Stratification of unresponsive patients by an independently validated index of brain complexity

ObjectiveValidating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousnessthe Perturbational Complexity Index (PCI)in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). MethodsThe benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). ResultsWe found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. InterpretationGiven its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718-729Prin "Connage" (Italian Government)European Union (EU)James S. McDonnell Foundation Scholar AwardBelgian National Fund for Scientific ResearchTempleton World Charity FoundationMcDonnell FoundationDistinguished Chair in Consciousness Science at the University of WisconsinUniv Milan, Dept Biomed & Clin Sci L Sacco, Via GB Grassi 74, I-20157 Milan, ItalyFdn Europea Ric Biomed, Milan, ItalyUniv Milano Bicocca, Sch Med & Surg, Dept Hlth Sci, Monza, ItalyUniv Fed Sao Paulo, Inst Sci & Technol, Sao Jose Dos Campos, BrazilFdn Don Gnocchi Onlus, Ist Ricovero & Cura Carattere Sci, Milan, ItalyUniv Wisconsin, Dept Psychiat, Madison, WI 53706 USAUniv Wisconsin, Dept Neurol, Madison, WI 53706 USAUniv Liege, Coma Sci Grp, GIGA, Liege, BelgiumUniv Liege, Dept Neurol, Liege, BelgiumUniv Hosp Liege, Liege, BelgiumGrande Osped Metropolitano Niguarda Ca Granda, Neurocrit Care Unit, Azienda Sociosanit Terr, Dept Neurosci, Milan, ItalyInstitute of Science and Technology, Universidade Federal de São Paulo (UNIFESP), São José dos Campos, BrazilEU: 600806EU: 686764EU: 720270Web of Scienc