Neuroinflammation During ICU-associated Delirium in Critically Ill Patients and Its Association With Structural and Functional Brain Alterations: a Nested Case-control Study

Study Overview
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Brief Summary
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With the present study, the authors aim to improve the knowledge of the pathophysiology of ICU-related delirium. In particular, the authors would like to clarify the possible correlation between neuroinflammation, evaluated longitudinally by serum dosage of 20 different neuroinflammation biomarkers, and brain structural and functional alterations (using brain fMRI).

Detailed Description
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Pathophysiology of delirium is poorly understood; neuroinflammation and brain network disruption are claimed as possible causes of delirium. The authors want to clarify the role of the alterations of different cellular components of neuroinflammation (neurons, glial cells, and endothelium) in delirium development. Moreover, the authors want to understand whether the neuroinflammation process could cause permanent structural and functional brain damage. In a nested cross-sectional longitudinal case-control observational study in ICU admitted patients. The objectives of the studies are as follow: 1) Neuroinflammation biomarkers evaluation in non-neurological ICU patients who develop delirium during ICU-stay (case) compared to matched non-delirious ICU patients (control), and 2) their correlation with brain structural and functional alterations evaluated with a resting-state fMRI protocol and PET.

Official Title
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Neuroinflammation During ICU-associated Delirium in Critically Ill Patients and Its Association With Structural and Functional Brain Alterations: a Nested Case-control Study

Conditions
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Delirium, Critical Illness

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age>18 All patients admitted that would be expected to stay in ICU for at least 3 days Exclusion Criteria: Acute neurological condition Chronic neurological condition (i.e., seizures, stroke, muscular illness). Hematological malignancy or immunological disease. Blood transfusion in the last 2 weeks Ongoing sedation Any condition which contraindicates MRI execution (presence of non-compatible devices or hemodynamic or respiratory instability).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case<br>All patients aspected to stay in ICU for at least 3 days who will develop delirium | |
| Control<br>All patients aspected to stay in ICU for at least 3 days who will not develop delirium (1:1 matched with the controls with a propensity score method). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Neuroinflammation biomarkers in patients developing delirium. | Comparison of neuroinflammation biomarkers in patients developing delirium vs patients who do not develop delirium. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fMRI alteration | Evaluation of brain functional alterations during delirium development (evaluated through resting state fMRI). | 6 months | 
| Correlation between biomarkers alterations and fMRI alterations | Evaluation of the correlation between serum neuroinflammation biomarkers alteration during delirium development and the alterations noted in during resting state fMRI | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuroinflammation, fMRI, Functional MRI, ICU related delirium