Introduction: the source of embolic stroke , in thrombotic embolism , is of unknown origin in 30-40% of cases. Fortunately , Mechanical thrombectomy provide a direct method to retrieve the stroke-incriminated clots from stroke patients for possibility of exo-autopsy analysis.

Introduction: the source of embolic stroke , in thrombotic embolism , is of unknown origin in 30-40% of cases. Fortunately , Mechanical thrombectomy provide a direct method to retrieve the stroke-incriminated clots from stroke patients for possibility of exo-autopsy analysis.

Aim of the study : collecting stroke-incriminated clots from definite known etiological sources, could build a matchable markers database (MMD) to identify the source of cryptogenic embolism in the near-future. Identification of that markers is done by novel RNA sequencing technology to identify the clot composition in direct way.

Methodology: This is a prospective REB-approved study of acute LVO ischemic stroke in patients receiving mechanical thrombectomy at a multiple centers . Immediately after thrombi will be retrieved by mechanical thrombectomy, they will be placed in RNA stabilization and storage solution (RNAlater). Each sample will be extracted for total RNA by the one approved regional university's Human Genomics lab using a standard protocol. NanoDrop Microvolume Spectrophotometers and Fluorometer will be used for RNA quantification.

Thrombi weight will be recorded among other patient data , risk factors , procedural data, usage of adjunctive drugs and macroscopic morphology of each clot . Pearson correlation was used for correlation analysis.

all clots will be handled in double blinded control manner ; where clots analysis will be divided into 2 groups where Group A : include clots with definite stroke etiology and submitted to the RNA analysis in blinded coded label .

Group B: include all clots with unknown stroke etiology and submitted to RNA analysis in cryptogenic label .

the trial will be conducted over 4 years period from 2018 to 2022, with expected sample size of 350 cases with 7 : 3 ratio of enrollment in both groups ( a, b).

all analysis will be re-audited in central genome analysis lab of Alexandria University .

Inclusion Criteria:

1. Informed consent as documented by signature
2. Age ≥ 18 to < 86 years
3. Clinical signs consistent with an acute ischemic stroke
4. Neurological deficit with a NIHSS of ≥ 8 and < 30
5. Patient is eligible for intravenous thrombolysis
6. Patient is eligible for endovascular treatment
7. Randomization no later than 4 hours 15 minutes after stroke symptom onset and initiation of IV t-PA must be started within 4 hours 30 minutes of stroke symptoms onset (onset time is measured from the time when the subject was last seen well)
8. Occlusion (TICI 0-1) of the intracranial internal carotid artery (ICA), the M1 segment of the middle cerebral artery (MCA), or both confirmed by CT or MR angiography, accessible for MT
9. Core-infarct volume of Alberta Stroke Program Early CT Score (ASPECTS) greater than or equal to 6 (≥6) based on baseline CT or MR imaging (MRI)

Exclusion Criteria:

1. Acute intracranial hemorrhage
2. Any contraindication for IV t-PA
3. Pre-treatment with IV t-PA
4. In-hospital stroke
5. Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential.
6. Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys
7. Known current participation in a clinical trial (investigational drug or medical device)
8. Renal insufficiency as defined by a serum creatinine > 2.0 mg/dl (or 176.8 µmol/l) or glomerular filtration rate (GFR) < 30 mL/min or requirement for hemodialysis or peritoneal dialysis
9. Severe comorbid condition with life expectancy less than 90 days at baseline
10. Known advanced dementia or significant pre-stroke disability (mRS score of ≥2)
11. Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad)
12. Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments.
13. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day).
14. Known history of arterial tortuosity, pre-existing stent, other arterial disease and/or known disease at the femoral access site that would prevent the device from reaching the target vessel and/or preclude safe recovery after MT
15. Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)
16. Radiological confirmed evidence of cerebral vasculitis
17. CTA or MRA evidence of carotid artery dissection
18. Evidence of additional distal intracranial vessel occlusion in another territory (i.e. A2 segment of anterior cerebral artery or M3, M4 segment of MCA) on initial NCCT/MRI or CTA/MRA