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Traditional data sources are not sufficient for measuring the United Nations Sustainable Development Goals. New and non-traditional sources of data are required. Citizen science is an emerging example of a non-traditional data source that is already making a contribution. In this Perspective, we present a roadmap that outlines how citizen science can be integrated into the formal Sustainable Development Goals reporting mechanisms. Success will require leadership from the United Nations, innovation from National Statistical Offices and focus from the citizen-science community to identify the indicators for which citizen science can make a real contribution.

Aims To find out which variables may be associated with comfort of patients in an epilepsy monitoring unit. Design Exploratory, quantitative study design. Methods Data were collected from October 2018 to November 2019 in Austria and Southern Germany. A total of 267 patients of 10 epilepsy centres completed the Epilepsy Monitoring Unit Comfort Questionnaire which is based on Kolcaba's General Comfort Questionnaire. Secondary data analysis were conducted by using descriptive statistics and an exploratory model building approach, including different linear regression models and several sensitivity analyses. Results Total comfort scores ranged from 83 to 235 points. Gender, occupation and centre turned out to be possible influential variables. On average, women had a total comfort score 4.69 points higher than men, and retired persons 28.2 points higher than high school students ≥18 years. Comfort scores of younger patients were lower than those of older patients. However, age did not show a statistically significant effect. The same could be observed in marital status and educational levels. Conclusion When implementing comfort measures, nurses must be aware of variables which could influence the intervention negatively. Especially, high school students ≥18 years should be supported by epilepsy specialist nurses, in order to reduce uncertainty, anxiety and discomfort. But, since the identified variables account only for a small proportion of the inter-individual variability in comfort scores, further studies are needed to find out additional relevant aspects and to examine centre-specific effects more closely. Impact Nurses ensure patient comfort during a hospital stay. However, there are variables that may impair the effectiveness of the nursing measures. Our study showed that the experience of comfort was highly individual and could be explained by sociodemographic variables only to a limited extent. Nurses must be aware that additional factors, such as the situation in the individual setting, may be relevant.

Purpose The purpose of the study was to evaluate the psychometric properties of the newly developed Epilepsy Monitoring Unit Comfort Questionnaire (EMUCQ) according to the consensus-based standards for the selection of health measurements instruments (COSMIN). Moreover, we aimed to assess changes in comfort-levels. Methods From October 2018 to November 2019, a total of 267 patients participated in a quantitative study in ten epilepsy centers in Austria and southern Germany. For basic item analysis, descriptive analysis and correlational analysis were computed. An exploratory factor analysis (EFA) was undertaken to detect the factor structure. Reliability was checked through internal consistency (Cronbach's alpha) and the measurement error. In the validity domain, convergent validity and structural validity were estimated. t-Tests were used to detect changes in comfort-levels. Results Due to unfavorable statistical properties, two items were removed. Exploratory factor analysis showed a three-factorial solution. The EMUCQ was found to be a reliable instrument (Cronbach's alpha 0.77–0.81 for the subscales, 0.88 for the scale total comfort); convergent validity could be supported, too. Confirmatory factor analysis (CFA) supported the hypothesis that structural validity for the three subscales holds. The patients' comfort levels were lower at the end of the stay than at the beginning and lower in nonseizure-free patients compared with seizure-free patients. Conclusion Validity and reliability are supported for the 42-item EMUCQ in the three-factorial solution. Owing to the item reduction and modifications made in the CFA, a new test should be carried out on a different sample.

Zusammenfassung Im Rahmen der SANTE-Studie (7) konnte gezeigt werden, dass die Stimulation im Nucleus anterior des Thalamus (ANT) zu einer signifikanten Reduktion der Anfallshaufigkeit bei therapieschwieriger Epilepsie fuhrt. Ebenfalls signifikante Effekte konnten auch bei der Stimulation des Hippocampus gezeigt werden (8,10,16,19,32) die aber in Deutschland bisher nicht etabliert ist. Andere Stimulationstargets spielen im breiteren klinischen Einsatz ebenfalls keine Rolle. Die vielversprechenden Ergebnisse der SANTE-Studie liesen sich nach nun siebenjahriger Anwendung in Deutschland nur teilweise reproduzieren. In diesem Artikel sollen mogliche Grunde fur die von der SANTE-Studie abweichenden Ergebnisse analysiert und der aktuelle Stellenwert der Tiefen Hirnstimulation bei der therapieschwierigen Epilepsie diskutiert werden.

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) approved for monotherapy (in the USA) and adjunctive treatment of focal (partial-onset) seizures in adults, at a dose range of 50–200 mg/day taken in two equal doses, with a recommended starting dose of 100 mg/day. Two Phase III, randomized, double-blind, multicenter, historical-controlled, conversion-to-monotherapy studies (N01276, NCT00698581; N01306, NCT00699283) were conducted to evaluate the efficacy, safety, and tolerability of conversion to BRV 50 mg/day monotherapy in adults with uncontrolled focal seizures. Patients aged 16–75 years, with 2–40 focal seizures per 4 weeks during an 8-week baseline, and on stable doses of 1–2 AEDs were enrolled. Patients were randomized to BRV 50 or 100 mg/day (3:1) in two equal doses without titration. The treatment period comprised 1-week BRV add-on, 8-week baseline AED tapering, and 8-week BRV monotherapy periods. Primary efficacy endpoint was Kaplan-Meier estimate of the cumulative exit rate due to pre-defined exit criteria at Day 112 (50 mg/day, efficacy population). The upper 95% confidence interval (CI) was compared with the historical control threshold (0.722). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs; intent-to-treat population). After randomization of 150 patients (N01276: 88; N01306: 62), both studies were terminated due to the confounding effects of a higher-than-expected discontinuation rate. For BRV 50 mg/day, ≥1 exit criterion was met by 26/67 (38.8%) patients (study N01276) and 18/45 (40.0%) patients (study N01306). In both studies, the cumulative exit rate was lower than the historical control threshold (N01276: 0.487, 95% CI 0.347, 0.626; N01306: 0.474, 95% CI 0.310, 0.638). However, with maximum 10% censoring due to early withdrawal (sensitivity analysis), cumulative exit rates were above historical control (N01276: 0.652, 95% CI 0.532, 0.772; N01306: 0.704, 95% CI 0.563, 0.844). Overall incidence of TEAEs was 110/150, 73.3% (treatment period); 78/147, 53.1% (baseline AED tapering period); 41/84, 48.8% (BRV monotherapy period). In conclusion, BRV 50 mg/day monotherapy demonstrated an exit rate lower than historical control. Results should be interpreted with caution as, following termination of both studies, patient numbers were too low to evaluate the efficacy of BRV monotherapy. These are the first published safety and tolerability data for BRV monotherapy. Monotherapy was well tolerated, with a relatively low incidence of TEAEs, though this should be interpreted with the caveat that the majority of common TEAEs were likely to have occurred earlier in the course of treatment with BRV. No new safety concerns were identified, supporting the favorable safety profile of BRV observed in adjunctive studies.

Background This long-term follow-up (LTFU) trial was conducted to evaluate the long-term safety and tolerability of brivaracetam (BRV) at individualized doses (maximum of 200 mg/day) in patients with focal seizures. The secondary objective was to evaluate the efficacy of BRV over time. Methods Two Phase III, randomized, double-blind, historical-controlled conversion-to-monotherapy trials (N01276: NCT00698581; N01306: NCT00699283) were conducted in patients aged ≥16 years with uncontrolled focal seizures. Patients who completed either of these core trials or who met a protocol-defined exit criterion could enter this LTFU trial (N01315; NCT00761774). Patients entered LTFU at a recommended BRV dose of 100 mg/day, with flexible dosing of 50–200 mg/day, as monotherapy or adjunctive therapy; additional AEDs could be prescribed and adapted in dose if clinically indicated. Safety variables included treatment-emergent adverse events (TEAEs). Efficacy variables included duration of continuous monotherapy, reduction in focal seizure frequency and seizure freedom. Safety and efficacy variables were assessed for all patients in the safety set or efficacy set, respectively, regardless of BRV treatment regimen. In addition, a post hoc subgroup analysis was conducted for patients who completed the BRV monotherapy period in either core trial, and entered the LTFU on BRV monotherapy. For this subgroup, TEAEs were summarized by 3-month time intervals over the first 12 months of LTFU. Results 108 patients were enrolled in the LTFU trial between November 2008 and February 2010. 79 (73.1 %) patients discontinued the LTFU trial, most commonly due to lack of efficacy [37 (34.3 %)] and adverse events [16 (14.8 %)]. At core trial baseline, patients had a median of 6.3 focal seizures/28 days and 53 (49.1 %) had failed ≥5 previous lifetime AEDs. During LTFU, 70 (64.8 %) patients had ≥12 months and 56 (51.9 %) patients had ≥24 months of BRV treatment. TEAEs were reported by 98 (90.7 %) patients; most commonly (≥15 % of patients) convulsion (17.6 %), nasopharyngitis (17.6 %), depression (16.7 %) and fatigue (15.7 %). Median percent reduction from baseline in focal seizure frequency/28 days was 56.8 %. Among 86 patients who completed at least 6 months of treatment, 29 (33.7 %) patients were seizure-free for ≥6 months and 22 (25.6 %) were seizure-free for ≥12 months. 50/108 patients were included in the BRV monotherapy subgroup; 33/50 (66.0 %) patients reported a TEAE in the core trials, while 26/50 (52.0 %), 15/37 (40.5 %), 14/33 (42.4 %) and 9/27 (33.3 %) patients reported any TEAE during LTFU months 1–3, 4–6, 7–9 and 10–12, respectively. In the BRV monotherapy subgroup, the most common TEAEs (≥5% of patients) during LTFU months 1–3 were fatigue [3/50 (6.0 %)] and dizziness [3/50 (6.0 %)]. Interpretation Results from the LTFU trial support the long-term safety of BRV at individualized doses of up to 200 mg/day as a well-tolerated, and effective treatment for patients with focal seizures. Efficacy analyses indicate that seizure reductions with brivaracetam were generally maintained over time.

Depression and anxiety are highly prevalent among people with epilepsy (PwE) but often remain unrecognized and treated inadequately. Effective psychosocial treatments such as cognitive behavioral therapy (CBT) are rarely available to most PwE, which is one reason electronically delivered CBT (eCBT) is regarded as promising. This study examined an eCBT intervention, termed Emyna, that was tailored to suit the needs of PwE. It includes CBT-related content on depression, stress and anxiety, seizure triggers and auras, and lifestyle habits. The trial examined the efficacy of Emyna in reducing symptoms of depression (primary outcome) and anxiety as well as improving quality of life.Participants (N = 200) with epilepsy, a diagnosis of a depressive disorder, and at least moderate depressive symptoms were randomized to Emyna or care as usual. At baseline and after 3, 6, and 9 months, participants were invited to complete online questionnaires. The primary outcome was improvement of depressive symptoms at 3 months.Relative to the control group, intervention group participants experienced significantly greater improvements in depression, anxiety, stress, social-occupational impairment, and epilepsy-related quality of life, in both intention-to-treat (ITT) and per-protocol analyses. In ITT analyses, effects of medium magnitude were observed, as measured by the Patient Health Questionnaire-9 items (Cohen d = 0.54, 95% confidence interval [CI] = 0.25-0.82, P 0.001) and the Neurological Disorders Depression Inventory for Epilepsy (d = 0.51, 95% CI = 0.23-0.79, P 0.01). At 3 months, intervention group participants also reported fewer illness-related days off work and fewer days hospitalized over the preceding months, compared to control group participants (P ≤ 0.05), whereas no such differences were present at baseline (P 0.30).These findings showed that Emyna, used adjunctively to usual care, could help improve mental health, social-occupational functioning, and quality of life among PwE. The program provides an additional treatment option that could produce clinically relevant symptom reductions and reduce key cost drivers (ie, hospitalization rates and illness-related inability to work).

Spatial phenomena like the expansion of artificial land and the decrease of agricultural land lead to significant change rates over time for the main land cover types. For European policies, comparable information on land cover change in all European countries is required. The Statistical Office of the European Union (Eurostat) uses the nomenclature of the Land Use/Cover Area Frame Survey (LUCAS) as a basis for compiling areal statistics across the entire EUs territory. As there is presently no dataset in Germany which can be used as a stand-alone source to fulfill Eurostat´s requirements, the project Cop4Stat_2015plus was initiated. The aim is to assess the feasibility of providing the needed land cover information by using remote sensing techniques and satellite data from the Copernicus program and contributing missions. In this study, a method for classification of high-resolution RapidEye time series images for the year 2015 in a study area in Germany is presented. Machine-learning algorithms in combination with topographic reference data as training and validation datasets are used for an object-based classification of artificial land, cropland, woodland, shrubland, grassland and water bodies. For a better separation between shrubland and woodland a normalized digital surface model is used. Classification results show an overall accuracy of above 95 %. The accuracies for the classes range between 76 % for shrubland and 98 % for water bodies. The information of the near infrared band, the red edge band and the height show the highest relevance for good classification results. At the edge of forests, shrublands are partly misclassified instead of forest or cropland because the height of trees and the height of the neighboring objects are averaged and the outcome then corresponds to the height of shrubland. The results will subsequently be compared with official areal statistics and will be tested to support the provision of areal statistics for national and European purposes.

Summary Objective Evidence for the efficacy and safety of adjunctive lacosamide in the treatment of partial‐onset seizures (POS) was gained during placebo‐controlled clinical trials in patients with treatment‐resistant seizures who were taking one to three concomitant antiepileptic drugs (AEDs). The VITOBA study (NCT01098162) evaluated the effectiveness and tolerability of adjunctive lacosamide added to one baseline AED in real‐world clinical practice. Methods We conducted a 6‐month observational study at 112 sites across Germany. Adult patients (≥16 years) with POS received lacosamide adjunctive to only one baseline AED. Seizure frequency reduction at the end of the observation period was compared with a 3‐month retrospective baseline period. Results Five hundred seventy‐one patients received lacosamide at least once (Safety Set [SS]); 520 provided evaluable seizure records (Full Analysis Set [FAS]); and 499 took in‐label dosages of lacosamide (up to 400 mg) and were evaluated for effectiveness (modified FAS). Median baseline seizure frequency was 2.0 per 28 days: 47.1% of patients (235/499, mFAS) took a concomitant sodium channel–blocking (SCB) AED; 38.1% (190/499) had only one lifetime AED; and 18.4% (92/499) were aged ≥65 years (mFAS). At the final visit, 72.5% (358/494) of patients showed a ≥50% reduction in seizure frequency from baseline, 63.8% (315/494) showed a ≥75% reduction, and 45.5% (225/494) were seizure‐free. Seizure freedom rates were higher in patients aged ≥65 years (56.7%) compared with patients aged 5 years duration (41.0%), and when added to first monotherapy (60.5%) rather than as a later therapy option. Treatment‐emergent adverse events (TEAEs) were reported by 48.5% (277/571) of patients (SS), with a profile similar to that observed in pivotal trials; 466 of patients (81.6%, SS) continued lacosamide therapy after the trial. Significance These results suggest that lacosamide use, added to one concomitant AED, was effective at improving seizure control and was well tolerated in patients treated in routine clinical practice.

In this article, we give an overview of the state of scientific knowledge on inflation hedging. Specifically, we distill the results of several decades of research analysing the relationship between major asset classes (common stocks, gold, fixed income securities, real estate) and inflation. Even though previous studies have brought forth important facts characterising the interplay of asset returns and inflation rates (e.g., time-dependency, asymmetry, outlier-sensitivity and a tendency towards long-term but limited short-term inflation protection), there is still no consensus on the subject because sample, data and methodology issues preclude strict comparison of most studies. Thus, from a synthesis of the insights gained from our review, we also outline possible directions for future research that may help to establish consensus among researchers.

Objective To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects.

We report on a young lady suffering from adult neuroblastoma and anti-Hu associated paraneoplastic encephalomyelitis (PEM) with a tumour free survival of nine years up to now. Treatment included tumour surgery, radiation, high dose chemotherapy, and stem cell transplantation. Serological testing demonstrated a marked decline in anti-Hu antibody titres under therapy, and subsequent disappearance of the antibody 31 months after second tumour resection.

Lacosamid (LCM, R-2-Acetamido-N-benzyl-3-methoxypropionamid) gehort zu der Gruppe der funktionalisierten Aminosauren. In tierexperimentellen Studien erwies sich LCM als ein wirksames Medikament gegen fokale Anfalle und beeinflusst zudem moglicherweise Mechanismen der Entstehung von Epilepsien. LCM wirkt uber die Verstarkung der langsamen Inaktivierung von Natriumkanalen ohne die schnelle Inaktivierung spannungsregulierter Natriumkanale, die fur andere Antiepileptika wie Carbamazepin, Phenytoin oder Lamotrigin bekannt ist, zu beeinflussen. Zudem bindet LCM an das „Collapsin-Response Mediator Protein 2“ (CRMP-2), wobei der resultierende Effekt bisher noch nicht geklart ist. Die Pharmakokinetik von LCM ist durch eine schnelle und vollstandige Aufnahme der Substanz gekennzeichnet. Ein Vorteil fur die klinische Anwendung besteht darin, dass LCM von der Nahrungsaufnahme unabhangig resorbiert wird. Erganzend zur oralen Verabreichung (Tablette, Sirup) ist LCM auch intravenos infundierbar. Aufgrund der Halbwertszeit von 13 Stunden ist eine 2x tagliche Verabreichung moglich. Wegen der renalen Ausscheidung ist bei altersabhangigen oder sonstigen schweren Nierenfunktionsstorung die Dosierung zu verringern. Cytochrom-P-450-Enzyme werden durch LCM weder induziert noch inhibiert. Es wurden keine klinisch relevanten Interaktionen von LCM mit anderen Antiepileptika beobachtet. Dies ist ein wichtiger klinischer Vorteil im Vergleich zu stark enzyminduzierenden Substanzen wie Carbamazepin, Phenobarbital, Phenytoin, aber auch Substanzen mit geringerem Interaktionspotential wie Oxcarbazepin und Lamotrigin. Die Zugabe von LCM war in randomisierten, placebokontrollierten Studien bei fokalen Epilepsien in Dosierungen von 200-600 mg/Tag wirksamer als Placebo. LCM kann rasch (1-3 Wochen bis zur zugelassenen Erhaltungsdosis) aufdosiert werden. Die Vertraglichkeit von LCM war sowohl bei der parenteralen Applikation als auch der oralen Verabreichung bis auf die fur Antiepileptika ublichen dosisabhangigen zentral-nervosen Nebenwirkungen gut. Psychiatrische Nebenwirkungen traten bei 4% der Patienten auf, Veranderungen des Korpergewichts wurden nicht beobachtet. Fur die dosisabhangige Zunahme des PR-Intervalls im Elektrokardiogramm um 14,3 ms bei einer Tagesdosis von 400 mg (unter Placebo 11,2 ms) gab es keinen Zusammenhang mit klinischen Symptomen. Dennoch bedarf es weiterer klinischer Beobachtung. Zusammengefasst sprechen Wirksamkeit, schnelle Aufdosierungsmoglichkeit, gunstiges Interaktionsprofil und geringes psychiatrisches Nebenwirkungspotential fur LCM.

Es wird ein Patient mit kompletter Paraplegie und Anasthesie der Beine, die uber mehr als ein Jahr bestanden, beschrieben. Bei Verdacht auf eine psychogen-funktionelle Ursache der Symptome wurden im Schlaflabor Beinbewegungen dokumentiert. Die Videoaufzeichnung, auf der Beinbewegungen zu sehen waren, wurde dem Patienten gezeigt. Dies fuhrte zu einer raschen Besserung der Paraplegie und zu inzwischen mehr als 3-jahriger Beschwerdefreiheit. Das Beispiel legt die Bewusstmachung der intakten Funktion als Therapiekonzept mit dauerhaften Erfolgsaussichten bei psychogen-funktionellen Lahmungen nahe.

Semantically bounded disorders of verbal processing that result in selective dysnomias for items belonging to specific semantic categories have been well documented in lesion studies. Most commonly dissociations between the categories of living versus non-living things have been reported. Processing of living things such as animals seems to be impaired after bilateral lesions, whereas lesions resulting in impairment of processing of non-living things such as tools seem to be restricted to the left hemisphere. In this study, we tested the naming capabilities of epilepsy patients with subdural electrodes implanted for localization of the epileptogenic zone and preoperative mapping of cognitive functions. Tool and animal items were used, and the results show that during stimulation of the left hemisphere dysnomias for tool items were more pronounced than for animal items. This asymmetry is discussed within a model of more widely bilaterally distributed processing of living category members as compared to more restricted left-sided representation of non-living category members.

Combined heat and power generation (CHP) is a way of providing both electric power and thermal heat for industrial and domestic facilities at high fuel efficiencies. Often small and medium sized gas powered internal combustion (IC) engines, rated at electric power outputs of 50–600 kW, are used for such applications. During the time when the available thermal heat is used, the fuel efficiency of such CHP plants is very high, but it drops to the efficiencies of simple power generation when there is no heat demand, e.g. during summer. In these cases, the exhaust heat is blown off, especially as CHP units are mainly heat-lead, i.e. designed to cover the heat demand rather than the demand for electrical power. Moreover, as the cooling water heat rejection is also more difficult at elevated ambient temperatures, these units are then operated at part load or even switched off, hence having a lower degree of capacity utilization. The approach of the work presented here is to replace the turbocharger system commonly used for IC engines and to use an electric driven compression device instead, while the turbine serves to generate additional electric power from the exhaust gas. Furthermore, for periods with low thermal heat demand, steam is generated from the turbine exhaust heat. The steam is injected in front of the turbine in order to increase the turbine work output further. Thus, at least part of the exhaust heat available is used and the power output as well as the electric efficiency is increased. In the present work, two configurations of the described setup using a medium sized gas powered IC engine CHP unit are modeled in order to assess the impact on plant performance and the characteristics of such a facility. In both cases the engine cooling circuit is integrated. Depending on the configuration used, the plant power output increases by up to 7% only because of the power turbine. Additional steam injection to use the waste heat increases the power output further. The relative electric efficiency increase with steam injection is in the range of 3–5%. Apart from the higher output of electric power, this approach allows longer operating hours to be achieved, as the exhaust heat available is utilized and the heat load for the cooling water circuit is reduced.

Myelinolysis may occur as a severe complication of eating disorders, especially anorexia nervosa (AN). One of the most important reasons can be a rapid correction of hyponatremia caused by tubulopathy, water intoxication (WI), or abuse of diuretics in individuals with AN. Method and Results We report on a 24-year-old female patient with an 8-year history of AN. A rapid correction of severe hyponatremia and hypokalemia induced by WI led to central pontine myelinolysis, which was confirmed by magnetic resonance imaging (MRI) examination. Besides affective lability, incoherence, and an acute confusional state, surprisingly, no severe neurological symptoms emerged. Conclusion Thus, physicians should be aware of the risk of pontine myelinolysis with new psychiatric symptoms emerging in the absence of obvious neurological deficits. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 30: 462–466, 2001.

Purpose: Comparison of regional reduction of GABA receptor binding and seizure onset zone in patients with extratemporal epilepsy due to focal cortical dysplasia.Methods: Two patients with frontal lobe epilepsy who remained seizure free after partial frontal lobe resection were investigated with magnetic resonance imaging, positron emission tomography (PET) with F-18-fluoro-deoxy-glucose (FDG) and C-11-flumazenil, subdural EEG-video recordings, and postoperative benzodiazepine (BDZ)-receptor autoradiography.Results: The area of reduced BDZ-receptor binding as documented by preoperative flumazenil-PET and postoperative BDZ-receptor autoradiography corresponded to the seizure on-set zone and was smaller than the interictal hypometabolism documented by FDG-PET.Conclusion: Flumazenil-PET is a useful tool for localization of the epileptogenic zone in patients with extratemporal epilepsy caused by focal cortical dysplasia. Neuronal distribution of BDZ-receptor density confirms in vivo flumazenil-PET findings. The regional reduction of BDZ-receptor binding in focal cortical dysplasia seems to be confined to the seizure onset zone and not to the extent of dysplastic cortex.

Wir stellen ein nichtinvasives Protokoll fur die epilepiechirurgische Diagnostik vor, demzufolge bei 50 von 173 Patienten mit pharmakoresistenten fokalen Epilepsien ein resektiver epilepsiechirurgischer Eingriff durchgefuhrt wurde. Die lokalisatorische Ubereinstimmung von Befunden des nichtinvasiven EEG-Video-Monitorings, der Magnet-Resonanz-Tomographie (MRT), der interiktalen Positronen-Emissions-Tomographie (PET) und der iktalen SPECT (Single-Photon-Emissions-Computer-Tomographie) bildete die Grundlage der Fokuslokalisation. Bei 46 (92%) der Patienten lagen temporale und bei 4 (8%) extratemporale Epilepsien vor. 78% (n=39) aller 50 Patienten wurden anfallsfrei oder hatten nur noch sehr selten Anfalle. Extratemporale Resektionen konnten ohne invasive EEG-Untersuchungen erfolgen, wenn umschriebene MRT-Lasionen vorlagen und die Resektionen in ausreichendem Abstand vom eloquenten Kortex durchgefuhrt werden konnten. Anfallsfreiheit konnte so bei insgesamt 3 der 4 extratemporalen Patienten erreicht werden. Wir folgern aus unseren Ergebnissen, das bei einer Reihe von ausgewahlten Patienten mit pharmakoresistenten fokalen, insbesondere temporalen Epilepsien nichtinvasive EEG-Ableitungen in der prachirurgischen Diagnostik ausreichen und so das Risiko invasiver EEG-Untersuchungen vermieden werden kann.

The purpose of this study was to evaluate the utility of magnetic resonance (MR) relative cerebral blood volume (rCBV) maps for studying regional hemodynamic changes in interictal and ictal epilepsy patients. Ten epilepsy patients were examined on a 1.5 T MR system. Nine patients were investigated interictally and one patient ictally. In the nine interictal patients, the dynamic plane was defined coronally through the hippocampus symmetrically. For the ictal patient, an axial dynamic plane was defined and the patient was scanned during seizure. Positron emission tomography (PET) studies were performed in 8 of the 10 patients. Lower rCBV of the left hippocampus was predicted by rCBV maps in seven of the nine interictal patients. The mean ratios of rCBV were 1.96 for left hippocampus/white matter and 2.49 for right hippocampus/ white matter. The difference between these two ratios is statistically significant (P = 0.01, t-test). In two of the nine interictal temporal lobe epilepsy patients, lower rCBV areas were observed in the right hippocampus. In the ictal patient, the regional rCBV map demonstrated increased blood volume in the lesions. In eight of eight patients who underwent PET studies, MR rCBV findings were consistent with PET findings. The results show that regional hemodynamic changes in epilepsy can be evaluated with dynamic contrast-enhanced MR imaging. MR rCBV maps are sensitive to characterize seizure foci both ictally and interictally.J. Magn. Reson. Imaging 1999; 9:435–440. © 1999 Wiley-Liss, Inc.

Although ictal single-photon emission tomography (SPET) with technetium-99m ethyl cysteinate dimer (ECD) has a well-established role in the diagnostic evaluation of patients with temporal lobe epilepsy who are being considered for epilepsy surgery, its use in cases of extratemporal epilepsy is still limited. We investigated the influence of the propagation of extratemporal epileptic seizure activity on the regional increase in cerebral blood flow, which is usually associated with epileptic seizure activity. Forty-two consecutive patients with extratemporal epilepsies were prospectively evaluated. All patients underwent ictal SPET studies with simultaneous electroencephalography (EEG) and video recordings of habitual seizures and imaging studies including cranial magnetic resonance imaging and positron emission tomography with 2-[18F]-fluoro-2 deoxy-d-glucose. Propagation of epilptic seizure activity (PESA) was defined as the absence of hyperperfusion on ictal ECD SPET in the lobe of seizure onset, but its presence in another ipsilateral or contralateral lobe. Observers analysing the SPET images were not informed of the other results. PESA was observed in 8 of the 42 patients (19%) and was ipsilateral to the seizure onset in five (63%) of these eight patients. The time between clinical seizure onset and injection of the ECD tracer ranged from 14 to 61 s (mean 34 s). Seven patients (88%) with PESA had parieto-occipital epilepsy and one patient had a frontal epilepsy. PESA was statistically more frequent in patients with parieto-occipital lobe epilepsies (58%) than in the remaining extratemporal epilepsy syndromes (3%) (P

Recent advances in epileptology and epilepsy surgery require revision of the currently used International Classification of Epileptic Seizures, which was published 1981. We present a classification of epileptic seizures which is based purely on the clinical seizure semiology. The advantages of a semiological seizure classification are stressed.

National land monitoring activities are moving towards a harmonized integration of national datasets with pan-European LC/LU initiatives. A growing number of European countries derive their contributions to pan-European land cover and land use datasets following the principles of a bottom-up approach. In the case of Germany this concept is put into practice by using the topographic reference data of the Federal Stateś land surveying authorities (ATKIS ® Basis-DLM) as the main input to create a homogeneous LC/LU dataset for the entire country, supported by remote sensing methods. For the reason of temporal consistency the reference year of DLM-DE production has been synchronized with the Corine Land cover (CLC) phase 2012.

We studied the relationship of regional cerebral glucose consumption (rCMRGlc) and striatal dopamine D2 receptor binding as assessed with positron emission tomography (PET) with the structural abnormalities of the brain in magnetic resonance images (MR), and the degree of neurological impairment in 18 patients with Wilson's disease (WD). The rCMRGlc was determined in the. basal ganglia, the thalamus, the cerebral cortex, and the cerebellar hemispheres. The severity of neurological signs, defined by semiquantitative motor impairment scores, correlated highly ( r = −0.80) with the reduction of striatal rCMRGlc. Clinical scores, striatal rCMRGlc, and the degree of MRI abnormalities showed no correlation with different indices of dopamine D2 receptor binding. Sequential PET measurements in three patients during treatment with chelating agents revealed a moderate increase of striatal rCMRGlc (in two patients) and a moderate to marked increase of striatal D2 receptor binding (in three patients) in association with clinical improvement. Our data suggest that the rCMRGlc represents a sensitive and objective measure for assessing and monitoring striatal and extrastriatal involvement in WD. The lack of correlation between the dopamine D2 receptor binding and striatal rCMRGlc and structural abnormalities may be explained by the wide spectrum of clinical manifestations and different responses to treatment in WD patients.

The aim of this study was to investigate the change of health related quality of life (HRQoL), anxiety and depression in adult patients in whom an adjunctive treatment with levetiracetam (LEV) was converted to a LEV monotherapy. A prospective, open, investigator initiated multicenter study enrolled 140 patients in whom LEV was added to the existing antiepileptic medication. A total of 65 patients who benefited from the 16-week add-on treatment with LEV (>= 50% seizure reduction) were converted to LEV monotherapy (16-week follow-up). In LEV responders, HRQoL, anxiety and depression improved after add-on of LEV. The subsequent conversion to LEV monotherapy did not lead to a significant change in HRQoL, anxiety and depression. However, comparing baseline with LEV monotherapy, the improvements remained significant for most dimensions of HRQoL and for anxiety and depression. Patients' ratings of efficacy of LEV were related with their HRQoL after the conversion to monotherapy. Add-on therapy of LEV improved HRQoL, anxiety and depression in LEV responders. Conversion to a LEV monotherapy did not inevitably improve HRQoL in LEV responders, but the positive effect was maintained in the majority of the patients. The effects were highly related to seizure reduction. (c) 2012 Elsevier B.V. All rights reserved.

Background Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy. Methods A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher9s exact test, α=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged ≥12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed. Results The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07). Conclusions There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm. Clinical trial registration number ClinicalTrials.gov identifier NCT00242606.

Vocalizations may occur in focal epileptic seizures, which typically arise from frontal and temporal regions. They are commonly associated with other motor phenomena such as automatisms, tonic posturing, or head version. We report on a patient whose seizures were documented by video-EEG monitoring, but in whom the observable ictal semiology consisted solely of a brief, monotonous vocalization. Ictal EEGs showed left frontal seizure patterns. Isolated vocalizations can constitute an ictal epileptic event and may be the only observable clinical manifestation of a left frontal lobe epilepsy. [Published with video sequences].

The classification of status epilepticus (SE) has been a subject of discussion for many years, yet no satisfactory agreement has been reached. Due to their complexity, status episodes often defy classification according to the current international classification scheme. The semiological seizure classification (SSC) has been in use in several epilepsy centers for more than a decade, and has proven to be a valid approach to the classification of epileptic seizures. Based on the detailed analysis of more than 100 episodes of SE documented with video-EEG recordings, the authors now present a proposal for a semiological classification of status epilepticus (SCSE). The SCSE reflects the assumption implied by all modern definitions of SE that "there are as many types of status as there are types of seizures" and relies on the same principles as the SSC, focusing on the main clinical manifestations and the evolution of the status episode. The clinical manifestations of SE are subdivided into semiological components and classified along three axes: the type of brain function predominantly compromised by the seizure activity, the body part involved, and the evolution over time. Each axis contains several subcategories, so that many different levels of accuracy are possible. The SCSE, just like the SSC, is meant to be part of a comprehensive epilepsy classification which classifies as independent variables (epileptogenic zone, ictal semiology, etiology, related medical conditions) the main features of the patient's epilepsy, allowing for each variable maximum flexibility.

Ictal heart rate was investigated in otherwise subclinical epileptic seizures to test the hypothesis as to whether ictal tachycardia is physiological and not a physical or psychological stress response. In addition, we aimed to evaluate the localizing significance of pure ictal tachycardia. We included 21 epilepsy patients, who showed an ictal EEG seizure pattern during 22, otherwise subclinical seizures. All patients underwent ictal video-EEG recordings to evaluate the possibility of resective epilepsy surgery. The changes in heart rate in these patients were investigated in order to determine their relationship to localization and duration of EEG seizure patterns. Ictal tachycardia was observed in 41% of the otherwise subclinical seizures (nine out of 22), and significantly more often in seizures arising from the temporal lobe than from extratemporal regions (62% versus 11%, p0.0018). The seizure duration as defined by EEG was significantly positively correlated with an increase of heart rate (p = 0.043). Ictal heart rate can increase as a result of epileptic activation of autonomic cortex, reflecting a temporal lobe autonomic influence. Thus, measurement of heart rate should be included in the evaluation of otherwise subclinical epileptic seizures, because of its localizing value.

We evaluated whether mesial temporal lobe epilepsy (MTE) and neocortical temporal lobe epilepsy (NTE) can be distinguished on electroclinical grounds. One hundred and twenty-two consecutive MTE (n = 86) and NTE (n = 36) patients were included in this prospective study. All patients underwent prolonged EEG-video monitoring and high resolution magnetic-resonance imaging (MRI). MTE was defined as epilepsy with purely mesial temporal lesion in the absence of extramesial temporal pathology, based on pre-operative MRI or post-operative histology. NTE was defined as neocortical temporal MRI lesions, depth recorded neocortical temporal seizure onset and lack of mesial temporal lesions on MRI or histology. One thousand two hundred and fourty-nine epileptic seizures were analyzed. Congenital malformation (NTE 19% versus MTE 3%, P0.01), nonspecific auras (NTE 25% versus MTE 8%, P0.001) and early clonic activity following automatisms (NTE 22% versus MTE 8%, P0.03) were more frequent in NTE. In contrast, a history of febrile seizures (MTE 29% versus NTE 3%, P0,001), abdominal auras (MTE 62% versus NTE 33%, P0.005) and contralateral hand dystonia (MTE 43% versus NTE 22%, P0.03) were more often documented in MTE. Interictal epileptiform discharges in MTE occurred predominantly (67%) over the ipsilateral mesial temporal regions (MTE 65% versus NTE 33%, P0.001). No MTE patient had lateral neocortical temporal spike predominance (NTE 22%, P0.001). Multiple logistic regression revealed that a history of febrile seizures, abdominal auras, contralateral dystonic posturing and predominance of ipsilateral mesial temporal spikes point to MTE, with an accuracy of 73% (PPV 81%, NPV 70%). Analyzing clinical and EEG features, particularly the distribution of interictal epileptiform discharges, helps to differentiate between MTE and NTE.

Summary: Purpose: To determine whether the clinical features of tonic seizures (TSZ) are useful for lateralization of epileptic syndromes and the differential diagnosis of focal epileptic syndromes. Methods: From a group of 481 patients, 123 patients with TSZ (44 females; mean age, 22.9 years; mean age at onset, 7 years; mean duration of epilepsy, 16 years) were selected. A total of 1595 epileptic seizures, documented during video-electroencephalographic monitoring, were analyzed. Patients who had had surgery for epilepsy previously were excluded. Seizures were classified using a semiological seizure classification. Epilepsy syndromes were classified using all test data (electroencephalography, magnetic resonance imaging, computed tomography, positron emission tomography, and single-photon emission tomography). Data were compared using χ2 analysis or the Fisher exact test. Results: More patients with TSZ had extratemporal than temporal lobe epilepsies (79% vs. 1.7%; p < 0.0001) among those with an epilepsy localized to one lobe (n = 306). In the 123 patients, TSZ were part of 170 different seizure evolutions. Seizure evolutions began with TSZ as the first seizure type more often in patients with frontal lobe epilepsy (FLE) compared with patients with parieto-occipital lobe epilepsy (POLE) (40% in POLE vs. 67% in FLE; p < 0.05). In contrast, TSZ in POLE were more likely to be preceded by auras (50% in POLE vs. 26% in FLE; p < 0.05). TSZ were bilateral in 129 (76%) and unilateral in 41 (24%) seizure evolutions. Unilateral TSZ correctly lateralized the epilepsy syndrome to the contra-lateral hemisphere. Conclusion: Analysis of seizure semiology and evolution in patients with TSZ is helpful for differentiating between focal epilepsies of temporal, frontal, and parieto-occipital origin. Unilateral TSZ provide useful information for the lateralization of the epileptic syndrome.

Acute hypersensitivity reactions are serious complications of reexposure to aprotinin. Previous contact via infusions or fibrin tissue adhesives can induce specific antibodies. In this study, we aimed to elucidate the preoperative prevalence of aprotinin-specific antibodies in patients scheduled for cardiac operations. Sera of 520 consecutive cardiosurgical patients were collected preoperatively and screened retrospectively for aprotinin-specific IgG using a standard enzyme-linked immunosorbent assay (ELISA). Positive sera were analyzed also for aprotinin-specific IgA (ELISA) and IgE (fluorescence enzyme immunoassay). The histories of all patients were reviewed with focus on aprotinin preexposure. Of 520 patients, 22 (4%) had specific IgG. Only three of these had a documented aprotinin preexposure. Of 448 patients exposed to aprotinin intraoperatively, 15 had preformed specific antibodies. The only patient presenting with severe anaphylaxis was positive for both IgG and IgE, and had a recent IV preexposure in cardiovascular surgery. The presence of aprotinin-specific IgG alone seems not to induce adverse reactions on exposure. Exposure history alone is not sensitive enough to identify patients with aprotinin-specific antibodies.Anaphylaxis on IV reexposure to aprotinin is a medical emergency. The clinical significance of preformed aprotinin-specific IgG remains questionable, whereas preformed IgE was present in the only patient who suffered from severe anaphylaxis on reexposure to aprotinin. Preformed antibodies are not reliably predicted by exposure history.

Voraussetzung fur die chirurgische Behandlung pharmakoresistenter fokaler Epilepsien ist eine genaue Lokalisation des epileptogenen Fokus. Invasive elektrophysiolo-gische Methoden erlauben zwar eine genaue Lokalisation mit einer hohen Spezifitat, beinhalten aber zusatzliche Komplikationsmoglichkeiten fur den Patienten. Daher werden die nichtinvasiven bzw. semiinvasiven elektrophysioligschen Verfahren mit den ebenfalls nichtinvasiven struktur- und funktionsabbildenden Verfahren (MRT und PET) erganzt. Es sollte in dieser Studie der Frage nachgegangen werden, wie hoch die Sensitivitat des interiktalen FDG-PET in der Detektion eines epileptogenen Herdes bei fokalen Epilepsien temporalen (TLE) als auch frontalen (FLE) Ursprungs ist. Zudem sollte der positiv pradiktive Wert in Bezug auf die Anfallsfreiheit bzw. signifikante Anfallsreduktion (≥90%) nach Operation der nichtinvasiven prachirurgischen Untersuchungsmethoden bestimmt werden.

Objective: To evaluate the efficacy and safety of lacosamide when added to a single antiepileptic drug (AED) in patients with partial-onset seizures (POS). Background Lacosamide was approved as adjunctive treatment for adults with POS based on results from three pivotal Phase II/III trials in which highly refractory patients (45.2% had >7 lifetime AEDs) were treated according to strict dosing regimens and titration schedules. Design/Methods: VITOBA is a 6-month prospective, non-interventional study with a planned enrollment of 500 evaluable adult patients. Efficacy measures include seizure freedom and Clinical Global Impression of Change score. Safety and tolerability are also being evaluated. Results: Efficacy data are available for 99 patients (FAS) and safety data for 109 (SS). Patients were less refractory than those in the pivotal trials with 73.4% (SS) having a history of 1–3 lifetime AEDs, and only 6.4% (SS) having >6. Over the final three months of the study period, 77.8% and 64.6% of patients experienced a ≥50% and ≥75% reduction in seizure frequency and 43.4% were seizure free at study endpoint. Patients with a history of one lifetime AED experienced greater benefit with lacosamide than the overall population: 86.7% and 80.0% showed a ≥50% and ≥75% reduction in seizure frequency, and 66.7% experienced seizure freedom. Overall, treating physicians judged symptoms in 23.2% and 40.4% of patients as “very much improved” or “much improved.” The incidence of TEAEs (50.5%) was lower than in the pooled pivotal Phase II/III trials (81.0% for all doses). The most common TEAEs (≥5%) were fatigue (11.9%), dizziness (10.1%) and convulsion (5.5%). The mean lacosamide maintenance dose was 250mg/day and the median was 200mg/day. Conclusions: In this interim analysis, patients with less refractory POS treated with lacosamide as add-on to monotherapy derived therapeutic benefits that exceed those observed in the pivotal controlled trials of lacosamide for POS. Supported by: UCB Pharma. Disclosure: Dr. Noack-Rink has received personal compensation for activities with UCB Pharma. Dr. Mayer has nothing to disclose. Dr. Arnold has received personal compensation for activities with DESITIN, Eisai, Inc., and UCB Pharma. Dr. Kumke has received personal compensation for activities with UCB Pharma as an employee. Dr. Runge has received personal compensation for activities with Eisai and UCB.Dr. Runge has received research support from UCB.

Depression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet-administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual. This randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3). Results of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety. ClinicalTrials.gov: NCT02791724 . Registered 01 June 2016.