Status epilepticus in patients with brain tumors and metastases: A multicenter cohort study of 208 patients and literature review.

OBJECTIVE: Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population. METHODS: This retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017. RESULTS: The 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult-type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1-57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1-46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post-SE at discharge (p < 0.001). Mortality at discharge was 17.3% (n = 36), with the greatest occurring in patients with metastatic disease (26.4%, p = 0.031) and those that met the radiological criteria for tumor progression (25%, p < 0.001). Long-term mortality at one year (65.9%) was highest in those diagnosed with adult-type diffuse gliomas (68.1%) and metastatic disease (79.2%). Refractory status epilepticus cases showed lower survival rates than non-refractory SE patients (log-rank p = 0.02) and those with signs of tumor progression (log-rank p = 0.001). CONCLUSIONS: SE occurrence contributed to a decline in functional status in all cases, regardless of tumor type, tumor progression status, and SE refractoriness, while long-term mortality was increased in those with malignant tumor entities, tumor progressions, and refractory SE. SE prevention may preserve functional status and improve survival in individuals with brain tumors.

First seizure in elderly patients: Need to treat? Evidence from a retrospective study.

BACKGROUND: The risk of seizure recurrence after a first unprovoked epileptic seizure is reported to be approximately 40%. Little is known about the recurrence risk after a first seizure in elderly patients, who may be at higher risk due to an increased rate of structural lesions, encephalopathy, subcortical arteriosclerotic encephalopathy or brain atrophy. METHODS: In a retrospective approach, the recurrence rate in 304 patients aged 60 years and above who presented with a first seizure between 2004 and 2017 was analyzed. Hierarchical Cox regression was used to investigate the impact of EEG and neuroimaging results, age or the prescription of anti-seizure medication (ASM) on seizure recurrence. RESULTS: Seizure recurrence rates were 24.5% and 34.4% after one and two years, respectively. Anti-seizure medication was started in 87.8% of patients, in 28.8% despite the absence of clear epileptogenic lesions on neuroimaging or epileptiform potentials in the EEG. Medical treatment significantly reduced the risk of recurrence (hazard ratio = 0.47). Epileptiform potentials in the EEG, epileptogenic lesions in neuroimaging and age had no significant effect on seizure recurrence. Age and the presence of neurodegenerative and psychiatric comorbidities showed a significant association with ASM prescription. CONCLUSIONS: The present data show a strong protective effect of ASM on seizure recurrence in patients above the age of 60, even in the absence of pathologic neuroimaging or EEG results needed for the diagnosis of epilepsy. Treatment with ASM therefore seems beneficial for reducing the recurrence risk in elderly patients. The lack of a significant association between seizure recurrence and epileptogenic lesions might be related to other confounding factors like encephalopathy, subcortical arteriosclerotic encephalopathy, neurodegenerative diseases or brain atrophy.

Brivaracetam and topiramate serum levels during pregnancy and delivery: a case report and a review of literature.

BACKGROUND: An increasing use of newer antiseizure medication (ASM) such as SV2A ligand brivaracetam is observed. However, data on newer antiseizure medication and therapeutic drug monitoring during pregnancy is scarce. METHODS: Therapeutic drug monitoring of brivaracetam (BRV) and topiramate (TPM) serum levels were performed during pregnancy, delivery and in the umbilical cord blood at delivery in a 34-year-old female patient with severe drug-resistant epilepsy. RESULTS: During pregnancy, the serum levels of brivaracetam and topiramate remained stable. At 39th week of pregnancy, the patient gave birth to a healthy daughter. 1.5 h after the last ASM intake, the penetration rate measured in umbilical cord blood was 45% lower for BRV and 35% lower for TPM. CONCLUSIONS: While the pharmacokinetics of topiramate are well known and its use during pregnancy should only be undertaken under special circumstances, there have been few studies on newer ASM in pregnancy such as brivaracetam. Based on our results and other case reports of BRV use during pregnancy, further studies are necessary to confirm its pharmacokinetics and safety during pregnancy.

First epileptic seizure and quality of life - A prospective study.

OBJECTIVE: Impaired QoL and depression are common in patients with chronic epilepsies; however, data on the impact of a first seizure on QoL are sparse. According to the current ILAE-definition of epilepsy, patients may be diagnosed with epilepsy immediately after the first seizure, if EEG and/or imaging findings are abnormal. Patients with normal findings in imaging and EEG are not diagnosed as having epilepsy. We investigated QoL in patients after a first seizure with and without a consecutive diagnosis of epilepsy to detect differences between groups within the first year after seizure. METHODS: We examined patients (n = 152) after a first epileptic seizure and six and 12 months thereafter using demographic, clinical and QoL-related questionnaire data (Short Form-36 Health Survey (SF-36), Quality of Life in Epilepsy Inventory-31 (QOLIE-31), Beck's depression inventory II (BDI-II)). RESULTS: Patients diagnosed with epilepsy after the first seizure showed a tendency of reduced mental health-related QoL six (p =.098) and 12 months (p =.092) after the first seizure compared to patients who were not diagnosed with epilepsy, but were diagnosed as having had a single first seizure. There were no significant differences between the two groups in physical health-related QoL. Multiple regression analyses showed that especially depressive symptoms explained 22.0 - 48.7 % of the variance in mental health-related QoL six (p <.001) and 12 months (p <.001) after the first seizure. Physical health-related QoL was especially predicted by age (p <.001), group (p =.002) and recurrent seizures (p = < 0.001). In PWE, there was a statistical trend with improving QOLIE-31 overall scores from six to 12 months (p =.086). CONCLUSION: Our results suggest that QoL may be impaired in patients diagnosed with epilepsy early, immediately after the onset of disease. Early follow-up monitoring from the beginning of patient career is important for possible interventions and to improve patients' daily life in the long term.

Morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative patients with first unprovoked seizure.

OBJECTIVE: The aim of the study was to evaluate the benefits of morphometric magnetic resonance imaging (MRI) postprocessing in patients presenting with a first seizure and negative MRI results and to investigate these findings in the context of the clinical and electroencephalographic data, seizure recurrence rates, and epilepsy diagnosis in these patients. METHODS: We retrospectively reviewed 97 MRI scans of patients with first unprovoked epileptic seizure and no evidence of epileptogenic lesion on clinical routine MRI. Morphometric Analysis Program (MAP; v2018), automated postprocessing software, was used to identify subtle, potentially epileptogenic lesions in the three-dimensional T1-weighted MRI data. The resulting probability maps were examined together with the conventional MRI images by a reviewer who remained blinded to the patients' clinical and electroencephalographical data. Clinical data were prospectively collected between February 2018 and May 2023. RESULTS: Among the apparently MRI-negative patients, a total of 18 of 97 (18.6%) showed cortical changes suggestive of focal cortical dysplasia. Within the population with positive MAP findings (MAP+), seizure recurrence rates were 61.1% and 66.7% at 1 and 2 years after the first unprovoked seizure, respectively. Conversely, patients with negative MAP findings (MAP-) had lower seizure recurrence rates of 27.8% and 34.2% at 1 and 2 years after the first unprovoked seizure, respectively. Patients with MAP+ findings were significantly more likely to be diagnosed with epilepsy than those patients with MAP- findings (χ2 [1, n = 97] = 14.820, p < .001, odds ratio = 21.371, 95% CI = 2.710-168.531) during a mean follow-up time of 22.51 months (SD = 16.7 months, range = 1-61 months). SIGNIFICANCE: MRI postprocessing can be a valuable tool for detecting subtle epileptogenic lesions in patients with a first seizure and negative MRI results. Patients with first seizure and MAP+ findings had high seizure recurrence rates, meeting the criteria for beginning epilepsy.

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.

Undiagnosed obstructive sleep apnea syndrome as a treatable cause of new-onset sleepiness in some post-COVID patients.

BACKGROUND AND PURPOSE: Infection with COVID-19 can lead to persistent sequelae, such as fatigue, daytime sleepiness or disturbed sleep, that can remain for more than 12 weeks and that are summarized as post-COVID syndrome. The causes remain unclear. The present study investigated the presence of sleep disorders in patients with post-COVID syndrome using polysomnography. METHODS: Thirty-four patients with post-COVID syndrome and new-onset fatigue and sleepiness after a SARS-CoV2 infection underwent polysomnography in accordance with American Association of Sleep Medicine (AASM) standards as part of their clinical workup. Analysis was performed visually based on AASM criteria (scoring manual version 2.6, 2020). RESULTS: Polysomnography revealed a sleep efficiency of <80% in 50% of patients and a mean respiratory disturbance index (RDI) of 9.9 ± 15.4/h. Excluding central apneas, 12 patients (35%) had an RDI of ≥5/h, pointing to obstructive sleep apnea syndrome (OSAS; AASM 2014). Patients with a high RDI were significantly older (p = 0.01) and showed a trend towards a higher body mass index (p = 0.08) than patients with a normal RDI but had no other risk factors for OSAS. Six patients agreed to long-term treatment of their OSAS and all reported discontinuation of daytime symptoms. CONCLUSIONS: Post-COVID symptoms such as daytime sleepiness, fatigue and memory and concentration problems may in part be a result of reduced sleep efficiency and sleep apnea in a relevant percentage of patients. This possibly treatable cause of the symptoms should be kept in mind in patients presenting with post-COVID syndrome.

Verbal memory depends on structural hippocampal subfield volume.

Objective: To investigate correlates in hippocampal subfield volume and verbal and visual memory function in patients with temporal lobe epilepsy (TLE), mild amnestic cognitive impairment (MCI) and heathy participants (HP). Methods: 50 right-handed participants were included in this study; 11 patients with temporal lobe epilepsy (TLE), 18 patients with mild amnestic cognitive impairment (MCI) and 21 healthy participants (HP). Verbal memory performance was evaluated via the verbal memory test (VLMT) and visual memory performance via the diagnosticum for cerebral damage (DCM). Hippocampal subfield volumes of T1-weighted Magnetic Resonance Imaging (MRI) scans were computed with FreeSurfer version 7.1. Stepwise correlation analyses were performed between the left hippocampal subfield volumes and learning, free recall, consolidation and recognition performance scores of the VLMT as well as between right hippocampal subfield volumes and visual memory performance. Results: The volume of the left subicular complex was highly correlated to learning performance (ß = 0.284; p = 0.042) and free recall performance in the VLMT (ß = 0.434; p = 0.001). The volume of the left CA3 subfield showed a significant correlation to the consolidation performance in the VLMT (ß = 0.378; p = 0.006) and recognition performance in the VLMT (ß = 0.290; p = 0.037). There was no significant correlation identified between the right hippocampal subfields and the visual memory performance. Conclusion: The results of this study show verbal memory correlates with hippocampal subfields and support the role of left subiculum and left CA2/CA3 in verbal memory performance.

Driving regulations for epilepsy in Europe.

BACKGROUND: Across Europe, there are differences regarding driving restrictions for patients with epilepsies and seizures. In the light of increasing mobility, knowledge about those different regulations is of high importance for counseling patients, and physicians. METHODS: A structured online survey was sent to the official representatives of the different European ILAE chapters, asking for the local driving restrictions for patients with epilepsies, first seizures, syncopes, and psychogenic non-epileptic seizures. RESULTS: The survey was sent to 38 chapters or representatives of 47 European Countries. 33 chapters answered. The majority of countries require 1 year of seizure-freedom for the ability to drive (Group 1, former categories A, B, B + E, F, G. H, K, L, and P; driving license which authorizes its holder to drive vehicle classes categories of the motor vehicle), usually with the need to continue antiseizure medication (ASM). Some countries have much stricter regulations before allowing for driving. Legal regulations after a first unprovoked seizure differ between 6 months for Group 1 license holders in most European countries, and one year in Luxembourg and Malta. In Serbia, there is no legal regulation for this special situation. The situation after a first seizure is even more complex for Group 2 license holders (former categories C1, C1+E, C, C + E, D1, D1+E, D, D + E). CONCLUSION: Knowledge of the different recommendations of the individual European countries is of high relevance in the counseling of epilepsy patients. Europe-wide regulations, e.g. following the IBE-recommendations are needed to facilitate the patients' situation.

Effect of transcutaneous vagus nerve stimulation on stress-reactive neuroendocrine measures in a sample of persons with temporal lobe epilepsy.

OBJECTIVE: Dysregulation of stress-reactive neuroendocrine measures, as well as subjective stress, have been found to worsen epilepsy. Transcutaneous vagus nerve stimulation (tVNS) is a relatively new treatment option for epilepsy. We were interested in its effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) as well as subjective stress and tiredness in patients with temporal lobe epilepsy (TLE). METHODS: Twenty patients (age 44 ± 11 years, 13 women) were enrolled in the study. They were free of seizures for more than 1 year. All took part in two sessions with 4 h of stimulation (tVNS vs. sham) in a randomized order. Saliva samples and subjective stress and tiredness levels were measured at five time points each session (before and after stimulation and three time points every hour in between). Data were analyzed using repeated measures analysis of variance as well as paired t-tests. RESULTS: There was a dampened salivary cortisol (sCort) decrease during tVNS (time × condition effect: F[2.38, 38.15] = 6.50, P = 0.002, partial η2 = 0.29). Furthermore, we detected a dampened increase in salivary flow rate during tVNS (time × condition effect: F[3.28, 55.67] = 2.82, P = 0.043, partial η2 = 0.14). There was neither a difference in overall sCort or salivary alpha-amylase (sAA) levels nor in subjective stress or tiredness levels between conditions. sAA levels at the last measurement point were slightly higher during tVNS (t(19) = 2.26, P = 0.035, d = 0.51), but this effect failed to reach significance when controlled for multiple comparisons. SIGNIFICANCE: Our results partially support that tVNS influences the regulation of stress-reactive neuroendocrine systems (namely the HPA axis and ANS) in epilepsy. More research with larger samples is needed on the difference between short-term and repeated long-term stimulation.

Effect of the revised definition of epilepsy on treatment decisions and seizure recurrence after a first epileptic seizure.

BACKGROUND: Studies on risk factors for epilepsy and seizure recurrence after a first seizure are usually based on the old definition of epilepsy with the need for two unprovoked seizures. The current definition of epilepsy allows diagnosis and treatment of epilepsy after a first seizure if the recurrence risk is >60%. We evaluate treatment decisions, seizure recurrence and risk factors for epilepsy related to the application of the new definition of epilepsy. METHODS: Data of 629 patients with a first seizure were analyzed to investigate changes of treatment decisions and seizure recurrence after the revised definition of epilepsy. We used binary logistic regression to investigate the impact of multiple factors influencing seizure recurrence like electroencephalogram (EEG) and magnetic resonance imaging (MRI) results and administration of antiseizure medication (ASM). RESULTS: The proportion of patients receiving ASM significantly increased from 70.4% to 80.5% (p = 0.015) following the new epilepsy definition, without any significant changes in the recurrence rate (40.8% vs. 45.5% after 2 years, p > 0.05). The presence of interictal epileptiform discharges (IED) in the EEG increased (OR = 1.98) and administration of ASM decreased (OR = 0.43) recurrence rates significantly. CONCLUSIONS: The new definition of epilepsy was associated with increased application of ASM, but not with reduced recurrence rates. The study confirms the presence of IED as a strong risk factor for seizure recurrence and the protective effect of ASM. The influence of imaging findings, which have a strong impact on the new definition of epilepsy, could not be confirmed.

Morphometric correlates in patients with functional seizures with and without comorbid epilepsy.

OBJECTIVE: Functional seizures (FS) or psychogenic, non-epileptic seizures (PNES) are episodic alterations of behaviour with similar semiology to epileptic seizures but which are not caused by epileptic brain activity. Epilepsy patients show a high risk in developing FS; therefore, the purpose of this study is to examine morphometric correlates in patients with FS as well as in epilepsy patients with FS by comparing them separately to healthy controls (HC). METHODS: Twenty-one clinical three-dimensional (3D) T1-magnetic resonance imaging (MRI) scans of patients with FS (FS group) and 15 patients with FS and epilepsy (EFS group) were retrospectively compared with one control group of 21 age- and gender-matched HC. Two separate general linear model analyses were conducted via FreeSurfer version 6.0. RESULTS: The study population consisted of 21 FS patients (66.7% females, n = 14) with a median age at the time of the scan of 24 years (range 17-44 years); 15 EFS patients (80% females, n = 12) with a median age at the time of the scan of 27 years (range 16-43 years); and 21 healthy subjects (66.7% females, n = 14) with a median age at the time of the scan of 24 years (range 19-38 years). Both patient groups showed an increased Cth in the right prefrontal lobe: in the FS group in the right superior frontal, rostral middle frontal gyri and the right orbitofrontal cortex and, in the EFS group, in the right superior frontal gyrus and the right orbitofrontal cortex. Decreases in Cth were present in the right lateral occipital lobe in the FS group, while also in both hemispheres in the EFS group, namely the left paracentral, superior frontal, caudal middle frontal, lateral occipital and right superior frontal gyri. Neither group showed changes in curvature. CONCLUSION: These results suggest alterations in regions of emotional processing and executive control in patients with FS regardless of the presence of epilepsy.

Prospective, longitudinal, multicenter study on the provision of information regarding sudden unexpected death in epilepsy to adults with epilepsy.

OBJECTIVE: Despite increased awareness of the serious epilepsy complication sudden unexpected death in epilepsy (SUDEP), a substantial population of people with epilepsy (PWE) remain poorly informed. Physicians indicate concern that SUDEP information may adversely affect patients' health and quality of life. We examined SUDEP awareness and the immediate and long-term effects of providing SUDEP information to PWE. METHODS: Baseline knowledge and behaviors among PWE and behavioral adjustments following the provision of SUDEP information were evaluated in a prospective, multicenter survey using the following validated scales: Neurological Disorders Depression Inventory for Epilepsy for depression symptoms, the EuroQoL five-dimension scale for health-related quality of life (HRQoL), a visual analog scale for overall health, the revised Epilepsy Stigma Scale for perceived stigma, and the Seizure Worry Scale for seizure-related worries. The prospective study collected data through semiquantitative interviews before (baseline), immediately after, and 3 months after the provision of SUDEP information. RESULTS: In total, 236 participants (mean age = 39.3 years, range = 18-77 years, 51.7% women) were enrolled, and 205 (86.9%) completed long-term, 3-month follow-up. One patient died from SUDEP before follow-up. No worsening symptoms from baseline to 3-month follow-up were observed on any scale. At baseline, 27.5% of participants were aware of SUDEP. More than 85% of participants were satisfied with receiving SUDEP information. Three quarters of participants were not concerned by the information, and >80% of participants recommended the provision of SUDEP information to all PWE. Although most patients reported no behavioral adjustments, 24.8% reported strong behavioral adjustments at 3-month follow-up. SIGNIFICANCE: The provision of SUDEP information has no adverse effects on overall health, HRQoL, depressive symptoms, stigma, or seizure worry among PWE, who appreciate receiving information. SUDEP information provision might improve compliance among PWE and reduce but not eliminate the increased mortality risk.

Temporal encephaloceles and coexisting epileptogenic lesions.

OBJECTIVE: This study was performed to identify coexisting structural lesions in patients with epilepsy and known temporal encephaloceles (TEs). METHODS: Forty-seven structural magnetic resonance imaging (MRI) scans of patients with epilepsy and radiologically diagnosed TEs were retrospectively reviewed visually and using an automated postprocessing software, the Morphometric Analysis Program v2018 (MAP18), to depict additional subtle, potentially epileptogenic lesions in the 3D T1-weighted MRI data. All imaging findings were evaluated in the context of clinical and electroencephalographical findings. RESULTS: The study population consisted of 47 epilepsy patients (38.3% female, n = 18). The median age at the time of the scan was 40 years (range 12-81 years). Twenty-one out of 47 MRI scans (44.7%) showed coexisting lesions in the initial MRI evaluation; in 38.3% (n = 18) of patients, those lesions were considered probably epileptogenic. After postprocessing, probable epileptogenic lesions were identified in 53.2% (n = 25) of patients. Malformations of cortical development had initially been reported in 17.0% (n = 8) of patients with TEs, which increased to 38.3% (n = 18) after postprocessing. TEs and other epileptogenic lesions were considered equally epileptogenic in 21.3% (n = 10) of the cases in the initial MR reports and 25.5% (n = 12) of the cases after postprocessing. SIGNIFICANCE: Temporal encephaloceles are a potential cause of MRI-negative temporal lobe epilepsy. According to our data, TEs can occur with other lesions, suggesting that increased awareness is also required in patients with lesional epilepsy. TEs may not always be epileptogenic; hence, their occurrence with other structural pathologies may influence the presurgical evaluation and surgical approach. Finally, TEs can be associated with malformations of cortical development, which may indicate a common developmental etiology of those lesions.

Diffusion magnetic resonance imaging connectome features are predictive of functional lateralization of semantic processing in the anterior temporal lobes.

Assessment of regional language lateralization is crucial in many scenarios, but not all populations are suited for its evaluation via task-functional magnetic resonance imaging (fMRI). In this study, the utility of structural connectome features for the classification of language lateralization in the anterior temporal lobes (ATLs) was investigated. Laterality indices for semantic processing in the ATL were computed from task-fMRI in 1038 subjects from the Human Connectome Project who were labeled as stronger rightward lateralized (RL) or stronger leftward to bilaterally lateralized (LL) in a data-driven approach. Data of unrelated subjects (n = 432) were used for further analyses. Structural connectomes were generated from diffusion-MRI tractography, and graph theoretical metrics (node degree, betweenness centrality) were computed. A neural network (NN) and a random forest (RF) classifier were trained on these metrics to classify subjects as RL or LL. After classification, comparisons of network measures were conducted via permutation testing. Degree-based classifiers produced significant above-chance predictions both during cross-validation (NN: AUC-ROC[CI] = 0.68[0.64-0.73], accuracy[CI] = 68.34%[63-73.2%]; RF: AUC-ROC[CI] = 0.7[0.66-0.73], accuracy[CI] = 64.81%[60.9-68.5]) and testing (NN: AUC-ROC[CI] = 0.69[0.53-0.84], accuracy[CI] = 68.09[53.2-80.9]; RF: AUC-ROC[CI] = 0.68[0.53-0.84], accuracy[CI] = 68.09[55.3-80.9]). Comparison of network metrics revealed small effects of increased node degree within the right posterior middle temporal gyrus (pMTG) in subjects with RL, while degree was decreased in the right posterior cingulate cortex (PCC). Above-chance predictions of functional language lateralization in the ATL are possible based on diffusion-MRI connectomes alone. Increased degree within the right pMTG as a right-sided homologue of a known semantic hub, and decreased hubness of the right PCC may form a structural basis for rightward-lateralized semantic processing.

Impact of COVID-19 pandemic on physical and mental health status and care of adults with epilepsy in Germany.

BACKGROUND: To mitigate the potential consequences of the coronavirus disease 2019 (COVID-19) pandemic on public life, the German Federal Government and Ministry of Health enacted a strict lockdown protocol on March 16, 2020. This study aimed to evaluate the impact of the COVID-19 pandemic on physical and mental health status and the supply of medical care and medications for people with epilepsy (PWE) in Germany. METHODS: The Epi2020 study was a large, multicenter study focused on different healthcare aspects of adults with epilepsy. In addition to clinical and demographic characteristics, patients were asked to answer a questionnaire on the impact of the first wave of the COVID-19 pandemic between March and May 2020. Furthermore, the population-based number of epilepsy-related admissions in Hessen was evaluated for the January-June periods of 2017-2020 to detect pandemic-related changes. RESULTS: During the first wave of the pandemic, 41.6% of PWE reported a negative impact on their mental health, while only a minority reported worsening of their seizure situation. Mental and physical health were significantly more negatively affected in women than men with epilepsy and in PWE without regular employment. Moreover, difficulties in ensuring the supply of sanitary products (25.8%) and antiseizure medications (ASMs; 19.9%) affected PWE during the first lockdown; no significant difference regarding these impacts between men and women or between people with and without employment was observed. The number of epilepsy-related admissions decreased significantly during the first wave. CONCLUSIONS: This analysis provides an overview of the general and medical care of epilepsy patients during the COVID-19 pandemic. PWE in our cohort frequently reported psychosocial distress during the first wave of the pandemic, with significant adverse effects on mental and physical health. Women and people without permanent jobs especially reported distress due to the pandemic. The COVID-19 pandemic has added to the mental health burden and barriers to accessing medication and medical services, as self-reported by patients and verified in population-based data on hospital admissions. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00022024. Registered October 2, 2020, http://www.drks.de/DRKS00022024.

Psychophysiological interaction analysis for the detection of stimulus-specific networks in reflex epilepsy.

We report detailed functional MRI (fMRI) analyses in a patient with reflex seizures elicited by driving along a specific rural crossroad or by watching a video thereof. Semiology consisted of epigastric aura, followed by a sensory seizure of the left hand and sporadic automotor seizures. The right amygdala-region (rh-amygdala) was surgically and electroclinically confirmed as the epileptogenic zone. Presurgical task-fMRI was performed, during which videos of the driving along that specific crossroad (IC), of another crossroad (NC) or noise were presented. Independent component analysis was conducted, and one component was used to aid in selection of a seed region within the rh-amygdala for subsequent psychophysiological interaction analysis (PPI). Here, the following regions showed stronger connectivity with the rh-amygdala seed during the IC condition compared to NC: right > left visual cortex, bilateral insulae, and right secondary somatosensory cortex (S2), potentially explaining epigastric aura and left somatosensory seizure semiology. Contralateral analyses did not reproduce these results. Overall, the ictogenic stimulus elicited enhanced connectivity of the epileptogenic rh-amygdala with visual cortex and further regions of potential seizure spread (S2, insula) as a putative mechanism of ictogenesis. Our results highlight the potential of PPI in the analysis of stimulus-dependent networks in patients with reflex epilepsies to gain insight into seizure generation.

Non-invasive vagus nerve stimulation in epilepsy patients enhances cooperative behavior in the prisoner's dilemma task.

The vagus nerve constitutes a key link between the autonomic and the central nervous system. Previous studies provide evidence for the impact of vagal activity on distinct cognitive processes including functions related to social cognition. Recent studies in animals and humans show that vagus nerve stimulation is associated with enhanced reward-seeking and dopamine-release in the brain. Social interaction recruits similar brain circuits to reward processing. We hypothesize that vagus nerve stimulation (VNS) boosts rewarding aspects of social behavior and compare the impact of transcutaneous VNS (tVNS) and sham stimulation on social interaction in 19 epilepsy patients in a double-blind pseudo-randomized study with cross-over design. Using a well-established paradigm, i.e., the prisoner's dilemma, we investigate effects of stimulation on cooperative behavior, as well as interactions of stimulation effects with patient characteristics. A repeated-measures ANOVA and a linear mixed-effects model provide converging evidence that tVNS boosts cooperation. Post-hoc correlations reveal that this effect varies as a function of neuroticism, a personality trait linked to the dopaminergic system. Behavioral modeling indicates that tVNS induces a behavioral starting bias towards cooperation, which is independent of the decision process. This study provides evidence for the causal influence of vagus nerve activity on social interaction.

Persistent knowledge gaps between 2005 and 2020 in women with epilepsy: Comparison of multicenter studies from Germany.

OBJECTIVE: Epilepsy is a chronic condition that can affect patients of all ages. Women with epilepsy (WWE) require access to specific counseling and information regarding issues related to contraception, pregnancy, and hormonal effects on seizure control and bone mineral density. This study investigated the knowledge among WWE regarding their condition, and whether epilepsy-specific knowledge has improved over the last 15 years. METHODS: A total of 280 WWE aged 18 to 82 years participated in this multicenter, questionnaire-based study. The study was conducted at four epilepsy centers in Germany, between October 2020 and December 2020. Sociodemographic and epilepsy-specific data for participating women were analyzed and compared with the results of a similar survey performed in 2003-2005 among 365 WWE in Germany. RESULTS: The questionnaire-based survey revealed considerable knowledge deficits without significant improvements over the last 15 years, particularly among those with less education and with regards to information on the more pronounced effects of epilepsy in older WWE (>50 years), including interactions with menopause and osteoporosis. In WWE ≤29 years, a significant increase in the knowledge score was observed in 2020 compared with this age group in 2005 (mean 7.42 vs. 6.5, p = .036). Mothers frequently reported epilepsy-related concerns regarding childrearing, particularly of seizures scaring their child and the need to rely on other people. CONCLUSION: WWE continue to demonstrate inadequate epilepsy-related knowledge. Despite increasing information availability and the aspiration toward better awareness among medical professionals, overall knowledge has not increased sufficiently compared with the levels observed in recent studies.