Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intra-arterial Autologous Bone-marrow Mononuclear Cells Infusion for Acute Ischemic Stroke. A Phase II, Open-label, Multicenter, Randomized and Controlled Clinical Trial.
Brief Summary: This trial aims to test that intra-arterial injection of autologous bone marrow mononuclear cells in acute ischemic stroke patients is safe and improves neurological outcomes.


Options:
A: Inclusion Criteria:

1. Sudden onset of focal neurologic deficit or impairment of consciousness.
2. CT or MRI scan of head showing no haematoma and relevant lesions within the MCA and ACA territory.
3. Age between 30 -70 years (after amendment 18 -70 years).
4. \>7 to \</=30 days passed since the onset of the qualifying event.
5. Glasgow Coma Scale score of \>8 at the time of randomization, in aphasic Eye and Motor score of \>6.
6. Modified Barthel Index score of 50 or less at the time of randomization.
7. NHISS score of 7 or more points and inability to walk unaided or raise upper limb by 90 degree.
8. Patient is stable. ( normal respiration, afebrile, BP less than mean arterial pressure of 125 mm of Hg, fasting blood sugar \< 200 mg% and normal urea/electrolytes for at least 48 hours.)

Exclusion Criteria: -

1. Lacunar syndrome
2. Intubation
3. Posterior circulation stroke
4. Co morbidity likely to limit survival to less than 3 years eg. Hepatic or renal failure.
5. Inaccessibility for follow up.
6. Allergy to local anaesthetic.
7. Unwillingness to provide written informed consent.
8. Symptom of acute myocardial infarction or acute involvement of any other organ.
9. Pregnancy 10. HIV positive 11. Patient is a part of any other trial in last 6 months.
B: Inclusion Criteria:

1. Men or women (women must be of non-child bearing potential), age 30-75 yrs.
2. Have a stroke that is observed within 90 days of the onset of symptoms
3. Radiologically

   1. Relevant lesions within the middle cerebral artery territory (MCA) as assessed using diffusion-weighted imaging (DWI).
   2. The maximum diameter of the stroke region in any dimension must be ≥15 mm.
   3. Not involving more than a half of the ipsilateral periventricular zone
4. Clinically (National Institutes of Health stroke scale, NIHSS)

   1. Moderate-to severe persistent neurologic deficit (NIHSS of 6-21 inclusive)
   2. New onset of extremity paresis on the affected side, defined as a score of 2-4 on the NIHSS Motor Arm (item 5) or Leg (item 6) question.
   3. Must be alert or drowsy but easily arousable as defined by score of 0-1 on the NIHSS Level of Consciousness question (item 1).
   4. "Slow recovery" defined as Change in NIHSS ≤1 point/3 days
5. Willingness

   1. Reasonable likelihood of receiving standard physical, occupational and speech rehabilitation therapy as indicated for the post stroke deficits.
   2. Able to participate in the evaluation process to the point of accurate assessment.
   3. Willing and able to comply with scheduled visits, lifestyle guidelines, treatment plan, laboratory tests, and other study procedures.
   4. Evidence of a personally signed and dated informed consent document.

Exclusion Criteria:

1. Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke modified Rankin score of 2 or more.
2. Have a stroke that is either

   1. lacunar infarction
   2. Hematologic cause of stroke
   3. Recurrent or progressive stroke within 1 week at the time of screening.
3. Hematologic disorders or bone marrow suppression.
4. Have a severe medical illness

   1. Severe heart failure
   2. Severe febrile illness
   3. Hepatic or renal dysfunction
   4. Active cancer
   5. Any evidence of chronic co-morbid condition or unstable acute systemic illnesses which, in the opinion of the investigator, could shorten the subject's survival or limit ability to complete the study.
5. Presence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis on admission blood tests
6. Presence of depression that is active and not adequately controlled such that it interfere with major activities of daily living immediately prior to the current stroke.
7. Presence of dementia prior to the current stroke that is likely to confound clinical evaluation.
8. Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test or lactating females.
9. Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol
10. Subjects unwilling to undergo bone marrow aspiration
C: Inclusion Criteria:

* Patients with middle cerebral artery (MCA) acute ischemic stroke.
* Time of stroke onset is known and treatment can be started between day 1 and 7 of onset.
* DWI-MRI has reliably shown acute MCA ischemic lesions
* Magnetic resonance angiography (MRA) must confirm ipsilateral MCA permeability
* National Institute of Health Stroke Scale score of 6-20 at inclusion
* Age 18-80 years
* Written informed consent has been obtained

Exclusion Criteria:

* Hemorrhagic stroke or symptomatic hemorrhagic transformation
* Lacunar infarction
* Preocclusive stenosis or total occlusion of ipsilateral carotid artery
* Worsening of ≥4 points in National Institute of Health Stroke Scale in the 24 hours previous to inclusion, attributable to edema or hemorrhagic transformation or suspicious of malignant edema
* Decrease of consciousness with a Glasgow Coma Scale of \<8 points
* Patients with present or previous malignant disease during the last 5 years, except for basal cell carcinoma
* Contraindication for MRI or for bone marrow harvest
* Previous diagnosis of neurodegenerative disease
* Acute heart failure
* Hepatic or renal dysfunction (creatinine \>2mg/dL)
* Coagulopathy
* Severe co-morbidity
* Pregnancy, childbearing potential (unless it is certain that pregnancy is not possible) or breast feeding
* Modified Rankin Score (mRS) before stroke of ≥2
* Participation in any clinical trial in the last 3 months
D: Inclusion Criteria:

* Documented history of one completed ischemic stroke in subcortical region of MCA or lenticulostriate artery with or without cortical involvement
* Between 6 and 60 months post-stroke, and having a motor neurological deficit
* No significant further improvement with physical therapy/rehabilitation
* Able and willing to undergo computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) scans of the head

Exclusion Criteria:

* History of more than 1 symptomatic stroke
* History of seizures
* History or presence of any other major neurological disease
* Myocardial infarction within prior 6 mos.
* Known presence of any malignancy except squamous or basal cell carcinoma of the skin
* Participation in any other investigational trial within 4 weeks of initial screening and within 7 weeks of study entry
* Contraindications to head CT, MRI, or PET
* Pregnant or lactating

Answer: C