Clinical trial NCT04737369: Multimodal Neuromonitoring
Official title: Multimodal Neuromonitoring: an Explorative Study in Neurocritical Care Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Subarachnoid Hemorrhage
Intracerebral Hemorrhage
Traumatic Brain Injury
Cortical Spreading Depolarization and Depression
Seizures
Ictal-Interictal Continuum
Keywords: Multimodal Neuromonitoring
Electrocorticography
Cerebral Microdialysis
Neuropharmacology
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Karl Landsteiner Institute for Clinical Epilepsy Research
First posted: 2021-02-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Individuals between 18-80 years with poor grade aneurysmal SAH (World Federation Neurosurgical Societies \>3), severe ICH (ICH Score \>3) or severe TBI (Glasgow Coma Scale \<9).

Brief summary: Theoretical Framework \& Background

Cortical spreading depressions (CSD) and seizures, are crucial in the development of delayed cerebral ischemia and poor functional outcome in patients suffering from acute brain injuries such as subarachnoid hemorrhage. Multimodal neuromonitoring (MMNM) provides the unique possibility in the sedated and mechanically ventilated patients to record these electrophysiological phenomena and relate them to measures of cerebral ischemia and malperfusion. MMNM combines invasive (e.g. electrocorticography, cerebral microdialysis, brain tissue oxygenation) and noninvasive (e.g. neuroimaging, continuous EEG) techniques. Additionally, cerebral microdialysis can measure the unbound extracellular drug concentrations of sedatives, which potentially inhibit CSD and seizures in various degrees, beyond the blood-brain barrier without further interventions.

Hypotheses

1. Online multimodal neuromonitoring can accurately detect changes in neuronal metabolic demand and pathological neuronal bioelectrical changes in highly vulnerable brain tissue.
2. Online multimodal neuromonitoring can accurately detect the impact of pathological neuronal bioelectrical changes on metabolic demand in highly vulnerable brain tissue.
3. The occurrence and duration of pathological neuronal bioelectrical changes are dependent on sedatives and antiepileptic drug concentrations
4. The occurrence and duration of pathological neuronal bioelectrical changes have a negative impact on functional and neurological long-term patient outcome.
5. Simultaneous invasive and non-invasive multimodal neuromonitoring can identify a clear relationship of both methods regarding pathological neuronal bioelectrical changes and metabolic brain status.

Methods

Systematic analysis of MMNM measurements following standardized criteria and correlation of electrophysiological phenomena with cerebral metabolic changes in all included patients. In a second step neuroimaging, cerebral extracellular sedative drug concentrations and neurological functional outcome, will be correlated with both electrophysiologic and metabolic changes. Due to numerous high-resolution parameters, machine learning algorithms will be used to correlate comprehensive data on group and individual levels following a holistic approach.

Level of originality

Extensive, cutting edge diagnostic methods are used to get a better insight into the pathophysiology of electrophysiological and metabolic changes during the development of secondary brain damage. Due to the immense amount of high-resolution data, a computer-assisted evaluation will be applied to identify relationships in the development of secondary brain injury. For the first time systematic testing of several drug concentrations beyond the blood-brain barrier will be performed. With these combined methods, we will be able to develop new cerebroprotective treatment concepts on an individual basis.


Eligibility criteria: Inclusion Criteria:

* Individuals between 18-80 years with poor grade aneurysmal SAH (World Federation Neurosurgical Societies \>3), severe ICH (ICH Score \>3) or severe TBI (Glasgow Coma Scale \< 9). The diagnosis of SAH, ICH and TBI will be established by computed tomography (CT).
* Individuals that are unlikely to regain consciousness within the following 48 hours.
* Individuals that are expected to survive for the next 48 hours.

Exclusion Criteria:

* Individuals younger than 18 years old and older than 80 years.
* Pregnant women (documented via positive ß-HCG test).
* Patients, who do not want to participate in the study. As the patient is not able to consent prior to the study, information about the study details will be given to the patient in case of clinical improvement. The patient information sheet will be handed out.

Thereafter, the patient has the possibility to withdraw permission of study-participation.

Primary outcomes:
measure: Count of SD during electrocorticography
timeFrame: up to 21 days
measure: Daily pattern duration of CSD during electrocorticography
timeFrame: up to 21 days
measure: Daily pattern duration of NCSE during electrocorticography
timeFrame: up to 21 days
measure: Daily pattern duration of RPPIIC during electrocorticography
timeFrame: up to 21 days
measure: Daily duration of metabolic crisis
timeFrame: up to 21 days
measure: Daily duration of mitochondrial dysfunction
timeFrame: up to 21 days
measure: Daily duration of ischemia
timeFrame: up to 21 days
measure: Daily duration of elevated intracranial pressure (ICP)
timeFrame: up to 21 days
measure: Neuropharmacology Cmax)
timeFrame: up to 21 days
measure: Neuropharmacology (AUC)
timeFrame: up to 21 days
measure: Neuropharmacology (t1/2)
timeFrame: up to 21 days
measure: Neuroimaging
timeFrame: up to 28 days
measure: Functional patient outcome
timeFrame: up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Neurosurgery, Medical University of Vienna
Study officials:
affiliation: Department of Neurosurgery, Medical University of Vienna
name: Johannes Herta, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: