OBJECTIVE:This study aims to characterize the spatiotemporal dynamics of hippocampal atrophy and epileptogenicity in mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS), and to investigate their relationship with disease duration. METHODS:We conducted a cross-sectional study integrating structural magnetic resonance imagingandstereoelectroencephalographic (SEEG) data from 156 mTLE-HS patients. Hippocampal subfield volumetry was performed. In patients with SEEG (n = 67), interictal periodic and aperiodic components were quantified using the FOOOF ("fitting oscillations and one over f") algorithm, and ictal epileptogenicity index (EI) was calculated. Correlation analysis, along with linear statistical model and restricted cubic splines (RCS), were employed to examine the relationships between disease duration, hippocampal volumetry, and electrophysiological metrics, focusing on anterior versus posterior hippocampus. RESULTS:Hippocampal volume showed a negative correlation with disease duration in all subfields (head: r = -.185, p = .021; body: r = -.237, p = .003; tail: r = -.253, p = .001). RCS analysis indicated a nonlinear association, where the slope linking disease duration to volume loss appeared steeper (suggestive of accelerated atrophy) beyond approximately 15 years (p < .001). Electrophysiologically, the aperiodic exponent decreased significantly in both anterior (r = -.271, p = .012) and posterior hippocampus (r = -.323, p = .009). A significant positive correlation was found between disease duration and the EI specifically in the posterior hippocampus (r = .550, p < .001), and the group with high EI (≥.3) had a significantly longer disease duration compared to the low EI group (16.0 ± 8.0 vs. 11.3 ± 7.5 years, p = .015). SIGNIFICANCE:mTLE-HS is characterized by a dual pattern of association with disease duration: a nonlinear (potentially accelerating) association with structural atrophy beyond ~15 years and an association between longer duration and higher epileptogenicity in posterior hippocampal regions. This spatiotemporal pattern provides a mechanistic basis for considering individualized extension of surgical resection in chronic cases, a strategy requiring prospective evaluation.
Background The globus pallidus (GP) is a critical basal ganglia nucleus for motor and cognitive control. However, traditional single-modality parcellations provide an incomplete understanding of its internal organization, thereby increasing the risk of imprecision and side effects during therapeutic targeting of its subregions.Methods In this study, we developed a multi-modal approach that combines structural and functional connectivity, termed hybrid pallidum parcellation (HPP), to parcellate the GP into anterior (aGP), middle (mGP), and posterior (pGP) subregions. This approach was rigorously evaluated for reproducibility and homogeneity in healthy individuals and behavioral prediction accuracy in healthy individuals and patients with Parkinson's disease (PD). Connectivity and behavioral prediction analyses were further used to explore the structural and functional differences in the GP subregions.Results Compared with unimodal (structural or functional connectivity-based) and two public parcellations, HPP demonstrated superior reproducibility and homogeneity. In addition, the HPP-based subregions revealed a posterior-to-anterior structural and functional connectivity gradient in GP, reflecting a transition from primary to higher-order networks. Specifically, the pGP dominated in sensorimotor function prediction and the aGP in emotional processing, while the mGP exhibited a more flexible pattern in cognition and higher-order motor control. Furthermore, the HPP parcellation demonstrated generalizability and superiority in better predicting behavioral measures than other parcellations in both healthy individuals and patients with PD.Conclusions Overall, HPP provides new insights into the GP's hierarchical functional organization and its subregional roles in PD motor and non-motor symptoms, offering potential to improve patient stratification for PD and related disorders.
INTRODUCTION:Hypothalamic hamartoma (HH) causes drug-resistant epilepsy, with gelastic seizures (GS) progressing to non-gelastic seizures (nGS). MRI-guided laser interstitial thermal therapy (MRgLITT) is first-line treatment, but robust prognostic models with external validation are lacking. OBJECTIVES:To evaluate MRgLITT outcomes for HH-related epilepsy and develop externally validated predictive nomograms for GS and nGS recurrence. METHODS:This retrospective study included 169 patients (training: n = 121; validation: n = 48). Multivariate Cox regression identified prognostic factors. Nomograms were developed in the training cohort and externally validated in the independent cohort. RESULTS:Seizure freedom rates were 76.4% (GS) and 81.8% (nGS). GS recurrence correlated with larger HH volume (HR = 4.32), incomplete ablation (HR = 0.268/0.212), and cognitive impairment (HR = 2.51). nGS recurrence associated with bilateral PET hypometabolism (HR = 60.53), nGS duration (HR = 1.14), automatisms (HR = 7.90), and sGTCS (HR = 3.84). External validation confirmed GS and nGS nomogram generalizabilities (C-index = 0.731, 0.844). Complications included transient hyperphagia (26.7%), persistent obesity (12%), and permanent hypothyroidism (1.8%). Caregiver-reported cognitive outcomes were exploratory. CONCLUSION:MRgLITT is safe and effective for HH-related epilepsy, with lesion-centric (GS) versus network-level (nGS) prognostic pathways. Externally validated nomograms offer actionable tools for clinical decision-making.
OBJECTIVE:The Five Sign is a previously underrecognized ictal hand posture characterized by full extension and spreading of the fingers. We aimed to determine its localizing value and underlying network basis in patients with drug-resistant focal epilepsy. METHODS:We retrospectively analyzed 510 patients with drug-resistant focal epilepsy, including 34 patients exhibiting Five Sign-positive seizures. The association between Five Sign and epileptogenic zone (EZ) localization was quantified using sensitivity, specificity, likelihood ratios, and odds ratios. Hierarchical cluster analysis was performed to characterize co-occurring semiological features, and the relationship between the temporal evolution of the Five Sign and EZ distribution was examined. Multimodal evaluation included interictal Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) group analysis and stereoelectroencephalography (SEEG)-based epileptogenicity mapping. RESULTS:Five Sign demonstrated a strong preferential association with insulo-opercular (IO) epilepsy, showing the highest prevalence in IO cases (23.7%) and the highest positive predictive value for IO localization (64.7%). The presence of Five Sign significantly increased the likelihood of IO localization (p < .001). Hierarchical cluster analysis revealed a distinct temporal organization of Five Sign seizures, with aura symptoms typically preceding the sign, orofacial, tonic, and autonomic manifestations co-occurring with it, and complex motor behaviors emerging afterward. Temporal phase analysis showed that early-phase Five Sign was strongly associated with IO EZs, whereas later-phase Five Sign was more frequently associated with extra-insular EZs (p < .01). Group-level 18F-FDG-PET analysis revealed hypometabolism centered in the anterior-mid-dorsal insula with extension to striatum and medial pulvinar. Epileptogenicity mapping demonstrated convergent seizure-onset involvement within the IO region and premotor cortex, supporting a distributed motor-related network. SIGNIFICANCE:The Five Sign is a highly specific semiological marker of IO epilepsy and reflects engagement of a distinct cortico-subcortical network centered on the posterior IO region. Recognition of the Five Sign may refine presurgical localization hypotheses and guide invasive monitoring strategies.
OBJECTIVE:To investigate the epileptogenicity of the hippocampus in patients with PNH using functional connectivity (FC). METHODS:PNH patients with intracranial electrodes implanted in both heterotopic nodules (HNs) and the hippocampus, and who achieved seizure freedom postoperatively, were retrospectively enrolled.Hippocampal epileptogenicity was determined based on the surgical outcomes after hippocampus coagulation or not. The epileptogenicity index (EI) was calculated for both HNs and hippocampal channels. Interchannel FC during the interictal state (cortico-cortical evoked potential, CCEP) and ictal state (h2 coefficient) was calculated and compared. A logistic regression model was developed using significant ictal FC biomarkers to predict hippocampal epileptogenicity. RESULTS:A total of 8 patients were enrolled, with 6 undergoing CCEP. No significant EI differ-ences were observed between HNs and hippocampal channels. In patients with hippocampal epileptogenicity, connectivity from the hippocampus to HNs was stronger during both interictal and ictal states compared to the reverse. This trend was not seen in patients without hippocampal epileptogenicity. A logistic regression model incorporating ictal FC differences distinguished hippocampal epileptogenicity with an ac-curacy of 0.79 and an AUC of 0.81. CONCLUSION:A classification model based on ictal FC effectively differentiates hippocampal epileptogenicity in PNH patients and may serve as a valuable tool for guiding surgical decisions.
AIMS:To summarize the anatomo-electro-clinical characteristics of parietal lobe epilepsy (PLE) subgroups using unsupervised cluster analysis. METHODS:This retrospective cohort study included patients with drug-resistant PLE with seizure freedom after surgery and evaluated scalp video-electroencephalography (EEG) recordings from three epilepsy centers. Hierarchical cluster analysis associated interictal/ictal patterns and initial ictal semiology with anatomical subgroups. RESULTS:We analyzed 79 interictal EEG, 141 ictal EEG, and 141 semiological patterns in 47 patients. Cluster analysis associated interictal and ictal discharges from lateral superior parietal lobule epilepsy with centroparietal region distributions on scalp EEG, whereas discharges from other subgroups involved broader regions. Cluster heatmaps of the initial ictal semiology showed: Chapeau de gendarme, affective phenomena, and forced eye deviation in intraparietal sulcus; contralateral limb tonic/clonic or akinetic, affective phenomena, and visual illusions in SPL-lateral; Chapeau de gendarme, behavioral arrest, and vestibular in parieto-occipital sulcus; behavioral arrest in angular gyrus; distal gestural automatisms and cephalic sensations in posterior cingulate; body-perception illusion and contralateral versive in supramarginal gyrus; contralateral facial tonic/clonic in parietal operculum. CONCLUSION:PLE subgroups exhibited distinct scalp EEG features and ictal semiology, reflecting unique propagation networks and highlighting the importance of detailed video-EEG for identifying the epileptogenic zone and guiding intracranial electrode placement.
OBJECTIVE:Magnetic resonance imaging (MRI)-negative type II focal cortical dysplasia (FCD) is challenging to localize and treat. Emerging evidence suggests that the sulcal bottom is the critical site of epileptogenicity. This study investigated whether MRI-negative type II FCD represents a subtle form of bottom-of-sulcus dysplasia (BOSD) and evaluated the safety and efficacy of sulcus bottom-targeted minimally invasive therapy. METHODS:Fifty-eight patients (mean age = 18.0 ± 10.0 years, range = 4-41) with drug-resistant epilepsy and MRI-negative scans were clinically diagnosed with FCD type II and included in the study. Of these, 27 met inclusion criteria for stereoelectroencephalographic (SEEG) analysis to compare interictal spike counts, high-frequency oscillation (HFO) counts, and epileptogenicity index (EI) values between sulcal bottom and nonbottom contacts. Histopathological analysis (n = 15) evaluated the spatial distribution of dysmorphic neurons (DNs) and balloon cells (BCs) using nonphosphorylated neurofilament (SMI32), phospho-S6 ribosomal protein (pS6), and Nestin immunoreactivity. An additional 19 patients received magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) targeting the sulcal bottom, with seizure outcomes and ablation coverage systematically evaluated. RESULTS:SEEG demonstrated significantly higher spike counts, HFOs, and EI values at sulcal bottom contacts than at nonbottom regions (all p < .0001), showing strong negative correlations with distance from the sulcal bottom (R = -.85 to -.68). Histopathology revealed a consistent spatial gradient, with DN density and diaminobenzidine intensity significantly enriched at the sulcal bottom across SMI32 and pS6 labeling (all p < .05). BCs, when present, were confined to the sulcal bottom. In the MRgLITT cohort, sulcus bottom-targeted ablation achieved seizure freedom (Engel IA) in 73.7% of patients, with a mean ablation coverage of 28.3% and no permanent neurological deficits. SIGNIFICANCE:MRI-negative type II FCD exhibits sulcus bottom-centered epileptogenicity, consistent with a subtle form of BOSD. These findings support sulcus bottom-targeted MRgLITT as a safe and effective minimally invasive therapy and provide a rationale for sulcus bottom-centered surgical planning in MRI-negative FCD II.
OBJECTIVE:The objective of this study was to propose fiber insertion strategies for MRI-guided laser interstitial thermal therapy (MRgLITT) tailored to anatomical subtypes of insulo-opercular focal cortical dysplasia (FCD), as previously defined, and to evaluate the safety and efficacy of these strategies. METHODS:The authors retrospectively reviewed patients with insulo-opercular FCD who underwent LITT at Beijing Tiantan Hospital between January 2020 and November 2024. Lesions were classified as insular, peri-insular, or opercular subtypes on the basis of anatomical criteria previously established by their group, and individualized fiber trajectories were planned accordingly. Seizure outcomes were assessed using the Engel classification. Additionally, the authors evaluated the effects of laser-induced thermal injury on adjacent motor fiber tracts and arterial structures. RESULTS:Sixteen patients (6 females) were included: 5 insular, 4 peri-insular, and 7 opercular subtypes. The median age at the time of LITT was 16 years, and 75% (12/16) of the patients underwent stereoelectroencephalography (SEEG). At a median follow-up of 2 years, 75% (95% CI 53.8%-96.2%) achieved Engel class IA outcomes. Transient neurological deficits occurred in 6 patients (37.5%, 95% CI 14.0%-61.0%), with no permanent morbidity. In insular cases, a thermal-blocking effect involving the external capsule or putamen was observed, while the posterior limb of the internal capsule remained intact. Postoperative imaging confirmed preserved perfusion of the adjacent M2-M3 segments of the middle cerebral artery (MCA), with no ischemic lesions detected on follow-up MRI. CONCLUSIONS:Fiber insertion strategies for LITT based on anatomical subtypes of insulo-opercular FCD are both safe and effective. This approach enables precise ablation of epileptogenic tissue while minimizing the risk of injury to motor fiber tracts and adjacent vasculature.
ABSTRACT Background Epilepsy is a common neurological disorder imposing significant global health burdens. A comprehensive understanding of its temporal and spatial trends is critical for informing policies and guiding interventions. Methods This study assessed the burden of epilepsy from 1990 to 2021 worldwide, in Asia, and in China, and projected trends to 2050. We used data from the Global Burden of Disease 2021 study to evaluate the incidence, prevalence, mortality, and disability‐adjusted life years (DALYs) related to epilepsy. Joinpoint regression, age‐period‐cohort analysis, and autoregressive integrated moving average forecasting were used to examine temporal trends and project future patterns. We also assessed the influence of socioeconomic development, health service coverage, and risk factors on the epilepsy burden, focusing on regional disparities. Results From 1990 to 2021, the incidence and prevalence of epilepsy showed a significant upward trend, while mortality and DALY rates showed a significant downward trend. China exhibited sharper reductions in mortality (average annual percent change = −2.64) and DALY rates (average annual percent change = −1.79). Inequalities persist, with low socio‐demographic index countries showing a disproportionately higher epilepsy burden. In China, improved universal health coverage and socioeconomic development are correlated with a decreasing burden. Alcohol use remains a key modifiable risk factor, particularly among men. Projections suggest a continued shift in the epilepsy burden toward older adults, with those aged ≥ 70 years contributing the largest share of future cases. Conclusions Epilepsy remains a major global health concern with a substantial and uneven disease burden. Comprehensive burden analyses are essential for guiding public health policy, optimizing resource allocation, and developing targeted prevention and intervention strategies.
Background Epilepsy is a common neurological disorder imposing significant global health burdens. A comprehensive understanding of its temporal and spatial trends is critical for informing policies and guiding interventions. Methods This study assessed the burden of epilepsy from 1990 to 2021 worldwide, in Asia, and in China, and projected trends to 2050. We used data from the Global Burden of Disease 2021 study to evaluate the incidence, prevalence, mortality, and disabilityu2010adjusted life years (DALYs) related to epilepsy. Joinpoint regression, ageu2010periodu2010cohort analysis, and autoregressive integrated moving average forecasting were used to examine temporal trends and project future patterns. We also assessed the influence of socioeconomic development, health service coverage, and risk factors on the epilepsy burden, focusing on regional disparities. Results From 1990 to 2021, the incidence and prevalence of epilepsy showed a significant upward trend, while mortality and DALY rates showed a significant downward trend. China exhibited sharper reductions in mortality (average annual percent change = u22122.64) and DALY rates (average annual percent change = u22121.79). Inequalities persist, with low sociou2010demographic index countries showing a disproportionately higher epilepsy burden. In China, improved universal health coverage and socioeconomic development are correlated with a decreasing burden. Alcohol use remains a key modifiable risk factor, particularly among men. Projections suggest a continued shift in the epilepsy burden toward older adults, with those aged u2265 70 years contributing the largest share of future cases. Conclusions Epilepsy remains a major global health concern with a substantial and uneven disease burden. Comprehensive burden analyses are essential for guiding public health policy, optimizing resource allocation, and developing targeted prevention and intervention strategies.
The brainstem is a highly conserved integrative hub that is essential for arousal, emotion, and motor control, which are functions profoundly affected in Parkinson’s disease (PD). However, low signal-to-noise ratios in neuroimaging of subcortical nuclei hinder the construction of brainstem parcellations that integrate complementary functional and structural information, limiting our understanding of circuit-specific pathology. Here, we developed the Multimodal Consensus Brainstem Parcellation (MCBP), a fine-grained atlas that integrates high-resolution naturalistic 7 T functional MRI and diffusion MRI acquired in the Human Connectome Project (N = 160). The MCBP exhibits high reproducibility, symmetry, and homogeneity. Using this parcellation, we find a pronounced structure–function dissociation within the brainstem. Furthermore, MCBP reveals a hierarchical brainstem organization aligned with the unimodal-to-transmodal axis, distinguishing motor execution from visually guided motor preparation that closely resembles the Somato-Cognitive Action Network (SCAN). Crucially, in an independent PD cohort, MCBP-derived connectivity improved disease classification and symptom-severity prediction compared with existing brainstem atlases, supporting its sensitivity to both categorical disease status and dimensional clinical variation. Feature decoding revealed a dual-system pattern of PD-related alterations across sensorimotor and cognitive–affective networks. Notably, it identified a specific brainstem–limbic circuit linked to emotional heterogeneity, providing circuit-level insights for distinguishing anxiety- and depression-related neuropsychiatric PD subtypes independent of motor severity. Beyond distinguishing and grading disease, the MCBP-derived connectivity measure also outperformed those derived from existing atlases in predicting multidimensional behavioral traits in a large healthy participant cohort (N = 976). Together, MCBP offers a fine-grained, biologically grounded brainstem parcellation and a framework for probing circuit-specific changes in neurodegenerative disorders.
Objective To compare the consistency between immunohistochemical (IHC) staining and next-generation sequencing (NGS) in detecting BRAF alterations in ganglioglioma, to provide a reference for clinical selection of diagnostic approaches. Methods Ninety patients diagnosed with ganglioglioma who underwent surgical resection at Beijing Tiantan Hospital, Capital Medical University between October 2023 and May 2025 were included in this study. All patients were tested for BRAF mutation status via both IHC staining and NGS. Kappa test was performed to evaluate the consistency of the two detection methods. Results Among the 90 patients, IHC staining identified 43 BRAF V600E positive cases (47.78%) and 47 negative cases (52.22%). For NGS, 42 cases (46.67%) harbored isolated BRAF V600E mutation, 12 cases (13.33%) carried multiple non-BRAF V600E mutations, 7 cases (7.78%) presented BRAF gene fusion, and 29 cases (32.22%) showed no detectable BRAF alteration. IHC staining exhibited good consistency with NGS for BRAF V600E detection (κ=0.888, P=0.000), with a sensitivity of 95.24% and a specificity of 93.75%. Conclusions Combined application of IHC staining and NGS improves the diagnostic accuracy for ganglioglioma. IHC staining is suitable for rapid initial screening, while NGS is recommended for complex cases and patient selection for precision targeted therapy.
Memory impairment is a major source of disability in temporal lobe epilepsy (TLE), yet how focal pathology relates to distributed circuit alterations underlying memory dysfunction remains unclear. We performed an integrative multiscale circuit-level analysis in 250 patients with TLE to characterize memory dysfunction across focal structural damage, white matter disconnection, and distributed metabolic network organization, and to estimate individualized deviations in relation to memory performance. Auditory memory impairment was associated with damage to medial temporal structures centered on the hippocampus and parahippocampal cortex, as well as disruption of a key hippocampo-cingulate white matter pathway. Memory deficits were linked to abnormal metabolic organization within a limbic-centered network, with greater metabolic deviation associated with more severe global memory impairment. Spatial correspondence analyses showed that memory-related hypometabolism aligns with serotonergic, GABAergic, and synaptic receptor distributions, with additional associations observed for inhibitory interneuron and mitochondrial signatures. Together, these findings delineate a multiscale circuit architecture underlying memory dysfunction. This framework provides a biologically grounded basis for understanding cognitive vulnerability and may inform individualized risk assessment in epilepsy surgery.
Parkinson's disease (PD) is associated with widespread structural and functional brain abnormalities, yet whether morphology-constrained functional organization is disrupted in a frequency-specific manner remains unclear. To address this gap, we derived frequency-resolved features of morphology-constrained functional organization in PD by integrating morphological networks from T1-weighted magnetic resonance imaging with resting-state functional signals in the graph spectral domain. Low- and high-frequency eigenmodes and the relative decoupling index (RDI) were used to identify abnormal patterns of morphology-function coupling in PD. We further evaluated the cognitive relevance, biological significance, and disease-related discriminative information of these features using meta-analytic decoding, behavioral prediction, gene expression analysis, and exploratory patient-control classification. Our results revealed that low-frequency eigenmode abnormalities in PD were predominantly localized to the default mode network, dorsal and ventral attention networks, limbic network, and subcortical network. In contrast, high-frequency eigenmode and RDI abnormalities were primarily observed in the limbic network and subcortical network. In addition, low-frequency alterations were linked to social cognition and anxiety functions, while high-frequency changes were associated with motor and memory functions. Spatial patterns of abnormal regions showed preliminary spatial correspondence with gene expression profiles enriched for ABC transporter activity and fatty acid metabolism. Classification analyses indicated that frequency-resolved features contained disease-related discriminative information, with selected features preferentially involving motor, attentional and limbic systems. Together, these findings indicate that morphology-function coupling is disrupted in PD in a frequency-resolved manner and suggest that frequency-resolved morphology-constrained functional features may provide candidate MRI-derived features for further disease characterization.
Introduction Drug-resistant mesial temporal lobe epilepsy (mTLE) is a common and disabling focal epilepsy syndrome for which surgery offers the best chance of seizure freedom. Traditional open surgery (eg, anterior temporal lobectomy or selective amygdalohippocampectomy) is effective but may be associated with perioperative morbidity and neurocognitive sequelae. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative with encouraging observational outcomes but high-quality comparative evidence versus open surgery remains limited. The MINE trial is designed to compare MRgLITT with open surgery in patients with mTLE.Methods and analysis MINE is a prospective, randomised, open-label, blinded-endpoint trial. Eligible adults with drug-resistant TLE who complete a comprehensive presurgical evaluation and are deemed suitable for surgical treatment will be enrolled at participating centres. Participants will be randomised 1:1 (block randomisation) to receive MRgLITT or open surgery. Because of the nature of surgical interventions, participants and treating teams will not be blinded; however, outcome assessors and statistical analysts will remain blinded to treatment allocation. The primary outcome is seizure-free rate at 12 months after surgery, defined as International League Against Epilepsy (ILAE) Class 1. Secondary outcomes include: (1) broader seizure outcomes (ILAE class distribution, seizure frequency and seizure severity) assessed at 6 and 12 months; (2) cognitive and memory function assessed at 6 and 12 months; (3) postoperative safety outcomes collected from surgery through discharge and at follow-up visits at 6 and 12 months, and (4) healthcare utilisation and health-economic outcomes: length of hospital stay measured during hospitalisation; and reoperation, antiseizure medication reduction and quality of life assessed at 6 and 12 months. Safety outcomes include perioperative adverse events (AEs) and serious AEs (SAEs), collected from surgery through discharge and at follow-up visits at 6 and 12 months. This trial is powered as a non-inferiority study on the primary outcome, which based on prior data reporting 12-month seizure-free rates of 76.9% for MRgLITT and 76.0% for open surgery, the assumed absolute difference is 0.009. The non-inferiority margin was set at -0.23, informed by the minimum acceptable benefit threshold reported in patient preference research.Ethics and dissemination The study has received ethics approval from the Institutional Review Board of Beijing Tiantan Hospital (KY2025-073-01). Written informed consent will be obtained from all participants prior to enrolment. Results will be disseminated through peer-reviewed publications and academic presentations.Trial registration number NCT06720922.
OBJECTIVE:This study aims to determine whether the anatomically heterogeneous lesions that cause hyperkinetic seizures (HKS) are connected to a common functional network. METHODS:We identified patients from the Beijing Tiantan-Fengtai Epilepsy Center with HKs as the primary ictal semiology. These included patients had focal seizure-onset zone, here referred to as a "lesion." The network of brain regions functionally connected to each lesion was identified using whole-brain functional connectivity from a functional magnetic resonance imaging (fMRI) dataset of healthy participants (n = 1000). Network maps were overlapped to identify regions functionally connected to most lesions. Specificity was evaluated using a case-control design. Therapeutic relevance was assessed using a cohort that underwent deep brain stimulation to the anterior nucleus of the thalamus to improve seizure control. RESULTS:Lesion locations for patients with HKS (n = 50) and patients without HKS (n = 47 for automatisms; n = 53 for elementary motor signs) were included. Based on the lesion brain network, the most sensitive and specific region with HKS was the anterior cingulate cortex (ACC) (>90% overlap). Reversed connectivity patterns between the ACC and the whole brain encompassed most lesion locations that caused HKS (47/50, 94%). In addition, the functional connectivity between ACC and deep brain stimulation sites was associated with improved seizure control (r = .49, p < .01) in 27 patients with drug-resistant epilepsy. SIGNIFICANCE:These findings indicated that HKS might be a symptom of brain network disruption that resulted from lesions in various brain regions commonly connected to ACC, emphasizing the ACC as a potential target for therapeutic intervention in HKS.
This study aimed to explore the predictive value of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) metabolic activity in determining postoperative motor function outcomes in patients with Rolandic focal cortical dysplasia (FCD). We conducted a retrospective analysis of 62 patients with FCD who underwent resective surgery in the Rolandic area. Of these, 15 patients underwent task-based functional magnetic resonance imaging (fMRI). Motor functional reorganization and its relationship with PET metabolism were analyzed. Patients were classified into deficit and non-deficit groups according to their postoperative motor function status. PET metabolism in the resected motor cortex was compared between the two groups, and its correlation with postoperative muscle strength was further evaluated in the deficit group. Among the 15 patients who underwent fMRI evaluation, the extent of motor reorganization was negatively correlated with PET metabolism (P = 0.0006). PET analysis revealed significantly higher PET metabolic T-values in the resected Rolandic cortex of the motor deficit group compared to the non-deficit group (P = 0.0004). Furthermore, within the deficit group, PET metabolic T-values were negatively correlated with postoperative muscle strength (P = 0.017). The prediction model for postoperative motor function, demonstrated strong performance in cross-validation, with an area under the curve (AUC) of 0.82, a sensitivity of 83
OBJECTIVE:The pulvinar is increasingly recognized as a promising target for neuromodulation in drug-resistant epilepsy (DRE). Despite growing interest, empirical evidence substantiating the efficacy and mechanism of its deep brain stimulation (DBS) in patients with epilepsy remains scarce. This study endeavors to address this knowledge gap by investigating the electrophysiological properties of pulvinar. METHODS:We enrolled 35 patients with DRE who underwent stereoelectroencephalography with electrodes extended to the pulvinar and analyzed the pulvinar's involvement in seizures originating from different brain lobes. Repeated single electrical pulse stimulation (RSEPS) was employed to map the connectivity of the pulvinar. We also evaluated the effect of pulvinar DBS on interictal epileptic discharges within the epileptogenic zone. RESULTS:We observed that greater involvement of the pulvinar exists in temporal lobe epilepsy, with the medial pulvinar (PuM) showing stronger engagement. Findings with RSEPS highlighted significant connections from the PuM to parietal, occipital, and temporal regions, as well as robust connections from the mesial temporal lobes to PuM. Lastly, we found high-frequency stimulation (140-150 Hz) of PuM significantly reduced interictal epileptic discharges. SIGNIFICANCE:Our study supports emerging evidence for pulvinar involvement in seizure propagation. The data with RSEPS also map PuM causal connectivity in the human brain. Although the clinical utility of pulvinar neuromodulation in patients with DRE remains to be determined by prospective clinical trials, our findings provide a convincing link between PuM neuromodulation and the reduction of epileptic activity.
INTRODUCTION:Temporal lobe epilepsy (TLE), the most common type of drug-resistant epilepsy (DRE), has a postoperative seizure-free rate of ~70%. Furthermore, precisely localizing the epileptogenic zone and determining the surgical resection area have been established as the key factors influencing surgical outcomes. Herein, we innovatively coupled the surgical resection area with characteristics of effective connectivity via intracranial electroencephalography (iEEG) to predict patients' surgical prognosis. METHODS:This study involved 56 patients who underwent TLE surgery and were followed up for over 1 year. All patients underwent stereo-electroencephalography (SEEG) electrode implantation and single-pulse electrical stimulation (SPES) tests. After comparing patients' RMS value of N1/N2 (Z-score standardized) from cortico-cortical evoked potentials (CCEP) with different surgical outcomes, an interpretable machine learning (ML) model based on support vector machine (SVM) for predicting patients' surgical prognosis was constructed. RESULTS:Patients with various surgical outcomes exhibited differences in effective connectivity. Furthermore, compared to the seizure-free group (Engel I), patients in the nonseizure-free group (Engel II-IV) exhibited stronger connectivity between the seizure onset zone (SOZ) and regions outside the surgical resection area. The nonseizure-free group also exhibited stronger connectivity between the surgical resection area and regions outside the resection area. Our prediction model demonstrated high-accuracy performance, with accuracy and area under the curve (AUC) values of 0.800 and 0.893, respectively. CONCLUSIONS:This study confirmed the potential value of integrating the surgical resection area and effective connectivity characteristics in predicting patients' surgical outcomes; offering a novel approach that could be leveraged to precisely determine the surgical resection area and improve TLE patients' surgical prognosis.