A multicenter, matched case-control analysis comparing burden of illness among patients with tuberous sclerosis complex related epilepsy, generalized idiopathic epilepsy, and focal epilepsy in Germany.

BACKGROUND: Depending on the underlying etiology and epilepsy type, the burden of disease for patients with seizures can vary significantly. This analysis aimed to compare direct and indirect costs and quality of life (QoL) among adults with tuberous sclerosis complex (TSC) related with epilepsy, idiopathic generalized epilepsy (IGE), and focal epilepsy (FE) in Germany. METHODS: Questionnaire responses from 92 patients with TSC and epilepsy were matched by age and gender, with responses from 92 patients with IGE and 92 patients with FE collected in independent studies. Comparisons were made across the main QoL components, direct costs (patient visits, medication usage, medical equipment, diagnostic procedures, ancillary treatments, and transport costs), indirect costs (employment, reduced working hours, missed days), and care level costs. RESULTS: Across all three cohorts, mean total direct costs (TSC: €7602 [median €2620]; IGE: €1919 [median €446], P < 0.001; FE: €2598 [median €892], P < 0.001) and mean total indirect costs due to lost productivity over 3 months (TSC: €7185 [median €11,925]; IGE: €3599 [median €0], P < 0.001; FE: €5082 [median €2981], P = 0.03) were highest among patients with TSC. The proportion of patients with TSC who were unemployed (60%) was significantly larger than the proportions of patients with IGE (23%, P < 0.001) or FE (34%, P = P < 0.001) who were unemployed. Index scores for the EuroQuol Scale with 5 dimensions and 3 levels were significantly lower for patients with TSC (time-trade-off [TTO]: 0.705, visual analog scale [VAS]: 0.577) than for patients with IGE (TTO: 0.897, VAS: 0.813; P < 0.001) or FE (TTO: 0.879, VAS: 0.769; P < 0.001). Revised Epilepsy Stigma Scale scores were also significantly higher for patients with TSC (3.97) than for patients with IGE (1.48, P < 0.001) or FE (2.45, P < 0.001). Overall Quality of Life in Epilepsy Inventory-31 items scores was significantly lower among patients with TSC (57.7) and FE (57.6) than among patients with IGE (66.6, P = 0.004 in both comparisons). Significant differences between patients with TSC and IGE were also determined for Neurological Disorder Depression Inventory for Epilepsy (TSC: 13.1; IGE: 11.2, P = 0.009) and Liverpool Adverse Events Profile scores (TSC: 42.7; IGE: 37.5, P = 0.017) with higher score and worse results for TSC patients in both questionnaires. CONCLUSIONS: This study is the first to compare patients with TSC, IGE, and FE in Germany and underlines the excessive QoL burden and both direct and indirect cost burdens experienced by patients with TSC.

The impact of referring patients with drug-resistant focal epilepsy to an epilepsy center for presurgical diagnosis.

BACKGROUND: Epilepsy surgery is an established treatment for drug-resistant focal epilepsy (DRFE) that results in seizure freedom in about 60% of patients. Correctly identifying an epileptogenic lesion in magnetic resonance imaging (MRI) is challenging but highly relevant since it improves the likelihood of being referred for presurgical diagnosis. The epileptogenic lesion's etiology directly relates to the surgical intervention's indication and outcome. Therefore, it is vital to correctly identify epileptogenic lesions and their etiology presurgically. METHODS: We compared the final histopathological diagnoses of all patients with DRFE undergoing epilepsy surgery at our center between 2015 and 2021 with their MRI diagnoses before and after presurgical diagnosis at our epilepsy center, including MRI evaluations by expert epilepsy neuroradiologists. Additionally, we analyzed the outcome of different subgroups. RESULTS: This study included 132 patients. The discordance between histopathology and MRI diagnoses significantly decreased from 61.3% for non-expert MRI evaluations (NEMRIs) to 22.1% for epilepsy center MRI evaluations (ECMRIs; p < 0.0001). The MRI-sensitivity improved significantly from 68.6% for NEMRIs to 97.7% for ECMRIs (p < 0.0001). Identifying focal cortical dysplasia (FCD) and amygdala dysplasia was the most challenging for both subgroups. 65.5% of patients with negative NEMRI were seizure-free 12 months postoperatively, no patient with negative ECMRI achieved seizure-freedom. The mean duration of epilepsy until surgical intervention was 13.6 years in patients with an initial negative NEMRI and 9.5 years in patients with a recognized lesion in NEMRI. CONCLUSIONS: This study provides evidence that for patients with DRFE-especially those with initial negative findings in a non-expert MRI-an early consultation at an epilepsy center, including an ECMRI, is important for identifying candidates for epilepsy surgery. NEMRI-negative findings preoperatively do not preclude seizure freedom postoperatively. Therefore, patients with DRFE that remain MRI-negative after initial NEMRI should be referred to an epilepsy center for presurgical evaluation. Nonreferral based on NEMRI negativity may harm such patients and delay surgical intervention. However, ECMRI-negative patients have a reduced chance of becoming seizure-free after epilepsy surgery. Further improvements in MRI technique and evaluation are needed and should be directed towards improving sensitivity for FCDs and amygdala dysplasias.

Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012-2021) from a University Hospital in Germany.

BACKGROUND AND OBJECTIVES: Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials. METHODS: The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly. RESULTS: This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021. CONCLUSION: Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.

Determinants of quality of life in adults with epilepsy: a multicenter, cross-sectional study from Germany.

BACKGROUND: Assessment of quality of life (QoL) has become an important indicator for chronic neurological diseases. While these conditions often limit personal independence and autonomy, they are also associated with treatment-related problems and reduced life expectancy. Epilepsy has a tremendous impact on the QoL of patients and their families, which is often underestimated by practitioners. The aim of this work was to identify relevant factors affecting QoL in adults with epilepsy. METHODS: This cross-sectional, multicenter study was conducted at four specialized epilepsy centers in Germany. Patients diagnosed with epilepsy completed a standardized questionnaire focusing on QoL and aspects of healthcare in epilepsy. Univariate regression analyses and pairwise comparisons were performed to identify variables of decreased QoL represented by the overall Quality of Life in Epilepsy Inventory (QOLIE-31) score. The variables were then considered in a multivariate regression analysis after multicollinearity analysis. RESULTS: Complete datasets for the QOLIE-31 were available for 476 patients (279 [58.6%] female, 197 [41.4%] male, mean age 40.3 years [range 18-83 years]). Multivariate regression analysis revealed significant associations between low QoL and a high score on the Liverpool Adverse Events Profile (LAEP; beta=-0.28, p < 0.001), Hospital Anxiety and Depression Scale - depression subscale (HADS-D; beta=-0.27, p < 0.001), Neurological Disorders Depression Inventory in Epilepsy (NDDI-E; beta=-0.19, p < 0.001), revised Epilepsy Stigma Scale (beta=-0.09, p = 0.027), or Seizure Worry Scale (beta=-0.18, p < 0.001) and high seizure frequency (beta = 0.14, p < 0.001). CONCLUSION: Epilepsy patients had reduced QoL, with a variety of associated factors. In addition to disease severity, as measured by seizure frequency, the patient's tolerability of anti-seizure medications and the presence of depression, stigma, and worry about new seizures were strongly associated with poor QoL. Diagnosed comorbid depression was underrepresented in the cohort; therefore, therapeutic decisions should always consider individual psychobehavioral and disease-specific aspects. Signs of drug-related adverse events, depression, fear, or stigmatization should be actively sought to ensure that patients receive personalized and optimized treatment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00022024; Universal Trial Number: U1111-1252-5331).

The Long-Term Use of Diagnostic Subdural Electroencephalogram Electrodes and Subdural Hematoma: A Prospective Cohort Study.

OBJECTIVES: Seizures and status epilepticus (SE) are frequent complications of acute subdural hematoma (aSDH) associated with increased morbidity and mortality. Therefore, we aimed to evaluate whether invasive subdural electroencephalogram recording leads to earlier seizure detection and treatment initiation in patients with aSDH. DESIGN: Prospective, single-center, cohort trial. SETTING: Neurologic and neurosurgical ICUs of one academic hospital in Germany. PATIENTS: Patients with aSDH undergoing surgical treatment. In total, 76 patients were enrolled in this study, 31 patients (40.8%) were assigned to the invasive electroencephalogram (iEEG) monitoring group and 45 patients (59.2%) to control group. INTERVENTIONS: The electrode group was implanted with a subdural strip electrode providing up to 7 days of real-time electroencephalogram recording in the neurointensive care unit, whereas the control group received regular normal surface electroencephalograms during the 7-day period. The primary outcomes were the prevalence and time to seizures and SE occurrence. Secondary outcomes included neurologic outcomes assessed using the Glasgow Outcome Scale (GOS) at discharge and 6-month follow-up and the prevalence of focal structural epilepsy within 2 years after discharge. MEASUREMENTS AND MAIN RESULTS: The trial was stopped after a study committee meeting when the prespecified criteria were met. The iEEG and control groups were well-matched for clinical characteristics at admission. Frequencies of seizures and SE detection were significantly higher in the iEEG group than in the control group (61% vs 15.6%; p < 0.001 and 38.7% vs 11.1%; p = 0.005). Time to seizure and SE detection was significantly earlier (median 29.2 vs 83.8 hr; p = 0.018 and 17.2 vs 83.8 hr; p = 0.033) in the iEEG group than in the control group. Favorable outcomes (GOS 4-5) were more frequently achieved in the iEEG group than in the control group (58% vs 31%; p = 0.065). No significant differences were detected in long-term mortality or post-traumatic epilepsy. CONCLUSIONS: Invasive subdural electroencephalogram monitoring is valuable and safe for early seizure/SE detection and treatment and might improve outcomes in the neurocritical care of patients with aSDH.

Clinical characteristics and outcomes of patients with recurrent status epilepticus episodes.

BACKGROUND: Multiple studies have focused on medical and pharmacological treatments and outcome predictors of patients with status epilepticus (SE). However, a sufficient understanding of recurrent episodes of SE is lacking. Therefore, we reviewed recurrent SE episodes to investigate their clinical characteristics and outcomes in patients with relapses. METHODS: In this retrospective, multicenter study, we reviewed recurrent SE patient data covering 2011 to 2017 from the university hospitals of Frankfurt and Marburg, Germany. Clinical characteristics and outcome variables were compared among the first and subsequent SE episodes using a standardized form for data collection. RESULTS: We identified 120 recurrent SE episodes in 80 patients (10.2% of all 1177 episodes). The mean age at the first SE episode was 62.2 years (median 66.5; SD 19.3; range 21-91), and 42 of these patients were male (52.5%). A mean of 262.4 days passed between the first and the second episode. Tonic-clonic seizure semiology and a cerebrovascular disease etiology were predominant in initial and recurrent episodes. After subsequent episodes, patients showed increased disability as indicated by the modified Rankin Scale (mRS), and 9 out of 80 patients died during the second episode (11.3%). Increases in refractory and super-refractory SE (RSE and SRSE, respectively) were noted during the second episode, and the occurrence of a non-refractory SE (NRSE) during the first SE episode did not necessarily provide a protective marker for subsequent non-refractory episodes. An increase in the use of intravenous-available anti-seizure medication (ASM) was observed in the treatment of SE patients. Patients were discharged from hospital with a mean of 2.8 ± 1.0 ASMs after the second SE episode and 2.1 ± 1.2 ASMs after the first episode. Levetiracetam was the most common ASM used before admission and on discharge for SE patients. CONCLUSIONS: This retrospective, multicenter study used the mRS to demonstrate worsened outcomes of patients at consecutive SE episodes. ASM accumulations after subsequent SE episodes were registered over the study period. The study results underline the necessity for improved clinical follow-ups and outpatient care to reduce the health care burden from recurrent SE episodes.

Adverse Event Profiles of Antiseizure Medications and the Impact of Coadministration on Drug Tolerability in Adults with Epilepsy.

BACKGROUND: Antiseizure medication (ASM) as monotherapy or in combination is the treatment of choice for most patients with epilepsy. Therefore, knowledge about the typical adverse events (AEs) for ASMs and other coadministered drugs (CDs) is essential for practitioners and patients. Due to frequent polypharmacy, it is often difficult to clinically assess the AE profiles of ASMs and differentiate the influence of CDs. OBJECTIVE: This retrospective analysis aimed to determine typical AE profiles for ASMs and assess the impact of CDs on AEs in clinical practice. METHODS: The Liverpool AE Profile (LAEP) and its domains were used to identify the AE profiles of ASMs based on data from a large German multicenter study (Epi2020). Following established classifications, drugs were grouped according to their mode of action (ASMs) or clinical indication (CDs). Bivariate correlation, multivariate ordinal regression (MORA), and artificial neural network (ANNA) analyses were performed. Bivariate correlation with Fisher's z-transformation was used to compare the correlation strength of LAEP with the Hospital Anxiety and Depression Scale (HADS) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to avoid LAEP bias in the context of antidepressant therapy. RESULTS: Data from 486 patients were analyzed. The AE profiles of ASM categories and single ASMs matched those reported in the literature. Synaptic vesicle glycoprotein 2A (SV2A) and voltage-gated sodium channel (VGSC) modulators had favorable AE profiles, while brivaracetam was superior to levetiracetam regarding psychobehavioral AEs. MORA revealed that, in addition to seizure frequency, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) modulators and antidepressants were the only independent predictors of high LAEP values. After Fisher's z-transformation, correlations were significantly lower between LAEP and antidepressants than between LAEP and HADS or NDDI-E. Therefore, a bias in the results toward over interpreting the impact of antidepressants on LAEP was presumed. In the ANNA, perampanel, zonisamide, topiramate, and valproic acid were important nodes in the network, while VGSC and SV2A modulators had low relevance for predicting relevant AEs. Similarly, cardiovascular agents, analgesics, and antipsychotics were important CDs in the ANNA model. CONCLUSION: ASMs have characteristic AE profiles that are highly reproducible and must be considered in therapeutic decision-making. Therapy using perampanel as an AMPA modulator should be considered cautiously due to its relatively high AE profile. Drugs acting via VGSCs and SV2A receptors are significantly better tolerated than other ASM categories or substances (e.g., topiramate, zonisamide, and valproate). Switching to brivaracetam is advisable in patients with psychobehavioral AEs who take levetiracetam. Because CDs frequently pharmacokinetically interact with ASMs, the cumulative AE profile must be considered. TRIAL REGISTRATION: DRKS00022024, U1111-1252-5331.

Large-vessel-occlusion in patients with previous ischemic stroke: an analysis of adherence to secondary preventive medication for different etiologies.

BACKGROUND: Large vessel occlusion (LVO) is a severe condition that carries a high risk of morbidity and mortality, underscoring the importance of effective prevention strategies. This retrospective study aimed to analyze the intake of preventive medication at the time of hospitalization in a cohort of recurrent stroke patients presenting with acute LVO. METHODS: The study assessed the intake of either platelet aggregation inhibitors (PAI), oral anticoagulants (OAC) or statins at admission in patients with recurrent stroke and correlated it with the final classification of LVO. The frequency of those secondary preventive medication in recurrent stroke patients was defined as primary endpoint. The Modified Rankin Scale (mRS) at discharge was used as a functional outcome and defined as a secondary outcome measure. RESULTS: This study included 866 patients who were treated for LVO between 2016 and 2020, of whom 160 (18.5%) had a recurrent ischemic stroke. OAC (25.6% vs. 14.1%, p < 0.01), PAI (50.0% vs. 26.0%, p < 0.01), or statin therapy (50.6% vs. 20.8%, p < 0.01) at admission were significantly more frequent in recurrent stroke patients compared to patients with a first-time stroke. Concerning LVO etiology in recurrent stroke patients, OAC at admission was taken in 46.8% of cardioembolic LVO, whereas PAI and statin at admission in macroangiopathic LVO were administered to 40.0%; neither PAI nor OAC was taken in 26.0%, 28.3%, and 31.6% of cardioembolic, macroangiopathic, or cryptogenic strokes, respectively. Regardless of stroke recurrence or etiology, there was an increase in mRS at discharge. CONCLUSIONS: Despite high-quality healthcare, this study suggested a significant proportion of patients with recurrent stroke who were either non-adherent or insufficiently adherent to secondary preventive medication. Given the disability associated with LVO, improving patients' medication adherence and identifying unknown stroke causes are crucial for effective prevention strategies.

Unemployment and early retirement among patients with epilepsy - A study on predictors, resilience factors and occupational reintegration measures.

The primary aim of this study was to identify predictors and resilience factors for unemployment and early retirement in patients with epilepsy of working age based on data from a multicenter German cohort study performed in 2020 (n = 456) by using multivariate binary logistic regression analysis. A second aim was to assess the assumed working ability of patients as well as the use of occupational reintegration measures. The unemployment rate was 8.3%, and 18% of patients had retired early due to epilepsy. Multivariate binary logistic regression analysis identified the presence of a relevant disability and frequent seizures as significant predictors of unemployment and early retirement, while seizures in remission were the only resilience factor associated with job retention. Regarding occupational incapacity, at the time of the survey, most of the patients in early retirement or unemployment were fit for work in their original or extended occupational setting. The proportion of patients with recent epilepsy-related occupational retraining (0.4%) or job changes (0.9%) was low, and only 2.4% reported an epilepsy-related reduction in work time. These findings underline the persistent disadvantage of patients with epilepsy in the professional field and the urgent need for effective, comprehensive work reintegration measures that must be made accessible for all patients.

The neurovasculature as a target in temporal lobe epilepsy.

The blood-brain barrier (BBB) is a physiological barrier maintaining a specialized brain micromilieu that is necessary for proper neuronal function. Endothelial tight junctions and specific transcellular/efflux transport systems provide a protective barrier against toxins, pathogens, and immune cells. The barrier function is critically supported by other cell types of the neurovascular unit, including pericytes, astrocytes, microglia, and interneurons. The dysfunctionality of the BBB is a hallmark of neurological diseases, such as ischemia, brain tumors, neurodegenerative diseases, infections, and autoimmune neuroinflammatory disorders. Moreover, BBB dysfunction is critically involved in epilepsy, a brain disorder characterized by spontaneously occurring seizures because of abnormally synchronized neuronal activity. While resistance to antiseizure drugs that aim to reduce neuronal hyperexcitability remains a clinical challenge, drugs targeting the neurovasculature in epilepsy patients have not been explored. The use of novel imaging techniques permits early detection of BBB leakage in epilepsy; however, the detailed mechanistic understanding of causes and consequences of BBB compromise remains unknown. Here, we discuss the current knowledge of BBB involvement in temporal lobe epilepsy with the emphasis on the neurovasculature as a therapeutic target.

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

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

Repetitive Electroencephalography as Biomarker for the Prediction of Survival in Patients with Post-Hypoxic Encephalopathy.

Predicting survival in patients with post-hypoxic encephalopathy (HE) after cardiopulmonary resuscitation is a challenging aspect of modern neurocritical care. Here, continuous electroencephalography (cEEG) has been established as the gold standard for neurophysiological outcome prediction. Unfortunately, cEEG is not comprehensively available, especially in rural regions and developing countries. The objective of this monocentric study was to investigate the predictive properties of repetitive EEGs (rEEGs) with respect to 12-month survival based on data for 199 adult patients with HE, using log-rank and multivariate Cox regression analysis (MCRA). A total number of 59 patients (29.6%) received more than one EEG during the first 14 days of acute neurocritical care. These patients were analyzed for the presence of and changes in specific EEG patterns that have been shown to be associated with favorable or poor outcomes in HE. Based on MCRA, an initially normal amplitude with secondary low-voltage EEG remained as the only significant predictor for an unfavorable outcome, whereas all other relevant parameters identified by univariate analysis remained non-significant in the model. In conclusion, rEEG during early neurocritical care may help to assess the prognosis of HE patients if cEEG is not available.

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

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

Benzodiazepines in the Management of Seizures and Status Epilepticus: A Review of Routes of Delivery, Pharmacokinetics, Efficacy, and Tolerability.

Status epilepticus (SE) is an acute, life-threatening medical condition that requires immediate, effective therapy. Therefore, the acute care of prolonged seizures and SE is a constant challenge for healthcare professionals, in both the pre-hospital and the in-hospital settings. Benzodiazepines (BZDs) are the first-line treatment for SE worldwide due to their efficacy, tolerability, and rapid onset of action. Although all BZDs act as allosteric modulators at the inhibitory gamma-aminobutyric acid (GABA)A receptor, the individual agents have different efficacy profiles and pharmacokinetic and pharmacodynamic properties, some of which differ significantly. The conventional BZDs clonazepam, diazepam, lorazepam and midazolam differ mainly in their durations of action and available routes of administration. In addition to the common intravenous, intramuscular and rectal administrations that have long been established in the acute treatment of SE, other administration routes for BZDs-such as intranasal administration-have been developed in recent years, with some preparations already commercially available. Most recently, the intrapulmonary administration of BZDs via an inhaler has been investigated. This narrative review provides an overview of the current knowledge on the efficacy and tolerability of different BZDs, with a focus on different routes of administration and therapeutic specificities for different patient groups, and offers an outlook on potential future drug developments for the treatment of prolonged seizures and SE.

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

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

Trends in antiseizure medication prescription patterns among all adults, women, and older adults with epilepsy: A German longitudinal analysis from 2008 to 2020.

INTRODUCTION: The prescription patterns of antiseizure medication (ASM) are subject to new scientific evidence and sociodemographic and practical aspects. This study analyzed trends in ASM prescription patterns among all adults with epilepsy, with special consideration for women of childbearing potential (WOCBP) and older adult (≥65 years old) patients. METHODS: Data from four questionnaire-based cohort studies, conducted in 2008, 2013, 2016, and 2020, were analyzed for ASM prescription frequencies and common mono- and dual therapy regimens. Statistical comparisons were performed with the Chi-square test and one-way analysis of variance. RESULTS: Overall, the individual prescription patterns among 1,642 adult patients with epilepsy were analyzed. A significant increase in the prescription frequency of third-generation ASMs, from 59.3% to 84.2% (p = 0.004), was accompanied by a decrease in the frequency of first- and second-generation ASMs (5.4% to 2.1% and 34.9% to 12.6%, respectively). This trend was accompanied by a significant decrease in the use of enzyme-inducing ASMs, from 23.9% to 4.6% (p = 0.004). Among frequently prescribed ASMs, prescriptions of carbamazepine (18.6% to 3.1%, p = 0.004) and valproate (15.4% to 8.7%, p = 0.004) decreased, whereas prescriptions of levetiracetam (18.0% up to 32.4%, p = 0.004) increased significantly. The prescription frequency of lamotrigine remained largely constant at approximately 20% (p = 0.859). Among WOCBP, the prescription frequencies of carbamazepine (11.4% to 2.0%, p = 0.004) and valproate (16.1% to 6.1%, p = 0.004) decreased significantly. Levetiracetam monotherapy prescriptions increased significantly (6.6% to 30.4%, p = 0.004) for WOCBP, whereas lamotrigine prescriptions remained consistent (37.7% to 44.9%, p = 0.911). Among older adult patients, a significant decrease in carbamazepine prescriptions (30.1% to 7.8%, p = 0.025) was the only relevant change in ASM regimens between 2008 and 2020. In patients with genetic generalized epilepsies, levetiracetam was frequently used as an off-label monotherapy (25.0% to 35.3%). CONCLUSION: These results show a clear trend toward the use of newer and less interacting third-generation ASMs, with lamotrigine, levetiracetam, and lacosamide representing the current ASMs of choice, displacing valproate and carbamazepine over the last decade. In WOCBP, prescription patterns shifted to minimize teratogenic effects, whereas, among older adults, the decrease in carbamazepine use may reflect the avoidance of hyponatremia risks and attempts to reduce the interaction potential with other drugs and ASMs. Levetiracetam is frequently used off-label as a monotherapy in patients with genetic generalized epilepsy.

Predicting Poststroke Pneumonia in Patients With Anterior Large Vessel Occlusion: A Prospective, Population-Based Stroke Registry Analysis.

OBJECTIVE: To assess predictive factors for poststroke pneumonia (PSP) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) of the anterior circulation, with special regard to the impact of intravenous thrombolysis (IVT) and endovascular treatment (EVT) on the risk of PSP. As a secondary goal, the validity of the A2DS2, PNEUMONIA, and ISAN scores in LVO will be determined. METHODS: Analysis was based on consecutive data for the years 2017 to 2019 from the prospective inpatient stroke registry covering the entire federal state of Hesse, Germany, using the Kruskal-Wallis test and binary logistic regression. RESULTS: Data from 4,281 patients with LVO were included in the analysis (54.8% female, median age = 78 years, range = 18-102), of whom 66.4% (n = 2,843) received recanalization therapy (RCT). In total, 19.4% (n = 832) of all LVO patients developed PSP. Development of PSP was associated with an increase in overall in-hospital mortality of 32.1% compared with LVO patients without PSP (16.4%; p < 0.001). Incidence of PSP was increased in 2132 patients with either EVT (n = 928; 25.9% PSP incidence) or combined EVT plus IVT (n = 1,204; 24.1%), compared with 2,149 patients with IVT alone (n = 711; 15.2%) or conservative treatment only (n = 1,438; 13.5%; p < 0.001). Multivariate analysis identified EVT (OR 1.5) and combined EVT plus IVT (OR 1.5) as significant independent risk factors for PSP. Furthermore, male sex (OR 1.9), age ≥ 65 years (OR 1.7), dysphagia (OR 3.2) as well as impaired consciousness at arrival (OR 1.7) and the comorbidities diabetes (OR 1.4) and atrial fibrillation (OR 1.3) were significantly associated risk factors (each p < 0.001). Minor stroke (NIHSS ≤ 4) was associated with a significant lower risk of PSP (OR 0.5). Performance of risk stratification scores varied between A2DS2 (96.1% sensitivity, 20.7% specificity), PNEUMONIA (78.2% sensitivity and 45.1% specificity) and ISAN score (98.0% sensitivity, 20.0% specificity). CONCLUSION: Nearly one in five stroke patients with LVO develops PSP during acute care. This risk of PSP is further increased if an EVT is performed. Other predictive factors are consistent with those previously described for all AIS patients. Available risk stratification scores proved to be sensitive tools in LVO patients but lack specificity.

Multicenter, cross-sectional study of the costs of illness and cost-driving factors in adult patients with epilepsy.

OBJECTIVE: This study was undertaken to quantify epilepsy-related costs of illness (COI) in Germany and identify cost-driving factors. METHODS: COI were calculated among adults with epilepsy of different etiologies and severities. Multiple regression analysis was applied to determine any epilepsy-related and sociodemographic factors that serve as cost-driving factors. RESULTS: In total, 486 patients were included, with a mean age of 40.5 ± 15.5 years (range = 18-83 years, 58.2% women). Mean 3-month COI were estimated at €4911, €2782, and €2598 for focal, genetic generalized, and unclassified epilepsy, respectively. The mean COI for patients with drug-refractory epilepsy (DRE; €7850) were higher than those for patients with non-DRE (€4720), patients with occasional seizures (€3596), or patients with seizures in remission for >1 year (€2409). Identified cost-driving factors for total COI included relevant disability (unstandardized regression coefficient b = €2218), poorer education (b = €2114), living alone (b = €2612), DRE (b = €1831), and frequent seizures (b = €2385). Younger age groups of 18-24 years (b = -€2945) and 25-34 years (b = -€1418) were found to have lower overall expenditures. A relevant disability (b = €441), DRE (b = €1253), frequent seizures (b = €735), and the need for specialized daycare (b = €749) were associated with higher direct COI, and poorer education (b = €1969), living alone (b = €2612), the presence of a relevant disability (b = €1809), DRE (b = €1831), and frequent seizures (b = €2385) were associated with higher indirect COI. SIGNIFICANCE: This analysis provides up-to-date COI data for use in further health economics analyses, highlighting the high economic impacts associated with disease severity, disability, and disease-related loss of productivity among adult patients with epilepsy. The identified cost drivers could be used as therapeutic and socioeconomic targets for future cost-containment strategies.

EuroQOL-5D-3L does not adequately map quality-of-life deterioration in severely affected patients with epilepsy.

INTRODUCTION: The steadily increasing impact of health-related quality of life (HRQOL) on reasonable diagnostic and therapeutic decisions makes the correct mapping of HRQOL indispensable in modern epileptology. The aim of this study was to address the reliability of the often-used generic HRQOL screening questionnaire EuroQOL 5-dimension, 3-level (EQ-5D-3L) by comparing its normalized index value (calculated via the time trade-off method) and visual analog scale (VAS) to the gold standard of the extensive Quality of Life in Epilepsy Inventory (QOLIE-31). QOLIE-10 scores were compared with the extensive QOLIE-31 and EQ-5D-3L TTO. METHODS: We conducted a retrospective analysis of a monocentric study of 184 patients with epilepsy. Bivariate Spearman correlation analysis and Fisher's r-to-z transformation were used to compare the strengths of correlations of EQ-5D-3L, QOLIE-10 and QOLIE-31 with different epilepsy-specific domains (disease severity, drug interactions, emotional well-being, stigmatization, seizure-related anxiety, cognitive impairment). RESULTS: The different metrics of EQ-5D-3L, QOLIE-10 and QOLIE-31 showed moderate to very strong intra- and inter-metric correlations for overall HRQOL. Quality of Life in Epilepsy Inventory-31 VAS and EQ-5D-3L VAS did not show any significantly different strengths of correlations with respect to the domains studied. In contrast, the correlation strength of the normalized EQ-5D-3L index value differed significantly from the QOLIE-31 T-score for several domains, for example, for drug-related adverse events, neuropsychological deficits, symptoms of depression and seizure worry. In seizure-free patients, EQ-5D-3L VAS and EQ-5D-3L index values correlated significantly less with the domain of "cognitive impairment" than the QOLIE-31 T-score. In patients without relevant neuropsychological deficits, the strengths of correlations with the assessed domains did not differ significantly between EQ-5D-3L metrics and the QOLIE-31 T-score. The HRQOL mapping probability of QOLIE-10 was inferior to QOLIE-31 and comparable to EQ-5D-3L regarding the analyzed domains. CONCLUSION: In contrast to the EQ-5D-3L VAS, EQ-5D-3L index values do not adequately map health-related quality of life in severely affected patients with epilepsy and therefore should not be used as screening tools. The QOLIE-31 T-score remains the gold standard for HRQOL assessment in patients with epilepsy.

Simulation-based training improves process times in acute stroke care (STREAM).

BACKGROUND: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care. METHODS: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm. RESULTS: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04). CONCLUSION: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.