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Background: Activated clotting time (ACT) measurements are frequently used to monitor unfractionated heparin activity during noncardiac arterial procedures (NCAP). Accuracy of ACT-guided heparinization is mandatory to prevent heparin under and overdosing, thereby minimizing thrombo-embolic complications (TECs) and bleeding risk. The main objective of this study was to investigate accuracy of ACT to monitor heparin activity during NCAP using the Hemostasis Management System Plus (HMS) with high-range (HR) cartridges. ACT values were compared with anti-Xa measurements, regarded as the standard test to measure active heparin., Methods: This was a single-center, prospective, observational cohort study. Perioperative blood samples of patients undergoing NCAP between December 2022 and September 2023 were used to perform bedside ACT measurements and anti-Xa assays in the clinical laboratory. Primary outcome was the association between ACT and anti-Xa measurements. TEC, mortality, and bleeding complications within 30 days postoperatively or during primary admission were also scored., Results: 196 pairs of ACT and anti-Xa measurements were performed in 34 patients. Strong correlation was observed between anti-Xa and ACT measurements (Pearson's correlation coefficient = 0.84, 95% CI = 0.79-0.87, P < 0.001). Apart from anti-Xa, no additional variables were associated with ACT in multivariate linear regression analyses (regression coefficient β = 36.7, 95% CI = 33.3-40.1, P < 0.001). Bleeding complications occurred in 29% of the patients, while both TEC and mortality were observed in one patient., Conclusions: Strong correlation and an independent association were observed between heparin activity measured by anti-Xa and ACT using the HMS Plus., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Outside of the work reported in this paper, H.M. Hamer has served on the scientific advisory boards of Arvelle, Bial, Corlieve, Eisai, GW, Novartis, Sandoz, UCB Pharma and Zogenix. He has been part of the speakers’ bureaus of or received unrestricted grants from Amgen, Ad-Tech, Alnylam, Bracco, Desitin, Eisai, GW, Nihon Kohden, Novartis, Pfizer, and UCB Pharma. The remaining authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

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., Competing Interests: Conflicts of interest All authors declare no conflicts of interest related to this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest Tamara M. Müller, Rüdiger Hopfengärtner, Stephan Rampp, Johannes Lang, Jenny Stritzelberger, Caroline Reindl, Maximilian I. Sprügel, Müjgan Dogan Onugoren, Iris Muehlen, Joji B. Kuramatsu, Stefan Schwab: report no disclosures. Stephanie Gollwitzer reports personal fees from Desitin, Eisai, UCB, outside the submitted work. Dominik Madžar reports grants from UCB Pharma and BayerVitalGmbH, outside submitted work. Hagen B. Huttner reports grants from Novartis, grants and personal fees from Bayer AG, grants and personal fees from Daiichi Sankyo, grants and personal fees from Medtronic, grants and personal fees from Portola Pharmaceuticals, outside the submitted work. Hajo M. Hamer: reports personal fees from UCB, Desitin, Eisai, GW, Novartis, IQWiG, Hexal, facetoface, grants from Amgen, Ad-Tech, Bracco, Pfizer, Micromed, Nihon Kohden, personal fees from Arvelle, outside the submitted work., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Chronic kidney disease (CKD) promotes development of cardiac abnormalities and is highly prevalent in patients with heart failure, particularly in those with preserved ejection fraction. CKD is associated with endothelial dysfunction, however, whether CKD can induce impairment of endothelium-to-cardiomyocyte crosstalk leading to impairment of cardiomyocyte function is not known. The sodium-glucose co-transporter 2 inhibitor, empagliflozin, reduced cardiovascular events in diabetic patients with or without CKD, suggesting its potential as a new treatment for heart failure with preserved ejection fraction. We hypothesized that uremic serum from patients with CKD would impair endothelial control of cardiomyocyte relaxation and contraction, and that empagliflozin would protect against this effect. Using a co-culture system of human cardiac microvascular endothelial cells with adult rat ventricular cardiomyocytes to measure cardiomyocyte relaxation and contraction, we showed that serum from patients with CKD impaired endothelial enhancement of cardiomyocyte function which was rescued by empagliflozin. Exposure to uremic serum reduced human cardiac microvascular endothelial cell nitric oxide bioavailability, and increased mitochondrial reactive oxygen species and 3-nitrotyrosine levels, indicating nitric oxide scavenging by reactive oxygen species. Empagliflozin attenuated uremic serum-induced generation of endothelial mitochondrial reactive oxygen species, leading to restoration of nitric oxide production and endothelium-mediated enhancement of nitric oxide levels in cardiomyocytes, an effect largely independent of sodium-hydrogen exchanger-1. Thus, empagliflozin restores the beneficial effect of cardiac microvascular endothelial cells on cardiomyocyte function by reducing mitochondrial oxidative damage, leading to reduced reactive oxygen species accumulation and increased endothelial nitric oxide bioavailability., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: The present study validates the results of automated hippocampal subfield segmentation with histopathology in epilepsy patients undergoing epilepsy surgery., Methods: We performed an automated hippocampal subfield segmentation on presurgical three-dimensional, T1-weighted magnetization Prepared Rapid Acquisition of Gradient Echoes Magnetic Resonance Imaging (MRI) data of 25 patients with unilateral mesial temporal lobe epilepsy due to hippocampal sclerosis (HS), using Freesurfer Version 6.0. The resulting volumes of cornu ammonis (CA) subfields CA1, CA2/3, CA4 and the dentate gyrus (DG) were compared to the histopathological cell count., Results: We found a significant correlation between histopathology in subregion CA2 and automated segmentation of subregion CA1 (p = 0.0062), CA2/3 (p = 0.004), CA4 (p = 0.0062) and the DG (p = 0.0054), between histopathology in CA3 and automated segmentation of CA1 (p = 0.0132), CA2/3 (p = 0.0004), CA4 (p = 0.0032) and the DG (p = 0.0037), as well as between histopathology in the DG and automated segmentation of CA1 (p = 0.0115), CA2/3 (p < 0.0001), CA4 (p < 0.0001) and the DG (p = 0.0001). The histopathological finding of HS type 1 could correctly be classified in all cases on MRI., Significance: The present study shows significant correlations between histopathological evaluation and results of the automated segmentation of the hippocampus, thereby validating the automated segmentation method. As the differential involvement of different hippocampal subfields may be associated with clinical parameters and the outcome after epilepsy surgery, the automated segmentation is also promising for prognostic purposes., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: To evaluate psychosocial long-term outcome in patients diagnosed with psychogenic nonepileptic seizures (PNES) and to predict outcome of PNES, economic status, and quality of life (QoL) at follow-up., Methods: Patients diagnosed with PNES in the video-EEG-monitoring unit at our Epilepsy center between 2002-2016 were contacted by phone 1-16 years after communicating the diagnosis. Patients underwent a structured interview asking for current PNES status, psychosocial situation (economic status, marital status, setting of living, driving), depression, and QoL., Results: Of 70 PNES patients without comorbid epilepsy (age: 41.1 ± 13.5 years; 74 % female, follow-up: 5.2 ± 4.2 years), 23 patients (33 %) reported to be free of PNES during the last 12 months. Patients with cessation of PNES were younger at PNES onset (p < .01) and diagnosis (p < .01) and had a higher education (p < .05). At follow-up, the proportion of economically active patients only increased in individuals with cessation of PNES (p < .001) while an increased number of patients with persisting PNES relied on governmental support (p < .001). Cessation of PNES was associated with better mood (p < .01) and QoL (p < .001). In multiple regression models, cessation of PNES was only predicted by younger age at onset, while good economic outcome was determined by younger age and good economic status at diagnosis and cessation of PNES at follow-up. Good QoL at follow-up was predicted by low depressive symptoms, freedom of PNES, and economic activity at follow-up., Conclusion: Long-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and QoL., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Current trials on adjunctive treatment with antiseizure drugs often do not reveal results which are relevant for clinical practice., Method: Therefore, an interdisciplinary group of German experts discussed a new framework for future antiseizure drug (ASD) trials in adults. This group included members of the executive board of the German Society of Epileptology, of the German institutes for health technology assessment (HTA), of patient organizations and of drug manufacturers. Agreement was reached by consensus decision making after intensive discussion of the findings of a narrative review of the current literature., Results: The group jointly recommends that ASD trials in adults should be based on and include relevant patient groups, e.g. elderly patients and patients with relevant co-morbidities, should adopt a study duration of at least 12 months, should avoid placebo arms, should include active comparators of clinical relevance, may be designed as open label trials with blinded outcome measurements, should focus on patient relevant outcomes that reflect the impact of benefits and harms of treatments on daily living, such as seizure freedom and seizure severity as well as retention rate, functional outcomes and quality of life as compound measures, and should avoid arbitrary and non-sensitive primary endpoints such as dichotomized changes in seizure frequency., Conclusions: This paper focused on improved head-to-head trials on adjunctive treatment with antiseizure drugs. The group welcomes any further work and discussion to enhance future studies which can be applied to the entire spectrum of potentially meaningful study populations and outcomes., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: New antiepileptic drugs (AEDs) are increasingly applied in second-line therapy of status epilepticus (SE). In our study, we analyzed the impact of the choice of second-line AEDs on the course and prognosis of SE., Methods: This retrospective single- center study used data of an 8 year cohort of SE in adults from 2007 to 2014. Based on the year of market introduction with a cutoff at 1990, we classified AEDs as traditional or new. Prescription pattern associated differences in prognosis were measured through univariate and multivariable analysis of 3 endpoints: occurrence of refractory SE (RSE), functional outcome in survivors to discharge (good: mRS at discharge <3 or identical to admission mRS; otherwise poor), and in-hospital mortality., Results: From 362 SE episodes during the study period, 222 episodes were included into the study, among those 150 episodes treated with new and 72 with traditional AEDs. Use of new AEDs increased during the study period. After adjustment for confounders, treatment with new AEDs was on the one hand associated with higher rate of RSE occurrence (OR 1.95, 95 % CI 1.05-3.62, p = 0.03), but, on the other hand, also with better functional outcome at discharge (OR 2.64, 95 % CI 1.16-6.00, p = 0.02), while it was not an independent predictor of in- hospital mortality (OR 0.88, 95 % CI 0.33-2.33, p = 0.80)., Conclusion: Our observation that new AEDs may be associated with a higher rate of RSE development and relatively better functional outcome when adjusted for the premorbid mRS needs confirmation in prospective studies., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To identify factors correlating with poorer quality of life (QoL) in children and adolescents with epilepsy and regarding QoL and depression of their caregivers in Germany., Method: A cross-sectional multicenter study on QoL and depression was performed in two representative German states (Hessen and Schleswig-Holstein). Variance analysis, linear regression, and bivariate correlation were used to identify correlating factors for poorer QoL and symptoms of depression., Results: Data from 489 children and adolescents (mean age 10.4 ± 4.2 years, range 0.5-17.8; 54.0% male) and their caregivers were collected. We identified missing seizure freedom (p = 0.046), concomitant diseases (p = 0.007), hospitalization (p = 0.049), recent status epilepticus (p = 0.035), living in a nursing home or with foster parents (p = 0.049), and relevant degree of disability (p = 0.007) to correlate with poorer QoL in children and adolescents with epilepsy. Poorer QoL of caregivers was associated with longer disease duration (p = 0.004), non-idiopathic (mainly structural-metabolic) epilepsy (p = 0.003), ongoing seizures (p = 0.003), concomitant diseases (p = 0.003), relevant disability (p = 0.003), or status epilepticus (p = 0.003) as well as with unemployment of the primary caretaker (p = 0.010). Symptoms of depression of caregivers were associated with non-idiopathic epilepsy (p = 0.003), concomitant diseases (p = 0.003), missing seizure freedom (p = 0.007), status epilepticus (p = 0.004), or a relevant disability (p = 0.004) of their ward. A poorer QoL value of the children and adolescents correlated with a poorer QoL value of the caregivers (p < 0.001)., Conclusions: Epilepsy shows a considerable impact on QoL and symptoms of depression. Early and effective therapy should focus on reduction of seizure frequency and the probability for developing status epilepticus. Furthermore, comprehensive care should pay attention at comorbidities, consequences of disability and dependency on others., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to identify the C11-oxy C 19 and C11-oxy C 21 steroids in male and female neonate plasma. At birth, the most abundant C11-oxy steroids detected in neonatal plasma were 11β-hydroxyandrostenedione, ∼13 nM, and 11-ketoprogesterone, ∼23 nM. C11-oxy C 19 steroids were higher than C 19 steroids in neonatal plasma, 22.2 nM vs 5.4 nM. The inclusion of C11-oxy C 19 and C 21 steroid reference ranges in routine steroid analyses will assist the characterization of disorders associated with impaired steroidogenic enzyme expression and the identification of potential biomarkers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Epilepsy surgery for focal cortical dysplasia type II (FCD II) offers good chances for seizure freedom, but remains a challenge with respect to lesion detection, defining the epileptogenic zone and the optimal resection strategy. Integrating results from magnetic source imaging from magnetoencephalography (MEG) with magnetic resonance imaging (MRI) including MRI postprocessing may be useful for optimizing these goals., Methods: We here present data from 21 adult FCD II patients, investigated during a 10 year period and evaluated including magnetic source imaging. 16 patients had epilepsy surgery, i.e. histopathologically verified FCD II, and a long follow up. We present our analysis of epileptogenic zones including MEG in relation to structural data according to MRI data and relate these results to surgical outcomes., Results: FCD II in our cohort was characterized by high MEG yield and localization accuracy and MEG showed impact on surgical success-rates. MEG source localizations were detected in 95.2% of patients and were as close as 12.3 ± 8,1 mm to the MRI-lesion. After a mean follow up of >3 years, we saw >80% Engel I outcomes, with more favourable outcomes when the MEG source was completely resected (Fishers exact test 0,033)., Conclusion: We argue for a high value of conducting a combined MEG-MRI approach in the presurgical workup and the resection strategy in patients with FCD II related epilepsy.

Purpose: The incidence of epilepsy in older adults is growing, as does the incidence of comorbidities. Therefore, when it comes to epilepsy surgery in medically intractable epilepsy, age is often seen as a limiting factor. To investigate the outcome after epilepsy surgery in a population of older adults, we compared the benefit for patients aged 50-59 years with those aged 60 years and older in respect of efficacy and safety., Method: Patients aged ≥50 years with medically intractable epilepsy who underwent epilepsy surgery from 1990 to 2013 were selected from the database of a German epilepsy center. All of them received a standardised and detailed presurgical diagnostic evaluation. Follow-up included at least four scheduled visits with EEG, MRI and neuropsychological testing. Outcome was assessed using the Engel outcome scale., Results: 79 patients aged between 50 and 67 years were followed-up for a median of 4.7 years (2-16 years). 68% of patients were free of disabling seizures (Engel class I, ≥60 years: 75%) and 58% were seizure-free (Engel class IA, ≥60 years: 70%). 90% of our patients suffered from temporal lobe epilepsy (TLE), 9% from frontal lobe epilepsy (FLE) and one occipital lobe epilepsy (OLE). After surgery, 9% discontinued or tapered their medication. Permanent surgical complications occurred in 10% of cases and transient neurological deficits were seen in 11%. Older patients had a higher risk for postoperative hygroma (≥60 years 15%; <60 years 8%) and were more prone to postoperative memory deficits (≥60 years 45%), especially after resection of the dominant temporal lobe. Verbal and figural memory testing did not differ significantly between the groups., Conclusions: The results support the view that in selected older patients, epilepsy surgery shows equal or even higher success rates as compared to younger patients. However, patients of older age may be at greater risk for postoperative hygroma and memory deficits, especially after dominant temporal lobe resections., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Several scoring tools have been developed for the prognostication of outcome after status epilepticus (SE). In this study, we compared the performances of STESS (Status Epilepticus Severity Score), mSTESS (modified STESS), EMSE-EAL (Epidemiology-based Mortality Score in Status Epilepticus- Etiology, Age, Level of Consciousness) and END-IT (Encephalitis-NCSE-Diazepam resistance-Image abnormalities-Tracheal intubation) in predicting in-hospital mortality after SE., Method: Data collected retrospectively from a cohort of 287 patients with SE were used to calculate STESS, mSTESS, EMSE-EAL, and END-IT scores. The differences between the scores' performances were determined by means of area under the ROC curve (AUC) comparisons and McNemar testing., Results: The in-hospital mortality rate was 11.8%. The AUC of STESS (0.628; 95% confidence interval (CI), 0.529-0.727) was similar to that of mSTESS (0.620; 95% CI, 0.510-0.731), EMSE-EAL (0.556; 95% CI, 0.446-0.665), and END-IT (0.659; 95% CI, 0.550-0.768; p > .05 for each comparison) in predicting in-hospital mortality. STESS with a cutoff of 3 was found to have lowest specificity and number of correctly classified episodes. EMSE-EAL with a cutoff at 40 had highest specificity and showed a trend towards more correctly classified episodes while sensitivity tended to be low. END-IT with a cutoff of 3 had the most balanced sensitivity-specificity ratio., Conclusions: EMSE-EAL is as easy to calculate as STESS and tended towards higher diagnostic accuracy. Adding information on premorbid functional status to STESS did not enhance outcome prediction. END-IT was not superior to other scores in prediction of in-hospital mortality despite including information of diagnostic work-up and response to initial treatment., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Focal cortical dysplasia (FCD) is one important cause of drug-resistant epilepsy potentially curable by epilepsy surgery. We investigated the options of using neuronavigation and intraoperative magnetic-resonance tomographical imaging (MRI) to avoid residual epileptogenic tissue during resection of patients with FCD II to improve seizure outcome., Methods: Altogether, 24 patients with FCD II diagnosed by MRI (16 female, 8 male; mean age 34 ± 10 years) suffered from drug-resistant electroclinical and focal epilepsy for a mean of 20.7 ± 5 years. Surgery was performed with preoperative stereoelectroencephalography (in 15 patients), neuronavigation, and intraoperative 1.5T-iopMRI in all 24 investigated patients., Results: In 75% of patients (18/24), a complete resection was performed. In 89% (16/18) of completely resected patients, we documented an Engel I seizure outcome after a mean follow-up of 42 months. All incompletely resected patients had a worse outcome (Engel II-III, P < 0.0002). Patients with FCD IIB had also significant better seizure outcome compared with patients diagnosed as having FCD IIA (82% vs. 28%, P < 0.02). In 46% (11/24) of patients, intraoperative second-look surgeries due to residual lesions detected during the intraoperative MRI were performed. In these 11 patients, there were significant more completely seizure free patients (73% vs. 38% Engel IA), compared with 13 patients who finished surgery after the first intraoperative MRI (P < 0.05)., Conclusions: Excellent seizure outcome after surgery of patients with FCD II positively correlated with the amount of resection, histologic subtype, and the use of intraoperative MRI, especially when intraoperative second-look surgeries were performed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Super-refractory status epilepticus (SRSE) represents a challenging medical condition with high morbidity and mortality. In this study, we aimed to establish variables related to SRSE development and outcome., Methods: We retrospectively screened our databases for refractory SE (RSE) and SRSE episodes between January 2001 and January 2015. Baseline demographics, SE characteristics, and variables reflecting the clinical course were compared in order to identify factors independently associated with SRSE occurrence. Within the SRSE cohort, predictors of in-hospital mortality as well as good functional outcome in survivors to discharge were established through univariate and multivariable analyses., Results: A total of 131 episodes were included, among those 46 (35.1%) meeting the criteria of SRSE. Comparison of RSE and SRSE episodes revealed a lower premorbid mRS score (odds ratio (OR) per mRS point, 0.769; p=0.039) and non-convulsive SE (NCSE) in coma (OR, 4.216; p=0.008) as independent predictors of SRSE. SRSE in-hospital mortality was associated with age (OR, 1.091 per increasing year; p=0.020) and worse premorbid functional status (OR, 1.938 per mRS point; p=0.044). Good functional outcome in survivors was independently related to shorter SRSE duration (OR, 0.714 per day; p=0.038)., Conclusion: Better premorbid functional status and NCSE in coma as worst seizure type indicate a role of acute underlying etiologies in the development of SRSE. In-hospital mortality in SRSE is determined by nonmodifiable factors, while functional outcome in survivors depends on seizure duration underscoring the need of achieving rapid seizure termination., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Studying the muscle protein synthetic response to food intake in elderly is important, as it aids the development of interventions to combat sarcopenia. Although sarcopenic elderly are the target group for many of these nutritional interventions, no studies have assessed basal or post-prandial muscle protein synthesis rates in this population., Objective: To assess the basal and post-prandial muscle protein synthesis rates between healthy and sarcopenic older men., Design: A total of 15 healthy (69 ± 1 y) and 15 sarcopenic (81 ± 1 y) older men ingested a leucine-enriched whey protein nutritional supplement containing 21 g of protein, 9 g of carbohydrate, and 3 g of fat. Stable isotope methodology combined with frequent collection of blood and muscle samples was applied to assess basal and post-prandial muscle protein fractional synthetic rates. Handgrip strength, muscle mass, and gait speed were assessed to identify sarcopenia, according to international criteria., Results: Basal mixed muscle protein fractional synthetic rates (FSR) averaged 0.040 ± 0.005 and 0.032 ± 0.003%/h (mean ± SEM) in the sarcopenic and healthy group, respectively (P = 0.14). Following protein ingestion, FSR increased significantly to 0.055 ± 0.004 and 0.053 ± 0.004%/h in the post-prandial period in the sarcopenic (P = 0.003) and healthy groups (P < 0.001), respectively, with no differences between groups (P = 0.45). Furthermore, no differences were observed between groups in muscle protein synthesis rates during the early (0.058 ± 0.007 vs 0.060 ± 0.008%/h, sarcopenic vs healthy, respectively) and late (0.052 ± 0.004 vs 0.048 ± 0.003%/h) stages of the post-prandial period (P = 0.93 and P = 0.34, respectively)., Conclusions: Basal muscle protein synthesis rates are not lower in sarcopenic older men compared to healthy older men. The ingestion of 21 g of a leucine-enriched whey protein effectively increases muscle protein synthesis rates in both sarcopenic and healthy older men. Public trial registry number: NTR3047., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

According to current diagnosis criteria, first seizures constitute beginning epilepsy when they carry recurrence risks of ≥60% over the next 10 years. This is frequently the case and warrants AED treatment. Evidence argues against deferring treatment when provoking factors such as sleep deprivation are reported. There are several characteristics of first seizures which markedly increase recurrence risk but not clearly beyond 60%. This includes status epilepticus or seizure flurries at first manifestation or focal semiology indicating focal epilepsy. In this situation, there are still various medical, social and individual aspects supporting early initiation of AED. Modern AED allow this safely and at low dosages., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: In this study, we use a novel automated method for localization and quantitative comparison of magnetoencephalographic (MEG) delta activity in patients with and without recurrent seizures after epilepsy surgery as well as healthy controls., Methods: We identified the generators of delta activity by source location in frequency domain between 1 and 4 Hz in spontaneous MEG data. Comparison with healthy control subjects by z-transform emphasized relative changes of activation in patients. The individual results were compared to spike localizations and statistical group analysis was performed. Additionally, MEG results were compared to 1-4 Hz activity in invasive EEG (iEEG) in two patients, in whom this data was available., Results: Patients with recurrent seizures exhibited significantly increased focal MEG delta activity both in comparison to healthy controls and seizure free patients. This slow activity showed a correlation to interictal epileptic activity and was not explained by consequences of the resection alone. In two patients with iEEG, iEEG analysis was concordant with the MEG findings., Significance: The quantity of delta activity could be used as a diagnostic marker for recurrent seizures. The close relation to epileptic spike localizations and the resection volume of patients with successful second surgery imply involvement in seizure recurrence. This initial evidence suggests a potential application in the planning of second epilepsy surgery.

Objective: Various complex techniques for depth electrode insertion in refractory epilepsy using preoperative imaging have been investigated. We evaluated a simple, accurate, cost-effective, and timesaving method using intraoperative magnetic resonance imaging (MRI)., Methods: A neuronavigation-guided insertion tube attached to bone facilitated the placement of stereotactic percutaneous drill holes, bolt implantation, and frameless stereotactic insertion of depth electrodes. Image registration was carried out by head coil fiducials with trajectory planning and intraoperative electrode correction., Results: In 6 patients with refractory epilepsy (3 women and 3 men; mean age, 30.0 years; range, 20-37 years), 58 depth electrodes (9-11 per patient) were placed. The mean length of the inserted electrodes was 37.3 mm ± 8.8 (mean ± SD) (range, 22.1-84.4 mm). The overall target point accuracy was 3.2 mm ± 2.2 (range, 0-8.6 mm), which was significantly different from the overall entry point accuracy of 1.4 mm ± 1.2 (P < 0.0001). All electrodes functioned perfectly, enabling high-quality stereo-electroencephalography recordings over a period of 7.3 days ± 0.5 (range, 7-8 days). The mean implantation time for 9-11 electrodes per patient was 115 minutes ± 36.3 (range, 75-160 minutes; 12 minutes for 1 electrode on average) including the intraoperative MRI (T1 three-dimensional magnetization-prepared rapid acquisition gradient echo, T2, and diffusion tensor imaging). There was no hemorrhage, infection, or neurologic deficit related to the procedure., Conclusions: Our frameless technique of depth electrode insertion using intraoperative MRI guidance is an accurate, reliable, cost-effective, and timesaving method for stereo-electroencephalography., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Various brain stimulation techniques are in use to treat epilepsy. These methods usually require surgical implantation procedures. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive technique to stimulate the left auricular branch of the vagus nerve at the ear conch., Objective: We performed a randomized, double-blind controlled trial (cMPsE02) to assess efficacy and safety of tVNS vs. control stimulation in patients with drug-resistant epilepsy., Methods: Primary objective was to demonstrate superiority of add-on therapy with tVNS (stimulation frequency 25 Hz, n = 39) versus active control (1 Hz, n = 37) in reducing seizure frequency over 20 weeks. Secondary objectives comprised reduction in seizure frequency from baseline to end of treatment, subgroup analyses and safety evaluation., Results: Treatment adherence was 84% in the 1 Hz group and 88% in the 25 Hz group, respectively. Stimulation intensity significantly differed between the 1 Hz group (1.02 ± 0.83 mA) and the 25 Hz group (0.50 ± 0.47 mA; p = 0.006). Mean seizure reduction per 28 days at end of treatment was -2.9% in the 1 Hz group and 23.4% in the 25 Hz group (p = 0.146). In contrast to controls, we found a significant reduction in seizure frequency in patients of the 25 Hz group who completed the full treatment period (20 weeks; n = 26, 34.2%, p = 0.034). Responder rates (25%, 50%) were similar in both groups. Subgroup analyses for seizure type and baseline seizure frequency revealed no significant differences. Adverse events were usually mild or moderate and comprised headache, ear pain, application site erythema, vertigo, fatigue, and nausea. Four serious adverse events were reported including one sudden unexplained death in epilepsy patients (SUDEP) in the 1 Hz group which was assessed as not treatment-related., Conclusions: tVNS had a high treatment adherence and was well tolerated. Superiority of 25 Hz tVNS over 1 Hz tVNS could not be proven in this relatively small study, which might be attributed to the higher stimulation intensity in the control group. Efficacy data revealed results that justify further trials with larger patient numbers and longer observation periods., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Localization of seizure onset during presurgical video-EEG monitoring is indispensable for successful epilepsy surgery. Sometimes analysis of ictal EEG and video fails to identify this zone. Therefore, this study explored the hypothesis that ictal EMG recordings contribute to the lateralization or localization of focal epilepsy., Methods: All patients with automotor or dialeptic seizures with or without secondary generalization were prospectively included during presurgical video-EEG monitoring over a 5years study period. We analyzed characteristics of ictal biceps EMG and compared the results to EEG and video findings., Results: 79 patients with 185 seizures were included (51.9% male; 73.5% automotor and 26.5% dialeptic seizures; 24.3% seizures secondarily generalized). Even in dialeptic seizures, muscle tone increased bilaterally within seconds after EEG seizure onset (66.7%) without clinical movements. Bilateral "spindle-shaped" EMG activity during the automotor phase predicted secondary generalization in 88.7%. Increase of muscle activity in the contralateral side of the body in the beginning of the secondarily generalized tonic-clonic phase was detected in 78.1% after automotor seizures whereas this phenomenon was less pronounced after dialeptic seizures (69.2%). 38.5% of dialeptic seizures evolved into generalized tonic-unilateral clonic seizures., Conclusion: Ictal EMG recordings provide lateralizing signs especially in secondarily generalized automotor seizures. In addition, the study suggested that secondary generalization in automotor seizures is determined early already during the automotor phase. Dialeptic seizures can evolve only unilaterally into a tonic-clonic seizure while the other side of the body remains tonic., Significance: Ictal biceps EMG can provide further information regarding lateralization of epileptic seizures., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objectives: Delayed cerebral infarction (DCI) has a significant impact on mortality and morbidity of patients with subarachnoid hemorrhage (SAH). The aim of this study was to define quantitative EEG (qEEG) parameters for the early and reliable prediction of DCI and compare the validity and time course of qEEG to standard procedures., Methods: 12 consecutive unselected SAH patients (8 female, mean age 52 years, Hunt-and-Hess grade I-IV) were prospectively examined. Continuous six channel EEG monitoring was started within 48 h after admission (mean duration 5.2 days; range: 2-12 days). All raw and unselected EEG signal underwent automated artifact rejection, Short Time Fast Fourier Transformation and a detrending procedure in order to analyze regional spectral power changes in different frequency bands. According to clinical standards, transcranial Doppler sonography (TCD) was performed at least on alternate days and repeat cerebral computer tomography (CCT) as needed., Results: 6 patients (50%) developed vasospasm/DCI. Decrease of ⩾40% in power persisting over ⩾5h in the alpha band and ⩾6h in the theta band marked the optimal cut-off to detect DCI (sensitivity 89%, specificity 77% for alpha). EEG changes preceded detection of vasospasm/DCI in standard procedures by 2.3d ays. Changes in the beta and delta band as well as in the alpha/delta ratio demonstrated lower correlation with imminent DCI., Conclusions: Focal reduction in alpha power may represent a valid, observer independent, non-invasive and continuous marker for vasospasm/DCI in SAH patients., Significance: qEEG indicates imminent ischemia earlier than established diagnostic tools, such as TCD., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: The slow digestion and amino acid absorption kinetics of isolated micellar casein have been held responsible for its relatively lower postprandial muscle protein synthetic response compared with rapidly digested proteins such as isolated whey. However, casein is normally consumed within a milk matrix. We hypothesized that protein digestion and absorption kinetics and the subsequent muscle protein synthetic response after micellar casein ingestion are modulated by the milk matrix., Objective: The aim of this study was to determine the impact of a milk matrix on casein protein digestion and absorption kinetics and postprandial muscle protein synthesis in older men., Methods: In a parallel-group design, 32 healthy older men (aged 71 ± 1 y) received a primed continuous infusion of L-[ring-(2)H5]-phenylalanine, L-[ring-3,5-(2)H2]-tyrosine, and L-[1-(13)C]-leucine, and ingested 25 g intrinsically L-[1-(13)C]-phenylalanine and L-[1-(13)C]-leucine labeled casein dissolved in bovine milk serum (Cas+Serum) or water (Cas). Plasma samples and muscle biopsies were collected in the postabsorptive state and for 300 min in the postprandial period to examine whole-body and skeletal muscle protein metabolism., Results: Casein ingestion increased plasma leucine and phenylalanine concentrations and L-[1-(13)C]-phenylalanine enrichments, with a more rapid rise after Cas vs. Cas+Serum. Nonetheless, dietary protein-derived phenylalanine availability did not differ between Cas+Serum (47 ± 2%, mean ± SEM) and Cas (46 ± 3%) when assessed over the 300-min postprandial period (P = 0.80). The milk matrix did not modulate postprandial myofibrillar protein synthesis rates from 0 to 120 min (0.038 ± 0.005 vs. 0.031 ± 0.007%/h) or from 120 to 300 min (0.052 ± 0.004 vs. 0.067 ± 0.005%/h) after Cas+Serum vs. Cas. Similarly, no treatment differences in muscle protein-bound L-[1-(13)C]-phenylalanine enrichments were observed at 120 min (0.003 ± 0.001 vs. 0.002 ± 0.001) or 300 min (0.015 ± 0.002 vs. 0.016 ± 0.002 mole percent excess) after Cas+Serum vs. Cas., Conclusions: Casein ingestion in a milk matrix delays protein digestion and absorption but does not modulate postprandial muscle protein synthesis when compared to the ingestion of micellar casein only in healthy older men. This trial was registered at Nederlands Trial Register as NTR4429., (© 2015 American Society for Nutrition.)

Purpose: There is growing evidence that complex interactions between seizures and the immune system shape the course of epilepsy. However, systematic analyses of the effects of antiepileptic drugs (AED) on the immune system in humans are rare. We performed a prospective study on the influence of the widely used AED valproate and levetiracetam on interictal immunological parameters., Methods: 36 patients were prospectively included. 15 were started on valproate (5 female (33%), age 54±27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10 female (48%), age 45±19 years, 17 (81%) on monotherapy). Before treatment and after 3 months, we performed a differential blood count and analyzed the distribution of CD3(+)CD4(+)-, CD3(+)CD8(+)- and CD4(+)CD25(+)-leukocyte subsets using flow cytometry. In addition, we determined the concentrations of IL-1β, IL-6, TNF-α and MCP-1 in the peripheral blood using ELISAs., Results: Valproate intake resulted in a significant decrease of the total white blood count (6.96±1.23/nl vs. 6.13±1.57/nl, p=0.026) and of absolute count and percentage of neutrophils (4.60±1.05/nl vs. 3.69±1.30/nl, p=0.01; 65.4±7.9% vs. 59.5±11.5%, p=0.01, respectively). The percentage of CD3(+)CD4(+)-lymphocytes dropped significantly (50.4±10.9% vs. 45.3±12.3%, p=0.002). Levetiracetam treatment resulted in a decrease of the percentage of CD4(+)CD25(+)-lymphocytes (26.1±8.0% vs. 21.5±9.2%, p=0.01) but did not significantly alter absolute counts. Neither valproate nor levetiracetam were associated with significant changes in cytokines., Conclusion: Valproate intake results in profound changes of white blood cell count and subset distribution. Cytokine levels were not influenced by valproate or levetiracetam., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the value of intraoperative MR imaging (iopMRI) combined with neuronavigation to avoid intraoperative underestimation of the resection amount during surgery of lesional temporal lobe epilepsy (LTLE) patients., Methods: We retrospectively investigated 88 patients (40 female, 48 male, mean age 37.2 yrs, from 12 to 69 yrs, 41 left sided lesions) with LTLE operated at our department, including 40.9% gangliogliomas (GG), 26.1% cavernomas (CM), 10.2% dysembryoplastic neuroepithelial tumours (DNT) and 11.4% focal cortical dysplasias (FCD), excluding hippocampal sclerosis., Results: Complete resection was achieved in 85 of 88 patients (96.6%), as proven by postoperative MRI 6 months after surgery. In contrast, the routine first iopMR imaging before closure revealed radical resection in only 66 of these 88 patients (75%). After re-intervention, the second iopMR imaging demonstrated complete resection in 19 more patients. Thus, as a direct effect of iopMRI and neuronavigation, overall resection rate was increased by 21.6%. An excellent seizure outcome Engel Class I was found in 76.1% of patients during a mean follow-up of 26.4 months, irrespective of histological entity (74% in CM, 75% in GG, 78% in DNT and 60% in FCD). No severe postoperative complications occurred; permanent superior visual field defects were detected in 10.2% and permanent dysphasia/dyscalculia in 1.1%., Conclusion: Refined surgery using neuronavigation combined with iopMR imaging in LTLE surgery led to radical resection in 96.6% of the patients, due to immediate correction of underestimated resection in 21.6% of patients. This protocol resulted in a favourable seizure outcome and a low complication rate., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Status epilepticus (SE) is an important neurological emergency and a significant source of direct costs related to hospitalization; however, no cost-of-illness (COI) studies have been performed in Europe. The objective of this study was to determine and characterize hospital costs related to the acute inpatient treatment of SE and to provide national estimates of SE hospitalization costs., Methods: Adult inpatient treatment costs related to SE and costs attributable to epilepsy-related hospital admissions were derived from billing data of participating hospitals., Results: During the 4-month study period a total of 96 patients (59.5 ± 21.6 years; 52 male) received inpatient treatment for epilepsy-related reasons, 10 of these (10.4%) were treated for SE. Epilepsy was newly diagnosed in 30/96 patients (31.3%), of whom five presented with SE. The admission costs related to SE (€8347 ± 10,773 per patient per admission) were significantly higher than those related to admissions of patients with newly diagnosed (€1998 ± 1089; p = 0.014) or established epilepsy (€3475 ± 4413; p = 0.026). Of the total inpatient costs (€346,319) 24.4% were attributable to SE, 14.4% to newly diagnosed epilepsy without SE (n = 25) and 61.2% to complications of established epilepsy (n = 61). Extrapolation to the whole of Germany (population 82 million) indicates that SE causes hospital costs of more than €83 million per year while the total of epilepsy-related inpatient treatment costs amounts to €342 million., Conclusion: Acute treatment of SE is responsible for a high proportion of hospital costs associated with epilepsy. With a high incidence of SE in the elderly population, the health care systems will face an increasing number of presentations with SE and its associated costs, underlining the necessity to further evaluate the burden and optimize the treatment of SE., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To further elucidate possible immune-modulatory effects of valproate (VPA) or levetiracetam (LEV), we investigated their influence on apoptosis and cytotoxic function of CD8+ T lymphocytes in humans., Methods: In 15 healthy subjects (9 female (60%), 35.7±12.1 years), apoptosis and cytotoxic function of CD8+ T lymphocytes were measured using flow cytometry following in vitro exposure to LEV (5 mg/L and 50 mg/L) and VPA (10mg/L and 100 mg/L). Apoptosis rates were determined after incubation with LEV or VPA for 1 h or 24 h. Cytotoxic function was assessed following 2h stimulation with mixed virus peptides, using perforin release, CD107a/b expression and proliferation. The presence of synaptic vesicle protein 2A (SV2A) was investigated in human CD8+ T lymphocytes by flow cytometry analysis, Western blot and real time polymerase chain reaction (rtPCR)., Results: High concentration of LEV decreased perforin release of CD8+ T lymphocytes (LEV 50 mg/L vs. CEF only: 21.4% (interquartile range (IQR) 16.5-35.9%) vs. 16.6% (IQR 12-24.9%), p=0.002). LEV had no influence on apoptosis and proliferation (p>0.05). VPA (100 mg/L) slowed apoptosis of CD8() T lymphocytes after 24h (VPA 100mg/L vs. control: 7.3% (IQR 5.4-9.5%) vs. 11.3% (IQR 8.2-15.1%), p<0.001), but had no effects on perforin release (p>0.05). SV2A protein was detected in CD8+ T lymphocytes., Conclusion: LEV decreased degranulation of CD8+ T lymphocytes which may contribute to the increased incidence of upper respiratory tract infections in LEV treated patients. Inhibition of SV2A may be responsible for this effect., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: It has been speculated that the amount of leucine in a meal largely determines the post-prandial muscle protein synthetic response to food intake. The present study investigates the impact of leucine co-ingestion on subsequent post-prandial muscle protein accretion following the ingestion of a single bolus of dietary protein in elderly males., Methods: Twenty-four elderly men (74.3±1.0 y) were randomly assigned to ingest 20 g intrinsically L-[1-(13)C]phenylalanine-labeled casein protein with (PRO+LEU) or without (PRO) 2.5 g crystalline leucine. Ingestion of specifically produced intrinsically labeled protein allowed us to create a plasma phenylalanine enrichment pattern similar to the absorption pattern of phenylalanine from the ingested protein and assess the subsequent post-prandial incorporation of L-[1-(13)C] phenylalanine into muscle protein., Results: Plasma amino acid concentrations increased rapidly following protein ingestion in both groups, with higher leucine concentrations observed in the PRO+LEU compared with the PRO group (P<0.01). Plasma L-[1-(13)C]phenylalanine enrichments increased rapidly and to a similar extent in both groups following protein ingestion. Muscle protein-bound L-[1-(13)C]phenylalanine enrichments were significantly greater after PRO+LEU when compared with PRO at 2 h (72%; 0.0078±0.0010 vs. 0.0046±0.00100 MPE, respectively; P<0.05) and 6 h (25%; 0.0232±0.0015 vs. 0.0185±0.0010 MPE, respectively; P<0.05) following protein ingestion. The latter translated into a greater muscle protein synthetic rate following PRO+LEU compared with PRO over the entire 6 h post-prandial period (22%; 0.049±0.003 vs. 0.040±0.003% h(-1), respectively; P<0.05)., Conclusion: Leucine co-ingestion with a bolus of pure dietary protein further stimulates post-prandial muscle protein synthesis rates in elderly men., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Minocycline, a tetracycline family antibiotic, is known to inhibit microglial activation and proinflammatory cytokine release in animal models. Experimental data show that these immune processes may play a role in epilepto- and ictogenesis. We present the case of a patient with marked reduction in seizure frequency during minocycline therapy with severe symptomatic epilepsy due to an astrocytoma., (Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Epilepsy is a common chronic neurological disorder affecting approximately 8 out of 1000 people. Its pathophysiology, however, has remained elusive in many regards. Consequently, adequate seizure control is still lacking in about one third of patients. Cytokines are soluble mediators of cell communication that are critical in immune regulation. In recent years, studies have shown that epileptic seizures can induce the production of cytokines, which in turn influence the pathogenesis and course of epilepsies. At the time of this review, the focus is mostly on interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα). In this review, we summarize the current knowledge regarding these cytokines and their potential roles in epilepsy. The focus concentrates on their expression and influence on induced seizures in animal models of epilepsy, as well as findings in human studies. Both proconvulsive and anticonvulsive effects have been reported for each of these molecules. One possible explanation for this phenomenon is that cytokines play dichotomous roles through multiple pathways, each of which is dependent on free concentration and available receptors. Furthermore, the immune-mediated leakage in the blood-brain-barrier also plays an important role in epileptogenesis. Nonetheless, these observations demonstrate the multifarious nature of cytokine networks and the complex relationship between the immune system and epilepsy. Future studies are warranted to further clarify the influence of the immune system on epilepsy and vice versa., (Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Involvement of the innate immune system in the pathogenesis of epilepsies has been suggested but possible interactions between the immune system and human epilepsy remain unclear. We analyzed the interictal immuno-phenotype of leukocyte subsets and proinflammatory cytokine profiles in epileptic patients and correlated them with the epilepsy syndrome., Methods: 101 patients with active focal or generalized epilepsy were prospectively included and compared to 36 healthy controls. Immuno-phenotype of leukocyte subsets and cytokines IL-1β, IL-6 and tnfα were measured in peripheral blood. Multivariate analyses were performed to test group differences., Results: As compared to controls, the patients showed an elevated percentage of monocytes (18.06±7.08% vs. 12.68±4.55%, p<0.001), NK cells (14.88±7.08% vs. 11.43±5.41%, p=0.019) and IL-6 concentration (3.33±3.11 pg/ml vs. 1.5±1.36 pg/ml, p=0.002). This remained true when focal epilepsies or generalized epilepsies were compared separately to controls but only focal epilepsies showed additionally a decrease in B lymphocyts (8.16±3.76% vs. 11.54±4.2%, p<0.001). Treatment with lamotrigine was associated with a higher percentage of B lymphocytes and valproate with an increased percentage of CD4(+) T lymphocytes. Therapy with levetiracetam showed a trend towards decreased CD8(+) T cell counts. No significant differences were seen between focal and generalized epilepsies and between temporal and extratemporal lobe epilepsies., Conclusion: Patients with active epilepsy revealed interictal alterations of the immune system which varied among specific syndromes and were influenced by antiepileptic drug treatment., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background & Aims: Butyrate, produced by colonic fermentation of dietary fibers is often hypothesized to beneficially affect colonic health. This study aims to assess the effects of butyrate on inflammation and oxidative stress in subjects with chronically mildly elevated parameters of inflammation and oxidative stress., Methods: Thirty-five patients with ulcerative colitis in clinical remission daily administered 60 ml rectal enemas containing 100mM sodium butyrate (n=17) or saline (n=18) during 20 days (NCT00696098). Before and after the intervention feces, blood and colonic mucosal biopsies were obtained. Parameters of antioxidant defense and oxidative damage, myeloperoxidase, several cytokines, fecal calprotectin and CRP were determined., Results: Butyrate enemas induced minor effects on colonic inflammation and oxidative stress. Only a significant increase of the colonic IL-10/IL-12 ratio was found within butyrate-treated patients (p=0.02), and colonic concentrations of CCL5 were increased after butyrate compared to placebo treatment (p=0.03). Although in general butyrate did not affect colonic glutathione levels, the effects of butyrate enemas on total colonic glutathione appeared to be dependent on the level of inflammation., Conclusion: Although UC patients in remission were characterized by low-grade oxidative stress and inflammation, rectal butyrate enemas showed only minor effects on inflammatory and oxidative stress parameters., (Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The mucus layer is an important dynamic component of the epithelial barrier. It contains mucin glycoproteins and other compounds secreted by the intestinal epithelium, such as secretory IgA. However, a standardized in vivo sampling technique of mucus in humans is not yet available., Aim: To assess the validity and feasibility of mucin and protein determinations in human colonic mucus collected under physiological conditions., Subjects and Methods: Triplicate colonic mucus samples were collected in 11 healthy volunteers using cytology brushes during sigmoidoscopy. As an indication of the quantity of collected mucus, total protein and mucin concentrations were determined by measuring oligosaccharide equivalents and monosaccharides. Also secretory IgA and sialic acid concentrations were determined and proteomic analysis was performed using surface enhanced laser desorption/ionization-time of flight-mass spectrometry., Results: Mean values of secretory IgA and sialic acid corrected for the amount of mucus ranged from 0.16 to 1.81 g secretory IgA/mmol oligosaccharide equivalents and from 12.6 to 48.6g sialic acid/mmol oligosaccharide equivalents. Proteomic analysis of mucus is feasible and cluster analysis showed subject specific profiles., Conclusion: Using cytology brushes, human colonic mucus can be sampled and under physiological conditions. These samples could give information on the composition and quality of the mucus layer.

Background & Aims: Butyrate, a short-chain fatty acid produced by colonic microbial fermentation of undigested carbohydrates, has been implicated in the maintenance of colonic health. This study evaluates whether butyrate plays a role in oxidative stress in the healthy colonic mucosa., Methods: A randomized, double blind, cross-over study with 16 healthy volunteers was performed. Treatments consisted of daily rectal administration of a 60 ml enema containing 100 mM sodium butyrate or saline for 2 weeks. After each treatment, a blood sample was taken and mucosal biopsies were obtained from the sigmoid colon. In biopsies, the trolox equivalent antioxidant capacity, activity of glutathione-S-transferase, concentration of uric acid, glutathione (GSH), glutathione disulfide and malondialdehyde, and expression of genes involved in GSH and uric acid metabolism was determined. Secondary outcome parameters were CRP, calprotectin and intestinal fatty acid binding protein in plasma and histological inflammatory scores., Results: Butyrate treatment resulted in significantly higher GSH (p<0.05) and lower uric acid (p<0.01) concentrations compared to placebo. Changes in GSH and uric acid were accompanied by increased and decreased expression, respectively, of their rate limiting enzymes determined by RT-PCR. No significant differences were found in other parameters., Conclusions: This study demonstrated that butyrate is able to beneficially affect oxidative stress in the healthy human colon.

Purpose: The pathophysiology of catamenial epilepsy is still unclear. Therefore, we investigated the cortical excitability of women with catamenial epilepsy during different phases of the menstrual cycle., Methods: Using transcranial magnetic stimulation, six patients suffering from catamenial epilepsy were investigated during ovulatory cycles. On days 8, -14, -7 and 2 of the cycle (day 1 being the first day of menstrual bleeding), resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. The non-parametric Friedman-test for multiple comparisons and Wilcoxon signed rank test were used for statistical analysis., Results: Five patients suffered from focal epilepsy (three right hemispheric, one bitemporal, one unknown origin) and one patient had idiopathic generalized epilepsy. All patients experienced perimenstrual seizure clustering and two also showed an increased seizure frequency during the luteal phase. In the right hemispheres there was a significant change of CSP duration in the course of the menstrual cycle (chi(2)=8.3, P=0.041), due to a shorter CSP during the luteal phase (Z=-2.0, P=0.043) and menstruation (Z=-2.2, P=0.028) as compared to the follicular phase. There was no significant variation of CSP in the left hemispheres. RMT, ICI and ICF showed no significant changes in the course of the menstrual cycle., Conclusions: The CSP changes suggest a decreased inhibition involving GABA-ergic neurotransmission during the luteal phase and menstruation. These TMS alterations correlated with the clinical course of the epilepsies and were found in the hemispheres containing the majority of the epileptogenic zones.

Purpose: To report that iopamidol myelography can induce status epilepticus (SE) in patients carrying the diagnosis of symptomatic epilepsy and to estimate the incidence of seizures in patients undergoing iopamidol myelography., Methods: We retrospectively identified all patients with seizures/SE associated with 1350 iopamidol myelographies during the last 5 years at our institution. The impact of cervical versus lumbar myelography was analysed., Results: Induced by iopamidol myelography two non-epileptic patients suffered from first generalised tonic-clonic seizures and a 67-year-old women with symptomatic epilepsy after a remote ischemic stroke developed a generalised tonic-clonic seizure evolving into a dialeptic and right nystagmus SE (i.e. complex focal status) of 5-hour duration. The incidence of seizures in non-epileptic patients was 0.15%. The incidence of seizure induction for lumbar myelography was lower than for myelographies that included the cervical subarachnoid space., Conclusions: Iopamidol myelography (especially if cervical) is associated with a risk of seizures in non-epileptic individuals and can induce SE in patients with epilepsy. Patients should be informed about the risk of seizure induction.

The aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of the primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down's syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer's disease (AD) and Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged.

The aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down's syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer's disease (AD) and Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged., (Copyright 2001 BEA Trading Ltd.)

Several medications such as baclofen, amitriptyline and even antiepileptic drugs such as carbamazepine or vigabatrin are known to induce absence status epilepticus in patients with generalized epilepsies. Tiagabine (TGB) is effective in patients with focal epilepsies. However, TGB has also been reported to induce non-convulsive status epilepticus in several patients with focal epilepsies and in one patient with juvenile myoclonic epilepsy. In animal models of generalized epilepsy, TGB induces absence status with 3-5 Hz spike-wave complexes. We describe a 32-year-old patient with absence epilepsy and primary generalized tonic-clonic seizures since 11 years of age, who developed her first absence status epilepticus while treated with 45 mg of TGB daily. Administration of lorazepam and immediate reduction in TGB dosage was followed by complete clinical and electroencephalographic remission. This case demonstrates that TGB can induce typical absence status epilepticus in a patient with primary generalized epilepsy., (Copyright 1999 BEA Trading Ltd.)

We report three consecutive patients with hypersensitivity syndrome (HSS) due to phenytoin and carbamazepine and successful treatment with gabapentin. HSS is a rare but potentially fatal reaction to multiple drugs including several anticonvulsants. Cross-reactivity among drugs may occur. Immediate withdrawal of the offending drug is the most important step in treatment. Benzodiazepines acutely and, after resolution of the hepatitis, valproic acid have been successfully used for seizure control in patients with HSS. Our cases indicate that gabapentin is also a safe anticonvulsant in HSS., (Copyright 1999 BEA Trading Ltd.)