Window On the Brain (WOB)

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Status: Enrolling

Conditions: Disorders of Consciousness

Treatments: Device: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT06693492

PNRR-MAD-2022-12375863

Details and patient eligibility

About

Disorders of consciousness (DOC) diagnosis suffers from the difficulty to measure the level of consciousness due to the variability associated with behavioural assessments and the difficulty in detecting the residual level of consciousness in patients who do not show any behavioural signs during the behavioural assessment. This issue could be overcome by using instrumental tools, that are expensive and not always available in clinical settings. The ultrasound-based techniques could represent a valid low-cost and more feasible alternative to deep the knowledge about physio-pathological mechanisms underlying DOC and their chronicization. These techniques could be tailored to treat acute and chronic DOC patients from a personalised medicine perspective. Improving the knowledge, management and care pathways of DOC patients and finding new therapeutic options would benefit not only patients but also public health systems.

Full description

After acquired brain injuries, Disorders of Consciousness (DOC) may occur and persist for up to many years. DOC range from Unresponsive Wakefulness Syndrome (UWS; presence of reflexive behaviours) to the emergence from Minimally Conscious State (eMCS; presenting signs of functional communication and/or object use). A correct diagnosis affects the legal decisions, prognosis, and potential therapeutic and rehabilitative interventions. Although DOC diagnosis relies on behavioural assessment (Coma Recovery Scale-Revised; CRS-R), several studies highlight the importance of instrumental tools (e.g., neuroimaging and electrophysiology) for improving diagnosis and prognosis despite their complexity, high costs, and low availability. The ultrasound techniques can represent a valid alternative, allowing both to acquire bedside structural and functional data with low costs and less invasiveness, and perform stimulation to boost consciousness improvement and/or recovery. However, limited evidence exists to date about the use of ultrasound techniques for clinical characterization of DOC patients, and only one registered trial is exploring the effectiveness of ultrasound stimulation for consciousness recovery in this clinical population. For these reasons, we aim to explore the brain functioning and morphology with direct ultrasound (US) in DOC patients, providing both anatomical and functional information in real-time. Specifically, the measures extracted from US examination might provide data regarding DOC's physiopathology in a bedside and affordable manner. Moreover, although clinical trials with low-intensity ultrasound modulation of subcortical structures and thalamic nuclei are already in progress, targeting is still empirical. Thus, understanding US parameters in DOC could provide the ground to improve deep brain structures' targeting, tailoring low-intensity ultrasound parameters according to patient's specific needs for improving their level of consciousness.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Aim 1

Inclusion criteria:

• an established diagnosis of DOC (UWS or MCS according to the CRS-R criteria and/or a CRS-R total score ≤22) following severe acquired brain injury;
• age>18 years old;
• written informed consent obtained from each patient's representative.

Exclusion criteria:

• previous psychiatric, neurological, or drug abuse history;
• on-going mechanical ventilation.

From the population enrolled for aim 1, we plan to select ten patients

Inclusion criteria:

• 18<age<65 years;
• medical stability over the previous 30 days;
• presence of the following US variables: low brain stiffness, high elasticity, and adequate level of tissue perfusion;
• written informed consent obtained from each patient's representative;
• structural integrity of both thalami as assessed by MRI.

Exclision criteria:

• contraindications to MRI examination;
• presence of decompressive craniectomy or cranioplasty performed within 30 days;
• presence of epileptogenic features on the EEG and/or drug resistant epileptic crisis history;
• presence of severe muscoloskeletal impairments which are likely to interfere with the correct positioning required for the intervention.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Chronic patients (DOC duration >=1 year)

Experimental group

Description:

* Assessment with US technique to characterized the pathophysiological features of chronic DOC * For the Interventional part of the project, the selected patients in this arm will be treated with a single session of US neuromodulation and the following measures will be collected before and after the intervention: Coma Recovery Scale-revised; Resting state fMRI; EEG-based neurophysiological indices

Treatment:

Device: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention

Post-acute patients (DOC duration <1 year)

Experimental group

Description:

* Assessment with US technique to characterized the pathophysiological features of post-acute DOC and explore its predictive value for chronicization * For the Interventional part of the project, the selected patients in this arm will be treated with a single session of US neuromodulation and the following measures will be collected before and after the intervention: Coma Recovery Scale-revised; Resting state fMRI; EEG-based neurophysiological indices

Treatment:

Device: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention