Prognosis and recovery trajectories in prolonged disorders of consciousness: protocol for the PDOCC 5-year prospective cohort study.

BACKGROUND: Prolonged disorders of consciousness (pDoC), encompassing vegetative state (VS) and minimally conscious state (MCS), represent a formidable clinical challenge characterized by substantial uncertainty in prognostic assessment. Although prior studies have yielded several short-term observational findings, large-scale, long-term longitudinal data delineating the 5-year natural history of pDoC remain scarce-particularly within the Chinese healthcare context. Moreover, existing studies have frequently lacked standardized multimodal assessment protocols and have failed to account for competing risks (e.g., mortality) in statistical models, thereby limiting the accuracy of currently available prognostic tools. The present study aims to address this critical evidence gap through the establishment of a high-quality prospective cohort.

METHODS: The PDOCC study is a single-center, prospective cohort investigating 5-year disease trajectories in 1,000 patients (aged 18-80) with prolonged disorders of consciousness (VS or MCS ≥ 28 days post-brain injury) (traumatic and non-traumatic etiologies) enrolled at Guangdong Sanjiu Brain Hospital. Data collection includes standardized clinical assessments (CRS-R, GOS-E, DRS, EQ-5D, SF-36), neuroimaging (MRI/DTI/fMRI), and biomarkers (NfL, GFAP, S100B). Follow-up assessments at 3, 6, 12, 24, 36, 48, and 60 months combine in-person evaluations (all timepoints) with remote telephone interviews (3-month intervals after the 6-month visit). Neuroimaging and biomarkers are assessed at baseline and at 6, 12, 24, 36, 48 and 60 months. Primary outcomes are: (1) consciousness recovery, defined as emergence from MCS (eMCS) according to the CRS-R criteria (i.e., consistent functional communication and/or functional object use) sustained for ≥4 consecutive weeks; (2) all-cause mortality; and (3) major cardiovascular events (myocardial infarction, heart failure hospitalization, stroke). Secondary outcomes include: (1) functional status changes (GOS-E, DRS); (2) dynamic biomarker changes (NfL, S100B, GFAP); (3) health-related quality of life (EQ-5D); and (4) rehospitalization rate. Time-to-event analyses will use Fine-Gray competing-risk models to account for mortality as a competing event. Prognostic prediction modeling will be conducted in three sequential stages: a clinical model, a neuroimaging-augmented model (DTI/fMRI), and a fully integrated multimodal model additionally incorporating serum biomarkers (NfL, GFAP, S100B).

DISCUSSION: The PDOCC study will generate the first comprehensive longitudinal dataset characterizing long-term (5-year) outcomes of pDoC in a southern Chinese population. Through the incorporation of competing-risk analysis and a hybrid follow-up strategy, this protocol mitigates methodological biases that are prevalent in disorders of consciousness (DoC) research. The prognostic prediction models developed are anticipated to inform individualized rehabilitation decision-making, optimize the allocation of healthcare resources, and provide a methodological framework for future multicenter collaborative investigations.

CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/bin/project/edit?pid=246240, Identifier ChiCTR2400091315.