The investigators recently identified Brain-derived tau (BD-tau) as a sensitive blood-based biomarker for brain injury in acute ischemic stroke: in patients with acute ischemic stroke, plasma BD-tau was associated with imaging-based metrics of brain injury upon admission, increased within the first 24 hours in correlation with infarct progression, and at 24 hours was superior to final infarct volume in predicting 90-day functional outcome. While informing on the relation of BD-tau with imaging-based metrics of brain injury, this cross-sectional study was restricted to BD-tau assessments upon admission and at day 2 and could not inform on key characteristics of the evolution of plasma BD-tau, including when exactly it starts to rise, how long it continues to rise, and how it is determined by infarct characteristics as well as comorbidities. Here, the investigators aim to assess plasma BD-tau every hour from admission to 48 hours after onset to evaluate the hypothesis that BD-tau rises immediately after onset and plateaus between three and 48 hours after onset.
clinical diagnosis of acute ischemic stroke
presentation within 9 hours of symptom onset
large- or medium-vessel occlusion (i.e. an occlusion of the ICA, MCA [segments M1-M4], ACA [segments A1-A3], basilar artery, or PCA [segments P1 to P3]) confirmed by CT or MRI angiography
at least 18 years of age
CT or MRI showing intracranial hemorrhage upon admission
A history of ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, subdural hematoma, epidural hematoma, CNS tumor, meningitis, or encephalitis within the last three months
dementia
pre-stroke disability defined as a premorbid modified Rankin Scale score > 2
Patients will be recruited upon admission to a tertiary care hospital.
Cohort
Prospective
Plasma levels of BD-tau
Diagnostic testPlasma levels of BD-tau will be assessed using a single-molecule array assay.
The primary outcome are plasma BD-tau levels in acute ischemic stroke.
The evolution of BD-tau levels will be characterized by: * the time point when plasma BD-tau levels start to rise after onset (defined as the earliest time point \[in relation to onset\] that showed higher BD-tau levels compared with the previous assessment and lower levels compared with the next assessment), * the type of rise (e.g. linear, exponential, or logarithmic), and * until when plasma BD-tau levels continue to rise (defined as the time point \[in relation to onset\] compared to which BD-tau levels do not increase by ≥ 5 % compared to 1h, 2h, and 3h afterwards). 5 % were chosen without prior knowledge and in an attempt to account for assay-dependent variations of BD-tau quantifications (coefficient of variation 8-9 %)18 while keeping a biologically and clinically plausible value (rather than e.g. 10 %).
ASPECTS on non-contrast CT
Ischemic core volume on CT perfusion
Regional leptomeningeal collateral score on CT angiography
Final infarct volume
Final infarct volume will be assessed on delayed neuroimaging (CT or MRI), at least 48 after symptom onset.
Plasma levels of NfL
Plasma levels of NfL will be assessed at an hourly basis using a single-molecule array assay.
Plasma levels of GFAP
Plasma levels of GFAP will be assessed at an hourly basis using a single-molecule array assay.
Plasma proteome and metabolome composition
Plasma proteome and metabolome composition will be assessed using mass spectrometry or alternatives.
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