To the Editor: From February 28 through March 21, 2020, in three hospitals in northern Italy, we examined five patients who had Guillain-Barré syndrome after the onset of coronavirus disease 2019 , the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During that period, an estimated 1000 to 1200 patients with Covid-19 were admitted to these hospitals. Four of the patients in this series had a positive nasopharyngeal swab for SARS-CoV-2 at the onset of the neurologic syndrome, and one had a negative nasopharyngeal swab and negative bronchoalveolar lavage but subsequently had a positive serologic test for the virus. Detailed case reports are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.The first symptoms of Guillain-Barré syndrome were lower-limb weakness and paresthesia in four patients and facial diplegia followed by ataxia and paresthesia in one patient (Table 1). Generalized, flaccid tetraparesis or tetraplegia evolved over a period of 36 hours to 4 days in four patients; three received mechanical ventilation. The interval between the onset of symptoms of Covid-19 and the first symptoms of Guillain-Barré syndrome ranged from 5 to 10 days (Table 1 and Fig. S1 in the Supplementary Appendix). None of the patients had dysautonomic features.On analysis of the cerebrospinal fluid (CSF), two patients had a normal protein level and all the patients had a white-cell count of less than 5 per cubic millimeter. Antiganglioside antibodies were absent in the three patients who were tested. In all the patients, a real-time polymerase-chain-reaction assay of the CSF was negative for SARS-CoV-2. Results of electrophysiological studies are shown in Table S1. Compound muscle action potential amplitudes were low but could be obtained; two patients had prolonged motor distal latencies. On electromyography, fibrillation potentials were pres-* Covid-19 denotes coronavirus disease 2019, CSF cerebrospinal fluid, ICU intensive care unit, IVIG intravenous immune globulin, MRI magnetic resonance imaging, PCR polymerase chain reaction, and SARS-CoV-2 severe acute respiratory syndrome coronavirus 2. † On CSF analysis, all the patients had a normal glucose level and IgG index and a polyclonal pattern on electrophoresis. The normal range for the protein level is 15 to 45 mg per deciliter. ‡ An enzyme-linked immunosorbent assay was used to test for antibodies to GM1, GQ1b, and GD1b.

See Morris and Weil (doi: ) for a scientific commentary on this article. In a prospective multicentre study involving 1280 patients with idiopathic RBD, Postuma et al. show that approximately 6% of patients each year (>73.5% over 12 years) convert to full neurodegenerative disease. They test the predictive power of 21 prodromal markers of neurodegeneration, providing a template for planning neuroprotective trials.

Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early Computed Tomography score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early Computed Tomography score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04406090.

In the last decade, the use of high-density electrode arrays for EEG recordings combined with the improvements of source reconstruction algorithms has allowed the investigation of brain networks dynamics at a sub-second scale. One powerful tool for investigating large-scale functional brain networks with EEG is timevarying effective connectivity applied to source signals obtained from electric source imaging. Due to computational and interpretation limitations, the brain is usually parcelled into a limited number of regions of interests (ROIs) before computing EEG connectivity. One specific need and still open problem is how to represent the time-and frequency-content carried by hundreds of dipoles with diverging orientation in each ROI with one unique representative time-series. The main aim of this paper is to provide a method to compute a signal that This is a pre-print of an article published in Brain Topography.

Study Objectives To search for a specific neuropsychological profile in idiopathic REM sleep behavior disorder (iRBD), able to predict the onset of neurodegenerative disorders. Methods In a longitudinal follow-up study of 63 consecutive iRBD patients (follow-up duration 6.7 ± 3.8 years), the baseline cognitive profile of converters to neurodegenerative disease was compared with that of the nonconverters. Five cognitive domains were assessed: memory, attention-working memory, executive functions, visuospatial abilities, language. Mild cognitive impairment (MCI) was diagnosed according to the Movement Disorder Society’s diagnostic criteria for Parkinson’s disease. Results 30 subjects (47.6%) developed a neurodegenerative disease (latency to conversion 60.33 ± 44.81 months). MCI was found in 50% of the converters and 12% of the nonconverters (p = .001), and its presence conferred a neurodegenerative disease risk of 10% at 3 years, 36% at 5 years, and 73% at 10 years (p = .002). Pathological equivalent scores on at least one neuropsychological test were detected in 46.7% of the converters versus 21.2% of the nonconverters in the memory domain (p = .032), in 40.0% versus 6.1% in that of executive functions (p = .002), and in 20.0% versus 3% in the visuospatial abilities domain (p = .047). On multivariate analysis, impaired executive functions significantly correlated with phenoconversion (p = .018). Lower Mini Mental State Examination (MMSE) scores (p = .004) and memory deficits (p = .031) were found in patients who developed dementia first. Conclusions Cognitive profile is useful for stratifying risk of phenoconversion in patients with iRBD. The presence of MCI and impaired executive functions, memory, and visuospatial abilities discriminated the converters. Lower MMSE scores and memory deficits may characterize those subjects who first develop dementia.

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Background There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. Aims We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. Methods From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. Results The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p < 0.01; OR 1.82, 95% CI: 1.21–2.73) and large vessel occlusion site (carotid-T, p < 0.03; OR 3.05, 95% CI: 1.13–8.19; M2-segment-MCA, p < 0.01; OR 4.54, 95% CI: 1.66–12.44) were associated with a higher risk of subarachnoid hemorrhage/arterial perforation. Thrombectomy alone (p < 0.01; OR 0.50, 95% CI: 0.31–0.83) and younger age (p < 0.04; OR 0.98, 95% CI: 0.97–0.99) revealed a lower risk of developing dissection. M2-segment-MCA occlusion (p < 0.01; OR 0.35, 95% CI: 0.19–0.64) and hypertension (p < 0.04; OR 0.77, 95% CI: 0.6–0.98) were less related to clot embolization. Higher NIHSS at onset (p < 0.01; OR 1.04, 95% CI: 1.02–1.06), longer groin-to-reperfusion time (p < 0.01; OR 1.05, 95% CI: 1.02–1.07), diabetes (p < 0.01; OR 1.67, 95% CI: 1.25–2.23), and LVO site (carotid-T, p < 0.01; OR 1.96, 95% CI: 1.26–3.05; M2-segment-MCA, p < 0.02; OR 1.62, 95% CI: 1.08–2.42) were associated with a higher risk of developing symptomatic intracerebral hemorrhage compared to no/asymptomatic intracerebral hemorrhage. The subgroup of patients treated with thrombectomy alone presented a lower risk of symptomatic intracerebral hemorrhage (p < 0.01; OR 0.70; 95% CI: 0.55–0.90). Subarachnoid hemorrhage/arterial perforation and symptomatic intracerebral hemorrhage after endovascular thrombectomy worsen both functional independence and mortality at three-month follow-up (p < 0.01). Distal embolization is associated with neurological deterioration (p < 0.01), while arterial dissection did not affect clinical outcome at follow-up. Conclusions Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits.

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