Evan S Lutkenhoff1, Jeffrey Chiang1, Luaba Tshibanda2, Evelyn Kamau3, Murielle Kirsch2,4, John D Pickard3, Steven Laureys2, Adrian M Owen5, Martin M Monti1,6. 1. Department of Psychology, University of California, Los Angeles, Los Angeles, CA. 2. Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium. 3. Division of Neurosurgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom. 4. Department of Anesthesia and Intensive Care Medicine, Liège University Hospital, Liège, Belgium. 5. Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada. 6. Brain Injury Research Center, Department of Neurosurgery, Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
Abstract
OBJECTIVE: What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. METHODS: Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. RESULTS: Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. INTERPRETATION: These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.
OBJECTIVE: What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. METHODS: Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. RESULTS: Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. INTERPRETATION: These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.
Authors: Caroline Schnakers; Evan S Lutkenhoff; Branden J Bio; David L McArthur; Paul M Vespa; Martin M Monti Journal: J Neurol Neurosurg Psychiatry Date: 2018-06-28 Impact factor: 10.154
Authors: John C O'Donnell; Kevin D Browne; Todd J Kilbaugh; H Isaac Chen; John Whyte; D Kacy Cullen Journal: Neurosci Biobehav Rev Date: 2018-12-11 Impact factor: 8.989
Authors: Evan S Lutkenhoff; Vikesh Shrestha; Jesus Ruiz Tejeda; Courtney Real; David L McArthur; Dominique Duncan; Marianna La Rocca; Rachael Garner; Arthur W Toga; Paul M Vespa; Martin M Monti Journal: J Neurol Neurosurg Psychiatry Date: 2020-08-26 Impact factor: 10.154