Serial multimodal functional brain network evaluation in children with acute disorders of consciousness, covert consciousness, and brain death: a novel demonstrative case series
Authors: Boerwinkle Varina L. , Agarwal Sonika , Sussman Bethany L. , Scher Mark S. 
Published: February 2022

Background: Although disorders of consciousness (DOC) are common manifestations after acute brain injury (ABI) in the pediatric population, there are no definitions or consensus reports regarding disorders in neonatal, pre-language children or older pediatric patients. Adult guidelines support multimodal brain network evaluations (MBNE) by functional MRI (fMRI) and EEG to diagnose DOC and covert consciousness. However, the utility in children is unknown. The feasibility and application of serial MBNE to characterize DOC in children with ABI will be discussed using illustrative case studies. Methods: MBNE was performed without sedating medications in three pediatric patients, who were hospitalized in the Phoenix Children’s Hospital pediatric ICU between April 2017 and August 2021, (2 months, 6 and 11 years of age), with ABI-DOC and outcomes described. Diagnostic studies were integrated into clinical care, including continuous video electroencephalogram, visual/somatosensory/brainstem-auditory evoked responses, developmentally appropriate active and passive task-based functional MRI (tb-fMRI), and resting state fMRI (rs-fMRI). Tb-fMRI included passive movements of the hand, passive checkerboard visual stimulation, active command to imagine moving the arm, command to move the arm, move the leg, repeat words (subvocalize), and listen for animal words in lists of common words. Results: Initial (patient 1, 2, and 3 on day 2, 19, 4) and repeat (patient 1 and 2 on day 10, 254) MBNE were performed. Initial clinical examinations included observed unarousable unconsciousness in all children. In patient 1, repeat MBNE reflected covert consciousness after treatment with antiseizure medication (day 6-10) of pathological rs-fMRI signals suggesting epileptogenicity in deep brain locations, not seen on EEG. His subsequent improvement was first detected by MBNE, then present on clinical exams later demonstrating regained consciousness, with the capacity for facial communication despite quadriplegia. Withdrawal of life sustaining therapies (WLST) was presented as a care option prior to, but not after, detection of covert consciousness in the acute period. In patient 2, MBNE showed potential for return of consciousness via intact whole brain resting state networks and abnormal rs-fMRI signal, which were treated with antiseizure medication. He had delayed repeat testing due to lack of standardized protocol at that time. He gradually recovered to full consciousness over 63 days, and near complete physical and cognitive recovery over one year, with commensurate rs-fMRI resolution of abnormal signals. WLST was considered amongst care providers, with unclear MBNE influence on the group of providers, though ultimately no formal discussion occurred with the family despite prolonged suppression of consciousness. Patient 3, the youngest, , who had no detectable networks, thus no network evidence of covert consciousness or potential for consciousness by MBNE, a day prior to succumbing to brain death. WLST was discussed with infant’s family early in the course prior to and after consistent and poor rs-fMRI results. Conclusions: Determinations to escalate therapy and continue supportive care were influenced by MBNE. Serial MBNE in children with ABI-DOC is a feasible diagnostic strategy. Potential benefits include more precise DOC endotyping, increased therapeutic options, outcome predictions and more rational withdrawal of support. Discussion of these critical care pathways will facilitate standardization of care among pediatric neurointensivists.