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The Society of Neurocritical Care has launched a new campaign to encourage research that enables clinicians to better understand not only acute coma but also disorders of consciousness broadly, including patients with altered consciousness. Efforts will also focus on better understanding the anatomical and physiological commonalities across disorders.

In response to huge gaps in the way patients in a coma with disorders of consciousness (DoC) are treated, the Scientific Advisory Council of the Neurocritical Care Society (NCS) has initiated an ambitious initiative, the Curing Coma Campaign, to identify critical areas of research and treatment protocols.

The campaign, described in an August paper in Neurocritical Care, identified three major pillarsthe identification of endotypes, development of biomarkers, and initiation of proof-of-concept trialsas essential to a grand effort that NCS leaders are likening to a moonshot. The campaign aims to jump start research but also to expand the curing coma community to ensure broad participation of clinicians, scientists, and patient advocates with the goal of developing treatments to improve the outcome of patients.

The way we treat coma and disorders of consciousness has not been sufficient, and there are huge gaps in our understanding and in the way, we are caring for patients, said J. Claude Hemphill, MD, FAAN, professor of neurology at the University of California, San Francisco, a lead author of the paper.

We know this is not going to be easy. It's a grand challenge, and it will not be quick. We have set out a ten-year scientific road map recognizing that advances will come incrementally over time.

Dr. Hemphill emphasized that the campaign is aimed at better understanding not only acute coma but also disorders of consciousness broadly, encompassing patients with altered consciousness that may be less complete than coma. And the campaign aims to move beyond the traditional focus on disease-specific DoCcardiac arrest, traumatic brain injury, brainstem stroketo better understand the anatomical and physiological commonalities across disorders.

We have had a lot of failed clinical trials in neurocritical care using a one-size-fits-all approach, Dr. Hemphill said. Instead of saying, `let's study this treatment or clinical approach for this disease-related DoC,' we need to step back and try to understand the fundamental underpinning of all DoC.

Toward that end, The Curing Coma Campaign Scientific Advisory Committee met for the first time in person during the NCS Annual Meeting in Vancouver in October 2019, where the council outlined three overarching, interrelated areas of research necessary to move the field forward: 1) endotypingdeveloping a better understanding of the different types of coma, 2) biomarkersevaluating current tools and their shortcomings in understanding coma and its prognosis, and developing new biomarkers that accurately determine DOC endotypes, and 3) proof-of-concept clinical trialsidentifying early interventional studies to evaluate new treatment protocols and inform clinical trial design.

Dr. Hemphill said the campaign grew out of a 2017 strategic planning meeting of the NCS looking at what they referred to as blue-ocean endeavorsthose research and treatment areas that are under-investigated but which are high-priority because they cut across all of the disorders treated by neurocritical care experts.

It was very clear that the biggest problem we face in neurocritical care is the care of coma and DoC, he said. We deliberately framed the campaign as a grand challenge that would galvanize people across the field to come together and participate.

Dr. Hemphill said the Curing Coma Campaign is not restricted to researchers but actively solicits the participation of the entire community of clinicians, hospitals and health systemsas well as patients and familiesinvolved in neurocritical care. He noted that in September, the National Institutes of Health and the National Institute of Neurological Disorders and Stroke sponsored a two-day virtual symposium on neurocritical care of DOC. Additionally, NCS is sponsoring World Coma Day on March 22, 2021. He urged researchers, clinicians, and families to visit the Curing Coma Campaign website: https://www.curingcoma.org/home.

The campaign is also sponsoring a survey of clinicians involved in neurocritical carehttps://www.curingcoma.org/research/come-togetherdesigned to inform the coma scientific community about current prevailing concepts of coma and assess the spectrum of practice variability.

In order for the campaign to be successful, it requires a fundamental change in the understanding of coma, and for this, we need to leverage the wider community to participate, Dr. Hemphill told Neurology Today.

He said the ambitiousness of the campaign goals reflects an urgency felt by families and clinicians when a patient with DOC is in the neurocritical care unit: Will they wake up? Can they wake up? What can be done to help them wake up?

The gaps in understating of coma result often in a self-fulfilling prophesy of poor outcomes. There is probably not a single neurocritical care provider who doesn't have a dramatic story of a patient who they thought would never wake up, but after aggressive treatment recovered and did, he said. The problem is that currently, it is very challenging to identify at the time who those patients are going to be.

Experts who reviewed the paper for Neurology Today said the campaign is extraordinary in its visionand long overdue. We are not good at neuro-prognostication, said Gunjan Parikh, MD, associate medical director of the division of neurocritical care and emergency neurology at the University of Maryland.

Care withdrawal based on inadequate data persists, he said. Diagnostic error and misclassification of coma recovery potential in the ICU phase of care remain alarmingly high. Clinical consensus by the medical team after review of imprecise testing remains the primary means by which DoC diagnosis is made.

Dr. Parikh added that the agenda of the campaign is realistic and attainable but will require NCS to partner with public and private organizations already involved in the ongoing NIH BRAIN Initiative. Mapping the brain circuitry underlying consciousness is far more complex and open-ended than mapping the genome, he said. Localized neural circuits can involve one million cells in a complex, recursive network; however, consciousness is an emergent property of a more complex, distributed network of interconnected neural circuitry.

Shraddha Mainali, MD, assistant professor of clinical neurology at Ohio State University, said she believes the goal is ambitious, but not impossible. The authors have rightly pointed out the existing barriers in advancing coma science, she said.

Existing clinical classification of disorders of consciousness does not address distinctions based on underlying biological/pathophysiological mechanisms or functional/anatomical integrity of neural pathways necessary to maintain consciousness, Dr. Mainali added.

We lack biomarkers that can accurately assess severity, functional integrity and related connectivity (or lack thereof) of neural networks. Of the available tools to detect biomarkers, several are not easily available and are difficult to administer in the acute ICU setting. Such limitations in biomarkers and endotyping of individual patients have made it difficult to develop clinical trials in the acute phase of the disease.

Dr. Mainali added that there is wide variability in management, including practice regarding the withdrawal of care of patients with DOC, which accounts for a large proportion of deaths in this population.

The lack of precise biomarkers and prognostic models has led to such variability, as individual treating teams are obligated to come up with their own best estimate of disease severity and prognosis.

Dr. Parikh said a necessary first step is more widespread adoption of validated behavioral assessments in the acute phase. Sufficient behavioral sampling with serial examination after maximal arousal and accounting for all ICU confounders is paramount for progress, he said. Collaboration between intensivists, rehab specialists and physical therapists during the acute ICU phase is key for tracking the progress of arousal potential, whether in the neuro ICU, cardiothoracic ICU or medical ICU.

What are the implications for individual clinicians? A working understanding of bedside decision-support tools leveraging computational workflows that continuously improve coma recovery prediction models, based on real-time ICU data streams in individual patients, will become routine and a part of the competency assessment of future trainees, Dr. Parikh said.

Dr. Hemphill said he is hopeful that the complete net cast by the Curing Coma Campaign will ultimately make this moonshot successful. Some of the advances are going to be from scientific advances, but others from the community coming together and thinking about how to improve care right now with this patientbeing careful about prognostication and targeting aggressive therapies. Advances will also come from educating clinicians about the ability of patients to recover and families about what is and is not possible.

Drs. Hemphill, Parikh, and Mainali had no relevant disclosures.

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