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The diagnosis and prognosis of disorders of consciousness (DOC) such as coma, unresponsive wakefulness syndrome, or minimally conscious state are especially challenging in children. In some paediatric patients with severe acquired brain injury, medical comorbidities or developmental factors may obscure the detection of signs of consciousness via clinical assessments, thus leading to misdiagnosis. To circumvent these biases, patients benefit from multimodal assessments that combine behavioural, neuroimaging, and neurophysiological measures. In this review, we provide original data for such diagnostic procedures in children. Neuroimaging is largely underdocumented in children and most neurophysiological research consists of a cohort study design aimed at providing prognostic markers for clinical outcomes. The scarcity of available data on complementary diagnostic approaches in children makes it difficult to establish clear paediatric guidelines. Although there is preliminary evidence for the applicability of paradigms involving event‐related potentials as support for diagnosis in children, more well‐designed studies need to be conducted to promote evidence‐based practices in paediatric DOC.

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BackgroundImproving the functional recovery of patients with DoC remains one of the greatest challenges of the field. Different theories exist about the role of the anterior (prefrontal areas) versus posterior (parietal areas) parts of the brain as hotspots for the recovery of consciousness. Repetitive transcranial magnetic stimulation (rTMS) is a powerful non-invasive brain stimulation technique for the treatment of DoC. However, a direct comparison of the effect of TMS treatment on the front versus the back of the brain has yet to be performed. In this study, we aim to assess the short- and long-term effects of frontal and parietal rTMS on DoC recovery and characterize responders phenotypically.Methods/designNinety patients with subacute and prolonged DoC will be included in a two-part multicenter prospective study. In the first phase (randomized controlled trial, RCT), patients will undergo four rTMS sessions in a crossover design over 10 days, targeting (i) the left dorsolateral prefrontal cortex (DLPFC) and (ii) the left angular gyrus (AG), as well as (iii & iv) their sham alternatives. In the second phase (longitudinal personalized trial), patients will receive personalized stimulations for 20 working days targeting the brain area that showed the best results in the RCT and will be randomly assigned to either active or sham intervention. The effects of rTMS on neurobehavioral and neurophysiological functioning in patients with DoC will be evaluated using clinical biomarkers of responsiveness (i.e., the Coma Recovery Scale-Revised; CRS-R), and electrophysiological biomarkers (e.g., power spectra, functional and effective connectivity, perturbational complexity index before and after intervention). Functional long-term outcomes will be assessed at 3 and 6 months post-intervention. Adverse events will be recorded during the treatment phase.DiscussionThis study seeks to identify which brain region (front or back) is best to stimulate for the treatment of patients with DoC using rTMS, and to characterize the neural correlates of its action regarding recovery of consciousness and functional outcome. In addition, we will define the responders’ profile based on patients’ characteristics and functional impairments; and develop biomarkers of responsiveness using EEG analysis according to the clinical responsiveness to the treatment.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04401319, Clinicaltrials.gov, n° NCT04401319.