Natural eye blinking to help tell levels of consciousness

Spontaneous Eye Blinking as a Diagnostic and Prognostic Marker in Patients With Disorders of Consciousness After Severe Acquired Brain Injury

This study will test whether patterns of natural eye blinking can help distinguish between unresponsive wakefulness and minimally conscious patients after recent severe brain injury.

Quick facts

• Study type: Observational
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fondazione Don Carlo Gnocchi Onlus (other)
• Locations: 8 sites (Liège, Belgium and 7 other locations)
• Trial ID: NCT06323031 on ClinicalTrials.gov

What this trial studies

This is a multicenter prospective observational study enrolling adults with disorders of consciousness after severe acquired brain injury at European rehabilitation and research centers. Investigators will record spontaneous eye-blink parameters (rate, amplitude, duration, variability) using EEG‑EOG during two 20‑minute resting sessions 24 hours apart, within two weeks of study entry. The planned sample includes about 70 patients across diagnostic groups (UWS, MCS–, MCS+) and 23 age- and sex-matched healthy controls, with clinical data collected alongside routine care and consent provided by legal representatives. Data will be analyzed to determine whether blink features relate to diagnosis and short-term prognosis without altering standard clinical management.

Who should consider this trial

Good fit: Adults (≥18 years) within 6 months of a severe acquired brain injury who have a clinical diagnosis of UWS, MCS–, or MCS+ and who are medically stable, free of recent sedatives, and whose legal representative can provide consent are ideal candidates.

Not a fit: Patients more than 6 months post-injury, those with unstable medical conditions, ophthalmic or eyelid motor disorders, recent sedative use, or additional brain events after admission are unlikely to benefit from the measurements in this protocol.

Why it matters

Potential benefit: If successful, this approach could provide a simple, bedside biomarker to improve diagnostic accuracy and help guide prognosis and rehabilitation planning for patients with disorders of consciousness.

How similar studies have performed: Previous smaller studies have shown differences in blink rate between consciousness levels (reported effect size d≈0.68), but comprehensive diagnostic and prognostic use of multiple blink features remains preliminary.

Eligibility criteria

Inclusion Criteria:

* clinical diagnosis of DoC (UWS, MCS minus, MCS plus) following repeated clinical evaluation (at least four CRS-R in a week)
* age ≥ 18 years
* time post-onset ≤6 months
* Previous sABI of any etiology (traumatic, vascular, anoxic, mixed, etc.)
* Negative anamnesis for neurological or psychiatric disorders.

Exclusion Criteria:

* unstable clinical conditions (e.g. respiratory failure, fever, status epilepticus, etc.);
* ophthalmic diseases, or clinically detected peripheral damage in eyelid motility (e.g. orbital fracture);
* intake of sedative drugs in the preceding 24 hours;
* additional brain event following admission (e.g., stroke).

Where this trial is running

Liège, Belgium and 7 other locations

• Coma Science Group, GIGA-Consciousness, University of Liege — Liège, Belgium, Belgium (NOT_YET_RECRUITING)
• Therapiezentrum Burgau — Burgau, Germany, Germany (RECRUITING)
• Dipartimento di Neurologia, LMU Hospital, LMU Munich — Munich, Germany, Germany (RECRUITING)
• Polo Specialistico Riabilitativo Fondazione Don Carlo Gnocchi ONLUS — Sant'Angelo dei Lombardi, AV, Italy (RECRUITING)
• Unità Gravi Cerebrolesioni - Dipartimento Neuroscienze - Azienda Ospedaliera - Universitaria Ferrara — Ferrara, Italy, Italy (RECRUITING)
• IRCCS Fondazione Don Gnocchi ONLUS — Florence, Italy, Italy (RECRUITING)
• IRCCS Santa Maria Nascente Fondazione Don Gnocchi ONLUS — Milan, Italy, Italy (RECRUITING)
• Instituto de Rehabilitación Neurológica IRENEA — Valencia, Spain, Spain (RECRUITING)

Study contacts

• Study coordinator: Anna Estraneo, MD

Conditions: Disorders of Consciousness, blinking, diagnosis, prognosis, rehabilitation