Early sleep apnea treatment in stroke (eSATIS) - a multicentre, randomised controlled, rater-blinded, clinical trial: The association of post-stroke cognition with sleep-disordered breathing and its treatment.

Sleep-disordered breathing (SDB) is linked to cognitive dysfunction. Although SDB is common in stroke patients, the impact of SDB and its early treatment on cognitive functioning after stroke remains poorly investigated. Therefore, we explored the association between SDB and post-stroke cognitive functioning, including the impact of early SDB treatment with adaptive servo-ventilation (ASV) on cognitive recovery from acute event to 3 months post-stroke. We used data from two studies, which included ischaemic stroke patients (n = 131) and no-stroke controls (n = 37) without SDB (apnea-hypopnea index, AHI <5/h) and with SDB (AHI≥20/h). Cognitive functioning was assessed within 7 days and 3 months post-stroke in stroke patients, or at study inclusion in no-stroke control group, respectively. Stroke patients with SDB were randomized to ASV treatment (ASV+) or usual care (ASV-). Linear regression adjusted for main confounders assessed the impact of SDB and its treatment on cognitive recovery. The intention-to-treat analysis did not show significant associations of SDB ASV+ (n = 30) versus SDB ASV- (n = 29) with cognitive recovery. In an exploratory subanalysis, compliant SDB ASV+ (n = 14) versus SDB ASV- showed improvements with ASV in visual memory and cognitive flexibility. Combining the stroke and non-stroke datasets, SDB (n = 85) versus no-SDB (n = 83) was associated with deficits in visual memory and response inhibition independently of stroke. SDB ASV- versus no-SDB (n = 51) was associated with less improvement in visual memory. There was no substantial evidence for benefits of intention-to-treat ASV on cognitive recovery. Exploratory analysis indicated that compliant ASV treatment could benefit visual memory and cognitive flexibility, whereas untreated SDB could contribute to a poor recovery of visual memory.

The history of the European Neurological Society (1986-2014)-10 years later.

BACKGROUND AND PURPOSE: The European Academy of Neurology (EAN) was a merger from two parent societies: the European Neurological Association (ENS, founded in 1986) and the European Federation of Neurological Societies (EFNS, founded in 1987). METHODS: This article was written by nine former presidents, three of whom were also founders of the ENS, and is based on recollections and documents. It follows up on a review of the ENS history stored in the EAN archive. RESULTS: The first European society (ENS) was founded by eight individual European academic clinician-neuroscientists aiming at joining with other qualified European neuroscientists on an individual membership basis. After 1990 members were also invited from behind the former Iron Curtain. A principal goal was holding neurology meetings (700 participants in 1988 and over 3000 in 2010), promoting collaborative research projects with exchange of junior neuroscientists, and providing teaching and education independent from nationality. Health politics were not part of the agenda. The executive boards (4-year term) were staffed with academic scientists from all subspecialties of neurology. Numerous bursaries and fellowships were established for junior neurologists. The impact of ENS members on research activities of young investigators was appreciated by academia at large. After years of negotiations ENS and EFNS joint efforts resulted in forming the EAN covering all fields of neurology and neuroscience under one roof. CONCLUSION: The basic principles of the ENS were successfully integrated into the new EAN in particular documented by the number of individual members rising to over 4000 in 2024.

Sleep Capital: Linking Brain Health to Wellbeing and Economic Productivity Across the Lifespan.

INTRODUCTION AND FRAMEWORK: Sleep capital contributes to individual and societal wellbeing, productivity, and economic outcomes and involves a novel aspect of brain capital. It encompasses the quality and quantity of sleep as integral components that influence cognitive abilities, mental and brain health, and physical health, affecting workplace productivity, learning, decision-making, and overall economic performance. Here, we bring a framework to understand the complex relationship between sleep quality, health, wellbeing, and economic productivity. Then we outline the multilevel impact of sleep on cognitive abilities, mental/brain health, and economic indicators, providing evidence for the substantial returns on investment in sleep health initiatives. Moreover, sleep capital is a key factor when considering brain health across the lifespan, especially for the aging population. DISCUSSION: We propose specific elements and main variables to develop specific indexes of sleep capital to address its impacts on health, wellbeing and productivity. CONCLUSION: Finally, we suggest policy recommendations, workplace interventions, and individual strategies to promote sleep health and brain capital. Investing in sleep capital is essential for fostering a healthier, happier, fairer and more productive society.

Dose-response of daridorexant in insomnia disorder: An analysis of Phase 2 and 3 studies.

OBJECTIVE: Daridorexant is approved for the treatment of insomnia at two dose levels (25 and 50 mg). Dose-efficacy and -safety response relationships were evaluated using Phase 2 and 3 data. METHODS: Data (N = 2153) from one Phase 2 (daridorexant 5, 10, 25, 50 mg, placebo once daily for 1 month) and two Phase 3 studies (daridorexant 10 and 25 or 25 and 50 mg, placebo once daily for 3 months) were pooled. Dose-response analyses at 1 month of double-blind treatment were performed using a linear regression and a two-stage meta-analysis approach. Efficacy endpoints were polysomnography-derived wake after sleep onset, latency to persistent sleep (LPS), self-reported total sleep time and the Insomnia Daytime Symptoms and Impacts Questionnaire total score (only Phase 3 data for the latter). Safety endpoints were the incidence of total adverse events (AEs) and AEs corresponding to somnolence/fatigue. RESULTS: Dose-responses for all efficacy endpoints were significant in the observed dose range (both statistical approaches, p < 0.01). All dose-response relationships were linear except for LPS (two-stage meta-analysis) which showed a change in slope above 10 mg without reaching a plateau. No significant dose-response was observed for any AE (both approaches, p > 0.05). The incidence of AEs corresponding to somnolence/fatigue was low at all doses and, without linear assumption (two-stage meta-analysis) there was no dose-dependency (p = 0.369). CONCLUSIONS: The data support the use of 50 mg as the preferred daridorexant dose in patients with insomnia disorder to provide the greatest opportunity for efficacy with no increased risk for AEs, including somnolence/fatigue, compared to lower doses.

Bridging AI and Clinical Practice: Integrating Automated Sleep Scoring Algorithm with Uncertainty-Guided Physician Review.

Purpose: This study aims to enhance the clinical use of automated sleep-scoring algorithms by incorporating an uncertainty estimation approach to efficiently assist clinicians in the manual review of predicted hypnograms, a necessity due to the notable inter-scorer variability inherent in polysomnography (PSG) databases. Our efforts target the extent of review required to achieve predefined agreement levels, examining both in-domain (ID) and out-of-domain (OOD) data, and considering subjects' diagnoses. Patients and Methods: A total of 19,578 PSGs from 13 open-access databases were used to train U-Sleep, a state-of-the-art sleep-scoring algorithm. We leveraged a comprehensive clinical database of an additional 8832 PSGs, covering a full spectrum of ages (0-91 years) and sleep-disorders, to refine the U-Sleep, and to evaluate different uncertainty-quantification approaches, including our novel confidence network. The ID data consisted of PSGs scored by over 50 physicians, and the two OOD sets comprised recordings each scored by a unique senior physician. Results: U-Sleep demonstrated robust performance, with Cohen's kappa (K) at 76.2% on ID and 73.8-78.8% on OOD data. The confidence network excelled at identifying uncertain predictions, achieving AUROC scores of 85.7% on ID and 82.5-85.6% on OOD data. Independently of sleep-disorder status, statistical evaluations revealed significant differences in confidence scores between aligning vs discording predictions, and significant correlations of confidence scores with classification performance metrics. To achieve κ ≥ 90% with physician intervention, examining less than 29.0% of uncertain epochs was required, substantially reducing physicians' workload, and facilitating near-perfect agreement. Conclusion: Inter-scorer variability limits the accuracy of the scoring algorithms to ~80%. By integrating an uncertainty estimation with U-Sleep, we enhance the review of predicted hypnograms, to align with the scoring taste of a responsible physician. Validated across ID and OOD data and various sleep-disorders, our approach offers a strategy to boost automated scoring tools' usability in clinical settings.

Baseline characteristics, reperfusion treatment secondary prevention and outcome after acute ischemic stroke in three different socioeconomic environments in Europe.

INTRODUCTION: The differences in vascular risk factors' and stroke burden across Europe are notable, however there is limited understanding of the influence of socioeconomic environment on the quality of secondary prevention and outcome after acute ischemic stroke. PATIENTS AND METHODS: In this observational multicenter cohort study, we analyzed baseline characteristics, reperfusion treatment, outcome and secondary prevention in patients with acute ischemic stroke from three tertiary-care teaching hospitals with similar service population size in different socioeconomic environments: Bern/CH/n = 293 (high-income), Gdansk/PL/n = 140 (high-income), and Lutsk/UA/n = 188 (lower-middle-income). RESULTS: We analyzed 621 patients (43.2% women, median age = 71.4 years), admitted between 07 and 12/2019. Significant differences were observed in median BMI (CH = 26/PL = 27.7/UA = 27.8), stroke severity [(median NIHSS CH = 4(0-40)/PL = 11(0-33)/UA = 7(1-30)], initial neuroimaging (CT:CH = 21.6%/PL = 50.7%/UA = 71.3%), conservative treatment (CH = 34.1%/PL = 38.6%/UA = 95.2%) (each p < 0.001), in arterial hypertension (CH = 63.8%/PL = 72.6%/UA = 87.2%), atrial fibrillation (CH = 28.3%/PL = 41.4%/UA = 39.4%), hyperlipidemia (CH = 84.9%/PL = 76.4%/UA = 17%) (each p < 0.001) and active smoking (CH = 32.2%/PL = 27.3%/UA = 10.2%) (p < 0.007). Three-months favorable outcome (mRS = 0-2) was seen in CH = 63.1%/PL = 50%/UA = 59% (unadjusted-p = 0.01/adjusted-p CH-PL/CH-UA = 0.601/0.981), excellent outcome (mRS = 0-1) in CH = 48.5%/PL = 32.1%/UA = 27% (unadjusted-p < 0.001/adjusted-p CH-PL/CH-UA = 0.201/0.08 and adjusted-OR CH-UA = 2.09). Three-months mortality was similar between groups (CH = 17.2%/PL = 15.7%/UA = 4.8%) (unadjusted-p = 0.71/adjusted-p CH-PL/CH-UA = 0.087/0.24). Three-months recurrent stroke/TIA occurred in CH = 3.1%/PL = 10.7%/UA = 3.1%, adjusted-p/OR CH-PL = 0.04/0.32). Three-months follow-up medication intake rates were the same for antihypertensives. Statin/OAC intake was lowest in UA = 67.1%/25.5% (CH = 87.3%/39.2%/unadjusted-p < 0.001/adjusted-p CH-UA = 0.02/0.012/adjusted-OR CH-UA = 2.33/2.18). Oral intake of antidiabetics was lowest in CH = 10.8% (PL = 15.7%/UA = 16.1%/unadjusted-p = 0.245/adjusted-p CH-PL/CH-UA = 0.061/0.002/adjusted-OR CH-UA = 0.25). Smoking rates decreased in all groups during follow-up. DISCUSSION AND CONCLUSION: Substantial differences in presentation, treatment and secondary prevention measures, are linked to a twofold difference in adjusted 3-months excellent outcome between Switzerland and Ukraine. This underscores the importance of socioeconomic factors that influence stroke outcomes, emphasizing the necessity for targeted interventions to address disparities in treatment and secondary prevention strategies.

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

The European Academy of Neurology NeuroCOVID-19 Task Force: A lesson for the future.

BACKGROUND: The COVID-19 pandemic has made its mark on world history forever causing millions of deaths, and straining health systems, economies, and societies worldwide. The European Academy of Neurology (EAN) reacted promptly. A special NeuroCOVID-19 Task Force was set up at the beginning of the pandemic to promote knowledge, research, international collaborations, and raise awareness about the prevention and treatment of COVID-19-related neurological issues. METHODS: Activities carried out during and after the pandemic by the EAN NeuroCOVID-19 Task Force are described. The main aim was to review all these initiatives in detail as an overarching lesson from the past to improve the present and be better prepared in case of future pandemics. RESULTS: During the pandemic, the Task Force was engaged in several initiatives: the creation of the EAN NEuro-covid ReGistrY (ENERGY); the launch of several surveys (neurological manifestations of COVID-19 infection; the pandemic's impact on patients with chronic neurological diseases; the pandemic's impact of restrictions for clinical practice, curricular training, and health economics); the publication of position papers regarding the management of patients with neurological diseases during the pandemic, and vaccination hesitancy among people with chronic neurological disorders; and the creation of a dedicated "COVID-19 Breaking News" section in EANpages. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force was immediately engaged in various activities to participate in the fight against COVID-19. The Task Force's concerted strategy may serve as a foundation for upcoming global neurological emergencies.

Outcome predictors of post-COVID conditions in the European Academy of Neurology COVID-19 registry.

Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5 months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations.

General neurology: Current challenges and future implications.

BACKGROUND AND PURPOSE: In the coming decades, the world will face an increasing burden of neurological disorders (ND) and an urgent need to promote brain health. These challenges contrast with an insufficient neurological workforce in most countries, as well as decreasing numbers of general neurologists and neurologists attracted to work in general neurology (GN). This white paper aims to review the current situation of GN and reflect on its future. METHODS: The European Academy of Neurology (EAN) task force (TF) met nine times between November 2021 and June 2023. During the 2023 EAN annual meeting, attendees were asked to answer five questions concerning the future of GN. The document was sent for suggestions and eventually approval to the board and the presidents of the 47 national societies of the EAN. RESULTS: The TF first identified four relevant current and future challenges related to GN: (i) definition, (ii) practice, (iii) education, and (iv) research. The TF then identified seven initiatives to further develop GN at both the academic and community level. Finally, the TF formulated 16 recommendations to promote GN in the future. CONCLUSIONS: GN will remain essential in the coming decades to provide rapid, accessible, and comprehensive management of patients with ND that is affordable and cost-effective. There is also a need for research, education, and other initiatives aiming to facilitate improved working conditions, recognition, and prestige for those pursuing a career in GN.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study: feasibility of long-term monitoring with Fitbit smartwatches in central disorders of hypersomnolence and extraction of digital biomarkers in narcolepsy.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a multicenter research initiative to identify new biomarkers in central disorders of hypersomnolence (CDH). Whereas narcolepsy type 1 (NT1) is well characterized, other CDH disorders lack precise biomarkers. In SPHYNCS, we utilized Fitbit smartwatches to monitor physical activity, heart rate, and sleep parameters over 1 year. We examined the feasibility of long-term ambulatory monitoring using the wearable device. We then explored digital biomarkers differentiating patients with NT1 from healthy controls (HC). A total of 115 participants received a Fitbit smartwatch. Using a adherence metric to evaluate the usability of the wearable device, we found an overall adherence rate of 80% over 1 year. We calculated daily physical activity, heart rate, and sleep parameters from 2 weeks of greatest adherence to compare NT1 (n = 20) and HC (n = 9) participants. Compared to controls, NT1 patients demonstrated findings consistent with increased sleep fragmentation, including significantly greater wake-after-sleep onset (p = .007) and awakening index (p = .025), as well as standard deviation of time in bed (p = .044). Moreover, NT1 patients exhibited a significantly shorter REM latency (p = .019), and sleep latency (p = .001), as well as a lower peak heart rate (p = .008), heart rate standard deviation (p = .039) and high-intensity activity (p = .009) compared to HC. This ongoing study demonstrates the feasibility of long-term monitoring with wearable technology in patients with CDH and potentially identifies a digital biomarker profile for NT1. While further validation is needed in larger datasets, these data suggest that long-term wearable technology may play a future role in diagnosing and managing narcolepsy.

Swiss trial of decompressive craniectomy versus best medical treatment of spontaneous supratentorial intracerebral haemorrhage (SWITCH): an international, multicentre, randomised-controlled, two-arm, assessor-blinded trial.

RATIONALE: Decompressive craniectomy (DC) is beneficial in people with malignant middle cerebral artery infarction. Whether DC improves outcome in spontaneous intracerebral haemorrhage (ICH) is unknown. AIM: To determine whether DC without haematoma evacuation plus best medical treatment (BMT) in people with ICH decreases the risk of death or dependence at 6 months compared to BMT alone. METHODS AND DESIGN: SWITCH is an international, multicentre, randomised (1:1), two-arm, open-label, assessor-blinded trial. Key inclusion criteria are age ⩽75 years, stroke due to basal ganglia or thalamic ICH that may extend into cerebral lobes, ventricles or subarachnoid space, Glasgow coma scale of 8-13, NIHSS score of 10-30 and ICH volume of 30-100 mL. Randomisation must be performed <66 h after onset and DC <6 h after randomisation. Both groups will receive BMT. Participants randomised to the treatment group will receive DC of at least 12 cm in diameter according to institutional standards. SAMPLE SIZE: A sample of 300 participants randomised 1:1 to DC plus BMT versus BMT alone provides over 85% power at a two-sided alpha-level of 0.05 to detect a relative risk reduction of 33% using a chi-squared test. OUTCOMES: The primary outcome is the composite of death or dependence, defined as modified Rankin scale score 5-6 at 6 months. Secondary outcomes include death, functional status, quality of life and complications at 180 days and 12 months. DISCUSSION: SWITCH will inform physicians about the outcomes of DC plus BMT in people with spontaneous deep ICH, compared to BMT alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02258919.

Magnetic resonance imaging in acute meningoencephalitis of viral and unknown origin: frequent findings and prognostic potential.

Background: Magnetic resonance imaging (MRI) findings in meningoencephalitis have mainly been described in terms of their diagnostic value rather than their prognostic potential, except for herpes simplex virus (HSV) encephalitis. The aims of our study were to describe frequency and anatomic locations of MRI abnormalities specific to limbic, circadian and motor systems in a cohort of meningoencephalitis patients, as well as to investigate the prognostic value of these MRI findings. Methods: A secondary, selective analysis of a retrospective database including all meningitis, meningoencephalitis and encephalitis cases treated between 2016 and 2018 in the University hospital of Bern, Switzerland was performed. Patients with meningitis of any cause, bacterial or autoimmune causes of encephalitis were excluded. Results: MRI scans and clinical data from 129 meningoencephalitis cases found that the most frequent causes were tick-borne encephalitis (TBE, 42%), unknown pathogens (40%), VZV (7%), and HSV1 (5%). At discharge, median modified Rankin Score (mRS) was 3 (interquartile range, IQR, 1), 88% of patients had persisting signs and symptoms. After a median of 17 months, median Glasgow Outcome Score (GOS) was 5 (IQR 1), 39% of patients still had residual signs or symptoms. All patients with HSV, 27% with TBE and 31% of those with meningoencephalitis of unknown etiology had fluid-attenuated inversion recovery (FLAIR) and to a lesser extent diffusion-weighted imaging (DWI) lesions in their initial MRI, with highly overlapping anatomical distribution. In one fifth of TBE patients the limbic system was affected. Worse outcome was associated with presence of DWI and/or FLAIR lesions and lower normalized apparent diffusion coefficient (ADC) signal intensities. Conclusion: Presence of FLAIR lesions, restricted diffusion as well as the extent of ADC hypointensity in initial MRI are parameters which might be of prognostic value regarding the longterm clinical outcome for patients with meningoencephalitis of viral and of unknown origin. Although not described before, affection of limbic structures by TBE is possible as shown by our results: A substantial proportion of our TBE patients had FLAIR signal abnormalities in these regions.

Trajectories of self-reported daytime sleepiness post-ischemic stroke and transient ischemic attack: A propensity score matching study versus non-stroke patients.

INTRODUCTION: Severe sleep apnea (SA) affects one-third of stroke patients. Sleepiness, one of the cardinal symptoms of SA, negatively impacts functional stroke outcomes. The impact of continuous positive airway pressure (CPAP) on post-stroke sleepiness is poorly described. We aimed to compare through a propensity score matching the trajectories of self-reported sleepiness post-stroke with matched individuals including SA patients adherent or not to CPAP. PATIENTS AND METHODS: Sixty five (80.2%) ischemic stroke and 16 (19.8%) TIA patients (median [Q1;Q3] age = 67.0 [58.0;74.0] years, 70.4% male, body mass index [BMI] = 26.1 [24.5;29.8] kg·m-2, admission NIHSS = 3.0 [1.0;5.0]), with polysomnography and an Epworth Sleepiness Scale (ESS) performed within 1 year following stroke and with a follow-up ESS (delay = 236 [147;399] days) were included in the analysis. A 2:1 propensity score matching based on age, gender, BMI, and the apnea-hypopnea index was performed to identify 162 matched individuals referred for SA suspicion, free of stroke or TIA. Multivariable negative binomial regression models were performed to identify the determinants of sleepiness trajectories post-stroke. RESULTS: Baseline ESS was comparable between stroke/TIA and matched individuals (median [Q1; Q3] ESS = 7 [4;10] versus 6 [4;10], p = 0.86). The range of improvement in ESS was higher in stroke patients compared to controls (∆ESS = -2 [-4;1] vs -1 [-3;2], p = 0.03). In multivariable analysis, comorbid SA and CPAP treatment did not influence trajectories of sleepiness post-stroke. DISCUSSION AND CONCLUSION: Sleepiness improvement was unexpectedly higher in stroke patients compared to matched individuals, with no significant influence of comorbid SA and CPAP on its trajectory. Sleepiness may not be primarily indicative of SA in stroke or TIA patients.

Vagus nerve stimulation for the treatment of narcolepsy.

BACKGROUND AND OBJECTIVE: No study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy. METHODS: In our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups. RESULTS: Compared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups. CONCLUSION: In this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy.

Impact of Comorbid Sleep-Disordered Breathing and Atrial Fibrillation on the Long-Term Outcome After Ischemic Stroke.

BACKGROUND: Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke. METHODS: In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events. RESULTS: Among 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 [95% CI, 1.18-5.24]) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 [95% CI, 1.12-4.50]). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 [95% CI, 0.62-4.36]). CONCLUSIONS: Comorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739.

Anti-amyloid antibody treatments for Alzheimer's disease.

Our aim is to review the most recent evidence on novel antibody therapies for Alzheimer's disease directed against amyloid-ß. This is a joint statement of the European Association of Neurology and the European Psychiatric Association. After numerous unsuccessful endeavors to create a disease-modifying therapy for Alzheimer's disease, substantial and consistent evidence supporting the clinical effectiveness of monoclonal antibodies aimed at amyloid-ß is finally emerging. The latest trials not only achieved their primary objective of slowing the progression of the disease over several months but also demonstrated positive secondary clinical outcomes and a decrease in amyloid-ß levels as observed through positron emission tomography scans. Taken as a whole, these findings mark a significant breakthrough by substantiating that reducing amyloid-ß yields tangible clinical benefits, beyond mere changes in biomarkers. Concurrently, the regular utilization of the new generation of drugs will determine whether statistical efficacy translates into clinically meaningful improvements. This may well signify the dawning of a new era in the development of drugs for Alzheimer's disease.

A strategic neurological research agenda for Europe: Towards clinically relevant and patient-centred neurological research priorities.

BACKGROUND AND PURPOSE: Neurological disorders constitute a significant portion of the global disease burden, affecting >30% of the world's population. This prevalence poses a substantial threat to global health in the foreseeable future. A lack of awareness regarding this high burden of neurological diseases has led to their underrecognition, underappreciation, and insufficient funding. Establishing a strategic and comprehensive research agenda for brain-related studies is a crucial step towards aligning research objectives among all pertinent stakeholders and fostering greater societal awareness. METHODS: A scoping literature review was undertaken by a working group from the European Academy of Neurology (EAN) to identify any existing research agendas relevant to neurology. Additionally, a specialized survey was conducted among all EAN scientific panels, including neurologists and patients, inquiring about their perspectives on the current research priorities and gaps in neurology. RESULTS: The review revealed the absence of a unified, overarching brain research agenda. Existing research agendas predominantly focus on specialized topics within neurology, resulting in an imbalance in the number of agendas across subspecialties. The survey indicated a prioritization of neurological disorders and research gaps. CONCLUSIONS: Building upon the findings from the review and survey, key components for a strategic and comprehensive neurological research agenda in Europe were delineated. This research agenda serves as a valuable prioritization tool for neuroscientific researchers, as well as for clinicians, donors, and funding agencies in the field of neurology. It offers essential guidance for creating a roadmap for research and clinical advancement, ultimately leading to heightened awareness and reduced burden of neurological disorders.