Deleterious effect of sustained neuroinflammation in pediatric traumatic brain injury.

INTRODUCTION: Despite improved management of traumatic brain injury (TBI), it still leads to lifelong sequelae and disability, particularly in children. Chronic neuroinflammation (the so-called tertiary phase), in particular, microglia/macrophage and astrocyte reactivity, is among the main mechanisms suspected of playing a role in the generation of lesions associated with TBI. The role of acute neuroinflammation is now well understood, but its persistent effect and impact on the brain, particularly during development, are not. Here, we investigated the long-term effects of pediatric TBI on the brain in a mouse model. METHODS: Pediatric TBI was induced in mice on postnatal day (P) 7 by weight-drop trauma. The time course of neuroinflammation and myelination was examined in the TBI mice. They were also assessed by magnetic resonance, functional ultrasound, and behavioral tests at P45. RESULTS: TBI induced robust neuroinflammation, characterized by acute microglia/macrophage and astrocyte reactivity. The long-term consequences of pediatric TBI studied on P45 involved localized scarring astrogliosis, persistent microgliosis associated with a specific transcriptomic signature, and a long-lasting myelination defect consisting of the loss of myelinated axons, a decreased level of myelin binding protein, and severe thinning of the corpus callosum. These results were confirmed by reduced fractional anisotropy, measured by diffusion tensor imaging, and altered inter- and intra-hemispheric connectivity, measured by functional ultrasound imaging. In addition, adolescent mice with pediatric TBI showed persistent social interaction deficits and signs of anxiety and depressive behaviors. CONCLUSIONS: We show that pediatric TBI induces tertiary neuroinflammatory processes associated with white matter lesions and altered behavior. These results support our model as a model for preclinical studies for tertiary lesions following TBI.

Prognostic value of early EEG abnormalities in severe stroke patients requiring mechanical ventilation: a pre-planned analysis of the SPICE prospective multicenter study.

INTRODUCTION: Prognostication of outcome in severe stroke patients necessitating invasive mechanical ventilation poses significant challenges. The objective of this study was to assess the prognostic significance and prevalence of early electroencephalogram (EEG) abnormalities in adult stroke patients receiving mechanical ventilation. METHODS: This study is a pre-planned ancillary investigation within the prospective multicenter SPICE cohort study (2017-2019), conducted in 33 intensive care units (ICUs) in the Paris area, France. We included adult stroke patients requiring invasive mechanical ventilation, who underwent at least one intermittent EEG examination during their ICU stay. The primary endpoint was the functional neurological outcome at one year, determined using the modified Rankin scale (mRS), and dichotomized as unfavorable (mRS 4-6, indicating severe disability or death) or favorable (mRS 0-3). Multivariable regression analyses were employed to identify EEG abnormalities associated with functional outcomes. RESULTS: Of the 364 patients enrolled in the SPICE study, 153 patients (49 ischemic strokes, 52 intracranial hemorrhages, and 52 subarachnoid hemorrhages) underwent at least one EEG at a median time of 4 (interquartile range 2-7) days post-stroke. Rates of diffuse slowing (70% vs. 63%, p = 0.37), focal slowing (38% vs. 32%, p = 0.15), periodic discharges (2.3% vs. 3.7%, p = 0.9), and electrographic seizures (4.5% vs. 3.7%, p = 0.4) were comparable between patients with unfavorable and favorable outcomes. Following adjustment for potential confounders, an unreactive EEG background to auditory and pain stimulations (OR 6.02, 95% CI 2.27-15.99) was independently associated with unfavorable outcomes. An unreactive EEG predicted unfavorable outcome with a specificity of 48% (95% CI 40-56), sensitivity of 79% (95% CI 72-85), and positive predictive value (PPV) of 74% (95% CI 67-81). Conversely, a benign EEG (defined as continuous and reactive background activity without seizure, periodic discharges, triphasic waves, or burst suppression) predicted favorable outcome with a specificity of 89% (95% CI 84-94), and a sensitivity of 37% (95% CI 30-45). CONCLUSION: The absence of EEG reactivity independently predicts unfavorable outcomes at one year in severe stroke patients requiring mechanical ventilation in the ICU, although its prognostic value remains limited. Conversely, a benign EEG pattern was associated with a favorable outcome.

Secondary Neurologic Deterioration After Moderate Traumatic Brain Injury: Development of a Multivariable Prediction Model and Proposition of a Simple Triage Score.

BACKGROUND: Identifying patients at risk of secondary neurologic deterioration (SND) after moderate traumatic brain injury (moTBI) is a challenge, as such patients will need specific care. No simple scoring system has been evaluated to date. This study aimed to determine clinical and radiological factors associated with SND after moTBI and to propose a triage score. METHODS: All adults admitted in our academic trauma center between January 2016 and January 2019 for moTBI (Glasgow Coma Scale [GCS] score, 9-13) were eligible. SND during the first week was defined either by a decrease in GCS score of >2 points from the admission GCS in the absence of pharmacologic sedation or by a deterioration in neurologic status associated with an intervention, such as mechanical ventilation, sedation, osmotherapy, transfer to the intensive care unit (ICU), or neurosurgical intervention (for intracranial mass lesions or depressed skull fracture). Clinical, biological, and radiological independent predictors of SND were identified by logistic regression (LR). An internal validation was performed using a bootstrap technique. A weighted score was defined based on beta (ß) coefficients of the LR. RESULTS: A total of 142 patients were included. Forty-six patients (32%) showed SND, and 14-day mortality rate was 18.4%. Independent variables associated with SND were age above 60 years (odds ratio [OR], 3.45 [95% confidence interval {CI}, 1.45-8.48]; P = .005), brain frontal contusion (OR, 3.22 [95% CI, 1.31-8.49]; P = .01), prehospital or admission arterial hypotension (OR, 4.86 [95% CI, 2.03-12.60]; P = .006), and a Marshall computed tomography (CT) score of 6 (OR, 3.25 [95% CI, 1.31-8.20]; P = .01). The SND score was defined with a range from 0 to 10. The score included the following variables: age >60 years (3 points), prehospital or admission arterial hypotension (3 points), frontal contusion (2 points), and Marshall CT score of 6 (2 points). The score was able to detect patients at risk of SND, with an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI, 0.65-0.82). A score of 3 had a sensitivity of 85%, a specificity of 50%, a VPN of 87%, and a VPP of 44 % to predict SND. CONCLUSIONS: In this study, we demonstrate that moTBI patients have a significant risk of SND. A simple weighted score at hospital admission could be able to detect patients at risk of SND. The use of the score may enable optimization of care resources for these patients.

Safety and practicality study of using an exoskeleton in acute neurosurgery patients.

INTRODUCTION: Early mobilization is key in neurologically impaired persons, limiting complications and improving long-term recovery. Self-balanced exoskeletons are used in rehabilitation departments to help patients stand and walk. We report the first case series of exoskeleton use in acute neurosurgery and intensive care patients, evaluating safety, clinical feasibility and patients' satisfaction. METHODS: We report a retrospective observational study including individuals hospitalized in the neurosurgical intensive care and neurosurgery departments. We included patients with a medical prescription for an exoskeleton session, and who met no contraindication. Patients benefited from standing sessions using a self-balanced exoskeleton (Atalante, Wandercraft, France). Patients and sessions data were collected. Safety, feasibility and adherence were evaluated. RESULTS: Seventeen patients were scheduled for 70 standing sessions, of which 27 (39%) were completed. They were typically hospitalized for intracranial hemorrhage (74%) and presented with unilateral motor impairments, able to stand but with very insufficient weight shifting to the hemiplegic limb, requiring support (MRC 36.2 ± 3.70, SPB 2.0 ± 1.3, SPD 0.7 ± 0.5). The average duration of standing sessions was 16 ± 9 min. The only side effect was orthostatic hypotension (18.5%), which resolved with returning to seating position. The most frequent reason for not completing a session was understaffing (75%). All patients were satisfied and expressed a desire to repeat it. CONCLUSIONS: Physiotherapy using the exoskeleton is safe and feasible in the acute neurosurgery setting, although it requires adaptation from the staff to organize the sessions. An efficacy study is ongoing to evaluate the benefits for the patients.

One-Year Outcomes in Patients With Acute Stroke Requiring Mechanical Ventilation.

BACKGROUND: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU). METHODS: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors. RESULTS: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors. CONCLUSIONS: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03335995.

Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries.

Approximately 15 million babies are born prematurely every year and many will face lifetime motor and/or cognitive deficits. Children born prematurely are at higher risk of developing perinatal brain lesions, especially white matter injuries (WMI). Evidence in humans and rodents demonstrates that systemic inflammation-induced neuroinflammation, including microglial and astrocyte reactivity, is the prominent processes of WMI associated with preterm birth. Thus, a new challenge in the field of perinatal brain injuries is to develop new neuroprotective strategies to target neuroinflammation to prevent WMI. Serotonin (5-HT) and its receptors play an important role in inflammation, and emerging evidence indicates that 5-HT may regulate brain inflammation by the modulation of microglial reactivity and astrocyte functions. The present study is based on a mouse model of WMI induced by intraperitoneal (i.p.) injections of IL-1ß during the first 5 days of life. In this model, certain key lesions of preterm brain injuries can be summarized by (i) systemic inflammation, (ii) pro-inflammatory microglial and astrocyte activation, and (iii) inhibition of oligodendrocyte maturation, leading to hypomyelination. We demonstrate that Htr7 mRNA (coding for the HTR7/5-HT7 receptor) is significantly overexpressed in the anterior cortex of IL-1ß-exposed animals, suggesting it as a potential therapeutic target. LP-211 is a specific high-affinity HTR7 agonist that crosses the blood-brain barrier (BBB). When co-injected with IL-1ß, LP-211 treatment prevented glial reactivity, the down-regulation of myelin-associated proteins, and the apparition of anxiety-like phenotypes. Thus, HTR7 may represent an innovative therapeutic target to protect the developing brain from preterm brain injuries.

Physician experience improves ability to predict 6-month functional outcome of severe traumatic brain injury.

BACKGROUND: The functional prognosis of severe traumatic brain injury (TBI) during the acute phase is often poor and uncertain. We aimed to quantify the elements that shade the degree of uncertainty in prognostic determination of TBI and to better understand the role of clinical experience in prognostic quality. METHODS: This was an observational, prospective, multicenter study. The medical records of 16 patients with moderate or severe TBI in 2020 were randomly drawn from a previous study and submitted to two groups of physicians: senior and junior. The senior physician group had graduated from a critical care fellowship, and the junior physician group had at least 3 years of anesthesia and critical care residency. They were asked for each patient, based on the reading of clinical data and CT images of the first 24 h, to determine the probability of an unfavorable outcome (Glasgow Outcome Scale < 4) at 6 months between 0 and 100, and their level of confidence. These estimations were compared with the actual evolution. RESULTS: Eighteen senior physicians and 18 junior physicians in 4 neuro-intensive care units were included in 2021. We observed that senior physicians performed better than junior physicians, with 73% (95% confidence interval (CI) 65-79) and 62% (95% CI 56-67) correct predictions, respectively, in the senior and junior groups (p = 0.006). The risk factors for incorrect prediction were junior group (OR 1.71, 95% CI 1.15-2.55), low confidence in the estimation (OR 1.76, 95% CI 1.18-2.63), and low level of agreement on prediction between senior physicians (OR 6.78, 95% CI 3.45-13.35). CONCLUSIONS: Determining functional prognosis in the acute phase of severe TBI involves uncertainty. This uncertainty should be modulated by the experience and confidence of the physician, and especially on the degree of agreement between physicians.

Corticosteroid treatment for refractory intracranial hypertension: a rescue therapy in patients with severe traumatic brain injury with contusional lesions-a feedback.

INTRODUCTION: Refractory intracranial hypertension (rICH) is a severe complication among patients with severe traumatic brain injury (sTBI). Medical treatment may be insufficient, and in some cases, the only viable treatment option is decompressive hemicraniectomy. The assessment of a corticosteroid therapy against vasogenic edema secondary to severe brain injuries seems interesting to prevent this surgery in sTBI patients with rICH caused by contusional areas. METHODS: This is a monocentric retrospective observational study including all consecutive sTBI patients with contusion injuries and a rICH requiring cerebrospinal fluid drainage with external ventricular drainage between November 2013 and January 2018. Patient inclusion criterium was a therapeutic index load (TIL; an indirect measure of TBI severity) > 7. Intracranial pressure (ICP) and TIL were assessed before and 48 h after corticosteroid therapy (CTC). Then, we divided the population into two groups according to the evolution of the TIL: responders and non-responders to corticosteroid therapy. RESULTS: During the study period, 512 patients were hospitalized for sTBI, and among them, 44 (8.6%) with rICH were included. They received 240 mg per day [120 mg, 240 mg] of Solu-Medrol for 2 days [1; 3], 3 days after the sTBI. The average ICP in patients with rICH before the CTC bolus was 21 mmHg [19; 23]. After the CTC bolus, the ICP fell significantly to less than 15 mmHg (p < 0.0001) for at least 7 days. The TIL decreased significantly the day after the CTC bolus and until day 2. Among these 44 patients, 68% were included in the responder group (n = 30). DISCUSSION: Short and systemic corticosteroid therapy in patients with refractory intracranial hypertension secondary to severe traumatic brain injury seems to be a potentially useful and efficient treatment for lowering intracranial pressure and decreasing the need for more invasive surgeries.

PREDICT-TBI: Comparison of Physician Predictions with the IMPACT Model to Predict 6-Month Functional Outcome in Traumatic Brain Injury.

BACKGROUND: Predicting functional outcome in critically ill patients with traumatic brain injury (TBI) strongly influences end-of-life decisions and information for surrogate decision makers. Despite well-validated prognostic models, clinicians most often rely on their subjective perception of prognosis. In this study, we aimed to compare physicians' predictions with the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic model for predicting an unfavorable functional outcome at 6 months after moderate or severe TBI. METHODS: PREDICT-TBI is a prospective study of patients with moderate to severe TBI. Patients were admitted to a neurocritical care unit and were excluded if they died or had withdrawal of life-sustaining treatments within the first 24 h. In a paired study design, we compared the accuracy of physician prediction on day 1 with the prediction of the IMPACT model as two diagnostic tests in predicting unfavorable outcome 6 months after TBI. Unfavorable outcome was assessed by the Glasgow Outcome Scale from 1 to 3 by using a structured telephone interview. The primary end point was the difference between the discrimination ability of the physician and the IMPACT model assessed by the area under the curve. RESULTS: Of the 93 patients with inclusion and exclusion criteria, 80 patients reached the primary end point. At 6 months, 29 patients (36%) had unfavorable outcome. A total of 31 clinicians participated in the study. Physicians' predictions showed an area under the curve of 0.79 (95% confidence interval 0.68-0.89), against 0.80 (95% confidence interval 0.69-0.91) for the laboratory IMPACT model, with no statistical difference (p = 0.88). Both approaches were well calibrated. Agreement between physicians was moderate (κ = 0.56). Lack of experience was not associated with prediction accuracy (p = 0.58). CONCLUSIONS: Predictions made by physicians for functional outcome were overall moderately accurate, and no statistical difference was found with the IMPACT models, possibly due to a lack of power. The significant variability between physician assessments suggests prediction could be improved through peer reviewing, with the support of the IMPACT models, to provide a realistic expectation of outcome to families and guide discussions about end-of-life decisions.

Agreement between pulse oximetry and arterial oxygen saturation measurement in critical care patients during COVID-19: a cross-sectional study.

Some publications suggest that pulse oximetry measurement (SpO2) might overestimate arterial oxygen saturation (SaO2) measurement in COVID-19 patients. This study aims to evaluate the agreement between SpO2 and SaO2 among COVID-19 and non-COVID-19 patients. We conducted a multicenter, prospective study including consecutive intensive care patients from October 15, 2020, to March 4, 2021, and compared for each measurement the difference between SpO2 and SaO2, also called the systematic bias. The primary endpoint was the agreement between SpO2 and SaO2 measured with the Lin concordance coefficient and illustrated using the Bland and Altman method. Factors associated with systematic bias were then identified using a generalised estimating equation. The study included 105 patients, 66 COVID-19 positive and 39 COVID-19 negative, allowing for 1539 measurements. The median age was 66 [57; 72] years with median SOFA and SAPSII scores of, respectively, 4 [3; 6] and 37 [31; 47]. The median SpO2 and SaO2 among all measurements was respectively 97 [96-99] and 94 [92-96] with a systematic bias of 0.80 [- 0.6; 2.4]. This difference was, respectively, 0.80 [- 0.7; 2.5] and 0.90 [- 0.3; 2.0] among COVID-19 positive and negative patients. Overall agreement measured with the Lin correlation coefficient was 0.65 [0.63; 0.68] with 0.61 [0.57; 0.64] and 0.53 [0.45; 0.60] among the COVID-19 positive and negative groups, respectively. Factors independently associated with the variation of the SpO2-SaO2 difference were the PaO2/FiO2 ratio and need for mechanical ventilation. In our population, agreement between SpO2 and SaO2 is acceptable. During the COVID-19 pandemic, SaO2 remains an efficient monitoring tool to characterise the level of hypoxemia and follow therapeutic interventions. As is already known about general intensive care unit patients, the greater hypoxemia, the weaker the correlation between SpO2 and SaO2.

Brain Biopsy for Neurological Diseases of Unknown Etiology in Critically Ill Patients: Feasibility, Safety, and Diagnostic Yield.

OBJECTIVES: Brain biopsy is a useful surgical procedure in the management of patients with suspected neoplastic lesions. Its role in neurologic diseases of unknown etiology remains controversial, especially in ICU patients. This study was undertaken to determine the feasibility, safety, and the diagnostic yield of brain biopsy in critically ill patients with neurologic diseases of unknown etiology. We also aimed to compare these endpoints to those of non-ICU patients who underwent a brain biopsy in the same clinical context. DESIGN: Monocenter, retrospective, observational cohort study. SETTING: A French tertiary center. PATIENTS: All adult patients with neurologic diseases of unknown etiology under mechanical ventilation undergoing in-ICU brain biopsy between January 2008 and October 2020 were compared with a cohort of non-ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 2,207 brain-biopsied patients during the study period, 234 biopsies were performed for neurologic diseases of unknown etiology, including 29 who were mechanically ventilated and 205 who were not ICU patients. Specific histological diagnosis and final diagnosis rates were 62.1% and 75.9%, respectively, leading to therapeutic management modification in 62.1% of cases. Meningitis on prebiopsy cerebrospinal fluid analysis was the sole predictor of obtaining a final diagnosis (2.3 [1.4-3.8]; p = 0.02). ICU patients who experienced therapeutic management modification after the biopsy had longer survival (p = 0.03). The grade 1 to 4 (mild to severe) complication rates were: 24.1%, 3.5%, 0%, and 6.9%, respectively. Biopsy-related mortality was significantly higher in ICU patients compared with non-ICU patients (6.9% vs 0%; p = 0.02). Hematological malignancy was associated with biopsy-related mortality (1.5 [1.01-2.6]; p = 0.04). CONCLUSIONS: Brain biopsy in critically ill patients with neurologic disease of unknown etiology is associated with high diagnostic yield, therapeutic modifications and postbiopsy survival advantage. Safety profile seems acceptable in most patients. The benefit/risk ratio of brain biopsy in this population should be carefully weighted.

Prevalence, characteristics and outcome of cardiac manifestations in critically-ill antiphospholipid syndrome patients.

AIMS: Antiphospholipid syndrome (APS) is a rare autoimmune disease defined by thrombotic events occurring in patients with persistent antiphospholipid antibodies. Cardiac manifestations in critically-ill APS patients are poorly investigated. We conducted a study to assess the prevalence, the characteristics and the prognosis of cardiac manifestations in thrombotic APS patients admitted to intensive care unit (ICU). METHODS AND RESULTS: A French, national, multicentre, retrospective study, conducted, from January 2000 to September 2018, including all APS patients admitted to 24 participating centres' ICUs with any new thrombotic (arterial, venous or microvascular) manifestation. Cardiac manifestations were defined as any new cardiac abnormalities relying on clinical examination, cardiac biomarkers, echocardiography, cardiac magnetic resonance (CMR) and coronarography. One hundred and thirty-six patients (female 72%) were included. Mean age at ICU admission was 46 ± 15years. Cardiac manifestations were present in 71 patients (53%). In patients with cardiac involvement, median left ventricular ejection fraction (LVEF) was 40% [28-55], troponin was elevated in 93% patients, coronary angiogram (n = 19, 27%) disclosing a coronary obstruction in 21%. CMR (n = 21) was abnormal in all cases, with late gadolinium enhancement in 62% of cases. Cardiac manifestations were associated with a non-significant increase of mortality (32% vs. 19%, p = 0.08). After 1-year follow-up, median LVEF was 57% [44-60] in patients with cardiac involvement. CONCLUSION: Cardiac involvement is frequent in critically-ill thrombotic APS patients and may be associated to more severe outcome. Increased awareness on this rare cause of myocardial infarction with or without obstructive coronary artery is urgently needed.

One-year patient outcomes based on lung morphology in acute respiratory distress syndrome: secondary analysis of LIVE trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) has different phenotypes and distinct short-term outcomes. Patients with non-focal ARDS have a higher short-term mortality than focal ones. The aim of this study was to assess the impact of the morphological phenotypes of ARDS on long-term outcomes. METHODS: This was a secondary analysis of the LIVE study, a prospective, randomised control trial, assessing the usefulness of a personalised ventilator setting according to lung morphology in moderate-to-severe ARDS. ARDS was classified as focal (consolidations only in the infero-posterior part of the lungs) or non-focal. Outcomes were assessed using mortality and functional scores for quality of life at the 1-year follow-up. RESULTS: A total of 124 focal ARDS and 236 non-focal ARDS cases were included. The 1-year mortality was higher for non-focal ARDS than for focal ARDS (37% vs. 24%, p = 0.012). Non-focal ARDS (hazard ratio, 3.44; 95% confidence interval, 1.80-6.59; p < 0.001), age, McCabe score, haematological cancers, SAPS II, and renal replacement therapy were independently associated with 1-year mortality. This difference was driven by mortality during the first 90 days (28 vs. 16%, p = 0.010) but not between 90 days and 1 year (7 vs. 6%, p = 0.591), at which point only the McCabe score was independently associated with mortality. Morphological phenotypes had no impact on patient-reported outcomes. CONCLUSION: Lung morphologies reflect the acute phase of ARDS and its short-term impact but not long-term outcomes, which seem only influenced by comorbidities. TRIAL REGISTRATION: NCT02149589; May 29, 2014.

Exclusion treatment of ruptured and unruptured low-grade brain arteriovenous malformations: a systematic review.

PURPOSE: To assess the obliteration rate, functional outcome, hemorrhagic complication, and mortality rates of exclusion treatment of low-grade brain arteriovenous malformations (BAVMs) (Spetzler and Martin grades (SMGs) 1 and 2), either ruptured or unruptured. METHODS: Electronic databases-Ovid MEDLINE and PubMed-were searched for studies in which there was evidence of exclusion treatment of low-grade BAVMs treated either by endovascular, surgical, radiosurgical, or multimodality treatment. The primary outcome of interest was angiographic obliteration post-treatment and at follow-up. The secondary outcomes of interest were functional outcome (mRS), mortality rate, and hemorrhagic complication. Descriptive statistics were used to calculate rates and means. RESULTS: Eleven studies involving 1809 patients with low-grade BAVMs were included. Among these, 1790 patients treated by either endovascular, surgical, radiosurgical, or multimodality treatment were included in this analysis. Seventy-two percent of BAVMs were Spetzler-Martin grade II. The overall (i.e., including all exclusion treatment modalities) complete obliteration rate ranged from 36.5 to 100%. The overall symptomatic hemorrhagic complication rate ranged from 0 to 7.3%; procedure-related mortality ranged from 0 to 4.7%. CONCLUSION: Our systematic review of the literature reveals a high overall obliteration rate for low-grade BAVMs, either ruptured or unruptured, with low mortality rate and an acceptable post-treatment hemorrhagic complication rate. These results suggest that exclusion treatment of low-grade BAVMs may be safe and effective, regardless of the treatment modality chosen.

Outpatient stereotactic brain biopsies.

Outpatient neurosurgery is rising popularity leading to patients' satisfaction and cost-savings. Although several North-American teams have shown the safety of outpatient stereotactic brain biopsies, few data from other countries with different health care systems are available. We therefore conducted a feasibility and safety study on the outpatient stereotactic brain biopsies. We prospectively examined all the consecutive stereotactic brain biopsies performed in an outpatient setting at our tertiary medical center, between June 2018 and September 2020. Among the 437 patients who underwent stereotactic brain biopsy during the study period, 40 (9.2%) patients were enrolled for an outpatient management. The sex ratio was 1 and the median age on biopsy day was 55 [41-66] years. The median distance from patients' home to hospital was 17 km [3-47]. 95% of patients had pre-biopsy ASA score of 1 or 2 and mRs equal to 2 or less. The rate of same-day discharge was 100%. No patient experienced post-biopsy symptomatic complication necessitating readmission within the month following the biopsy. One patient (2.5%) resorted to an unplanned consultation. Histological findings obtained from brain biopsy led to a diagnosis in all patients; the most frequently found were neoplastic lesions (77.5%). Stereotactic brain biopsies can therefore be safely achieved on an outpatient setting in carefully selected patients. This process could be more widely adopted in other neurosurgical centers, without affecting the quality of patient's health care and safety. In this article, we propose management guidelines and pre-biopsy checklist for performing ambulatory stereotactic brain biopsies.

Anterior interhemispheric approach for anterior fossa dural arteriovenous fistulas.

Anterior fossa dural arteriovenous fistulas (AF-DAVF) usually display a cortical venous drainage and are therefore at risk for rupture. Microsurgery is traditionally considered in many centers as the first-line treatment since endovascular treatment (EVT) entails a lower cure rate and significant ophthalmic risks. The anterior interhemispheric approach (AIA), originally described by Mayfrank in 1996, seems to offer the effectiveness of microsurgery while limiting the risks related to subfrontal craniotomy. The objective of this study was to analyze the surgical outcomes of patients who underwent this surgical approach for the treatment of AF-DAVF. We hereby describe our 10 years' experience of patients treated for an AF-DAVF with this technique in our institution and retrospectively analyzed our results. In addition, we describe our operative technique and its specificities. Eleven patients with AF-DAVF were included in our study. The definitive cure of the fistula was confirmed in all cases with postoperative cerebral angiography. All patients had a good neurological outcome and no major complication occurred. Brain retractors were never used during surgery, the frontal sinus was never opened neither, and anosmia was never observed after surgery. Anterior interhemispheric approach seems to be safe and effective to treat AF-DAVF with lower risks than other surgical approaches. This technique could be more widely considered when facing such midline vascular lesion.

A One-Day Prospective National Observational Study on Sedation-Analgesia of Patients with Brain Injury in French Intensive Care Units: The SEDA-BIP-ICU (Sedation-Analgesia in Brain Injury Patient in ICU) Study.

BACKGROUND: Sedation/analgesia is a daily challenge faced by intensivists managing patients with brain injury (BI) in intensive care units (ICUs). The optimization of sedation in patients with BI presents particular challenges. A choice must be made between the potential benefit of a rapid clinical evaluation and the potential exacerbation of intracranial hypertension in patients with impaired cerebral compliance. In the ICU, a pragmatic approach to the use of sedation/analgesia, including the optimal titration, management of multiple drugs, and use of any type of brain monitor, is needed. Our research question was as follows: the aim of the study is to identify what is the current daily practice regarding sedation/analgesia in the management of patients with BI in the ICU in France? METHODS: This study was composed of two parts. The first part was a descriptive survey of sedation practices and characteristics in 30 French ICUs and 27 academic hospitals specializing in care for patients with BI. This first step validates ICU participation in data collection regarding sedation-analgesia practices. The second part was a 1-day prospective cross-sectional snapshot of all characteristics and prescriptions of patients with BI. RESULTS: On the study day, among the 246 patients with BI, 106 (43%) had a brain monitoring device and 74 patients (30%) were sedated. Thirty-nine of the sedated patients (53%) suffered from intracranial hypertension, 14 patients (19%) suffered from agitation and delirium, and 7 patients (9%) were sedated because of respiratory failure. Fourteen patients (19%) no longer had a formal indication for sedation. In 60% of the sedated patients, the sedatives were titrated by nurses based on sedation scales. The Richmond Agitation Sedation Scale was used in 80% of the patients, and the Behavioral Pain Scale was used in 92%. The common sedatives and opioids used were midazolam (58.1%), propofol (40.5%), and sufentanil (67.5%). The cerebral monitoring devices available in the participating ICUs were transcranial Doppler ultrasound (100%), intracranial and intraventricular pressure monitoring (93.3%), and brain tissue oxygenation (60%). Cerebral monitoring by one or more monitoring devices was performed in 62% of the sedated patients. This proportion increased to 74% in the subgroup of patients with intracranial hypertension, with multimodal cerebral monitoring in 43.6%. The doses of midazolam and sufentanil were lower in sedated patients managed based on a sedation/analgesia scale. CONCLUSIONS: Midazolam and sufentanil are frequently used, often in combination, in French ICUs instead of alternative drugs. In our study, cerebral monitoring was performed in more than 60% of the sedated patients, although that proportion is still insufficient. Future efforts should stress the use of multiple monitoring modes and adherence to the indications for sedation to improve care of patients with BI. Our study suggests that the use of sedation and analgesia scales by nurses involved in the management of patients with BI could decrease the dosages of midazolam and sufentanil administered. Updated guidelines are needed for the management of sedation/analgesia in patients with BI.

Neuro-Inflammation Modulation and Post-Traumatic Brain Injury Lesions: From Bench to Bed-Side.

Head trauma is the most common cause of disability in young adults. Known as a silent epidemic, it can cause a mosaic of symptoms, whether neurological (sensory-motor deficits), psychiatric (depressive and anxiety symptoms), or somatic (vertigo, tinnitus, phosphenes). Furthermore, cranial trauma (CT) in children presents several particularities in terms of epidemiology, mechanism, and physiopathology-notably linked to the attack of an immature organ. As in adults, head trauma in children can have lifelong repercussions and can cause social and family isolation, difficulties at school, and, later, socio-professional adversity. Improving management of the pre-hospital and rehabilitation course of these patients reduces secondary morbidity and mortality, but often not without long-term disability. One hypothesized contributor to this process is chronic neuroinflammation, which could accompany primary lesions and facilitate their development into tertiary lesions. Neuroinflammation is a complex process involving different actors such as glial cells (astrocytes, microglia, oligodendrocytes), the permeability of the blood-brain barrier, excitotoxicity, production of oxygen derivatives, cytokine release, tissue damage, and neuronal death. Several studies have investigated the effect of various treatments on the neuroinflammatory response in traumatic brain injury in vitro and in animal and human models. The aim of this review is to examine the various anti-inflammatory therapies that have been implemented.

Pathomechanisms behind cognitive disorders following ruptured anterior communicating aneurysms: A diffusion tensor imaging study.

INTRODUCTION: After the rupture of anterior communicating aneurysms, most patients experience debilitating cognitive disorders; and sometimes even without showing morphological anomaly on MRI examinations. Diffusion Tensor Imaging (DTI) may help understanding the pathomechanisms leading to such disorders in this subset of patients. METHODS: After independent assessment, we constituted a population of patients with normal morphological imaging (ACOM group). Then, a case-control study comparing volumetric and voxel-based DTI parameters between the ACOM group and a control population was performed. All patients underwent the full imaging and neuropsychological assessments at 6 months after the aneurysm rupture. Results were considered significant when p<2.02.10-4. RESULTS: Twelve patients were included in the ACOM group: 75% had at least one disabled cognitive domain. Significant differences in DTI parameters of global white matter were noted (average Fractional Anisotropy: 0.915 [±0.05] in ACOM group versus 0.943 (±0.03); p = 1.10-5) and in frontal white matter tracts (superior fronto-occipital fasciculus and anterior parts of the corona radiata) as well as in the fornix. CONCLUSION: Cognitive disorders are under-estimated, and DTI confirmed that, even when conventional MRI examinations were normal, there were still signs of diffuse neuronal injuries that seemed to dominate in frontal areas, close to the site of rupture.

Outpatient vagus nerve stimulation surgery in patients with drug-resistant epilepsy with severe intellectual disability.

PURPOSE: Vagus nerve stimulation (VNS) implantation is increasingly proposed in outpatient procedure. Some epilepsy syndromes are associated with severe neurodevelopmental disabilities (intellectual disability, autism) and often motor or sensory handicaps, making ambulatory surgery more complex. METHODS: We prospectively assessed the feasibility and safety of outpatient VNS implantation in 26 adult patients with drug-resistant epilepsy with severe intellectual disability between December 2017 and October 2020. RESULTS: The male-to-female ratio was 0.9 and the mean age on surgery day was 23.1 years. Seventeen patients (65.4%) suffered from epileptic encephalopathy, 7 (26.9%) from cryptogenic or genetic generalized epilepsy, and 2 (7.7%) from severe multifocal epilepsy. Postoperatively, all patients were discharged the day of surgery. No patient was admitted to a hospital or have consulted within one month due to postoperative complications. There was no surgery-related complication during patients' follow-up. CONCLUSION: Our study highlights the safety and feasibility of VNS surgery in an outpatient setting for patients with severe intellectual disability. We report detailed protocol and preoperative checklist to optimize outpatient VNS surgery in these not able-bodied patients. Severe disabilities or epilepsy-associated handicaps should not be an exclusion criterion when considering ambulatory VNS implantation.