Safety Escalating Repeat IV, in Stroke Patients

Inclusion Criteria

• Have a confirmed diagnosis of stroke
• Stroke onset must be within the last 24-72 hours.
• Have a stroke that is either:
• radiologically confirmed to be ischaemic and supratentorial. The diameter of the ischemic lesion is >15mm in any singlle direction or the volume is >4cc. OR
• radiologically confirmed to be an intracerebral hemorrhage that is supratentorial, deep (i.e., blood must not directly contact cerebral cortex) and with minimal or no intraventricular extension. The Intracerebral Hemorrahage (CH) score must be 0-2 and is calculated based on age, Galsgow coma Scale score ad the initial CT or MRI findings for the index stroke. See the SOM for the full calculation procedure.
• Have a total NIHSS score of 3-21.
• Have an upper and/or lower limb deficit defined as:
• Score of 1-3 on the NIHSS Motor Arm question, and palpable and observable voluntary extension or flexion of the fingers. AND/OR b. Score of 1-3 on the NIHSS Motor Leg question
• Aged 18-90, inclusive.
• Male subjects and females of non-child-bearing potential are allowed to participate in this study.
• Females of child-bearing potential are also allowed to participate in this study provided they are using a contraceptive method with a failure rate of 2.
• Presence of depression that is active and not adequately controlled such that it interferred with major activities of daily living immediately prior to the current stroke.
• Subjects who are not alert or are unresponsive as defined by a score of 2 or 3 on the NIHSS Level of Consciousness question (question #1a).
• Presence of significant aphasia as likely to confound or interfere with completion of the study assessments.
• Presence of peripheral neuropathy, including diabetic neuropathy, which is clinically active and symptomatic at time of screening.
• Presence of neurological or psychiatric disease, such as dementia or mild cognitive impairment, prior to study entry that is likely to confound clinical evaluations.
• Presence of a demyelinating disease, such as multiple sclerosis.
• Evidence of other chronic co-morbid conditions or unstable acute systemic illnesses which, in the opinion of the investigator, could shorten the subject's survival or limit his/her ability to complete the study.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Presence of QTcB > 500 msec; or uncorrected QT >600msec (machine or manual over-read) on baseline ECG.
• Contraindication to TMS, such as:
• have metal present, such as hardware or plate on the scalp in the area to which TMS will be applied, implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials
• occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan.
• concomitant use of drugs that substantially lower seizure threshold (e.g., tricyclic antidepressants and neuroleptics)
• known history of seizures or epilepsy
• brain tumor, recent brain injury (within 5 years) associated with definite loss of consciousness, or any history of brain surgery
• Contraindication to MRI, such as:
• have metal present, such as implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials, permanent tattooed metallic eye-liner
• occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan.
• claustrophobia
• Participation in any investigational rehabilitation paradigm targeting stroke recovery during the duration