The model achieved high specificity in predicting long-term seizure recurrence, which supports its potential clinical utility for postoperative risk stratification and counseling rather than surgical exclusion and underscores the translational potential of network-level biomarkers to complement conventional predictors.
Abstract
Background
AND
Objectives
Patients with temporal lobe epilepsy (TLE) can achieve seizure freedom in the early period after surgery, yet up to half experience seizure recurrence in the following years (i.e., long-term). TLE is associated with disruption of highly connected brain regions (hubs), which may reduce the likelihood of long-term surgical success. We tested whether disruption of physiologic (normative) hubs predicts long-term seizure outcomes.
Methods
In a prospective, multimodal cohort of patients with drug-resistant TLE from 6 centers who underwent resective or laser ablative surgery and had more than 2 years of follow-up (mean = 5.4 years, SD = 3.2 years), we derived structural and functional connectomes from preoperative diffusion-weighted MRI and resting-state fMRI. Using a large multicenter healthy-control cohort, we identified normative connector hubs and quantified patient-specific disruption within these hubs using the graph-theory measure-participation coefficient. To classify seizure-free (positive class) and non-seizure-free (negative class) outcomes, we trained machine learning models using patient-specific disruption of the participation coefficient derived from structural and functional connectomes and their combination (multimodal approach). We evaluated model performance in an independent cohort. Models further incorporated clinical and demographic variables, as well as gray and white matter volumes.
Results
In our cohort of 175 patients, the multimodal approach outperformed a model based on clinical and demographic variables only and unimodal approaches, achieving high specificity (mean = 80.0%, SD = 9.9%) and moderate-to-high negative predictive value (mean = 63.9%, SD = 3.6%). Using 362 healthy controls to define normative connector hubs, Shapley Additive Explanation analyses identified disruption of the participation coefficient in the hippocampi and connector hubs of the dorsal attention network as predictive of long-term seizure recurrence, which includes areas not typically targeted in TLE surgery.
Discussion
Disruption of normative hub architecture provides biologically interpretable biomarkers of long-term seizure outcomes in TLE. Contrary to previous studies, the model achieved high specificity in predicting long-term seizure recurrence, which supports its potential clinical utility for postoperative risk stratification and counseling rather than surgical exclusion. By validating performance in an independent cohort under conservative evaluation, our study underscores the translational potential of network-level biomarkers to complement conventional predictors.
OBJECTIVE
Resective surgery achieves seizure freedom in approximately 60%-80% of patients with drug-resistant temporal lobe epilepsy (TLE), yet the extent to which seizure cessation permits recovery of disrupted functional brain networks remains unclear. Increasing evidence suggests that recurrent seizures alter subcortical-cortical communication involved in arousal and cognition, contributing to chronic interictal deficits, such as in executive function. Prior work demonstrates that the nucleus basalis of Meynert (NBM), the primary source of cortical cholinergic input to the cortex, exhibits aberrant functional connectivity in patients with TLE. We examined NBM connectivity in patients with TLE before and after surgery using patient-specific NBM segmentations. We sought to investigate whether seizure freedom is associated with recovery of NBM functional connectivity, consistent with previous observations of interictal network dysfunction reversal in other subcortical arousal structures.
METHODS
Resting-state functional magnetic resonance imaging was analyzed in 75 patients with TLE, including 34 patients postoperatively, and 106 controls. Patient-specific NBM segmentations were used to compute functional connectivity between the NBM and frontoparietal association cortex (FPAC) and across the whole brain. Subcortical arousal network community structure was assessed using community detection. Postoperative network changes were evaluated relative to seizure outcome.
RESULTS
Prior to surgery, patients exhibited reduced bilateral NBM connectivity to the FPAC and whole brain compared to controls, indicating widespread cholinergic network disruption beyond the ipsilateral hemisphere. Following surgery, NBM connectivity increased and no longer differed from controls. Seizure-free patients demonstrated greater postoperative increases in ipsilateral NBM-FPAC connectivity than non-seizure-free patients, which was not explained by time to postoperative scan or volumetric change. Subcortical arousal community structure remained altered postoperatively.
SIGNIFICANCE
Successful TLE surgery is associated with partial restoration of cholinergic arousal network connectivity, supporting the idea that seizure cessation enables recovery of brain networks disrupted by recurrent seizures. These findings position the NBM as a potential biomarker of network recovery following epilepsy surgery.
Addison C Cavender, Derek J. Doss, Ghassan S Makhoul et al.· Epilepsia· 0 citations
PURPOSE
Surgery is the treatment of choice for drug-resistant temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS). We assessed whether interictal epileptiform discharges (IEDs) on early postoperative EEG predicted seizure outcome after surgery.
METHODS
We retrospectively included consecutive patients aged >16 years who underwent surgery for drug-resistant TLE with pathologically confirmed HS at Pitié-Salpêtrière Hospital, Paris, between 2003 and 2023. Eligible patients had at least 1 year of follow-up and an early postoperative EEG performed within 1 month after surgery. IED frequency was classified as high frequency (≥1/min) or low frequency (<1/min). Favourable 1-year outcome was defined as ILAE class 1. Long-term worsening was defined as any increase in ILAE class after the 1-year visit.
RESULTS
Among 168 patients, 131 (78.0%) were ILAE class 1 at 1 year. EEG was performed a median of 7 days after surgery. IEDs were present in 81 patients (48.2%), including 48 with low-frequency and 33 with high-frequency IEDs. EEG features, including IED presence and frequency, did not differ between patients with and without ILAE class 1 outcome at 1 year. During longer follow-up, high-frequency IEDs were associated with worsening compared with no IEDs in the whole cohort (HR 2.25, 95% CI 1.01-4.98; p=0.046) and among patients seizure-free at 1 year (HR 2.59, 95% CI 1.10-6.11; p=0.03). Low-frequency IEDs were not associated with worsening.
CONCLUSION
High-frequency IEDs on early postoperative EEG may identify patients at increased risk of long-term deterioration after surgery for HS-related TLE. Prospective studies are needed before modifying routine follow-up strategies.
Kate Durbano, Q. Calonge, Valerio Frazzini et al.· Seizure· 0 citations
OBJECTIVE
Resective surgery is a significant therapeutic option for patients with drug-resistant mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). Numerous studies have demonstrated the efficacy of epilepsy surgery in the short to median term. However, studies on long-term outcomes are limited in number. The objective of this study was to document the long-term prognosis and associated factors of patients undergoing resective surgery for MTLE.
METHODS
A retrospective analysis was conducted on the data of patients with drug-resistant MTLE due to HS who underwent resective surgery between 2001 and 2013 at our epilepsy centre. The demographics and clinical variables of the patients were documented and analysed in order to ascertain their long-term prognosis. The postoperative outcomes were evaluated in accordance with the Engel classification system.
RESULTS
Of the 45 patients (mean age: 44.64 ± 8.96, range: 31-67), 31 (68.89%) were male. The age at onset of epilepsy, age at surgery, and the duration of epilepsy at the time of surgery ranged from 0.25 to 26 years (11.51 ± 7.07), from 12 to 47 years (26.82 ± 8.14), and from 2 to 33 years (16.03 ± 7.85), respectively. The patients were followed up for 10-23 years (17.73 ± 2.96). HS was identified in 23 (51.11%) of the patients on the right side and 22 (48.89%) on the left. The pre-operative EEG recordings revealed temporal discharges in 40 (88.89%) patients unilaterally. 22 patients (48.89%) underwent amygdalohippocampectomy with a temporal lobectomy (AH+ATL), while 23 patients (51.11%) underwent selective amygdalohippocampectomy (SAH). 28 (62.22%) patients were classified as Engel I. The patients did not have any statistically significant difference in terms of gender, age at epilepsy onset, age at surgery, duration of epilepsy at surgery, side of HS, and surgical procedure according to Engel classification (p = 0.64, 0.08, 0.60, 0.25, 0.67, 0.10, respectively). Executive and memory functions were improved after surgery at 5th year.
CONCLUSION
62% of the patients were classified as Engel I. Although previous studies have suggested that certain factors may influence prognosis, our findings did not yield any statistically significant results in this regard. It is crucial that patients undergo surgical evaluation without delay to achieve seizure control and improve cognitive function.
Günay Gül, Fulya Eren, Melek Kandemir Yilmaz et al.· Clinical neurology and neuro...· 0 citations
OBJECTIVE
Postoperative seizure recurrence in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) has been linked to alterations in structural network organization. However, existing studies have primarily focused on white matter pathways, while gray matter wiring attributes remain largely unknown. This study aimed to investigate whether alterations in gray matter wiring costs are associated with postoperative seizure recurrence in mTLE with HS.
METHODS
Forty-seven patients with unilateral mTLE who underwent surgery and 48 matched healthy controls were enrolled in the study. All patients had pathologically confirmed HS and were classified as seizure-free (SF; n = 27) or non-seizure-free (NSF; n = 20) with ≥ 2 years of follow-up. Based on preoperative 3D T1-weighted MRI, surface-based geodesic metrics were computed as proxies of cortical wiring costs. Global and local wiring costs were compared across groups, and a support vector machine (SVM) classifier was used to determine their individual-level classification value for postoperative seizure outcomes.
RESULTS
Global wiring costs decreased in the ipsilateral temporal cortex in patients with mTLE-HS, with a more significant and widespread reduction in the NSF group. Local wiring costs showed diffuse intra- and interregional abnormalities within the sensorimotor and default mode networks in patient groups, with more pronounced disturbances in the NSF group. These wiring abnormalities were not affected by hippocampal subfield atrophy, epilepsy duration, or antiseizure medications, and could train SVM models to distinguish NSF patients from SF patients (area under the receiver operating characteristic curve = 0.86).
CONCLUSIONS
Abnormalities of cortical wiring costs were observed in mTLE-HS, particularly in patients with postoperative seizure recurrence. These abnormalities may reflect increased long-range connectivity and short-range reorganization within gray matter, offering novel insights into the underlying pathophysiology of this illness and providing potential for outcome prediction.
Fei Zhu, Bo Tao, Yue Li et al.· Journal of Neurosurgery· 0 citations
OBJECTIVE
Depression is common in mesial temporal lobe epilepsy (mTLE), but its neuroanatomical basis-and overlap with major depressive disorder (MDD)-remains poorly defined. We investigated whether the cortical and subcortical alterations reported in MDD are also present in mTLE and leveraged the frequent occurrence of depression after epilepsy surgery to test whether such changes predate the onset of post-surgical depression.
METHODS
Eighty-nine mTLE patients scheduled for anterior temporal lobectomy were classified as never depressed (NoD, n = 42), depressed before surgical evaluation (PreD, n = 23), or developing de-novo depression after surgery (PostD, n = 22). Pre-operative 3 T MRI (1 mm T1, T2, FLAIR) was processed with FreeSurfer v6.3. Six frontotemporal-limbic regions showing the largest MDD effects in ENIGMA studies-orbitofrontal cortex, rostral anterior cingulate, insula, fusiform gyrus, hippocampus, posterior cingulate-were analyzed using a latent variable model.
RESULTS
Depression status significantly influenced combined morphology in both hemispheres (p < 0.05). Relative to NoD, both PreD and PostD groups showed reduced cortical thickness in the orbitofrontal cortex, fusiform gyrus, insula, and rostral anterior cingulate (Cohen's d = -0.04 to -0.14). Hippocampal volume and posterior cingulate thickness did not differ between groups.
SIGNIFICANCE
Four of the six frontotemporal regions showing the largest morphometric alterations in MDD also exhibit reduced cortical thickness in mTLE patients with past or future depression. This shared frontotemporal thinning pattern supports depression in mTLE as an expression of network pathology common to MDD, while residual regional differences may help explain the distinct phenotypic presentations of depression in these neuropsychiatric disorders. In PostD patients, these abnormalities were already present pre-operatively, consistent with a pre-existing vulnerability rather than a purely psychosocial reaction to surgery or epilepsy per se.
Philip Fink-Jensen, B. Ozenne, Ane G. Kloster et al.· Epileptic disorders· 0 citations
Background: Frontal lobe epilepsy (FLE) surgery often requires complex presurgical evaluations and intraoperative monitoring, which may not be readily available in resource-limited settings. We report our experience establishing FLE surgical services in Indonesia to develop strategies for a simple but reliable service in low- and middle-income countries. Methods: We included patients who underwent FLE surgery between 2003 and 2023 in Semarang, Indonesia. These patients underwent surgery with at least 12 months of follow-up. Univariate and multivariate Firth penalized logistic regression analyses were performed to identify factors associated with surgical outcome, stratified by follow-up duration. Kaplan–Meier survival analysis and log-rank tests were performed to assess time-to-seizure recurrence across subgroups. Results: 87 FLE surgeries were performed over a period of 20 years. Approximately 60% of the patients were pediatric. Most patients (63.2%) showed visible focal cortical dysplasia on imaging. At the ≥5-year follow-up group, 56.8% of the patients had Engel Class I disease, with 79.3% have favorable (productive) functional outcomes. Among factors associated with postoperative outcomes, the number of anti-seizure medicines ≥3 was a significant seizure-free predictor at ≥5-year follow-up (odds ratio 0.18, 95% confidence interval 0.04–0.87, p = 0.033). The median seizure-free survival was 10.0 years for the overall cohort. Conclusion: Despite several limitations, this research suggests that establishing routine FLE services in countries with limited resources is feasible. To maintain a simple but reliable service, a streamlined surgery pathway should be introduced, together with strengthening national capacity and adopting cost-efficient technology.
Zainal Muttaqin, J. Bunyamin, Novanda Rizky Radityatama et al.· Surgical neurology internati...· 0 citations
A new method for surgically removing training examples from a model reveals that as datasets grow, the link between what a model learns and what it produces dissolves.
