Use of Brain Structural and Functional Connectomes for the Prediction of Neurological Recovery in Coma Patients After Cardiac Arrest
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 263
- 试验地点
- 1
- 主要终点
- performance of a predictive model to predict 6 months neurological outcome
研究概览
简要总结
To assess the performance of a predictive model resulting from the analysis of sMRI/fMRI/contrast-enhanced MRI-derived personalized connectomic data, as compared with standard predictors (clinical examination, electrophysiology, serum biomarker, standard neuroimaging) collected ≥ 72h from sedation withdrawal and in normothermia condition, to predict anoxoischemic coma neurological outcome at 6 months.
详细描述
There is a major need for timely, reliable and generalizable methods to predict outcomes in anoxo-ischemic coma patients. Standard predictors of poor outcome after cardiac arrest (CA) include clinical, electrophysiological and serum biomarkers data. All have substantial limitations in terms of reliability and generalizability. By providing whole-brain structural and functional connectivity maps, or connectomes, advanced MRI techniques have precisely revealed the brain network damages induced by CA. Because these individualized connectomic profiles contains critical information about consciousness recovery potential after CA, it can be hypothesized that these whole-brain quantitative data can be used to elaborate highly performant predictive algorithms for anoxo-ischemic coma patients.
Regarding advanced structural MRI (sMRI), two recent studies, including one from the investigators group, have shown a high sensitivity and specificity of these advanced techniques (diffusion tensor imaging -DTI; voxel-based morphometry -VBM) for predicting poor neurological recovery in anoxo-ischemic patients. However, these two studies collected data using poorly defined time window for MRI, across lengthy data collection periods (> 8 years) and did not apply a strict protocol of withdrawal or limitation-of-care decision to control from misclassification of outcome due to so-called selffulfilling prophecies. Concerning functional MRI (fMRI), a recent study from the investigators group reports that the strength of frontoparietal functional connectivity differs between anoxo-ischemic coma patients who recover and those who eventually score an unfavorable outcome at 3 months.
Furthermore, converging evidence suggest that task-based fMRI can be used to detect active, command-following modulation of cortical activity and, hence, consciousness in behaviorally unresponsive patients. This task-based fMRI pattern named Cognitive Motor Dissociation (CMD) show promise of radically improving good outcome neuroprognostication after CA. Finally, aiming to maximize the performance of MRI-derived predictive models, the investigators group have recently reported in a " proof-of-concept " study that a combined sMRI/fMRI connectomes and contrast-enhanced MRI data analysis, synergistically outperform alternative predictive models based on sMRI or fMRI data in isolation.
As recommended in recent guidelines for the management of anoxo-ischemic coma patients[7-9], a standard multimodal prognostication procedure will be followed, including the collection of standard predictors after at least 72h from complete withdrawal of sedation in normothermia condition: i) clinical examination and behavioral data (Day 1, 3 and 7 after inclusion): Glasgow Coma Scale - GCS, Full Outline of UnResponsiveness - FOUR, Coma Recovery Scale Revised - CRSR; and standardized brainstem reflex testing (FOUR, Glasgow-Liège score); ii) severity stratification scoring (Day 1 after inclusion): Cardiac Arrest Hospital Prognosis - CAHP, Out-of-Hospital Cardiac Arrest - OHCA, iii) laboratory findings (Day 1, 3 and 7 after inclusion) : NSE blood level (Day 1); iv) electrophysiological assessments: standard EEG using ACNS classification (once between Day 1 and Day 15 after inclusion); v) standard neuroimaging (once between Day 1 and Day 15 after inclusion): standard brain CT or MRI data (T1, T2*, SWI, DWI, FLAIR).
In addition to standard clinical neuroprognostication procedure, an advanced whole-brain sMRI/fMRI/contrast-enhanced MRI scan will be acquired at least after 72h from complete withdrawal of sedation in normothermia condition (between Day 1 and Day 7 after inclusion).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (male or female ≥ 18 years).
- •Coma, as indicated by a Glasgow Coma Scale (GCS) ≤ 8 (motor score ≤ 2) immediately after CA resuscitation and before sedation onset.
- •Persisting unconsciousness, defined as the inability to obey verbal commands, after at least 72 hours from complete withdrawal of sedation in normothermia conditions.
- •Written informed consent from patient's legal representative.
- •Affiliation or beneficiary to the French social security system.
排除标准
- •Brain death.
- •Coma explained by other cause than CA.
- •Likely poor neurological outcome based on early predictors, following ERC-ESCIM 2021 recommendations. In a comatose patient with GCS motor score ≤ 3 at ≥ 72 h from ROSC, in the absence of confounders, the identification of at least two of the following: bilaterally absent pupillary light and corneal reflexes at ≥ 72h, bilaterally absent N20 SSEP ≥ 24h; neuron-specific enolase (NSE) > 60 μg/l at 48h and/or 72h, status myoclonus ≤72h.
- •Decision of WLST previous to patient recruitment, based on early predictors of poor neurological outcome, age, co-morbidity, general organ function and patient's preferences.
- •Life expectancy shorter than 6 months based on pre-morbid conditions.
- •Former neurological functional disability (mRS > 2 before CA).
- •MRI contraindication: medical material not MRI compatible, claustrophobia
- •Known hypersensitivity to gadoteric acid, meglumin or any drug containing gadolinium
- •Severe kidney failure defined as a KDIGO score > 3 (glomerular filtration rate < 30 ml/min/1.73 m2 or renal replacement therapy).
- •Hemodynamic shock or severe respiratory failure precluding patient's transport and MRI scanning.
- •Pregnancy or nursing woman.
- •Patient under juridical protection.
研究组 & 干预措施
anoxo-ischemic coma patients
Standard multimodal prognostication procedure will be followed, including the collection of standard predictors:
i) clinical examination and behavioral data (Day 1, 3 and 7 after inclusion): Glasgow Coma Scale - GCS, Full Outline of UnResponsiveness - FOUR,Coma Recovery Scale Revised - CRS-R; and standardized brainstem reflex testing (FOUR, Glasgow-Liège score); ii) severity stratification scoring (Day 1 after inclusion): Cardiac Arrest Hospital Prognosis - CAHP, Out-of-Hospital Cardiac Arrest - OHCA, iii) laboratory findings (Day 1) : NSE blood level iv) electrophysiological assessments (once between Day 1 and Day 15 after inclusion): standard EEG following current guidelines and using ACNS classification; v) standard neuroimaging (once between Day 1 and Day 15 after inclusion): standard brain CT or MRI data (T1, T2*, SWI, DWI, FLAIR).
An advanced wholebrain sMRI/fMRI/contrast-enhanced MRI scan will be acquired (between Day 1 and Day 7 after inclusion).
干预措施: advanced whole-brain sMRI/fMRI/contrast-enhanced MRI scan (Other)
结局指标
主要结局
performance of a predictive model to predict 6 months neurological outcome
时间窗: month 6
Comparison between the area under the Receiver Operating Characteristic (ROC) curves of outcomes prediction models, based on either MRI-derived indicators (structural, functional and contrast-enhanced MRI), or built upon standard predictors (clinical examination, electrophysiology, serum biomarker, standard neuroimaging) both collected ≥ 72h from sedation withdrawal and in normothermia condition, to predict 6 months neurological outcome as measured by the dichotomized Rankin Scale (mRS).
次要结局
- Performance of a predictive model to predict neurological outcome at hospital discharge(Hospital discharge)
- Performance of a predictive model to predict neurological outcome at 3 months after CA(month 3)