Please select the eligibility criteria that correspond to the clinical trial below.
Title: Protective Effects of Long-term Remote Limb Ischemic Preconditioning For Carotid Artery Stenting
Brief Summary: Remote limb ischemic preconditioning (RIPC) has neuro-protective and anti-inflammatory effects on ischemia- reperfusion injury. As the extent of its effect is unknown, the investigators will use clinical outcome, serum biochemical markers and brain magnetic resonance imaging (MRI) to determine whether RIPC has neuro-protective and anti-inflammatory effects on patients undergoing carotid artery stenting.


Options:
A: General Inclusion Criteria:

1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, and subject belongs to one of the following subgroups:

   1. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 min after administration)
   2. Subject is contraindicated for IV t-PA administration
2. Age ≥18
3. Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume)
4. Subject can be randomized between with 6 to 24 hours after time last known well
5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1)
6. Anticipated life expectancy of at least 6 months
7. Subject willing/able to return for protocol required follow up visits
8. Subject or subject's Legally Authorized Representative (LAR) has signed the study Informed Consent form\*

   * If approved by local ethics committee and country regulations, the investigator is allowed to enroll a patient utilizing emergency informed consent procedures if neither the patient nor the representative or person of trust is available to sign the informed consent form. However, as soon as possible, the patient is informed and his/her consent is requested for the possible continuation of this research. (Not applicable to U.S. Sites.)

Imaging Inclusion Criteria:

1. \< 1/3 MCA territory involved, as evidenced by CT or MRI
2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA
3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or CTP-rCBF maps:

   1. 0-\<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old)
   2. 0-\<31 cc core infarct and NIHSS ≥ 10 (and age \< 80 years old)
   3. 31 cc to \<51 cc core infarct and NIHSS ≥ 20 (and age \< 80 years old)

General Exclusion Criteria:

1. History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history
2. Rapid improvement in neurological status to an NIHSS \<10 or evidence of vessel recanalization prior to randomization
3. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept)
4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment
5. Baseline blood glucose of \<50mg/dL (2.78 mmol) or \>400mg/dL (22.20 mmol)
6. Baseline hemoglobin counts of \<7 mmol/L
7. Baseline platelet count \< 50,000/uL
8. Abnormal baseline electrolyte parameters as defined by sodium concentration \<130 mmol/L, potassium concentration \<3 mEq/L or \>6 mEq/L
9. Renal failure as defined by a serum creatinine \>3.0 mg/dL (264 µmol/L) NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels
10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR \> 3.0 or PTT \> 3 times normal. Patients on factor Xa inhibitor for 24-48 hours ago must have a normal PTT.
11. Any active or recent hemorrhage within the past 30 days
12. History of severe allergy (more than rash) to contrast medium
13. Severe, sustained hypertension (Systolic Blood Pressure \>185 mmHg or Diastolic Blood Pressure \>110 mmHg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication the subject can be enrolled
14. Female who is pregnant or lactating at time of admission
15. Current participation in another investigational drug or device study
16. Presumed septic embolus, or suspicion of bacterial endocarditis
17. Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization

Imaging Exclusion Criteria:

1. Evidence of intracranial hemorrhage on CT/MRI
2. CTA or MRA evidence of flow limiting carotid dissection, high-grade stenosis, or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy).
3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude device delivery/deployment
4. Suspected cerebral vasculitis based on medical history and CTA/MRA
5. Suspected aortic dissection based on medical history and CTA/MRA
6. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the Trevo device
7. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical evidence of bilateral strokes or strokes in multiple territories
8. Significant mass effect with midline shift as confirmed on CT/MRI
9. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI
B: Inclusion Criteria:

* Significant ischemic stroke suspicion (NIHSS 1-24) and paresis of an extremity.
* Treatment with rtPa within 4.5 hours from debut of symptoms.
* Age above 18 (changed from 01.01.2010 to no upper age limit)
* Independent in daily living before the acute onset of symptoms. (mrs\</=2)
* MR scan showing DWI lesion, consistent with acute ischemic stroke.

Exclusion Criteria:

* Contraindications for iv rtPA
* Onset of symptoms older than 4.5 hours
* Previous diseases of the brain: Intracranial aneurisms or arteriovenous malformations. Brain surgery or hemorrhagic stroke. Former ischemic stroke within the last 3 months.
* Heart diseases: Infectious endocarditis or suspicion of septic emboli, pericarditis, ventricular thrombosis, aneurisms of the heart wall or major heart failure.
* Serious diseases: Cancer, AIDS, dementia, significant abuse, renal failure, liver diseases such as liver failure, cirrhosis, portal hypertension, active hepatitis.
* Pregnancy
* Major ischemic stroke where the patient is unconscious.(NIHSS \> 25).
* Symptoms suspect for migraine, Multiple sclerosis, TIA or another neurological disease than ischemic stroke.

MR scan:

* Contraindications for MRI scans
* Tumor cerebri, cerebral abscesses
* Known hypersensitivity to Gadovist or any of its ingredients, acute or chronic severe renal impairment (GFR \< 30 ml/min/1.73m2), acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period.
* Caution with using Gadovist to patients with severe cardiovascular disease, and only to be used after a risk-benefit assessment.
* Caution with using Gadovist in patients with low threshold for seizures.

Lab data:

* Blood glucose \< 2, 8 mmol/l or \> 22 mmol/l
C: Inclusion Criteria:

1. age between 80 to 95 years old
2. Trial of Org 10172 in Acute Stroke Treatment-1 (TOAST-1) subtype
3. National Institutes of Health Stroke Scale (NIHSS) score 0-15, and Modified Rankin Scale (mRS) score 0-4
4. ABCD2 score between 6 to 7
5. stable vital signs, normal hepatic and renal functions
6. no hemorrhagic tendencies

Exclusion Criteria:

1. within 72 hrs of intra-artery or intravenous thrombolysis
2. intracranial hemorrhage or large area of cerebral infarction (more than 1/3 middle cerebral artery perfusion territory)
3. any soft tissue, orthopedic, or vascular injury, wounds or fractures in extremities which may pose a contraindication for application of the preconditioning cuffs
4. acute myocardial infarction
5. systolic blood pressure more than 200 mmHg after drug control
6. peripheral blood vessel disease
7. hematologic disease
8. severe hepatic and renal dysfunction
9. severe or unstable concomitant disease
10. cannot tolerate BLIPC or without informed consent
D: Inclusion Criteria:

1. Symptomatic or asymptomatic carotid artery stenosis. In symptomatic patients the degree of stenosis should more than 60% (Based on NASCET Criteria), in asymptomatic patients the degree of stenosis should more than 70% (Based on NASCET Criteria);
2. Tolerance to any of the study medications, including clopidogrel, aspirin and statins;
3. Can cooperate with and complete brain MRI examination;
4. Has a negative pregnancy test within 7 days before randomization and no childbearing potential;
5. Vascular ultrasound excluded intravascular thrombosis and unstable plaques in blood vessels of the bilateral upper limbs;
6. No hemorrhagic tendency;
7. Stable vital sign, normal renal and hepatic functions;
8. Informed consent.

Exclusion Criteria:

1. Evolving stroke;
2. Prior major ipsilateral stroke, if likely to confound study endpoints;
3. Severe dementia;
4. Hemorrhagic conversion of an ischemic stroke within the past 60 days;
5. Chronic atrial fibrillation;
6. Myocardial infarction within previous 30 days;
7. Inability to understand and cooperate with study procedures or provide informed consent;
8. Participating in other device or drug trial that has not completed the required protocol follow-up period;
9. Any conditions that hampers proper angiographic assessment or makes percutaneous arterial access unsafe;
10. High risk candidates defined as the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST);
11. Any vascular, extremity soft tissue or orthopedic injury that may contraindicate bilateral arm ischemic preconditioning (e.g. superficial wounds and fractures of the arm);
12. Blood pressure cannot be controlled lower than 200 mmHg by medications;
13. Peripheral blood vessel disease (especially subclavian arterial and upper limb artery stenosis or occlusion).

Answer: D