Rehabilitation in patients with newly diagnosed epilepsy: A controlled, 1-year follow-up study on a specialized inpatient rehabilitation program.

OBJECTIVES: To evaluate the efficacy of a specialized inpatient rehabilitation program in patients with newly diagnosed epilepsy (NDE), who had been referred within 1 year after diagnosis. METHODS: We performed an open, prospective, controlled study comparing a 1-year follow-up assessment of patients with NDE after completing a rehabilitation program at an epilepsy center (rehabilitation group) with a control group of patients with similar epilepsy duration, but without rehabilitation in the first year after diagnosis. Primary outcome measures comprised emotional adaptation to epilepsy, depression and anxiety; and secondary outcome measures were overall quality of life (QoL), overall health, perceived restrictions because of epilepsy, level of information about epilepsy, and employment status. RESULTS: Comparison of the admission data of 74 rehabilitation group patients (mean age and SD 47.7 ± 13.0 years) with the pre-rehabilitation assessment of 56 control patients (45.5 ± 12.1 years) revealed no significant differences concerning sociodemographic and health data. Comparison of the follow-up assessment of the rehabilitation group and the pre-rehabilitation assessment of the control group showed significantly better values for the rehabilitation group on emotional adaptation to epilepsy (p = .003), overall QoL (p = .006) and overall health (p = .011), perceived restrictions because of epilepsy, and subjective level of information about epilepsy (both p's < .001). There were no statistically significant differences concerning depression and anxiety or employment status (all p's > .50). One year after rehabilitation, patients in the rehabilitation group were more often seizure-free and less often on sickness absence than control group patients (both p's < .001). SIGNIFICANCE: Since reduced QoL shortly after diagnosis of NDE is associated with seizure recurrence, an early identification of patients with a greater need for support seems important. This epilepsy-related rehabilitation program showed lasting effects on several aspects of adaptation to epilepsy and QoL.

Validation of Conversion Factors for Therapeutic Drug Monitoring of Lacosamide, Lamotrigine, and Levetiracetam in Dried Capillary Blood.

BACKGROUND: Estimation of serum concentrations of antiseizure medications (ASMs) based on dried capillary blood is an alternative method for therapeutic drug monitoring of epilepsy. The aim of this study was to validate the conversion factors for lacosamide (LCM), lamotrigine (LTG), and levetiracetam (LEV), which were determined in an independent patient sample in a previous study, and identify the most accurate conversion method (simple ratio and regression). METHODS: Venous and capillary blood samples were collected from adult inpatients with epilepsy treated with LCM (n = 25), LTG (n = 27), and/or LEV (n = 29) before the morning dose (T1) and approximately 2 hours after (T2). Capillary blood was collected using volumetric absorptive microsampling, and the ASM concentrations were measured using a validated liquid chromatography-mass spectrometry method for dried blood samples. Serum concentrations were estimated using conversion factors and compared with those measured using routine laboratory methods. RESULTS: For all 3 ASMs, the simple ratio approach performed better than the regression approach. Intraclass correlation coefficients revealed a high agreement between the estimated and measured serum concentrations (LCM T1: 0.93, T2: 0.90; LTG T1: 0.91, T2: 0.91; and LEV T1: 0.97, T2: 0.94). The criteria of the European Medicines Agency for cross-validation were fulfilled for LCM (T1: 72%; T2: 75%) and LEV (T1: 86%; T2: 75%), whereas for LTG, this was only true for capillary blood concentrations ≤11 µ g/mL [42.9 µ mol/L; T1: 72% (vs. 63% for total range), T2: 67% (vs. 62%)]. CONCLUSIONS: Estimating serum concentrations using capillary blood concentrations is feasible and accurate for LCM and LEV over a wide concentration range, as found in clinical practice. The applicability of this mehod for LTG is limited by its greater variability at higher concentrations; however, acceptable results were achieved for the large proportion of patients with low and medium LTG concentrations.

Efficacy of a specialized inpatient rehabilitation program in patients with early versus chronic epilepsy.

OBJECTIVE: To evaluate the efficacy of a specialized inpatient rehabilitation program in patients with early in comparison with chronic epilepsy. METHODS: We performed a prospective, open pre/post study using a parallel group design. Patients with early epilepsy (EE, treatment with anti-seizure medication [ASM] ≤ 1 year) or with chronic epilepsy (CE, ASM treatment > 5 years) completed questionnaires at the time of their admission to the rehabilitation program and at discharge. Outcome measures comprised scales from the PESOS questionnaire (PErformance, SOciodemographic aspects, Subjective estimation; e.g., emotional adaptation to epilepsy) as well as screening instruments for depression (Neurological Disorders Depression Inventory for Epilepsy, NDDI-E) and anxiety (Generalized Anxiety Disorder Scale, GAD-7). Linear mixed models (LMMs) were used to determine the effects of the program in the total group and to compare the effects between patients with EE and CE. RESULTS: The analyses included 79 patients with EE and 157 patients with CE. Baseline comparisons revealed differences in disease-related and sociodemographic variables (e.g., patients with EE were older, those with CE had a higher seizure frequency and a higher rate of unemployment; all p < .01). LMMs showed significant improvements in emotional adaptation to epilepsy, depression, anxiety, overall quality of life and overall health as well as in perceived overall restrictions because of epilepsy and the subjective level of information about epilepsy (all p < .001). Despite the different duration of epilepsy, baseline levels as well as improvements did not differ between patients with EE and CE (all p > .05) except for the perceived level of information, which was significantly lower in patients with EE at admission and improved to a higher extent in this group (both p < .001). CONCLUSION: Both patients with EE and patients with CE who are referred to a specialized comprehensive rehabilitation program benefit from the participation in this program with respect to emotional adaptation to epilepsy, aspects of quality of life, and level of information about epilepsy.

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

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

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

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

Therapeutic Drug Monitoring of Lamotrigine, Lacosamide, and Levetiracetam in Dried Capillary Blood-Determination of Conversion Factors for Serum-Based Reference Ranges.

BACKGROUND: Drug concentrations of antiepileptic drugs (AEDs) are routinely determined from blood serum or plasma at trough levels (before intake of morning dose). In capillary blood collection, blood is taken from the fingertip with the aid of a disposable tool and dried on absorbent material. The volumetric absorptive microsampling technique offers several advantages over the use of filter paper cards. The aim of this study was to determine conversion factors for the estimation of AED serum concentrations from capillary blood concentrations. METHODS: Venous and capillary blood samples were collected from adult inpatients with epilepsy who were treated with lacosamide (LCM, n = 30), lamotrigine (LTG, n = 40), and/or levetiracetam (LEV, n = 36). A validated liquid chromatography-mass spectrometry (LC-MS) method for dried blood samples for these AEDs was compared with routine serum laboratory methods. Method agreement was evaluated using different regression techniques, and the conversion factors were calculated. RESULTS: Regression analyses revealed a linear relationship between serum and capillary blood concentrations for all 3 AEDs (r ≥ 0.95). For LTG, the regression intercept was significantly different from 0, indicating that the relationship was linear, but not necessarily proportional. Although LEV and LCM concentrations tended to be lower in capillary blood than in serum (mean ratio of serum concentration to capillary blood concentration: 1.14 and 1.22, respectively), LTG concentrations were higher in capillary blood (mean ratio = 0.85). CONCLUSIONS: The estimation of serum concentrations from measured capillary blood concentrations is feasible for LCM, LTG, and LEV. A simple ratio approach using the mean ratio and Passing-Bablok regression showed the best results for all 3 AEDs. The volumetric absorptive microsampling technique facilitates the quantitative sample collection of capillary blood and overcomes the drawbacks associated with the classical dried blood spot technique.

Epilepsy associated with tuberous sclerosis complex in childhood: Long-term outcome in children after epilepsy surgery and children non-eligible for epilepsy surgery.

OBJECTIVE: Drug-resistant epilepsy is one of the major disease burdens in patients with tuberous sclerosis complex (TSC). Epilepsy surgery has been shown to be effective in TSC, but making a decision for surgery is often more complex than in other surgically amenable epilepsy syndromes and not all patients with TSC are eligible. We investigated long-term outcomes (after ≥one year; median, 6.4 years) with a special interest in general developmental level, health-related quality of life, parental concerns due to epilepsy, impact on family, and social adaptation in children who underwent epilepsy surgery and in children who were not eligible for surgery. METHODS: Eighty-five children (median age at intervention: 3.3 years, interquartile range [IQR]: 1.8-6.3 years) with TSC-related epilepsy had a presurgical investigation, and 34 of this group underwent epilepsy surgery. At follow-up (median age: 11.5 years, IQR: 7.8-15.5 years), we assessed seizure outcome, health-related quality of life, social adaptation, parental concerns due to epilepsy, and general developmental level based on established questionnaires and a standardized interview. Generalized linear models were performed for statistical evaluation. RESULTS: At follow-up, 53% (18/34) of the operated patients were seizure free for ≥12 months and 30% (15/50) of the patients non-eligible for epilepsy surgery (p = 0.037). In the surgical group, developmental level was significantly higher in seizure-free patients, in comparison to non-seizure-free patients (p = 0.004); this was also observed in the non-surgical group, but less marked (p = 0.089). Furthermore, developmental level was significantly (p ≤ 0.001) related to quality of life, social adaptation, impact on family, and parental concerns. In both cohorts, parental concerns were less pronounced if children became seizure free (p < 0.001 and p = 0.018, respectively). SIGNIFICANCE: In children with TSC-related epilepsy, quality of life, social adaptation, and impact on family were related to general developmental level, which in turn was significantly related to seizure freedom. Consequent epilepsy management aiming at seizure freedom, including presurgical evaluation and, if indicated, epilepsy surgery in a center specifically experienced with TSC-related epilepsy, is a worthwhile effort to improve quality of life in patients with TSC and their families.

Effects of a specialized inpatient treatment program on epilepsy-related impairments of patients with epilepsy and intellectual disability as rated by relatives and professional caregivers.

INTRODUCTION: The aim of the study was to determine the impact of a comprehensive inpatient treatment program for persons with epilepsy and intellectual disability (ID) on the concerns of relatives and caregivers, quality of life (QoL), and global health and clinical aspects, assessed by a questionnaire for relatives and caregivers. METHODS: We performed an open, controlled pre/post study in inpatients with epilepsy and ID or acquired brain damage treated for at least 14 days in a tertiary referral center for epilepsy. Questionnaires were administered to relatives/professional caregivers shortly before admission and 6 months after discharge for the treatment group (TG). The control group (CG) was recruited from the waiting list; questionnaires were answered at the time of application for treatment and 3-6 months later. The questionnaire was the GEOS-43G, the German version of the Glasgow Epilepsy Outcome Scale (GEOS-35), which was extended by eight additional questions from the GEOS-90. Furthermore, QoL, global health, and clinical aspects were assessed using a short questionnaire. Generalized estimation equations (GEEs) were used for statistical analyses. RESULTS: One-hundred and eight subjects were evaluable in the TG, and 90 in the CG. Concerns about seizures, injuries/risks, medical treatment, diagnostic issues, and the GEOS-43G total score decreased significantly in the TG in contrast to the CG. For the TG, improvements were also significant for global QoL, global health, efficacy, tolerability of AEDs, and for seizure frequency. Caregivers reported larger improvements compared to relatives. CONCLUSION: The evaluation of the relatives and caregivers in our study indicates that inpatient treatment in a specialized center with a dedicated multi-professional program led to significant improvements regarding the concerns of relatives or caregivers, and in the QoL and related aspects in persons with epilepsy and ID. This shows that specialized inpatient treatment may be helpful for persons with epilepsy and ID.

Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).

OBJECTIVE: To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. METHODS: Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. RESULTS: Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. INTERPRETATION: In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432.

Influence of dose and antiepileptic comedication on brivaracetam serum concentrations in patients with epilepsy.

The aim of this study was to investigate the influence of concomitant antiepileptic drugs (AEDs) on brivaracetam (BRV) trough serum concentrations. A total number of 368 routinely collected blood samples from 148 inpatients from Mara Hospital (Bethel Epilepsy Center) and von Bodelschwingh Foundation Bethel were retrospectively evaluated. Generalized estimation equations (GEEs) were used for statistical analysis. GEE analyses showed that BRV trough serum concentrations were significantly lower in patients with strong enzyme-inducing AEDs (carbamazepine, phenytoin, and/or phenobarbital/primidone, -49%), but were not affected by concomitant intake of oxcarbazepine or eslicarbazepine. Age and gender did not have a significant effect. An alternative GEE model analyzing the BRV level-to-dose ratios yielded comparable results. Our results from routine therapeutic drug monitoring data indicate that the effect of enzyme-inducing AEDs on BRV serum concentrations is stronger than the 20%-30% reduction in BRV exposure previously reported in pharmacokinetics studies. Further research is necessary to evaluate these differences and to elucidate possible clinical consequences.

Operative posterior disconnection in epilepsy surgery: Experience with 29 patients.

OBJECTIVE: It has been suggested that multilobar epilepsies caused by lesions restricted to the posterior cerebral quadrant (ie, the parietal, temporal, and occipital lobes) can be treated successfully by a procedure termed posterior disconnection. The objective of the present paper was to identify determinants of the epileptological outcome following posterior disconnection surgery. METHODS: The authors retrospectively analyzed a series of 29 consecutive patients undergoing posterior disconnection surgery between 2005 and 2017 for the treatment of refractory posterior quadrantic epilepsy. Specifically, all presurgical and postoperative magnetic resonance (MR) studies were reviewed to identify cases with an incomplete disconnection, or the presence of a more widespread pathology involving the whole hemisphere rather than only its posterior quadrant. In addition, we reevaluated all presurgical video-electroencephalography (EEG) reports. RESULTS: Seizure-free (International League Against Epilepsy [ILAE] 1) after surgery were 3/3 patients with EEG findings restricted to the posterior quadrant, 0/7 patients who had propagation of epileptic activity to the contralateral frontal lobe, and 11/19 (57.9%) who showed propagation to ipsilateral frontal and/or contralateral posterior. Eleven of 13 (84.6%) patients with purely posterior quadrantic magnetic resonance imaging (MRI) findings (as retrospectively diagnosed by neuroimaging) vs 3/16 (18.8%) cases with additional subtle abnormalities outside the posterior quadrant became seizure-free (P = .001). Eleven of 16 (68.8%) patients with complete disconnections were seizure-free vs only 3/13 (23.0%) cases with leftover temporal lobe tissue with contact to the insula (P = .025, both Fisher's exact test). SIGNIFICANCE: A posterior disconnection is a technically demanding but very effective operation for posterior quadrantic epilepsy. Good epileptologic outcomes require not only that the epileptogenic lesion does not extend beyond the confines of the disconnected cerebral volume but also the absence of subtle MRI abnormalities, more widespread than the clear-cut lesion of the posterior quadrant. Hemispheric or contralateral (particularly frontal) propagation of the epileptic activity may also indicate the presence of a hemispheric rather than posterior quadrantic pathology.

Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014.

OBJECTIVE: Surgical volumes at large epilepsy centers are decreasing. Pediatric cohorts, however, show a trend toward more resections and superior outcome. Differences in pediatric and adult epilepsy surgery were investigated in our cohort. METHODS: The Bethel database between 1990 and 2014 was retrospectively analyzed. RESULTS: A total of 1916 adults and 1300 children underwent presurgical workup. The most common etiologies were medial temporal sclerosis (35.4%) in adults, and focal cortical dysplasias (21.1%) and diffuse hemispheric pathologies (14.7%) in children. Only 1.4% of the total cohort had normal histopathology. A total of 1357 adults (70.8%) and 751 children (57.8%) underwent resections. Surgery types for children were more diverse and showed a higher proportion of extratemporal resections (32.8%) and functional hemispherectomies (20.8%). Presurgical evaluations increased in both groups; surgical numbers remained stable for children, but decreased in the adult group from 2007 on. The patients' decision against surgery in the adult nonoperated cohort increased over time (total = 44.9%, 27.4% in 1995-1998 up to 53.2% in 2011-2014; for comparison, in children, total = 22.1%, stable over time). Postsurgical follow-up data were available for 1305 adults (96.2%) and 690 children (91.9%) 24 months after surgery. The seizure freedom rate was significantly higher in children than in adults (57.8% vs 47.5%, P < 0.001) and significantly improved over time (P = 0.016). SIGNIFICANCE: Pediatric epilepsy surgery has stable surgical volumes and renders more patients seizure-free than epilepsy surgery in adults. A relative decrease in hippocampal sclerosis, the traditional substrate of epilepsy surgery, changes the focus of epilepsy surgery toward other pathologies.

No differences in microbiome changes between anti-adhesive and antibacterial ingredients in toothpastes during periodontal therapy.

AIM: This subgroup analysis of a 12-week randomized, double-blind, and two-center trial aimed to evaluate whether two different toothpaste formulations can differentially modulate the dental microbiome. MATERIAL AND METHODS: Forty one mild to moderate periodontitis patients used as an adjunct to periodontal treatment either a toothpaste with anti-adhesive zinc-substituted carbonated hydroxyapatite (HA) or with antimicrobial and anti-adhesive amine fluoride/stannous fluoride (AmF/SnF2 ) during a 12-week period. Plaque samples from buccal/lingual, interproximal, and subgingival sites were taken at baseline, 4 weeks after oral hygiene phase, and 8 weeks after periodontal therapy. Samples were analyzed with paired-end Illumina Miseq 16S rDNA sequencing. The differences and changes on community level (alpha and beta diversity) and on the level of single agglomerated ribosomal sequence variants (aRSV) were calculated with analysis of covariance (ANCOVA) and likelihood ratio test (LRT). RESULTS: Interproximal and subgingival sites harbored predominately Fusobacterium and Prevotella species associated with periodontitis, whereas buccal/lingual sites harbored mainly Streptococcus and Veillonella species associated with periodontal health. Alpha and beta diversity did not change noticeably differently between both toothpaste groups (P > 0.05, ANCOVA). Furthermore, none of the aRSVs showed a noticeably different change between the tested toothpastes during periodontal therapy (Padj . > 0.05, LRT). CONCLUSION: The use of a toothpaste containing anti-adhesive HA did not induce statistically noticeably different changes on microbial composition compared to an antimicrobial and anti-adhesive AmF/SnF2 formulation.

Decreasing SUDEP incidence in a tertiary epilepsy center between 1981 and 2016: Effects of better patient supervision.

OBJECTIVE: The objective of this study was to investigate the incidence of sudden unexpected death in epilepsy (SUDEP) in a tertiary epilepsy center in the years 1981-2016 with an emphasis on patient supervision and nursing intervention in different departments. METHODS: We identified 14 SUDEP cases (probable, definite, definite plus). Patient-years (PY) and incidence were calculated for the periods of six years for the general epileptology wards (adults and children) and, in addition, for the epilepsy monitoring unit (EMU) since 1990. RESULTS: The incidence of SUDEP showed a decreasing trend over time (r = -0.81; p = 0.053, two-sided; Pearson correlation coefficient). This is especially true in children (no SUDEP occurred in pediatric general epileptology since 1992). Additionally, in the EMU (314 PY since the start of 1990), no SUDEP occurred. Sudden unexpected death in epilepsy incidence was highest (6.8/1000 PY) in the early time periods (1981-1992) and lowest (1.7/1000 PY) in the later time periods (1999-2010). In the general epileptology wards (3579 PY), the overall incidence was 3.9 per 1000 PY (95% confidence interval (CI): 2.1-6.6). CONCLUSIONS: We assume that the decreased SUDEP incidence is an effect of better supervision by the use of technical means (e.g., video cameras, pulse oximeters, seizure detection systems) and rooming-in of parents or family.

Sustained Effort Network for treatment of Status Epilepticus (SENSE) - A multicenter prospective observational registry.

Status epilepticus (SE) is an important neurological emergency lacking adequate evidence for efficacy and safety of treatment beyond the application of benzodiazepines as first treatment step. To bridge the gap between the few pivotal trials and retrospective uncontrolled case series, we established a prospective multicenter registry recruiting patients in experienced centers in German-speaking countries. We could document 1179 episodes of 1049 patients over a period of 5 years. First data analysis showed that in the majority of the episodes, established treatment guidelines were not followed. Latency between status onset and different treatment steps were longer, and bolus doses lower than recommended. Moreover, a relevant proportion of the patients did not receive a benzodiazepine but levetiracetam as first treatment step. Although SE could be controlled in more than 90% of the episodes, lower bolus dose and longer treatment latency were associated with refractoriness of the SE in multivariate analysis. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

Assessment of the correlations of lacosamide concentrations in saliva and serum in patients with epilepsy.

Therapeutic drug monitoring of antiepileptic drugs is based on patient serum samples. In this study, we evaluated the correlation between lacosamide (LCM) steady state concentrations in serum and saliva samples. Additionally, we investigated the relation with daily dose, and assessed the feasibility of saliva collection. This was an open-label, single center study including data from 25 patients at the Bethel Epilepsy Center treated with LCM (50-650 mg/d). Samples were collected in the morning (fasting values) and in selected cases at 50 minutes to 5 hours after the morning dose. Nonsignificant differences in the mean LCM morning (trough) concentration in serum and saliva were observed. Serum and saliva concentrations across all samples were highly correlated, (r = .874), with a slightly lower correlation when only fasting values were analyzed (r = .860). Higher correlation with daily dosages was observed in serum samples (r = .773) than in saliva samples (r = .604). Serum and saliva concentrations increased significantly after intake of the LCM morning dose (P < .001). The median absolute and percentage increase of LCM in serum were moderately lower than in saliva samples, with a few outliers in saliva samples. Consequently, saliva could offer great clinical potential to monitor drug concentrations and guide LCM treatment in epileptic patients.

Influence of Dose and Antiepileptic Comedication on Lacosamide Serum Concentrations in Patients With Epilepsy of Different Ages.

BACKGROUND: Lacosamide (LCM) is a new antiepileptic drug (AED). The purpose of the study was to investigate the effects of LCM dose, body weight, height, sex, age, and concomitant AEDs on LCM trough serum concentrations (at a steady state) in patients with epilepsy. METHODS: A total number of 3154 blood samples of 973 consecutive patients of the Mara Hospital (Bethel Epilepsy Centre) were evaluated. Generalized estimating equation (GEE) models were used for statistical analyses. RESULTS: GEE analyses showed that LCM trough serum concentrations were significantly correlated with the body weight-normalized LCM dose (range: 0.44-25.7 mg/kg; 45-1050 mg) and significantly dependent on comedication and age. Compared with adults (18-60 years), the LCM trough serum concentrations of children aged 6-12 years and children younger than 6 years were significantly lower (-21% to -38%, respectively) and those of elderly patients (>60 years) were significantly higher (+20%). Sex had no significant influence. Carbamazepine, phenytoin, primidone, phenobarbital, and methsuximide decreased LCM trough serum concentrations significantly by 30%, 32%, 34%, 39%, and 41%, respectively, whereas other AEDs (eg, oxcarbazepine, eslicarbazepine acetate, valproate) had no significant or only a minor impact (zonisamide) on LCM trough concentrations. In children, the effect of enzyme-inducing AEDs was more marked. Of note, the number of blood samples (n = 151) of patients younger than 12 (n = 78) was comparatively low. Alternative GEE models confirmed the effect of comedication, whereas the effect of age, especially in children, depended on adjustment of LCM dosage to body weight, body surface area, or approximated volume of distribution. CONCLUSIONS: In accordance with previous therapeutic drug monitoring studies, our results confirmed that enzyme inducers reduce the LCM trough serum concentrations by 30%-40%. In children, the effects of comedication are more pronounced but should be confirmed by further studies.

Psychometric evaluation of the Epilepsy-related Fears in Parents Questionnaire.

OBJECTIVE: The aim of the article was to examine the psychometric properties of the Epilepsy-related Fears in Parents Questionnaire (EFPQ). METHOD: Internal consistency, factor structure, and construct validity were analyzed based on data from 291 parents participating in the baseline assessment of a quasi-experimental study on the efficacy of the FAMOSES (modulares Schulungsprogramm Epilepsie für Familien) parents' program. The control group of this study was used to calculate the test-retest reliability, while the responsiveness of the questionnaire was evaluated by comparing matched groups of FAMOSES participants and control parents. RESULTS: An exploratory factor analysis revealed two factors of epilepsy-related fears, "Fears about short-term consequences of the child's epilepsy" (8 items) and "Fears about the future development of the child and the child's epilepsy" (9 items). Both showed good reliability (Cronbach's α=.89 and .91, resp.; test-retest reliability: ICC=.77 and .80, resp.), and construct validity was confirmed by correlations with epilepsy-related variables and psychosocial outcomes, e.g., with the Impact on Family Scale (r=.48 and .61, resp.). The FAMOSES parents' program significantly reduced epilepsy-related fears (p<.05 for both subscales). CONCLUSION: The EFPQ proved to be a reliable, valid, and responsive instrument for the assessment of parental fears about their child's epilepsy and can be recommended for use in future studies.

Patients' perspectives on management and barriers of regular antiepileptic drug intake.

PURPOSE: The aim of our study was to assess the management of drug intake and potential barriers to adherence reported by two different patient groups. METHODS: The study was performed in cooperation with the Regional Chamber of Pharmacists of Rhineland-Palatinate and three neurologists in private practice specialized in epileptology. In total, 108 patients surveyed in 43 pharmacies (Group P) and 118 patients treated by the specialized neurologists (Group N) completed anonymously a questionnaire on intake of antiepileptic drugs (AEDs). The statistical evaluation was performed using nonparametric tests and logistic regression analyses. RESULTS: Group N more often used adherence aids, compared with Group P (68.6% vs. 46.3%, p<0.01), and the number of doses per day was significantly lower in Group N (Mann-Whitney test, p=0.046), but the percentage of patients who reported problems with the regular intake of their medication did not differ significantly between groups (Group N vs. P: 47.0% vs. 40.0%). If patients noticed that they missed a dose, 45.3% completely skipped the missed dose (Group N vs. P: 43.0% vs. 48.1%, n.s.). In a multivariate analysis, significant risk factors of problems with regular drug intake were age<25yrs. (p<0.01) and patient-reported adverse effect of AED (p<0.01), followed by the number of AED doses per day (p<0.05), while gender, intake habits, usage of adherence aids, and patient-rated efficacy of AEDs were not significant. CONCLUSION: Patients treated by neurologists specialized in epileptology did not report less problems with adherence than patients surveyed in pharmacies. Since barriers for a regular intake are diverse, the use of a short questionnaire on management of drug intake may lead to an individually tailored counseling of patients to improve adherence.

Characteristics and healthcare situation of adult patients with tuberous sclerosis complex in German epilepsy centers.

OBJECTIVE: The objective of the present study was to collect systematic data on the care of adult patients with tuberous sclerosis complex (TSC) in German epilepsy centers, to describe the characteristics of patients in this age group, and to clarify whether and how the recommended interdisciplinary care is implemented. METHODS: This retrospective survey involved 12 major epilepsy centers in Germany. Aggregated data were collected based on an electronic questionnaire that addressed the sociodemographic data, characteristics of the epilepsy syndromes, and general healthcare setting of adult patients with TSC. RESULTS: The survey included 262 patients (mean age: 36.2±9.0years) with TSC, most of whom were reported to live in either a home for persons with a disability (37.0%), a residential care home (6.9%), or with their parents (31.1%). A further 13.0% were self-sustaining, and 8.8% were living with a partner. Most patients presented with focal (49.6%) or multifocal (33.2%) epilepsy, with complex partial, dialeptic, and automotor seizures in 66% of patients and generalized tonic-clonic seizures in 63%. Drug-refractory epilepsy was seen in 78.2% of patients, and 17.6% were seizure-free at the time of the survey. Of the 262 patients, presurgical diagnostics were performed in 27% and epilepsy surgery in 9%, which rendered 50% of these patients seizure-free. Renal screening had been performed in 56.1% within the last three years and was scheduled to be performed in 58.0%. Cases of renal angiomyolipoma were present in 46.9% of the patients. Dermatologic and pulmonary screenings were known to be planned for only few patients. CONCLUSION: Despite TSC being a multisystem disorder causing considerable impairment, every fifth adult patient is self-sustaining or living with a partner. In clinical practice, uncontrolled epilepsy and renal angiomyolipoma are of major importance in adult patients with TSC. Most patients suffer from focal or multifocal epilepsy, but epilepsy surgery is performed in less than 10% of these patients. Interdisciplinary TSC centers may help to optimize the management of patients with TSC regardless of age and ensure early and adequate treatment that also considers the advances in new therapeutic options.