Distance from main arteries influences microstructural and functional brain tissue characteristics.

Given the substantial dependence of neurons on continuous supply of energy, the distribution of major cerebral arteries opens a question whether the distance from the main supply arteries constitutes a modulating factor for the microstructural and functional properties of brain tissue. To tackle this question, multimodal MRI acquisitions of 102 healthy volunteers over the full adult age span were utilised. Relaxation along a fictitious field in the rotating frame of rank n = 4 (RAFF4), adiabatic T1ρ, T2ρ,  and intracellular volume fraction (fICVF) derived from diffusion-weighted imaging were implemented to quantify microstructural (cellularity, myelin density, iron concentration) tissue characteristics and degree centrality and fractional amplitude of low-frequency fluctuations to probe for functional metrics. Inverse correlation of arterial distance with robust homogeneity was detected for T1ρ, T2ρ and RAFF4 for cortical grey matter and white matter, showing substantial complex microstructural differences between brain tissue close and farther from main arterial trunks. Albeit with wider variability, functional metrics pointed to increased connectivity and neuronal activity in areas farther from main arteries. Surprisingly, multiple of these microstructural and functional distance-based gradients diminished with higher age, pointing to uniformization of brain tissue with ageing. All in all, this pilot study provides a novel insight on brain regionalisation based on artery distance, which merits further investigation to validate its biological underpinnings.

Low prevalence of neural autoantibodies in perioperative cerebrospinal fluid samples of epilepsy surgery patients: A multicenter prospective study.

OBJECTIVE: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses. METHODS: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed. RESULTS: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]). Five patients' samples displayed CSF-restricted oligoclonal bands (OCBs; 6.6%): three cases with FCD (one with FCD II and two with FCD I), one with HS, and one with negative histology. Importantly, eight patients (one of them with CSF-restricted OCBs) had findings on antibody testing in individual serum and/or CSF tests that could not be confirmed by complementary tests and were thus classified as nonspecific, yet could have been considered specific without confirmatory testing. Of these, two had FCD, two gliosis, and four HS. No inflammatory changes or lymphocyte cuffing was observed histopathologically in any of the 76 patients. SIGNIFICANCE: Neural autoantibodies are a rare finding in perioperatively collected serum and CSF of our cohort of mostly MRI-lesional epilepsy surgery patients. Confirmatory testing is essential to avoid overinterpretation of autoantibody-positive findings.

Interictal high-frequency oscillations, spikes, and connectivity profiles: A fingerprint of epileptogenic brain pathologies.

OBJECTIVE: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for preresective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies. METHODS: Interictal awake stereoelectroencephalographic recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs. RESULTS: Statistically significant differences were found between the individual pathologies in HFO rates, spikes, and their characteristics, together with functional connectivity measures, with the highest values in the case of HS and NG/NT. A model to predict brain pathology based on all interictal measures achieved up to 84.0% prediction accuracy. SIGNIFICANCE: The electrophysiological profile of the various epileptogenic lesions in epilepsy surgery patients was analyzed. Based on this profile, a predictive model was developed. This model offers excellent potential to identify the nature of the underlying lesion prior to resection. If validated, this model may be particularly valuable for counseling patients, as depending on the lesion type, different outcomes are achieved after epilepsy surgery.

Vagus nerve stimulation outcome prediction: from simple parameters to advanced models.

Since its approval as an adjunct treatment for refractory partial epilepsy, the positive effects of vagus nerve stimulation (VNS) on seizure frequency and severity have been supported by many studies. Seizure reduction of more than 50 % can be expected in at least 50 % of patients. However, a complete post-VNS seizure freedom is rarely achieved and 25 % of patients do not benefit from VNS. Our study provides an overview of the potential predictors of VNS response, from the most simple and basic data to sophisticated EEG processing studies and functional imaging studying brain connectivity. The data support better outcomes in younger patients with early VNS implantation, in patients with posttraumatic epilepsy or tuberous sclerosis, and in patients without bilateral interictal epileptiform discharges. The variability of heart activity has also been studied with some promising results. Because the generally accepted hypothesis of the VNS mechanism is the modulation of synaptic activity in multiple cortical and subcortical regions of the brain, the studies of brain response to external stimulation and/or of brain connectivity were used for models predicting the effect of VNS in individual patients. Although the predictive value of these models is high, the required special equipment and sophisticated mathematical tools limit their routine use (Ref. 58). Keywords: epilepsy, vagus nerve stimulation, response predictor, EEG.

Rapid Eye Movement Sleep Sawtooth Waves Are Associated with Widespread Cortical Activations.

Sawtooth waves (STW) are bursts of frontocentral slow oscillations recorded in the scalp electroencephalogram (EEG) during rapid eye movement (REM) sleep. Little is known about their cortical generators and functional significance. Stereo-EEG performed for presurgical epilepsy evaluation offers the unique possibility to study neurophysiology in situ in the human brain. We investigated intracranial correlates of scalp-detected STW in 26 patients (14 women) undergoing combined stereo-EEG/polysomnography. We visually marked STW segments in scalp EEG and selected stereo-EEG channels exhibiting normal activity for intracranial analyses. Channels were grouped in 30 brain regions. The spectral power in each channel and frequency band was computed during STW and non-STW control segments. Ripples (80-250 Hz) were automatically detected during STW and control segments. The spectral power in the different frequency bands and the ripple rates were then compared between STW and control segments in each brain region. An increase in 2-4 Hz power during STW segments was found in all brain regions, except the occipital lobe, with large effect sizes in the parietotemporal junction, the lateral and orbital frontal cortex, the anterior insula, and mesiotemporal structures. A widespread increase in high-frequency activity, including ripples, was observed concomitantly, involving the sensorimotor cortex, associative areas, and limbic structures. This distribution showed a high spatiotemporal heterogeneity. Our results suggest that STW are associated with widely distributed, but locally regulated REM sleep slow oscillations. By driving fast activities, STW may orchestrate synchronized reactivations of multifocal activities, allowing tagging of complex representations necessary for REM sleep-dependent memory consolidation.SIGNIFICANCE STATEMENT Sawtooth waves (STW) present as scalp electroencephalographic (EEG) bursts of slow waves contrasting with the low-voltage fast desynchronized activity of REM sleep. Little is known about their cortical origin and function. Using combined stereo-EEG/polysomnography possible only in the human brain during presurgical epilepsy evaluation, we explored the intracranial correlates of STW. We found that a large set of regions in the parietal, frontal, and insular cortices shows increases in 2-4 Hz power during scalp EEG STW, that STW are associated with a strong and widespread increase in high frequencies, and that these slow and fast activities exhibit a high spatiotemporal heterogeneity. These electrophysiological properties suggest that STW may be involved in cognitive processes during REM sleep.

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.

Arterial Spin Labeling is a Useful MRI Method for Presurgical Evaluation in MRI-Negative Focal Epilepsy.

Arterial spin labeling (ASL) is an MRI technique measuring brain perfusion using magnetically labeled blood as a tracer. The clinical utility of ASL for presurgical evaluation in non-lesional epilepsy as compared with the quantitative analysis of interictal [18F] fluorodeoxyglucose PET (FDG-PET) was studied. In 10 patients (4 female; median age 29 years) who underwent a complete presurgical evaluation followed by surgical resection, the presurgical FDG-PET and ASL scans were compared with the resection masks using asymmetry index (AI) maps. The positive predictive value (PPV) and sensitivity (SEN), were calculated from the number of voxels inside the mask (true positive), and outside the mask (false positive). The comparison of the PPVs showed better PPV in 6 patients using ASL and in 2 patients with PET. SEN was better in 4 patients using ASL and in 5 patients with PET. According to the Wilcoxon signed rank test for PPV (p = 0.74) and for SEN (p = 0.43), these methods have similar predictive power. ASL is a useful method for presurgical evaluation in non-lesional epilepsy. The main benefits of ASL over PET are that it avoids radiation exposure for patients, and it offers lower costs, higher availability, and better time efficiency.

Atlas of the normal intracranial electroencephalogram: neurophysiological awake activity in different cortical areas.

In contrast to scalp EEG, our knowledge of the normal physiological intracranial EEG activity is scarce. This multicentre study provides an atlas of normal intracranial EEG of the human brain during wakefulness. Here we present the results of power spectra analysis during wakefulness. Intracranial electrodes are placed in or on the brain of epilepsy patients when candidates for surgical treatment and non-invasive approaches failed to sufficiently localize the epileptic focus. Electrode contacts are usually in cortical regions showing epileptic activity, but some are placed in normal regions, at distance from the epileptogenic zone or lesion. Intracranial EEG channels defined using strict criteria as very likely to be in healthy brain regions were selected from three tertiary epilepsy centres. All contacts were localized in a common stereotactic space allowing the accumulation and superposition of results from many subjects. Sixty-second artefact-free sections during wakefulness were selected. Power spectra were calculated for 38 brain regions, and compared to a set of channels with no spectral peaks in order to identify significant peaks in the different regions. A total of 1785 channels with normal brain activity from 106 patients were identified. There were on average 2.7 channels per cm3 of cortical grey matter. The number of contacts per brain region averaged 47 (range 6-178). We found significant differences in the spectral density distributions across the different brain lobes, with beta activity in the frontal lobe (20-24 Hz), a clear alpha peak in the occipital lobe (9.25-10.25 Hz), intermediate alpha (8.25-9.25 Hz) and beta (17-20 Hz) frequencies in the parietal lobe, and lower alpha (7.75-8.25 Hz) and delta (0.75-2.25 Hz) peaks in the temporal lobe. Some cortical regions showed a specific electrophysiological signature: peaks present in >60% of channels were found in the precentral gyrus (lateral: peak frequency range, 20-24 Hz; mesial: 24-30 Hz), opercular part of the inferior frontal gyrus (20-24 Hz), cuneus (7.75-8.75 Hz), and hippocampus (0.75-1.25 Hz). Eight per cent of all analysed channels had more than one spectral peak; these channels were mostly recording from sensory and motor regions. Alpha activity was not present throughout the occipital lobe, and some cortical regions showed peaks in delta activity during wakefulness. This is the first atlas of normal intracranial EEG activity; it includes dense coverage of all cortical regions in a common stereotactic space, enabling direct comparisons of EEG across subjects. This atlas provides a normative baseline against which clinical EEGs and experimental results can be compared. It is provided as an open web resource (https://mni-open-ieegatlas. RESEARCH: mcgill.ca).

Predictive value of preoperative statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: This study was designed to use statistical parametric mapping of interictal positron-emission tomography using [18F]Fluorodeoxyglucose (FDG-PET) to compare the brain metabolisms of patients with mesial temporal lobe epilepsy (MTLE)/hippocampal sclerosis and controls. Another aim of this study was to analyze the potential differences among patients in terms of epilepsy duration, side of hippocampal sclerosis, histopathological findings, insult in their history, and postoperative outcomes. METHODS: We analyzed FDG-PET scans from 49 patients with MTLE/hippocampal sclerosis and 24 control subjects. We analyzed the differences in regional glucose metabolism between the patients and the control group and within the patient group using multiple variables. RESULTS: We observed widespread hypometabolism in the patient group in comparison with the control group in temporal and extratemporal areas on the epileptogenic side (ES). On the nonepileptogenic side (NES), we observed the most hypometabolism in the thalamus and the anterior and middle cingulate gyrus. In the group of patients with more severe hippocampal sclerosis, we observed statistically significant hypometabolism in the insula on the ES. In patients with poor postoperative outcomes, we found statistically significant hypometabolism in the insula on the ES and the temporal pole (TP) on the NES. Patients with any insult in their history showed hypermetabolism in the TP on both sides. CONCLUSION: Our study showed that there are widespread changes in metabolism in patients with MTLE in comparison to controls, either inside or outside the temporal lobe. There are significant differences among these patients in terms of postoperative outcomes, degree of hippocampal sclerosis, and insults in their history.

Atypical handedness in mesial temporal lobe epilepsy.

OBJECTIVE: The main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population. METHODS: Handedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated. RESULTS: We found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p=0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8years of age [median; min-max 0.5-17] in left-handers versus 15years of age [median; min-max 3-30] in right-handers (p<0.001). CONCLUSIONS: Left-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE.

Differences between mesial and neocortical magnetic-resonance-imaging-negative temporal lobe epilepsy.

OBJECTIVE: The aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG). METHODS: According to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ-mesial MRI-negative TLE or neocortical SOZ-neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology. RESULTS: Thirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p=0.031) and more seizures without clear lateralization of ictal activity (p=0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found. CONCLUSIONS: According to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach.

Ictal and postictal semiology in patients with bilateral temporal lobe epilepsy.

Bilateral temporal lobe epilepsy is characterized by evidence of seizure onset independently in both temporal lobes. The main aim of the present study was to determine whether patients with evidence of independent bilateral temporal lobe epilepsy (biTLE) can be identified noninvasively on the basis of seizure semiology analysis. Thirteen patients with biTLE, as defined by invasive EEG, were matched with 13 patients with unilateral temporal lobe epilepsy (uniTLE). In all 26 patients, the frequency of predefined clusters of ictal and periictal signs were evaluated: ictal motor signs (IMSs), periictal motor signs (PIMSs), periictal vegetative signs (PIVSs), the frequency of early oroalimentary automatisms (EOAs), and the duration of postictal unresponsiveness (PU). Some other noninvasive and clinical data were also evaluated. A lower frequency of IMSs was noted in the group with biTLE (patients = 46.2%, seizures = 20.7%) than in the group with uniTLE (patients = 92.3%, seizures = 61.0%) (p = 0.030; p < 0.001, respectively). The individual IMS average per seizure was significantly lower in the group with biTLE (0.14; range = 0-1.0) than in the group with uniTLE (0.80; range = 0-2.6) (p = 0.003). Postictal unresponsiveness was longer than 5 min in more patients (75.0%) and seizures (42.9%) in the group with biTLE than in the group with uniTLE (patients = 30.8%, seizures = 18.6%) (p = 0.047; p = 0.002). The frequency of EOAs, PIMSs, PIVSs, and other clinical data did not differ significantly. There is a lower frequency of ictal motor signs and longer duration of postictal unresponsiveness in patients with biTLE.

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.

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.

Case report: Susac syndrome-two ends of the spectrum, single center case reports and review of the literature.

Susac syndrome is a rare and enigmatic complex neurological disorder primarily affecting small blood vessels in the brain, retina, and inner ear. Diagnosing Susac syndrome may be extremely challenging not only due to its rarity, but also due to the variability of its clinical presentation. This paper describes two vastly different cases-one with mild symptoms and good response to therapy, the other with severe, complicated course, relapses and long-term sequelae despite multiple therapeutic interventions. Building upon the available guidelines, we highlight the utility of black blood MRI in this disease and provide a comprehensive review of available clinical experience in clinical presentation, diagnosis and therapy of this disease. Despite its rarity, the awareness of Susac syndrome may be of uttermost importance since it ultimately is a treatable condition. If diagnosed in a timely manner, early intervention can substantially improve the outcomes of our patients.

Syncope with atypical trunk convulsions in a patient with malignant arrhythmia.

Syncope is a condition often misdiagnosed as epilepsy. Syncope caused by cardiac disturbance is a life-threatening condition and accurate diagnosis is crucial for patient outcome. We present a case study of a 71-year-old woman who was referred to our epilepsy centre with a diagnosis of refractory epilepsy. We diagnosed convulsive syncope caused by malignant cardiac arrhythmia based on the presence of cardiac asystole lasting for 20-30 seconds, which was caused by sick sinus syndrome combined with third-degree atrioventricular block. The most prominent feature of this syncope was atypical trunk (abdominal or thoracoabdominal) convulsions, which were accompanied by other motor signs (head and eye deviation and brief jerks of the extremities). In the periods between attacks, all investigations, including standard 12-lead ECG and 24-hour ECG monitoring, were normal. This case study highlights the challenge in differential diagnosis of sudden loss of consciousness. [Published with video sequences].

The effects of COVID-19 on sleep and general health of Czech patients with epilepsy.

Objectives: To assess the impact of COVID-19 illness and pandemic era on sleep, general health, health care, and social status in patients with epilepsy in the Czech Republic. Methods: Our designed and approved questionnaire consisted of 23 questions. We focused on (1) patients' demographic and epidemiological data regarding COVID-19, (2) subjective assessment of sleep; (3) epilepsy, and (4) perception of general health during the first year of the COVID-19 pandemic in the Czech Republic from March 2020 to May 2021. We administered the questionnaires during outpatient visits or by phone calls in three major university Czech epilepsy centers (Ostrava, Brno, Pilsen). Results: We enrolled 227 (100%) patients. The mean age (±SD) was 41.2 ± 14.82 years (min 18, max 86 years), and 138 (61%) were women. COVID-19 was confirmed using the PCR test method in 57 (25.1%) patients. In the pre-pandemic era, 62 (27.3%) patients reported sleep disturbances. Insomnia in 46 (74.2%) and excessive daytime sleepiness in 6 (9.7%) were the most mentioned sleep abnormalities. Nocturnal seizures predispose to sleep impairment (p = 0.014) and vivid dreams and nightmares (p = 0.033). COVID-19 infection significantly increased the risk of vivid dreams and nightmares in patients with diurnal seizures (p = 0.006). Sleep quality impairment and seizure frequency worsening [(p < 0.001) and (p = 0.001), respectively] were the most significant risk factors to perform general health deterioration regardless of having COVID-19 (p = 0.559). The most affected age group was 51+ years (p = 0.033). The three centers provided adequate outpatient care during the first year of the pandemic. The employment and social status of the patients remained unchanged (p = 0.074). Conclusions: COVID- 19 infection significantly increased the occurrence of vivid dreams and nightmares in patients with diurnal seizures. Sleep quality deterioration and seizure frequency worsening significantly negatively impacted general health performance.

White matter alterations in MR-negative temporal and frontal lobe epilepsy using fixel-based analysis.

This study focuses on white matter alterations in pharmacoresistant epilepsy patients with no visible lesions in the temporal and frontal lobes on clinical MRI (i.e. MR-negative) with lesions confirmed by resective surgery. The aim of the study was to extend the knowledge about group-specific neuropathology in MR-negative epilepsy. We used the fixel-based analysis (FBA) that overcomes the limitations of traditional diffusion tensor image analysis, mainly within-voxel averaging of multiple crossing fibres. Group-wise comparisons of fixel parameters between healthy controls (N = 100) and: (1) frontal lobe epilepsy (FLE) patients (N = 9); (2) temporal lobe epilepsy (TLE) patients (N = 13) were performed. A significant decrease of the cross-section area of the fixels in the superior longitudinal fasciculus was observed in the FLE. Results in TLE reflected widespread atrophy of limbic, thalamic, and cortico-striatal connections and tracts directly connected to the temporal lobe (such as the anterior commissure, inferior fronto-occipital fasciculus, uncinate fasciculus, splenium of corpus callosum, and cingulum bundle). Alterations were also observed in extratemporal connections (brainstem connection, commissural fibres, and parts of the superior longitudinal fasciculus). To our knowledge, this is the first study to use an advanced FBA method not only on the datasets of MR-negative TLE patients, but also MR-negative FLE patients, uncovering new common tract-specific alterations on the group level.

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.

Pregnancy Outcomes in Refractory Epilepsy Patients with Vagus Nerve Stimulation: Long-Term Single-Center Experience.

BACKGROUND AND STUDY AIMS: Vagus nerve stimulation (VNS) has been employed worldwide as an adjunctive therapy in drug-resistant epilepsy patients. However, the mechanisms of VNS action potentially increase the risk of obstetric complications. The study presents the long-term single-center experience with pregnancies and childbirth in women with VNS for refractory epilepsy based on prospectively collected epileptologic data and a retrospective analysis of pregnancy, childbirth, and data about long-term child development. MATERIAL AND METHODS: From a group of patients with VNS implanted for refractory epilepsy between October 1999 and January 2018, all the women of childbearing age (younger than 40 years) were identified. After checking their hospital records for data about any pregnancies, the women with confirmed childbirth during active VNS stimulation and their general practitioners were interviewed based on a prepared questionnaire regarding their gynecologic history, the course of pregnancy and childbirth, gestational week, birth weight and length, any congenital anomalies of the child, and the child's psychomotor development, school performance, and somatic health problems. RESULTS: From the group of 257 patients implanted with VNS for refractory epilepsy, 4 women (1.5%) became pregnant and gave birth (all on polypharmacotherapy). The mean interval from VNS implantation to birth was 44.3 months. Slight seizure worsening during the last trimester was reported in one woman. In one patient, acute caesarean section was required due to placental separation. Planned birth induction and caesarean section were used in the other two women because of their seizure disorder. No malfunction of the stimulation system was detected during pregnancy or after birth. No congenital malformations were observed. The two children who were of school age at the time of this study require special schooling. CONCLUSIONS: The study results confirmed a high rate of obstetric interventions in patients with VNS. Although no teratogenic effect of VNS has been proven, the higher incidence of children exposed to VNS needing special education requires attention.