Brain Network Disruptions Related to Traumatic Coma (Coma3D)

Whole Brain Connectivity Changes Induced by Traumatic Coma: Combined Structural, Functional and Neuroinflammatory Approaches

To provide a fine-grained description of the brain network dysfunctions induced by severe traumatic brain injury (TBI) or anoxic encephalopathy, that are responsible for the acute state of unarousable unawareness, named coma, this trial wants to explore the usefulness in this setting of a combined neuroimaging approaches encompassing several up-to-date techniques as structural MRI, fMRI and positron emission tomography (PET) scan (neuroinflammation ligands).

So far, the gold standard for neuroprognostication of severe traumatic brain injury (TBI) or anoxic encephalopathy is the bedside behavioural evaluation. Nevertheless, the predictive value of such an exclusive clinical approach has been consistently reported as limited and insufficient in this challenging clinical setting. Recent theoretical and experimental data converge towards the idea of the critical implication of long-range brain connection in consciousness access and maintain. Nevertheless, previous studies have focused on the specific analysis of some targeted connections (regions of interest), and have used exclusively a single approach in neuroimaging (structural or functional imaging), with no interest in the neuro-inflammatory and neurodegenerative mechanisms likely associated with these disconnection phenomena. So, cerebral disconnection characterization at the level of the whole brain, at different stages of pathological abolition of consciousness must be made, on an anatomical, functional and metabolic scale. This descriptive study represents a first step in the identification of relevant multimodal imaging biomarkers. This will then lead to a larger study to identify the prognostic impact of these different biomarkers obtained in the acute phase of patient management.

Subject with coma of traumatic or anoxic aetiology : PET examination with radiopharmaceutical drug [18F] DPA-714, MRI examination and Blood samples.

subject control : PET examination with radiopharmaceutical drug [18F] DPA-714, MRI examination and Blood samples.

Using a Biograph 6 Truepoint device. Establishment of a venous route. It will be injected 4 MBq / kg of 18F-DPA714 by the venous route with a maximum dose of 280 MBq. The patient will be placed along the orbito-meatal line. Brain acquisition will begin 60 minutes post-injection

MRI device Philips Achieva - 3Tesla. The acquisition of the data will include different sequences (anatomical MRI, diffusion MRI, resting fMRI) and will last a total of one hour (installation and removal of the patient in the machine included).anatomical MRI associated with FLAIR (Fluid Attenuation Inversion Recovery) and diffusion tensor (tractography).

The Glasgow Coma Scale is divided into three components : ocular response (assessment 1-4 points), motor response (assessment 1-6 points) verbal response (evaluation of 1-5 points). Scores for each component are added together to get the total that will range between a minimum of 3 points (which corresponds to a patient who does not open his eyes and no motor response to stimulation or verbal response) and a maximum value of 15 points (corresponding to a patient with open eyes, obeying orders and maintaining a consistent language). It has been considered that the GCS score between 15 and 13 points corresponds to a slight alteration of consciousness, a score of 12-9 points with moderate impairment and 8 points or less with a serious deterioration in level of consciousness.

The Coma Recovery Scale Revised is divided into three components : return to consciousness (RECUP), vegetative neurological state (ENV) or minimal state of consciousness (ECM). This scale has been validated in French, with a value of Cronbach's Alpha estimated at 0.8. It is a score whose values are between 100 (normal level of consciousness) and 10 (coma). ENV and ECM have intermediate values (approximately 30 and 60, respectively).

assessing the strength of connectivity between different regions for the whole brain, measurement of anatomical connectivity, measurement of cortical thickness. All this measure use voxel/volume unit of the brain

Inclusion criteria for patients: Male or female / age between 18 to 75 years. Coma of traumatic or anoxic aetiology (GCS < 10). Early (< 1 month after TBI) and after the complete withdrawal of sedative agents. Written agreement for participation (legal responsible). Inclusion criteria for controls: Male or female / age between 18 to 75 years, paired with patients (gender and age). Written agreement for participation Exclusion criteria: Patients without public insurance regime. Pregnancy. Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand). Exclusion criteria for controls: - pharmacological treatments which could interfere with consciousness (left to the judgement of the investigator)

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