Summary Background Surgery is increasingly used as treatment for refractory focal epilepsy; however, few rigorous reports of long-term outcome exist. We did this study to identify long-term outcome ...of epilepsy surgery in adults by establishing patterns of seizure remission and relapse after surgery. Methods We report long-term outcome of surgery for epilepsy in 615 adults (497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and seven palliative procedures corpus callosotomy, subpial transection), with prospective annual follow-up for a median of 8 years (range 1–19). We used Kaplan-Meier survival analysis to estimate time to first seizure, and investigated patterns of seizure outcome. Findings We used survival methods to estimate that 52% (95% CI 48–56) of patients remained seizure free (apart from simple partial seizures SPS) at 5 years after surgery, and 47% (42–51) at 10 years. Patients who had extratemporal resections were more likely to have seizure recurrence than were those who had anterior temporal resections (hazard ratio HR 2·0, 1·1–3·6; p=0·02); whereas for those having lesionectomies, no difference from anterior lobe resection was recorded. Those with SPS in the first 2 years after temporal lobe surgery had a greater chance of subsequent seizures with impaired awareness than did those with no SPS (2·4, 1·5–3·9). Relapse was less likely the longer a person was seizure free and, conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. 104 of 365 (28%) seizure-free individuals had discontinued drugs at latest follow-up. Interpretation Neurosurgical treatment is appealing for selected people with refractory focal epilepsy. Our data provide realistic expectations and indicate the scope for further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy. Funding UK Department of Health National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme, Epilepsy Society, Dr Marvin Weil Epilepsy Research Fund.
Quantification of brain morphology has become an important cornerstone in understanding brain structure. Measures of cortical morphology such as thickness and surface area are frequently used to ...compare groups of subjects or characterise longitudinal changes. However, such measures are often treated as independent from each other. A recently described scaling law, derived from a statistical physics model of cortical folding, demonstrates that there is a tight covariance between three commonly used cortical morphology measures: cortical thickness, total surface area, and exposed surface area. We show that assuming the independence of cortical morphology measures can hide features and potentially lead to misinterpretations. Using the scaling law, we account for the covariance between cortical morphology measures and derive novel independent measures of cortical morphology. By applying these new measures, we show that new information can be gained; in our example we show that distinct morphological alterations underlie healthy ageing compared to temporal lobe epilepsy, even on the coarse level of a whole hemisphere. We thus provide a conceptual framework for characterising cortical morphology in a statistically valid and interpretable manner, based on theoretical reasoning about the shape of the cortex.
We assessed preoperative structural brain networks and clinical characteristics of patients with drug-resistant temporal lobe epilepsy (TLE) to identify correlates of postsurgical seizure ...recurrences.
We examined data from 51 patients with TLE who underwent anterior temporal lobe resection (ATLR) and 29 healthy controls. For each patient, using the preoperative structural, diffusion, and postoperative structural MRI, we generated 2 networks: presurgery network and surgically spared network. Standardizing these networks with respect to controls, we determined the number of abnormal nodes before surgery and expected to be spared by surgery. We incorporated these 2 abnormality measures and 13 commonly acquired clinical data from each patient into a robust machine learning framework to estimate patient-specific chances of seizures persisting after surgery.
Patients with more abnormal nodes had a lower chance of complete seizure freedom at 1 year and, even if seizure-free at 1 year, were more likely to relapse within 5 years. The number of abnormal nodes was greater and their locations more widespread in the surgically spared networks of patients with poor outcome than in patients with good outcome. We achieved an area under the curve of 0.84 ± 0.06 and specificity of 0.89 ± 0.09 in predicting unsuccessful seizure outcomes (International League Against Epilepsy ILAE 3-5) as opposed to complete seizure freedom (ILAE 1) at 1 year. Moreover, the model-predicted likelihood of seizure relapse was significantly correlated with the grade of surgical outcome at year 1 and associated with relapses up to 5 years after surgery.
Node abnormality offers a personalized, noninvasive marker that can be combined with clinical data to better estimate the chances of seizure freedom at 1 year and subsequent relapse up to 5 years after ATLR.
This study provides Class II evidence that node abnormality predicts postsurgical seizure recurrence.
Objective
Cognitive problems, especially disturbances in episodic memory, and hippocampal sclerosis are common in temporal lobe epilepsy (TLE), but little is known about the relationship of ...hippocampal morphology with memory. We aimed to relate hippocampal surface‐shape patterns to verbal and visual learning.
Methods
We analyzed hippocampal surface shapes on high‐resolution magnetic resonance images and the Adult Memory and Information Processing Battery in 145 unilateral refractory TLE patients undergoing epilepsy surgery, a validation set of 55 unilateral refractory TLE patients, and 39 age‐ and sex‐matched healthy volunteers.
Results
Both left TLE (LTLE) and right TLE (RTLE) patients had lower verbal (LTLE 44 ± 11; RTLE 45 ± 10) and visual learning (LTLE 34 ± 8, RTLE 30 ± 8) scores than healthy controls (verbal 58 ± 8, visual 39 ± 6; p < 0.001). Verbal learning was more impaired the greater the atrophy of the left superolateral hippocampal head. In contrast, visual memory was worse with greater bilateral inferomedial hippocampal atrophy. Postsurgical verbal memory decline was more common in LTLE than in RTLE (reliable change index in LTLE 27% vs RTLE 7%, p = 0.006), whereas there were no differences in postsurgical visual memory decline between those groups. Preoperative atrophy of the left hippocampal tail predicted postsurgical verbal memory decline.
Interpretation
Memory deficits in TLE are associated with specific morphological alterations of the hippocampus, which could help stratify TLE patients into those at high versus low risk of presurgical or postsurgical memory deficits. This knowledge could improve planning and prognosis of selective epilepsy surgery and neuropsychological counseling in TLE. ANN NEUROL 2020 ANN NEUROL 2020;88:170–182
The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography ...(iEEG) performed in difficult-to-localize drug-resistant focal epilepsy.
The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit).
Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio OR = 1.4, 95% confidence interval CI 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE).
In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.
Objective
To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal ...epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans.
Methods
We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI‐visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG.
Results
Seizure‐onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG.
Significance
Computational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co‐located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery.
Temporal lobe surgical resection brings seizure remission in up to 80% of patients, with long-term complete seizure freedom in 41%. However, it is unclear how surgery impacts on the structural white ...matter network, and how the network changes relate to seizure outcome.
We used white matter fibre tractography on preoperative diffusion MRI to generate a structural white matter network, and postoperative T1-weighted MRI to retrospectively infer the impact of surgical resection on this network. We then applied graph theory and machine learning to investigate the properties of change between the preoperative and predicted postoperative networks.
Temporal lobe surgery had a modest impact on global network efficiency, despite the disruption caused. This was due to alternative shortest paths in the network leading to widespread increases in betweenness centrality post-surgery. Measurements of network change could retrospectively predict seizure outcomes with 79% accuracy and 65% specificity, which is twice as high as the empirical distribution. Fifteen connections which changed due to surgery were identified as useful for prediction of outcome, eight of which connected to the ipsilateral temporal pole.
Our results suggest that the use of network change metrics may have clinical value for predicting seizure outcome. This approach could be used to prospectively predict outcomes given a suggested resection mask using preoperative data only.
•Connection change pipeline predicts impact of epilepsy surgery on connectome.•Surgery leads to patient-specific reductions in efficiency, strength, region volumes.•Machine learning classifier retrospectively predicts outcome using network changes.•Pipeline could be used prospectively for intended surgery in future.
Objective
Amygdala enlargement can occur in temporal lobe epilepsy, and increased amygdala volume is also reported in sudden unexpected death in epilepsy (SUDEP). Apnea can be induced by amygdala ...stimulation, and postconvulsive central apnea (PCCA) and generalized seizures are both known SUDEP risk factors. Neurite orientation dispersion and density imaging (NODDI) has recently provided additional information on altered amygdala microstructure in SUDEP. In a series of 24 surgical temporal lobe epilepsy cases, our aim was to quantify amygdala cellular pathology parameters that could predict enlargement, NODDI changes, and ictal respiratory dysfunction.
Methods
Using whole slide scanning automated quantitative image analysis methods, parallel evaluation of myelin, axons, dendrites, oligodendroglia, microglia, astroglia, neurons, serotonergic networks, mTOR‐pathway activation (pS6) and phosphorylated tau (pTau; AT8, AT100, PHF) in amygdala, periamygdala cortex, and white matter regions of interest were compared with preoperative magnetic resonance imaging data on amygdala size, and in 13 cases with NODDI and evidence of ictal‐associated apnea.
Results
We observed significantly higher glial labeling (Iba1, glial fibrillary acidic protein, Olig2) in amygdala regions compared to cortex and a strong positive correlation between Olig2 and Iba1 in the amygdala. Larger amygdala volumes correlated with lower microtubule‐associated protein (MAP2), whereas higher NODDI orientation dispersion index correlated with lower Olig2 cell densities. In the three cases with recorded PCCA, higher MAP2 and pS6‐235 expression was noted than in those without. pTau did not correlate with SUDEP risk factors, including seizure frequency.
Significance
Histological quantitation of amygdala microstructure can shed light on enlargement and diffusion imaging alterations in epilepsy to explore possible mechanisms of amygdala dysfunction, including mTOR pathway activation, that in turn may increase the risk for SUDEP.
A normative electrographic activity map could be a powerful resource to understand normal brain function and identify abnormal activity. Here, we present a normative brain map using scalp EEG in ...terms of relative band power. In this exploratory study we investigate its temporal stability, its similarity to other imaging modalities, and explore a potential clinical application. We constructed scalp EEG normative maps of brain dynamics from 17 healthy controls using source-localised resting-state scalp recordings. We then correlated these maps with those acquired from MEG and intracranial EEG to investigate their similarity. Lastly, we use the normative maps to lateralise abnormal regions in epilepsy. Spatial patterns of band powers were broadly consistent with previous literature and stable across recordings. Scalp EEG normative maps were most similar to other modalities in the alpha band, and relatively similar across most bands. Towards a clinical application in epilepsy, we found abnormal temporal regions ipsilateral to the epileptogenic hemisphere. Scalp EEG relative band power normative maps are spatially stable across time, in keeping with MEG and intracranial EEG results. Normative mapping is feasible and may be potentially clinically useful in epilepsy. Future studies with larger sample sizes and high-density EEG are now required for validation.
To estimate the cost and time taken to evaluate adults with drug-resistant focal epilepsy for potentially curative surgery.
We reviewed data on 100 consecutive individuals at a tertiary referral ...center evaluated for epilepsy surgery in 2017. The time elapsed between referral and either surgery or a definitive decision not to progress was measured. National Health Service tariffs applicable to our setting were used to estimate the total cost of evaluation for individuals following different routes through the pre-surgical pathway. After surgery, self-reported seizure freedom rates were obtained from each individual to assess the approximate cost of pre-surgical evaluation per additional person seizure-free.
Of 100 individuals evaluated, 27 had surgery, 63 had a definitive decision not to have surgery, and ten were awaiting further investigations. The median duration of the pre-surgical evaluation was 29.7 months (IQR 18.6–44.1 months), with a median cost per person of £9138 (IQR £6984–£14,868). Those who proceeded to Stage Two investigations (including fluorodeoxyglucose positron emission tomography, ictal single-photon emission computerized tomography and intracranial electroencephalography) had a higher cost and extended evaluation length. After a median of 3.1 (IQR 2.3–3.7) years, 15/27 people who had surgery were seizure-free. This equated to an approximate cost of £123,500 spent per additional person seizure-free.
Pre-surgical evaluation is long and costly, particularly for those who require icEEG. For those with drug-resistant focal epilepsy, surgery is, however, associated with a greater chance of seizure freedom. The suitability and risk-benefit ratio of surgery should be considered at each step of the pre-surgical pathway.
•Surgery for selected people with drug-resistant focal epilepsy is associated with a higher chance of seizure freedom.•Evaluation for epilepsy surgery is lengthy and costly, particularly for those who require intracranial EEG.•Duration and cost of evaluation vary according to different pathways through the pre-surgical evaluation.•Suitability and risk-benefit ratio of surgery need consideration at each pre-surgical evaluation step.
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