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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.
Background: Tuberous sclerosis complex (TSC) is a monogenetic, multisystem disorder characterized by benign growths due to TSC1 or TSC2 mutations. This German multicenter study estimated the costs and related cost drivers associated with organ manifestations in adults with TSC.
Methods: A validated, three-month, retrospective questionnaire assessed the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket (OOP), and nursing care-level costs among adult individuals with TSC throughout Germany from a societal perspective (costing year: 2019).
Results: We enrolled 192 adults with TSC (mean age: 33.4 ± 12.7 years; range: 18–78 years, 51.6% [n = 99] women). Reported TSC disease manifestations included skin (94.8%) and kidney and urinary tract (74%) disorders, epilepsy (72.9%), structural brain defects (67.2%), psychiatric disorders (50.5%), heart and circulatory system disorders (50.5%), and lymphangioleiomyomatosis (11.5%). TSC1 and TSC2 mutations were reported in 16.7% and 25% of respondents, respectively. Mean direct health care costs totaled EUR 6452 (median EUR 1920; 95% confidence interval [CI] EUR 5533–7422) per patient over three months. Medication costs represented the major direct cost category (77% of total direct costs; mean EUR 4953), and mechanistic target of rapamycin (mTOR) inhibitors represented the largest share (68%, EUR 4358). Mean antiseizure drug (ASD) costs were only EUR 415 (6%). Inpatient costs (8%, EUR 518) and outpatient treatment costs (7%; EUR 467) were important further direct cost components. The mean care grade allowance as an approximator of informal nursing care costs was EUR 929 (median EUR 0; 95% CI EUR 780–1083) over three months. Mean indirect costs totaled EUR 3174 (median EUR 0; 95% CI EUR 2503–3840) among working-age individuals (< 67 years in Germany). Multiple regression analyses revealed mTOR inhibitor use and persistent seizures as independent cost-driving factors for total direct costs. Older age and disability were independent cost-driving factors for total indirect costs, whereas epilepsy, psychiatric disease, and disability were independent cost-driving factors for nursing care costs.
Conclusions: This three-month study revealed substantial direct healthcare, indirect healthcare, and medication costs associated with TSC in Germany. This study highlights the spectrum of organ manifestations and their associated treatment needs in the German healthcare setting. Trial registration: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.
Prospective evaluation of interrater agreement between EEG technologists and neurophysiologists
(2021)
We aim to prospectively investigate, in a large and heterogeneous population, the electroencephalogram (EEG)-reading performances of EEG technologists. A total of 8 EEG technologists and 5 certified neurophysiologists independently analyzed 20-min EEG recordings. Interrater agreement (IRA) for predefined EEG pattern identification between EEG technologists and neurophysiologits was assessed using percentage of agreement (PA) and Gwet-AC1. Among 1528 EEG recordings, the PA [95% confidence interval] and interrater agreement (IRA, AC1) values were as follows: status epilepticus (SE) and seizures, 97% [96–98%], AC1 kappa = 0.97; interictal epileptiform discharges, 78% [76–80%], AC1 = 0.63; and conclusion dichotomized as “normal” versus “pathological”, 83.6% [82–86%], AC1 = 0.71. EEG technologists identified SE and seizures with 99% [98–99%] negative predictive value, whereas the positive predictive values (PPVs) were 48% [34–62%] and 35% [20–53%], respectively. The PPV for normal EEGs was 72% [68–76%]. SE and seizure detection were impaired in poorly cooperating patients (SE and seizures; p < 0.001), intubated and older patients (SE; p < 0.001), and confirmed epilepsy patients (seizures; p = 0.004). EEG technologists identified ictal features with few false negatives but high false positives, and identified normal EEGs with good PPV. The absence of ictal features reported by EEG technologists can be reassuring; however, EEG traces should be reviewed by neurophysiologists before taking action.
Background: We aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs).
Methods: This was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011–2018.
Results: We identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy.
Conclusions; Isoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge.
Background: Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients. Methods: A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany. Results: The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7–21.8 years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088–5863, median EUR 2062] per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027–1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221–3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193–586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs. Conclusions: This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting.
Hintergrund: Das Dravet-Syndrom (DS) ist ein seltenes, in der frühen Kindheit beginnendes, therapierefraktäres Epilepsiesyndrom, das mit einer hohen Morbidität und Mortalität verbunden ist.
Fragestellung: Ziele der Querschnittsstudie „Dravet syndrome caregiver survey“ (DISCUSS) sind die Identifizierung und Beschreibung der Faktoren, die einen Einfluss auf die Krankheitslast von Patienten mit DS und ihre Betreuer haben können. Die Ergebnisse der deutschen Kohorte werden vorgestellt.
Material und Methoden: Die Datenerhebung erfolgte durch eine anonyme Befragung von Eltern. Die Ergebnisse wurden für die verschiedenen Altersgruppen statistisch ausgewertet.
Ergebnisse: Der Fragebogen wurde von 68 Eltern der DS-Patienten mit einem durchschnittlichen Alter von 10 Jahren (Median: 9, Spanne: 1–26) ausgefüllt. Nur 3 Patienten (4,4 %) waren in den letzten 3 Monaten anfallsfrei. Insgesamt hatten 97 % der Patienten, die älter als 5 Jahre waren (n = 45), mindestens eine Komorbidität. Die zum Befragungszeitpunkt am häufigsten eingenommenen Antiepileptika waren Valproat, Kaliumbromid, Stiripentol, Clobazam und Topiramat. In der Vergangenheit wurden Natriumkanalblocker, Phenobarbital und Levetiracetam eingesetzt, aktuell fanden diese Antiepileptika nur selten Verwendung. Die Lebensqualität der Patienten war niedriger als die der Allgemeinbevölkerung. Die Erkrankung eines Familienmitglieds mit DS beeinflusst Eltern und Geschwister in hohem Maße.
Diskussion: Trotz individueller Kombinationstherapien sind die meisten Patienten mit DS nicht anfallsfrei. Insgesamt hat sich der Einsatz von beim DS wenig wirksamer Medikamente und der kontraindizierten Natriumkanalblocker zugunsten von wirksameren Medikamenten verschoben. Neue Therapie- und Versorgungskonzepte sind notwendig, um die Versorgung der Patienten mit DS zu verbessern und Eltern und Geschwister zu entlasten.
Hintergrund: In den vergangenen 10 Jahren wurden an verschiedenen Epilepsiezentren in Deutschland (Bochum, Erlangen, Greifswald, Berlin Brandenburg, Frankfurt Rhein-Main) Projekte entwickelt, die sich mit telemedizinischen Arzt-zu-Arzt-Anwendungen im Bereich der Epilepsieversorgung beschäftigen.
Ziel der Arbeit: Im Folgenden wird ein Überblick über die aktuell laufenden telemedizinischen Projekte in der Epilepsieversorgung in Deutschland gegeben.
Material und Methoden: Die Verantwortlichen der einzelnen Projekte stellen ihr Projekt anhand einer vorgegebenen Struktur dar.
Ergebnisse und Diskussion: In allen Projekten konnte gezeigt werden, dass eine technische Lösung für die telemedizinische Arzt-zu-Arzt Anwendung im Bereich Epileptologie geschaffen werden kann. Die dargestellten Projekte unterscheiden sich zum Teil hinsichtlich des Zieles und der Umsetzung, zum Teil zeigen sich Übereinstimmungen. Perspektivisches Ziel ist es, aus den Erfahrungen der einzelnen Projekte eine gemeinsame Strategie zur Förderung epileptologischer Telemedizin und ihrer Überführung in die Regelversorgung zu entwickeln.
Purpose: 10-year retrospective study to assess burden of illness in individuals with tuberous sclerosis complex (TSC) identified from German healthcare data. Methods: Patients with TSC were identified by International Classification of Diseases code Q85.1. Patients with epilepsy were identified by epilepsy diagnosis or antiseizure medication (ASM) prescription after TSC diagnosis. Results: Using data from 2016 (final study year), 100 patients with TSC were identified (mean [range] age: 38 [1–86] years; male: 40%); prevalence: 7.9 per 100,000 (TSC), 2.2 per 100,000 (TSC with epilepsy). During the 10-year study period (2007–2016), 256 patients with TSC were identified and followed up for 1,784 patient- years (epilepsy: 36%, 616 patient-years). TSC manifestations/comorbidities (apart from epilepsy) were identi- fied more frequently in patients with epilepsy than without. Mean annual healthcare costs for patients with TSC were €6,139 per patient-year (PPY), mostly attributable to medication (35%) and inpatient care (29%). Patients with epilepsy incurred costs more than double those without. Mean (standard deviation [SD]) annual hospi- talisation rate (AHR) and length of stay (LOS) PPY: 0.5 (1.0) and 5.9 (18.6) days for TSC. AHR and LOS were greater in patients with epilepsy than without. Mean (SD) number of ASMs prescribed (TSC with epilepsy): 3.0 (2.3) over the entire observable time per patient. Mortality rates (vs. control): 5.08% (vs. 1.69%, p<0.001) for TSC, 7.53% (vs. 0.98%, p<0.001) for TSC with epilepsy, 3.68% (vs. 2.03%, p = 0.003) for TSC without epilepsy. Conclusion: Healthcare costs, resource utilisation, and mortality were greater in patients with TSC and epilepsy than those without epilepsy.
Purpose: Epileptic seizures frequently result in distinct physical injuries, fractures, traumatic brain injuries and minor trauma. The aim of this study was to retrospectively determine the frequent injury patterns due to seizure episode and to analyze consecutive acute medical care.
Methods: This retrospective mono-center study was conducted at Frankfurt University Hospital, Frankfurt am Main, Germany between January 2007 and December 2017. Epilepsy patients with seizure-related fractures admitted to the emergency department were identified via a retrospective systematic query in the hospital information system using the ICD-10 German modification codes G40.0–G40.9. Patients with an unclear diagnosis of epilepsy were excluded. Sociodemographic as well as disease specific aspects were analyzed. Descriptive and Kruskal–Wallis one-way analysis of variance were used for statistical analysis.
Results: A total number of 62 epilepsy patients were included. The mean age was 58.1 years. Fractures concerned the upper extremity most frequently (43.5%, n = 20), and 70.0% (14/20) were humerus fractures. Admission to intensive care unit for acute trauma care was necessary in 29.0% patients (n = 18), and surgery in 45.2% patients (n = 28). Twenty-five patients (26.6%) showed clinical or radiological signs of traumatic brain injury. Provoking factors were identified in 20 patients (32.3%), i.e., acute withdrawal or excess of alcohol (n = 15), relevant sleep deprivation (n = 2), and intoxication or withdrawal of other illegal drugs or trivial infect (n = 1 for each) and non-compliance with anti-seizure drugs (n = 1). A decreased T-score (−1.04 ± 1.15) and Z-score (−0.84 ± 0.75) compared to healthy subjects were found.
Conclusion: Fractures in upper extremities, trunk and craniocerebral trauma occur frequently as seizure-induced injuries. Alcohol excess and withdrawal are important provoking factors and should be targeted with preventive measurements to avoid seizure related injuries and accidents.
In recent years, the clinical usefulness of the Wada test (WT) has been debated among researchers in the field. Therefore, we aimed to assess its contribution to the prediction of change in verbal learning and verbal memory function after epilepsy surgery. Data from 56 patients with temporal lobe epilepsy who underwent WT and subsequent surgery were analyzed retrospectively. Additionally, a standard neuropsychological assessment evaluating attentional, learning and memory, visuospatial, language, and executive function was performed both before and 12 months after surgery. Hierarchical linear regression analyses were used to determine the incremental value of WT results over socio-demographic, clinical, and neuropsychological characteristics in predicting postsurgical change in patients’ verbal learning and verbal memory function. The incorporation of WT results significantly improved the prediction models of postsurgical change in verbal learning (∆R2 = 0.233, p = .032) and verbal memory function (∆R2 = 0.386, p = .005). Presurgical performance and WT scores accounted for 41.8% of the variance in postsurgical change in verbal learning function, and 51.1% of the variance in postsurgical change in verbal memory function. Our findings confirm that WT results are of significant incremental value for the prediction of postsurgical change in verbal learning and verbal memory function. Thus, the WT contributes to determining the risks of epilepsy surgery and, therefore, remains an important part of the presurgical work-up of selected patients with clear clinical indications.