Pilot Study of Pre-Ischemic Conditioning for Intracranial Atherosclerosis

Inclusion Criteria: 1. Symptomatic cerebral infarction within 30 days of enrollment attributed to 70-99% stenosis of a major intracranial artery (carotid artery, MCA stem (M1), vertebral artery, or basilar artery) that is documented by any of the following: MRA, CTA, or catheter angiography. Percent stenosis will be measured according to WASID criteria (= 1 - \[Ds / Dn\]) x 100% with Ds \[diameter of stenosis\] and Dn \[diameter of normal vessel\]).19 2. Modified Rankin score of ≤ 3 3. Age ≥ 30 years and ≤ 90 years. Subjects 30-49 years are required to meet at least one additional criteria (i-vi) provided in the table below to qualify for the study. This additional requirement is to increase the likelihood that the symptomatic intracranial stenosis in subjects 30-49 years is atherosclerotic. * i. insulin dependent diabetes for at least 15 years * ii. at least 2 of the following atherosclerotic risk factors: hypertension (BP \> 140/90 or on antihypertensive therapy); dyslipidemia (LDL \> 130 mg /dl or HDL \< 40 mg/dl or fasting triglycerides \> 150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery in parent or sibling who was \< 55 years of age for men or \< 65 for women at the time of the event * iii. history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease * iv. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic * v. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography * vi. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic 4. Recent (within 30 days) negative pregnancy test in a female who has had any menses in the last 12 months 5. Subject is willing and able to return in 30 days for close-out visit for the study 6. Subject is available by phone 7. Subject is able to apply the conditioning device or has access to another person (family member, friend) who can assist with application of conditioning device if needed 8. Subject understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent 9. Subject is able to undergo brain MRI Exclusion Criteria: 1. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform one of these procedures 2. Plan to perform concomitant angioplasty or stenting of an extracranial vessel tandem to an intracranial stenosis 3. Intracranial tumor (except meningioma) or any intracranial vascular malformation 4. Thrombolytic therapy within 24 hours prior to enrollment 5. Progressive neurological signs within 24 hours prior to enrollment 6. Any intracranial hemorrhage (parenchmal, subarachnoid, subdural, epidural) within 90 days 7. Any untreated chronic subdural hematoma 8. Intracranial arterial stenosis due to arterial dissection, Moya Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with CSF pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; post-partum angiopathy; suspected vasospastic process, suspected recanalized embolus 9. Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction less than 30% 10. History of upper extremity ischemia, known subclavian or brachial artery stenosis, subclavian steal syndrome, any upper extremity soft tissue, orthopedic or vascular injury, or mastectomy or other procedure that may contraindicate taking blood pressure or having a cuff on the arm for the conditioning treatment 11. Difference in systolic blood pressure of \> 15 mm Hg between both arms 12. Known allergy to aspirin or clopidogrel 13. Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets \< 100,000, hematocrit \< 30, INR \> 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic pressure \> 180 mm Hg or diastolic pressure \> 115 mm Hg), severe liver impairment (AST or ALT \> 3 x normal, cirrhosis), subject on dialysis 14. Major surgery (including open femoral, aortic, or carotid surgery, cardiac) within previous 30 days or planned in the next 30 days after enrollment 15. Indication for warfarin or heparin beyond enrollment (NOTE: exceptions allowed for subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis while hospitalized) 16. Diabetic subjects taking sulfonylurea drugs 17. Severe neurological deficit that renders the subject incapable of living independently 18. Dementia or psychiatric problem that prevents the subject from following the protocol reliably 19. Co-morbid conditions that may limit survival to less than 3 months 20. Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study 21. Claustrophobia requiring sedation for MRI 22. Enrollment in another study that would conflict with the current study