Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Random Controlled, Double-Blind Clinical Trial: Remote Ischemic Preconditioning and Cerebral Small Vessel Disease
Brief Summary: The hypothesis of this study is that remote ischemic preconditioning (RIPC) might have a beneficial effect on outcomes of cerebral small vessel disease (CSV).


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:

1. Subjects aged 40-80 years;
2. Ischemic cerebrovascular event onset, if any, must be within 6 months;
3. TCD and carotid ultrasound exclude vascular narrow that can cause hemodynamic changes (usually \>50% narrow lumen);
4. MRI confirmed the presence of lacunar infarction and / or generalized white matter lesions;
5. Written consent was obtained from the subject.

Exclusion Criteria:

1. History of intracranial hemorrhage;
2. Significant bleeding from other parts of the body;
3. History of atrial fibrillation;
4. History of myocardial infarction within six months;
5. Moyamoya disease or vasculitis;
6. Hereditary small vessel disorders, such as CADASIL, FABRY, and mitochondrial encephalo-myopathy;
7. Significant bleeding-coagulation dysfunction;
8. Abnormal blood pressure, glucose and/or lipids after restrict treatment regimen;
9. Severe liver/kidney disease, cancer or critical illness of internal medicine and surgery.
C: Inclusion Criteria:

* adult patients undergoing cardiac surgery

Exclusion Criteria:

* emergent operation
* preoperative use of inotropics or mechanical assist device,
* left ventricular ejection fraction less than 30%,
* severe liver, renal and pulmonary disease,
* recent myocardial infarction (within 7 days),
* recent systemic infection or sepsis (within 7 days)
* peripheral vascular disease affecting upper limbs
* amputation of the upper limbs
* major combined operation such as aortic surgery or carotid endarterectomy
* descending thoracic aortic surgery
* rare surgeries; cardiac transplantation, correction of complicated congenital anomalies, pulmonary thromboembolectomy, etc
D: 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

Answer: B