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Background: A Core Outcome Set (COS) is a standardised list of outcomes that should be reported as a minimum in all clinical trials. In epilepsy, the choice of outcomes varies widely among existing studies, particularly in clinical trials. This diminishes opportunities for informed decision-making, contributes to research waste and is a barrier to integrating findings in systematic reviews and meta-analyses. Furthermore, the outcomes currently being measured may not reflect what is important to people with epilepsy. Therefore, we aim to develop a COS specific to clinical effectiveness research for adults with epilepsy using Delphi consensus methodology.Methods: The EPSET Study will comprise of three phases and follow the core methodological principles as outlined by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Phase 1 will include two focused literature reviews to identify candidate outcomes from the qualitative literature and current outcome measurement practice in phase III and phase IV clinical trials. Phase 2 aims to achieve international consensus to define which outcomes should be measured as a minimum in future trials, using a Delphi process including an online consensus meeting involving key stakeholders. Phase 3 will involve dissemination of the ratified COS to facilitate uptake in future trials and the planning of further research to identify the most appropriate measurement instruments to use to capture the COS in research practice.Discussion: Harmonising outcome measurement across future clinical trials should ensure that the outcomes measured are relevant to patients and health services, and allow for more meaningful results to be obtained.Core Outcome Set Registration: COMET Initiative as study 118 . [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that people with focal epilepsy experience diagnostic delays that may be associated with preventable morbidity, particularly when seizures have only nonmotor symptoms, we compared time to diagnosis, injuries, and motor vehicle accidents (MVAs) in people with focal nonmotor versus focal seizures with motor involvement at epilepsy onset. Methods: This retrospective study analyzed the enrollment data from the Human Epilepsy Project, which enrolled participants between 2012 and 2017 across 34 sites in the USA, Canada, Europe, and Australia, within 4 months of treatment for focal epilepsy. A total of 447 participants were grouped by initial seizure semiology (focal nonmotor or focal with motor involvement) to compare time to diagnosis and prediagnostic injuries including MVAs. Results: Demographic characteristics were similar between groups. There were 246 participants (55%) with nonmotor seizures and 201 participants (45%) with motor seizures at epilepsy onset. Median time to diagnosis from first seizure was 10 times longer in patients with nonmotor seizures compared to motor seizures at onset (P <.001). The number and severity of injuries were similar between groups. However, 82.6% of MVAs occurred in patients with undiagnosed nonmotor seizures. Significance: This study identifies reasons for delayed diagnosis and consequences of delay in patients with new onset focal epilepsy, highlighting a treatment gap that is particularly significant in patients who experience nonmotor seizures at epilepsy onset. [ABSTRACT FROM AUTHOR]

Objectives: To assess tolerability and efficacy of lacosamide in adults with cerebrovascular epilepsy etiology (CVEE). Materials and methods: Exploratory post hoc analyses of a double‐blind, initial monotherapy trial of lacosamide vs carbamazepine‐controlled release (carbamazepine‐CR) (SP0993; NCT01243177); a double‐blind conversion to lacosamide monotherapy trial (SP0902; NCT00520741); and an observational study of adjunctive lacosamide added to one antiepileptic drug (SP0973 VITOBA; NCT01098162). Patients with CVEE were identified based on epilepsy etiology recorded at baseline. Results: In the initial monotherapy trial, 61 patients had CVEE (lacosamide: 27; carbamazepine‐CR: 34). 20 (74.1%) patients on lacosamide (27 [79.4%] on carbamazepine‐CR) reported treatment‐emergent adverse events (TEAEs), most commonly (≥10%) headache, dizziness, and fatigue (carbamazepine‐CR: headache, dizziness). A numerically higher proportion of patients on lacosamide than carbamazepine‐CR completed 6 months (22 [81.5%]; 20 [58.8%]) and 12 months (18 [66.7%]; 17 [50.0%]) treatment without seizure at last evaluated dose. In the conversion to monotherapy trial, 26/30 (86.7%) patients with CVEE reported TEAEs, most commonly (≥4 patients) dizziness, convulsion, fatigue, headache, somnolence, and cognitive disorder. During lacosamide monotherapy, 17 (56.7%) patients were 50% responders and six (20.0%) were seizure‐free. In the observational study, 36/83 (43.4%) patients with CVEE reported TEAEs, most commonly (≥5%) fatigue and dizziness. Effectiveness was assessed for 75 patients. During the last 3 months, 60 (80%) were 50% responders and 42 (56.0%) were seizure‐free. Conclusions: These exploratory post hoc analyses suggested lacosamide was generally well tolerated and effective in patients with CVEE, with data from the initial monotherapy trial suggesting numerically better efficacy than carbamazepine‐CR. [ABSTRACT FROM AUTHOR]

Background: Transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) can be used to explore the dynamical state of neuronal networks. In patients with epilepsy, TMS can induce epileptiform discharges (EDs) with a stochastic occurrence despite constant stimulation parameters. This observation raises the possibility that the pre-stimulation period contains multiple covert states of brain excitability some of which are associated with the generation of EDs. Objective: To investigate whether the interictal period contains "high excitability" states that upon brain stimulation produce EDs and can be differentiated from "low excitability" states producing normal appearing TMS-EEG responses. Methods: In a cohort of 25 patients with Genetic Generalized Epilepsies (GGE) we identified two subjects characterized by the intermittent development of TMS-induced EDs. The high-excitability in the pre-stimulation period was assessed using multiple measures of univariate time series analysis. Measures providing optimal discrimination were identified by feature selection techniques. The "high excitability" states emerged in multiple loci (indicating diffuse cortical hyperexcitability) and were clearly differentiated on the basis of 14 measures from "low excitability" states (accuracy = 0.7). Conclusion: In GGE, the interictal period contains multiple, quasi-stable covert states of excitability a class of which is associated with the generation of TMS-induced EDs. The relevance of these findings to theoretical models of ictogenesis is discussed. [ABSTRACT FROM AUTHOR]

Objective To compare the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients with newly diagnosed epilepsy. Methods This unblinded, randomised, 52-week superiority trial (NCT00175903) recruited patients (=16 years of age) with =2 unprovoked seizures in the previous 2 years and =1 in the previous 6 months. The physician chose VPA or CBZ as preferred standard treatment; each patient was randomised to standard treatment or LEV. The primary outcome was time to treatment withdrawal (LEV vs standard antiepileptic drugs (AEDs)). Analyses also compared LEV with VPAER, and LEV with CBZ-CR. Findings 1688 patients (mean age 41 years; 44% female) were randomised to LEV (n=841) or standard AEDs (n=847). Time to treatment withdrawal was not significantly different between LEV and standard AEDs: HR (95% CI) 0.90 (0.74 to 1.08). Time to treatment withdrawal (HR (95% CI)) was 1.02 (0.74 to 1.41) for LEV/VPA-ER and 0.84 (0.66 to 1.07) for LEV/CBZ-CR. Time to first seizure (HR, 95% CI) was significantly longer for standard AEDs, 1.20 (1.03 to 1.39), being 1.19 (0.93 to 1.54) for LEV/VPA-ER and 1.20 (0.99 to 1.46) for LEV/CBZ-CR. Estimated 12-month seizure freedom rates from randomisation: 58.7% LEV versus 64.5% VPA-ER; 50.5% LEV versus 56.7% CBZ-CR. Similar proportions of patients within each stratum reported at least one adverse event: 66.1% LEV versus 62.0% VPA-ER; 73.4% LEV versus 72.5% CBZ-CR. Conclusions LEV monotherapy was not superior to standard AEDs for the global outcome, namely time to treatment withdrawal, in patients with newly diagnosed focal or generalised seizures. [ABSTRACT FROM AUTHOR]

Purpose: Patients with epilepsy are at greater risk for cognitive impairment than are age- and education-matched controls. Cognitive decline is a significant adverse event associated with many first-generation anticonvulsant drugs (AEDs); however, the past decade has seen the introduction of several new AEDs with more-favorable cognitive profiles. Tiagabine (TGB) is indicated as adjunctive therapy for the treatment of partial seizures. The cognitive effects of TGB and carbamazepine (CBZ) monotherapy were evaluated in adult epilepsy patients with partial seizures. Methods: This analysis pooled data from two randomized studies with similar populations, dosing, and cognitive assessments. TGB was titrated to 20–30 mg/day and CBZ to 400–800 mg/day over a 6-week period. A control or no-drug group of untreated patients with a single epileptic seizure was included for comparison. Cognitive function was assessed at baseline and 52 weeks. Results: Of the 105 epilepsy patients enrolled, 79 completed the 52 weeks of monotherapy (TGB, 74%; CBZ, 77%). Altogether, 19 untreated patients composed the no-drug group. During the 52-week follow-up, only one statistically significant difference was found between the treatment groups and the no-drug group [verbal fluency task: F(2, 92) = 3.16; p = 0.047]. On further analysis, it was determined that this statistical difference was solely based on the patients receiving CBZ performing worse than the control group (p = 0.048). Statistically significant improvements (p < 0.05) were found on six (26%) of 23 variables with TGB and CBZ, as well as the no-drug group, although the variables differed between the groups. Significant worsening in the test scores was not seen in any of the study groups. Conclusions: The results of this 52-week, follow-up study show that successful TGB monotherapy with 20–30 mg/day has a cognitive profile similar to that of successful long-term CBZ monotherapy with 400–800 mg/day in newly diagnosed patients with epilepsy and to that of untreated patients with a single seizure. We observed no significant decline in cognitive scores associated with TGB monotherapy. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated obstetric and neonatal outcome in a community-based cohort of women with active epilepsy (WWAE) compared with the general pregnant population receiving modern obstetric care. Methods: We reviewed the total population who gave birth between January 1989 and October 2000 at Kuopio University Hospital. Obstetric, demographic, and epilepsy data were collected prospectively from 179 singleton pregnancies of women with epilepsy and from 24,778 singleton pregnancies of unaffected controls. The obstetric data from the pregnancy register was supplemented with detailed neurologic data retrieved from the medical records. The data retrieved were comprehensive because of a follow-up strategy according to a predecided protocol. Results: During pregnancy, the seizure frequency was unchanged, or the change was for the better in the majority (83%) of the patients. We found no significant differences between WWAE and controls in the incidence of preeclampsia, preterm labor, or in the rates of caesarean sections, perinatal mortality, or low birth weight. However, the rate of small-for-gestational-age infants was significantly higher, and the head circumference was significantly smaller in WWAE. Apgar score at 1 min was lower in children of WWAE, and the need for care in the neonatal ward and neonatal intensive care were increased as compared with controls. The frequency of major malformations was 4.8% (−0.6–10.2%; 95% confidence interval) in the 127 children of WWAE. Conclusions: Pregnancy course is uncomplicated and neonatal outcome is good in the majority of cases when a predecided protocol is used for the follow-up of WWAE in antenatal and neurologic care. Long-term follow-up of the neurologic and cognitive development of the children of WWAE is still needed. [ABSTRACT FROM AUTHOR]

Summary: Purpose:: To investigate whether initial valproate (VPA) monotherapy for the treatment of epilepsy causes visual field defects and visual dysfunction. Methods:: In a cross-sectional study, visual fields were examined with the kinetic Goldmann and automated Humphrey perimeters, contrast sensitivity function with the Pelli–Robson letter chart and colour vision with the Standard Pseudoisochromatic Plates Part 2 (SPP2) and Farnsworth–Munsell 100 Hue test (FM100) in eighteen epilepsy patients (aged 18–50 years, 30.2.±10 years, mean±S.D.) treated with initial valproate monotherapy for 2–20 years (8.4±5.1 years). Results:: None had vigabatrin-type, concentric visual field defect with the kinetic Goldmann or automated Humphrey perimetries. In the Humphrey perimetry, the mean deviation for the group was within normal limits varying from −2.53 to 0.59dB (−0.74±0.80dB) in the right eye and from −2.66 to 0.67dB (−0.78±0.82dB) in the left eye. In the FM100 test, acquired colour vision deficiency was found in two out of 18 patients (11%, 95% CI: 0–25%). However, the mean total error score was lower in the patient group than in the control group. All patients had normal contrast sensitivity function. Conclusions:: The use of VPA in the treatment of epilepsy is not associated with visual field defects similar to vigabatrin, but may induce abnormalities in colour vision. [Copyright &y& Elsevier]

• Quality of life (QoL) in people with drug-resistant epilepsy (DRE) perceives a considerable burden of disease, which goes beyond the direct effects of seizure frequency and type. • Their QoL is impaired by the interference of medical and psychological comorbidities in their daily activities and anxiety in engaging in social interactions. • Neurologists can work with the patient towards a better QoL by acting on several fronts: addressing side effects and what the patient is willing to tolerate in favour of seizure reduction, taking advantage of added benefits of newer antiseizure medications (ASMs), promptly referring patients with complex management to specialized centres as needed, or to less-known interventions such as cognitive rehabilitation. Despite the many therapeutic options for epilepsy available today, a third of patients still have poorly controlled epilepsy. Over the years, their transition through lines of treatment exposes them to increased risk of disease progression, mortality, morbidity, mental distress, and not least significantly impaired quality of life (QoL). The present review explores the multiple factors contributing to the impairment of health-related QoL in PWE–including both seizure-related and non seizure-related. The analysis aims to identify potential areas of intervention and strategies for a more holistic approach to epilepsy care and inform policy-makers and healthcare providers in their approach to this condition. [ABSTRACT FROM AUTHOR]

Objectives To ensure the development of new effective treatments in medicine, clinical trials (CTs) need to be conducted. The study was aimed at assessing knowledge of and attitudes toward clinical drug trials among patients with epilepsy, along with factors that motivate them to participate in CTs. Use of this information could improve recruitment for future trials and enhance their quality. Methods A 45-item questionnaire on the views of patients with epilepsy about CTs was developed. It included statements that the respondents assessed on a Likert scale from 1 (‘strongly disagree’) to 5 (‘strongly agree’). The questionnaire was mailed to a random sample ( n = 1875) of members of the Finnish Epilepsy Association aged at least 18 years. In all, 342 questionnaires were returned, and 325 were accepted after exclusion. Results The analysis indicates that the general attitudes of patients with epilepsy toward CTs are positive. Most of the patients with epilepsy saw participation in clinical trials as indispensable to new treatments becoming available. Retired respondents and persons who had developed epilepsy when young had inadequate knowledge of general issues related to CTs. Level of education and number of antiepileptic medications (AEDs) were significant predictors for failure to understand the nature and purpose of clinical research — i.e., for therapeutic misconception (TM). Additionally, strong correlation was found between TM and respondents' willingness to participate in clinical trials. Conclusions The new treatments are often studied in patients with a high risk of TM and impaired comprehension of general procedures associated with CTs. Clinically, it may be worthwhile for the investigators to be able to recognize vulnerable individuals and pay special attention to the information provided on the purposes and methods of the trial, to contribute to high-quality AED studies. [ABSTRACT FROM AUTHOR]

Summary Background Unverricht–Lundborg disease (EPM1) is characterized by stimulus-sensitive and action-activated myoclonus, tonic–clonic seizures and ataxia. Several disease-related alterations in cortical structure and excitability have been associated with the motor symptoms of EPM1. This study aimed to elucidate possible alterations in cortical activation related to motor performance in EPM1. Methods Fifteen EPM1-patients and 15 healthy volunteers matched for age and sex underwent motor functional MRI. Group differences in activations were evaluated in the primary and supplementary motor cortices and sensory cortical areas. Furthermore, in EPM1 patients, the quantitative fMRI parameters were correlated with the severity of the motor symptoms. Results The EPM1-patients exhibited decreased activation in the left inferior frontal junction (IFJ) during right hand voluntary motor task when compared with controls. In the quantitative analysis, EPM1-patients had significantly weaker activation than controls in the hand knob and supplementary motor areas (SMA). The volume of activation in M1 decreased with age and duration of disease in the patient group, whereas the volume increased with age in controls. Negative correlations were observed between fMRI parameters of SMA and disease duration or age in patients but not in controls. Conclusions The weaker motor fMRI activation observed in EPM1 patients parallels previous neurophysiological findings and correlates with the motor symptoms of the disease. Thus, the observed decrease in IFJ activation in EPM1 patients may be associated with the difficulties in initiation or termination of motor execution, a typical clinical symptom in EPM1. The fMRI findings reflect the progressive nature of this disease. [ABSTRACT FROM AUTHOR]