Spontaneous Eye Blinking Evaluation for Cognitive Assessment of Individuals With Severe Acquired Brain Injury

Acquired Brain Injury Clinical Trial

— SEE-ABI  

Official title:

Spontaneous Eye Blinking Evaluation for Cognitive Assessment of Individuals With Severe Acquired Brain Injury

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06464549
• Other study ID #: SEE-ABI
• Status: Not yet recruiting
• Start date: June 25, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2024
• Source: Fondazione Don Carlo Gnocchi Onlus
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Assessment of consciousness and attention in individuals with severe Acquired Brain Injury (sABI) is crucial for planning rehabilitation, but it is often hindered by coexisting sensory-motor and/or cognitive-behavioural disorders.

This project aims at evaluating the value of spontaneous eye blinking features to assess patients' attentional abilities and to distinguish patients with unresponsive wakefulness syndrome (UWS) from those in minimally conscious state (MCS).

Patients will undergo an EEG-EOG recording at rest and during an auditory oddball task. Eye blinking features on EOG will be analysed and compared to that of healthy individuals. A machine-learning-based algorithm using blinking features for the diagnosis of patients with sABI will be studied and validated preliminarily.

This project will help to stratify patients with sABI using easy-to-detect clinical markers, supporting clinicians' decision-making about patient's management. Additionally, blinking patterns related to residual attentional abilities in patients emerged from disorders of consciousness will be investigated.

Description:

Overall aim: to provide preliminary results on the value of spontaneous eye blinking features (i.e., rate, amplitude, duration, and variability in intervals between blinks), which do not rely on voluntary behavioural responses, for improving the assessment of attentional abilities and consciousness in patients with sABI.

Specific aims:

1. to confirm the diagnostic value of EBR in pDoC patients, as in Magliacano et al.'s (2021) study;

2. to improve diagnostic accuracy of patients with prolonged Disorders of Consciousness (pDoC) by evaluating additional blinking features (i.e., amplitude, duration, variability in intervals between blinks) for discriminating patients in UWS from those in MCS or conscious.

3. to explore the usefulness of eye blinking features analysis for assessing residual attentional abilities in full-conscious patients recovering from pDoC.

4. prototyping a machine-learning-enabled pipeline for supporting consciousness diagnosis based on Eye Blink Rate (EBR) and EOG-derived features. The interpretability and reliability aspects will be carefully evaluated to obtain a clinically usable solution for supporting diagnostic procedures and planning tailored cognitive rehabilitation.

Overall, this study is proposing a preliminary investigation, with pilot samples of both healthy and test population, for the analysis of EBR and EOG-derived biomarkers. These results will lay the foundations for the development and validation of multifactorial decisional algorithms for patients' diagnostic and prognostic stratification, based on easily collectable clinical markers.

This project has an observational, cross-sectional design. All patients with sABI consecutively admitted will be screened. We plan to enrol a convenience test sample of 35 patients with sABI including 10 patients with pDoC (5 in UWS, 5 in MCS) and 25 patients who recovered full consciousness after sABI.

A benchmark population of 20 healthy individuals, balanced for age and sex with the patient sample, will be also enrolled, by means of word-of-mouth according to a snowball sampling. This population will undergo anamnestic interview, and neurological and primary cognitive examination for excluding history or presence of neurological disorders. At study entry, patients' demographic (e.g., age, sex), anamnestic (e.g., aetiology, time post-injury, brain lesion location), and clinical data will be collected. Patients' clinical diagnosis and cognitive functioning will be classified according to their best score on the repeated Coma Recovery Scale-Revised (CRS-R) and on Levels of Cognitive Functioning (LCF), respectively.

Within 2 weeks from study entry, each patient will attend an electroencephalogram-electrooculogram (EEG-EOG) recording session. Eye blinking will be examined during a rest condition (duration: 8 min) and during an active auditory oddball task (duration: 8 min), consisting of randomly intermixed tones (non-target: 500 Hz, overall probability: 80%, n=312; target: 1000 Hz, overall probability: 20%, n=78) presented with a 1-s inter-stimulus interval through headphones. To complement clinical assessment, the background activity on resting EEG and the presence of the P300 component on event-related potentials following the auditory oddball paradigm will be evaluated. Patients' consciousness (CRS-R) and cognitive functioning (LCF) levels will be gathered on the day of the EEG-EOG recording session, and considered for statistical analysis.

Control participants will undergo the same EEG-EOG recording as the patients. For both participant groups, blinks will be defined as a sharp positive peak followed by a shallow negative deflection in a time window of <400 ms on the EOG. Moreover, to prevent awareness of blink recording affects blink features, throughout recording sessions participants will be never informed of the blinking recording, but they will be encouraged to stay relaxed with their eyes open. This procedure will be conducted regardless of the participant (patient or control) group.

Biostatistical analyses will be exploited for the investigation of associations between EOG-derived biomarkers and residual attentional abilities in conscious sABI patients under different acquisition paradigms, in response to Objective 3. Objective 4 will be addressed through the development of Machine Learning-based prototypes for the diagnosis of patients with pDoC using information derived from EOG signals, complemented by EEG and clinical data. The interpretability and error analyses will pose the premises for the identification of eventual covert patterns contained in EOG data.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 55
• Est. completion date: September 30, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• diagnosis of severe acquired brain injury;

• age=18 years;

• time post-injury=28 days

• written informed consent by patient or, where necessary, by primary caregiver

Exclusion criteria will be:

• large craniectomy interfering with EEG recording;

• unstable clinical conditions;

• presence of ophthalmic disorders, or central or peripheral impairments in eyelid motility on clinical evaluation;

• administration of sedative medication in the previous 24h;

• previous history of neurological or psychiatric diseases

Related Conditions & MeSH terms

• Acquired Brain Injury
• Brain Injuries
• Consciousness Disorders
• Disorders of Consciousness
• Wounds and Injuries

Intervention

Diagnostic Test:
• EEG-EOG recording at rest and during an auditory oddball paradigm
Participants will attend an electroencephalogram-electrooculogram (EEG-EOG) recording session. Eye blinking will be examined during a rest condition (duration: 8 min) and during an active auditory oddball task (duration: 8 min), consisting of randomly intermixed tones (non-target: 500 Hz, overall probability: 80%, n=312; target: 1000 Hz, overall probability: 20%, n=78) presented with a 1-s inter-stimulus interval through headphones.

Locations

Country	Name	City	State
Italy	IRCCS Fondazione Don Carlo Gnocchi Firenze	Firenze
Italy	Polo Specialistico Riabilitativo Fondazione Don Carlo Gnocchi ONLUS	Sant'Angelo dei Lombardi	AV

Sponsors (1)

Lead Sponsor	Collaborator
Alfonso Magliacano

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Magliacano A, Rosenfelder M, Hieber N, Bender A, Estraneo A, Trojano L. Spontaneous eye blinking as a diagnostic marker in prolonged disorders of consciousness. Sci Rep. 2021 Nov 17;11(1):22393. doi: 10.1038/s41598-021-01858-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Coma Recovery Scale-Revised	The Coma Recovery Scale-Revised is a clinical scale with a total score ranging from 0 to 23, with higher scores indicating a higher level of consciousness	Within 2 weeks from study entry
Primary	Levels of Cognitive Functioning	Levels of Cognitive Functioning is a clinical scale with a score ranging from 1 to 8, with higher scores indicating a higher level of cognitive functioning	Within 2 weeks from study entry