Measuring Brain Complexity to Detect and Predict Recovery of Consciousness in the ICU

Massachusetts General Hospital120 enrolled

Overview

Disorders of consciousness (DoC) caused by severe brain injury affect millions of people worldwide each year. A patient's level of consciousness in the intensive care unit (ICU) significantly influences the recovery from disability and may affect family decisions about withdrawal of life-sustaining therapy (WLST). Transcranial magnetic stimulation-electroencephalography (TMS-EEG) has shown the best performance in detecting signs of consciousness in patients with chronic DoC. The goals of this multi-center observational study are to demonstrate the diagnostic performance and prognostic utility of TMS-EEG in patients with DoC caused by severe brain injuries in the ICU. Through this research, we aim to demonstrate that: * TMS-EEG can detect 95% of conscious patients who are defined as conscious by a combination of tests that aim to detect overt and covert consciousness. * TMS-EEG measurements can predict 6-month outcomes on the Disability Rating Scale (DRS) in patients in an acute vegetative state, controlling for age, Glasgow Coma Scale (GCS) score, and injury mechanism All participants will undergo repeated behavioral assessments, task-based electroencephalography (EEG), and TMS-EEG. Of note, conventional brain magnetic resonance imaging (MRI) and task-based functional MRI are optional.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

Interventions

Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEGOTHER

The presence of consciousness will be classified considering the highest level of consciousness revealed by repeated behavioral examinations, functional electroencephalography (task-based EEG), and functional brain imagery (task-based fMRI). Based on the results of this composite standard reference, we will evaluate the diagnostic and prognostic accuracy of TMS-EEG measurements of brain complexity

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age greater than or equal to 18 2. Functionally independent at baseline 3. Acquired brain injury within the last 28 days 4. Disorder of consciousness, as defined by no instance of following commands (i.e., Glasgow Coma Scale motor score = 6) on two or more consecutive assessments 5. Continuous intravenous sedation able to be discontinued for at least 10 minutes 6. ICU clinicians approve safe placement of 64-electrode EEG cap on the scalp Additional inclusion criteria are present in the study protocol. Exclusion Criteria: 1. Status epilepticus or uncontrolled seizure disorder 2. No head CT scan from current hospital admission AND contraindications for MRI: conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the head (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments) 3. Medical instability, restlessness, or other factors identified by the PI that would either prevent safe participation or compromise data acquisition 4. Hemicraniectomy If a subject meets a contraindication for MR imaging, the subject may participate in all other aspects of the study except MRI.

Outcomes

Primary Outcomes

Presence of consciousness as defined by a composite reference standard for consciousness that combines behavior, task-based EEG, and task-based fMRI

Behavioral assessments of consciousness (up to 5): The CRS-R consists of 6 subscales designed to assess auditory function, receptive and expressive language, visuoperception, communication ability, motor functions, and arousal level. The lowest score on each sub-scale represents reflexive activity; the highest represents behaviors mediated by cognitive input. The total score ranges between 0 (worst) and 23 (best). The CRSR-FAST assesses only those CRS-R behaviors that differentiate conscious (i.e., MCS) from unconscious (i.e., coma/VS) patients. Functional assessments of covert consciousness: A participant is classified as being conscious on task-based EEG if the probability with which the classifier distinguished task from rest conditions is p \< 0.05 and the accuracy value that indicates the classifier's performance is ≥ 60%. A participant is classified as being conscious on task-based fMRI if there is one statistical activation within a pre-specified region of interest.

Time frame: 48 hours after the end of the TMS-EEG assessment

Disability Rating Scale (DRS) total score

The Disability Rating Scale (DRS) provides quantitative information regarding functional disability in patients recovering from severe brain injury. The total score on the DRS ranges from 0 to 29 with higher scores indicating a greater degree of disability. DRS subscale scores include eye opening \[score range 0-3\], communication \[score range 0-4\], motor response \[score range 0-5\], cognitive ability for feeding \[score range 0-3\], cognitive ability for toileting \[score range 0-3\], cognitive ability for grooming \[score range 0-3\], level of function \[score range 0-5\], and employability \[score range 0-3\]. Subscale scores are summed to produce the total score.

Time frame: 6 months post injury

Measuring Brain Complexity to Detect and Predict Recovery of Consciousness in the ICU

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Central Contacts