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.

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.

Disentangling the complex landscape of sleep-wake disorders with data-driven phenotyping: A study of the Bernese center.

BACKGROUND AND PURPOSE: The diagnosis of sleep-wake disorders (SWDs) is challenging because of the existence of only few accurate biomarkers and the frequent coexistence of multiple SWDs and/or other comorbidities. The aim of this study was to assess in a large cohort of well-characterized SWD patients the potential of a data-driven approach for the identification of SWDs. METHODS: We included 6958 patients from the Bernese Sleep Registry and 300 variables/biomarkers including questionnaires, results of polysomnography/vigilance tests, and final clinical diagnoses. A pipeline, based on machine learning, was created to extract and cluster the clinical data. Our analysis was performed on three cohorts: patients with central disorders of hypersomnolence (CDHs), a full cohort of patients with SWDs, and a clean cohort without coexisting SWDs. RESULTS: A first analysis focused on the cohort of patients with CDHs and revealed four patient clusters: two clusters for narcolepsy type 1 (NT1) but not for narcolepsy type 2 or idiopathic hypersomnia. In the full cohort of SWDs, nine clusters were found: four contained patients with obstructive and central sleep apnea syndrome, one with NT1, and four with intermixed SWDs. In the cohort of patients without coexisting SWDs, an additional cluster of patients with chronic insomnia disorder was identified. CONCLUSIONS: This study confirms the existence of clear clusters of NT1 in CDHs, but mainly intermixed groups in the full spectrum of SWDs, with the exception of sleep apnea syndromes and NT1. New biomarkers are needed for better phenotyping and diagnosis of SWDs.

The 2022 European postgraduate (residency) programme in neurology in a historical and international perspective.

BACKGROUND AND PURPOSE: Neurology residency programmes, which were first established at the beginning of the 20th century, have become mandatory all over Europe in the last 40-50 years. The first European Training Requirements in Neurology (ETRN) were published in 2005 and first updated in 2016. This paper reports the most recent revisions of the ETRN. METHODS: Members of the EAN board performed an in depth revision of the ETNR 2016-version, which was reviewed by members of the European Board and Section of Neurology of the UEMS, the Education and Scientific Panels, the Resident and Research Fellow Section and the Board of the EAN, as well as the presidents of the 47 European National Societies. RESULTS: The new (2022) ETRN suggest a 5-year training subdivided in three phases: a first phase (2 years) of general neurology training, a second phase (2 years) of training in neurophysiology/neurological subspecialties and a third phase (1 year) to expand clinical training (e.g., in other neurodisciplines) or for research (path for clinical neuroscientist). The necessary theoretical and clinical competences as well as learning objectives in diagnostic tests have been updated, are newly organized in four levels and include 19 neurological subspecialties. Finally, the new ETRN require, in addition to a programme director, a team of clinician-educators who regularly review the resident's progress. The 2022 update of the ETRN reflects emerging requirements for the practice of neurology and contributes to the international standardization of training necessary for the increasing needs of residents and specialists across Europe.

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.

Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study.

The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.

T cells in patients with narcolepsy target self-antigens of hypocretin neurons.

Narcolepsy is a chronic sleep disorder caused by the loss of neurons that produce hypocretin. The close association with HLA-DQB1*06:02, evidence for immune dysregulation and increased incidence upon influenza vaccination together suggest that this disorder has an autoimmune origin. However, there is little evidence of autoreactive lymphocytes in patients with narcolepsy. Here we used sensitive cellular screens and detected hypocretin-specific CD4+ T cells in all 19 patients that we tested; T cells specific for tribbles homologue 2-another self-antigen of hypocretin neurons-were found in 8 out of 13 patients. Autoreactive CD4+ T cells were polyclonal, targeted multiple epitopes, were restricted primarily by HLA-DR and did not cross-react with influenza antigens. Hypocretin-specific CD8+ T cells were also detected in the blood and cerebrospinal fluid of several patients with narcolepsy. Autoreactive clonotypes were serially detected in the blood of the same-and even of different-patients, but not in healthy control individuals. These findings solidify the autoimmune aetiology of narcolepsy and provide a basis for rapid diagnosis and treatment of this disease.

REM sleep and muscle atonia in brainstem stroke: A quantitative polysomnographic and lesion analysis study.

Important brainstem regions are involved in the regulation of rapid eye movement sleep. We hypothesized that brainstem stroke is associated with dysregulated rapid eye movement sleep and related muscle activity. We compared quantitative/qualitative polysomnography features of rapid eye movement sleep and muscle activity (any, phasic, tonic) between 15 patients with brainstem stroke (N = 46 rapid eye movement periods), 16 patients with lacunar/non-brainstem stroke (N = 40 rapid eye movement periods), 15 healthy controls (N = 62 rapid eye movement periods), and patients with Parkinson's disease and polysomnography-confirmed rapid eye movement sleep behaviour disorder. Further, in the brainstem group, we performed a magnetic resonance imaging-based lesion overlap analysis. The mean ratio of muscle activity to rapid eye movement sleep epoch in the brainstem group ("any" muscle activity 0.09 ± 0.15; phasic muscle activity 0.08 ± 0.14) was significantly lower than in the lacunar group ("any" muscle activity 0.17 ± 0.2, p < 0.05; phasic muscle activity 0.16 ± 0.19, p < 0.05), and also lower than in the control group ("any" muscle activity 0.15 ± 0.17, p < 0.05). Magnetic resonance imaging-based lesion analysis indicated an area of maximum overlap in the medioventral pontine region for patients with reduced phasic muscle activity index. For all groups, mean values of muscle activity were significantly lower than in the patients with Parkinson's disease and polysomnography-confirmed REM sleep behaviour disorder group ("any" activity 0.51 ± 0.26, p < 0.0001 for all groups; phasic muscle activity 0.42 ± 0.21, p < 0.0001 for all groups). For the tonic muscle activity in the mentalis muscle, no significant differences were found between the groups. In the brainstem group, contrary to the lacunar and the control groups, "any" muscle activity index during rapid eye movement sleep was significantly reduced after the third rapid eye movement sleep phase. This study reports on the impact of brainstem stroke on rapid eye movement atonia features in a human cohort. Our findings highlight the important role of the human brainstem, in particular the medioventral pontine regions, in the regulation of phasic muscle activity during rapid eye movement sleep and the ultradian distribution of rapid eye movement-related muscle activity.

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Multiple sleep-wake disturbances after stroke predict an increased risk of cardio-cerebrovascular events or death: A prospective cohort study.

BACKGROUND AND PURPOSE: Contradictory evidence on the impact of single sleep-wake-disturbances (SWD), such as sleep-disorderd breating (SDB) or insomnia, in patients with stroke, on the risk of subsequent cardio- and cerebrovascular events (CCE) and death, exists. Very recent studies in the general population suggest that the presence of multiple SWD increases cardio-cerebrovascular risk. Hence, the aim of this study was to asssess whether a novel score capturing the burden of multiple SWD, a so called "sleep burden index", is predictive for subsequent CCE including death in a prospectively followed cohort of stroke patients. METHODS: Patients with acute ischemic stroke or transient ischemic attack (TIA) were prospectively recruited. Four SWD were analyzed: (i) SDB with respirography; (ii) insomnia (defined using the insomnia severity index [ISI]); (iii) restless legs syndrome (RLS; defined using the International RLS Study Group rating scale); and (iv) self-estimated sleep duration at 1 and 3 months. A "sleep burden index", calculated using the mean of z-transformed values from assessments of these four SWD, was created. The occurrence of CCE was recorded over a mean ± standard deviation (SD) follow-up of 3.2 ± 0.3 years. RESULTS: We assessed 437 patients (87% ischemic stroke, 13% TIA, 64% males) with a mean ± SD age of 65.1 ± 13.0 years. SDB (respiratory event index ≥ 5/h) was present in 66.2% of these patients. Insomnia (ISI ≥ 10), RLS and extreme sleep duration affected 26.2%, 6.4% and 13.7% of the patients 3 months post-stroke. Seventy out of the 437 patients (16%) had at least one CCE during the follow-up. The sleep burden index was associated with a higher risk for subsequent CCE, including death (odds ratio 1.80 per index unit, 95% confidence interval 1.19-2.72; p = 0.0056). CONCLUSION: The presence of multiple SWDs constitutes a risk for subsequent CCE (including death) within the first 3 years following stroke. Larger systematic studies should assess the utility of the sleep burden index for patients' risk stratification in clinical practice.

Decreasing incidence of stroke, ischaemic heart disease and dementia in Norway, 1990-2019, a Global Burden of Disease study: an opportunity.

BACKGROUND AND PURPOSE: The declining incidence of stroke, ischaemic heart disease (IHD) and dementia (the 'triple threat') in Norway encourages further investigation. The risks and trends of the three conditions were analysed using data from the Global Burden of Disease study. METHODS: Global Burden of Disease 2019 estimations were used for age-, sex- and risk-factor-specific incidence and prevalence of the 'triple threat', their risk-factor-attributed deaths and disability combined, their age-standardized rates per 100,000 population in 2019 and their changes during 1990-2019. Data are presented as means and 95% uncertainty intervals. RESULTS: In 2019, 71.1 thousand Norwegians were living with dementia, 157.2 thousand with IHD and 95.2 thousand with stroke. In 2019, there were 9.9 thousand (8.5 to 11.3) new cases of dementia (35.0% increase since 1990), 17.0 thousand (14.6 to 19.6) with IHD (3.6% decrease) and 8.0 thousand (7.0 to 9.1) with stroke (12.9% decrease) in Norway. During 1990-2019, their age-standardized incidence rates decreased significantly-dementia by -5.4% (-8.4% to -3.2%), IHD by -30.0% (-31.4% to -28.6%) and stroke by -35.3% (-38.3% to -32.2%). There were significant declines in the attributable risks to both environmental and behavioural factors in Norway, but contradictory trends for metabolic risk factors during 1990-2019. CONCLUSIONS: The risk of the 'triple threat' conditions is declining in Norway, despite the increased prevalence. This offers the opportunity to find out why and how and to accelerate their joint prevention through new approaches and the promotion of the National Brain Health Strategy.

Connecting Women in Neurosciences: A networking project to sustain mutual empowerment in young, female clinical neuroscientists.

Simultaneously acquiring broad clinical knowledge and scientific expertise is a major challenge for young clinical scientists. Female researchers may face additional hurdles in their career, for example, due to unconscious bias. We aimed to address clinical, research, and gender-related challenges among young female clinical neuroscientists. We implemented a peer-led networking group dedicated to increasing clinical and scientific knowledge, improve soft skills, and encourage exchange between fellow residents. In monthly meetings, two participants hold short presentations on a clinical topic or scientific method, followed by a discussion and feedback to the presenter. Afterwards, participants network and discuss challenges they face in their daily experience. Nine neurology residents at a Swiss University Hospital with ≤3 years of training participated in the Connecting Women in Neurosciences project from August 2020 to June 2021. In a qualitative evaluation, participants reported they felt empowered by these meetings and profited from their new network. We identified several challenges in combining clinical and research activities, some of which participants perceived to be gender-related. In addition to women-only meetings, we will promote events addressing all interested researchers. Peer-to-peer networking is an easy and low-budget intervention to encourage female residents to engage in research activities, profit from each other's expertise, and promote interdisciplinary teamwork. It can provide a protected environment to discuss and overcome in particular gender-related challenges. We encourage young colleagues to regularly engage in structured networking activities with their local peers.

Prioritization process for European Academy of Neurology clinical practice guidelines.

BACKGROUND AND PURPOSE: The development of high-quality clinical practice guidelines (CPGs) takes substantial time, effort, and resources. During the past years, the European Academy of Neurology (EAN) guideline production was significantly increased, so the need to develop clear, transparent, and methodologically solid criteria for prioritizing guideline topics became apparent. With this paper, we aim to define a set of criteria to be applied for prioritizing topics for future EAN guidelines, as well as the procedure for their implementation. METHODS: After review of the literature, we identified a recent systematic review that reported on the main prioritization criteria used by health organizations. Based on these, we developed a list of 20 preliminary criteria, which were voted on through a Delphi consensus procedure, including 160 stakeholders. Finally, we established a working procedure on how to submit and select new guideline topic proposals within the EAN. This procedure was reviewed by the EAN Scientific Committee and the Board. RESULTS: The first round, 61.3% of the participants voted, and 86% of them participated in the second round. Seven criteria were approved with this procedure. After the selection of the criteria, a prioritization procedure was launched, and the first 30 topics are reported in this paper. This bottom-up process that involved the whole EAN community was followed by a top-down process, using additional criteria for further selection by the EAN board members. CONCLUSIONS: We describe the development of prioritization criteria to be applied in the process of topic selection for future EAN CPGs. We will perform regular reviews and adjustments of the process.

Comparative features and outcomes of major neurological complications of COVID-19.

BACKGROUND AND PURPOSE: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations. METHODS: The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors. RESULTS: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N = 449, 29.5%), stroke (N = 392, 25.7%), sleep-wake disturbances (N = 250, 16.4%), dysautonomia (N = 224, 14.7%), peripheral neuropathy (N = 145, 9.5%), movement disorders (N = 142, 9.3%), ataxia (N = 134, 8.8%), and seizures (N = 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome. CONCLUSIONS: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19.

Evolution of Neuropsychological Deficits in First-Ever Isolated Ischemic Thalamic Stroke and Their Association With Stroke Topography: A Case-Control Study.

BACKGROUND: The thalamus plays an essential role in cognition. Cognitive deficits have to date mostly been studied retrospectively in chronic thalamic stroke in small cohorts. Studies prospectively evaluating the evolution of cognitive deficits and their association with thalamic stroke topography are lacking. This knowledge is relevant for targeted patient diagnostics and rehabilitation. METHODS: Thirty-seven patients (57.5±17.5 [mean±SD] years, 57% men) with first-ever acute isolated ischemic stroke covering the anterior (n=5), paramedian (n=12), or inferolateral (n=20) thalamus and 37 in-patient controls without stroke with similar vascular risk factors matched for age and sex were prospectively studied. Cognition was evaluated using predefined tests at 1, 6, 12, and 24 months. Voxel-based lesion-symptom mapping was used to determine associations between neuropsychological deficits and stroke topography. RESULTS: Patients with anterior thalamic stroke revealed severe deficits in verbal memory (median T score [Q1-Q3]: 39.1 [36.1-44.1]), language (31.8 [31.0-43.8]), and executive functions (43.8 [35.5-48.1]) at 1 month compared with controls (verbal memory: 48.5 [43.6-61.0], language: 55.7 [42.3-61.1], executive functions: 51.3 [50.1-56.8]). Patients with paramedian thalamic stroke showed moderate language (44.7 [42.8-55.9]) and executive (49.5 [44.3-55.1]) deficits and no verbal memory deficits (48.1 [42.5-54.7]) at 1 month compared with controls (59.0 [47.0-64.5]; 59.6 [51.1-61.3]; 52.5 [44.2-55.3]). The language and executive deficits in paramedian thalamic stroke patients almost completely recovered during follow-up. Intriguingly, significant deficits in verbal memory (44.7 [41.5-51.9]), language (47.5 [41.8-54.1]), and executive functions (48.2 [46.2-59.7]) were found in inferolateral thalamic stroke patients at 1 month compared with controls (50.5 [46.7-59.9]; 57.0 [51.2-62.9]; 57.4 [51.2-60.7]). Language, but not executive deficits persisted during follow-up. Voxel-based lesion-symptom mapping revealed an association of verbal memory deficits with anterior thalamus lesions and an association of non-verbal memory, language, and executive deficits with lesions at the anterior/paramedian/inferolateral border. CONCLUSIONS: All 3 stroke topographies exhibited significant deficits in diverse cognitive domains, which recovered to a different degree depending on the stroke localization. Our study emphasizes the need for comprehensive neuropsychological diagnostics to secure adequate patient rehabilitation.

Thalamic Influence on Slow Wave Slope Renormalization During Sleep.

OBJECTIVE: Slow waves are thought to mediate an overall reduction in synaptic strength during sleep. The specific contribution of the thalamus to this so-called synaptic renormalization is unknown. Thalamic stroke is associated with daytime sleepiness, along with changes to sleep electroencephalography and cognition, making it a unique "experiment of nature" to assess the relationship between sleep rhythms, synaptic renormalization, and daytime functions. METHODS: Sleep was studied by polysomnography and high-density electroencephalography over 17 nights in patients with thalamic (n = 12) and 15 nights in patients with extrathalamic (n = 11) stroke. Sleep electroencephalographic overnight slow wave slope changes and their relationship with subjective daytime sleepiness, cognition, and other functional tests were assessed. RESULTS: Thalamic and extrathalamic patients did not differ in terms of age, sleep duration, or apnea-hypopnea index. Conversely, overnight slope changes were reduced in a large cluster of electrodes in thalamic compared to extrathalamic stroke patients. This reduction was related to increased daytime sleepiness. No significant differences were found in other functional tests between the 2 groups. INTERPRETATION: In patients with thalamic stroke, a reduction in overnight slow wave slope change and increased daytime sleepiness was found. Sleep- and wake-centered mechanisms for this relationship are discussed. Overall, this study suggests a central role of the thalamus in synaptic renormalization. ANN NEUROL 2021;90:821-833.

European Academy of Neurology 2019 - 2022.

BACKGROUND: The EAN was founded in 2014 with the mission of reducing the burden of neurological disorders. METHODS: In 2019 the society defined four strategic priorities: education, science, membership, and advocacy. This paper reviews the EAN development in the last 3 years. RESULTS: The outbreak of COVID-19 pandemic in 2020 had a profound impact on the entire world and triggered profound changes in the EAN including the implementation of new digital technologies. Education The virtual congress in 2020 was the best attended in history (43,844 registrations). The European Training Requirements for Neurology was revised. A mentorship program and a student section were created. A state-of-the-art eLearning platform will be launched in 2022. Research To assess neurological manifestations of COVID-19 an international registry (ENERGY) was created. Studies on the burden of neurological disorders and sleep disorders, respectively, were started. The first EAN science school took place in 2022. Membership The EAN includes 45,000 members and 47 national societies. New task forces were created on gender and diversity, tele- and general neurology. Advocacy In 2022 the EAN supported the adoption of the Global Action Plan on epilepsy and other neurological disorders by the WHO and the neurological community in the Ukraine. The same year the EAN launched a Brain Health Strategy promoting a non-disease and -age centred, lifelong holistic approach ('one brain, one life, one approach'). CONCLUSION: The ongoing pandemic and wars demonstrate the fragility of our political and health systems and the need for people centeredness, international collaborations, solidarity, and digitalization. The EAN will continue promoting excellence in neurological care, science and education as well as brain health for all.

Physicians' decision-making when managing pediatric patients with prolonged disorders of consciousness: A qualitative study.

BACKGROUND AND PURPOSE: Advances in medicine have resulted in treatments that can extend the survival of patients with prolonged disorders of consciousness (PDOC) for several years. However, several diagnostic and prognostic uncertainties remain, particularly in the care of pediatric patients. In the absence of international guidelines, we aimed to explore physicians' decision-making when managing pediatric patients with PDOC. METHODS: We conducted a qualitative study using semistructured, individual interviews and employed an inductive thematic analytical approach to explore physicians' subjective experiences and decision-making when managing pediatric patients with PDOC. We recruited a purposive sample of 19 Italian-speaking physicians currently or previously employed in intensive care units or pediatric, internal medicine, or neurology departments in Switzerland. RESULTS: Participants stated that making clinical decisions involving pediatric patients with PDOC is extremely challenging, because the decisional process requires finding a balance between several contending factors. We found that physicians experienced ambivalence in three domains of care (time, goals of care, and target of care), and that they were aware of the risk of self-fulfilling prophecies for both prognosis and main clinical outcomes. CONCLUSIONS: Our study confirmed that experienced clinicians acknowledge the complex nature and challenge of clinical decision-making in the care of pediatric patients with PDOC. More research is warranted to improve and expand existing guidelines aimed at assisting and facilitating clinical and ethical decision-making, and improving physicians' awareness of the factors affecting their decisions when dealing with patients with PDOC.

How to approach a neurogenetics diagnosis in different European countries: The European Academy of Neurology Neurogenetics Panel survey.

BACKGROUND AND PURPOSE: Seven thousand rare diseases have been identified; most of them are of genetic origin. The diagnosis of a neurogenetic disease is difficult, and management and training programs are not well defined through Europe. To capture and assess care needs, the Neurogenetics Panel of the European Academy of Neurology (EAN) has performed an explorative survey. METHODS: The survey covering multiple topics of neurogenetics was sent to all neurologists and neuropediatricians affiliated with the EAN practicing in Europe. RESULTS: We collected answers from 239 members based in 40 European member states. Even though most of the responders were aware of neurogenetic diseases, when we came to amenability of carrying out a complete genetic diagnosis, almost one-third of the responders declared they were not happy with the current way of ordering genetic analyses in their countries. Furthermore, although single-gene analysis is diffusely present in Europe, whole exome and genome sequencing are not easily accessible, with considerable variabilities among countries. Almost 10% of the responders did not know if presymptomatic and prenatal diagnosis was available in their countries, and 47.3% were not aware of which newborn screening programs were available. Finally, 96.3% of responders declared that there is a need for education and training in neurogenetics. CONCLUSIONS: We believe that this survey may be of importance for all European stakeholders in neurogenetics in identifying key priorities, targeting areas to encourage education/travel fellowships, and educational seminars in the future, because this area will only accelerate, and diagnostic requirements will expand.

The European Academy of Neurology Brain Health Strategy: One brain, one life, one approach.

BACKGROUND AND PURPOSE: Brain health is essential for health, well-being, productivity and creativity across the entire life. Its definition goes beyond the absence of disease embracing all cognitive, emotional, behavioural and social functions which are necessary to cope with life situations. METHODS: The European Academy of Neurology (EAN) Brain Health Strategy responds to the high and increasing burden of neurological disorders. It aims to develop a non-disease-, non-age-centred holistic and positive approach ('one brain, one life, one approach') to prevent neurological disorders (e.g., Alzheimer's disease and other dementias, stroke, epilepsy, headache/migraine, Parkinson's disease, multiple sclerosis, sleep disorders, brain cancer) but also to preserve brain health and promote recovery after brain damage. RESULTS: The pillars of the EAN Brain Health Strategy are (1) to contribute to a global and international brain health approach (together with national and subspecialty societies, other medical societies, the World Health Organization, the World Federation of Neurology, patients' organizations, industry and other stakeholders); (2) to support the 47 European national neurological societies, healthcare and policymakers in the implementation of integrated and people-centred campaigns; (3) to foster research (e.g., on prevention of neurological disorders, determinants and assessments of brain health); (4) to promote education of students, neurologists, general practitioners, other medical specialists and health professionals, patients, caregivers and the general public; (5) to raise public awareness of neurological disorders and brain health. CONCLUSIONS: By adopting this 'one brain, one life, one approach' strategy in cooperation with partner societies, international organizations and policymakers, a significant number of neurological disorders may be prevented whilst the overall well-being of individuals is enhanced by maintaining brain health through the life course.