Refine
Document Type
- Article (60)
- Preprint (2)
- Conference Proceeding (1)
Has Fulltext
- yes (63)
Is part of the Bibliography
- no (63)
Keywords
- Epilepsy (13)
- epilepsy (13)
- seizure (7)
- Seizure (5)
- temporal lobe epilepsy (4)
- Quality of life (3)
- Status epilepticus (3)
- Tele-EEG (3)
- levetiracetam (3)
- seizures (3)
Institute
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.
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: There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable detection in biofluids. Altered levels of circulating microRNAs have been reported in human epilepsy, but most studies collected samples from one clinical site, used a single profiling platform or conducted minimal validation.
Method: Using a case-control design, we collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated findings in a large (>250) cohort of samples that included patients with psychogenic non-epileptic seizures (PNES).
Findings: After profiling and validation, we identified miR-27a-3p, miR-328-3p and miR-654-3p with biomarker potential. Plasma levels of these microRNAs were also changed in a mouse model of TLE but were not different to healthy controls in PNES patients. We determined copy number of the three microRNAs in plasma and demonstrate their rapid detection using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Analysis of the microRNAs within the exosome-enriched fraction provided high diagnostic accuracy while Argonaute-bound miR-328-3p selectively increased in patient samples after seizures. In situ hybridization localized miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics predicted targets linked to growth factor signaling and apoptosis.
Interpretation: This study demonstrates the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms.
Einleitung: Die stereotaktische Laserthermoablation (SLTA) stellt eine minimal-invasive Behandlung für therapierefraktäre Epilepsien auf dem Boden eines hypothalamischen Hamartoms (HH) dar. Durch die weitreichenden Folgen einer therapierefraktären Epilepsie können hohe direkte Kosten entstehen, die durch eine zu erzielende Anfallsfreiheit gesenkt werden können.
Methoden: Anhand einer Patientin mit einem HH sollen die Auswirkungen einer solchen Erkrankung beleuchtet und der Krankheitsverlauf nach erfolgter SLTA dargestellt werden. Zur Beurteilung der Kosteneffizienz der SLTA wurden die direkten Kosten, basierend auf den Krankenversicherungsdaten der Patientin, über die Versicherungsjahre 2017 bis 2020 analysiert.
Ergebnisse:
Bei der Patientin bestand eine hochaktive, medikamentenrefraktäre Epilepsie mit erhöhtem Verletzungsrisiko und zunehmender Verschlechterung der schulischen Leistung und der psychischen Verfassung. Begleitend bestand durch das HH eine Pubertas praecox. Nach SLTA entwickelte die Patientin mit einem Follow-up von 26 Monaten eine vollständige Anfallsfreiheit sowie eine endokrinologische Stabilisierung, sodass die antikonvulsive als auch die hormonelle Medikation im Verlauf beendet werden konnten. Relevante persistierende Komplikationen wurden nicht beobachtet. Die direkten jährlichen Kosten (stationär [ausschließlich der SLTA selbst]/ambulant/Medikamente) reduzierten sich von € 6603 in 2017 und € 12.903 in 2018 auf € 3609 in 2019 und zuletzt € 617 in 2020, was einer Reduktion von bis zu 95 % (2018 gegenüber 2020) entsprach. Zusätzlich konnten die Kosten einer geplanten Integrationsassistenz von schätzungsweise € 18.000/Jahr eingespart werden.
Schlussfolgerung: Die SLTA stellt eine effektive und risikoarme Behandlung von HH dar und führt bereits nach 2 Jahren zu einer relevanten Einsparung der direkten Kosten, was bei der Kosten-Nutzen-Abwägung der SLTA einzubeziehen ist.
The article Therapeutic Options for Patients with Refractory Status Epilepticus in Palliative Settings or with a Limitation of Life‑Sustaining Therapies: A Systematic Review, written by Laurent M. Willems, Sebastian Bauer, Kolja Jahnke, Martin Voss, Felix Rosenow, Adam Strzelczyk, was originally published Online First without Open Access. After publication in volume 34, issue 8, pages 801–826 the author decided to opt for Open Choice and to make the article an Open Access publication. Post-publication open access was funded by Projekt DEAL. Therefore, the copyright of the article has been changed to © The Author(s) 2021 and the article is forthwith distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. The original article has been corrected.
Recent data have suggested that performing recanalizing therapies in ischemic stroke might lead to an increased risk of acute symptomatic seizures. This applies to both intravenous thrombolysis and mechanical thrombectomy. We therefore determined the frequency of acute symptomatic seizures attributable to these two recanalization therapies using a large, population-based stroke registry in Central Europe. We performed two matched 1:1 case–control analyses. In both analyses, patients were matched for age, stroke severity on admission and pre-stroke functional status. The first analysis compared patients treated with intravenous thrombolysis to a non-recanalization control group. To isolate the effect of mechanical thrombectomy, we compared patients with both mechanical thrombectomy and intravenous thrombolysis to those with only intravenous thrombolysis treatment in a second analysis. From 135,117 patients in the database, 13,356 patients treated with only intravenous thrombolysis, and 1013 patients treated with both intravenous thrombolysis and mechanical thrombectomy were each matched to an equivalent number of controls. Patients with intravenous thrombolysis did not suffer from clinically apparent acute symptomatic seizures significantly more often than non-recanalized patients (treatment = 199; 1.5% vs. control = 237; 1.8%, p = 0.07). Mechanical thrombectomy in addition to intravenous thrombolysis also was not associated with an increased risk of acute symptomatic seizures, as the same number of patients suffered from seizures in the treatment and control group (both n = 17; 1.7%, p = 1). In a large population-based stroke registry, the frequency of clinically apparent acute symptomatic seizures was not increased in patients who received either intravenous thrombolysis alone or in conjunction with mechanical thrombectomy.
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.
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
Objective To evaluate the success of initiation of adjunctive brivaracetam in patients who required a change in antiepileptic drug (AED) regimen and substituted at least one AED with brivaracetam. Methods In this retrospective noninterventional study conducted in specialized epilepsy centers across Germany, patients initiated adjunctive brivaracetam between February 15, 2016, and August 31, 2016, as part of an intended change in AED regimen. The primary effectiveness variable was the proportion of patients who continued on brivaracetam after 3 months, and withdrew at least one AED either before or within 6 months after brivaracetam initiation. Results Five hundred and six patients had at least one brivaracetam dose and were included in the safety set (SS). Four hundred and seventy patients started to reduce the dose of one AED before/after brivaracetam initiation, had at least one concomitant AED at brivaracetam initiation, and were included in the full analysis set (FAS) for effectiveness analyses. At baseline, patients had a median of seven lifetime AEDs and a median of 3.8 seizures/28 days. In the SS, 85.2% of patients withdrew one AED before/after initiation of brivaracetam, most commonly levetiracetam (49.4%). 46.2% of patients substituted another AED with brivaracetam within 24 hours (fast withdrawal). The proportions of patients (FAS) who continued on brivaracetam after 3 and 6 months and withdrew one AED were 75.5% and 46.6%, respectively. After 6 months, 32.1% of patients were 50% responders; 13.0% were seizure‐free. In the SS, 34.6% of patients reported treatment‐emergent adverse events (TEAEs); 21.9% had TEAEs that were assessed by the treating physician as drug‐related. Incidences of behavioral AEs before (3‐month baseline) and after brivaracetam initiation in patients who withdrew levetiracetam were 19.2% and 8.0%, respectively (5.0% and 7.7% in patients who withdrew other AEDs). Significance Brivaracetam was effective and well‐tolerated in patients who required a change in AED drug regimen and initiated adjunctive brivaracetam in German clinical practice.