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Background: Management of status epilepticus (SE) is focused on the early seizure termination. Refractory SE is an indication for sedation in patients with SE, but up to 75% of patients may be ventilated due to a neurological or respiratory failure. In patients requiring sedation, the clinical assessment is not sufficient to assess seizure control. Identifying those at risk of recurrent seizures could be useful to adapt their management. On the other hand, patients with low risk could benefit from an early withdrawal of sedation to avoid the impact of inappropriate sedation on outcome., Objective: To determine the prevalence and the predictors of uncontrolled SE and its impact on outcome in patients with generalized convulsive SE (GCSE) requiring mechanical ventilation (MV)., Methods: We retrospectively included patients admitted to the intensive care unit with GCSE requiring MV. Uncontrolled SE was defined as persistent or recurrent seizures during sedation or within 24hours following withdrawal. A multivariable logistic regression model was used to assess the associated factors., Results: Uncontrolled SE occurred in 37 out of 220 patients (17%). Persistent seizures at admission, higher SAPS II and central nervous system infection were associated with a higher risk of uncontrolled SE. Acute toxic or metabolic etiologies were associated with a decreased risk of uncontrolled SE. In a supplementary analysis, decrease of albumin blood levels was associated with uncontrolled SE. Uncontrolled SE was associated with a poor functional outcome and mortality at 90 days., Conclusions: Seventeen percent of patients with a GCSE requiring MV suffered from uncontrolled SE. Etiology and persistent seizures at admission were the main predictors of uncontrolled SE. Patients with uncontrolled SE had a longer duration of sedation and MV, a poor functional outcome and a higher mortality. Further studies are required to determine the impact of continuous electroencephalogram monitoring on the clinical course., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Astrocytes are thought to play a crucial role in brain iron homeostasis. How they accomplish this regulation in vivo is unclear. In a recent transcriptomic analysis, we showed that polysomal Ftl1 and Fth1 mRNAs, encoding the ferritin light (Ftl) and heavy (Fth) chains that assemble into ferritin, a critical complex for iron storage and reduction, are enriched in perisynaptic astrocytic processes as compared to astrocytic soma. These data suggested that ferritin translation plays a specific role at the perisynaptic astrocytic interface and is tighly regulated by local translation. Here, we used our recently described AstroDot 3D in situ methodology to study the density and localization of ferritin mRNAs in astrocytes in the hippocampus in three different contexts in which local or systemic iron overload has been documented: aging, the hepcidin knock-out mouse model of hemochromatosis and the APP/PS1dE9 mouse model of Alzheimer's disease (AD). Our results showed that in wild type mice, Fth1 mRNA density was higher than Ftl1 and that both mRNAs were mostly distributed in astrocyte fine processes. Aging and absence of hepcidin caused an increased Fth1/Ftl1 ratio in astrocytes and in the case of aging, led to a redistribution of Fth1 mRNAs in astrocytic fine processes. In contrast, in AD mice, we observed a lower Fth1/Ftl1 ratio. Fth1 mRNAs became more somatic and Ftl1 mRNAs redistributed in large processes of astrocytes proximal to Amyloid beta (Aß) deposits. Hence, we propose that regulation of ferritin mRNA density and distribution in astrocytes contribute to iron homeostasis in physiology and pathophysiology., (© 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Suspicion of bacterial aspiration pneumonia (BAP) is frequent during generalized convulsive status epilepticus (GCSE). Early identification of BAP is required in order to avoid useless antibiotic therapy. In this retrospective monocentric study, we aimed to determine the incidence of aspiration syndrome and BAP in GCSE requiring mechanical ventilation (MV) and factors associated with the occurrence of BAP. Patients were older than 18 years and had GCSE requiring MV. To distinguish BAP from pneumonitis, tracheal aspirate and quantitative microbiological criterion were used. Out of 226 consecutive patients, 103 patients (46%) had an aspiration syndrome, including 54 (52%) with a BAP. Staphylococcus aureus represented 33% of bacterial strains. No relevant baseline characteristics differed, including serum levels of CRP, PCT, and albumin. The median duration of treatment for BAP was 7 days (5-7). Patients with BAP did not have a longer duration of MV ( p = 0.18) and ICU stay ( p = 0.18) than those with pneumonitis. At 3 months, 24 patients (44%) with BAP and 10 (27%) with pneumonitis had a poor functional outcome ( p = 0.06). In conclusion, among patients with GCSE, half of the patients had an aspiration syndrome and one-quarter suffered from BAP. Clinical characteristics and biomarkers were not useful for differentiating BAP from pneumonitis. These results highlight the need for a method to rapidly differentiate BAP from pneumonitis, such as polymerase-chain-reaction-based techniques.

Intensive care unit (ICU)-acquired weakness (ICU-AW) is defined as clinically detected weakness in critically ill patients in whom there is no plausible etiology other than critical illness. Using electrophysiological methods, patients with ICU-AW are classified in three subcategories: critical illness polyneuropathy, critical illness myopathy and critical illness neuromyopathy. ICU-AW is a frequent complication occurring in critical ill patients. Risk factors include illness severity and organ failure, age, hyperglycemia, parenteral nutrition, drugs and immobility. Due to short- and long-term complications, ICU-AW results in longer hospital stay and increased mortality. Its management is essentially preventive avoiding modifiable risk factors, especially duration of sedation and immobilization that should be as short as possible. Pharmacological approaches have been studied but none have proven efficacy. In the present review, we propose practical questions that the clinician should ask in case of acquired weakness during ICU stay: when to suspect ICU-AW, what risk factors should be identified, how to diagnose ICU-AW, what is the prognosis and how can recovery be improved?, (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To describe EEG patterns of critical Coronavirus Disease 2019 (COVID-19) patients with suspicion of encephalopathy and test their association with clinical outcome., Methods: EEG after discontinuation of sedation in all patients, and somesthesic evoked potentials and brainstem auditive evoked potentials when EEG did not show reactivity, were performed. Clinical outcome was assessed at day 7 and 14 after neurophysiological explorations., Results: 33 patients were included for analysis. We found slowed background activity in 85% of cases, unreactive activity in 42% of cases, low-voltage activity in 21% of cases and rhythmic or periodic delta waves in 61% of cases. EEG epileptic events were never recorded. Clinical outcome at day 14 was associated with unreactive background activity and tended to be associated with rhythmic or periodic delta waves and with low-voltage activity. Results of multimodal evoked potentials were in favor of a preservation of central nervous system somatosensory and auditory functions., Conclusions: Among critical COVID-19 patients with abnormal arousal at discontinuation of sedation, EEG patterns consistent with encephalopathy are found and are predictive for short term clinical outcome., Significance: The abnormal EEG with presence of periodic discharges and lack of reactivity could be related to encephalopathy linked to COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Local translation is a conserved mechanism conferring cells the ability to quickly respond to local stimuli. In the brain, it has been recently reported in astrocytes, whose fine processes contact blood vessels and synapses. Yet the specificity and regulation of astrocyte local translation remain unknown. We study hippocampal perisynaptic astrocytic processes (PAPs) and show that they contain the machinery for translation. Using a refined immunoprecipitation technique, we characterize the entire pool of ribosome-bound mRNAs in PAPs and compare it with the one expressed in the whole astrocyte. We find that a specific pool of mRNAs is highly polarized at the synaptic interface. These transcripts encode an unexpected molecular repertoire, composed of proteins involved in iron homeostasis, translation, cell cycle, and cytoskeleton. Remarkably, we observe alterations in global RNA distribution and ribosome-bound status of some PAP-enriched transcripts after fear conditioning, indicating the role of astrocytic local translation in memory and learning., Competing Interests: Declaration of Interests The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Astrocytes are morphologically complex and use local translation to regulate distal functions. To study the distribution of mRNA in astrocytes, we combined mRNA detection via in situ hybridization with immunostaining of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). mRNAs at the level of GFAP-immunolabelled astrocyte somata, and large and fine processes were analysed using AstroDot, an ImageJ plug-in and the R package AstroStat. Taking the characterization of mRNAs encoding GFAP-α and GFAP-δ isoforms as a proof of concept, we showed that they mainly localized on GFAP processes. In the APPswe/PS1dE9 mouse model of Alzheimer's disease, the density and distribution of both α and δ forms of Gfap mRNA changed as a function of the region of the hippocampus and the astrocyte's proximity to amyloid plaques. To validate our method, we confirmed that the ubiquitous Rpl4 (large subunit ribosomal protein 4) mRNA was present in astrocyte processes as well as in microglia processes immunolabelled for ionized calcium binding adaptor molecule 1 (Iba1; also known as IAF1). In summary, this novel set of tools allows the characterization of mRNA distribution in astrocytes and microglia in physiological or pathological settings., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Background: Stroke of unknown time of onset (UTOS) accounts for one-third of contra-indications for revascularization procedures. With modern neuroimaging techniques it is possible to differentiate the core infarcts and the presence of penumbra., Objective: To evaluate outcomes in patients with UTOS, treated with intravenous (i.v.) recombinant tissue-plasminogen activator (rt-PA), mechanical thrombectomy (MT), or both., Method: We conducted this observational study in patients treated by i.v. rt-PA, MT, or both, selected by a diffusion-weighted image/fluid-attenuated inversion recovery mismatch. We evaluated outcomes with the modified Rankin scale (mRS) at 3 months., Results: Of 992 consecutive patients (522 women, 52.6%; median age 76 years; median baseline national institutes of health stroke scale [NIHSS] 10), 153 (15.4%) had UTOS, including 101 with wake-up strokes. Compared to other patients, they were more likely to have pre-existing mRS scores >2 (P=0.022), multiple infarcts (P<0.001), middle cerebral artery occlusions (P=0.023), and to undergo MT (P=0.003), and less likely to receive i.v. rt-PA (P<0.001). They had higher NIHSS scores (P<0.001) and longer discovery to treatment initiation times (P<0.001). They were more likely to develop pulmonary (P=0.001) and urinary (P=0.006) infections, and pulmonary embolism (P=0.019), and tended to have a higher mortality rate (P=0.052) within 7 days. After adjustment, there was no association of UTOS with any of these outcome measures anymore., Conclusion: Patients with UTOS have more severe strokes and more comorbidities, but after adjustment, their outcomes did not differ from those of other patients., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Hospitals admitting acute strokes should offer access to mechanical thrombectomy (MT), but local organisations are still based on facilities available before MT was proven effective. MT rates and outcomes at population levels are needed to adapt organisations. We evaluated rates of MT and outcomes in inhabitants from the North-of-France (NoF) area., Method: We prospectively evaluated rates of MT and outcomes of patients at 3 months, good outcomes being defined as a modified Rankin scale (mRS) 0 to 2 or like the pre-stroke mRS., Results: During the study period (2016-2017), 666 patients underwent MT (454, 68.1% associated with intravenous thrombolysis [IVT]). Besides, 1595 other patients received IVT alone. The rate of MT was 81 (95% confidence interval [CI] 72-90) per million inhabitants-year, ranging from 36 to 108 between districts. The rate of IVT was 249 (95% CI 234-264) per million inhabitants-year, ranging from 155 to 268. After 3 months, 279 (41.9%) patients who underwent MT had good outcomes, and 167 (25.1%) had died. Patients living outside the district of Lille where the only MT centre is, were less likely to have good outcomes at 3 months, after adjustment on age, sex, baseline severity, and delay., Conclusion: The rate of MT is one of the highest reported up to now, even in low-rate districts, but outcomes were significantly worse in patients living outside the district of Lille, and this is not only explained by the delay., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Spontaneous intracerebral haemorrhage is defined as a collection of blood in the cerebral parenchyma that is not caused by trauma. It represents roughly 10-20% of all strokes. The clinical presentation is unspecific and the diagnosis requires brain imaging. ICH is a medical emergency and ICH patients have to be admitted in an acute stroke unit. The priority is to fight against ICH expansion. The first step consists in the administration of a specific antagonist of the antithrombotic treatment when available, and in the strict control of blood pressure. Clinicians should keep in mind that the concept of so-called "primary" ICH is misleading since many causes should be searched for. During follow-up, the risk of recurrence may depend on the underlying vessel disease and blood pressure should be strictly managed. ICH patients are at high risk of dementia: cognitive evaluation should regularly be performed during follow-up., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)