Multimodal Neuromonitoring at the ICU (NEMO-RETRO)

Neurocritical care has become a distinct discipline within the field of intensive care medicine with a major focus on the treatment of patients with acute damage to the most complex organ of the human body, the brain. The main indications for acute neurocritical care concern aneurysmal Subarachnoid Hemorrhage (SAH) and severe Traumatic Brain Injury (TBI). These disease entities form a major health and socioeconomic problem as they afflict young patients and the rate of death and disability is high. The pathology and treatment of these patients is heterogeneous and complex. Despite advances in basic neuroscience which have increased our understanding of processes in the injured brain, approaches to management are largely unfocused and adhere to the concept of a 'one pill for everybody' approach. Novel monitoring technology and new neuroimaging techniques now offer opportunities for advancing the care for these patients to a more individualized targeted management.

In the period of 2010-2014, a prospective trial was conducted in the Antwerp University Hospital, including 50 patients with either SAH or TBI, who underwent extensive monitoring, known as "Individualized targeted management in neurocritical care".

In NEMO-RETRO, the investigators want to answer proposed and new research questions in retrospective analyses, using current insights and methodologies.

Objectives:

1. Cerebral blood flow monitoring

   1. Investigate the effect of changes in therapy (nature/intensity) on Cerebral Blood Flow (CBF) measured by thermal diffusion flowmetry and Transcranial Doppler (TCD)
   2. Determine the added value of continuous CBF monitoring for the early detection of vasospasm and ischaemia

2. Brain tissue oxygen tension

   1. Investigate the effect of changes in therapy (nature/intensity) on cerebral oxygenation as measured by Brain Tissue Oxygen Tension (PTiO2)
   2. Investigate the relation between PTiO2 and hemodynamic parameters such as CBF, CPP, and ICP

3. Systemic effects of brain specific therapy

   1. Investigate the effects of brain-targeted therapy on cardiac output and lung function
   2. Determine the relation of CBF to cardiac output, in particular following triple H therapy

4. Neuroimaging

   1. Accurately document structural brain damage following TBI and SAH
   2. Document vasospasm and quantify flow and perfusion
   3. Quantify the degree of secondary ischaemic damage to the brain
   4. Differentiate swelling from edema
   5. Train and validate models to interpret neuroimaging

5. Outcome

   1. Assess global functional outcome at 6 months post-injury
   2. Assess health-related quality of life at 6 months after injury

6. Integrated approach analysis

   1. Describe the effects of brain-targeted therapy on cerebral and systemic parameters
   2. Define the added value of extended multimodality monitoring and advanced neuroimaging to detect vasospasm and secondary ischaemic damage, defined by markers of neuronal injury and cell death
   3. Develop recommendations for individualized targeted management

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Subarachnoid Aneurysm Hemorrhage
• Intervention / Treatment: Device: Multimodal neuromonitoring

• Study Type: Observational
• Enrollment (Actual): 50

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Primarily admitted to the Antwerp University Hospital

Description

This study is based on the 50 patients recruited for the original study.

For TBI:

Inclusion Criteria:

• male or female patients aged 18 to 70 years, inclusive
• sustained head injury within the previous 24 hours
• TBI diagnosed by history, clinical examination with a GCS of 12 or less
• evidence of TBI confirmed by abnormalities on CT scan
• clinical indication to monitor ICP
• informed consent is obtained from the patient or from a legally acceptable representative

Exclusion Criteria:

• life expectancy of less than 24 hours as determined by the investigator
• any spinal cord injury
• coma suspected to be primarily due to causes other than head injury, such as drug or alcohol overdose
• clinically significant or active gastro-intestinal, renal, hepatic, endocrine or CNS disease or chronic condition (e.g.psychiatric disorder) that can be ascertained at the time of admission and could affect functional outcome
• respiratory/hemodynamic instability, refractory to treatment and precluding transport for neuroimaging studies
• pregnancy
• special exclusion criteria for MRI, such as non-removable metals, artificial joints, electronic devices (pacemaker, pumps etc.)
• informed consent is obtained from a legally acceptable representative, prior to any study related activity

For aneurysmal subarachnoid hemorrhage:

Inclusion Criteria:

• male or female patients aged 18 to 70 years, inclusive
• ruptured aneurysm, demonstrated by CT angiography or DSA
• onset of SAH clinical symptoms within the preceding 72 hours
• World Federation of Neurosurgery (WFNS) grade III-IV and grade V patients, who improve within 24 hours after ventriculostomy
• indication for ICP monitoring or CSF drainage
• informed consent is obtained from the patient or a legally acceptable representative

Exclusion Criteria:

• non-aneurysmal subarachnoid hemorrhage
• admission in a clinical state with extremely poor prognosis (e.g. wide, non-reactive pupils for more than 1 hour)
• significant coagulation disturbances (thrombocytes < 80 per mL, partial thromboplastin time > 45 sec, INR > 1.5)
• cytostatic therapy in patients with malignant disease
• pregnancy
• special exclusion criteria for MRI, such as non-removable metals, artificial joints, electronic devices (pacemaker, pumps etc.)
• respiratory and/or hemodynamic instability precluding

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute brain injury; Patients with acute brain injury (TBI or aSAH)	Device: Multimodal neuromonitoring; Imaging: CT, MRI, XA Neuromonitoring: Brain Tissue Monitoring Probe, Hemedex, External ventricular drain, Cortical microdialysis catheter Other monitoring: Arterial catheter, Jugular bulb catheter, routine vital parameters

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with a favourable neurological outcome	Glasgow Outcome Scale - Extended (GOSE; 1 = Dead, 8 = Upper good recovery)	From enrollment to the end of follow-up at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in abnormalities on neuroimaging through CT, MRI or XA	Change based on evolution of bleeding areas, ischemic areas, edema	From enrollment to the end of the study at 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in NSE	Measurement of neuron-specific enolase (ng/mL, plasma/CSF)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in GFAP	Measurement of glial fibrillary acidic protein (ng/mL, plasma/CSF)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in S100B	Measurement of S100 calcium-binding protein B (ng/mL, plasma/CSF)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in NFL	Measurement of neurofilament light chain (ng/mL, plasma/CSF)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in UCH-L1	Measurement of ubiquitin carboxy-terminal hydrolase L1 (ng/mL, plasma/CSF)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in MDA	Measurement of malondialdehyde (µmol/L)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in Ferritin	Measurement of ferritin (ng/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in Hepcidin	Measurement of hepcidin (ng/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in GDF-15	Measurement of growth differentiation factor 15 (ng/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in CHI3L1	Measurement of chitinase-3-like protein 1 (ng/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in TfR	Measurement of transferrin receptor (ng/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in IL-1α	Measurement of interleukin-1 alpha (pg/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in Fe²⁺	Measurement of ferrous iron (µmol/L)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in Syndecan	Measurement of syndecan (ng/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in IL-1β	Measurement of interleukin-1 beta (pg/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in IL-6	Measurement of interleukin-6 (pg/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in IL-10	Measurement of interleukin-10 (pg/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in IL-18	Measurement of interleukin-18 (pg/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in IL-23	Measurement of interleukin-23 (pg/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in IL-1RA	Measurement of interleukin-1 receptor antagonist (pg/mL)	From enrollment up to 12 days, unless earlier ICU discharge
Change from baseline in TNFα	Measurement of tumor necrosis factor alpha (pg/mL)	From enrollment up to 12 days, unless earlier ICU discharge

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Collaborators: Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek); CENTER TBI

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2010
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 12, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Neuromonitoring
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: EDGE 4584

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) will be shared in accordance with the defined research questions. All data will be anonymized prior to analysis, and transfer procedures will be carried out in full compliance with hospital regulations.
• IPD Sharing Time Frame: Beginning 3 months and ending 1 year after publication of results.
• IPD Sharing Access Criteria: Researchers may request data by contacting the original investigators. An official application must be submitted to the original investigators, who will determine whether data sharing is approved. In the event of approval, a formal data-sharing agreement will be established between the requesting researchers and the original investigators. All data sharing will be conducted in accordance with the local regulations of Antwerp University Hospital.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No