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Background and purpose The European Academy of Neurology (EAN) has adhered to the global plan for reducing the burden of neurological disorders and promoting brain health launched by the World Health Organisation (WHO), the WHO Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders. This study reports the results of an EAN survey among national neurological societies (NNSs) on their awareness of brain health policies. Methods The EAN survey on the current state of national brain health policies was conducted among the 47 presidents of the NNSs affiliated with the EAN, with the aim of developing the best strategy for close collaboration among stakeholders. Results From June 2023 to February 2024, 36/47 responses (77%) were collected. Among respondents, 67% were in contact with their Ministry of Health and 78% were aware of and in contact with one or more national neurological patient organisation, while 17% had no contacts with any association. Ninety‐two percent declared a high to medium degree of awareness of the need to support brain health and of brain health plans and strategies in their country. Conclusions Our findings suggest good awareness of the importance of brain health and of the strategies implemented at the national level among the EAN‐affiliated NNSs and representatives. Efforts towards improvement may be directed towards cooperation between NNSs and political institutions, as well as patient organisations, to optimise brain and global public health and neurological care in each country.

Triaging acute ischemic stroke patients is difficult in prehospital settings. We investigated if a quickly applicable and compact EEG recording system is usable for stroke patients in the ambulance. The EEG of 10 acute stroke patients from Kuopio University Hospital, Finland was recorded using a forehead EEG electrode set and compact EEG amplifier-recorder during their ambulance transfer to another healthcare facility. The recordings were transmitted wirelessly in real time to our server, and their quality and the interruptions and technical difficulties in the wireless data transfer were analysed. In 9 of the 10 recordings, the signal quality was sufficient for interpreting at least half of the recording. The signal quality suffered from artefacts caused by the patients' movements and the loosening of the electrode contacts. Only 50-Hz AC artefacts that affected the reference electrode were considered obtrusive and required digital filtering in two recordings. We demonstrated that adequate-quality EEG can be recorded in an ambulance using a quickly applicable and compact recording system and reliably transferred to a remote server for real-time review. This system can be used to measure EEG in acute indications in the prehospital setting.

Management of drug resistant epilepsy (DRE) represents a challenge to the treating clinician. This manuscript addresses DRE and provides an overview of treatment options, medical, surgical, and dietary. It addresses treatment strategies in polytherapy, then focuses on the role cenobamate (CNB) may play in reducing the burden of DRE while providing practical advice for its introduction. CNB is a recently approved, third generation, anti‐seizure medication (ASM), a tetrazole‐derived carbamate, thought to have a dual mechanism of action, through its effect on sodium channels as well as on GABA A receptors at a non‐benzodiazepine site. CNB, having a long half‐life, is an effective add‐on ASM in refractory focal epilepsy with a higher response rate and a higher seizure‐freedom rate than is usually seen in regulatory clinical trials. Experience post‐licensing, though still limited, supports the findings of clinical trials and is encouraging. Its spectrum of action in relation to generalized epilepsies and seizures remains to be established, and there are no data on its efficacy in monotherapy. At the time of writing, CNB has been prescribed for some 50 000 individuals with DRE and focal epilepsy. A larger number is needed to fully establish its safety profile. It should at all times be introduced slowly to minimize the risk of serious allergic drug reactions. It has clinically meaningful interactions which must be anticipated and managed to maximize tolerability and likelihood of successful treatment. Despite the above, it may well prove to be of major benefit in the treatment of many patients with drug resistant epilepsy.

The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be of interest to study intellectual disability (ID) and the contribution of ARID. Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7 Mb deletion covering DYRK1A and KCNJ6. Overall, a pathogenic or likely pathogenic variant was identified in 64% (25/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (UBA7, DDX47, DHX58) and discuss potential candidate genes for ID, including SYPL1 and ERGIC3 with homozygous founder variants and de novo variants in POLR2F and DNAH3. In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case.

Objective In the current study, we aimed to assess the diagnostic delay and the impact of diagnostic delay on seizure outcome in a cohort of newly diagnosed patients with focal epilepsy. Methods The study material was compiled from eight clinical antiseizure medication monotherapy trials conducted at Kuopio Epilepsy Center during 1995‐2016. We analyzed the time from first seizure to diagnosis, the number of seizures before diagnosis, and the response to treatment at five years. Results Of the 176 patients (age range 15‐75 years) in the cohort, 135 (77%) had had more than two seizures before treatment. The majority of these (79 patients, 45%) had had three to ten seizures. Median number of all seizures before diagnosis was 5 (range 2‐2000). Focal aware seizures and focal impaired awareness seizures were more frequent than focal to bilateral tonic‐clonic seizures; median number 45 (range 2‐2000), 11 (range 2‐220), and 3 (range 2‐30), respectively (P < .001). Median delay was 12 months (range 0‐362). Diagnostic delay alone did not correlate with the treatment response at five years. However, an increasing number of seizures before diagnosis indicated a worse seizure outcome (P < .001). Significance This study shows that patients with focal epilepsy experience significant delays in diagnosis even in developed countries, especially with seizure types other than tonic‐clonic seizures. In these cases, a long delay in diagnosis alone might not affect the long‐term outcome. However, when accompanied with recurrent seizures misinterpreted by the patient or healthcare providers, the effect of such delay on prognosis can be considerable.

Background The aim was to determine predictors of hospital and 1-year mortality in patients with intensive care unit (ICU)-treated refractory status epilepticus (RSE) in a population-based study. Methods This was a retrospective study of the Finnish Intensive Care Consortium (FICC) database of adult patients (16 years of age or older) with ICU-treated RSE in Finland during a 3-year period (2010–2012). The database consists of admissions to all 20 Finnish hospitals treating RSE in the ICU. All five university hospitals and 11 out of 15 central hospitals participated in the present study. The total adult referral population in the study hospitals was 3.92 million, representing 91% of the adult population of Finland. Patients whose condition had a post-anoxic aetiological basis were excluded. Results We identified 395 patients with ICU-treated RSE, corresponding to an annual incidence of 3.4/100,000 (95% confidence interval (CI) 3.04–3.71). Hospital mortality was 7.4% (95% CI 0–16.9%), and 1-year mortality was 25.4% (95% CI 21.2–29.8%). Mortality at hospital discharge was associated with severity of organ dysfunction. Mortality at 1 year was associated with older age (adjusted odds ratio (aOR) 1.033, 95% CI 1.104–1.051, p  = 0.001), sequential organ failure assessment (SOFA) score (aOR 1.156, CI 1.051–1.271, p  = 0.003), super-refractory status epilepticus (SRSE) (aOR 2.215, 95% CI 1.20–3.84, p  = 0.010) and dependence in activities of daily living (ADL) (aOR 2.553, 95% CI 1.537–4.243, p  < 0.0001). Conclusions Despite low hospital mortality, 25% of ICU-treated RSE patients die within a year. Super-refractoriness, dependence in ADL functions, severity of organ dysfunction at ICU admission and older age predict long-term mortality. Trial registration Retrospective registry study; no interventions on human participants.

Progressive myoclonus epilepsy type 1 (EPM1) is an autosomal recessively inherited childhood–adolescence onset neurodegenerative disease caused by mutations in the cystatin B ( CSTB gene). The key clinical manifestation in EPM1 is progressive, stimulus-sensitive, in particular action-induced myoclonus. The cystatin B-deficient mouse model, Cstb −/− , has been described to present with myoclonic seizures and progressive ataxia. Here we describe results from in-depth behavioral phenotyping of the Cstb −/− mouse model in pure isogenic 129S2/SvHsd background covering ages from 1.5 to 6 months. We developed a method for software-assisted detection of myoclonus from video recordings of the Cstb −/− mice. Additionally, we observed that the mice were hyperactive and showed reduced startle response, problems in motor coordination and lack of inhibition. We were, however, not able to demonstrate an ataxic phenotype in them. This detailed behavioral phenotyping of the Cstb −/− mice reveals new aspects of this mouse model. The nature of the motor problems in the Cstb −/− mice seems to be more complex and more resembling the human phenotype than initially described.

Efficacious and safe monotherapy options are needed for adult patients with newly diagnosed epilepsy. As an adjunctive treatment for partial seizures, pregabalin compares favourably with lamotrigine and is an effective, approved treatment. We studied the efficacy and safety of pregabalin as monotherapy, using a design that complied with European regulatory requirements and International League Against Epilepsy guidelines. This phase 3, double-blind, randomised, non-inferiority study compared the efficacy and tolerability of pregabalin and lamotrigine monotherapy in patients with newly diagnosed partial seizures at 105 centres, mostly in Europe and Asia. Randomisation to treatment groups (1:1 ratio) was by a computer-generated pseudorandom code (random permuted blocks), with patients sequentially assigned numbers by telephone. Investigators, site staff, and patients were masked to the assigned treatment. After randomisation, patients were titrated to either 75 mg oral pregabalin or 50 mg oral lamotrigine twice daily during a 4-week dose-escalation phase, followed by a 52-week efficacy assessment phase during which the daily dose could be increased as needed to a maximum of 600 mg and 500 mg, respectively. The primary efficacy endpoint was the proportion of patients who remained seizure-free for 6 or more continuous months during the efficacy assessment phase; analysis included all patients who were randomly assigned to treatment groups and received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT00280059. 660 patients were randomly assigned to treatment groups (330 pregabalin, 330 lamotrigine), of whom 622 entered the efficacy assessment phase (314 pregabalin, 308 lamotrigine). Fewer patients in the pregabalin group than in the lamotrigine group became seizure-free for 6 or more continuous months (162 [52%] vs 209 [68%]; difference in proportion, −0·16, 95% CI −0·24 to −0·09). The overall incidence of adverse events was similar between the groups and consistent with that in previous studies; dizziness (55 [17%] vs 45 [14%] patients), somnolence (29 [9%] vs 14 [4%]), fatigue (27 [8%] vs 19 [6%]), and weight increase (21 [6%] vs 7 [2%]) were numerically more common in the pregabalin group than in the lamotrigine group. Pregabalin has similar tolerability but seems to have inferior efficacy to lamotrigine for the treatment of newly diagnosed partial seizures in adults. Inferior efficacy of pregabalin might have been attributable to limitations in the study design, as treatment doses might have not been optimised adequately or early enough. Pfizer Inc.

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 .

Background The outcome of status epilepticus (SE) can be improved by facilitating early recognition and treatment with antiepileptic drugs. The purpose of this study was to analyze the treatment delay of SE in a prospectively recruited patient cohort. Improvements to the treatment process are suggested. Methods Consecutive adult patients with SE were recruited in the emergency department of Kuopio University Hospital (KUH) between March 23 and December 31, 2015. SE was defined as a prolonged (> 5 min) epileptic seizure or recurrent tonic-clonic seizures (≥ 3 seizures within any 24 h). Diagnostic and treatment delays and the features of SE were subject to statistical analysis. Results We recorded 151 cases of SE during the study period. First-line treatment was initiated outside of hospital in 79 cases (52.3%), with a significantly shorter median delay compared to intrahospital initiation (28 min vs. 2 h 5 min, p  < 0.001). Forty-six episodes of SE (30.5%) were not recognized during the prehospital phase. The median delay in recognition of tonic-clonic SE (23 min) was significantly shorter than in focal aware (2 h 0 min, p  = 0.045) or focal impaired awareness SE (2 h 25 min, p  < 0.001). Second-line treatment was used in 91 cases (60.3%), with a median delay of 2 h 42 min. Anesthesia was used in seven cases (4.6%) with refractory SE, with a median delay of 6 h 40 min. Conclusions SE is often not recognized during the prehospital phase of treatment, which delays the initiation of first-line treatment. Intrahospital delay could be reduced by streamlining patient transition between the three lines of treatment.