Severe memory decline along with unaffected executive functions under 400 mg/day of cenobamate leading to a collapse in school performance.

Cenobamate (CNB) is one of the newer antiseizure medications for the treatment of focal-onset seizures. The cognitive profile of CNB is not yet known in detail. Here we present the case of an 18-year-old male high school student with epilepsy who received adjunctive CNB. Under 400 mg/d of CNB in combination with lamotrigine, a neuropsychological reassessment revealed a severe deterioration of the formerly normal episodic memory functions, while executive functions remained unaffected. The de novo memory deficit had already led to a collapse in school performance and he unexpectedly failed to obtain the general qualification for university entrance. Given the beneficial effect of CNB on seizure control, a dose reduction of CNB to 200 mg/d and introduction of valproic acid was performed. This led to a full recovery of objective memory performance. To our knowledge this is the very first report of a dose-dependent, selective and severe decline in episodic memory performance under CNB, potentially impeding academic achievement. The findings call for a cognitive monitoring of CNB which also addresses episodic memory in addition to executive functions. Systematic studies on episodic memory upon CNB treatment would help to appreciate the scope of this apparently reversible adverse effect.

Long-term seizure outcome after epilepsy surgery of neuroglial tumors.

Purpose: Neuroglial tumors are frequently associated with pharmacorefractory epilepsies. However, comprehensive knowledge about long-term outcomes after epilepsy surgery and the main prognostic factors for outcome is still limited. We sought to evaluate long-term outcomes and potential influencing factors in a large cohort of patients who underwent surgery for neuroglial tumors in a single-center setting. Methods: The study analyzed the outcomes of 107 patients who underwent epilepsy surgery for neuroglial tumors between 2001 and 2020 at the Department of Epileptology, University Hospital Bonn, in Germany. The outcomes were evaluated using Engel classification. Differences in outcome related to potential prognostic factors were examined using the Chi2-test, Fisher's exact test and sign test. Additionally, stepwise logistic regression analysis was employed to identify independent prognostic factors. Results: Complete seizure freedom (Engel Class IA) was achieved in 75% of the operated patients at 12 months, and 56% at the last follow-up visit (70.4 ± 6.2 months, median: 40 months). Completeness of resection was a crucial factor for both 12-month follow-up outcomes and the longest available outcomes, whereas lobar tumor localization, histology (ganglioglioma vs. dysembryoplastic neuroepithelial tumor), history of bilateral tonic-clonic seizures prior to surgery, invasive diagnostics, side of surgery (dominant vs. non-dominant hemisphere), age at epilepsy onset, age at surgery, and epilepsy duration did not consistently impact postsurgical outcomes. Among temporal lobe surgeries, patients who underwent lesionectomy and lesionectomy, including hippocampal resection, demonstrated similar outcomes. Conclusion: Neuroglial tumors present as excellent surgical substrates in treating structural epilepsy. To achieve an optimal postsurgical outcome, a complete lesion resection should be pursued whenever possible.

Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABABR Antibodies: Implications for Return to Driving.

BACKGROUND AND OBJECTIVES: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. METHODS: This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. RESULTS: We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. DISCUSSION: Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

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

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

Short-term effects of transcutaneous auricular vagus nerve stimulation on T-wave alternans in people with focal epilepsy - An exploratory pilot study.

High levels of T-wave alternans (TWA) are linked to an increased risk of sudden cardiac death. People with epilepsy display elevated TWA levels that are decreased by chronic vagus nerve stimulation via implanted devices after 2-4 weeks or later. Our objective was to explore short-term effects of transcutaneous auricular vagus nerve stimulation (tVNS) on TWA. Five patients (3 female) with focal epilepsy undergoing video-EEG monitoring were included. TWA levels were determined using a one-channel modified lead I ECG via an open-source TWA-algorithm on two consecutive days, 1 h before, during and after tVNS via the left auricle. Data are given as mean ± SE. Mean TWA at baseline was 3.8 ± 0.4 µV and 3.0 ± 0.6 µV during stimulation on day 2. Stimulations on the second day were associated with TWA reductions by 22 ± 13 % that exceeded stimulation effects on the first day relative to baseline (p < 0.05). Linear mixed-models revealed effects of both stimulation (p < 0.05) and stimulation number (p < 0.005). Normalized TWA showed reproducible peak reductions at both days within 35 min after the initiation of tVNS (p < 0.05). Our observations suggest that tVNS has short-term effects on TWA, supporting the notion that vagus nerve stimulation has a beneficial impact on electrical cardiac properties.

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

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

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

[Incidence of sudden death in epilepsy (SUDEP): update and limitations]. / Inzidenz des plötzlichen Epilepsietodes (SUDEP): Update und Limitationen.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is in most cases probably due to a fatal complication of tonic-clonic seizures and plays a significant role in the premature mortality of individuals with epilepsy. The reported risks of SUDEP vary considerably depending on the study population, so that an up-dated systematic review of SUDEP incidence including most recent studies is required to improve the estimated SUDEP risk and the counseling of individuals with epilepsy. OBJECTIVE: To provide an overview of the current research landscape concerning SUDEP incidence across different patient populations and discuss potential conclusions and existing limitations. MATERIAL AND METHODS: A systematic literature review on SUDEP incidence was conducted in MEDLINE and EMBASE, supplemented by a manual search in June 2023. Out of a total of 3324 publications, 50 were reviewed for this study. RESULTS: The analyzed studies showed significant heterogeneity concerning cohorts, study design and data sources. Studies conducted without specific criteria and relying on comprehensive registers indicated an incidence of 0.78-1.2 per 1000 patient-years. Research providing incidences across various age groups predominantly show an increase with age, peaking in middle age. DISCUSSION: Due to varying methods of data collection and incidence calculation, comparing between studies is challenging. The association with age might be due to an underrepresentation of children, adolescents and patients over 60 years. CONCLUSION: Considering all age groups and types of epilepsy it is estimated that about 1 in 1000 individuals with epilepsy dies of SUDEP annually. With an assumed epilepsy prevalence of 0.6% in Germany, this could lead to more than one SUDEP case daily. Standardization of research methods is essential to gain more profound insights.

Expert opinion on diagnosis and management of epilepsy-associated comorbidities.

Apart from seizure freedom, the presence of comorbidities related to neurological, cardiovascular, or psychiatric disorders is the largest determinant of a reduced health-related quality of life in people with epilepsy (PwE). However, comorbidities are often underrecognized and undertreated, and clinical management of comorbid conditions can be challenging. The focus of a comprehensive treatment regimen should maximize seizure control while optimizing clinical management of treatable comorbidities to improve a person's quality of life and overall health. A panel of four European epileptologists with expertise in their respective fields of epilepsy-related comorbidities combined the latest available scientific evidence with clinical expertise and collaborated to provide consensus practical advice to improve the identification and management of comorbidities in PwE. This review provides a critical evaluation for the diagnosis and management of sleep-wake disorders, cardiovascular diseases, cognitive dysfunction, and depression in PwE. Whenever possible, clinical data have been provided. The PubMed database was the main search source for the literature review. The deleterious pathophysiological processes underlying neurological, cardiovascular, or psychiatric comorbidities in PwE interact with the processes responsible for generating seizures to increase cerebral and physiological dysfunction. This can increase the likelihood of developing drug-resistant epilepsy; therefore, early identification of comorbidities and intervention is imperative. The practical evidence-based advice presented in this article may help clinical neurologists and other specialist physicians responsible for the care and management of PwE.

Volumetric gray matter findings in autonomic network regions of people with focal epilepsy.

BACKGROUND AND PURPOSE: Voxel-based morphometry (VBM) studies of people with focal epilepsies revealed gray matter (GM) alterations in brain regions involved in cardiorespiratory regulation, which have been linked to the risk of sudden unexpected death in epilepsy (SUDEP). It remains unclear whether the type and localization of epileptogenic lesions influence the occurrence of such alterations. METHODS: To test the hypothesis that VBM alterations of autonomic network regions are independent of epileptogenic lesions and that they reveal structural underpinnings of SUDEP risk, VBM was performed in 100 people with focal epilepsies without an epileptogenic lesion identifiable on MRI (mean age ± standard deviation = 35 ± 11 years, 56 female). The group was further stratified in high (sample size n = 29) and low risk of SUDEP (n = 71). GM volumes were compared between these two subgroups and to 100 matched controls. RESULTS: People with epilepsy displayed higher GM volume in both amygdalae and parahippocampal gyri and lower GM volume in the cerebellum and occipital (p<.05, familywise error corrected). There were no significant volumetric differences between high and low SUDEP risk subgroups. CONCLUSION: Our findings confirm that autonomic networks are structurally altered in people with focal epilepsy and they question VBM as a suitable method to show structural correlates of the SUDEP risk score.

Value of drug level concentrations of brivaracetam, lacosamide, and perampanel in care of people with epilepsy.

OBJECTIVE: The aim of this study was to determine whether clinical efficacy and reported adverse effects (AEs) of the newer antiseizure medications (ASMs) brivaracetam (BRV), lacosamide (LCM), and perampanel (PER) have been associated with plasma levels of these ASMs. We also investigated whether plasma levels outside the reference range has led to dose adjustments. METHODS: Plasma levels of 300 people with epilepsy (PWE) seen at our tertiary epilepsy center were determined by liquid chromatography-tandem mass spectrometry. PWE received BRV (n = 100), LCM (n = 100), or PER (n = 100), in most cases in polytherapy. Demographic and clinical data were retrospectively analyzed and related to plasma levels. Clinical efficacy of BRV, LCM, or PER was assessed retrospectively by comparing seizure frequency at the time of current blood draw with seizure frequency at the time of first administration. AEs were also recorded and, if reported, compared retrospectively with the time of first administration. RESULTS: No significant associations were found between plasma levels of BRV, LCM, or PER and seizure freedom (BRV, p = 1.000; LCM, p = .243; PER, p = .113) or responder status (BRV, p = .118; LCM, p = .478; PER, p = .069) at presentation. There was also no pattern between plasma levels and the occurrence of AEs. In the majority of cases, drug levels outside the reference ranges have not led to adjustments in the daily doses of BRV (93.5%), LCM (93.9%), or PER (89.1%). SIGNIFICANCE: Plasma levels at a given time point did not allow conclusions to be drawn about seizure control or the occurrence of AEs. Our findings indicate that efficacy and tolerability cannot be predicted based on averaged data from a single plasma measurement due to high interindividual variability. Instead, individual reference values should be established when sufficient clinical data are available, in line with the 2008 International League Against Epilepsy position paper on therapeutic drug monitoring.

Subcortical grey matter volume and asymmetry in the long-term course of Rasmussen's encephalitis.

Rasmussen's encephalitis is characterized by drug-resistant focal seizures and chronic inflammation of one hemisphere leading to progressive loss of hemispheric volume. In this cohort study, we aimed to investigate subcortical grey matter volumes and asymmetries in Rasmussen's encephalitis longitudinally in clinically relevant subgroups. We retrospectively included all T1-weighted MRI scans of all people with Rasmussen's encephalitis who were treated at the University Hospital Bonn between 1995 and 2022 (n = 56, 345 scans, median onset 8 years, 36 female). All cases were classified as type 1 (onset ≤ 6 years) or type 2 (onset > 6 years). Subcortical segmentations were performed using FreeSurfer. Longitudinal trajectories of subcortical volumes and hemispheric ratios (ipsi-/contralesional) were assessed using linear mixed-effect models. Unihemispheric cortical degeneration was accompanied by ipsilesional atrophy of the nucleus accumbens, caudate nucleus, putamen, thalamus and contralesional atrophy of the nucleus accumbens and caudate nucleus both in type 1 (all P ≤ 0.014) and type 2 (all P < 0.001). In type 1, however, contralesional volume increase of the amygdala, hippocampus, pallidum and thalamus was found (all P ≤ 0.013). Both ipsilesional and contralesional subcortical atrophies, like cortical atrophy, are most probably caused by neurodegeneration following chronic neuroinflammation. We speculate that contralesional volume increase in type 1 could be related to either neuroplasticity or ongoing acute neuroinflammation, which needs to be investigated in further studies.

Highly dynamic inflammatory and excitability transcriptional profiles in hippocampal CA1 following status epilepticus.

Transient brain insults including status epilepticus (SE) can initiate a process termed 'epileptogenesis' that results in chronic temporal lobe epilepsy. As a consequence, the entire tri-synaptic circuit of the hippocampus is fundamentally impaired. A key role in epileptogenesis has been attributed to the CA1 region as the last relay station in the hippocampal circuit and as site of aberrant plasticity, e.g. mediated by acquired channelopathies. The transcriptional profiles of the distinct hippocampal neurons are highly dynamic during epileptogenesis. Here, we aimed to elucidate the early SE-elicited mRNA signature changes and the respective upstream regulatory cascades in CA1. RNA sequencing of CA1 was performed in the mouse pilocarpine-induced SE model at multiple time points ranging from 6 to 72 h after the initial insult. Bioinformatics was used to decipher altered gene expression, signalling cascades and their corresponding cell type profiles. Robust transcriptomic changes were detected at 6 h after SE and at subsequent time points during early epileptogenesis. Major differentially expressed mRNAs encoded primarily immediate early and excitability-related gene products, as well as genes encoding immune signalling factors. Binding sites for the transcription factors Nfkb1, Spi1, Irf8, and two Runx family members, were enriched within promoters of differentially expressed genes related to major inflammatory processes, whereas the transcriptional repressors Suz12, Nfe2l2 and Rest were associated with hyperexcitability and GABA / glutamate receptor activity. CA1 quickly responds to SE by inducing transcription of genes linked to inflammation and excitation stress. Transcription factors mediating this transcriptomic switch represent targets for new highly selected, cell type and time window-specific anti-epileptogenic strategies.

Globally altered microstructural properties and network topology in Rasmussen's encephalitis.

Rasmussen's encephalitis is an immune-mediated brain disorder characterised by progressive unilateral cerebral atrophy, neuroinflammation, drug-resistant seizures and cognitive decline. However, volumetric changes and epileptiform EEG activity were also observed in the contralateral hemisphere, raising questions about the aetiology of contralateral involvement. In this study, we aim to investigate alterations of white matter integrity, structural network topology and network efficiency in Rasmussen's encephalitis using diffusion-tensor imaging. Fourteen individuals with Rasmussen's encephalitis (11 female, median onset 6 years, range 4-22, median disease duration at MRI 5 years, range 0-42) and 20 healthy control subjects were included. All subjects underwent T1-weighted structural and diffusion-tensor imaging. Diffusion-tensor images were analysed using the fixel-based analysis framework included in the MRtrix3 toolbox. Fibre density and cross-section served as a quantitative measure for microstructural white matter integrity. T1-weighted structural images were processed using FreeSurfer, subcortical segmentations and cortical parcellations using the Desikan-Killiany atlas served as nodes in a structural network model, edge weights were determined based on streamline count between pairs of nodes and compared using network-based statistics. Global efficiency was used to quantify network integration on an intrahemispheric level. All metrics were compared cross-sectionally between individuals with Rasmussen's encephalitis and healthy control subjects using sex and age as regressors and within the Rasmussen's encephalitis group using linear regression including age at onset and disease duration as independent variables. Relative to healthy control subjects, individuals with Rasmussen's encephalitis showed significantly (family-wise-error-corrected P < 0.05) lower fibre density and cross-section as well as edge weights in intrahemispheric connections within the ipsilesional hemisphere and in interhemispheric connections. Lower edge weights were noted in the contralesional hemisphere and in interhemispheric connections, with the latter being mainly affected within the first 2 years after disease onset. With longer disease duration, fibre density and cross-section significantly (uncorrected P < 0.01) decreased in both hemispheres. In the contralesional corticospinal tract, fibre density and cross-section significantly (uncorrected P < 0.01) increased with disease duration. Intrahemispheric edge weights (uncorrected P < 0.01) and global efficiency significantly increased with disease duration in both hemispheres (ipsilesional r = 0.74, P = 0.001; contralesional r = 0.67, P = 0.012). Early disease onset was significantly (uncorrected P < 0.01) negatively correlated with lower fibre density and cross-section bilaterally. Our results show that the disease process of Rasmussen's encephalitis is not limited to the cortex of the lesioned hemisphere but should be regarded as a network disease affecting white matter across the entire brain and causing degenerative as well as compensatory changes on a network level.

Poor midterm clinical outcomes and a high percentage of unsatisfying results are reported after seizure-related shoulder injuries, especially after posterior proximal humerus fracture-dislocations.

BACKGROUND: Treating seizure-related shoulder injuries is challenging, and an evidence-based consensus to guide clinicians is lacking. The aim of this prospective single-center observational clinical trial was to evaluate the clinical results of a cohort of patients undergoing treatment of seizure-related shoulder injuries, to categorize them according to the lesion's characteristics, with special focus on patients with proximal humerus fracture-dislocations (PHFDs), and to define groups at risk of obtaining unsatisfactory results. We hypothesized that patients with a PHFD, considered the worst-case scenario among these injuries, would report worse clinical results in terms of the quick Disabilities of the Arm, Shoulder, and Hand questionnaire (qDASH) as compared to the other patients. METHODS: Patients referred to a tertiary epilepsy center who have seizure-related shoulder injuries and with a minimum follow-up of 1 year were included. A quality-of-life assessment instrument (EQ-5D-5L), a district-specific patient-reported outcome measure (qDASH), and a pain assessment tool (visual analog scale [VAS]) were used for the clinical outcome evaluation. Subjective satisfaction and fear of new shoulder injuries was also documented. Categorization and subgroup analysis according to the presence and features of selected specific lesions were performed. RESULTS: A total of 111 patients were deemed eligible and 83 were available for follow-up (median age 38 years, 30% females), accounting for a total of 107 injured shoulders. After a median follow-up of 3.9 (1.6-8.2) years, overall moderate clinical results were reported. In addition, 34.1% of the patients reported a VAS score ≥35 mm, indicating moderate to severe pain, and 34.1% a qDASH score ≥40 points, indicating severe disability of an upper limb. These percentages rose to, respectively, 45.5% and 48.5% in the subgroup of patients with PHFDs and to 68.8% and 68.8% in patients experiencing posterior PHFD. Overall, 46.9% of the patients considered themselves unsatisfied with the treatment and 62.5% reported a persistent fear of a new shoulder injury. CONCLUSIONS: Patients with seizure-related shoulder injuries reported only moderate clinical results at their midterm follow-up. Older age, male sex, and absence or discontinuation of antiepileptic drug (AED) treatment were identified as characterizing features of patients with posterior dislocation episodes. In patients with PHFD, a tendency to worse clinical results was observed, with posterior PHFD patients emerging as a definite subgroup at risk of reporting unsatisfying results after treatment.

Distinct neuronal representation of small and large numbers in the human medial temporal lobe.

Whether small numerical quantities are represented by a special subitizing system that is distinct from a large-number estimation system has been debated for over a century. Here we show that two separate neural mechanisms underlie the representation of small and large numbers. We performed single neuron recordings in the medial temporal lobe of neurosurgical patients judging numbers. We found a boundary in neuronal coding around number 4 that correlates with the behavioural transition from subitizing to estimation. In the subitizing range, neurons showed superior tuning selectivity accompanied by suppression effects suggestive of surround inhibition as a selectivity-increasing mechanism. In contrast, tuning selectivity decreased with increasing numbers beyond 4, characterizing a ratio-dependent number estimation system. The two systems with the coding boundary separating them were also indicated using decoding and clustering analyses. The identified small-number subitizing system could be linked to attention and working memory that show comparable capacity limitations.

Report of the ILAE SUDEP Task Force on national recommendations and practices around the world regarding the use of wearable seizure detection devices: A global survey.

Wearable seizure detection devices have the potential to address unmet needs of people with epilepsy. A recently published evidence-based international guideline recommends using such devices for safety indications in patients with tonic-clonic seizures (TCS). Our objective was to map existing guidelines and clinical practices at national level. We conducted a survey of the International League Against Epilepsy (ILAE) chapters regarding national recommendations and practical circumstances for prescribing seizure detection devices, and another survey of physicians in the ILAE constituency anywhere in the world, concerning their views and practices regarding recommendations for and prescription of such devices. Fifty-eight ILAE chapters (response rate 48%) and 157 physicians completed the surveys. More than two-thirds of responding countries do not have standards on wearables for seizure detection, although they indicated availability of such devices. The most often recognized indications were safety and objective seizure quantification. In nearly half of countries, devices are purchased by patients or caregivers, and either lack a uniform reimbursement scheme (41%) or patients pay the full cost for the device (48%). Tonic-clonic seizure frequency, nocturnal seizures, and previous injuries were the main factors that influenced the surveyed physicians to recommend wearable seizure detection devices. Our results document the need to implement international clinical practice guidelines at national level and to consider these when deciding upon reimbursement of seizure detection devices.

An open presurgery MRI dataset of people with epilepsy and focal cortical dysplasia type II.

Automated detection of lesions using artificial intelligence creates new standards in medical imaging. For people with epilepsy, automated detection of focal cortical dysplasias (FCDs) is widely used because subtle FCDs often escape conventional neuroradiological diagnosis. Accurate recognition of FCDs, however, is of outstanding importance for affected people, as surgical resection of the dysplastic cortex is associated with a high chance of postsurgical seizure freedom. Here, we make publicly available a dataset of 85 people affected by epilepsy due to FCD type II and 85 healthy control persons. We publish 3D-T1 and 3D-FLAIR, manually labeled regions of interest, and carefully selected clinical features. The open presurgery MRI dataset may be used to validate existing automated algorithms of FCD detection as well as to create new approaches. Most importantly, it will enable comparability of already existing approaches and support a more widespread use of automated lesion detection tools.

Digital health applications in the self-management of epilepsy-A survey on patients' perspective.

OBJECTIVE: Digital health applications can be prescribed since 2019 in Germany, which is likely to facilitate a broad use of epilepsy self-management applications, possibly directly connected to clinical systems via telematics infrastructures. This article reports on patients' interest in digital support for epilepsy self-management, influencing factors and patients' knowledge about digitization of health care in Germany. METHODS: This work is based on self-reported data from 115 people with epilepsy participating in an anonymous online survey with a total of 54 questions covering several topics, including sociodemographics and epilepsy manifestation, use of technology in general and for treatment support, training programs, affinity for technology, knowledge on the digital infrastructure in Germany, and self-efficacy in dealing with chronic illness. The self-constructed questionnaire uses existing instruments like TA-EG, SES6G, and Hoffmeyer-Zlotnik sociodemographic questionnaire. To analyze the knowledge about digitalization in health care, a combination of self-assessment and knowledge quiz was used. The analysis was performed using descriptive methods and inferential statistics (t-test, reliability analysis, and correlations). RESULTS: Participants were most interested in seizure alerting and documentation with the possibility to share documentation with physicians. The analysis of technology affinity showed medium enthusiasm, with positively perceived consequences being rated higher than the negatively perceived consequences of technology use. Knowledge on national health infrastructures was mediocre and training on this was judged to be essential and desired. Furthermore, a significant correlation was found between interest in use and affinity for technology (enthusiasm for technology [r = 0.29; P = 0.00]) and positively perceived consequences of technology (r = 0.33; P = 0.00). SIGNIFICANCE: Our results underline the high relevance of digital solutions for patients and the importance of individual training opportunities in digital health literacy, thereby enabling patients to decide competently for or against offered digital solutions.