This is a pilot study of thrombolytic therapy in patients with ischemic stroke who present with stroke symptoms upon awakening.

Patients with ischemic stroke are currently only eligible for the treatment with intravenous thrombolysis if the stroke is diagnosed within 4.5 hours from known onset of symptoms.

Many patients awaken with stroke and are excluded from this therapy, following current guidelines.

Patients who suffer from a stroke just before or after waking up may be candidates for thrombolysis and our study will use advanced neuroimaging to select those patients.

Inclusion Criteria:

1. Age ≥22
2. Stroke upon awakening
3. Measurable deficit by NIHSS
4. No deficit before sleep or last seen normal before to sleep
5. Head CT with no evidence of intracranial hemorrhage.
6. Able to receive IV t-PA treatment within 2.5 hrs after patient awoke with deficit.
7. Written informed consent signed and dated by the patient (or patient's authorized representative)
8. Core lesion: ASPECTS ≥7 on MRI-DWI, CTP-CBV or CTA source imaging.
9. Mismatch of at least 20% measured by CT CVB/MMT or DWI/TTP

Exclusion Criteria:

1. Stroke or serious head trauma within the preceding 3 months
2. Major surgery or serious trauma within 14 days
3. History of intracranial hemorrhage
4. Systolic blood pressure above 185 mm Hg or diastolic blood pressure above 110 mm Hg that is not controlled after aggressive measures.
5. Rapidly improving or minor symptoms
6. Symptoms suggestive of subarachnoid hemorrhage.
7. Gastrointestinal hemorrhage or urinary tract hemorrhage within the previous 21 days.
8. Arterial puncture at a non-compressible site within the previous 7 days
9. Seizure at the onset of stroke and considered the cause for the neurological symptom.
10. Patients who are taking anticoagulants or who had received heparin within the 48 hours preceding the onset of stroke and have an elevated partial-thromboplastin time, INR>1.7 or platelet counts below 100,000/mm3
11. Finger sticks glucose below 50 mg/dl (2.7 mmol/ Lt) or above 400 mg per deciliter (22.2 mmol/Lt) and considered the cause for the neurological symptom.
12. Active internal bleeding
13. Pregnancy in women of child-bearing potential (must have pregnancy test, urine or blood, prior to therapy).
14. Lumbar puncture within 7 days.
15. Known co-morbid conditions likely to complicate therapy or interfere with patient assessment, such us: heart failure stage 4, severe dementia, end-stage AIDS, pericarditis, cirrhosis or known cancer.
16. Unable to obtain CTA or perfusion brain studies (PWI or CTP)