Structural connectivity as a predictive factor for perampanel response in patients with epilepsy.

OBJECTIVES: This study aimed to identify clinical characteristics that could predict the response to perampanel (PER) and determine whether structural connectivity is a predictive factor. METHODS: We enrolled patients with epilepsy who received PER and were followed-up for a minimum of 12 months. Good PER responders, who were seizure-free or presented with more than 50 % seizure reduction, were classified separately from poor PER responders who had seizure reduction of less than 50 % or non-responders. A graph theoretical analysis was conducted based on diffusion tensor imaging to calculate network measures of structural connectivity among patients with epilepsy. RESULTS: 106 patients with epilepsy were enrolled, including 26 good PER responders and 80 poor PER responders. Good PER responders used fewer anti-seizure medications before PER administration compared to those by poor PER responders (3 vs. 4; p = 0.042). Early PER treatment was more common in good PER responders than poor PER responders (46.2 vs. 21.3 %, p = 0.014). Regarding cortical structural connectivity, the global efficiency was higher and characteristic path length was lower in good PER responders than in poor PER responders (0.647 vs. 0.635, p = 0.006; 1.726 vs. 1,759, p = 0.008, respectively). For subcortical structural connectivity, the mean clustering coefficient and small-worldness index were higher in good PER responders than in poor PER responders (0.821 vs. 0.791, p = 0.009; 0.597 vs. 0.560, p = 0.009, respectively). CONCLUSION: This study demonstrated that early PER administration can predict a good PER response in patients with epilepsy, and structural connectivity could potentially offer clinical utility in predicting PER response.

Seizure Outcome After Intraoperative Electrocorticography-Tailored Epilepsy Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic method. We assessed the current evidence to use ioECoG-tailored epilepsy surgery for improving postsurgical outcome. METHODS: PubMed and Embase were searched for original studies reporting on ≥10 cases who underwent ioECoG-tailored surgery for epilepsy, with a follow-up of at least 6 months. We used a random-effects model to calculate the overall rate of patients achieving favorable seizure outcome (FSO), defined as Engel class I, ILAE class 1, or seizure-free status. Meta-regression was used to investigate potential sources of heterogeneity. We calculated the odds ratio (OR) for estimating variables on FSO:ioECoG vs non-ioECoG-tailored surgery (if included studies contained patients with non-ioECoG-tailored surgery), ioECoG-tailored epilepsy surgery in children vs adults, temporal (TL) vs extratemporal lobe (eTL), MRI-positive vs MRI-negative, and complete vs incomplete resection of tissue that generated interictal epileptiform discharges (IEDs). A Bayesian network meta-analysis was conducted for underlying pathologies. We assessed the evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Eighty-three studies (82 observational studies, 1 trial) comprising 3,631 patients with ioECoG-tailored surgery were included. The overall pooled rate of patients who attained FSO after ioECoG-tailored surgery was 74% (95% CI 71-77) with significant heterogeneity, which was predominantly attributed to pathologies and seizure outcome classifications. Twenty-two studies contained non-ioECoG-tailored surgeries. IoECoG-tailored surgeries reached a higher rate of FSO than non-ioECoG-tailored surgeries (OR 2.10 [95% CI 1.37-3.24]; p < 0.01; very low certainty). Complete resection of tissue that displayed IEDs in ioECoG predicted FSO better compared with incomplete resection (OR 3.04 [1.76-5.25]; p < 0.01; low certainty). We found insignificant difference in FSO after ioECoG-tailored surgery in children vs adults, TL vs eTL, or MRI-positive vs MRI-negative. The network meta-analysis showed that the odds of FSO was lower for malformations of cortical development than for tumors (OR 0.47 95% credible interval 0.25-0.87). DISCUSSION: Although limited by low-quality evidence, our meta-analysis shows a relatively good surgical outcome (74% FSO) after epilepsy surgery with ioECoG, especially in tumors, with better outcome for ioECoG-tailored surgeries in studies describing both and better outcome after complete removal of IED areas.

Non-Specific Epileptic Activity, EEG, and Brain Imaging in Loss of Function Variants in SATB1: A New Case Report and Review of the Literature.

SATB1 (MIM #602075) is a relatively new gene reported only in recent years in association with neurodevelopmental disorders characterized by variable facial dysmorphisms, global developmental delay, poor or absent speech, altered electroencephalogram (EEG), and brain abnormalities on imaging. To date about thirty variants in forty-four patients/children have been described, with a heterogeneous spectrum of clinical manifestations. In the present study, we describe a new patient affected by mild intellectual disability, speech disorder, and non-specific abnormalities on EEG and neuroimaging. Family studies identified a new de novo frameshift variant c.1818delG (p.(Gln606Hisfs*101)) in SATB1. To better define genotype-phenotype associations in the different types of reported SATB1 variants, we reviewed clinical data from our patient and from the literature and compared manifestations (epileptic activity, EEG abnormalities and abnormal brain imaging) due to missense variants versus those attributable to loss-of-function/premature termination variants. Our analyses showed that the latter variants are associated with less severe, non-specific clinical features when compared with the more severe phenotypes due to missense variants. These findings provide new insights into SATB1-related disorders.

Variantes normales de aspecto epileptiforme en el electroencefalograma. Revisión de la bibliografía e implicaciones clínicas / Normal variants with an epileptiform appearance in electroencephalograms. A literature review and clinical implications

Las variantes normales de aspecto epileptiforme, o variantes epileptiformes benignas, son un reto diagnóstico en la interpretación de los electroencefalogramas que requiere su conocimiento y una amplia experiencia por parte de los responsables del informe electroencefalográfico. Incluyen un grupo heterogéneo de hallazgos, algunos muy infrecuentes, que inicialmente se relacionaron con epilepsia y patologías neurológicas diversas. En la actualidad, la mayoría se consideran variantes sin significado patológico, y su sobreinterpretación habitualmente acarrea diagnósticos erróneos y tratamientos innecesarios. Los datos de prevalencia de estas variantes son muy diversos y proceden habitualmente de poblaciones seleccionadas, por lo que son difícilmente extrapolables a población sana. No obstante, estudios con electrodos invasivos y series más recientes vuelven a asociar algunas de estas variantes con epilepsia. Nuestro objetivo es revisar las características y la prevalencia de las principales variantes epileptiformes benignas y actualizar su significado clínico. (AU)

Evaluation of MRI post-processing methods combined with PET in detecting focal cortical dysplasia lesions for patients with MRI-negative epilepsy.

OBJECTIVE: Accurate detection of focal cortical dysplasia (FCD) through magnetic resonance imaging (MRI) plays a pivotal role in the preoperative assessment of epilepsy. The integration of multimodal imaging has demonstrated substantial value in both diagnosing FCD and devising effective surgical strategies. This study aimed to enhance MRI post-processing by incorporating positron emission tomography (PET) analysis. We sought to compare the diagnostic efficacy of diverse image post-processing methodologies in patients presenting MRI-negative FCD. METHODS: In this retrospective investigation, we assembled a cohort of patients with negative preoperative MRI results. T1-weighted volumetric sequences were subjected to morphometric analysis program (MAP) and composite parametric map (CPM) post-processing techniques. We independently co-registered images derived from various methods with PET scans. The alignment was subsequently evaluated, and its correlation was correlated with postoperative seizure outcomes. RESULTS: A total of 41 patients were enrolled in the study. In the PET-MAP(p = 0.0189) and PET-CPM(p = 0.00041) groups, compared with the non-overlap group, the overlap group significantly associated with better postoperative outcomes. In PET(p = 0.234), CPM(p = 0.686) and MAP(p = 0.672), there is no statistical significance between overlap and seizure-free outcomes. The sensitivity of using the CPM alone outperformed the MAP (0.65 vs 0.46). The use of PET-CPM demonstrated superior sensitivity (0.96), positive predictive value (0.83), and negative predictive value (0.91), whereas the MAP displayed superior specificity (0.71). CONCLUSIONS: Our findings suggested a superiority in sensitivity of CPM in detecting potential FCD lesions compared to MAP, especially when it is used in combination with PET for diagnosis of MRI-negative epilepsy patients. Moreover, we confirmed the superiority of synergizing metabolic imaging (PET) with quantitative maps derived from structural imaging (MAP or CPM) to enhance the identification of subtle epileptogenic zones (EZs). This study serves to illuminate the potential of integrated multimodal techniques in advancing our capability to pinpoint elusive pathological features in epilepsy cases.

Subclinical epileptiform discharges in Alzheimer's disease are associated with increased hippocampal blood flow.

BACKGROUND: In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer's disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus. METHODS: A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG. RESULTS: No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value < 0.001). Changes in areas that typically show group differences (temporal-parietal cortex) were found in patients with AD, compared to HC. CONCLUSIONS: Increased spike frequency was accompanied by a hemodynamic response of increased blood flow in the hippocampus in patients with AD. This phenomenon has also been shown in patients with epilepsy and supports the hypothesis of hyperexcitability in patients with AD. The lack of a significant difference in hippocampal rCBF may be due to an increased frequency of epileptiform discharges in patients with AD. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov (NCT04436341).

Association of Localizing 18F-FDG-PET Hypometabolism and Outcome Following Epilepsy Surgery: Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Although commonly used in the evaluation of patients for epilepsy surgery, the association between the detection of localizing 18fluorine fluorodeoxyglucose PET (18F-FDG-PET) hypometabolism and epilepsy surgery outcome is uncertain. We conducted a systematic review and meta-analysis to determine whether localizing 18F-FDG-PET hypometabolism is associated with favorable outcome after epilepsy surgery. METHODS: A systematic literature search was undertaken. Eligible publications included evaluation with 18F-FDG-PET before epilepsy surgery, with ≥10 participants, and those that reported surgical outcome at ≥12 months. Random-effects meta-analysis was used to calculate the odds of achieving a favorable outcome, defined as Engel class I, International League Against Epilepsy class 1-2, or seizure-free, with localizing 18F-FDG-PET hypometabolism, defined as concordant with the epilepsy surgery resection zone. Meta-regression was used to characterize sources of heterogeneity. RESULTS: The database search identified 8,916 studies, of which 98 were included (total patients n = 4,104). Localizing 18F-FDG-PET hypometabolism was associated with favorable outcome after epilepsy surgery for all patients with odds ratio (OR) 2.68 (95% CI 2.08-3.45). Subgroup analysis yielded similar findings for those with (OR 2.64, 95% CI 1.54-4.52) and without epileptogenic lesion detected on MRI (OR 2.49, 95% CI 1.80-3.44). Concordance with EEG (OR 2.34, 95% CI 1.43-3.83), MRI (OR 1.69, 95% CI 1.19-2.40), and triple concordance with both (OR 2.20, 95% CI 1.32-3.64) was associated with higher odds of favorable outcome. By contrast, diffuse 18F-FDG-PET hypometabolism was associated with worse outcomes compared with focal hypometabolism (OR 0.34, 95% CI 0.22-0.54). DISCUSSION: Localizing 18F-FDG-PET hypometabolism is associated with favorable outcome after epilepsy surgery, irrespective of the presence of an epileptogenic lesion on MRI. The extent of 18F-FDG-PET hypometabolism provides additional information, with diffuse hypometabolism associated with worse surgical outcome than focal 18F-FDG-PET hypometabolism. These findings support the incorporation of 18F-FDG-PET into routine noninvasive investigations for patients being evaluated for epilepsy surgery to improve epileptogenic zone localization and to aid patient selection for surgery.

Lesion volume and spike frequency on EEG impact perfusion values in focal cortical dysplasia: a pediatric arterial spin labeling study.

Arterial spin labelling (ASL), an MRI sequence non-invasively imaging brain perfusion, has yielded promising results in the presurgical workup of children with focal cortical dysplasia (FCD)-related epilepsy. However, the interpretation of ASL-derived perfusion patterns remains unclear. Hence, we compared ASL qualitative and quantitative findings to their clinical, EEG, and MRI counterparts. We included children with focal structural epilepsy related to an MRI-detectable FCD who underwent single delay pseudo-continuous ASL. ASL perfusion changes were assessed qualitatively by visual inspection and quantitatively by estimating the asymmetry index (AI). We considered 18 scans from 15 children. 16 of 18 (89%) scans showed FCD-related perfusion changes: 10 were hypoperfused, whereas six were hyperperfused. Nine scans had perfusion changes larger than and seven equal to the FCD extent on anatomical images. Hyperperfusion was associated with frequent interictal spikes on EEG (p = 0.047). Perfusion changes in ASL larger than the FCD corresponded to larger lesions (p = 0.017). Higher AI values were determined by frequent interictal spikes on EEG (p = 0.004). ASL showed FCD-related perfusion changes in most cases. Further, higher spike frequency on EEG may increase ASL changes in affected children. These observations may facilitate the interpretation of ASL findings, improving treatment management, counselling, and prognostication in children with FCD-related epilepsy.

Association of Age-Related Neuropathologic Findings at Autopsy With a Claims-Based Epilepsy Diagnosis in Older Adults.

BACKGROUND AND OBJECTIVES: Epilepsy is 1 of the 3 most common neurologic diseases of older adults, but few studies have examined its underlying pathologies in older age. We examined the associations of age-related brain pathologies with epilepsy in older persons. METHODS: Clinical and pathologic data came from 2 ongoing clinical pathologic cohort studies of community-dwelling older adults. Epilepsy was ascertained using Medicare fee-for-service Parts A and B claims data that were linked to data from the cohort studies. The postmortem pathologic assessment collected indices of 9 pathologies including Alzheimer disease, hippocampal sclerosis, macroinfarcts, and cerebral amyloid angiopathy. The fixed brain hemisphere was imaged using 3T MRI scanners before the pathologic assessments in a subgroup of participants. RESULTS: The participants (n = 1,369) were on average 89.3 (6.6) years at death, and 67.0% were women. Epilepsy was identified in 58 (4.2%) participants. Cerebral amyloid angiopathy (odds ratio [OR] = 2.21, 95% CI 1.24-3.95, p = 0.007) and cortical macroinfarcts (OR = 2.74, 95% CI 1.42-5.28, p = 0.003) were associated with a higher odds of epilepsy. Of note, hippocampal sclerosis and Alzheimer disease pathology were not associated with epilepsy (both p's > 0.25), although hippocampal sclerosis was not common and thus hard to examine with the modest number of epilepsy cases here. In 673 participants with MRI data, the association of cerebral amyloid angiopathy and cortical macroinfarcts with epilepsy did not change after controlling for cortical gray matter atrophy, which was independently associated with a higher odds of epilepsy (OR = 1.06, 95% CI 1.02-1.10, p = 0.003). By contrast, hippocampal volume was not associated with epilepsy. DISCUSSION: Cerebrovascular pathologies and cortical atrophy were associated with epilepsy in older persons.

Clinical features and outcome of 10 dogs with suspected idiopathic vestibular epilepsy.

BACKGROUND: In humans, vestibular epilepsy (VE) is described as focal seizures with transient signs of vestibular disease. In dogs, 2 cases of vestibular episodes, called vestibular paroxysmia, are reported. HYPOTHESIS/OBJECTIVES: The objective of this study was to define the clinical features, phenotypical manifestation, and outcome of suspected VE in dogs. ANIMALS: Ten dogs with recurrent vestibular episodes. METHODS: Retrospective study. Medical records between 2009 and 2023 were reviewed, and dogs with a normal neurological examination, a history of transient signs of vestibular disease, absence of abnormalities detected on blood exams and brain magnetic resonance imaging (MRI) or computed tomography (CT), besides a minimum 10-month follow-up were included. Clinical improvement was defined as a ≥50% reduction in frequency or the cessation of clinical signs after the onset of antiseizure medications (ASMs). RESULTS: Pugs were the most prevalent breed (5/10; 50%). In 2 cases, additional generalized tonic-clonic (GTC) seizures were reported. MRI exam was performed in most cases (9/10; 90%), whereas 1 dog underwent a CT scan (1/10; 10%). Electroencephalography (EEG) was carried out in 3 dogs that showed interictal spikes in the fronto-temporal and fronto-parietal areas. All cases received ASMs, with clinical improvement in 10/10 dogs (100%). CONCLUSION AND CLINICAL IMPORTANCE: The presence of GTC seizures, EEG interictal spikes, and responsiveness to ASMs supported the hypothesis of an epileptic origin of vestibular episodes and thus the existence of VE in these dogs, with a presumed idiopathic cause and apparent favorable outcome.

Evidence for interictal blood-brain barrier dysfunction in people with epilepsy.

OBJECTIVE: Interictal blood-brain barrier dysfunction in chronic epilepsy has been demonstrated in animal models and pathological specimens. Ictal blood-brain barrier dysfunction has been shown in humans in vivo using an experimental quantitative magnetic resonance imaging (MRI) protocol. Here, we hypothesized that interictal blood-brain barrier dysfunction is also present in people with drug-resistant epilepsy. METHODS: Thirty-nine people (21 females, mean age at MRI ± SD = 30 ± 8 years) with drug-resistant epilepsy were prospectively recruited and underwent interictal T1-relaxometry before and after administration of a paramagnetic contrast agent. Likewise, quantitative T1 was acquired in 29 people without epilepsy (12 females, age at MRI = 48 ± 18 years). Quantitative T1 difference maps were calculated and served as a surrogate imaging marker for blood-brain barrier dysfunction. Values of quantitative T1 difference maps inside hemispheres ipsilateral to the presumed seizure onset zone were then compared, on a voxelwise level and within presumed seizure onset zones, to the contralateral side of people with epilepsy and to people without epilepsy. RESULTS: Compared to the contralateral side, ipsilateral T1 difference values were significantly higher in white matter (corrected p < .05), gray matter (uncorrected p < .05), and presumed seizure onset zones (p = .04) in people with epilepsy. Compared to people without epilepsy, significantly higher T1 difference values were found in the anatomical vicinity of presumed seizure onset zones (p = .004). A subgroup of people with hippocampal sclerosis demonstrated significantly higher T1 difference values in the ipsilateral hippocampus and in regions strongly interconnected with the hippocampus compared to people without epilepsy (corrected p < .01). Finally, z-scores reflecting the deviation of T1 difference values within the presumed seizure onset zone were associated with verbal memory performance (p = .02) in people with temporal lobe epilepsy. SIGNIFICANCE: Our results indicate a blood-brain barrier dysfunction in drug-resistant epilepsy that is detectable interictally in vivo, anatomically related to the presumed seizure onset zone, and associated with cognitive deficits.

The role of magnetoencephalography in preoperative localization and postoperative outcome prediction in patients with posterior cortical epilepsy.

OBJECTIVE: We aimed to explore the value of magnetoencephalography in the presurgical evaluation of patients with posterior cortex epilepsy. METHODS: A total of 39 patients with posterior cortex epilepsy (PCE) and intact magnetoencephalography (MEG) images were reviewed from August 2019 to July 2022. MEG dipole clusters were classified into single clusters, multiple clusters, and scatter dipoles based on tightness criteria. The association of the surgical outcome with MEG dipole classifications was evaluated using Fisher's exact tests. RESULTS: Among the 39 cases, there were 24 cases of single clusters (61.5%), nine cases of multiple clusters (23.1%), and six cases of scattered dipoles (15.4%). Patients with single dipole clusters were more likely to become seizure-free. Among single dipole cluster cases (n = 24), complete MEG dipole resection yielded a more favorable surgical outcome than incomplete resection (83.3% vs. 16.7%, p = 0.007). Patients with concordant MRI and MEG findings achieved a significantly more favorable surgical outcome than discordant patients (66.7% vs. 33.3%, p = 0.044), especially in single dipole cluster patients (87.5% vs. 25.0%, p = 0.005). SIGNIFICANCE: MEG can provide additional valuable information regarding surgical candidate selection, epileptogenic zone localization, electrode implantation schedule, and final surgical planning in patients with posterior cortex epilepsy.

Morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative patients with first unprovoked seizure.

OBJECTIVE: The aim of the study was to evaluate the benefits of morphometric magnetic resonance imaging (MRI) postprocessing in patients presenting with a first seizure and negative MRI results and to investigate these findings in the context of the clinical and electroencephalographic data, seizure recurrence rates, and epilepsy diagnosis in these patients. METHODS: We retrospectively reviewed 97 MRI scans of patients with first unprovoked epileptic seizure and no evidence of epileptogenic lesion on clinical routine MRI. Morphometric Analysis Program (MAP; v2018), automated postprocessing software, was used to identify subtle, potentially epileptogenic lesions in the three-dimensional T1-weighted MRI data. The resulting probability maps were examined together with the conventional MRI images by a reviewer who remained blinded to the patients' clinical and electroencephalographical data. Clinical data were prospectively collected between February 2018 and May 2023. RESULTS: Among the apparently MRI-negative patients, a total of 18 of 97 (18.6%) showed cortical changes suggestive of focal cortical dysplasia. Within the population with positive MAP findings (MAP+), seizure recurrence rates were 61.1% and 66.7% at 1 and 2 years after the first unprovoked seizure, respectively. Conversely, patients with negative MAP findings (MAP-) had lower seizure recurrence rates of 27.8% and 34.2% at 1 and 2 years after the first unprovoked seizure, respectively. Patients with MAP+ findings were significantly more likely to be diagnosed with epilepsy than those patients with MAP- findings (χ2 [1, n = 97] = 14.820, p < .001, odds ratio = 21.371, 95% CI = 2.710-168.531) during a mean follow-up time of 22.51 months (SD = 16.7 months, range = 1-61 months). SIGNIFICANCE: MRI postprocessing can be a valuable tool for detecting subtle epileptogenic lesions in patients with a first seizure and negative MRI results. Patients with first seizure and MAP+ findings had high seizure recurrence rates, meeting the criteria for beginning epilepsy.

Stereo-EEG-based ictal functional connectivity in patients with periventricular nodular heterotopia-related epilepsy.

Nodular heterotopia (NH)-related drug-resistant epilepsy is challenging due to the deep location of the NH and the complexity of the underlying epileptogenic network. Using ictal stereo-electroencephalography (SEEG) and functional connectivity (FC) analyses in 14 patients with NH-related drug-resistant epilepsy, we aimed to determine the leading structure during seizures. For this purpose, we compared node IN and OUT strength between bipolar channels inside the heterotopia and inside gray matter, at the group level and at the individual level. At seizure onset, the channels within NH belonging to the epileptogenic and/or propagation network showed higher node OUT-strength than the channels within the gray matter (p = .03), with higher node OUT-strength than node IN-strength (p = .03). These results are in favor of a "leading" role of NH during seizure onset when involved in the epileptogenic- or propagation-zone network (50% of patients). However, when looking at the individual level, no significant difference between NH and gray matter was found, except for one patient (in two of three seizures). This result confirms the heterogeneity and the complexity of the epileptogenic network organization in NH and the need for SEEG exploration to characterize more precisely patient-specific epileptogenic network organization.

Asymmetrical cortical surface area decrease in epilepsy patients with postictal generalized electroencephalography suppression.

Postictal generalized electroencephalographic suppression is a possible electroencephalographic marker for sudden unexpected death in epilepsy. We aimed to investigate the cortical surface area abnormalities in epilepsy patients with postictal generalized electroencephalographic suppression. We retrospectively included 30 epilepsy patients with postictal generalized electroencephalographic suppression (PGES+), 21 epilepsy patients without postictal generalized electroencephalographic suppression (PGES-), and 30 healthy controls. Surface-based analysis on high-resolution T1-weighted images was conducted and cortical surface areas were compared among the three groups, alongside correlation analyses with seizure-related clinical variables. Compared with PGES- group, we identified reduced surface area in the bilateral insula with more extensive distribution in the right hemisphere in PGES+ group. The reduced right insular surface area was associated with younger seizure-onset age. When compared with healthy controls, PGES- group presented reduced surface area in the left caudal middle frontal gyrus; PGES+ group presented more widespread surface area reductions in the right posterior cingulate gyrus, left postcentral gyrus, middle frontal gyrus, and middle temporal gyrus. Our results suggested cortical microstructural impairment in patients with postictal generalized electroencephalographic suppression. The significant surface area reductions in the insular cortex supported the autonomic network involvement in the pathology of postictal generalized electroencephalographic suppression, and its right-sided predominance suggested the potential shared abnormal brain network for postictal generalized electroencephalographic suppression and sudden unexpected death in epilepsy.

EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy.

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

Optimizing Surgical Planning for Epilepsy Patients With Multimodal Neuroimaging and Neurophysiology Integration: A Case Study.

SUMMARY: Current preoperative evaluation of epilepsy can be challenging because of the lack of a comprehensive view of the network's dysfunctions. To demonstrate the utility of our multimodal neurophysiology and neuroimaging integration approach in the presurgical evaluation, we present a proof-of-concept for using this approach in a patient with nonlesional frontal lobe epilepsy who underwent two resective surgeries to achieve seizure control. We conducted a post-hoc investigation using four neuroimaging and neurophysiology modalities: diffusion tensor imaging, resting-state functional MRI, and stereoelectroencephalography at rest and during seizures. We computed region-of-interest-based connectivity for each modality and applied betweenness centrality to identify key network hubs across modalities. Our results revealed that despite seizure semiology and stereoelectroencephalography indicating dysfunction in the right orbitofrontal region, the maximum overlap on the hubs across modalities extended to right temporal areas. Notably, the right middle temporal lobe region served as an overlap hub across diffusion tensor imaging, resting-state functional MRI, and rest stereoelectroencephalography networks and was only included in the resected area in the second surgery, which led to long-term seizure control of this patient. Our findings demonstrated that transmodal hubs could help identify key areas related to epileptogenic network. Therefore, this case presents a promising perspective of using a multimodal approach to improve the presurgical evaluation of patients with epilepsy.

Grading system for assessing the confidence in the epileptogenic zone reported in published studies: A Delphi consensus study.

OBJECTIVE: This study was undertaken to develop a standardized grading system based on expert consensus for evaluating the level of confidence in the localization of the epileptogenic zone (EZ) as reported in published studies, to harmonize and facilitate systematic reviews in the field of epilepsy surgery. METHODS: We conducted a Delphi study involving 22 experts from 18 countries, who were asked to rate their level of confidence in the localization of the EZ for various theoretical clinical scenarios, using different scales. Information provided in these scenarios included one or several of the following data: magnetic resonance imaging (MRI) findings, invasive electroencephalography summary, and postoperative seizure outcome. RESULTS: The first explorative phase showed an overall interrater agreement of .347, pointing to large heterogeneity among experts' assessments, with only 17% of the 42 proposed scenarios associated with a substantial level of agreement. A majority showed preferences for the simpler scale and single-item scenarios. The successive Delphi voting phases resulted in a majority consensus across experts, with more than two thirds of respondents agreeing on the rating of each of the tested single-item scenarios. High or very high levels of confidence were ascribed to patients with either an Engel class I or class IA postoperative seizure outcome, a well-delineated EZ according to all available invasive EEG (iEEG) data, or a well-delineated focal epileptogenic lesion on MRI. MRI signs of hippocampal sclerosis or atrophy were associated with a moderate level of confidence, whereas a low level was ascribed to other MRI findings, a poorly delineated EZ according to iEEG data, or an Engel class II-IV postoperative seizure outcome. SIGNIFICANCE: The proposed grading system, based on an expert consensus, provides a simple framework to rate the level of confidence in the EZ reported in published studies in a structured and harmonized way, offering an opportunity to facilitate and increase the quality of systematic reviews and guidelines in the field of epilepsy surgery.

Evidence based noninvasive presurgical evaluation for patients with drug resistant epilepsies.

PURPOSE OF REVIEW: To review the current practices and evidence for the diagnostic accuracy and the benefits of presurgical evaluation. RECENT FINDINGS: Preoperative evaluation of patients with drug-resistant focal epilepsies and subsequent epilepsy surgery leads to a significant proportion of seizure-free patients. Even those who are not completely seizure free postoperatively often experience improved quality of life with better social integration. Systematic reviews and meta-analysis on the diagnostic accuracy are available for Video-electroencephalographic (EEG) monitoring, magnetic resonance imaging (MRI), electric and magnetic source imaging, and functional MRI for lateralization of language and memory. There are currently no evidence-based international guidelines for presurgical evaluation and epilepsy surgery. SUMMARY: Presurgical evaluation is a complex multidisciplinary and multiprofessional clinical pathway. We rely on limited consensus-based recommendations regarding the required staffing or methodological expertise in epilepsy centers.