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Background and Objective Status epilepticus in poststroke epilepsy is a challenging condition because of multiple vascular comorbidities and the advanced age of patients. Data on third-generation antiseizure medication (ASM) in this condition are limited. The aim of this study was to evaluate the efficacy of third-generation ASMs in the second- or third-line therapy of benzodiazepine-refractory status epilepticus in poststroke epilepsy following acute ischemic stroke. Methods Data on the effectiveness of third-generation ASMs in patients with status epilepticus in poststroke epilepsy were gathered from two German Stroke Registries and the Mainz Epilepsy Registry. We included only cases with epilepsy remote to the ischemic event. No patients with acute symptomatic seizures were included. The following third-generation ASMs were included: brivaracetam, lacosamide, eslicarbazepine, perampanel, topiramate, and zonisamide. The assessment of effectiveness was based on seizure freedom within 48 h since the start of therapy with the respective ASM. Seizure freedom was evaluated both clinically (clinical evaluation at least three times per day) and by daily electroencephalogram records. Results Of the 138 patients aged 70.8 ± 8.1 years with benzodiazepine-refractory status epilepticus in ischemic poststroke epilepsy, 33 (23.9%) were treated with lacosamide, 24 (17.4%) with brivaracetam, 23 (16.7%) with eslicarbazepine, 21 (15.2%) with perampanel, 20 (14.5%) with topiramate, and 17 (12.3%) with zonisamide. Seizure freedom within 48 h was achieved in 66.7% of patients with lacosamide, 65.2% with eslicarbazepine, 38.1% with perampanel, 37.5% with brivaracetam, 35.0% with topiramate, and 35.3% with zonisamide ( p < 0.05 for comparison of lacosamide or eslicarbazepine to other ASMs). Conclusions Based on these data, lacosamide and eslicarbazepine might be more favorable in the treatment of refractory status epilepticus in poststroke epilepsy, when administered as second- or third-line ASMs before anesthesia. Because of the fact that these ASMs share the same mechanism of action (slow inactivation of sodium channels), our findings could motivate further research on the role that this pharmaceutical mechanism of action has in the treatment of poststroke epilepsy. Clinical Trial Registration This study was registered at ClinicalTrials.gov (NCT05267405).

Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50–85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)1–40 between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ1–40 was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (–18·0 [range −1347·0 to 1068·5] for 0·2 g/kg, −364·3 [–5834·5 to 1953·5] for 0·5 g/kg, and −351·8 [–1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs −116·3 [–1379·0 to 5266·0] for placebo; and −13·8 [–1729·0 to 307·0] for 0·1 g/kg, and −32·5 [–1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ1–40 between the 0·4 g/kg every 2 weeks group (47·0 [range −341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease. Octapharma AG.

Objective The PERPRISE study (Study 509; NCT04202159) was a prospective, observational, non‐interventional study in a real‐world setting in Germany. This study was conducted to evaluate the effectiveness of perampanel as the only adjunctive treatment for 12 months in patients aged ≥18 years with focal to bilateral tonic–clonic seizures (FBTCS) or generalized tonic–clonic seizures (GTCS) in clinical practice. Methods Adult patients with FBTCS or GTCS received perampanel as an adjunctive therapy to anti‐seizure medication (ASM) monotherapy (add‐on therapy) or as a substitute for one ASM in dual therapy (substitution therapy) per the approved indication. The primary endpoint was the 12‐month retention rate of perampanel; the secondary endpoints were the 6‐month retention rate, seizure freedom for FBTCS or GTCS at 12 months, and safety and tolerability. Exploratory endpoints included efficacy assessments by seizure type at 6 and 12 months and patient‐reported outcomes. Results Of the 185 patients enrolled in the study, 183 patients were included in the full analysis set (add‐on, 86 patients; substitution, 96 patients; missing, 1 patient). The 12‐month retention rate was 66.7% (add‐on, 67.4%; substitution, 66.7%); the 6‐month retention rate was 80.3% (add‐on, 82.6%; substitution, 78.1%). At 12 months, the seizure‐freedom rate for FBTCS or GTCS was 42.3% (add‐on, 51.7%; substitution, 35.1%). Treatment‐emergent adverse events (TEAEs) occurred in 44.0% of patients; 6.0% of patients reported serious TEAEs, and 16.5% of patients withdrew from the study due to TEAEs. Treatment with perampanel did not adversely affect cognitive function in patients with FBTCS or GTCS, and improvements in quality of life were reported by patients at both 6 and 12 months following perampanel initiation. Significance Findings from the PERPRISE study suggest that perampanel as an only adjunctive therapy is associated with favorable retention rates and good tolerability in patients with FBTCS or GTCS in a real‐world clinical setting in Germany. Plain Language Summary Patients with epilepsy often take multiple treatments to control their seizures. It is important to look at how well they work in everyday life. This study looked at adult patients in Germany taking perampanel added to one other epilepsy treatment. After 1 year, 58 of 137 patients suffering from the most severe type of seizure were free of them. Side effects occurred in 80 patients (most commonly dizziness, fatigue, and nausea) and caused 30 of them to withdraw from treatment. Perampanel was effective and did not seem to negatively affect patients' thinking ability or quality of life.

Objective To report the interim results of the PERPRISE study (Study 509; NCT04202159), which is evaluating perampanel as the only adjunctive anti‐seizure medication (ASM) in adults with focal to bilateral tonic–clonic seizures (FBTCS) or primary generalized tonic–clonic seizures (GTCS). Methods PERPRISE is an ongoing 12‐month multicenter, prospective, observational, non‐interventional study of perampanel in a real‐world setting in Germany. Patients are aged ≥18 years with FBTCS or GTCS due to focal or idiopathic generalized epilepsy. Perampanel, as an adjunctive therapy to ASM monotherapy (‘add‐on therapy’) or as a substitute for one ASM in dual therapy (‘substitution therapy’), is prescribed in line with its SmPC. The Interim Analysis Set comprises the first 100 patients who received ≥1 dose of perampanel and attended or discontinued prior to the ~6‐month visit. Interim endpoints include retention rate, measures of effects on seizure frequency, and treatment‐emergent adverse events (TEAEs). Results One hundred patients were included in the Interim Analysis Set (add‐on, n = 43 [43.0%]; substitution, n = 55 [55.0%]; unknown, n = 2). The 6‐month retention rate was 78.0% (add‐on, 83.7%; substitution, 72.7%). For the overall population with GTCS and/or FBTCS, seizure‐freedom rate at 6 months was 58.8% (add‐on, 72.2%; substitution, 47.9%) and 50% responder rate at 6 months was 82.6% (add‐on, 89.2%; substitution, 76.6%). Retention rates and seizure outcomes were better with perampanel as an early‐line treatment than as a late‐line treatment. TEAEs were reported by 48 patients (48.0%), most commonly dizziness (n = 9), fatigue (n = 7), and irritability (n = 7). Sixteen patients (16.0%) withdrew from perampanel treatment due to TEAEs. Significance The interim analysis of PERPRISE offers insight into the real‐world use of perampanel in Germany, including for the first time, clinical practice data from patients with GTCS and switching ASMs within a dual therapy. Further data from PERPRISE will be of value to inform clinical decision‐making in this patient cohort. Plain Language Summary Patients with epilepsy often take more than one medication for seizure control. This 12month study looked at patients in Germany receiving perampanel as only add‐on medication. The interim analysis shows, that at 6 months, over 70% of the 100 patients continued to use perampanel; 59% experienced no seizures during treatment with perampanel, and in 83%, seizure frequency was reduced by half. Side effects occurred in 48% of patients (most commonly dizziness, fatigue, and irritability) and caused 16% to withdraw from the study. Overall, perampanel was a suitable as only add‐on medication for patients with epilepsy.

IntroductionA novel focal cortex stimulation (FCS) device has recently received approval in Europe for patients with focal drug-resistant epilepsy (DRE). After 6 months of stimulation, 17 of 32 patients achieved ≥50% reduction in seizure frequency compared with their prestimulation baseline (responders). Currently, there is no established method for predicting FCS treatment response prior to implantation.Methods and analysisThis is an ongoing combined retrospective-prospective non-interventional multicentre study. Clinical data of up to 100 patients treated with FCS are collected across 20 collaborating epilepsy centres in four European countries. The key outcome parameters, seizure frequency and severity, are measured along with metrics on cognition, mood and quality of life, both pre-electrode and postelectrode implantation. The data are complemented by demographics, medical history and information on antiseizure medication and FCS treatment parameters during the stimulation period. In addition to clinical data, MRI and electroencephalography registrations are used to gain insights into spatial and electrophysiological aspects of FCS. Multivariate statistical and machine learning analyses are employed to identify key predictive biomarkers associated with patient outcomes (responders vs non-responders). The primary goal is to improve counselling for DRE patients by identifying promising candidates for FCS treatment.Ethics and disseminationThis study has received approval from the ethics committee of the University of Freiburg, Germany (23–1540 S1; 23–1183_1-S1-retro). The same approval is applicable for all participating centres in Germany as part of a multicentre study. Ghent University Hospital, Belgium, has received approval for participation in the retrospective arm from their local ethics committee (ONZ-2024-0168). The final approvals for the participating Swiss and Austrian sites are still pending. The results will be made available to the public through peer-reviewed journals and conference presentations.

ObjectivesBrivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting.DesignRetrospective, observational multicentre study.SettingWe retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist.ParticipantsData of 615 epilepsy patients treated with BRV were included in the study.Primary and secondary outcome measuresEfficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X2 contingency tests and effect sizes were performed.ResultsOverall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV.ConclusionsThe present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV.

Neuromuscular disorders (NMD) are chronic devastating diseases. The aim of this multicenter cross-sectional study was to evaluate the socioeconomic impact of three NMDs in Germany. Patients ( n  = 107) with amyotrophic lateral sclerosis (ALS), myasthenia gravis (MG) or facioscapulohumeral muscular dystrophy (FSHD) were recruited consecutively in seven centers in Germany. The health-economic data were collected using a “bottom-up” approach consisting of comprehensive questionnaires and patient diaries. Costs were evaluated from the societal perspective in 2009 Euros (EUR). Total annual costs from the societal perspective were EUR 36,380 (95% CI 27,090–47,970) per patient in ALS, EUR 26,240 (95% CI 17,770–37,940) in FSHD and EUR 14,950 (95% CI 10,470–21,730) in MG. The main components of costs were the expenditures of health insurance and the loss of productivity of patients and their caregivers. The following independent cost-driving factors were identified: disease severity, assistance in activities of daily living (ADL), dementia and younger age in ALS, disease severity in FSHD and assistance in ADL, disease severity and assistance in ADL in MG. The socioeconomic burden of NMDs in Germany is considerable. Further studies evaluating both the health-economic and clinical effects of NMD treatment as well as disease management programs and benchmarking activities are necessary.

Neuromuscular disorders are rare diseases with a chronic and debilitating course. Unfortunately, data on the health-related quality of life (HRQoL) in neuromuscular diseases are limited. The objective of this multicentre cross-sectional study was to compare the HRQoL in patients with amyotrophic lateral sclerosis (ALS), facioscapulohumeral muscular dystrophy (FSHD) and myasthenia gravis (MG) and to identify the determinants of the HRQoL in these diseases. We recruited 91 consecutive outpatients with ALS ( n  = 37), FSHD ( n  = 17) or MG ( n  = 37) in seven specialized German health centres. The HRQoL was determined using the 36-Item Short Form Health Survey (SF-36) and the EuroQol (EQ-5D). Independent predictors of the HRQoL were identified using multiple regression analysis. The HRQoL in all domains of the SF-36, except for bodily pain, was significantly reduced. The domains related to physical health (physical functioning, physical role) were most affected. The EQ-5D-index score was most reduced in ALS (0.54) and least reduced in MG (0.89). Independent predictors of a reduced HRQoL were disease severity and depression in ALS, and disease severity, depression, older age and increased body-mass index in MG. The patterns of HRQoL-impairment in neuromuscular disorders share some common features, such as a more pronounced reduction in the HRQoL related to physical health, but there are a number of disease-specific features that should be considered in outcomes of clinical trials and treatment guidelines. In addition to the treatment of motor symptoms, greater attention should be paid to the treatment of depression, which was found to be among the independent predictors of the HRQoL in ALS and MG.

The costs of acute stroke care, length of hospital stay (LOS), and outcome in patients with cardioembolic stroke or cardioembolic transient ischemic attacks (TIA) were investigated with the aim of estimating the clinical and health-economic impacts of cerebral cardioembolism. The study population consisted of 511 consecutive patients with the diagnosis of ischemic stroke ( n  = 379) or TIA ( n  = 132) treated at the Department of Neurology, Philipps University, Marburg. Cerebral cardioembolism was defined according to the criteria of the Cerebral Embolism Task Force. Clinical status was assessed by means of Barthel index (BI) and modified Rankin Scale. Costs were calculated using a bottom-up approach. All costs (in Euros) were inflated to the 2008 level. Compared to non-cardioembolic stroke ( n  = 278) patients, patients who had suffered cardioembolic stroke ( n  = 101) had more severe clinical deficits on admission (BI 46.3 ± 27.0 vs. 59.3 ± 34.1; P  < 0.01), worse recovery (BI on discharge 59.2 ± 28.9 vs. 73.1 ± 33.4; P  < 0.01), and increased LOS (12.6 ± 5.7 vs. 10.0 ± 7.8 days; P  < 0.01). The latter also required a relatively higher daily resource utilization due to increased expenses for personnel and diagnostics. Mean costs of acute care for patients with cardioembolic stroke [€ 4890 per patient (95% confidence interval 4460–5200)] were significantly higher than those for patients with non-cardioembolic stroke [€ 3550 (95% confidence interval 3250–3850); P  < 0.01]. The clinical and health-economic impact of cardiogenic cerebral embolism on stroke care is considerable. Patients with cardioembolic stroke/TIA are more severely impaired, and they require longer hospital treatment and increased resource utilization. Costs of acute care of cardioembolic stroke/TIA patients may exceed those of non-cardioembolic stroke/TIA by up to 40%.

Electroencephalography (EEG) spikes and focal epileptic seizures are generated in circumscribed cerebral networks that have been insufficiently described. For precise time and spatial domain network characterization, we applied in patients with focal epilepsy dense array 256-channel EEG recordings with causal connectivity estimation by using time-resolved partial directed coherence and 3T-magnetic resonance imaging-derived cortical and thalamus integrity reconstruction. Before spike generation, significant theta and alpha bands driven information flows alterations were noted from both temporal and frontal lobes to the thalamus and from the thalamus to the frontal lobe. Medial dorsal and ventral anterior nuclei of the thalamus were delimited as possible pacemakers. Markedly reduced thalamic volumes and impaired cortical integrity in widespread areas predicted the altered information flows. Our data reveal distinct patterns of connectivity involving the thalamus and frontal cortex that are both directly and causally involved in spike generation. These structures might play an essential role in epileptogenesis and could be targeted in future therapeutic approaches.