Precision Medicine in Stroke

PROMISE aims at identifying novel diagnostic and prognostic circulating biomarkers for patients with acute stroke and at informing on crucial yet undetected pathophysiological mechanisms driving outcome after stroke by enriching all phenotypic information available from clinical routine with in-depth quantification of the circulating proteome and metabolome as well as other entities.

The heterogeneity of ischemic stroke (IS) poses a challenge for assigning patients to optimal treatment strategies and is a major reason for the large number of failed clinical trials. Current diagnostic algorithms are insufficient to explain clinical outcomes arguing for crucial yet undetected pathophysiological mechanisms. Diagnostic tests further leave stroke etiology undetermined in 40 % of IS patients thus impeding the allocation of these patients to optimal secondary prevention regimens. Heterogeneity is also seen at the level of neuronal injury, which greatly varies between IS patients, but can neither be assessed in the pre-hospital setting nor serially in the acute phase to monitor stroke progression and to develop individual trajectories of neuronal loss over time. The circulating proteome and metabolome capture pathophysiological events from multiple organs including local and systemic events (e.g. stress) related to acute stroke and might thus inform on neuronal injury and the mechanisms causing stroke. The circulating proteome and metabolome may further inform on i) the systemic effects of stroke, which contribute significantly to stroke outcome but are under-researched, and ii) how concepts from preclinical stroke research such as reperfusion injury translate to human stroke. The investigators hypothesize that the combination of detailed clinical phenotyping with advanced profiling technologies (genomics, proteomics, and metabolomics) will enable the identification of key molecular signatures of IS that inform on pathophysiological mechanisms and might also be utilized as diagnostic instruments.

Eligibility Criteria:
Inclusion Criteria:

* Patients with acute ischemic stroke:
* Age 18 years or older
* Diagnosis of an acute ischemic stroke defined by an acute focal neurological deficit in combination with a diffusion-weighted imaging-positive lesion on magnetic resonance imaging or a new lesion on a delayed CT scan.
* Time from last seen well to admission and first blood sampling \< 24 hours
* Blood samples collected upon admission (day 1), the next morning (day 2), day 3, and day 7 (or day of discharge if earlier)
* Informed consent in accord with ethical approval
* Patients with acute intracerebral hemorrhage:
* Age 18 years or older
* Diagnosis of an acute intracerebral hemorrhage defined by an acute focal neurological deficit in combination with imaging-based evidence of intracerebral hemorrhage.
* Time from last seen well to admission and first blood sampling \< 24 hours
* Blood samples collected upon admission (day 1)
* Informed consent in accord with ethical approval
* Patients with stroke mimics:
* Age 18 years or older
* Diagnosis of a stroke-mimicking disease defined by an acute focal neurological deficit in combination with a lack of infarction on neuroimaging.
* Time from last seen well to admission and first blood sampling \< 24 hours
* Blood samples collected upon admission (day 1), the next morning (day 2), day 3, and day 7
* Informed consent in accord with ethical approval
* Healthy subjects:
* Age 18 years or older
* Informed consent in accord with ethical approval

Exclusion Criteria:

* Patients with acute ischemic stroke:
* Lack of follow-up CT or MRI imaging
* Major surgery within the last four weeks
* In-house stroke
* Myocardial infarction, ischemic stroke, transient ischemic attacks, traumatic brain injury, cerebral venous sinus thrombosis, any intracranial hemorrhage, thrombosis, or pulmonary embolism within the last four weeks
* Chronic inflammatory bowel disease or percutaneous endoscopic gastrostomy
* Patients with acute intracerebral hemorrhage:
* Major surgery within the last four weeks
* In-house stroke
* Myocardial infarction, ischemic stroke, transient ischemic attacks, traumatic brain injury, cerebral venous sinus thrombosis, any intracranial hemorrhage, thrombosis, or pulmonary embolism within the last four weeks
* Chronic inflammatory bowel disease or percutaneous endoscopic gastrostomy
* Patients with stroke mimics:
* Major surgery within the last four weeks
* Myocardial infarction, ischemic stroke, transient ischemic attacks, traumatic brain injury, cerebral venous sinus thrombosis, any intracranial hemorrhage, thrombosis, or pulmonary embolism within the last four weeks
* Chronic inflammatory bowel disease or percutaneous endoscopic gastrostomy
* Healthy subjects:
* Major surgery within the last four weeks
* Myocardial infarction, ischemic stroke, transient ischemic attacks, traumatic brain injury, cerebral venous sinus thrombosis, any intracranial hemorrhage, thrombosis, or pulmonary embolism within the last four weeks
* Chronic inflammatory bowel disease or percutaneous endoscopic gastrostomy