title: Stratification of unresponsive patients by an independently validated index of brain complexity.
abstract: OBJECTIVE
  Validating 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 consciousness-the 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).
  
  
  METHODS
  The 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]).
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Given 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;80:718-729.
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Silvia
authors.identifier: http://orcid.org/0000-0002-7548-7664
authors.initials: S
authors.lastname: Casarotto
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Comanducci
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.|Fondazione Europea per la Ricerca Biomedica, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rosanova
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Sarasso
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fecchio
authors.affiliation: Department of Health Science, School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Napolitani
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pigorini
authors.affiliation: Institute of Science and Technology, Federal University of São Paulo, São José dos Campos, Brazil.
authors.forename: Adenauer
authors.initials: A
authors.lastname: G Casali
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Don Gnocchi Onlus, Milan, Italy.
authors.forename: Pietro D
authors.initials: PD
authors.lastname: Trimarchi
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison, WI, USA.|Department of Neurology, University of Wisconsin, Madison, WI, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Boly
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison, WI, USA.|Coma Science Group, GIGA, University of Liège, Liège, Belgium.
authors.forename: Olivia
authors.initials: O
authors.lastname: Gosseries
authors.affiliation: Coma Science Group, GIGA, University of Liège, Liège, Belgium.|Department of Neurology, University of Liège and University Hospital of Liège, Liège, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bodart
authors.affiliation: Neurocritical Care Unit, Department of Neuroscience, Azienda Socio-Sanitaria Territoriale, Grande Ospedale Metropolitano Niguarda Cà Granda, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Curto
authors.affiliation: Fondazione Europea per la Ricerca Biomedica, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Landi
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mariotti
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Don Gnocchi Onlus, Milan, Italy.
authors.forename: Guya
authors.initials: G
authors.lastname: Devalle
authors.affiliation: Coma Science Group, GIGA, University of Liège, Liège, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Laureys
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison, WI, USA.
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.|Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Don Gnocchi Onlus, Milan, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Massimini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001930:Brain Injuries / Q000150:complications / Q000175:diagnosis*; D002540:Cerebral Cortex / Q000503:physiopathology*; D003244:Consciousness Disorders / Q000145:classification / Q000175:diagnosis* / Q000209:etiology; D004569:Electroencephalography / Q000379:methods*; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D015599:Trauma Severity Indices; D055815:Young Adult