Consultation Requests and Satisfaction with a Telehealth Network for Epilepsy: Longitudinal Analysis of the Epilepsy Network Hessen Evaluation.

Background: Telemedicine improves access to specialized medical expertise, as required for paroxysmal disorders. The Epilepsy Network Hessen Evaluation (ENHE) is a pilot cross-sectoral teleconsultation network connecting primary neurologists and pediatricians with epilepsy centers in Hessen, a federal German state. Methods: We prospectively and longitudinally evaluated telehealthcare in the ENHE. Participating physicians rated each consultation for satisfaction and impact on further management. The survey was administered at each consultation and 3 months later. Results: We analyzed 129 consultations involving 114 adult and pediatric patients. Their mean age was 34 years (standard deviation: 26, range: 0.1-91 years), 48% were female, and 34% were children and adolescents. The most common consultation requests were co-evaluation of an electroencephalogram (electroencephalogram [EEG]; 76%) and therapeutic (33%) and differential diagnosis (24%) concerns. Physicians transmitted one paraclinical examination on average (range: 1-4), predominantly EEG (85%), followed by magnetic resonance imaging (17%) and written records (9%). Response rates were 72% for the initial and 67% for the follow-up survey. Across respondents, 99% (n = 92) were satisfied with the ENHE. Overall, 80% of the consultations contributed to the diagnosis, and 90% were considered helpful for treatment, influencing it in 71% of cases. Seizure frequency had decreased more often (96%) than increased (4%) at 3 months. The initial diagnosis was confirmed in 78% of patients. Discussion: In this pilot teleconsultation network for paroxysmal disorders, diagnostic and therapeutic advice was perceived as helpful. Clinical outcomes were largely positive, suggesting tele-epileptology is viable for paroxysmal (seizure) disorders.

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.

Use of Health-Related Apps and Telehealth in Adults with Epilepsy in Germany: A Multicenter Cohort Study.

Background: Telehealth can improve the treatment of chronic disorders, such as epilepsy. Telehealth prevalence and use increased during the coronavirus disease 2019 (COVID-19) pandemic. However, familiarity with and use of telehealth and health-related mobile applications (apps) by persons with epilepsy remain unknown. Methods: We investigated telehealth use, demographics, and clinical variables within the multicenter Epi2020 cross-sectional study. Between October and December 2020, adults with epilepsy completed a validated questionnaire, including individual questions regarding knowledge and use of apps and telehealth. Results: Of 476 included individuals (58.2% women; mean age 40.2 ± 15.4 years), 41.6% reported using health-related apps. Health apps were used more frequently (pedometer 32.1%, exercise app 17.6%) than medical apps (health insurance 15.1%, menstrual apps 12.2%) or apps designed for epilepsy (medication reminders 10.3%, seizure calendars 4.6%). Few used seizure detectors (i.e., apps as medical devices 1.9%) or mobile health devices (fitness bracelet 11.3%). A majority (60.9%) had heard the term telehealth, 78.6% of whom had a positive view. However, only 28.6% had a concrete idea of telehealth, and only 16.6% reported personal experience with telehealth. A majority (55%) would attend a teleconsultation follow-up, and 41.2% would in a medical emergency. Data privacy and availability were considered equally important by 50.8%, 21.8% considered data privacy more important, and 20.2% considered data availability more important. Current health-related app use was independently associated with younger age (p = 0.003), higher education (p < 0.001), and subjective COVID-19-related challenges (p = 0.002). Persistent seizure occurrence (vs. seizure freedom ≥12 months) did not affect willingness to use teleconsultations on multivariable logistic regression analysis. Conclusions: Despite positive telehealth views, few persons with epilepsy in Germany are familiar with specific apps or services. Socioeconomic factors influence telehealth use more than baseline epilepsy characteristics. Telehealth education and services should target socioeconomically disadvantaged individuals to reduce the digital care gap. German Clinical Trials Register (DRKS00022024; Universal Trial Number: U1111-1252-5331).

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.

Local glucose metabolism is unaltered in reversible splenial lesion syndrome.

BACKGROUND AND PURPOSE: Transient splenial oedema, also known as reversible splenial lesion syndrome (RESLES), is a rare magnetic resonance imaging (MRI) finding that presents as a round or ovoid focal oedema in the posterior corpus callosum, and is associated with a wide range of clinical conditions. The aetiology of RESLES is not fully clear. We aimed to investigate conflicting pathophysiological hypotheses by measuring local glucose metabolism in patients with RESLES. METHODS: We retrospectively analysed patients with RESLES after reductions in antiseizure medications during in-hospital video electroencephalography monitoring. We measured local glucose uptake using positron emission tomography/computed tomography and compared matched cohorts of patients with and without MRI evidence of RESLES using nonparametric tests. RESULTS: Local glucose metabolism in the splenium of seven patients with RESLES was not significantly different from the glucose metabolism of the seven patients in the matched cohort. This was true using both regular and normalized standardized glucose uptake value calculation methods (p = 0.902 and p = 0.535, respectively). CONCLUSION: We found no evidence of local glucose hypometabolism in RESLES, which supports previous pathophysiological considerations that suggest that RESLES is an intercellular, intramyelinic oedema rather than a typical intracellular cytotoxic oedema, which is not reversible.

Comparison of minimally invasive and traditional surgical approaches for refractory mesial temporal lobe epilepsy: A systematic review and meta-analysis of outcomes.

Magnetic resonance-guided laser interstitial laser therapy (MRgLITT) and radiofrequency ablation (RFA) represent two minimally invasive methods for the treatment of drug-refractory mesial temporal lobe epilepsy (mTLE). We performed a systematic review and a meta-analysis to compare outcomes and complications between MRgLITT, RFA, and conventional surgical approaches to the temporal lobe (i.e., anterior temporal lobe resection [ATL] or selective amygdalohippocampectomy [sAHE]). Forty-three studies (13 MRgLITT, 6 RFA, and 24 surgery studies) involved 554, 123, 1504, and 1326 patients treated by MRgLITT, RFA, ATL, or sAHE, respectively. Engel Class I (Engel-I) outcomes were achieved after MRgLITT in 57% (315/554, range = 33.3%-67.4%), RFA in 44% (54/123, range = 0%-67.2%), ATL in 69% (1032/1504, range = 40%-92.9%), and sAHE in 66% (887/1326, range = 21.4%-93.3%). Meta-analysis revealed no significant difference in seizure outcome between MRgLITT and RFA (Q = 2.74, p = .098), whereas ATL and sAHE were both superior to MRgLITT (ATL: Q = 8.92, p = .002; sAHE: Q = 4.33, p = .037) and RFA (ATL: Q = 6.42, p = .0113; sAHE: Q = 5.04, p = .0247), with better outcome in patients at follow-up of 60 months or more. Mesial hippocampal sclerosis (mTLE + hippocampal sclerosis) was associated with significantly better outcome after MRgLITT (Engel-I outcome in 64%; Q = 8.55, p = .0035). The rate of major complications was 3.8% for MRgLITT, 3.7% for RFA, 10.9% for ATL, and 7.4% for sAHE; the differences did not show statistical significance. Neuropsychological deficits occurred after all procedures, with left-sided surgeries having a higher rate of verbal memory impairment. Lateral functions such as naming or object recognition may be more preserved in MRgLITT. Thermal therapies are effective techniques but show a significantly lower rate of Engel-I outcome in comparison to ATL and sAHE. Between MRgLITT and RFA there were no significant differences in Engel-I outcome, whereby the success of treatment seems to depend on the approach used (e.g., occipital approach). MRgLITT shows a similar rate of complications compared to RFA, whereas patients undergoing MRgLITT may experience fewer major complications compared to ATL or sAHE and might have a more beneficial neuropsychological outcome.

[Decision support systems, assistance systems and telemedicine in epileptology]. / Decision-support-Systeme, Assistenzsysteme und Telemedizin in der Epileptologie.

BACKGROUND: Scientific knowledge about epilepsies and their clinical ramifications is rapidly expanding. This becomes an even greater challenge for non-specialists to process. Clinical decision support systems (CDSS) can play an important role as an expert-driven diagnostic and therapeutic tool which gives automated and individualized advice. In addition, medical apps and telemedical procedures for diagnostics and treatment and assistance systems for seizure detection in epilepsy patients have become available. OBJECTIVE: This article provides an overview on current tele-epileptological developments and the available telemedical applications. MATERIAL AND METHODS: Based on personal experience and a review of the literature, current epilepsy-specific CDSS, medical apps and assistance systems as well as telemedical applications are characterized and the clinical fields of application are presented. RESULTS AND CONCLUSION: Due to the chronic course and the complexity of the epilepsies and their sequelae, persons with epilepsy could profit from CDSS. Epilepsy-specific CDSS should be usable by medical professionals and patients themselves. Currently, medical apps for people with epilepsy are mostly used to document the clinical course, seizure frequency, medication compliance and side effects. Available seizure detection systems mainly detect generalized tonic-clonic seizures (GTCS). A clinical benefit of such devices is not yet sufficiently confirmed but appears to be likely, because these seizures are specifically associated with sudden unexpected death in epilepsy patients (SUDEP) and interventions are considered to be effective.

SARS-CoV-2-related rapid reorganization of an epilepsy outpatient clinic from personal appointments to telemedicine services: A German single-center experience.

INTRODUCTION: When the SARS-CoV-2 pandemic reached Europe in 2020, a German governmental order forced clinics to immediately suspend elective care, causing a problem for patients with chronic illnesses such as epilepsy. Here, we report the experience of one clinic that converted its outpatient care from personal appointments to telemedicine services. METHODS: Documentations of telephone contacts and telemedicine consultations at the Epilepsy Center Frankfurt Rhine-Main were recorded in detail between March and May 2020 and analyzed for acceptance, feasibility, and satisfaction of the conversion from personal to telemedicine appointments from both patients' and medical professionals' perspectives. RESULTS: Telephone contacts for 272 patients (mean age: 38.7 years, range: 17-79 years, 55.5% female) were analyzed. Patient-rated medical needs were either very urgent (6.6%, n = 18), urgent (23.5%, n = 64), less urgent (29.8%, n = 81), or nonurgent (39.3%, n = 107). Outpatient service cancelations resulted in a lack of understanding (9.6%, n = 26) or anger and aggression (2.9%, n = 8) in a minority of patients, while 88.6% (n = 241) reacted with understanding, or relief (3.3%, n = 9). Telemedicine consultations rather than a postponed face-to-face visit were requested by 109 patients (40.1%), and these requests were significantly associated with subjective threat by SARS-CoV-2 (p = 0.004), urgent or very urgent medical needs (p = 0.004), and female gender (p = 0.024). Telemedicine satisfaction by patients and physicians was high. Overall, 9.2% (n = 10) of patients reported general supply problems due to SARS-CoV-2, and 28.4% (n = 31) reported epilepsy-specific problems, most frequently related to prescriptions, or supply problems for antiseizure drugs (ASDs; 22.9%, n = 25). CONCLUSION: Understanding and acceptance of elective ambulatory visit cancelations and the conversion to telemedicine consultations was high during the coronavirus disease 2019 (COVID-19) lockdown. Patients who engaged in telemedicine consultations were highly satisfied, supporting the feasibility and potential of telemedicine during the COVID-19 pandemic and beyond.

Rapid discontinuation of sodium channel-blocking antiseizure drugs evokes focal edema in the splenium corporis callosi: A matched case-control study.

OBJECTIVE: Focal edema of the splenium of the corpus callosum (FESCC) is infrequently seen in patients with epilepsy who are undergoing video-electroencephalography (EEG) monitoring. It is diagnosed by qualitative visual inspection of the magnetic resonance imaging (MRI) and is usually assumed to be a dichotomous phenomenon. Rapid reduction of anticonvulsants has been proposed as a cause. In this study we investigate the relationship between dose reduction of anticonvulsants and the occurrence of FESCC, based on absolute drug doses. METHODS: We examined in detail the anticonvulsive therapy of all patients during video-EEG monitoring between 2014 and 2018. We compared patients with a radiologically diagnosed FESCC to controls in a 1:2 case-control analysis matched by age, epilepsy syndrome, and adjacent time of admission. In a separate correlation analysis, we examined quantitative effects of reduction of antiseizure drugs on diffusion restriction in the corpus callosum. RESULTS: Of 326 patients who had an MRI following video-EEG monitoring, 12 (3.7%) had FESCC. Antiseizure drugs were reduced to a significantly greater extent in FESCC patients than in the 24 controls (P < 0.001). Sodium channel-blocking antiseizure drugs were reduced (P < 0.001) and reintroduced (P < 0.001) significantly faster in FESCC patients, and the duration of anticonvulsant discontinuation was longer in FESCC patients (P < 0.001). The separate correlation analysis in 325 patients shows a weak correlation between diffusion restriction in the splenium and the reduction rate of sodium channel-blocking anticonvulsants (r = -0.15, P = 0.03) as well as the duration of their discontinuation (r = -0.16, P = 0.01). No such effects were found for anticonvulsants with other modes of action. SIGNIFICANCE: Our findings substantiate that FESCC is associated with high rates of dose reduction of anticonvulsants, specifically those acting on sodium channels. Our results cautiously suggest that reducing sodium-channel blockers has a small effect on diffusivity in the splenium below the visual threshold.

Burden and epidemiology of status epilepticus in infants, children, and adolescents: A population-based study on German health insurance data.

OBJECTIVE: Status epilepticus (SE) is an important medical emergency condition with particularly unfavorable outcome in refractory and superrefractory SE (SRSE). The economic impact of SE and especially of SRSE in the pediatric population remains unclear. We aimed to determine the burden of illness of SE in a pediatric patient population. METHODS: Insurance records for patients aged 0-18 years admitted between 2008 and 2015 were selected from a nationwide insurance research database utilizing International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes for SE (G41), epilepsy (G40), or febrile convulsions (R56). Patients were further classified based on admission to the intensive care unit and use of mechanical ventilation. RESULTS: The algorithm identified 11 693 seizure-related admissions and classified 4% as SE. Of these cases, 282 (60.4%) were classified by the algorithm as nonrefractory SE (NRSE), 125 (26.8%) as refractory SE (RSE), and 60 (12.8%) as SRSE. The crude SE incidence was 17.6/100 000, with NRSE being 11.4/100 000, RSE 3.9/100 000, and SRSE 2.3/100 000. SRSE incidence peaked in the 0- to 1-year-old age subgroup accounting for 48.3% of all pediatric SRSE admissions. The median length of stay (LOS) for all SE cases was 7 days, with median 44.5 days in SRSE, 5 days in NRSE, and 12 days in RSE. Mean admission costs for total SE were €15 880, with a mean expense for SRSE of €75 358, for NRSE of €4119, and for RSE of €13 864. The mean LOS for non-SE epilepsy admissions was 3 days, with mean costs of €2697 for epilepsy and €1614 for febrile convulsion admissions. There were no deaths in non-SE and NRSE admissions, whereas the overall mortality for SE was 3%, with 5.6% in RSE and 11.7% in SRSE. SIGNIFICANCE: Although cases classified as SE represented 4% of the seizure-associated admissions, they accounted for 22% of the overall costs. These costs were disproportionately represented by SRSE cases, which accounted for 62% of all SE-associated costs.

[Hypertrophic olivary degeneration : Cause of new neurological symptoms after stroke]. / Hypertrophe Degeneration der Olive : Ursache neuerlicher neurologischer Symptome nach Schlaganfall.

BACKGROUND: Hypertrophic olivary degeneration (HOD) occurs as a result of a lesion in the anatomical functional loop of the Guillain-Mollaret triangle. Frequent causes are intracerebral hemorrhage and brain infarction. After a latent period of weeks to months after the index event a hyperintensity can initially be observed in magnetic resonance imaging T2/FLAIR-weighting and finally an enlargement of the affected olive. Characteristic symptoms are a rhythmic palatal tremor, a primarily vertical pendular nystagmus as well as Holmes' tremor of the upper limbs. AIM OF THE STUDY: The goal of this study was to illustrate the course of the disease and its clinical presentation in order to provide an improved understanding of the pathophysiology of HOD after stroke. MATERIAL AND METHODS: The neuroradiological database of the Goethe University Hospital was screened for HOD and related keywords (in German). Between 2010 and 2017 a total of 27 cases of HOD were identified, of which 12 patients had suffered a stroke in their medical history. RESULTS: The mean age of the 12 patients was 51.4 years (±13.6 years) and one third of the patients were women. Of the patients eight had an intracerebral hemorrhage, three an ischemic stroke and one had a subarachnoid hemorrhage as the causative event. The lesions were located in the pons (n = 7), cerebellum (n = 4) and pontomesencephalon (n = 1). The median latent period from the causative index event to radiological diagnosis was 24 months (min. 4 months, max. 115 months). The leading symptoms of HOD were palatal tremor (55%), Holmes' tremor (18%), pendular nystagmus (18%) and dysarthria (73%). A logopedic examination with flexible endoscopic evaluation of swallowing (FEES) could determine a palatal tremor in five out of nine cases. The diagnosis of HOD was named in the medical report in only 50% of the cases. CONCLUSION: Analysis of the dataset provided confirmation of the results in the literature that lesions within the Guillain-Mollaret triangle more often lead to HOD. Patients with corresponding symptoms should be closely observed over time with respect to the occurrence of corresponding clinical and imaging leading symptoms. Even though the named clinical symptoms are characteristic for HOD, in many cases the diagnosis is hampered and delayed by imprecise examination and misinterpretation of the symptoms. A logopedic examination using FEES in this collective often provided indicative information. Currently, no reliable data are available on the incidence of HOD after brainstem lesions or on potential preventive and treatment options. Future epidemiological and translational studies could perspectively enable valuable insights to be gained.

Lacosamide in status epilepticus: Systematic review of current evidence.

OBJECTIVE: The intravenous formulation of lacosamide (LCM) and its good overall tolerability and safety favor the use in status epilepticus (SE). The aim of this systematic review was to identify and evaluate studies reporting on the use of LCM in SE. METHODS: We performed a systematic literature search of electronic databases using a combined search strategy from 2008 until October 2016. Using a standardized assessment form, information on the study design, methodologic framework, data sources, efficacy, and adverse events attributed to LCM were extracted from each publication and systematically reported. RESULTS: In total, 522 SE episodes (51.7% female) in 486 adults and 36 children and adolescents were evaluated with an overall LCM efficacy of 57%. Efficacy was comparable between use in nonconvulsive (57%; 82/145) and generalized-convulsive (61%; 30/49; p = 0.68) SE, whereas overall success rate was better in focal motor SE (92%; 34/39, p = 0.013; p < 0.001). The efficacy with later positioning of LCM decreased from 100% to 20%. The main adverse events during treatment of SE are dizziness, abnormal vision, diplopia, and ataxia. Overall, lacosamide is well tolerated and has no clinically relevant drug-drug interactions. SIGNIFICANCE: The available data regarding the use of LCM in SE are promising, with a success rate of 57%. The strength of LCM is the lack of interaction potential and the option for intravenous use in emergency situations requiring rapid uptitration.

Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany.

OBJECTIVE: To evaluate factors predicting efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice. METHODS: A multicenter, retrospective cohort study recruiting all patients who started BRV between February and November 2016 with observation time between 3 and 12 months. RESULTS: Of a total of 262 patients (mean age 40, range 5-81 years, 129 male) treated with BRV, 227 (87%) were diagnosed to have focal, 19 (7%) idiopathic generalized and 8 (3%) symptomatic generalized epilepsy, whereas 8 (3%) were unclassified. The length of exposure to BRV ranged from 1 day to 12 months, with a median retention time of 6.1 months, resulting in a total exposure time to BRV of 1,504 months. The retention rate was 79.4% at 3 months and 75.8% at 6 months. Efficacy at 3 months was 41.2% (50% responder rate) with 14.9% seizure-free for 3 months and, at 6 months, 40.5% with 15.3% seizure-free. Treatment-emergent adverse events were observed in 37.8% of the patients, with the most common being somnolence, dizziness, and behavioral adverse events (BAEs). BAE that presented under previous levetiracetam (LEV) treatment improved upon switch to BRV in 57.1% (20/35) and LEV-induced somnolence improved in 70.8% (17/24). Patients with BAE on LEV were more likely to develop BAE on BRV (odds ratio [OR] 3.48, 95% confidence interval [CI] 1.53-7.95). SIGNIFICANCE: BRV in broad clinical postmarketing use is a well-tolerated anticonvulsant drug with 50% responder rates, similar to those observed in the regulatory trials, even though 90% of the patients included had previously been exposed to LEV. An immediate switch from LEV to BRV at a ratio of 10:1 to 15:1 is feasible. The only independent significant predictor of efficacy was the start of BRV in patients not currently taking LEV. The occurrence of BAE during previous LEV exposure predicted poor psychobehavioral tolerability of BRV treatment. A switch to BRV can be considered in patients with LEV-induced BAE.

Changes of pH and energy state in subacute human ischemia assessed by multinuclear magnetic resonance spectroscopy.

BACKGROUND AND PURPOSE: In vivo changes in tissue pH and energy metabolism are key to understanding stroke pathophysiology. Our goal was to study pH changes in subacute ischemic stroke and their relation to energy metabolism, which, unlike acidosis in acute stroke, are not yet well understood. METHODS: We measured tissue pH and phospholipid as well as cell energy markers, including creatine, phosphocreatine, and N-acetyl-aspartate in subacute stroke with combined (1)H and (31)P magnetic resonance spectroscopy. We included 19 patients with first-ever ischemic stroke (mean time after stroke, 6 days). We then compared metabolite concentrations in the ischemic tissue to contralateral (healthy) tissue using multivariate ANOVA to assess significant differences in metabolite levels between both tissue compartments. RESULTS: In subacute stroke, a tissue fraction with significantly increased tissue pH was observed as compared with healthy contralateral tissue (pH, 7.09 versus 7.03; P=0.002) concurrent with splitting of the pH signal with 1 peak being more alkalotic. Furthermore, only a moderate decrease of energy-rich metabolites (phosphocreatine reduced by 17%, ATP reduced by 19%) was present, whereas total creatine was reduced by 51%. CONCLUSIONS: The finding of an alkalotic pH split in subacute ischemia is unprecedented. The pH split and only incomplete energy loss in subacute stroke suggest 2 differently viable cellular moieties, best explained by active compensatory mechanisms after acute cerebral ischemia.

A multicenter randomized controlled feasibility trial of a digital self-management intervention for adults with epilepsy.

OBJECTIVE: Self-management interventions may enhance health-related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone-delivered self-care treatment program for adults with epilepsy. METHODS: The 12-week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting-list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy-related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE-31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi-structured interviews were conducted with a heterogeneous sample of participants to assess user-friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). RESULTS: Ninety-two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. SIGNIFICANCE: Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self-care apps. Feedback loops allow the participatory development of tailored interventions. PLAIN LANGUAGE SUMMARY: In this study, we investigated the effectiveness of an app-based self-help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one-fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options.

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.

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.

Sleep quality, anxiety, symptoms of depression, and caregiver burden among those caring for patients with Dravet syndrome: a prospective multicenter study in Germany.

BACKGROUND: This study measured sleep quality among caregivers of patients with Dravet syndrome (DS) and assessed the impacts of mental health problems and caregiver burden on sleep quality. METHODS: This multicenter, cross-sectional study of patients with DS and their caregivers throughout Germany consisted of a questionnaire and a prospective 4-week diary querying disease characteristics, demographic data, living conditions, nocturnal supervision, and caregivers' work situations. Sleep quality was assessed using the Pittsburgh Sleeping Quality Index (PSQI). The Hospital Anxiety and Depression Scale (HADS) and the Burden Scale for Family Caregivers (BSFC) were used to measure anxiety, symptoms of depression, and caregiver burden. RESULTS: Our analysis included 108 questionnaires and 82 four-week diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 ± 10.0 years. Caregivers were 92.6% (n = 100) female, with a mean age of 44.7 ± 10.6 years. The overall mean PSQI score was 8.7 ± 3.5, with 76.9% of participants (n = 83) scoring 6 or higher, indicating abnormal sleep quality. The HADS for anxiety and depression had overall mean scores of 9.3 ± 4.3 and 7.9 ± 3.7, respectively; 61.8% and 50.9% of participants scored above the cutoff value of 8 for anxiety and depression, respectively. Statistical analyses revealed caregiver anxiety levels and patients' sleep disturbances as major factors influencing PSQI scores. The overall mean BSFC score of 41.7 ± 11.7 indicates a moderate burden, with 45.3% of caregivers scoring 42 or higher. CONCLUSIONS: Sleep quality is severely affected among caregivers of patients with DS, correlating with anxiety, comorbidities, and patients' sleep disturbances. A holistic therapeutic approach should be implemented for patients with DS and their caregivers, focusing on the sleep quality and mental health of caregivers. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00016967. Registered 27 May 2019, http://www.drks.de/DRKS00016967.

Predictive Factors of Acute Symptomatic Seizures in Patients With Ischemic Stroke Due to Large Vessel Occlusion.

Introduction: Acute symptomatic seizures (ASz) after ischemic stroke are associated with increased mortality; therefore, identifying predictors of ASz is important. The purpose of this study was to analyze predictors of ASz in a population of patients with ischemic stroke due to large arterial vessel occlusion (LVO). Materials and Methods: This retrospective study examined patients with acute ischemic stroke caused by LVO between 2016 and 2020. Identification of predictive factors was performed using univariate and subsequent multiple logistic regression analysis. In addition, subgroup analysis regarding seizure semiology and time of seizure occurrence (≤ 24 h and > 24 h after stroke) was performed. Results: The frequency of ASz among 979 patients was 3.9 % (n = 38). Univariate logistic regression analysis revealed an increased risk of ASz in patients with higher National Institutes of Health Stroke Scale (NIHSS) score at admission or 24 h after admission, hypernatremia at admission ≥ 145 mmol/L, and pneumonia. Further multiple logistic regression analysis revealed that NIHSS 24 h after admission was the strongest predictor of ASz, particularly relating to ASz occurring later than 24 h after stroke. Patients who experienced a seizure within the first 24 h after stroke were more likely to have a generalized tonic-clonic (GTCS) and focal motor seizure; beyond 24 h, seizures with impaired awareness and non-convulsive status epilepticus were more frequent. Conclusion: NIHSS score 24 h after admission is a strong predictive factor for the occurrence of ASz in patients with ischemic stroke caused by LVO. The semiology of ASz varied over time, with GTCS occurring more frequently in the first 24 h after stroke.

Mechanical thrombectomy does not increase the risk of acute symptomatic seizures in patients with an ischaemic stroke: a propensity score matching study.

BACKGROUND: Mechanical thrombectomy and systemic thrombolysis are important therapies for stroke patients. However, there is disagreement about the accompanying risk of acute symptomatic seizures. METHODS: A retrospective analysis of patients with an acute ischaemic stroke caused by large vessel occlusion was performed. The patients were divided into four groups based on whether they received either mechanical thrombectomy (MT) or systemic thrombolysis (ST; group 1: MT+/ST-; group 2: MT+/ST+; group 3: MT-/ST+; group 4: MT-/ST-). Propensity score matching was conducted for each group combination (1:3, 1:4, 2:3, 2:4, 1:2, 3:4) using the covariates "NIHSS at admission", "mRS prior to event" and "age". The primary endpoint was defined as the occurrence of acute symptomatic seizures. RESULTS: A total of 987 patients met the inclusion criteria, of whom 208, 264, 169 and 346 belonged to groups 1, 2, 3 and 4, respectively. Propensity score matched groups consisted of 160:160, 143:143, 156:156, 144:144, 204:204 and 165:165 patients for the comparisons 1:3, 1:4, 2:3, 2:4, 1:2 and 3:4, respectively. Based on chi-squared tests, there was no significant difference in the frequency of acute symptomatic seizures between the groups. Subgroups varied in their frequency of acute symptomatic seizures, ranging from 2.8 to 3.8%, 2.8-4.4%, 3.6-3.8% and 4.9-6.3% in groups 1, 2, 3 and 4, respectively. CONCLUSION: There was no association between MT or ST and an increased risk of acute symptomatic seizures in patients with an acute ischaemic stroke caused by large vessel occlusion who were treated at a primary stroke centre.