After a severe brain injury some patients survive but cannot communicate, and deciding early which of them are likely to recover consciousness remains one of the hardest problems in neurocritical care. Bedside examination alone misclassifies a substantial proportion of these patients.
CyDoC-MAP is a single-centre, prospective, observational cohort study conducted at Nicosia General Hospital, the sole trauma referral centre for Cyprus. It enrols patients aged 16 years or older who are intubated within 24 hours of a moderate-to-severe traumatic brain injury or a haemorrhagic stroke (intracerebral or subarachnoid haemorrhage), and who are subsequently classified as being in a vegetative state / unresponsive wakefulness syndrome (VS/UWS) or a minimally conscious state (MCS) on the Coma Recovery Scale-Revised (CRS-R).
Four assessment modalities are recorded: (1) the CRS-R, performed at least twice with an interval of at least 48 hours; (2) serum neuron-specific enolase (NSE) sampled within 24 hours of intubation; (3) the bispectral index (BIS), recorded at least twice with an interval of at least 48 hours, after five minutes of standardised noxious and auditory stimulation; and (4) in the traumatic subgroup only, 1.5 T magnetic resonance imaging performed 7-28 days after injury and graded 1-4 by lesion depth by two independent raters.
Level of consciousness is reassessed with the CRS-R 6 to 12 months after the index event, and the total CRS-R score (0-23) at that reassessment is the primary outcome. The primary aim is to estimate the strength of the association between the bispectral index recorded on the ward and that later CRS-R score, and to quantify what the bispectral index adds beyond the baseline clinical assessment. The number of eligible patients at a single national centre does not support the development of a prognostic model; the study is designed to produce effect-size estimates with confidence intervals that will inform a subsequent multicentre study.
The study is purely observational. No intervention is administered, no study procedure alters clinical management, and transfer to rehabilitation is never delayed for research purposes.
Age 16 years or older
Moderate-to-severe traumatic brain injury, or haemorrhagic stroke (intracerebral or subarachnoid haemorrhage)
Intubation for a reduced level of consciousness within 24 hours of the index event
Admitted to, or transferred to, Nicosia General Hospital
Severe pre-existing psychiatric disorder
History of ischaemic or haemorrhagic stroke
Pre-existing dementia
Reduction in Glasgow Coma Scale attributable to sedation or intoxicating substances
Consecutive patients aged 16 years or older admitted or transferred to Nicosia General Hospital with a disorder of consciousness following moderate-to-severe traumatic brain injury or haemorrhagic stroke, who required intubation within 24 hours of the index event and who are classified as VS/UWS or MCS on the Coma Recovery Scale-Revised.
Cohort
Prospective
Not listed
Total Coma Recovery Scale-Revised (CRS-R) score at 6-12 months
Total score on the Coma Recovery Scale-Revised at the 6-12 month reassessment, treated as a continuous variable. The CRS-R comprises six subscales (auditory, visual, motor, oromotor/verbal, communication and arousal); the total score ranges from 0 (worst) to 23 (best). The pre-specified primary analysis is the Spearman rank correlation between this score and the highest bispectral index value recorded at ward baseline, reported with a 95% confidence interval. Death before follow-up is reported separately and is not coded as a score of 0 in the primary analysis; a pre-specified sensitivity analysis assigns a value of 0 to those who died.
CRS-R diagnostic category at 6-12 months
Classification derived from the Coma Recovery Scale-Revised at follow-up as vegetative state / unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS) or emergence from the minimally conscious state (eMCS) - the clinically legible form of the primary outcome. Transitions between the ward baseline category and the follow-up category are presented descriptively, including the proportion of patients classified as VS/UWS at baseline who reach MCS or eMCS.
Serum neuron-specific enolase (NSE) - exploratory
Correlation between the serum NSE concentration (microgram/L) obtained within 24 hours of intubation and the total CRS-R score at follow-up, with a 95% confidence interval. Exploratory only: no correction for multiple comparisons is applied and no conclusion is drawn. The assay is not guaranteed in every enrolled patient, so the number of available observations is stated in every related table.
Incremental value of the bispectral index beyond the baseline clinical assessment
Incremental explained variance (delta R-squared), with a confidence interval, from a linear regression of the total CRS-R score at follow-up on two predictors only: the highest bispectral index value and the baseline total CRS-R score. No further predictor enters this model. The analysis is stated in advance to be underpowered - an incremental contribution of the order of 15% is detectable at the anticipated sample size, whereas 10% is not - and a negative result will not be interpreted as evidence of absence of effect.
MRI lesion depth grade, traumatic subgroup - exploratory
Correlation between the 1-4 lesion depth grade on 1.5 T MRI obtained 7-28 days after injury and the total CRS-R score at follow-up, in patients with traumatic brain injury (anticipated approximately 20). Exploratory only, without correction for multiple comparisons. In the non-traumatic group these data are characterised as structurally not applicable rather than missing, since MRI is performed by design only after trauma.
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