Age-dependent increase of perineuronal nets in the human hippocampus and precocious aging in epilepsy.

OBJECTIVE: Perineuronal nets (PNN) are specialized extracellular matrix (ECM) components of the central nervous system, frequently accumulating at the surface of inhibitory GABAergic interneurons. While an altered distribution of PNN has been observed in neurological disorders including Alzheimer's disease, schizophrenia and epilepsy, their anatomical distribution also changes during physiological brain maturation and aging. Such an age-dependent shift was experimentally associated also with hippocampal engram formation during brain maturation. Our aim was to histopathologically assess PNN in the hippocampus of adult and pediatric patients with temporal lobe epilepsy (TLE) compared to age-matched post-mortem control subjects and to compare PNN-related changes with memory impairment observed in our patient cohort. METHODS: Sixty-six formalin-fixed and paraffin-embedded tissue specimens of the human hippocampus were retrieved from the European Epilepsy Brain Bank. Twenty-nine patients had histopathologically confirmed hippocampal sclerosis (HS), and eleven patients suffered from TLE without HS. PNN were immunohistochemically visualized using an antibody directed against aggrecan and manually counted from hippocampus subfields and the subiculum. RESULTS: PNN density increased with age in both human controls and TLE patients. However, their density was significantly higher in all HS patients compared to age-matched controls. Intriguingly, TLE patients presented presurgically with better memory when their hippocampal PNN density was higher (p < 0.05). SIGNIFICANCE: Our results were compatible with age-dependent ECM specialization in the human hippocampus and its precocious aging in the epileptic condition. These observations confirm recent experimental animal models and also support the notion that PNN play a role in memory formation in the human brain. PLAIN LANGUAGE SUMMARY: "Perineuronal nets" (PNN) are a specialized compartment of the extracellular matrix (ECM), especially surrounding highly active neurons of the mammalian brain. There is evidence that PNN play a role in memory formation, brain maturation, and in some pathologies like Alzheimer's disease, schizophrenia or epilepsy. In this study, we investigated the role of PNN in patients suffering from drug-resistant focal epilepsy compared to controls. We found that with increasing age, more neurons are surrounded by PNN. Similarly, all epilepsy patients but especially patients with better memory performance also had more PNN. This study raises further interest in studying ECM molecules in the human brain under physiological and pathophysiological conditions.

Comprehensive 7 T CEST: A clinical MRI protocol covering multiple exchange rate regimes.

Chemical exchange saturation transfer (CEST) is a magnetic resonance (MR) imaging method providing molecular image contrasts based on indirect detection of low concentrated solutes. Previous CEST studies focused predominantly on the imaging of single CEST exchange regimes (e.g., slow, intermediate or fast exchanging groups). In this work, we aim to establish a so-called comprehensive CEST protocol for 7 T, covering the different exchange regimes by three saturation B1 amplitude regimes: low, intermediate and high. We used the results of previous publications and our own simulations in pulseq-CEST to produce a 7 T CEST protocol that has sensitivity to these three B1 regimes. With postprocessing optimization (simultaneous mapping of water shift and B1, B0-fitting, multiple interleaved mode saturation B1 correction, neural network employment (deepCEST) and analytical input feature reduction), we are able to shorten our initially 40 min protocol to 15 min and generate six CEST contrast maps simultaneously. With this protocol, we measured four healthy subjects and one patient with a brain tumor. We established a comprehensive CEST protocol for clinical 7 T MRI, covering three different B1 amplitude regimes. We were able to reduce the acquisition time significantly by more than 50%, while still maintaining decent image quality and contrast in healthy subjects and one patient with a tumor. Our protocol paves the way to perform comprehensive CEST studies in clinical scan times for hypothesis generation regarding molecular properties of certain pathologies, for example, ischemic stroke or high-grade brain tumours.

ILAE neuroimaging task force highlight: Subcortical laminar heterotopia.

The ILAE Neuroimaging Task Force publishes educational case reports that highlight basic aspects of neuroimaging in epilepsy consistent with the ILAE's educational mission. Subcortical laminar heterotopia, also known as subcortical band heterotopia (SBH) or "double cortex," is an intriguing and rare congenital malformation of cortical development. SBH lesions are part of a continuum best designated as agyria-pachygyria-band-spectrum. The malformation is associated with epilepsy that is often refractory, as well as variable degrees of developmental delay. Moreover, in an increasing proportion of cases, a distinct molecular-genetic background can be found. Diagnosing SBH can be a major challenge for many reasons, including more subtle lesions, and "non-classic" or unusual MRI-appearances. By presenting an illustrative case, we address the challenges and needs of diagnosing and treating SBH patients in epilepsy, especially the value of high-resolution imaging and specialized MRI-protocols.

Interictal Electrical Source Imaging.

SUMMARY: Interictal electrical source imaging (ESI) determines the neuronal generators of epileptic activity in EEG occurring outside of seizures. It uses computational models to take anatomic and neuronal characteristics of the individual patient into account. The presented article provides an overview of application and clinical value of interictal ESI in patients with pharmacoresistant focal epilepsies undergoing evaluation for surgery. Neurophysiological constraints of interictal data are discussed and technical considerations are summarized. Typical indications are covered as well as issues of integration into clinical routine. Finally, an outlook on novel markers of epilepsy for interictal source analysis is presented. Interictal ESI provides diagnostic performance on par with other established methods, such as MRI, PET, or SPECT. Although its accuracy benefits from high-density recordings, it provides valuable information already when applied to EEG with only a limited number of electrodes with complete coverage. Novel oscillatory markers and the integration of frequency coupling and connectivity may further improve accuracy and efficiency.

Perceived Health Benefits in Vestibular Schwannoma Patients with Long-Term Postoperative Headache: Insights from Personality Traits and Pain Coping-A Cross-Sectional Study.

Postoperative headaches (POHs) following retrosigmoid microsurgery for vestibular schwannoma (VS) can significantly impact patients' perceived health benefits (PHBs). In this cross-sectional observational study, 101 VS patients were investigated. For the assessment of pain, the Rostock Headache Compendium (RoKoKo) and the German pain processing questionnaire (FESV) were used. The perceived health benefits (PHBs) were assessed by the Glasgow Benefit Inventory (GBI) and Big Five personality traits were measured using the Ten-Item Personality Inventory (TIPI-G). We showed that 55% of the participants experienced POHs, leading to a marked reduction in overall PHBs compared to those without POHs. The correlation analysis revealed an association between decreased PHBs and elevated levels of pain-related helplessness, depression, anxiety, and anger. Positive correlations were identified between PHBs and action-planning competence, cognitive restructuring, and the experience of competence. Low emotional stability and openness yielded associations with pain-related psychological impairment. Hearing loss and facial paresis did not exert a significant impact on PHBs. The study highlights the influence of pain-related coping strategies on PHBs in long-term POH patients. Thus, coping mechanisms and personality traits should be assessed even before surgery for post-surgery pain prevention. The limitations of this study include a relatively small sample size, potential biases introduced by the overrepresentation of female patients, and the use of an online survey methodology. In conclusion, this research highlights that the interplay between headaches, PHBs, and psychological factors is also relevant in VS patients undergoing microsurgery. Short-term psychological interventions should therefore be taken into account to improve post-surgery adaptive coping strategies.

Standardized hierarchical adaptive Lp regression for noise robust focal epilepsy source reconstructions.

OBJECTIVE: To investigate the ability of standardization to reduce source localization errors and measurement noise uncertainties for hierarchical Bayesian algorithms with L1- and L2-norms as priors in electroencephalography and magnetoencephalography of focal epilepsy. METHODS: Description of the standardization methodology relying on the Hierarchical Bayesian framework, referred to as the Standardized Hierarchical Adaptive Lp-norm Regularization (SHALpR). The performance was tested using real data from two focal epilepsy patients. Simulated data that resembled the available real data was constructed for further localization and noise robustness investigation. RESULTS: The proposed algorithms were compared to their non-standardized counterparts, Standardized low-resolution brain electromagnetic tomography, Standardized Shrinking LORETA-FOCUSS, and Dynamic statistical parametric maps. Based on the simulations, the standardized Hierarchical adaptive algorithm using L2-norm was noise robust for 10 dB signal-to-noise ratio (SNR), whereas the L1-norm prior worked robustly also with 5 dB SNR. The accuracy of the standardized L1-normed methodology to localize focal activity was under 1 cm for both patients. CONCLUSIONS: Numerical results of the proposed methodology display improved localization and noise robustness. The proposed methodology also outperformed the compared methods when dealing with real data. SIGNIFICANCE: The proposed standardized methodology, especially when employing the L1-norm, could serve as a valuable assessment tool in surgical decision-making.

Expert accuracy and inter-rater agreement of "must-know" EEG findings for adult and child neurology residents.

OBJECTIVE: We published a list of "must-know" routine EEG (rEEG) findings for trainees based on expert opinion. Here, we studied the accuracy and inter-rater agreement (IRA) of these "must-know" rEEG findings among international experts. METHODS: A previously validated online rEEG examination was disseminated to EEG experts. It consisted of a survey and 30 multiple-choice questions predicated on the previously published "must-know" rEEG findings divided into four domains: normal, abnormal, normal variants, and artifacts. Questions contained de-identified 10-20-s epochs of EEG that were considered unequivocal examples by five EEG experts. RESULTS: The examination was completed by 258 international EEG experts. Overall mean accuracy and IRA (AC1) were 81% and substantial (0.632), respectively. The domain-specific mean accuracies and IRA were: 76%, moderate (0.558) (normal); 78%, moderate (0.575) (abnormal); 85%, substantial (0.678) (normal variants); 85%, substantial (0.740) (artifacts). Academic experts had a higher accuracy than private practice experts (82% vs. 77%; p = .035). Country-specific overall mean accuracies and IRA were: 92%, almost perfect (0.836) (U.S.); 86%, substantial (0.762) (Brazil); 79%, substantial (0.646) (Italy); and 72%, moderate (0.496) (India). In conclusion, collective expert accuracy and IRA of "must-know" rEEG findings are suboptimal and heterogeneous. SIGNIFICANCE: We recommend the development and implementation of pragmatic, accessible, country-specific ways to measure and improve the expert accuracy and IRA.

Deep histopathology genotype-phenotype analysis of focal cortical dysplasia type II differentiates between the GATOR1-altered autophagocytic subtype IIa and MTOR-altered migration deficient subtype IIb.

Focal cortical dysplasia type II (FCDII) is the most common cause of drug-resistant focal epilepsy in children. Herein, we performed a deep histopathology-based genotype-phenotype analysis to further elucidate the clinico-pathological and genetic presentation of FCDIIa compared to FCDIIb. Seventeen individuals with histopathologically confirmed diagnosis of FCD ILAE Type II and a pathogenic variant detected in brain derived DNA whole-exome sequencing or mTOR gene panel sequencing were included in this study. Clinical data were directly available from each contributing centre. Histopathological analyses were performed from formalin-fixed, paraffin-embedded tissue samples using haematoxylin-eosin and immunohistochemistry for NF-SMI32, NeuN, pS6, p62, and vimentin. Ten individuals carried loss-of-function variants in the GATOR1 complex encoding genes DEPDC5 (n = 7) and NPRL3 (n = 3), or gain-of-function variants in MTOR (n = 7). Whereas individuals with GATOR1 variants only presented with FCDIIa, i.e., lack of balloon cells, individuals with MTOR variants presented with both histopathology subtypes, FCDIIa and FCDIIb. Interestingly, 50% of GATOR1-positive cases showed a unique and predominantly vacuolizing phenotype with p62 immunofluorescent aggregates in autophagosomes. All cases with GATOR1 alterations had neurosurgery in the frontal lobe and the majority was confined to the cortical ribbon not affecting the white matter. This pattern was reflected by subtle or negative MRI findings in seven individuals with GATOR1 variants. Nonetheless, all individuals were seizure-free after surgery except four individuals carrying a DEPDC5 variant. We describe a yet underrecognized genotype-phenotype correlation of GATOR1 variants with FCDIIa in the frontal lobe. These lesions were histopathologically characterized by abnormally vacuolizing cells suggestive of an autophagy-altered phenotype. In contrast, individuals with FCDIIb and brain somatic MTOR variants showed larger lesions on MRI including the white matter, suggesting compromised neural cell migration.

Attentional Modulation of the Cortical Contribution to the Frequency-Following Response Evoked by Continuous Speech.

Selective attention to one of several competing speakers is required for comprehending a target speaker among other voices and for successful communication with them. It moreover has been found to involve the neural tracking of low-frequency speech rhythms in the auditory cortex. Effects of selective attention have also been found in subcortical neural activities, in particular regarding the frequency-following response related to the fundamental frequency of speech (speech-FFR). Recent investigations have, however, shown that the speech-FFR contains cortical contributions as well. It remains unclear whether these are also modulated by selective attention. Here we used magnetoencephalography to assess the attentional modulation of the cortical contributions to the speech-FFR. We presented both male and female participants with two competing speech signals and analyzed the cortical responses during attentional switching between the two speakers. Our findings revealed robust attentional modulation of the cortical contribution to the speech-FFR: the neural responses were higher when the speaker was attended than when they were ignored. We also found that, regardless of attention, a voice with a lower fundamental frequency elicited a larger cortical contribution to the speech-FFR than a voice with a higher fundamental frequency. Our results show that the attentional modulation of the speech-FFR does not only occur subcortically but extends to the auditory cortex as well.SIGNIFICANCE STATEMENT Understanding speech in noise requires attention to a target speaker. One of the speech features that a listener can use to identify a target voice among others and attend it is the fundamental frequency, together with its higher harmonics. The fundamental frequency arises from the opening and closing of the vocal folds and is tracked by high-frequency neural activity in the auditory brainstem and in the cortex. Previous investigations showed that the subcortical neural tracking is modulated by selective attention. Here we show that attention affects the cortical tracking of the fundamental frequency as well: it is stronger when a particular voice is attended than when it is ignored.

Network topology in brain tumor patients with and without structural epilepsy: a prospective MEG study.

Background: It was proposed that network topology is altered in brain tumor patients. However, there is no consensus on the pattern of these changes and evidence on potential drivers is lacking. Objectives: We aimed to characterize neurooncological patients' network topology by analyzing glial brain tumors (GBTs) and brain metastases (BMs) with respect to the presence of structural epilepsy. Methods: Network topology derived from resting state magnetoencephalography was compared between (1) patients and controls, (2) GBTs and BMs, and (3) patients with (PSEs) and without structural epilepsy (PNSEs). Eligible patients were investigated from February 2019 to March 2021. We calculated whole brain (WB) connectivity in six frequency bands, network topological parameters (node degree, average shortest path length, local clustering coefficient) and performed a stratification, where differences in power were identified. For data analysis, we used Fieldtrip, Brain Connectivity MATLAB toolboxes, and in-house built scripts. Results: We included 41 patients (21 men), with a mean age of 60.1 years (range 23-82), of those were: GBTs (n = 23), BMs (n = 14), and other histologies (n = 4). Statistical analysis revealed a significantly decreased WB node degree in patients versus controls in every frequency range at the corrected level (p1-30Hz = 0.002, pγ = 0.002, pß = 0.002, pα = 0.002, pθ = 0.024, and pδ = 0.002). At the descriptive level, we found a significant augmentation for WB local clustering coefficient (p1-30Hz = 0.031, pδ = 0.013) in patients compared to controls, which did not persist the false discovery rate correction. No differences regarding networks of GBTs compared to BMs were identified. However, we found a significant increase in WB local clustering coefficient (pθ = 0.048) and decrease in WB node degree (pα = 0.039) in PSEs versus PNSEs at the uncorrected level. Conclusion: Our data suggest that network topology is altered in brain tumor patients. Histology per se might not, however, tumor-related epilepsy seems to influence the brain's functional network. Longitudinal studies and analysis of possible confounders are required to substantiate these findings.

Age of epilepsy onset as modulating factor for naming deficit after epilepsy surgery: a voxel-based lesion-symptom mapping study.

Age at onset of epilepsy is an important predictor of deterioration in naming ability following epilepsy surgery. In 141 patients with left hemispheric epilepsy and language dominance who received epilepsy surgery at the Epilepsy Centre Erlangen, naming of objects (Boston naming test, BNT) was assessed preoperatively and 6 months postoperatively. Surgical lesions were plotted on postoperative MRI and normalized for statistical analysis using voxel-based lesion-symptom mapping (VBLSM). The correlation between lesion and presence of postoperative naming deterioration was examined varying the considered age range of epilepsy onsets. The VBLSM analysis showed that volumes of cortex areas in the left temporal lobe, which were associated with postoperative decline of naming, increased with each year of later epilepsy onset. In patients with later onset, an increasing left posterior temporobasal area was significantly associated with a postoperative deficit when included in the resection. For late epilepsy onset, the temporomesial expansion also included the left hippocampus. The results underline that early onset of epilepsy is a good prognostic factor for unchanged postoperative naming ability following epilepsy surgery. For later age of epilepsy onset, the extent of the area at risk of postoperative naming deficit at 6 months after surgery included an increasing left temporobasal area which finally also comprised the hippocampus.

Lateralization of delta band power in magnetoencephalography (MEG) in patients with unilateral focal epilepsy and its relation to verbal fluency.

INTRODUCTION: Delta power is a clinically established biomarker for abnormal brain processes. However, in patients with unilateral focal epilepsy (FE) it is still not well understood, how it relates to the epileptogenic zone and to neurocognitive functioning. The aim of the present study was thus to assess how delta power relates to the affected hemisphere, whether lateralization strength differs between the patients, and how changes in delta power correlate with cognitive functioning. METHOD: We retrospectively studied patients with left (LFE) and right FE (RFE) who had undergone a resting-state magnetoencephalography measurement. We computed global and hemispheric delta power and lateralization indices and examined whether delta power correlates with semantic and letter verbal fluency (former being a marker for language and verbal memory, latter for executive functions) in 26 FE patients (15 LFE, 11 RFE) and 10 healthy controls. RESULTS: Delta power was increased in FE patients compared to healthy controls. However, the increase across hemispheres was related to the site of the epileptic focus: On group level, LFE patients showed higher delta power in both hemispheres, whereas RFE patients primarily exhibited higher delta power in the ipsilateral right hemisphere. Both groups showed co-fluctuations of delta power between the hemispheres. Besides, delta power correlated negatively only with letter verbal fluency. CONCLUSION: The findings confirm and provide further evidence that delta power is a marker of pathological activity and abnormal brain processes in FE. Delta power dynamics differ between patient groups, indicating that delta power could offer additional diagnostic value. The negative association of delta power and letter verbal fluency suggests that executive dysfunctions are related to low frequency abnormalities.

Premorbid Psychological Factors Associated with Long-Term Postoperative Headache after Microsurgery in Vestibular Schwannoma-A Retrospective Pilot Study.

Associations between premorbid psychological factors and postoperative headache (POH) after microsurgical treatment via the retrosigmoid approach for vestibular schwannoma (VS) were investigated in this retrospective single-center study. A total of 101 VS patients completed the Rostock headache questionnaire (RoKoKo), the hospital and anxiety scale (HADS-D), and the screening for somatoform disorders (SOMS-2), all of which were used as short self-assessed questionnaires. Fifty-four patients with POH were compared with 47 non-POH patients in terms of premorbid psychological factors, somatization tendencies, and psychological burden using the chi2-test and Mann-Whitney U-test. Regression analyses were conducted to assess the weighted contribution of psychological and procedural factors to POH. In individuals with POH, mental ailments, preexisting headaches, premorbid chronic pain syndromes, and higher somatization tendencies were found to be significantly more common. POH was predicted by the number of premorbid psychosomatic symptoms, preexisting mental ailments, and premorbid chronic pain syndromes. Depression and anxiety were predicted by low emotional stability. Additionally, the number of premorbid psychosomatic symptoms predicted depression, anxiety, and overall psychological burden. It was observed that the reported symptoms of headache might fit into the classification of chronic postsurgical pain (CPSP) rather than being classified as secondary headaches after craniotomy. Premorbid psychological factors were found to play an important role in the emergence of POH in VS, particularly after microsurgery via the retrosigmoid approach. Therefore, it is suggested that psychological screening be incorporated into the treatment process.

Surgical Site Infections in Glioblastoma Patients-A Retrospective Analysis.

Surgical site infections (SSIs) after craniotomy lead to additional morbidity and mortality for patients, which are related to higher costs for the healthcare system. Furthermore, SSIs are associated with a longer hospital stay for the patient, which is particularly detrimental in glioblastoma patients due to their limited life expectancy. Risk factors for SSIs have already been described for craniotomies in general. However, there is limited data available for glioblastoma patients. As postoperative radiation influences wound healing, very early radiation is suspected to be a risk factor for SSI. Nevertheless, there are no data on the optimal timing of radiotherapy. To define risk factors for these patients, we analyzed our collective. We performed a retrospective analysis of all operations with histological evidence of a glioblastoma between 2012 and 2021. Open biopsy and tumor removal (gross total resection, subtotal resection) were included. Stereotactic biopsies were excluded. Demographic data such as age and gender, as well as duration of surgery, diameter of the trepanation, postoperative radiation with interval, postoperative chemotherapy, highest blood glucose level, previous surgery, ASA score, foreign material introduced, subgaleal suction drainage, ventricle opening and length of hospital stay, were recorded. The need for surgical revision due to infection was registered as an SSI. A total of 177 patients were included, of which 14 patients (7.9%) suffered an SSI. These occurred after a median of 45 days. The group with SSIs tended to include more men (57.1%, p = 0.163) and more pre-operated patients (50%, p = 0.125). In addition, foreign material and subgaleal suction drains had been implanted more frequently and the ventricles had been opened more frequently, without reaching statistical significance. Surprisingly, significantly more patients without SSIs had been irradiated (80.3%, p = 0.03). The results enable a better risk assessment of SSIs in glioblastoma patients. Patients with previous surgery, introduced foreign material, subgaleal suction drain and opening of the ventricle may have a slightly higher for SSIs. However, because none of these factors were significant, we should not call them risk factors. A less radical approach to surgery potentially involving these factors is not justified. The postulated negative role of irradiation was not confirmed, hence a rapid chemoradiation should be induced to achieve the best possible oncologic outcome.

Recurrences and progression following microsurgery of vestibular schwannoma.

Background: The treatment approach of vestibular schwannoma (VS) has seen a change in recent years, with a trend away from radical surgery towards preservation of cranial nerve function. A recent study reported recurrences as long as 20 years after complete removal of VS. Objective: To report the risk of recurrence and progression in our patient population the authors retrospectively reviewed outcomes of patients. Methods: Cases with unilateral VS who had undergone primary microsurgery via retrosigmoidal approach between 1995 and 2021 were investigated. Complete tumor removal was defined as gross total resection (GTR), a capsular remnant was categorized as near total resection (NTR) and residual tumor was designated as subtotal resection (STR). The primary endpoint was radiological recurrence-free survival. Results: 386 patients fulfilled the inclusion criteria of the study and were evaluated. GTR was achieved in 284 patients (73.6%), NTR was achieved in 63 patients (10.1%) and STR was present in 39 patients (16.3%). A total of 28 patients experienced recurrences with significant differences in the three subgroups. The strongest predictor of recurrence was the extent of resection, with patients who underwent STR having an almost 10-fold higher risk of recurrence and patients who had undergone NTR having an almost 3-fold higher risk than those treated with GTR. More than 20% of recurrences (6/28) occured after more than 5 years. Conclusion: The degree of resection is an important guide to the interval of follow-up, but long-term follow-up should be considered also in the case of GTR. The majority of recurrences occurs after 3-5 years. Nevertheless, a follow-up of at least 10 years should be carried out.

Neurocysticercosis and epilepsy: Imaging and clinical characteristics.

The ILAE Neuroimaging Task Force aimed to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Neurocysticercosis (NCC) is highly endemic in resource-limited countries and increasingly more often seen in non-endemic regions due to migration. Cysts with larva of the tapeworm Taenia solium lodge in the brain and cause several neurological conditions, of which seizures are the most common. There is great heterogeneity in the clinical presentation of neurocysticercosis because cysts vary in number, larval stage, and location among patients. We here present two illustrative cases with different clinical features to highlight the varying severity of symptoms secondary to this parasitic infestation. We also present several examples of imaging characteristics of the disease at various stages, which emphasize the central role of neuroimaging in the diagnosis of neurocysticercosis.

Focal epilepsies: Update on diagnosis and classification.

Correctly diagnosing and classifying seizures and epilepsies is paramount to ensure the delivery of optimal care to patients with epilepsy. Focal seizures, defined as those that originate within networks limited to one hemisphere, are primarily subdivided into focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures. Focal epilepsies account for most epilepsy cases both in children and adults. In children, focal epilepsies are typically subdivided in three groups: self-limited focal epilepsy syndromes (e.g., self-limited epilepsy with centrotemporal spikes), focal epilepsy of unknown cause but which do not meet criteria for a self-limited focal epilepsy syndrome, and focal epilepsy of known cause (e.g., structural lesions-developmental or acquired). In adults, focal epilepsies are often acquired and may be caused by a structural lesion such as stroke, infection and traumatic brain injury, or brain tumors, vascular malformations, metabolic disorders, autoimmune, and/or genetic causes. In addition to seizure semiology, neuroimaging, neurophysiology, and neuropathology constitute the cornerstones of a diagnostic evaluation. Patients with focal epilepsy who become drug-resistant should promptly undergo assessment in an epilepsy center. After excluding pseudo-resistance, these patients should be considered for presurgical evaluation as a means to identify the location and extent of the epileptogenic zone and assess their candidacy for a surgical procedure. The goal of this seminar in epileptology is to summarize clinically relevant information concerning focal epilepsies. This contributes to the ILAE's mission to ensure that worldwide healthcare professionals, patients, and caregivers continue to have access to high-quality educational resources concerning epilepsy.

MEG Node Degree for Focus Localization: Comparison with Invasive EEG.

Epilepsy surgery is a viable therapy option for patients with pharmacoresistant focal epilepsies. A prerequisite for postoperative seizure freedom is the localization of the epileptogenic zone, e.g., using electro- and magnetoencephalography (EEG/MEG). Evidence shows that resting state MEG contains subtle alterations, which may add information to the workup of epilepsy surgery. Here, we investigate node degree (ND), a graph-theoretical parameter of functional connectivity, in relation to the seizure onset zone (SOZ) determined by invasive EEG (iEEG) in a consecutive series of 50 adult patients. Resting state data were subjected to whole brain, all-to-all connectivity analysis using the imaginary part of coherence. Graphs were described using parcellated ND. SOZ localization was investigated on a lobar and sublobar level. On a lobar level, all frequency bands except alpha showed significantly higher maximal ND (mND) values inside the SOZ compared to outside (ratios 1.11-1.20, alpha 1.02). Area-under-the-curve (AUC) was 0.67-0.78 for all expected alpha (0.44, ns). On a sublobar level, mND inside the SOZ was higher for all frequency bands (1.13-1.38, AUC 0.58-0.78) except gamma (1.02). MEG ND is significantly related to SOZ in delta, theta and beta bands. ND may provide new localization tools for presurgical evaluation of epilepsy surgery.

Reorganization and Plasticity of the Language Network in Patients with Cerebral Gliomas.

Language is organized in large-scale networks in the human brain that show a strong potential for flexible interactions and adaptation. Neuroplasticity is the central mechanism that allows such dynamic modulation to changing conditions across the life span and is particularly important for network reorganization after brain lesions. Most studies on language reorganization focused on language recovery after stroke. Yet, a strong degree of adaptive neuroplasticity can also be observed in patients with brain tumors in language-eloquent brain areas. This review discusses key mechanisms for neural reorganization in patients with brain tumors. Our main aim is to elucidate the underlying mechanisms for intra- and interhemispheric plasticity in the language network in these patients. The following reorganization patterns are discussed: 1) Persisting function within the tumor; 2) Reorganization in perilesional regions; 3) Reorganization in a distributed network of the affected hemisphere; 4) Reorganization to the contralesional hemisphere. In this context, we shed light on language-related reorganization patterns in frontal and temporo-parietal areas and discuss their functional relevance. We also address tumor-related changes in structural and functional connectivity between eloquent brain regions. Thereby, we aim to expand the general understanding of the plastic potential of the neural language network and facilitate clinical decision-making processes for effective, function-preserving tumor treatment.