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.

Emergency Neurological Life Support: Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a subset of stroke due to spontaneous bleeding within the parenchyma of the brain. It is potentially lethal, and survival depends on ensuring an adequate airway, proper diagnosis, and early management of several specific issues such as blood pressure, coagulopathy reversal, and surgical hematoma evacuation for appropriate patients. ICH was chosen as an Emergency Neurological Life Support (ENLS) protocol because intervention within the first hours may improve outcome, and it is critical to have site-specific protocols to drive care quickly and efficiently.

Time from onset of SIRS to antibiotic administration and outcomes after subarachnoid hemorrhage.

INTRODUCTION: The interval from presentation with systemic inflammatory response syndrome (SIRS) to the start of antibiotic administration affects mortality in patients with sepsis. However, patients with subarachnoid hemorrhage (SAH) often develop SIRS directly from their brain injury, making it a less useful indicator of infection. We therefore hypothesized that SIRS would not be a suitable trigger for antibiotics in this population. METHODS: We examined the time from the development of SIRS until antibiotic initiation and its relationship to long-term neurological outcomes in patients with nontraumatic SAH. Patients' baseline characteristics, time of antibiotic administration, and hospital course were collected from retrospective chart review. The primary outcome, 6-month functional status, was prospectively determined using blinded, structured interviews incorporating the modified Rankin Scale (mRS). RESULTS: Sixty-six of 70 patients with SAH during the study period had 6-month follow-up and were included in this analysis. SIRS developed in 57 patients (86%, 95% CI 78-95%). In ordinal logistic regression models controlling for age and illness severity, the time from SIRS onset until antibiotic initiation was not associated with 6-month mRS scores (OR per hour, 0.994; 95% CI 0.987-1.001). CONCLUSIONS: In this cohort of patients with SAH, time from SIRS onset until antibiotic administration was not related to functional outcomes. Our results indicate that SIRS is nonspecific in patients with SAH, and support the safety of withholding antibiotics in those who lack additional evidence of infection or hemodynamic deterioration.

Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference.

Subarachnoid hemorrhage (SAH) is an acute cerebrovascular event which can have devastating effects on the central nervous system as well as a profound impact on several other organs. SAH patients are routinely admitted to an intensive care unit and are cared for by a multidisciplinary team. A lack of high quality data has led to numerous approaches to management and limited guidance on choosing among them. Existing guidelines emphasize risk factors, prevention, natural history, and prevention of rebleeding, but provide limited discussion of the complex critical care issues involved in the care of SAH patients. The Neurocritical Care Society organized an international, multidisciplinary consensus conference on the critical care management of SAH to address this need. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. A jury of four experienced neurointensivists was selected for their experience in clinical investigations and development of practice guidelines. Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury. Recommendations were developed using the GRADE system. Emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice. Strong consideration was given to providing guidance and recommendations for all issues faced in the daily management of SAH patients, even in the absence of high quality data.

Dynamic, multi-level network models of clinical trials.

While networks models have often been applied to complex biological systems, they are increasingly being implemented to investigate clinical questions. Clinical trials have been studied extensively by traditional statistical methods but never, to our knowledge, using networks. We obtained data for 6,847 clinical trials from five "Nervous System Diseases" (NSD) and five "Behaviors and Mental Disorders" (BMD) from the clinicaltrials.gov registry. We constructed networks of diseases and interventions for visualization and analysis using Cytoscape software. To standardize nomenclature and enable multi-level annotation, we used MeSH and UMLS terms. We then constructed separate BMD and NSD networks to study dynamics over time. To assess how topology features related to clinical significance, we constructed a sub-network of Multiple Sclerosis and Alzheimer's trials and identified which trials had been published in high-profile medical journals. We found that the BMD network has evolved into a large, decentralized topology and does not distinctly reflect the five diseases by which it was defined, while the NSD network does, though other diseases and sub-phenotypes have emerged as areas of research. We also found that high-profile trials have distinctive network characteristics. Future work is needed to address mathematical questions such as scale-dependence of network features, clinical questions such as trial design optimization, and methodological questions such as data quality improvement.

Intracranial hemorrhage following thrombolytic use for stroke caused by infective endocarditis.

BACKGROUND AND PURPOSE: Stroke is one of the most common neurological manifestations of infective endocarditis. The use of intravenous tissue plasminogen activator (t-PA) in the management of acute ischemic stroke is the accepted standard of practice. Current guidelines for intravenous (IV) t-PA therapy in acute ischemic stroke do not exclude patients with infective endocarditis. We present three patients who received IV t-PA for acute ischemic stroke in the setting of infective endocarditis and developed multifocal intracranial hemorrhage as a complication. CONCLUSION: Infective endocarditis related strokes are associated with a higher risk of hemorrhagic complications and our experience suggests that IV t-PA use may potentiate that risk.

Predictive values of age and the Glasgow Coma Scale in traumatic brain injury patients treated with decompressive craniectomy.

BACKGROUND: The use of decompressive craniectomy (DC) as an aggressive therapy for traumatic brain injury (TBI) has gained renewed interest. While age and the Glasgow Coma Scale (GCS) are frequently correlated with outcome in TBI, their prognostic values after decompressive craniectomy are ill-defined. METHODS: We retrospectively reviewed data from 103 TBI patients treated with DC from 2001 to 2003. Age, preoperative GCS, and injury severity scores were recorded. Outcome at time of discharge was measured with the Glasgow Outcome Scale (GOS). Patients were stratified into the following age groups: < 35, 35-49, 50-64, and > or = 65 years. Spearman's correlation coefficients between age, GCS, and GOS were calculated for the entire population and each age group. FINDINGS: Mortality rates for each age group were 19.2%, 66.7%, 60%, and 80%, respectively. There was a significant negative correlation between age and GOS (r = -0.42, p < 0.0001) and patients < 35 years had significantly better outcomes than patients > or = 35 years (p < 0.0001). The overall correlation between GCS and GOS did not reach significance (r = 0.18,p = 0.076). When stratified by age, there was a significant correlation between GCS and GOS only in patients 35-49 years (r = 0.51, p = 0.011). CONCLUSIONS: This data suggests that in TBI patients treated with DC, age correlates with outcome while the correlation between GCS and outcome is age-dependent.