Case report: Insulinoma masquerades as epilepsy - quantitative EEG analysis.

Insulinomas are rare gastrointestinal tumors with an incidence of 1-3 per million inhabitants annually. These tumors result in excessive insulin production, culminating in hypoglycemia. Such hypoglycemia triggers various central nervous system (CNS) manifestations, including headache, confusion, abnormal behavior, and epileptic seizures, which can lead to misdiagnosis as epilepsy. This case report documents a 46-year-old male who presented seizure-like episodes. Episodes occurred mainly during the night, lasting several minutes to hours. Initial seizures were characterized by bizarre behavior and altered responsiveness. Over time, seizure frequency, complexity, and severity escalated. We managed to record two episodes during long-term EEG and report, as the first ones, the detailed quantitative EEG analysis of these hypoglycemia-related events. EEG changes preceded the development of clear-cut pathological motor activity in tens of minutes and were present in all investigated frequency bands. The development of profound motor activity was associated with other increases in EEG power spectra in all frequencies except for delta. The most pronounced changes were found over the left temporal region, which can be the most susceptible to hypoglycemia. In our patient, the seizure-like episodes completely disappeared after the insulinoma removal, which demonstrates their relationship to hypoglycemia.

Eslicarbazepine-induced hyponatremia: A retrospective single-center real clinical practice study.

Hyponatremia is a typical side effect of antiseizure drugs from the dibenzazepine family. The study investigated the prevalence of hyponatremia in patients with epilepsy who were treated with eslicarbazepine. We aimed to determine the prevalence of hyponatremia, reveal the factors leading to the discontinuation of treatment, and identify possible risk factors for the development of hyponatremia including the dose dependency. The medical records of 164 patients with epilepsy taking eslicarbazepine in our center were analyzed. The overall prevalence of hyponatremia was 30.5%. The prevalence of mild hyponatremia, seen in 14%-20% of patients, was not dose dependent. The prevalence of moderate and severe hyponatremia was significantly dose dependent. The severity of hyponatremia was significantly dose dependent. Severe hyponatremia was found in 6.1% of patients. Hyponatremia was asymptomatic in the majority of cases, and in 48% did not require any management. Hyponatremia was the reason for discontinuation in 6.2% of patients. The major risk factor for developing hyponatremia was older age. The study shows that eslicarbazepine-induced hyponatremia is usually mild and asymptomatic. It usually does not require any management and seldom leads to treatment discontinuation. Hyponatremia is dose dependent. Another major risk for developing hyponatremia (besides dose) is older age.

Metabolic connectivity as a predictor of surgical outcome in mesial temporal lobe epilepsy.

OBJECTIVE: The study investigated metabolic connectivity (MC) differences between patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and healthy controls (HCs), based on [18 F]-fluorodeoxyglucose (FDG)-PET data. We focused on the MC changes dependent on the lateralization of the epileptogenic lobe and on correlations with postoperative outcomes. METHODS: FDG-PET scans of 47 patients with unilateral MTLE with histopathologically proven HS and 25 HC were included in the study. All the patients underwent a standard anterior temporal lobectomy and were more than 2 years after the surgery. MC changes were compared between the two HS groups (left HS, right HS) and HC. Differences between the metabolic network of seizure-free and non-seizure-free patients after surgery were depicted afterward. Network changes were correlated with clinical characteristics. RESULTS: The study showed widespread metabolic network changes in the HS patients as compared to HC. The changes were more extensive in the right HS than in the left HS. Unfavorable surgical outcomes were found in patients with decreased MC within the network including both the lesional and contralesional hippocampus, ipsilesional frontal operculum, and contralesional insula. Favorable outcomes correlated with decreased MC within the network involving both orbitofrontal cortices and the ipsilesional temporal lobe. SIGNIFICANCE: There are major differences in the metabolic networks of left and right HS, with more extensive changes in right HS. The changes within the metabolic network could help predict surgical outcomes in patients with HS. MC may identify patients with potentially unfavorable outcomes and direct them to a more detailed presurgical evaluation. PLAIN LANGUAGE SUMMARY: Metabolic connectivity is a promising method for metabolic network mapping. Metabolic networks in mesial temporal lobe epilepsy are dependent on lateralization of the epileptogenic lobe and could predict surgical outcomes.

Twenty-five years of epilepsy surgery at a Central European comprehensive epilepsy center-Trends in intervention delay and outcomes.

OBJECTIVE: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy. METHODS: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center. RESULTS: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001). Correspondingly, extratemporal resections have become more frequent with a significant increase in surgeries for focal cortical dysplasia (2%-8%-19%, P < 0.001). For resections, better outcomes (ILAE scores 1a-2) have been achieved in extratemporal lesional (0%-21%-61%, P = 0.01, at least 2-year follow-up) patients. In temporal lesional patients, outcomes remained unchanged (at least 77% success rate). A longer duration of epilepsy predicted a less favorable outcome for resective procedures (P = 0.024) in patients with disease duration of less than 25 years. SIGNIFICANCE: The spectrum of epilepsy surgery is shifting toward nonlesional and extratemporal cases. While success rates of extratemporal resections at our center are getting better, the average duration of epilepsy before surgical intervention is still very long and is not improving. This underscores the need for stronger collaboration between epileptologists and outpatient neurologists to ensure prompt and effective treatment for patients with drug-resistant epilepsy.

Multimodal combination of neuroimaging methods for localizing the epileptogenic zone in MR-negative epilepsy.

The objective was to determine the optimal combination of multimodal imaging methods (IMs) for localizing the epileptogenic zone (EZ) in patients with MR-negative drug-resistant epilepsy. Data from 25 patients with MR-negative focal epilepsy (age 30 ± 10 years, 16M/9F) who underwent surgical resection of the EZ and from 110 healthy controls (age 31 ± 9 years; 56M/54F) were used to evaluate IMs based on 3T MRI, FDG-PET, HD-EEG, and SPECT. Patients with successful outcomes and/or positive histological findings were evaluated. From 38 IMs calculated per patient, 13 methods were selected by evaluating the mutual similarity of the methods and the accuracy of the EZ localization. The best results in postsurgical patients for EZ localization were found for ictal/ interictal SPECT (SISCOM), FDG-PET, arterial spin labeling (ASL), functional regional homogeneity (ReHo), gray matter volume (GMV), cortical thickness, HD electrical source imaging (ESI-HD), amplitude of low-frequency fluctuation (ALFF), diffusion tensor imaging, and kurtosis imaging. Combining IMs provides the method with the most accurate EZ identification in MR-negative epilepsy. The PET, SISCOM, and selected MRI-post-processing techniques are useful for EZ localization for surgical tailoring.

Memory retrieval in temporal lobe epilepsy is related to functional segregation of the mesiotemporal structures.

OBJECTIVE: We analyzed the impact of temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) on functional connectivity (FC) between mesiotemporal structures. Functional connectivity modifications related to word retrieval were investigated. METHODS: High-density EEG of 21 patients with TLE with HS (12 left TLE and 9 right TLE) and 10 healthy controls (HCs) were recorded during a verbal subsequent memory paradigm. Electroencephalography data were reconstructed into the source space and FC was calculated from the source activity of regions of interest. RESULTS: A significant decrease in FC between the right- and left-sided mesiotemporal structures in TLE was observed. The decrease was significant only with words that were correctly recognized. The decrease in interhemispheric FC between mesiotemporal structures was found in the 8- to 20-Hz frequency range in both left and right TLE. SIGNIFICANCE: The decreased FC between the mesiotemporal structures in TLE is a condition for successful performance of a memory retrieval task. The successful memory retrieval in TLE is related to functional segregation of lesional from nonlesional mesiotemporal structures. This decrease was absent in non-successful responses.

Automated fusion of multimodal imaging data for identifying epileptogenic lesions in patients with inconclusive magnetic resonance imaging.

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand-alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR-negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel-wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue. We found a subset of two classes specific to tissue located in resected areas. The average classification accuracy (i.e., the probability of correct classification) was significantly higher than the level of chance in the training group (0.73) and even better in the validation surgery subgroup (0.82). Nuclear imaging, diffusion-weighted imaging, and source localization of interictal epileptic discharges were the strongest methods for classification accuracy. We showed that the automatic fusion of results can identify brain areas that show epileptogenic gray matter tissue features. The method might enhance the presurgical evaluations of MR-negative epilepsy patients.

Mozart effect in epilepsy: Why is Mozart better than Haydn? Acoustic qualities-based analysis of stereoelectroencephalography.

BACKGROUND AND PURPOSE: We aimed to confirm the Mozart effect in epileptic patients using intracerebral electroencephalography recordings and the hypothesis that the reduction of epileptiform discharges (EDs) can be explained by the music's acoustic properties. METHODS: Eighteen epilepsy surgery candidates were implanted with depth electrodes in the temporal medial and lateral cortex. Patients listened to the first movement of Mozart's Sonata for Two Pianos K. 448 and to the first movement of Haydn's Symphony No. 94. Musical features from each composition with respect to rhythm, melody, and harmony were analyzed. RESULTS: Epileptiform discharges in intracerebral electroencephalography were reduced by Mozart's music. Listening to Haydn's music led to reduced EDs only in women; in men, the EDs increased. The acoustic analysis revealed that nondissonant music with a harmonic spectrum and decreasing tempo with significant high-frequency parts has a reducing effect on EDs in men. To reduce EDs in women, the music should additionally be gradually less dynamic in terms of loudness. Finally, we were able to demonstrate that these acoustic characteristics are more dominant in Mozart's music than in Haydn's music. CONCLUSIONS: We confirmed the reduction of intracerebral EDs while listening to classical music. An analysis of the musical features revealed that the acoustic characteristics of music are responsible for suppressing brain epileptic activity. Based on our study, we suggest studying the use of musical pieces with well-defined acoustic properties as an alternative noninvasive method to reduce epileptic activity in patients with epilepsy.

Cognitive task-related functional connectivity alterations in temporal lobe epilepsy.

OBJECTIVE: We investigated cognitive task-related functional connectivity (FC) in patients with temporal lobe epilepsy (TLE). Using a visual three-stimulus paradigm (VTSP), we studied cognitive large-scale networks and the impact of TLE on connectivity outside the temporal lobe. METHODS: High-density electroencephalography (EEG) was recorded during the paradigm from nineteen patients with epilepsy with hippocampal sclerosis (HS) and ten healthy controls (HCs). Scalp data were reconstructed into the source space, and FC was computed. Correlating with the neuropsychological data, possible compensatory mechanisms were investigated. RESULTS: Significant changes were found in the FC of regions outside the epileptogenic network, particularly in the attentional network. These changes were more widespread in left TLE (LTLE). There were no significant differences in task performance (accuracy, time response) in comparison with HCs, implying that there must be some mechanism reducing the impact of connectivity changes on brain functions. When correlated with neuropsychological data, we found stronger compensatory mechanisms in right TLE (RTLE). SIGNIFICANCE: Our findings confirm the hypothesis that LTLE is the more pervasive form of the disease. Even though the network alterations in TLE are severe, some mechanisms reduce the impact of epilepsy on cognitive functions; these mechanisms are more potent in RTLE. We also suggest that there are maladaptive mechanisms in LTLE.

Human brain connectivity: Clinical applications for clinical neurophysiology.

This manuscript is the second part of a two-part description of the current status of understanding of the network function of the brain in health and disease. We start with the concept that brain function can be understood only by understanding its networks, how and why information flows in the brain. The first manuscript dealt with methods for network analysis, and the current manuscript focuses on the use of these methods to understand a wide variety of neurological and psychiatric disorders. Disorders considered are neurodegenerative disorders, such as Alzheimer disease and amyotrophic lateral sclerosis, stroke, movement disorders, including essential tremor, Parkinson disease, dystonia and apraxia, epilepsy, psychiatric disorders such as schizophrenia, and phantom limb pain. This state-of-the-art review makes clear the value of networks and brain models for understanding symptoms and signs of disease and can serve as a foundation for further work.

Large-scale cortico-subcortical functional networks in focal epilepsies: The role of the basal ganglia.

OBJECTIVES: The aim was to describe the contribution of basal ganglia (BG) thalamo-cortical circuitry to the whole-brain functional connectivity in focal epilepsies. METHODS: Interictal resting-state fMRI recordings were acquired in 46 persons with focal epilepsies. Of these 46, 22 had temporal lobe epilepsy: 9 left temporal (LTLE), 13 right temporal (RTLE); 15 had frontal lobe epilepsy (FLE); and 9 had parietal/occipital lobe epilepsy (POLE). There were 20 healthy controls. The complete weighted network was analyzed based on correlation matrices of 90 and 194 regions. The network topology was quantified on a global and regional level by measures based on graph theory, and connection-level changes were analyzed by the partial least square method. RESULTS: In all patient groups except RTLE, the shift of the functional network topology away from random was observed (normalized clustering coefficient and characteristic path length were higher in patient groups than in controls). Links contributing to this change were found in the cortico-subcortical connections. Weak connections (low correlations) consistently contributed to this modification of the network. The importance of regions changed: decreases in the subcortical areas and both decreases and increases in the cortical areas were observed in node strength, clustering coefficient and eigenvector centrality in patient groups when compared to controls. Node strength decreases of the basal ganglia, i.e. the putamen, caudate, and pallidum, were displayed in LTLE, FLE, and POLE. The connectivity within the basal ganglia-thalamus circuitry was not disturbed; the disturbance concerned the connectivity between the circuitry and the cortex. SIGNIFICANCE: Focal epilepsies affect large-scale brain networks beyond the epileptogenic zones. Cortico-subcortical functional connectivity disturbance was displayed in LTLE, FLE, and POLE. Significant changes in the resting-state functional connectivity between cortical and subcortical structures suggest an important role of the BG and thalamus in focal epilepsies.