Resting-State EEG Signature of Early Consciousness Recovery in Comatose Patients with Traumatic Brain Injury.

BACKGROUND: Resting-state electroencephalography (rsEEG) is usually obtained to assess seizures in comatose patients with traumatic brain injury (TBI). We aim to investigate rsEEG measures and their prediction of early recovery of consciousness in patients with TBI. METHODS: This is a retrospective study of comatose patients with TBI who were admitted to a trauma center (October 2013 to January 2022). Demographics, basic clinical data, imaging characteristics, and EEGs were collected. We calculated the following using 10-min rsEEGs: power spectral density, permutation entropy (complexity measure), weighted symbolic mutual information (wSMI, global information sharing measure), Kolmogorov complexity (Kolcom, complexity measure), and heart-evoked potentials (the averaged EEG signal relative to the corresponding QRS complex on electrocardiography). We evaluated the prediction of consciousness recovery before hospital discharge using clinical, imaging, and rsEEG data via a support vector machine. RESULTS: We studied 113 of 134 (84%) patients with rsEEGs. A total of 73 (65%) patients recovered consciousness before discharge. Patients who recovered consciousness were younger (40 vs. 50 years, p = 0.01). Patients who recovered also had higher Kolcom (U = 1688, p = 0.01), increased beta power (U = 1,652 p = 0.003) with higher variability across channels (U = 1534, p = 0.034) and epochs (U = 1711, p = 0.004), lower delta power (U = 981, p = 0.04), and higher connectivity across time and channels as measured by wSMI in the theta band (U = 1636, p = 0.026; U = 1639, p = 0.024) than those who did not recover. The area under the receiver operating characteristic curve for rsEEG was higher than that for clinical data (using age, motor response, pupil reactivity) and higher than that for the Marshall computed tomography classification (0.69 vs. 0.66 vs. 0.56, respectively; p < 0.001). CONCLUSIONS: We describe the rsEEG signature in recovery of consciousness prior to discharge in comatose patients with TBI. rsEEG measures performed modestly better than the clinical and imaging data in predicting recovery.

Practice Standards for the Use of Multimodality Neuromonitoring: A Delphi Consensus Process.

OBJECTIVES: To address areas in which there is no consensus for the technologies, effort, and training necessary to integrate and interpret information from multimodality neuromonitoring (MNM). DESIGN: A three-round Delphi consensus process. SETTING: Electronic surveys and virtual meeting. SUBJECTS: Participants with broad MNM expertise from adult and pediatric intensive care backgrounds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two rounds of surveys were completed followed by a virtual meeting to resolve areas without consensus and a final survey to conclude the Delphi process. With 35 participants consensus was achieved on 49% statements concerning MNM. Neurologic impairment and the potential for MNM to guide management were important clinical considerations. Experts reached consensus for the use of MNM-both invasive and noninvasive-for patients in coma with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial hemorrhage. There was consensus that effort to integrate and interpret MNM requires time independent of daily clinical duties, along with specific skills and expertise. Consensus was reached that training and educational platforms are necessary to develop this expertise and to provide clinical correlation. CONCLUSIONS: We provide expert consensus in the clinical considerations, minimum necessary technologies, implementation, and training/education to provide practice standards for the use of MNM to individualize clinical care.

Posttraumatic Stress Symptoms Among COVID-19 Survivors After Hospitalization.

OBJECTIVE: Limited data are available on posttraumatic stress symptoms (PTSS) among COVID-19 survivors. This study aimed to contribute to this knowledge base. METHODS: PTSS among COVID-19 survivors who had been hospitalized were investigated. Patients were identified as COVID-19 positive at hospital admission. COVID-19 survivors were surveyed with the Posttraumatic Stress Disorder Checklist (PCL-5) between March and October 2020 at 5- and 12-month postdischarge follow-up points. RESULTS: Of 411 patients, 331 (81%) survived to hospital discharge. Of these survivors, 83 (25%) completed the PCL-5 at the 5-month follow-up. Of those patients, 12 (14%) screened positive for PTSS. At the 12-month follow-up, four of eight patients remained PTSS positive. Mean age of follow-up participants was 62±15 years; 47% were women, 65% were White, and 63% were Hispanic. PTSS-positive patients were predominantly non-White (67% vs. 30%, p=0.02), and although the differences were not statistically significant, these patients tended to be younger (56 vs. 63 years, p=0.08) and have shorter intensive care unit stays (2.0 vs. 12.5 days, p=0.06). PTSS-positive and PTSS-negative groups did not differ significantly in prehospitalization neurological diagnoses (11% vs. 8%), psychiatric diagnoses (17% vs. 21%), and intensive care admission status (25% vs. 25%). More patients in the PTSS-positive group had returned to the emergency department (50% vs. 14%, p<0.01) and reported fatigue at follow-up (100% vs. 42%, p<0.001). In the multivariate logistic regression model, non-White race (OR=11, 95% CI=2-91) and returning to the emergency department (OR=19, 95% CI=3-252) were associated with PTSS-positive status. CONCLUSION: PTSS were twice as common among hospitalized COVID-19 survivors than among those in the general population.

Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness.

This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

Withdrawal of Life-Sustaining Treatment Mediates Mortality in Patients With Intracerebral Hemorrhage With Impaired Consciousness.

BACKGROUND AND PURPOSE: Impaired level of consciousness (LOC) on presentation at hospital admission in patients with intracerebral hemorrhage (ICH) may affect outcomes and the decision to withhold or withdraw life-sustaining treatment (WOLST). METHODS: Patients with ICH were included across 121 Florida hospitals participating in the Florida Stroke Registry from 2010 to 2019. We studied the effect of LOC on presentation on in-hospital mortality (primary outcome), WOLST, ambulation status on discharge, hospital length of stay, and discharge disposition. RESULTS: Among 37 613 cases with ICH (mean age 71, 46% women, 61% White, 20% Black, 15% Hispanic), 12 272 (33%) had impaired LOC at onset. Compared with cases with preserved LOC, patients with impaired LOC were older (72 versus 70 years), more women (49% versus 45%), more likely to have aphasia (38% versus 16%), had greater ICH score (3 versus 1), greater risk of WOLST (41% versus 18%), and had an increased in-hospital mortality (32% versus 12%). In the multivariable-logistic regression with generalized estimating equations accounting for basic demographics, comorbidities, ICH severity, hospital size and teaching status, impaired LOC was associated with greater mortality (odds ratio, 3.7 [95% CI, 3.1-4.3], P<0.0001) and less likely discharged home or to rehab (odds ratio, 0.3 [95% CI, 0.3-0.4], P<0.0001). WOLST significantly mediated the effect of impaired LOC on mortality (mediation effect, 190 [95% CI, 152-229], P<0.0001). Early WOLST (<2 days) occurred among 51% of patients. A reduction in early WOLST was observed in patients with impaired LOC after the 2015 American Heart Association/American Stroke Association ICH guidelines recommending aggressive treatment and against early do-not-resuscitate. CONCLUSIONS: In this large multicenter stroke registry, a third of ICH cases presented with impaired LOC. Impaired LOC was associated with greater in-hospital mortality and worse disposition at discharge, largely influenced by early decision to withhold or WOLST.

Effect of Race-Ethnicity and CT Angiography on Renal Injury During Blood Pressure Treatment for Intracerebral Hemorrhage.

BACKGROUND: Lowering blood pressure intensively in acute intracerebral hemorrhage (ICH) is associated with adverse renal events; Blacks and Hispanics have a higher incidence of ICH and kidney disease than Whites. In addition, CT angiography (CTA), which may also be associated with acute kidney injury (AKI), is often done in acute ICH. Our objective was to investigate the relationship between aggressive BP management, CTA, race-ethnicity and the risk of developing AKI in patients presenting with ICH. METHODS: We retrospectively calculated the difference between the highest and lowest systolic blood pressure during the first 24 h of admission in patients with spontaneous ICH over 30 months. Creatinine (Cr) levels at admission were compared to the highest Cr level during the first 7 days after admission. AKI was defined as any > 50% increase of baseline Cr during the first 7 days. Logistic regression models were used to assess the association between race-ethnicity and CTA and AKI. We also analyzed the incidence of AKI stratified by race-ethnicity. RESULTS: A total of 394 patients were included (mean age ± SD 63 ± 14 years), 160 patients (41%) were women, 162 (41%) Hispanic, 39 (10%) White and 189 (48%) Black. Most of the patients underwent CTA (73%). The prevalence of AKI was (18%), but no difference was found in AKI incidence (19% in Blacks vs. 17% in Whites vs. 18% in Hispanics (p = 0.940). In fully adjusted models, AKI was not associated with race-ethnicity (p = 0.665) or CTA (p = 0.187). The stratified analysis by race-ethnicity did not change our findings. CONCLUSION: We found no association between race-ethnicity or CTA and AKI during the acute management of ICH in a real-life stroke population. Our findings suggest that CTA can be safely obtained in acute ICH, even in populations of diverse race-ethnicity who may be more prone to adverse kidney events. CTA did not contribute to developing AKI.

What is the Role of Hyperosmolar Therapy in Hemispheric Stroke Patients?

The role of hyperosmolar therapy (HT) in large hemispheric ischemic or hemorrhagic strokes remains a controversial issue. Past and current stroke guidelines state that it represents a reasonable therapeutic measure for patients with either neurological deterioration or intracranial pressure (ICP) elevations documented by ICP monitoring. However, the lack of evidence for a clear effect of this therapy on radiological tissue shifts and clinical outcomes produces uncertainty with respect to the appropriateness of its implementation and duration in the context of radiological mass effect without clinical correlates of neurological decline or documented elevated ICP. In addition, limited data suggest a theoretical potential for harm from the prophylactic and protracted use of HT in the setting of large hemispheric lesions. HT exerts effects on parenchymal volume, cerebral blood volume and cerebral perfusion pressure which may ameliorate global ICP elevation and cerebral blood flow; nevertheless, it also holds theoretical potential for aggravating tissue shifts promoted by significant interhemispheric ICP gradients that may arise in the setting of a large unilateral supratentorial mass lesion. The purpose of this article is to review the literature in order to shed light on the effects of HT on brain tissue shifts and clinical outcome in the context of large hemispheric strokes, as well as elucidate when HT should be initiated and when it should be avoided.

Blood Pressure after Endovascular Therapy for Ischemic Stroke (BEST): A Multicenter Prospective Cohort Study.

Background and Purpose- To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan. Methods- Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0-2 versus 3-6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression. Results- Among 485 enrolled patients (median age, 69 [interquartile range, 57-79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52-3.29], P<0.01; adjusted odds ratio, 1.29 [0.81-2.06], P=0.28, after adjustment for prespecified variables). Conclusions- A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.

The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol.

The Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy (EpiBioS4Rx) is a longitudinal prospective observational study funded by the National Institute of Health (NIH) to discover and validate observational biomarkers of epileptogenesis after traumatic brain injury (TBI). A multidisciplinary approach has been incorporated to investigate acute electrical, neuroanatomical, and blood biomarkers after TBI that may predict the development of post-traumatic epilepsy (PTE). We plan to enroll 300 moderate-severe TBI patients with a frontal and/or temporal lobe hemorrhagic contusion. Acute evaluation with blood, imaging and electroencephalographic monitoring will be performed and then patients will be tracked for 2 years to determine the incidence of PTE. Validation of selected biomarkers that are discovered in planned animal models will be a principal feature of this work. Specific hypotheses regarding the discovery of biomarkers have been set forth in this study. An international cohort of 13 centers spanning 2 continents will be developed to facilitate this study, and for future interventional studies.

Emergency Neurologic Life Support: Spinal Cord Compression.

There are many causes of acute myelopathy including multiple sclerosis, systemic disease, and acute spinal cord compression (SCC). SCC should be among the first potential causes considered given the significant permanent loss of neurologic function commonly associated with SCC. This impairment can occur over a short period of time, and may be avoided through rapid and acute surgical intervention. Patients with SCC typically present with a combination of motor and sensory dysfunction that has a distribution referable to a spinal level. Bowel and bladder dysfunction and neck or back pain may also be part of the clinical presentation, but are not uniformly present. Because interventions are critically time-sensitive, the recognition and treatment of SCC was chosen as an ENLS protocol.

Emergency Neurological Life Support: Third Edition, Updates in the Approach to Early Management of a Neurological Emergency.

Emergency Neurologic Life Support (ENLS) is an educational program designed to provide users advisory instructions regarding management for the first few hours of a neurologic emergency. The content of the course is divided into 14 modules, each addressing a distinct category of neurological injury. The course is appropriate for practitioners and providers from various backgrounds who work in environments of variable medical complexity. The focus of ENLS is centered on a standardized treatment algorithm, checklists, to guide early patient care, and a structured format for communication of findings and concerns to other healthcare professionals. Certification and training in ENLS is hosted by the Neurocritical Care Society. This document introduces the concept of ENLS and describes revisions that constitute the third version.

Regional brain monitoring in the neurocritical care unit.

Regional multimodality monitoring has evolved over the last several years as a tool to understand the mechanisms of brain injury and brain function at the cellular level. Multimodality monitoring offers an important augmentation to the clinical exam and is especially useful in comatose neurocritical care patients. Cerebral microdialysis, brain tissue oxygen monitoring, and cerebral blood flow monitoring all offer insight into permutations in brain chemistry and function that occur in the context of brain injury. These tools may allow for development of individual therapeutic strategies that are mechanistically driven and goal-directed. We present a summary of the discussions that took place during the Second Neurocritical Care Research Conference regarding regional brain monitoring.

Global monitoring in the neurocritical care unit.

Effective methods of monitoring the status of patients with neurological injuries began with non-invasive observations and evolved during the past several decades to include more invasive monitoring tools and physiologic measures. The monitoring paradigm continues to evolve, this time back toward the use of less invasive tools. In parallel, the science of monitoring began with the global assessment of the patient's neurological condition, evolved to focus on regional monitoring techniques, and with the advent of enhanced computing capabilities is now moving back to focus on global monitoring. The purpose of this session of the Second Neurocritical Care Research Conference was to collaboratively develop a comprehensive understanding of the state of the science for global brain monitoring and to identify research priorities for intracranial pressure monitoring, neuroimaging, and neuro-electrophysiology monitoring.

International multidisciplinary consensus conference on multimodality monitoring: cerebral metabolism.

Microdialysis is a powerful technique, which enables the chemistry of the extracellular space to be measured directly. Applying this technique to patients in neurointensive care has increased our understanding of the pathophysiology of traumatic brain injury and spontaneous hemorrhage. In parallel, it is important to determine the place of microdialysis in assisting in the management of patients on an individual intention to treat basis. This is made possible by the availability of analyzers which can measure the concentration of glucose, pyruvate, lactate, and glutamate at the bedside. Samples can then be stored for later analysis of other substrate and metabolites e.g., other amino acids and cytokines. The objective of this paper is to review the fundamental literature pertinent to the clinical application of microdialysis in neurointensive care and to give recommendations on how the technique can be applied to assist in patient management and contribute to outcome. A literature search detected 1,933 publications of which 55 were used for data abstraction and analysis. The role of microdialysis was evaluated in three conditions (traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage) and recommendations focused on three fundamental areas (relationship to outcome, application of microdialysis to guide therapy, and the ability of microdialysis to predict secondary deterioration).

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

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.

The International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: evidentiary tables: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.