A Precision Medicine Framework for Classifying Patients with Disorders of Consciousness: Advanced Classification of Consciousness Endotypes (ACCESS)

Abstract

Background: Consciousness in patients with brain injury is traditionally assessed based on semiological evaluation at the bedside. This classification is limited because of low granularity, ill-defined and rigid nomenclatures incompatible with the highly fluctuating nature of consciousness, failure to identify specific brain states like cognitive motor dissociation, and neglect for underlying biological mechanisms. Here, the authors present a pragmatic framework based on consciousness endotypes that combines clinical phenomenology with all essential physiological and biological data, emphasizing recovery trajectories, therapeutic potentials and clinical feasibility. Methods:The Neurocritical Care Society's Curing Coma Campaign identified an international group of experts who convened in a series of online meetings between May and November 2020 to discuss and propose a novel framework for classifying consciousness. Results:The expert group proposes Advanced Classification of Consciousness Endotypes (ACCESS), a tiered multidimensional framework reflecting increasing complexity and an aspiration to consider emerging and future approaches. Tier 1 is based on clinical phenotypes and structural imaging. Tier 2 adds functional measures including EEG, PET and functional MRI, that can be summarized using the Arousal, Volition, Cognition and Mechanisms (AVCM) score (where "Volition" signifies volitional motor responses). Finally, Tier 3 reflects dynamic changes over time with a (theoretically infinite) number of physiologically distinct states to outline consciousness recovery and identify opportunities for therapeutic interventions. Conclusions:Whereas Tiers 1 and 2 propose an approach for low-resource settings and state-of-the-art expertise at leading academic centers, respectively, Tier 3 is a visionary multidimensional consciousness paradigm driven by continuous incorporation of new knowledge while addressing the Curing Coma Campaign's aspirational goals.

Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions

“…Mechanistic biomarkers that predict a therapeutic response are also needed to improve the efficiency of clinical trials by enrolling patients whose brain networks are amenable to therapeutic modulation. This precision medicine approach will require a broad range of methodological advances, including the rigorous characterization of patient endotypes [221].…”

Coma Science: The Territory and the Map

“…2 Departments of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3 Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4 Departments of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD,…”

“…CSWG modules were given a set of objectives and a time line, and were instructed to implement a gap analysis approach; in its simplified form, the latter requires the description of a desired state and a current state, and the elaboration of a strategic pathway bridging current to desired. White *Correspondence: rstevens@jhmi.edu 1 Division of Neurosciences Critical Care, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Phipps 455, Baltimore, MD 21287, USA Full list of author information is available at the end of the article papers summarizing the findings of each module appear in this issue of the journal [3][4][5][6].…”

“…The classification and endotypes module [3] takes as a starting point the serious limitations of current semiological-or phenotype-driven nosological structures of DOC, which fail to capture critical biological and physiological processes that may be pivotal for treatment and prognosis. This failure is most powerfully demonstrated in patients who are clinically unresponsive yet retain functional magnetic resonance imaging or electroencephalographic signatures of higher-level cortical processing and are capable of reliably executing mental imagery tasks [7,8].…”

“…The discovery of this novel category of patients with covert awareness or cognitive motor dissociation, perhaps more than anything else, signals the need for a different approach. To help resolve these shortcomings, Kondziella et al [3] propose two novel and potentially complementary systems. The Advanced Classification of Consciousness Endotypes (ACCESS) framework plots consciousness states along a four-dimensional matrix that considers phenotype, brain structure, and brain function; integrates features at multiple scales from the molecular to the behavioral level; and that integrates the inherently unstable, time-dependent nature of conscious processes.…”