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Purpose of ReviewOver the last years, the focus of clinical and animal research in subarachnoid hemorrhage (SAH) shifted towards the early phase after the bleeding based on the association of the early injury pattern (first 72 h) with secondary complications and poor outcome. This phase is commonly referenced as early brain injury (EBI). In this clinical review, we intended to overview commonly used definitions of EBI, underlying mechanisms, and potential treatment implications.Recent FindingsWe found a large heterogeneity in the definition used for EBI comprising clinical symptoms, neuroimaging parameters, and advanced neuromonitoring techniques. Although specific treatments are currently not available, therapeutic interventions are aimed at ameliorating EBI by improving the energy/supply mismatch in the early phase after SAH.SummaryFuture research integrating brain-derived biomarkers is warranted to improve our pathophysiologic understanding of EBI in order to ameliorate early injury patterns and improve patients’ outcomes.

Magnitude of intracranial pressure (ICP) elevations and their duration have been associated with worse outcomes in patients with traumatic brain injuries (TBI), however published thresholds for injury vary and uncertainty about these levels has received relatively little attention. In this study, we have analyzed high-resolution ICP monitoring data in 227 adult patients in the CENTER-TBI dataset. Our aim was to identify thresholds of ICP intensity and duration associated with worse outcome, and to evaluate the uncertainty in any such thresholds. We present ICP intensity and duration plots to visualize the relationship between ICP events and outcome. We also introduced a novel bootstrap technique to evaluate uncertainty of the equipoise line. We found that an intensity threshold of 18 ± 4 mmHg (2 standard deviations) was associated with worse outcomes in this cohort. In contrast, the uncertainty in what duration is associated with harm was larger, and safe durations were found to be population dependent. The pressure and time dose (PTD) was also calculated as area under the curve above thresholds of ICP. A relationship between PTD and mortality could be established, as well as for unfavourable outcome. This relationship remained valid for mortality but not unfavourable outcome after adjusting for IMPACT core variables and maximum therapy intensity level. Importantly, during periods of impaired autoregulation (defined as pressure reactivity index (PRx)>0.3) ICP events were associated with worse outcomes for nearly all durations and ICP levels in this cohort and there was a stronger relationship between outcome and PTD. Whilst caution should be exercised in ascribing causation in observational analyses, these results suggest intracranial hypertension is poorly tolerated in the presence of impaired autoregulation. ICP level guidelines may need to be revised in the future taking into account cerebrovascular autoregulation status considered jointly with ICP levels.

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Purpose To assess patient characteristics associated with health-related quality of life (HR-QoL) and its mental and physical subcategories 3 months after diagnosis with COVID-19. Methods In this prospective multicentre cohort study, HR-QoL was assessed in 90 patients using the SF-36 questionnaire (36-item Short Form Health Survey), which consists of 8 health domains that can be divided into a mental and physical health component. Mental health symptoms including anxiety, depression, and post-traumatic stress disorders were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Disorder Checklist-5 (PCL-5) 3 months after COVID-19. Using descriptive statistics and multivariable regression analysis, we identified factors associated with impaired HR-QoL 3 months after COVID-19 diagnosis. Results Patients were 55 years of age (IQR, 49–63; 39% women) and were classified as severe (23%), moderate (57%), or mild (20%) according to acute disease severity. HR-QoL was impaired in 28/90 patients (31%). Younger age [per year, adjOR (95%CI) 0.94 (0.88–1.00), p  = 0.049], longer hospitalization [per day, adjOR (95%CI) 1.07 (1.01–1.13), p  = 0.015], impaired sleep [adjOR (95%CI) 5.54 (1.2–25.61), p  = 0.028], and anxiety [adjOR (95%CI) 15.67 (3.03–80.99), p  = 0.001) were independently associated with impaired HR-QoL. Twenty-nine percent ( n  = 26) scored below the normal range on the mental health component of the SF-36 and independent associations emerged for anxiety, depression, and self-reported numbness. Impairments in the physical health component of the SF-36 were reported by 12 (13%) patients and linked to hypogeusia and fatigue. Conclusion Every third patient reported a reduction in HR-QoL 3 months after COVID-19 diagnosis and impairments were more prominent in mental than physical well-being.

Lumbar puncture (LP) is recommended in patients with thunderclap headache and negative computed tomography to rule out spontaneous subarachnoid haemorrhage (SAH). Blood contamination of cerebrospinal fluid (CSF) due to traumatic LP poses a diagnostic dilemma. Therefore, routine CSF parameters were investigated to distinguish between SAH and a traumatic LP. CSF red blood cell (RBC), white blood cell (WBC) count, total protein, CSF colour and supernatant were used for group comparisons of patients with SAH and ‘symptomatic controls’. Due to variable time intervals between bleeding onset and LP in SAH patients in contrast to patients with traumatic LP, where blood contamination of CSF occurs at the time of LP, CSF variables were adjusted for decay in time to allow comparability. Logistic regression analysis identified bloody CSF [odds ratio (OR) 32.6], xanthochromic supernatant [OR 15.5] and WBC adjusted [OR 4.5 (per increase of 100/µl)] as predictors of SAH, while age, sex and CSF total protein adjusted were no predictors. Optimal cut-point of RBC adjusted (determined at day 1 after bleeding) was > 3667/µl to identify SAH patients with a 97% sensitivity and 94% specificity. Combination of low RBC and clear CSF supernatant was found in none of SAH patients. Combined CSF RBC count and CSF supernatant reliably distinguished traumatic LP from SAH.

We aimed to determine the role of the European Psychiatric Association (EPA) and the European Academy of Neurology (EAN) in the management of post-COVID conditions. This is a joint statement from the EAN and the EPA on post-COVID. It is published in the official journals of the two associations, the European Journal of Neurology and European Psychiatry .

Introduction There is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites, including the pro-inflammatory cytokine interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9), which is indicative for disruption of the blood-brain barrier. Methods Twenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes, including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed by using a generalized estimating equation with an autoregressive function. Results The baseline cerebral metabolic profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days ( P <0.001). Brain tissue hypoxia (brain tissue oxygen tension of less than 20 mm Hg) was common (more than 60% of patients) in the first 24 hours of neuromonitoring and improved thereafter ( P <0.05). Baseline CMD-IL-6 and CMD-MMP-9 levels were elevated in all patients (median = 4,059 pg/mL, interquartile range (IQR) = 1,316 to 12,456 pg/mL and median = 851 pg/mL, IQR = 98 to 25,860 pg/mL) and significantly decreased over days ( P <0.05). A higher pro-inflammatory response was associated with the development of delayed cerebral ischemia ( P  = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels ( P <0.03). Brain metabolic distress and increased IL-6 levels were associated with poor functional outcome (modified Rankin Scale of more than 3, P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure, and disease severity as appropriate. Conclusions Multimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting EBI in poor-grade aSAH patients.

Little is known regarding the prevalence and predictors of prolonged cognitive and psychological symptoms of COVID-19 among community-dwellers. We aimed to quantitatively measure self-reported metrics of fatigue, cognitive dysfunction, anxiety, depression, and sleep and identify factors associated with these metrics among United States residents with or without COVID-19. We solicited 1000 adult United States residents for an online survey conducted February 3-5, 2021 utilizing a commercial crowdsourcing community research platform. The platform curates eligible participants to approximate United States demographics by age, sex, and race proportions. COVID-19 was diagnosed by laboratory testing and/or by exposure to a known positive contact with subsequent typical symptoms. Prolonged COVID-19 was self-reported and coded for those with symptoms ≥ 1 month following initial diagnosis. The primary outcomes were NIH PROMIS/Neuro-QoL short-form T-scores for fatigue, cognitive dysfunction, anxiety, depression, and sleep compared among those with prolonged COVID-19 symptoms, COVID-19 without prolonged symptoms and COVID-19 negative subjects. Multivariable backwards step-wise logistic regression models were constructed to predict abnormal Neuro-QoL metrics. Among 999 respondents, the average age was 45 years (range 18-84), 49% were male, 76 (7.6%) had a history of COVID-19 and 19/76 (25%) COVID-19 positive participants reported prolonged symptoms lasting a median of 4 months (range 1-13). Prolonged COVID-19 participants were more often younger, female, Hispanic, and had a history of depression/mood/thought disorder (all < 0.05). They experienced significantly higher rates of unemployment and financial insecurity, and their symptoms created greater interference with work and household activities compared to other COVID-19 status groups (all < 0.05). After adjusting for demographics, past medical history and stressor covariates in multivariable logistic regression analysis, COVID-19 status was independently predictive of worse Neuro-QoL cognitive dysfunction scores (adjusted OR 11.52, 95% CI 1.01-2.28, = 0.047), but there were no significant differences in quantitative measures of anxiety, depression, fatigue, or sleep. Prolonged symptoms occurred in 25% of COVID-19 positive participants, and NeuroQoL cognitive dysfunction scores were significantly worse among COVID-19 positive subjects, even after accounting for demographic and stressor covariates. Fatigue, anxiety, depression, and sleep scores did not differ between COVID-19 positive and negative respondents.

Background and purpose Cerebral sinus venous thrombosis (CSVT) is a rare but life-threatening disease and its diagnosis remains challenging. Blood biomarkers, including D-Dimer are currently not recommended in guidelines. Soluble endothelial receptor proteins (sICAM-1, sPECAM-1 and sVCAM-1) have been shown to be promising diagnostic biomarkers in deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, we examined endothelial receptor proteins as potential biomarkers for detecting CSVT. Methods In this bi-centre, prospective study, we quantified D-Dimer as well as sICAM-1, sPECAM-1 and sVCAM-1 in plasma of patients with clinically suspected CSVT managed in the neurological emergency department (ED) of a tertiary care hospital. All patients underwent cerebral magnetic resonance imaging (MRI) and were followed up after 3, 6 and 12 months to detect thrombus resolution. Results Twenty-four out of 75 (32%) patients with clinically suspected CSVT presenting with headache to the ED were diagnosed with acute CSVT. These patients had a mean age of 45 ± 16 years and 78% were female. In patients with CSVT, mean baseline D-dimer ( p  < 0.001) and sPECAM-1 ( p  < 0.001) were significantly higher compared to patients without CSVT. The combination of D-Dimer and sPECAM-1 yielded the best ROC-AUC (0.994; < 0.001) with a negative predictive value of 95.7% and a positive predictive value of 95.5%. In addition, higher baseline sPECAM-1 levels (> 198 ng/ml) on admission were associated with delayed venous thrombus resolution at 3 months (AUC = 0.83). Conclusion sPECAM-1 in combination with D-Dimer should be used to improve the diagnostic accuracy of acute CSVT and sPECAM-1 may predict long-term outcome of CSVT. Confirmatory results are needed in other settings in order to show their value in the management concept of CSVT patients.