Multimodal Assessment and Prognosis in Disorders of Consciousness After Severe Brain Injury (CyDoC-MAP)

NCT07736820 | Not Yet Recruiting

• 2 other identifiers: CyDoC-MAP-2025-47EEBK/EP 2025/47
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Consciousness Disorders; Persistent Vegetative State; Unresponsive Wakefulness Syndrome; Minimally Conscious State; Coma; Prolonged; Brain Injuries, Traumatic; Cerebral Hemorrhage; Subarachnoid Hemorrhage

Keywords

cognitive motor dissociation; covert consciousness; Coma Recovery Scale-Revised; bispectral index; neuron-specific enolase; multimodal prognostication; neurocritical care; Cyprus

Outcome Measures

Primary Outcomes (1)

• 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.

  6 to 12 months after the index event

Secondary Outcomes (6)

• CRS-R diagnostic category at 6-12 months

  Ward baseline to 6-12 months

• Serum neuron-specific enolase (NSE) - exploratory

  Within 24 hours of intubation to 6-12 months

• Incremental value of the bispectral index beyond the baseline clinical assessment

  Ward baseline to 6-12 months

• MRI lesion depth grade, traumatic subgroup - exploratory

  7-28 days after injury to 6-12 months

• Anatomical distribution of MRI lesions - descriptive only

  7-28 days after injury to 6-12 months

Study Arms (2)

VS/UWS

Patients classified as being in a vegetative state / unresponsive wakefulness syndrome on the Coma Recovery Scale-Revised at ward baseline.

MCS

Patients classified as being in a minimally conscious state (MCS- or MCS+) on the Coma Recovery Scale-Revised at ward baseline.

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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
• Classified as VS/UWS or MCS on the Coma Recovery Scale-Revised after discharge from the intensive care unit
• Written informed consent obtained from the next of kin (and from a legal guardian for participants aged 16-17)

You may not qualify if:

• 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
• Reduction in Glasgow Coma Scale attributable to severe extracranial injury (massive haemorrhage, generalised hypoxia)
• End-stage disease with a life expectancy of less than 6 months

Sponsors & Collaborators

• Nicosia General Hospital: lead

Study Sites (1)

Nicosia General Hospital, Department of Neurosurgery

Nicosia, 2029, Cyprus

Location

Related Publications (5)

• Kondziella D. The Gray Zone of Consciousness: Cognitive Motor Dissociation. Curr Neurol Neurosci Rep. 2025 Jul 18;25(1):49. doi: 10.1007/s11910-025-01438-2.

  PMID: 40679720 BACKGROUND

• Bodien YG, Allanson J, Cardone P, Bonhomme A, Carmona J, Chatelle C, Chennu S, Conte M, Dehaene S, Finoia P, Heinonen G, Hersh JE, Kamau E, Lawrence PK, Lupson VC, Meydan A, Rohaut B, Sanders WR, Sitt JD, Soddu A, Valente M, Velazquez A, Voss HU, Vrosgou A, Claassen J, Edlow BL, Fins JJ, Gosseries O, Laureys S, Menon D, Naccache L, Owen AM, Pickard J, Stamatakis EA, Thibaut A, Victor JD, Giacino JT, Bagiella E, Schiff ND. Cognitive Motor Dissociation in Disorders of Consciousness. N Engl J Med. 2024 Aug 15;391(7):598-608. doi: 10.1056/NEJMoa2400645.

  PMID: 39141852 BACKGROUND

• Schnakers C, Ledoux D, Majerus S, Damas P, Damas F, Lambermont B, Lamy M, Boly M, Vanhaudenhuyse A, Moonen G, Laureys S. Diagnostic and prognostic use of bispectral index in coma, vegetative state and related disorders. Brain Inj. 2008 Nov;22(12):926-31. doi: 10.1080/02699050802530565.

  PMID: 19005884 BACKGROUND

• Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science. 2006 Sep 8;313(5792):1402. doi: 10.1126/science.1130197.

  PMID: 16959998 BACKGROUND

• Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004 Dec;85(12):2020-9. doi: 10.1016/j.apmr.2004.02.033.

  PMID: 15605342 BACKGROUND

Related Links

• Study website (Greek and English)

MeSH Terms

Conditions

Consciousness Disorders; Persistent Vegetative State; Coma; Brain Injuries, Traumatic; Cerebral Hemorrhage; Subarachnoid Hemorrhage

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Unconsciousness; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Intracranial Hemorrhages; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes

Central Study Contacts

Constantinos Picolas, MD MA

CONTACT

+357 22603494; c.picolas@shso.org.cy

Iakovos Lytrides, MD MSc

CONTACT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: July 30, 2026
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): September 15, 2030
• Study Completion (Estimated): September 30, 2030
• Last Updated: July 30, 2026

Record last verified: 2026-07

Locations

CY (1)