy. We tested two hypotheses: (1) families with both generalized and focal epilepsy carry separate risk alleles for both types; and (2) within mixed families, the type of epilepsy each individual manifests is influenced by the relative burden of separate risk alleles for generalized epilepsies and focal epilepsies.
Methods: The Epi4K cohort included 711 individuals with epilepsy from 257 families (113 generalized families, 66 focal families, 78 mixed families). We calculated polygenic risk scores (PRSs) for genetic generalized epilepsy (GGE_PRS) and for focal epilepsy (Focal_PRS). We used mixed-effects models to compare these PRSs between and within families, accounting for relatedness.
Results: Compared to population controls, individuals in generalized families had elevated GGE_PRS (p < .001) but not elevated Focal_PRS (p = .50); focal family individuals had elevated Focal_PRS (p = .008) but not elevated GGE_PRS (p = .22); and individuals in mixed families had both elevated GGE_PRS and elevated Focal_PRS (both p < .001). Within mixed families, GGE_PRS was higher in individuals with generalized epilepsy than in individuals with focal epilepsy (p < .001), whereas we did not detect a difference in Focal_PRS between individuals with generalized and focal epilepsy (p = .46). The GGE_PRS value explained 10% of the variance in phenotype within mixed families.
Significance: The occurrence of families with both generalized and focal epilepsy in separate individuals is explained at least partly by the chance co-occurrence of distinct genetic risk alleles for generalized and focal epilepsies. Within mixed families, an individual's epilepsy type can be explained at least in part by the relative burden of risk alleles for genetic generalized epilepsy.
{"title":"Phenotypic heterogeneity in familial epilepsies is influenced by polygenic risk for generalized and focal epilepsies.","authors":"Colin A Ellis, Ruth Ottman, Michael P Epstein, Samuel F Berkovic, Karen L Oliver","doi":"10.1111/epi.18348","DOIUrl":"https://doi.org/10.1111/epi.18348","url":null,"abstract":"<p><strong>Objective: </strong>Although previous research shows that generalized and focal epilepsies have at least some distinct genetic influences, it remains uncertain why some families manifest both types of epilepsy. We tested two hypotheses: (1) families with both generalized and focal epilepsy carry separate risk alleles for both types; and (2) within mixed families, the type of epilepsy each individual manifests is influenced by the relative burden of separate risk alleles for generalized epilepsies and focal epilepsies.</p><p><strong>Methods: </strong>The Epi4K cohort included 711 individuals with epilepsy from 257 families (113 generalized families, 66 focal families, 78 mixed families). We calculated polygenic risk scores (PRSs) for genetic generalized epilepsy (GGE_PRS) and for focal epilepsy (Focal_PRS). We used mixed-effects models to compare these PRSs between and within families, accounting for relatedness.</p><p><strong>Results: </strong>Compared to population controls, individuals in generalized families had elevated GGE_PRS (p < .001) but not elevated Focal_PRS (p = .50); focal family individuals had elevated Focal_PRS (p = .008) but not elevated GGE_PRS (p = .22); and individuals in mixed families had both elevated GGE_PRS and elevated Focal_PRS (both p < .001). Within mixed families, GGE_PRS was higher in individuals with generalized epilepsy than in individuals with focal epilepsy (p < .001), whereas we did not detect a difference in Focal_PRS between individuals with generalized and focal epilepsy (p = .46). The GGE_PRS value explained 10% of the variance in phenotype within mixed families.</p><p><strong>Significance: </strong>The occurrence of families with both generalized and focal epilepsy in separate individuals is explained at least partly by the chance co-occurrence of distinct genetic risk alleles for generalized and focal epilepsies. Within mixed families, an individual's epilepsy type can be explained at least in part by the relative burden of risk alleles for genetic generalized epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566608","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}
Despite significant research into more flexible methods of ketogenic diet therapy initiation, there is only limited literature on the best practices to discontinue it. Both tradition and guidelines suggest weaning this treatment over 2-3 months; however, a more abrupt discontinuation has also been reported. Fifteen children and adults on ketogenic diet therapy, with various levels of seizure control, had their ketogenic diet therapy immediately discontinued. All were coincidentally admitted to inpatient units (typically an epilepsy monitoring unit), with intravenous access and electroencephalographic (EEG) monitoring. Patients and parents were counseled, regular foods or formula was ordered, and unlimited carbohydrates were provided to break ketosis under close supervision. Thirteen patients had no worsening in seizure frequency or EEG and were discharged home off of ketogenic diet therapy. Two patients, aged 4 and 33 years, had increased seizure frequency, and ketogenic diets were restarted prior to discharge. This method of safe, inpatient rapid diet discontinuation can be utilized as an alternative method to a more gradual weaning process.
{"title":"Immediate inpatient carbohydrate challenge: Novel method of ketogenic diet therapy discontinuation.","authors":"Eric H Kossoff, Zahava Turner","doi":"10.1111/epi.18350","DOIUrl":"https://doi.org/10.1111/epi.18350","url":null,"abstract":"<p><p>Despite significant research into more flexible methods of ketogenic diet therapy initiation, there is only limited literature on the best practices to discontinue it. Both tradition and guidelines suggest weaning this treatment over 2-3 months; however, a more abrupt discontinuation has also been reported. Fifteen children and adults on ketogenic diet therapy, with various levels of seizure control, had their ketogenic diet therapy immediately discontinued. All were coincidentally admitted to inpatient units (typically an epilepsy monitoring unit), with intravenous access and electroencephalographic (EEG) monitoring. Patients and parents were counseled, regular foods or formula was ordered, and unlimited carbohydrates were provided to break ketosis under close supervision. Thirteen patients had no worsening in seizure frequency or EEG and were discharged home off of ketogenic diet therapy. Two patients, aged 4 and 33 years, had increased seizure frequency, and ketogenic diets were restarted prior to discharge. This method of safe, inpatient rapid diet discontinuation can be utilized as an alternative method to a more gradual weaning process.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566607","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}
Kara B Miecznikowski, Hansel M Greiner, James Leach, Leonid Rozhkov, Francesco T Mangano, Darcy A Krueger, Mark W DiFrancesco
Objective: Patients with tuberous sclerosis complex (TSC)-related epilepsy often have drug-refractory epilepsy and numerous potential epileptogenic tubers. Current clinical methods target tubers for resection, but prediction of resulting seizure relief is difficult. This study describes implementation of lesion network mapping in TSC patients undergoing epilepsy surgery to associate resection zone with seizure outcomes.
Methods: Thirty-nine consecutive patients with TSC who underwent invasive electroencephalography (EEG) and resection or ablation of the seizure onset zone were included. After preprocessing, each resection zone was delineated as the region of interest. Lesion network mapping was performed to determine the association between cortical networks connected to the resection zone and postoperative outcome using a multiple regression, iterative model that included demographic and other variables obtained from analysis of invasive EEG.
Results: Of 39 patients, 20 (51%) had a good International League Against Epilepsy outcome (1-3). Resection regions connected to the default mode network and motor network were associated with better seizure outcome. Regions connected to the bilateral insula, visual associative regions, and putamen were associated with poor seizure outcome.
Significance: This study provides methodology for lesion network mapping in TSC-related epilepsy. The results suggest a tendency for better outcomes when the resection zone is connected to certain networks, including the default mode and motor networks, that may support sustainment of seizures.
{"title":"Prognostic application of lesion network mapping to epilepsy surgery outcomes in pediatric tuberous sclerosis complex.","authors":"Kara B Miecznikowski, Hansel M Greiner, James Leach, Leonid Rozhkov, Francesco T Mangano, Darcy A Krueger, Mark W DiFrancesco","doi":"10.1111/epi.18320","DOIUrl":"https://doi.org/10.1111/epi.18320","url":null,"abstract":"<p><strong>Objective: </strong>Patients with tuberous sclerosis complex (TSC)-related epilepsy often have drug-refractory epilepsy and numerous potential epileptogenic tubers. Current clinical methods target tubers for resection, but prediction of resulting seizure relief is difficult. This study describes implementation of lesion network mapping in TSC patients undergoing epilepsy surgery to associate resection zone with seizure outcomes.</p><p><strong>Methods: </strong>Thirty-nine consecutive patients with TSC who underwent invasive electroencephalography (EEG) and resection or ablation of the seizure onset zone were included. After preprocessing, each resection zone was delineated as the region of interest. Lesion network mapping was performed to determine the association between cortical networks connected to the resection zone and postoperative outcome using a multiple regression, iterative model that included demographic and other variables obtained from analysis of invasive EEG.</p><p><strong>Results: </strong>Of 39 patients, 20 (51%) had a good International League Against Epilepsy outcome (1-3). Resection regions connected to the default mode network and motor network were associated with better seizure outcome. Regions connected to the bilateral insula, visual associative regions, and putamen were associated with poor seizure outcome.</p><p><strong>Significance: </strong>This study provides methodology for lesion network mapping in TSC-related epilepsy. The results suggest a tendency for better outcomes when the resection zone is connected to certain networks, including the default mode and motor networks, that may support sustainment of seizures.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556206","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}
John R McLaren, Doyle Yuan, Sándor Beniczky, M Brandon Westover, Fábio A Nascimento
{"title":"The future of EEG education in the era of artificial intelligence.","authors":"John R McLaren, Doyle Yuan, Sándor Beniczky, M Brandon Westover, Fábio A Nascimento","doi":"10.1111/epi.18326","DOIUrl":"https://doi.org/10.1111/epi.18326","url":null,"abstract":"","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540632","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}