Cenobamate significantly improves seizure control in intellectually disabled patients with drug-resistant epilepsy and allows drug load reduction.

Introduction: Epilepsy patients with intellectual disability often suffer from drug-resistant epilepsy (DRE), which severely affects patients' quality of life. Cenobamate (CNB) is a recently approved novel and effective ASM that can achieve high rates of seizure freedom in previously drug-resistant patients. Methods: We performed a retrospective data analysis of the first patients treated with CNB at a single center. Outcome and treatment response were assessed at two different time points, and ASM burden was calculated. Results: A 12 patients (7 males and 5 females) began treatment at a median age of 43 years, six of whom had developmental and epileptic encephalopathies. Prior to treatment with CNB, patients had tried a median of 13 different ASM. At the start of CNB therapy, patients were taking a median of 3 ASM. Treatment outcomes were available for 11 patients. After the first follow-up period (median 9 months), 55% of patients showed a significant seizure reduction of more than 50%, with three patients showing a reduction of more than 75% (27%). One patient achieved complete seizure freedom, while one patient did not respond to treatment. These response rates were consistently maintained at second follow-up after a median of 22 months. Ten patients (83%) reported adverse events (AE), the most common of which were dizziness and fatigue. No cases of drug reactions with eosinophilia and systemic symptoms (DRESS) were observed. The majority of AEs were mild and resolved over time. In addition, most patients were able to reduce their concomitant ASM. Discussion: Cenobamate has been shown to be an effective ASM in patients with DRE and in patients with intellectual disabilities. After more than 1 year of treatment with CNB, close monitoring and management of drug-drug interactions may reduce enzyme-inducing ASMs and lead to better long-term outcomes. With CNB treatment, many patients can achieve a reduced overall drug burden while maintaining a reduction in seizures.

A Managed Care System with Telemedicine Support for Neurological Emergencies.

OBJECTIVES: Telemedicine is frequently used to provide remote neurological expertise for acute stroke workup and was associated with better functional outcomes when combined with a stroke unit system-of-care. We investigated whether such system-of-care yields additional benefits when implemented on top of neurological competence already available onsite. METHODS: Quality improvement measures were implemented within a "hub-and-spoke" teleneurology network in 11 hospitals already provided with onsite or telestroke expertise. Measures included dedicated units for neurological emergencies, standardization of procedures, multiprofessional training, and quality-of-care monitoring. Intervention effects were investigated in a controlled study enrolling patients insured at 3 participating statutory health insurances diagnosed with acute stroke or other neurological emergencies. Outcomes during the intervention period between November 2017 and February 2020 were compared with those pre-intervention between October 2014 and March 2017. To control for temporal trends, we compared outcomes of patients with respective diagnoses in 11 hospitals of the same region. Primary outcome was the composite of up-to-90-day death, new disability with the need of ambulatory or nursing home care, expressed by adjusted hazard ratio (aHR). RESULTS: We included 1,418 patients post-implementation (55% female, mean age 76.7 ± 12.8 year) and 2,306 patients pre-implementation (56%, 75.8 ± 13.0 year, respectively). The primary outcome occurred in 479/1,418 (33.8%) patients post-implementation and in 829/2,306 (35.9%) pre-implementation. The aHR for the primary outcome was 0.89 (95% confidence interval [CI]: 0.79-0.99, p = 0.04) with no improvement seen in non-participating hospitals between post- versus pre-implementation periods (aHR 1.04; 95% CI: 0.95-1.15). INTERPRETATION: Implementation of a multicomponent system-of-care was associated with a lower risk of poor outcomes. ANN NEUROL 2023;93:511-521.

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.

[Anxiety about Health of Patients Suffering from Epilepsy]. / Krankheitsängste bei Epilepsiepatient*innen.

BACKGROUND: The presence of somatic diseases makes diagnosis of health-related anxiety difficult. Studies have shown that a significant proportion of patients suffering from somatic diseases also suffer from illness anxiety. OBJECTIVE: Patients suffering from epilepsy were examined, for whom no data regarding their illness anxiety had previously been obtained. METHOD: 76 epileptics were analyzed regarding their psychological distress (Mini-SCL), fear of recurrence (PA-F) and hypochondriacal traits (MIHT). RESULTS: In general, epileptics experienced the same level of distress and fear in comparison to a norm sample. At the same time, 28% (overall distress) to 45% (anxiety) of the study participants were observed to have abnormal values. The fear of recurrence was low in comparison to other somatic diagnosis groups. Hypochondriac traits were seen in 7% (perceptive) to 13% (affective/behavioral) of the respondents. CONCLUSION: An increased awareness of illness anxiety in patients can help improve healthcare and quality of life of epileptics.

Effects of vagus nerve stimulation on symptoms of depression in patients with difficult-to-treat epilepsy.

PURPOSE: Vagus nerve stimulation (VNS) is well established in the treatment of epilepsy and disorders of depression. The prevalence of depression is high in patients with epilepsy, but still it remains unclear how patients with a comorbidity of epilepsy and symptoms of depression respond to VNS. METHODS: We investigated 59 patients with different subtypes of disorders of depression as a comorbidity of epilepsy, who underwent VNS-surgery. Before and one year after VNS surgery, the severity of symptoms of depression was evaluated by a psychiatrist using Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck-Depressions-Inventory (BDI). Response towards epilepsy was measured by a seizure reduction of at least 50%. RESULTS: Symptoms of depression ameliorated in response to VNS in the overall of all patients MADRS 29 to 18 (p < 0,001) and BDI 24 to 14 (p < 0,001) and all subtypes of disorders of depression. Seizure reduction of at least 50% was achieved in two out of three of all patients two years after VNS. CONCLUSION: We were able to show the beneficial effect of VNS in the treatment of patients with pharmacoresistant epilepsy and a comorbidity of symptoms of depression.

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.

Implantation of a new Vagus Nerve Stimulation (VNS) Therapy® generator, AspireSR®: considerations and recommendations during implantation and replacement surgery--comparison to a traditional system.

INTRODUCTION: The most widely used neuro-stimulation treatment for drug-resistant epilepsy is Vagus Nerve Stimulation (VNS) Therapy®. Ictal tachycardia can be an indicator of a seizure and, if monitored, can be used to trigger an additional on-demand stimulation, which may positively influence seizure severity or duration. A new VNS Therapy generator model, AspireSR®, was introduced and approved for CE Mark in February 2014. In enhancement of former models, the AspireSR has incorporated a cardiac-based seizure-detection (CBSD) algorithm that can detect ictal tachycardia and automatically trigger a defined auto-stimulation. To evaluate differences in preoperative, intraoperative and postoperative handling, we compared the AspireSR to a conventional generator model (Demipulse®). METHOD: Between February and September 2014, seven patients with drug-resistant epilepsy and ictal tachycardia were implanted with an AspireSR. Between November 2013 and September 2014, seven patients were implanted with a Demipulse and served as control group. Operation time, skin incision length and position, and complications were recorded. Handling of the new device was critically evaluated. RESULTS: The intraoperative handling was comparable and did not lead to a significant increase in operation time. In our 14 operations, we had no significant short-term complications. Due to its larger size, patients with the AspireSR had significantly larger skin incisions. For optimal heart rate detection, the AspireSR had to be placed significantly more medial in the décolleté area than the Demipulse. The preoperative testing is a unique addition to the implantation procedure of the AspireSR, which may provide minor difficulties, and for which we provide several recommendations and tips. The price of the device is higher than for all other models. CONCLUSIONS: The new AspireSR generator offers a unique technical improvement over the previous Demipulse. Whether the highly interesting CBSD feature will provide an additional benefit for the patients, and will rectify the additional costs, respectively, cannot be answered in the short-term. The preoperative handling is straightforward, provided that certain recommendations are taken into consideration. The intraoperative handling is equivalent to former models-except for the placement of the generator, which might cause cosmetic issues and has to be discussed with the patient carefully. We recommend the consideration of the AspireSR in patients with documented ictal tachycardia to provide a substantial number of patients for later seizure outcome analysis.

Quality of life, anxiety and depression in adult patients after add-on of levetiracetam and conversion to levetiracetam monotherapy.

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.