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Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group., Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness., Results: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (d max  = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (d max  = .47), crus I/II (d max  = .39), VIIIA (d max  = .45), and VIIIB (d max  = .40). Earlier age at seizure onset ( η ρ max 2  = .05) and longer epilepsy duration ( η ρ max 2  = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls., Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Inflammation plays an essential role in epilepsy. Studies indicate that cytokines and neurotrophic factors can act in neuroexcitability and epileptogenesis. We aimed to investigate the association between plasma inflammatory and neurotrophic markers, seizure frequency, and chronic epilepsy subtypes., Methods: We studied 446 patients with epilepsy and 166 healthy controls. We classified patients according to etiology and seizure frequency. We measured plasma levels of interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), soluble TNF receptor 1 (sTNFr1), sTNFr2, brain-derived neurotrophic factor (BDNF), neurotrophic factor 3 (NT3), NT4/5, ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) by enzyme-linked immunosorbent assay or cytometric bead array., Results: The plasma levels of BDNF, NT3, NGF, and sTNFr2 were higher, whereas IL-2, IL-4, IL-6, IL-10, IL-17, IFNγ, TNFα, CNTF, and sTNFr1 were lower in patients than controls. IL1, GDNF, and NT4/5 were similar between groups. These markers did not correlate with age, sex, and epilepsy duration. The molecule sTNFr2 was the best marker to discriminate patients from controls (area under the curve = .857), also differing between patients with frequent and infrequent seizures., Significance: This large cohort confirmed that patients with epilepsy have abnormal levels of plasma inflammatory and neurotrophic markers independent of the underlying etiology. Plasma level of sTNFr2 was related to seizure frequency and discriminated people with or without epilepsy with good accuracy, making it a potential biomarker for epilepsy and seizure burden., (© 2021 International League Against Epilepsy.)

Objective: This study aims to evaluate the role of scalp electroencephalography (EEG; ictal and interictal patterns) in predicting resective epilepsy surgery outcomes. We use the data to further develop a nomogram to predict seizure freedom., Methods: We retrospectively reviewed the scalp EEG findings and clinical data of patients who underwent surgical resection at three epilepsy centers. Using both EEG and clinical variables categorized into 13 isolated candidate predictors and 6 interaction terms, we built a multivariable Cox proportional hazards model to predict seizure freedom 2 years after surgery. Harrell's step-down procedure was used to sequentially eliminate the least-informative variables from the model until the change in the concordance index (c-index) with variable removal was less than 0.01. We created a separate model using only clinical variables. Discrimination of the two models was compared to evaluate the role of scalp EEG in seizure-freedom prediction., Results: Four hundred seventy patient records were analyzed. Following internal validation, the full Clinical + EEG model achieved an optimism-corrected c-index of 0.65, whereas the c-index of the model without EEG data was 0.59. The presence of focal to bilateral tonic-clonic seizures (FBTCS), high preoperative seizure frequency, absence of hippocampal sclerosis, and presence of nonlocalizable seizures predicted worse outcome. The presence of FBTCS had the largest impact for predicting outcome. The analysis of the models' interactions showed that in patients with unilateral interictal epileptiform discharges (IEDs), temporal lobe surgery cases had a better outcome. In cases with bilateral IEDs, abnormal magnetic resonance imaging (MRI) predicted worse outcomes, and in cases without IEDs, patients with extratemporal epilepsy and abnormal MRI had better outcomes., Significance: This study highlights the value of scalp EEG, particularly the significance of IEDs, in predicting surgical outcome. The nomogram delivers an individualized prediction of postoperative outcome, and provides a unique assessment of the relationship between the outcome and preoperative findings., (© 2021 International League Against Epilepsy.)

Objective: To evaluate the interactions of metabolic neuronal-glial changes with the presence and hemispheric-side of hippocampal sclerosis (HS) and its potential role in predicting pharmacoresistance in temporal lobe epilepsy (TLE)., Methods: We included structural magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ( 1 H-MRS) metabolic data for 91 patients with unilateral TLE and 50 healthy controls. We measured the values of total N-acetyl aspartate/total creatine (tNAA/tCr), glutamate/tCr (Glu/tCr), and myo-inositol/tCr (mIns/tCr). To assess the influence of the pharmacoresponse and hemispheric-side of HS on metabolic data, the relationship between clinical and MRI data, and the predictive value of NAA/Cr, we used analysis of variance/covariance and built a logistic regression model. We used bootstrap simulations to evaluate reproducibility., Results: Bilateral tNAA/tCr reduction was associated with pharmacoresistance and with left HS, a decrease of Glu/tCr ipsilateral to the seizure focus was associated with pharmacoresistance, and ipsilateral mIns/tCr increase was related to pharmacoresistance and the presence of left HS. The logistic regression model containing clinical and 1 H-MRS data discriminated pharmacoresistance (area under the curve [AUC] = 0.78). However, the reduction of tNAA/tCr was the main predictor, with the odds 2.48 greater for pharmacoresistance., Significance: Our study revealed a spectrum of neuronal-glial changes in TLE, which was associated with pharmacoresistance, being more severe in left-sided HS and less severe in MRI-negative TLE. These noninvasive, in vivo biomarkers provide valuable additional information about the interhemispheric differences in metabolic dysfunction, seizure burden, and HS, and may help to predict pharmacoresistance., (© 2020 International League Against Epilepsy.)

Objective: To analyze the lifetime trajectories in genetic generalized epilepsies (GGEs) and investigate the impact of symptoms of anxiety and depression on resting state functional connectivity (FC)., Methods: Seventy-four GGE patients were classified according to the pharmacological response as seizure-free (12 patients), pharmacoresistant (PhR; 14 patients), and fluctuating (FL; 48 patients). Fifty-four subjects completed both the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), and 38 also underwent 3-T resting state functional magnetic resonance imaging. These 38 patients were subdivided into a positive group (13 patients with concurrent symptoms of depression and anxiety) and a negative group (21 asymptomatic patients and four with mild anxiety or depression symptoms). For FC analysis of resting state networks, we matched 38 healthy asymptomatic volunteers and used the UF2C toolbox running on MATLAB2017/SPM12., Results: The PhR group presented shorter duration of epilepsy (P = 0.016) and follow-up (P < 0.001) compared to the FL group. The PhR group showed higher levels (median = 20) on the BAI and BDI. Myoclonic seizures were the most difficult to control, as 50% of subjects persisted with them at last appointment, compared to generalized tonic-clonic seizures and absence seizures (<40%). Patients with concurrent anxiety and depression symptoms were 7.7 times more likely to exhibit pharmacoresistant seizures, although an increase of 1 year of epilepsy duration was associated with a decrease in the odds of presenting pharmacoresistance by a factor of 0.9. Overall, FC was altered between default mode network (DMN) and visuospatial/dorsal attention. However, only the positive group displayed abnormal FC between DMN and left executive control network, and between salience and visuospatial/dorsal attention., Significance: Our findings may help clinicians to have a better understanding of GGE clinical course and increase attention to the potential relationship of psychopathologies and brain connectivity., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Objective: To compare surgical outcome in mesial temporal lobe epilepsy (MTLE) patients with unilateral hippocampal sclerosis (MTLE-HS) who had or did not have preoperative video-electroencephalographic monitoring (VEEG)., Methods: A prospective study was undertaken with 166 consecutive pharmacoresistant unilateral MTLE-HS patients. All patients were investigated with detailed seizure semiology, serial routine outpatient EEG, magnetic resonance imaging, neuropsychological evaluation, and if necessary, other examinations. Postoperative follow-up ranged between 2 and 16 years. Patients were divided into: (1) patients operated on based on routine outpatient EEG information, with >80% of EEGs with unilateral interictal epileptiform discharges (IEDs) ipsilateral to HS or ictal events (n = 71); and (2) patients submitted to preoperative VEEG (n = 95). To avoid the bias generated by ictal recordings, we performed a subanalysis of: (1) patients without preoperatively ictal recordings (n = 80) and (2) patients with ictal recordings in VEEG or routine outpatient EEG (n = 86)., Results: Groups were similar regarding gender, age at surgery, seizure onset, preoperative seizure frequency, and duration of follow-up. Overall, 136/166 (81.92%) were classified as Engel I seizure outcome, with no difference between groups; 76.84% and 88.73% of patients with and without VEEG, respectively, had Engel I postoperative seizure outcome (P = .77). The time lag until surgery was shorter in the group without VEEG (80 vs 38 months; P = .01). Considering ictal recordings, 76.74% of patients with seizures recorded and 87.50% without ictal recordings had Engel I outcome (P = .11)., Significance: We performed the first prospective study in a tertiary epilepsy center comparing surgical outcomes in unilateral MTLE-HS patients investigated preoperatively with and without VEEG. Based on the surgical outcome, VEEG is not imperative in patients with unilateral MTLE-HS who have compatible semiology and clearly ipsilateralized IEDs evaluated by a multidisciplinary and experienced epilepsy group., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)