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.

Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry.

Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15N-thymidine. Detection of 15N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo15N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly.

Status epilepticus in patients with glioblastoma: Clinical characteristics, risk factors, and epileptological outcome.

PURPOSE: Epilepsy is a common comorbidity in patients with glioblastoma, however, clinical data on status epilepticus (SE) in these patients is sparse. We aimed to investigate the risk factors associated with the occurrence and adverse outcomes of SE in glioblastoma patients. METHODS: We retrospectively analysed electronic medical records of patients with de-novo glioblastoma treated at our institution between 01/2006 and 01/2020 and collected data on patient, tumour, and SE characteristics. RESULTS: In the final cohort, 292/520 (56.2 %) patients developed seizures, with 48 (9.4 % of the entire cohort and 16.4 % of patients with epilepsy, PWE) experiencing SE at some point during the course of their disease. SE was the first symptom of the tumour in 6 cases (1.2 %) and the first manifestation of epilepsy in 18 PWE (6.2 %). Most SE episodes occurred postoperatively (n = 37, 77.1 %). SE occurrence in PWE was associated with postoperative seizures and drug-resistant epilepsy. Adverse outcome (in-house mortality or admission to palliative care, 10/48 patients, 20.8 %), was independently associated with higher status epilepticus severity score (STESS) and Charlson Comorbidity Index (CCI), but not tumour progression. 32/48 SE patients (66.7 %) were successfully treated with first- and second-line agents, while escalation to third-line agents was successful in 6 (12.5 %) cases. CONCLUSION: Our data suggests a link between the occurrence of SE, postoperative seizures, and drug-resistant epilepsy. Despite the dismal oncological prognosis, SE was successfully treated in 79.2 % of the cases. Higher STESS and CCI were associated with adverse SE outcomes.

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

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

Trends in the neurological emergency room, focusing on persons with seizures.

BACKGROUND AND PURPOSE: Previous studies in neurological emergency rooms (nERs) have reported many non-acute, self-presenting patients, patients with delayed presentation of stroke, and frequent visits of persons with seizures (PWS). The aim of this study was to evaluate trends during the last decade, with special focus on PWS. METHODS: We retrospectively analyzed patients who presented to our specialized nER during the course of 5 months in 2017 and 2019, and included information on admission/referral, hospitalization, discharge diagnosis, and diagnostic tests/treatment in the nER. RESULTS: A total of 2791 patients (46.6% male, mean age 57 ± 21 years) were included. The most common diagnoses were cerebrovascular events (26.3%), headache (14.1%), and seizures (10.5%). Most patients presented with symptoms lasting >48 h (41.3%). The PWS group included the largest proportion of patients presenting within 4.5 h of symptom onset (171/293, 58.4%), whereas only 37.1% of stroke patients presented within this time frame (273/735). Self-presentation was the most common admission pathway (31.1%), followed by emergency service referral (30.4%, including the majority of PWS: 197/293, 67.2%). Despite known diagnosis of epilepsy in 49.2%, PWS more often underwent accessory diagnostic testing including cerebral imaging, compared to the overall cohort (accessory diagnostics 93.9% vs. 85.4%; cerebral imaging 70.1% vs. 64.1%). Electroencephalography in the nER was only performed in 20/111 patients (18.0%) with a first seizure. Nearly half of the patients (46.7%) were discharged home after nER work-up, including most self-presenters (632/869, 72.7%) and headache patients (377/393, 88.3%), as well as 37.2% (109/293) of PWS. CONCLUSION: After 10 years, nER overuse remains a problem. Stroke patients still do not present early enough, whereas PWS, even those with known epilepsy, often seek acute and extensive assessment, indicating gaps in pre-hospital management and possible over-assessment.

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

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

Surgical planning, histopathology findings and postoperative outcome in MR-negative extra-temporal epilepsy using intracranial EEG, functional imaging, magnetoencephalography, neuronavigation and intraoperative MRI.

OBJECTIVE: MRI-negative drug-resistant epilepsy presents a challenge when it comes to surgical planning, and surgical outcome is worse than in cases with an identified lesion. Although increasing implementation of more powerful MRI scanners and artificial intelligence has led to the detection of previously unrecognizable lesions, in some cases even postoperative pathological evaluation of electrographically epileptogenic zones shows no structural alterations. While in temporal lobe epilepsy a standardized resection approach can usually be performed, the surgical management of extra-temporal lesions is always individual. Here we present a strategy for treating patients with extra-temporal MRI-negative epilepsy focus and report our histological findings and patient outcome. METHODS: Patients undergoing epilepsy surgery in the Department of Neurosurgery at the University Hospital Erlangen between 2012 and 2020 were included in the study. Inclusion criteria were: (1) failure to identify a structural lesion on preoperative high-resolution 3 Tesla MRI with a standardized epilepsy protocol and (2) preoperative intracranial EEG (iEEG) diagnostics. RESULTS: We identified 8 patients corresponding to the inclusion criteria. Second look MRI analysis by an experienced neuroradiologist including the most recent analysis algorithm utilized in our clinic revealed a possible lesion in two patients. One of the patients with a clear focal cortical dysplasia (FCD) finding on a second look was excluded from further analysis. Of the other 7 patients, in one patient iEEG was performed with subdural electrodes, whereas the other 6 were evaluated with depth electrodes. MEG was performed preoperatively in all but one patient. An MEG focus was implemented in resection planning in 3 patients. FDG PET was performed in all, but only implemented in one patient. Histopathological evaluation revealed one non-lesional case, 4 cases of FCD and 2 cases with mild developmental malformation. All patients were free from permanent neurological deficits and presented with Engel 1A or 1B outcome on the last follow-up. CONCLUSION: We demonstrate that extra-temporal MRI-negative epilepsy can be treated successfully provided an extensive preoperative planning is performed. The most important diagnostic was stereo-EEG, whereas additional data from MEG was helpful and FDG PET was rarely useful in our cohort.

[Status epilepticus-Detection and treatment in the intensive care unit]. / Status epilepticus ­ Detektion und Behandlung auf der Intensivstation.

Status epilepticus is characterized by persistent or repetitive seizures which, without successful treatment, can lead to neuronal damage, neurological deficits and death of the patient.While status epilepticus with motor symptoms can usually be clinically diagnosed, nonconvulsive status epilepticus is often clinically overlooked due to its ambiguous semiology, so that electroencephalography (EEG) recording is necessary. The treatment of status epilepticus is performed in four treatment steps, whereby a difficult to treat status epilepticus is present from the third step at the latest and intensive medical care of the patient is necessary. Timely initiation of treatment and sufficient dosage of anticonvulsive medication are decisive for the success of treatment. There is little evidence for the "late" stages of treatment. Intensive medical measures pose the risk of complications that worsen the prognosis. Especially in nonconvulsive status epilepticus, the use of anesthetics must be weighed against possible complications of mechanical ventilation.

Attitudes toward persons with epilepsy as friends: Results of a factorial survey.

OBJECTIVE: Discrimination against persons with epilepsy (PWEs) may persist. The aim of this study was to examine whether epilepsy is an obstacle to desired friendship. METHODS: A factorial survey (vignettes), which is less biased by social desirability, was applied to PWEs, their relatives, and lay persons. The vignettes described a person who was varied by the dimensions of age (younger, same age, older), gender (male, female), disease (healthy, mild epilepsy, severe epilepsy [generalized tonic-clonic seizures], diabetes), origin (German, non-German), contact (phone/internet, activities at home, activities outside), frequency of contacts (weekly, monthly), and distance (around the corner, 10 km away). Respondents rated their willingness to befriend the person on a 10-point Likert scale. Multivariate regression determined the contribution of each dimension on the judgment. RESULTS: Participants were 64 PWEs (age = 37.1 ± 14.0 years), 64 relatives of PWEs (age = 45.1 ± 13.6 years), and 98 controls without contact with PWEs (age = 24.4 ± 10.1 years). Controls were less interested in a friendship with a PWE with mild epilepsy (-3.4%) and even more avoided PWEs with severe epilepsy (-11.7%), whereas in PWEs with tonic-clonic seizures, a mild form of epilepsy was actually conducive to friendship (+7.0%). Controls preferred females (+5.0%) and disliked younger people (-12.3%) and contacts via the internet or telephone (-7.3%). PWEs were also less interested in younger people (-5.8%), and relatives of PWEs had a lower preference for friendships with longer distance (-2.3%). SIGNIFICANCE: PWEs still suffer from a risk of social avoidance, and this becomes more evident with generalized motor seizures.

Have attitudes toward epilepsy improved in Germany over the last 50 years?

OBJECTIVE: In Germany, six previous representative surveys on attitudes toward epilepsy (AE) have been conducted between 1967 and 2008 using the four original Caveness questions (CQs) from 1949 to 1980. The aims of this study were (1) to investigate changes in AE over the time span of 50 years, including the current survey in 2018 (2) to investigate the first-time emotional reactions measured with the Scales of Attitudes toward People with Epilepsy (SAPE) (3) to identify predictors of AE. METHODS: A representative face-to-face survey with CQ, in addition with the SAPE scales of Social Distance, Stereotypes, Personal Concerns, and Emotional Reactions was carried out in Germany in 2018. One thousand and twenty-six persons who ever had heard of epilepsy participated. Respondents who answered "don't know" in the CQs were subsequently asked to answer only yes/no. The analysis of trends from 1967 to 2018 was based on the pooled data of the surveys. The four CQs in the 2018 survey were included in the SAPE item pool and an exploratory principal axis factor analysis was performed. General linear models were performed to identify predictors. RESULTS: For all four CQs, the trend of improved AE was significant over the past 50 years. In the 2018 survey, excluding the "don't know" answer option increased the proportion of negative responses for contact of one's own children with a person with epilepsy (PWE) from 6.9% to 11.4% and for the marriage of one's own children with a PWE from 13.9% to 23.8%. When encountering a PWE, 30.1% would feel insecure or uncomfortable and nearly 60% were concerned that the PWE might be injured in case of a seizure. Knowing what to do in case of a seizure, knowing that seizures can be treated successfully, personal contact with a PWE along with younger age, and higher education were found to be the strongest predictors for positive AE identified by multivariate analyses. Exploratory principal axis factor analysis revealed that three of the four CQs items loaded > 0.30 at the factors of Social Distance and Stereotypes of SAPE but none on the factors measuring emotional reactions. SIGNIFICANCE: AE measured by CQs have markedly improved in Germany over the last 50 years. Germany is to our knowledge the only country with such a long-term trend investigation in AE. Negative AE may be underestimated by survey questions with "don't know" answer option. Emotional aspects of attitudes are underexposed resp. neglected in the CQs, which are used worldwide for measuring AE. Additional tools like SAPE can close this gap. The identified predictors may help to derive interventions against negative AE.

Surgical hematoma evacuation of cortical intracerebral hemorrhage ≥10 ml reduces risk of subsequent epilepsy by more than 70%: A retrospective monocenter study.

AIM: The aim of this study was to re-evaluate risk factors for post-ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH. BACKGROUND AND PURPOSE: Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain. METHODS: We retrospectively included patients with spontaneous ICH treated in our hospital in 2006-2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni- and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation. RESULTS: Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow-up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1-132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14-2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33-2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20-2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08-0.84]; p = 0.025). CONCLUSIONS: Post-ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH.

Resection of dominant fusiform gyrus is associated with decline of naming function when temporal lobe epilepsy manifests after the age of five: A voxel-based lesion-symptom mapping study.

OBJECTIVE: To determine patients' characteristics and regions in the temporal lobe where resections lead to a decline in picture naming. METHODS: 311 patients with left hemispheric dominance for language were included who underwent epilepsy surgery at the Epilepsy Center of Erlangen and whose picture naming scores (Boston Naming Test, BNT) were available preoperatively and 6-months postoperatively. Surgical lesions were mapped to an averaged template based on preoperative and postoperative MRI using voxel-based lesion-symptom mapping (VBLSM). Postoperative brain shifts were corrected. The relationship between lesioned brain areas and the presence of a postoperative naming decline was examined voxel-wise while controlling for effects of overall lesion size at first in the total cohort and then restricted to temporal lobe resections. RESULTS: In VBLSM in the total sample, a decline in BNT score was significantly related to left temporal surgery. When only considering patients with left temporal lobe resections (n = 121), 40 (33.1%) significantly worsened in BNT postoperatively. VBLSM including all patients with left temporal resections generated no significant results within the temporal lobe. However, naming decline of patients with epilepsy onset after 5 years of age was significantly associated with resections in the left inferior temporal (extent of BNT decline range: 10.8- 14.4%) and fusiform gyrus (decline range: 12.1-18.4%). SIGNIFICANCE: Resections in the posterior part of the dominant fusiform and inferior temporal gyrus was associated with a risk of deterioration in naming performance at six months after surgery in patients with epilepsy onset after 5 years of age but not with earlier epilepsy onset.

Antiseizure medication and perceived "fair" cost allocation: A factorial survey among neurologists, persons with epilepsy, their relatives, and a control group.

OBJECTIVE: Because resources are limited in modern health care systems, the decision on the allocation of expensive drugs can be supported by a public consent. This study examines how various factors influence subjectively perceived "fair" pricing of antiseizure medication (ASM) among four groups including physicians, persons with epilepsy (PWEs), their relatives, and a control group. METHODS: We conducted a factorial survey. Vignettes featured a fictional PWE receiving a fictional ASM. The characteristics of the fictional PWE, ASM, and epilepsy varied. Participants were asked to assess the subjectively appropriate annual cost of ASM treatment per year for each scenario. RESULTS: Fifty-seven PWEs (mean age (SD) 37.7 ± 12.3, 45.6% female), 44 relatives (age 48.4 ± 15.7, 51.1% female), 46 neurologists (age 37.1 ± 9.6, 65.2% female), and 47 persons in the control group (age 31.2 ± 11.2, 68.1% female) completed the questionnaire. The amount of money that respondents were willing to spend for ASM treatment was higher than currently needed in Germany and increased with disease severity among all groups. All groups except for PWEs accepted higher costs of a drug with better seizure control. Physicians and the control group, but not PWEs and their relatives, tended to do so also for minor or no side effects. Physicians reduced the costs for unemployed patients and the control group spent less money for older patients. SIGNIFICANCE: ASM effectiveness appears to justify higher costs. However, the control group attributed less money to older PWEs and physicians allocated fewer drug costs to unemployed PWEs.

Quantitative EEG may predict weaning failure in ventilated patients on the neurological intensive care unit.

Neurocritical patients suffer from a substantial risk of extubation failure. The aim of this prospective study was to analyze if quantitative EEG (qEEG) monitoring is able to predict successful extubation in these patients. We analyzed EEG-monitoring for at least six hours before extubation in patients receiving mechanical ventilation (MV) on our neurological intensive care unit (NICU) between November 2017 and May 2019. Patients were divided in 2 groups: patients with successful extubation (SE) versus patients with complications after MV withdrawal (failed extubation; FE), including reintubation, need for non-invasive ventilation (NIV) or death. Bipolar six channel EEG was applied. Unselected raw EEG signal underwent automated artefact rejection and Short Time Fast Fourier Transformation. The following relative proportions of global EEG spectrum were analyzed: relative beta (RB), alpha (RA), theta (RT), delta (RD) as well as the alpha delta ratio (ADR). Coefficient of variation (CV) was calculated as a measure of fluctuations in the different power bands. Mann-Whitney U test and logistic regression were applied to analyze group differences. 52 patients were included (26 male, mean age 65 ± 17 years, diagnosis: 40% seizures/status epilepticus, 37% ischemia, 13% intracranial hemorrhage, 10% others). Successful extubation was possible in 40 patients (77%), reintubation was necessary in 6 patients (12%), 5 patients (10%) required NIV, one patient died. In contrast to FE patients, SE patients showed more stable EEG power values (lower CV) considering all EEG channels (RB: p < 0.0005; RA: p = 0.045; RT: p = 0.045) with RB as an independent predictor of weaning success in logistic regression (p = 0.004). The proportion of the EEG frequency bands (RB, RA RT, RD) of the entire EEG power spectrum was not significantly different between SE and FE patients. Higher fluctuations in qEEG frequency bands, reflecting greater fluctuation in alertness, during the hours before cessation of MV were associated with a higher rate of complications after extubation in this cohort. The stability of qEEG power values may represent a non-invasive, examiner-independent parameter to facilitate weaning assessment in neurocritical patients.

Psychogenic nonepileptic seizures: clinical characteristics and outcome.

BACKGROUND: Clinical characteristics, outpatient situation, and outcome in patients with psychogenic nonepileptic seizures (PNES) remain to be elucidated. METHODS: Patients diagnosed with PNES after video-electroencephalography (EEG) monitoring (VEM) 03/2000-01/2016 at the Erlangen Epilepsy Center were surveyed between June 2016 and February 2017. Primary outcome was PNES cessation defined as no PNES episodes within > = 12 months prior to the interview. Secondary outcome variables included quality of life (QoL) and dependency. Sensitivity analysis included patients with proven PNES during VEM without comorbid epilepsy. RESULTS: Ninety-nine patients were included (median age 38 (interquartile range (IQR 29-52)) years; 68 (69%) females, follow-up 4 (IQR 2.1-7.7) years). Twenty-eight (28%) patients suffered from comorbid epilepsy. Twenty-five (25%) patients reported PNES cessation. Older age at symptom onset (odds ratio (OR) related to PNES cessation: 0.95 (95% CI 0.90-0.99)), comorbid epilepsy (OR 0.16 (95% CI 0.03-0.83)), anxiety disorder (OR 0.15 (95% CI 0.04-0.61)), and tongue biting (OR 0.22 (95% CI 0.03-0.91)) remained independently associated with ongoing PNES activity after adjustment. Sensitivity analysis (n = 63) revealed depressive disorder (OR 0.03 (95% CI 0.003-0.34)) instead of anxiety as independent predictor, while this seemed relevant only in patients older than 26 years at onset (OR 0.04 (95% CI 0.002-0.78) versus OR 0.21 (95% CI 0.02-1.84) in patients  younger than 26 years). PNES cessation was associated with increased median QoL (8 (IQR 7-9) versus 5.5 (IQR 4-7); p < .001) and an increased frequency of financial independency (14 (56%) versus 21 (28%); p = .01). CONCLUSIONS: We found poor outcomes in PNES especially in older patients at onset with comorbid depressive disorder. Comorbid epilepsy also seems to be a major risk factor of ongoing PNES activity, which in turn affects patients' daily living.

Attitudes toward epilepsy assessed by the SAPE questionnaire in Germany - Comparison of its psychometric properties and results in a web-based vs. face-to-face survey.

OBJECTIVE: The aims of this study were (1) to investigate psychometric properties of a new questionnaire (SAPE, Scales of the Attitudes toward People with Epilepsy) that assesses attitudes toward people with epilepsy (PWE) (2) to compare the effects of mode of survey administration (web-based vs. face-to-face) on attitudes, and (3) to identify predictors of attitudes. METHODS: A face-to-face and a web-based survey were performed in Germany. Weighting factors were used to achieve representative samples of the German population. Reliability and validity of the 6 scales of the SAPE (social distance, stereotypes, personal concerns, and emotional reactions differentiated by fear, anger, and pity) were evaluated and compared for both surveys. Epilepsy knowledge was also assessed. General linear models were performed to investigate predictors of attitudes toward PWE including the type of survey. RESULTS: In total, 1001 participants of the web-based survey and 1026 participants of face-to-face survey were included. Psychometric analyses indicated satisfactory reliability and validity of the scales and differed only slightly between modes of survey. In both surveys, fears and concerns were more pronounced than stereotypes and social distance. However, mean values of two scales were slightly or moderately higher in the face-to-face survey indicating more negative attitudes toward PWE (p < 0.001). Fewer participants of the face-to-face survey reported personal experience with PWE, claiming to know what to do in case of a seizure and claiming to know that seizures can be treated successfully (p < 0.001). These variables proved to be important predictors of positive attitudes toward PWE, besides demographic factors (e.g. age < 65, female gender). When controlling for them, the differences remained significant only for the scales Social Distance (moderately) and Fear (slightly). SIGNIFICANCE: In total, psychometric analyses show that web-based surveys using the SAPE may be an alternative to face-to-face surveys to assess attitudes toward PWE. This applies also to the scales Social Distance and Emotional Reactions that allow comparisons with other diseases, e.g. psychiatric disorders. Most scales differ only slightly between survey modes, except social distance. This indicates that single components of attitudes toward PWE may be dependent on the mode of survey or different characteristics of respondents.

Trends in resource utilization and cost of illness in patients with active epilepsy in Germany from 2003 to 2020.

OBJECTIVE: This study was undertaken to calculate epilepsy-related direct, indirect, and total costs in adult patients with active epilepsy (ongoing unprovoked seizures) in Germany and to analyze cost components and dynamics compared to previous studies from 2003, 2008, and 2013. This analysis was part of the Epi2020 study. METHODS: Direct and indirect costs related to epilepsy were calculated with a multicenter survey using an established and validated questionnaire with a bottom-up design and human capital approach over a 3-month period in late 2020. Epilepsy-specific costs in the German health care sector from 2003, 2008, and 2013 were corrected for inflation to allow for a valid comparison. RESULTS: Data on the disease-specific costs for 253 patients in 2020 were analyzed. The mean total costs were calculated at €5551 (±€5805, median = €2611, range = €274-€21 667) per 3 months, comprising mean direct costs of €1861 (±€1905, median = €1276, range = €327-€13 158) and mean indirect costs of €3690 (±€5298, median = €0, range = €0-€11 925). The main direct cost components were hospitalization (42.4%), antiseizure medication (42.2%), and outpatient care (6.2%). Productivity losses due to early retirement (53.6%), part-time work or unemployment (30.8%), and seizure-related off-days (15.6%) were the main reasons for indirect costs. However, compared to 2013, there was no significant increase of direct costs (-10.0%), and indirect costs significantly increased (p < .028, +35.1%), resulting in a significant increase in total epilepsy-related costs (p < .047, +20.2%). Compared to the 2013 study population, a significant increase of cost of illness could be observed (p = .047). SIGNIFICANCE: The present study shows that disease-related costs in adult patients with active epilepsy increased from 2013 to 2020. As direct costs have remained constant, this increase is attributable to an increase in indirect costs. These findings highlight the impact of productivity loss caused by early retirement, unemployment, working time reduction, and seizure-related days off.

Satisfaction with and reliability of in-hospital video-EEG monitoring systems in epilepsy diagnosis - A German multicenter experience.

OBJECTIVE: To analyze satisfaction with and reliability of video-electroencephalography-monitoring systems (VEMS) in epilepsy diagnostics. METHODS: A survey was conducted between December 2020 and January 2021 among German epilepsy centers using well-established customer satisfaction (CS) and quality assurance metrics. RESULTS: Among 16 participating centers, CS with VEMS was low, with only 13% of customers actively recommending their system. Only 50% of users were satisfied with the overall performance of their VEMS, and a low 18% were satisfied with the manufacturer's customer service. User interface, software stability, lack of regular updates, and missing customer-oriented improvements were reported as frequent problems jeopardizing diagnosis in approximately every 10th patient. The greatest potential for improvement was identified for software and hardware stability as well as customer service. CONCLUSION: Satisfaction with VEMS and their customer service was low, and diagnostics were regularly affected by software or hardware errors. Even if this can be partly explained by the technical complexity of VEMS, there is an urgent need for improvements with regard to the reliability and durability of system components as well as signal synchrony and data management. SIGNIFICANCE: This analysis highlights low consumer satisfaction of users with VEMS and uncovers frequent problems and potential for improvement.

Pre- and Postictal Changes in the Innate Immune System: Cause or Effect?

INTRODUCTION: Recent studies have shown that inflammatory processes might play a role in epileptogenesis. Their role in ictogenesis is much less clear. The aim of this study was to investigate peri-ictal changes of the innate immune system by analyzing changes of immune cells, as well as pro- and anti-inflammatory cytokines. METHODS: Patients with active epilepsy admitted for video-EEG monitoring for presurgical evaluation were included. Blood was sampled every 20 min for 5 h on 3 consecutive days until a seizure occurred. After a seizure, additional samples were drawn immediately, as well as 1 and 24 h later. To analyze the different populations of peripheral blood mononuclear cells, all samples underwent FACS for CD3, CD4, CD8, CD56, CD14, CD16, and CD19. For cytokine analysis, we used a custom bead-based multiplex immunoassay for IFN-γ, IL-1ß, IL-1RA, IL-4, IL-6, IL-10, IL-12, IL-17, MCP-1, MIP-1α, and TNFα. RESULTS: Fourteen patients with focal seizures during the sampling period were included. Natural killer (NK) cells showed a negative correlation (ρ = -0.3362, p = 0.0195) before seizure onset and an immediate increase to 1.95-fold afterward. T helper (TH) and B cells decreased by 2 and 8%, respectively, in the immediate postictal interval. Nonclassical and intermediate monocytes decreased not until 1 day after the seizures, and cytotoxic T (TC) cells showed a long-lasting postictal increase by 4%. IL-10 and MCP-1 increased significantly after seizures, and IL-12 decreased in the postictal phase. DISCUSSION/CONCLUSION: Our study argues for a role of the innate immune system in the pre- and postictal phases. NK cells might be involved in preictal changes or be altered as an epiphenomenon in the immediate preictal interval.

Alpha power decrease in quantitative EEG detects development of cerebral infarction after subarachnoid hemorrhage early.

OBJECTIVE: In subarachnoid hemorrhage (SAH), transcranial Doppler/color-coded-duplex sonography (TCD/TCCS) is used to detect delayed cerebral ischemia (DCI). In previous studies, quantitative electroencephalography (qEEG) also predicted imminent DCI. This study aimed to compare and analyse the ability of qEEG and TCD/TCCS to early identify patients who will develop later manifest cerebral infarction. METHODS: We analysed cohorts of two previous qEEG studies. Continuous six-channel-EEG with artefact rejection and a detrending procedure was applied. Alpha power decline of ≥ 40% for ≥ 5 hours compared to a 6-hour-baseline was defined as significant EEG event. Median reduction and duration of alpha power decrease in each channel was determined. Vasospasm was diagnosed by TCD/TCCS, identifying the maximum frequency and days of vasospasm in each territory. RESULTS: 34 patients were included (17 male, mean age 56 ± 11 years, Hunt and Hess grade: I-V, cerebral infarction: 9). Maximum frequencies in TCD/TCCS and alpha power reduction in qEEG were correlated (r = 0.43; p = 0.015). Patients with and without infarction significantly differed in qEEG parameters (maximum alpha power decrease: 78% vs 64%, p = 0.019; summed hours of alpha power decline: 236 hours vs 39 hours, p = 0.006) but showed no significant differences in TCD/TCCS parameters. CONCLUSIONS: There was a moderate correlation of TCD/TCCS frequencies and qEEG alpha power reduction but only qEEG differentiated between patients with and without cerebral infarction. SIGNIFICANCE: qEEG represents a non-invasive, continuous tool to identify patients at risk of cerebral infarction.