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Background and ObjectivesRecent studies fueled doubts as to whether all currently defined central disorders of hypersomnolence are stable entities, especially narcolepsy type 2 and idiopathic hypersomnia. New reliable biomarkers are needed, and the question arises of whether current diagnostic criteria of hypersomnolence disorders should be reassessed. The main aim of this data-driven observational study was to see whether data-driven algorithms would segregate narcolepsy type 1 and identify more reliable subgrouping of individuals without cataplexy with new clinical biomarkers.MethodsWe used agglomerative hierarchical clustering, an unsupervised machine learning algorithm, to identify distinct hypersomnolence clusters in the large-scale European Narcolepsy Network database. We included 97 variables, covering all aspects of central hypersomnolence disorders such as symptoms, demographics, objective and subjective sleep measures, and laboratory biomarkers. We specifically focused on subgrouping of patients without cataplexy. The number of clusters was chosen to be the minimal number for which patients without cataplexy were put in distinct groups.ResultsWe included 1,078 unmedicated adolescents and adults. Seven clusters were identified, of which 4 clusters included predominantly individuals with cataplexy. The 2 most distinct clusters consisted of 158 and 157 patients, were dominated by those without cataplexy, and among other variables, significantly differed in presence of sleep drunkenness, subjective difficulty awakening, and weekend-week sleep length difference. Patients formally diagnosed as having narcolepsy type 2 and idiopathic hypersomnia were evenly mixed in these 2 clusters.DiscussionUsing a data-driven approach in the largest study on central disorders of hypersomnolence to date, our study identified distinct patient subgroups within the central disorders of hypersomnolence population. Our results contest inclusion of sleep-onset REM periods in diagnostic criteria for people without cataplexy and provide promising new variables for reliable diagnostic categories that better resemble different patient phenotypes. Cluster-guided classification will result in a more solid hypersomnolence classification system that is less vulnerable to instability of single features.

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.

Background: REM-sleep behaviour disorder (RBD) is a parasomnia and a common comorbidity in Parkinson’s disease (PD). There is evidence that the presence of RBD is associated with more severe PD. The differences in the clinical manifestations and the natural history are likely to imply underlying differences in the pathophysiology among PD patients with and without RBD. The increasing number of neuroimaging studies support this notion. Objective: Our primary objective was to review the current evidence regarding the brain neuroimaging findings in PD patients with RBD (PDRBD). Methods: A systematic review of articles, published in PubMed between January 1, 2000 and September 23, 2020 was performed. We evaluate previous studies that assessed PD patients with RBD using various brain structural and functional magnetic resonance imaging (MRI) techniques and brain nuclear medicine imaging. Results: Twenty-nine studies, involving a total of 3,347 PD subjects among which 912 subjects with PDRBD, met the selection criteria and were included. The presence of RBD in PD patients is associated with structural and functional alterations in several brain regions, mainly in brainstem, limbic structures, frontotemporal cortex, and basal ganglia, raising the hypothesis of a PDRBD neuroimaging phenotype. Conclusion: The current review provides up-to-date knowledge in this field and summarizes the neurobiological/neuroimaging substrate of RBD in PD.

Neurologic disorders impact the ability of the brain to generate sleep, wake, and circadian functions. - Preexisting or de novo sleep-wake-circadian pathologies are generally underdiagnosed in neurologic patients despite their major impact on onset, evolution, and outcome of neurologic disorders. - Neurologic disorders are frequently accompanied by sleep-wake EEG changes. Extensive brain damage can lead to the absence of measurable differentiation between sleep and wakefulness (status dissociatus). - New technologies will facilitate early detection and (long-term) monitoring of neurologic patients and the optimization of their clinical management., Sleep Medicine Clinics, 16 (4)

BACKGROUND Due to the COVID-19 pandemic, scientific congresses are increasingly being organised as virtual congresses. In May 2020, the European Academy of Neurology (EAN) held a VC, free-of-charge. In the absence of systematic studies on this topic, the aim of this study is to evaluate the attendance and perceived quality of the 2020 EAN virtual congress (VC) compared to the 2019 EAN face-to-face congress (FFC). METHODS Analysis of demographic data of participants obtained from the online registration collected. Comparison of the two congresses based on a survey with questions on the perception of speakers' performance, quality of networking, and other aspects. RESULTS Of 43,596 registered participants, 20,694 active participants attended the VC. Compared to 2019, the number of participants tripled (6916 in 2019) and the cumulated number of participants attending the sessions was five times higher (169,334 in 2020 vs 33,024 in 2019). Out of active participants 55% were from outside Europe, 42% were board-certified neurologists (FFC: 80%), and 21% were students (FFC: 0.6%). The content of the congress was evaluated as 'above expectation' by 56% of the attendees (FFC: 41%). Out of the respondents who had been exposed to earlier EAN congresses 73% preferred the FFC congress compared to the VC (17%). CONCLUSION The VC fulfilled the main mission of organizing high quality EAN congresses despite the restrictions of the impersonal format. The geographical distribution of the participants prove the expected higher inclusivity of a VC. The large participation of students and neurologists in training opens new educational potentials for the EAN.

At present, the standard practices for home-based assessments of abnormal movements in Parkinson's disease (PD) are based either on subjective tools or on objective measures that often fail to capture day-to-day fluctuations and long-term information in real-life conditions in a way that patient's compliance and privacy are secured. The employment of wearable technologies in PD represents a great paradigm shift in healthcare remote diagnostics and therapeutics monitoring. However, their applicability in everyday clinical practice seems to be still limited. We carried out a systematic search across the Medline Database. In total, 246 publications, published until 1 June 2020, were identified. Among them, 26 reports met the inclusion criteria and were included in the present review. We focused more on clinically relevant aspects of wearables' application including feasibility and efficacy of the assessment, the number, type and body position of the wearable devices, type of PD motor symptom, environment and duration of assessments and validation methodology. The aim of this review is to provide a systematic overview of the current knowledge and state-of-the-art of the home-based assessment of motor symptoms and fluctuations in PD patients using wearable technology, highlighting current problems and laying foundations for future works.

Narcolepsy type 1 is a debilitating chronic neurological disorder, whose main symptoms of excessive daytime sleepiness and cataplexy may partially improve with time, but typically do not fully resolve. The irreversible loss of orexin neurons is considered to be the pivotal mechanistic link underlying the development of cataplectic attacks in narcolepsy type 1. Here we describe a case of untreated narcolepsy type 1with low cerebrospinal orexin levels (< 50 pg/mL), where cataplexy fully resolved in the first 5–6 years after disease onset, whereas excessive daytime sleepiness persisted. CITATION: Wasserman D, Bassetti CLA, Rosenzweig I. Narcolepsy with resolution of cataplexy and persisting orexin deficiency. J Clin Sleep Med. 2020;16(8):1383–1386.

Following the first descriptions of narcolepsy with cataplexy by Westphal, Gelineau, and Fischer (1878-1880), Russian authors started to report on "narcolepsy cases" in 1894. It was, however, only in 1925 that Mankovsky reported a (postencephalitic) case, satisfying current diagnostic criteria for the disease. In the following 66 years (the last publication appeared in 1991), Russian authors including Davidenkov, Vein, and Yakhno made interesting contributions on the clinical features, neurophysiological correlates (e.g., sleep states and boundary dyscontrol), pathogenesis (e.g., hypothalamic origin), etiology (e.g., infectious, postvaccinal triggers, focal encephalitis), and treatment (e.g., use of sodium oxybate) of narcolepsy. Until recently, Pavlov's theory of narcolepsy as a "cortical excitatory-inhibitory phenomenon" strongly influenced the Russian view on the disease, contrasting with the current neurobiological insights acknowledged internationally. A Narcolepsy Network, including currently 10 member centers, was recently founded to promote knowledge, awareness, management, and research on this still poorly known disease in Russia.

There is accumulating evidence about sleep-wake rhythm disturbances as potential modifiable risk factors of both incident and recurrent stroke and less favorable outcomes after stroke. To our best knowledge this is the first study designed to investigate clock genes expression profiles in ischemic stroke patients and their relations to other biological and behavioral sleep-wake rhythm biomarkers, sleep structural and clinical stroke features. Altogether, 27 ischemic stroke patients (20 males) with the median age of 56 years and 25 gender and age matched controls were investigated with neurological and objective examination, scales, polysomnography, actigraphy and 24-h blood sampling for melatonin and clock genes profiles. Median melatonin plasma concentrations at four time points at 7, 11 p.m., 3 a.m. and 12 p.m. did not differ significantly between patients and controls, only early morning melatonin concentration at 7 a.m. was significantly lower and cortisol plasma concentration - significantly higher among stroke patients. All four clock genes (ARNTL (BMAL1), NR1D1 (Rev-erbα/β), PER1, and PER3) showed significant time-of-day variation in both patients' and controls' groups, except expression of NR1D1 (Rev-erbα/β) at 7 a.m. and PER1 at 12 p.m. differed significantly. In conclusion, acute ischemic stroke patients tended to preserve most of diurnal variation of sleep-wake rhythm molecular patterns. Nevertheless, early morning time point showing higher cortisol and lower melatonin concentrations and lower NR1D1 (Rev-erbα/β) expression, as well as lower PER1 midday expression reflect specific circadian desynchrony features in different loops of the molecular circadian clock system.

During the COVID-19 pandemic, the risks and potential benefits of immunotherapies for the treatment of autoimmune disorders are still not well defined, and many cohort studies neither took the epidemiological dynamics of COVID-19 nor the potential capacities of the local healthcare systems in their outcome analysis into account. Due to a pronounced heterogeneity in the outcome reports of different participating countries, the large ‘COVID-19 Global Rheumatology Alliance registry’ addressed this issue using a ‘cluster design’ and shed light on factors associated with a more severe COVID-19 course in their study population.1 We here present data of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS),2 a postmarketing, self-reporting, open-access pharmacovigilance platform that contains international data of COVID-19 cases. Sources of FAERS are voluntary reports from healthcare professionals and consumers. We combine this data set with local measurements of the course of the pandemic (from Oxford University’s ‘Our World in Data’3) and the potential resiliency of the respective healthcare systems (from ‘World Bank’; see online supplemental table 1 for full source information). Only patients with the diagnosis of an autoimmune disorder and a single immunotherapy (required group size: n≥100) at the time point of COVID-19 were analysed by multivariable regression analysis (online supplemental figure 1), limiting the generalisability of our data, for example, concerning combination therapy scenarios (online supplemental figure 1).### Supplementary data [annrheumdis-2021-220679supp001.pdf] The mean age of patients in our cohort (n=2103) was 51.3 years (range 3–92 years; SD 14.9), female sex was more prevalent (1372/2103, 65.2%) and the majority of cases was reported in the USA/Canada (1285/2103, 61.1%). Inflammatory joint disease (846/2103, 40.2%), multiple sclerosis (474/2103, 22.5%) and inflammatory skin disease (435/2103, 20.7%) were the most prevalent diagnoses. Anti-tumour necrosis factor α (TNFα) therapies were the most frequently used medications for the …

Study Objectives This retrospective cross-sectional observational study explored the diagnostic value of selected sleep and vigilance tests (SVT) beyond the multiple sleep latency test to differentiate between various central disorders of hypersomnolence (CDH) and fatigue syndromes. Methods Data from patients who underwent the multiple sleep latency test and at least one additional SVT were extracted from the Bern sleep database (1997–2018). One thousand three hundred fifty-two patients with a CDH (106 narcolepsy type 1, 90 narcolepsy type 2, 119 idiopathic hypersomnia, 192 nonorganic hypersomnia, 205 insufficient sleep syndrome), fatigue syndromes (n = 183), and a subgroup of patients with sleep apnea (n = 457) were analyzed. Classification based on SVT parameters was compared with the final clinical diagnosis serving as a reference. Results An overall model predicted the final diagnosis in 49.5% of patients. However, for the pairwise differentiation of two clinically suspected diagnoses, many SVT parameters showed a sensitivity and specificity above 70%. While the overall discrimination power of the multiple sleep latency test was slightly better than the one of the maintenance of wakefulness test, the latter differentiated best between narcolepsy and idiopathic hypersomnia with prolonged sleep need. Disproportionally poor results in reaction tests (e.g. steer clear test), despite comparable or lower sleepiness levels (SLAT, WLAT), were valuable for differentiating nonorganic hypersomnia from idiopathic hypersomnia/sleep insufficiency syndrome. Conclusion This study demonstrates how the combination of a careful clinical assessment and a selection of SVTs can improve the differentiation of CDH, whereas it was not possible to establish an overall prediction model based on SVTs alone.

Background Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. Methods In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0.9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. Findings Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7 .3%, 95% CI -16.6 to 2.1, lower limit of one-sided 95% CI -15.1%, crossing the non-inferiority margin of - 12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy ( risk difference -1.0%, 95% CI -4.8 to 2 .7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [ 91%] of 201 vs 199 [96%] of 207, risk difference -5.1%, 95% CI -10.2 to 0. 0, p=0.047). Interpretation Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

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 extra-thalamic (n = 11) stroke. Sleep electroencephalography overnight slow wave slope changes, and their relationship with subjective daytime sleepiness, cognition, and other functional tests were assessed. RESULTS Thalamic and extra-thalamic 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 extra-thalamic stroke patients. This reduction was related to increased daytime sleepiness. No significant differences were found in other functional tests between the two 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. This article is protected by copyright. All rights reserved.

Coronavirus disease 2019 (COVID‐19), a multi‐organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID‐19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID‐19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long‐term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID‐19 Task Force intends to raise awareness of the potential impact of COVID‐19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.

Abnormal yawning is an underappreciated phenomenon in patients with ischemic stroke. We aimed at identifying frequently affected core regions in the supratentorial brain of stroke patients with abnormal yawning and contributing to the anatomical network concept of yawning control. Ten patients with acute anterior circulation stroke and ≥3 yawns/15 min without obvious cause were analyzed. The NIH stroke scale (NIHSS), Glasgow Coma Scale (GCS), symptom onset, period with abnormal yawning, blood oxygen saturation, glucose, body temperature, blood pressure, heart rate, and modified Rankin scale (mRS) were assessed for all patients. MRI lesion maps were segmented on diffusion-weighted images, spatially normalized, and the extent of overlap between the different stroke patterns was determined. Correlations between the period with abnormal yawning and the apparent diffusion coefficient (ADC) in the overlapping regions, total stroke volume, NIHSS and mRS were performed. Periods in which patients presented with episodes of abnormal yawning lasted on average for 58 h. Average GCS, NIHSS, and mRS scores were 12.6, 11.6, and 3.5, respectively. Clinical parameters were within normal limits. Ischemic brain lesions overlapped in nine out of ten patients: in seven patients in the insula and in seven in the caudate nucleus. The decrease of the ADC within the lesions correlated with the period with abnormal yawing (r = −0.76, Bonferroni-corrected p = 0.02). The stroke lesion intensity of the common overlapping regions in the insula and the caudate nucleus correlates with the period with abnormal yawning. The insula might be the long sought-after brain region for serotonin-mediated yawning. Electronic supplementary material The online version of this article (doi:10.1007/s00429-013-0684-6) contains supplementary material, which is available to authorized users.

Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

In this letter-to-the-editor the Task Force on Gender and Diversity issues in Neurology founded under the auspices of the European Academy of Neurology (EAN) addresses various gender issues that are arising during the COVID-19 pandemic. These issues concern different aspects, spanning from gender disparities in health care workforce to gender differences amongst patients suffering from COVID-19, risk factors, occurrence of neurological complications and (outcomes of) management. Due to the continuous flow of COVID-19 related papers this review cannot be comprehensive. We attempted to select the most relevant literature on this topic.

Immunization by means of vaccination is a global health success story, saving millions of lives every year. In this regard, the epidemiology of measles, rabies, polio, rubella, varicella, influenza and mumps infections, all of which can harm the nervous system, could be contained by global vaccination campaigns. In addition, toxoid vaccines against bacterial toxins such as tetanus and diphtheria are indispensable and effective interventions for toxin-mediated neurologic diseases.

Functional recovery after stroke is associated with a remapping of neural circuits. This reorganization is often associated with low-frequency, high-amplitude oscillations in the peri-infarct zone in both rodents and humans. These oscillations are reminiscent of sleep slow waves (SW) and suggestive of a role for sleep in brain plasticity that occur during stroke recovery; however, direct evidence is missing. Using a stroke model in male mice, we showed that stroke was followed by a transient increase in NREM sleep accompanied by reduced amplitude and slope of ipsilateral NREM sleep SW. We next used 5 ms optical activation of Channelrhodopsin 2-expressing pyramidal neurons, or 200 ms silencing of Archeorhodopsin T-expressing pyramidal neurons, to generate local cortical UP, or DOWN, states, respectively, both sharing similarities with spontaneous NREM SW in freely moving mice. Importantly, we found that single optogenetically evoked SW (SWopto) in the peri-infarct zone, randomly distributed during sleep, significantly improved fine motor movements of the limb corresponding to the sensorimotor stroke lesion site compared with spontaneous recovery and control conditions, while motor strength remained unchanged. In contrast, SWoptoduring wakefulness had no effect. Furthermore, chronic SWoptoduring sleep were associated with local axonal sprouting as revealed by the increase of anatomic presynaptic and postsynaptic markers in the peri-infarct zone and corresponding contralesional areas to cortical circuit reorganization during stroke recovery. These results support a role for sleep SW in cortical circuit plasticity and sensorimotor recovery after stroke and provide a clinically relevant framework for rehabilitation strategies using neuromodulation during sleep.SIGNIFICANCE STATEMENTBrain stroke is one of the leading causes of death and major disabilities in the elderly worldwide. A better understanding of the pathophysiological mechanisms underlying spontaneous brain plasticity after stroke, together with an optimization of rehabilitative strategies, are essential to improve stroke treatments. Here, we investigate the role of optogenetically induced sleep slow waves in an animal model of ischemic stroke and identify sleep as a window for poststroke intervention that promotes neuroplasticity and facilitates sensorimotor recovery.

We aimed to determine the incidence of all vestibular symptoms in a large interdisciplinary tertiary emergency department (ED) and to assess stroke prevalence, and frequency of other life-threatening aetiologies. In this 1-year retrospective study, we manually screened all medical records of 23,608 ED visits for descriptions of vestibular symptoms. Symptoms were classified according to the International Classification of Vestibular Disorders of the Barany Society. We evaluated all patients older than 16 years in whom vestibular symptoms were the main or accompanying complaint. We extracted clinical, radiological, and laboratory findings as well as aetiologies from medical records. We identified a total of 2596 visits by 2464 patients (11% of ED visits) who reported at least one vestibular symptom. In 1677/2596 visits (64.6%), vestibular symptoms were the main reason for the ED consultation. Vestibular symptoms were classified as dizziness (43.8%), vertigo (33.9%), postural symptoms (6.5%), or more than one symptom (15.8%). In 324/2596 visits (12.5%), cerebrovascular events were the aetiology of vestibular symptoms, and in 355/2596 visits (13.7%), no diagnosis could be established. In 23.8% of visits with vestibular symptoms as the main complaint, the underlying condition was life-threatening. Frequency and impact of vestibular symptoms in patients visiting the ED were higher than previously reported, and life-threatening aetiologies such as strokes are common. Therefore, awareness among physicians regarding the importance of vestibular symptoms has to be improved.

The pedunculopontine nucleus (PPN) is a reticular nucleus located in the mesencephalic and upper pontine tegmentum. Initially, characterized by its predominant cholinergic projection neurons, it was associated with the "mesencephalic locomotor region" and "reticular activating system". Furthermore, based on histopathological studies, the PPN was hypothesized to play a role in the manifestation of symptoms in movement disorders such as Parkinson's disease (PD). Since axial symptoms represent unmet needs of PD treatments, a series of pioneering experiments in Parkinsonian monkeys promoted the idea of a potential new target for deep brain stimulation (DBS) and much clinical interest was generated in the following years leading to a number of trials analysing the role of PPN for gait disorders. This review summarizes the historical background and more recent findings about the anatomy and function of the PPN and its implications in the basal ganglia network of the normal as well as diseased brain. Classical views on PPN function shall be challenged by more recent findings. Additionally, the current role and future perspectives of PPN DBS in PD patients shall be outlined.

Previous studies reported high sensitivity and specificity of the Swiss Narcolepsy Scale (SNS) for the diagnosis of narcolepsy type 1. We used data from the Bern Sleep-Wake Database to investigate the discriminating capacity of both the SNS and the Epworth Sleepiness Scale (ESS) to identify narcolepsy type 1 and type 2 in patients with central disorders of hypersomnolence (CDH) or sleepy patients with obstructive sleep apnea (OSA). In addition, we aimed to develop a simplified version of the SNS. We created the two-item short-form SNS (sSNS), based on the discriminative capability of the models including all possible combinations of the five questions of the SNS. Using the previously published co-efficiencies, we confirmed the high capacity of the SNS in identifying narcolepsy type 1. The updated SNS (based on new co-efficiencies and cutoff) and the sSNS showed high capacity and were both superior to ESS in identifying narcolepsy type 1. The sSNS correlated significantly with the SNS (r = - 0.897, p

When humans visually explore an image, they typically tend to start exploring its left side. This phenomenon, so-called pseudoneglect, is well known, but its time-course has only sparsely been studied. Furthermore, it is unclear whether age influences pseudoneglect, and the relationship between visuo-spatial attentional asymmetries in a free visual exploration task and a classical line bisection task has not been established. To address these questions, 60 healthy participants, aged between 22 and 86, were assessed by means of a free visual exploration task with a series of naturalistic, colour photographs of everyday scenes, while their gaze was recorded by means of a contact-free eye-tracking system. Furthermore, a classical line bisection task was administered, and information concerning handedness and subjective alertness during the experiment was obtained. The results revealed a time-sensitive window during visual exploration, between 260 and 960 ms, in which age was a significant predictor of the leftward bias in gaze position, i.e., of pseudoneglect. Moreover, pseudoneglect as assessed by the line bisection task correlated with the average gaze position throughout a time-window of 300–1490 ms during the visual exploration task. These results suggest that age influences visual exploration and pseudoneglect in a time-sensitive fashion, and that the degree of pseudoneglect in the line bisection task correlates with the average gaze position during visual exploration in a time-sensitive manner.

International audience; Background and aim: Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children.Methods: The European Academy of Neurology (EAN), European Sleep Research Society (ESRS) and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach.Results: A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong), methylphenidate, amphetamine derivates (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) excessive daytime sleepiness in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivates (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions.Conclusion: The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.

Bei welchen neurologischen Symptomen muss man an COVID-19 denken? Warum kommt es uberhaupt zu neurologischen Symptomen? Bedurfen sie einer speziellen Therapie? Ein Uberblick uber den derzeitigen Kenntnisstand.

The 'catalogue of knowledge and skills' for sleep medicine presents the blueprint for a curriculum, a textbook, and an examination on sleep medicine. The first catalogue of knowledge and skills was presented by the European Sleep Research Society in 2014. It was developed following a formal Delphi procedure. A revised version was needed in order to incorporate changes that have occurred in the meantime in the International Classification of Sleep Disorders, updates in the manual for scoring sleep and associated events, and, most important, new knowledge in sleep physiology and pathophysiology. In addition, another major change can be observed in sleep medicine: a paradigm shift in sleep medicine has taken place. Sleep medicine is no longer a small interdisciplinary field in medicine. Sleep medicine has increased in terms of recognition and importance in medical care. Consequently, major medical fields (e.g. pneumology, cardiology, neurology, psychiatry, otorhinolaryngology, paediatrics) recognise that sleep disorders become a necessity for education and for diagnostic assessment in their discipline. This paradigm change is considered in the catalogue of knowledge and skills revision by the addition of new chapters., info:eu-repo/semantics/published

Objectives Τhe association between Parkinson's disease (PD) and sleep apnea syndrome (SAS) is not fully elucidated and very few studies reported on SAS outcome after deep brain stimulation (DBS). Here, we compare the clinical profile of PD patients with and without SAS and assess, for the first time, the value of pre-DBS SAS as predictor of post-DBS outcome in PD. Methods Fifty patients were grouped into PD with SAS (PD-SAS+,n = 22) and without (PD-SAS-,n = 28), based on the Apnea-Hypopnea-Index (AHI≥5) in polysomnography. We used novel multivariate statistical models to compare pre-DBS profiles and assess post-DBS motor, non-motor and quality of life (QoL) changes in both groups. Results In the entire cohort, 44% of patients had at least mild SAS (AHI≥5), while 22% had at least moderate (AHI≥15). Mean AHI was 11/h (NREM-AHI = 10.2/h and REM-AHI = 13.5/h). The two groups had equal demographics and PD characteristics, and did not differ in respect to unified Parkinson's disease rating scale (UPDRS)-IIOFF, Body-Mass-Index, polysomnographic features, RBD, depression, sleepiness and QoL scores. The PD-SAS+ group had significantly higher scores in UPDRS-IIIOFF (41.1 ± 17.7 vs. 30.9 ± 11.7,p The groups did not differ in respect to post-DBS change in UPDRS-II, UPDRS-III, Epworth sleepiness scale, Hamilton depression rating scale and PDQ39 scores. Positive airway pressure therapy had no impact on post-DBS outcome. Conclusions In patients with PD and candidates for DBS, the presence of SAS is associated with increased motor signs, but not with a specific non-motor, QoL or sleep-wake profile. The presence of SAS prior to STN-DBS is not associated with worse outcome after surgery.

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH., Journal of Sleep Research, 30 (5), ISSN:0962-1105, ISSN:1365-2869

Background Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain. Methods eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI Discussion The trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes. Trial registration ClinicalTrials.gov NCT02554487, retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521).

A multiple sleep latency test (MSLT) with occurrence of sleep onset REM periods (SOREMP) is considered one of the central diagnostic criteria for narcolepsy according to the International Classification of Sleep Disorders, but its sensitivity and specificity have been questioned. This study aims to describe MSLT and polysomnography (PSG) findings, including frequency and distribution of SOREMP during the day, in a large cohort of patients with central disorders of hypersomnolence (CDH). We retrospectively analyzed electrophysiological data from MSLT and PSG in 370 consecutive patients with narcolepsy type 1 (NT1, n = 97), type 2 (NT2, n = 31), idiopathic hypersomnia (IH, n = 48), nonorganic hypersomnia (NOH, n = 116) and insufficient sleep syndrome (ISS, n = 78). NT1 and NT2 patients had a significantly shorter mean Sleep Latency (mSL) and REM-Latency (REML) in MSLT and PSG. SOREMP occurred more frequently in narcoleptic vs. non-narcoleptic patients in MSLT and PSG. Occurrence of 3 or more SOREMP in MSLT and a SOREMP in PSG had a very high specificity and positive predictive value (98%/96% and 100% respectively), however relatively low sensitivity (65% and 45% respectively). NT1 more than NT2 patients have shorter mSL and more frequent SOREMP in MSLT and shorter SL as well as REML during nocturnal PSG. Increasing numbers of SOREMP in MSLT and especially SOREMP during PSG increase specificity on the expense of sensitivity in diagnosing narcolepsy. Therefore, frequency of SOREMP in MSLT naps and PSG can help to discriminate but not clearly separate narcoleptic from non-narcoleptic patients.

Introduction: Postural tachycardia syndrome (POTS) is a chronic form of autonomic dysfunction characterized by symptoms of orthostatic intolerance, often accompanied by sudomotor dysfunction and gastrointestinal dysmotility. In a subgroup of patients with POTS, autoantibodies against adrenergic or cholinergic receptors suggest an immune-mediated etiology. Antiphospholipid syndrome (APS) is a hypercoagulative autoimmune disorder associated with anti-phospholipid-antibodies that causes arterial and venous thromboses. Concurrent occurrence of APS and immune-mediated POTS is rare. Methods and Results: Here, we report a 28-year-old female that experiences symptoms of orthostatic intolerance, vasovagal syncopes, gastrointestinal dysmotility and sudomotor dysfunction. She fulfills the formal diagnostic criteria of POTS showing a heart rate increment of ≥30 beats per minute (bpm) within 10 m of head-up tilt in the absence of orthostatic hypotension, accompanied by symptoms of orthostatic intolerance. The thermoregulatory sweat test reveals severe patchy anhidrotic areas. Gastric emptying scintigraphy shows an impaired gastrointestinal motility. Plasma norepinephrine levels and a skin biopsy appear normal. Finally, serological persistence of anti-alpha-1-adrenergic autoantibodies suggest an immune-mediated pathogenesis. Several years after initial presentation of POTS symptoms, the patient develops APS with recurrent venous emboli and persistent anti-phospholipid-antibodies. Recently the patient is diagnosed with Hashimoto’s thyroiditis (HT) expressing high levels of thyroid-stimulating hormone and high titers of anti-thyroid antibodies. Conclusion: To our knowledge, this is the first report of consecutive immune-mediated POTS, APS and HT in a young woman, possibly displaying a unique combination of three disorders of autoimmune etiology.

Neurology is focused on a model where patients receive their care through repeated visits to clinics and doctor’s offices. Diagnostic tests often require expensive and specialized equipment that are only available in clinics. However, this current model has significant drawbacks. First, diagnostic tests, such as daytime EEG and sleep studies, occur under artificial conditions in the clinic, which may mask or wrongly emphasize clinically important features. Second, early detection and high-quality management of chronic neurological disorders require repeat measurements to accurately capture the dynamics of the disease process, which is impractical to execute in the clinic for economical and logistical reasons. Third, clinic visits remain inaccessible to many patients due to geographical and economical circumstances. Fourth, global disruptions to daily life, such as the one caused by COVID-19, can seriously harm patients if access to in-person clinical visits for diagnostic and treatment purposes is throttled. Thus, translating diagnostic and treatment procedures to patients’ homes will convey multiple substantial benefits and has the potential to substantially improve clinical outcomes while reducing cost. NeuroTec was founded to accelerate the re-imagining of neurology and to promote the convergence of technological, scientific, medical and societal processes. The goal is to identify and validate new digital biomarkers that can close the last mile in neurology by enabling the translation of personalized diagnostics and therapeutic interventions from the clinic to the patient’s home., Clinical and Translational Neuroscience, 5 (2)

© 2021 European Academy of Neurology., Clinical guidelines are “statements that include recommendations, intended to optimize patient care, that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options”. Clinical guidelines are increasingly becoming a part of neurology clinical practice, most probably because they may improve patient clinical outcomes. Methods and strategies intended to increase guideline availability include electronic and computable guidelines integrated into process-oriented information systems with clinical decision support tools. The increased availability and the possibility of continuous update (living guidelines) will likely contribute to promoting compliance with guideline recommendations and to the overarching success of guidelines in improving the quality of care in the near future.