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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.

With the advent of advanced analytical methods applied to functional neuroimaging and neurophysiological data, cerebral conditions have been defined that challenge the established classification of disorders of consciousness. A subset of brain-damaged patients has been identified who cannot carry out motor commands, but who exhibit patterns of cerebral activation during mental imagery tasks that are indistinguishable from those in healthy controls. This condition, termed “cognitive motor dissociation,” has overturned many assumptions regarding the detection, diagnosis, prognosis, and care of patients with brain injury. Three factors are likely to influence efforts to improve the classification of disorders of consciousness in the near future: the types of data that will become available to characterize brain states, the modeling paradigms utilized for data analysis, and the ability to implement classification schemes in the clinical setting. Here we review past achievements, present states, and future projections for the classification of impaired consciousness and responsiveness.

Patients with traumatic brain injury (TBI) frequently require invasive mechanical ventilation and admission to an intensive care unit. Ventilation of patients with TBI poses unique clinical challenges, and careful attention is required to ensure that the ventilatory strategy (including selection of appropriate tidal volume, plateau pressure, and positive end-expiratory pressure) does not cause significant additional injury to the brain and lungs. Selection of ventilatory targets may be guided by principles of lung protection but with careful attention to relevant intracranial effects. In patients with TBI and concomitant acute respiratory distress syndrome (ARDS), adjunctive strategies include sedation optimization, neuromuscular blockade, recruitment maneuvers, prone positioning, and extracorporeal life support. However, these approaches have been largely extrapolated from studies in patients with ARDS and without brain injury, with limited data in patients with TBI. This narrative review will summarize the existing evidence for mechanical ventilation in patients with TBI. Relevant literature in patients with ARDS will be summarized, and where available, direct data in the TBI population will be reviewed. Next, practical strategies to optimize the delivery of mechanical ventilation and determine readiness for extubation will be reviewed. Finally, future directions for research in this evolving clinical domain will be presented, with considerations for the design of studies to address relevant knowledge gaps.

Sustained intracranial hypertension and acute brain herniation are "brain codes," signifying catastrophic neurological events that require immediate recognition and treatment to prevent irreversible injury and death. As in cardiac arrest, evidence supports the organized implementation of a stepwise management algorithm. Because there are multiple etiologies and many treatments that can potentially reverse cerebral herniation, intracranial hypertension and herniation was chosen as an Emergency Neurological Life Support (ENLS) protocol.

Coma is an acute failure of neuronal systems governing arousal and awareness and represents a neurological emergency. When encountering a comatose patient, the clinician must have an organized approach to detect easily remedial causes, prevent ongoing neurologic injury, and determine a hierarchy of diagnostic tests, treatments, and neuromonitoring. Coma was chosen as an Emergency Neurological Life Support (ENLS) protocol because timely medical and surgical interventions can be life-saving, and the initial work-up of such patients is critical to establishing a correct diagnosis.

Coma is an acute failure of neuronal systems governing arousal and awareness and represents a medical emergency. When encountering a comatose patient, the clinician must have an organized approach to detect easily remediable causes, prevent ongoing neurologic injury, and determine a hierarchical plan for diagnostic tests, treatments, and neuromonitoring. Coma was chosen as an Emergency Neurological Life Support protocol because timely medical and surgical interventions can be life-saving, and the initial work-up of such patients is critical to establishing a correct diagnosis.

Editors' Note: In WriteClick this week, authors Hannawi and Stevens respond to questions and comments about their article, “Resting brain activity in disorders of consciousness: A systematic review and meta-analysis.” Drs. Shen et al. report that they were unable to reproduce the authors' analysis using the provided settings. Drs. Garbarino and Sannita inquire whether viewing disorders of consciousness as a continuum may help explain heterogeneity in clinical measures. Author Schoenen outlines additional statistical analyses performed on the data presented in “Migraine prevention with a supraorbital transcutaneous stimulator: A randomized controlled trial.” An update related to this letter was published in the December 1, 2015, issue of Neurology® . —Megan Alcauskas, MD, and Robert C. Griggs, MD We read the article by Hannawi et al.1 on resting brain activity in disorders of consciousness. Activation likelihood estimate (ALE) meta-analysis allows the investigation of shared brain activation across individual experiments by quantitatively identifying brain locations consistently associated with different tasks or at resting state.2 When the datasets are too small for the analysis, it might not find significant convergence. The developers of GingerALE have warned that this may be the case for datasets smaller than 15 …