Critical Periods After Stroke Study (CPASS)

To perform an exploratory single center randomized study that will form the basis for a larger scale, more definitive randomized clinical trial to determine the optimal time after stroke for intensive motor training. The investigators will perform a prospective exploratory study of upper extremity (UE) motor training delivered at higher than usual intensity at three different time points after stroke:

* early (initiated within 30 days)
* subacute/outpatient (initiated within 2-3 months)
* chronic (initiated within 6-9 months)

The control group will not receive the therapy intervention during the 1-year study.

Outcome measures will be assessed at baseline, pre-treatment, post-treatment, 6 months and one year after stroke onset.

Compared to individuals randomized during the outpatient (2-3 months after stroke onset) or chronic (6-9 months after stroke onset) time points, participants randomized to early intensive motor training will show greater upper extremity motor improvement measured at one year post stroke.

Please see the following reference:

Dromerick, A.W., Edwardson, M., Edwards, D.F., Giannetti, M.L., Barth, J., Brady, K.P., Chan, E., Tan, M.T., Tamboli, I., Chia, R., Orquiza, M., Padilla, R.M., Cheema, A.K., Mapstone, M., Fiandaca, M.S., Federoff, H.J., \& Newport, E.L. (2015). Critical Periods after Stroke Study: Translating animal stroke recovery experiments into a clinical trial. Frontiers in Human Neuroscience, 9, 002231. PMCID: PMC4413691.

Eligibility Criteria:
Inclusion Criteria:

* Ischemic or hemorrhagic stroke (with confirmatory neuroimaging) within 28 days of admission to inpatient rehabilitation (allows those randomized to the early arm to begin study-related treatment within 30 days)
* Age \>21 years
* Able to participate in first study-related treatment session within 30 days of stroke onset
* Able to participate in all study-related activities, including one year follow up and blood draws
* Persistent hemiparesis leading to impaired upper extremity function. Hemiparesis as indicated by NIHSS Motor Arm score ≥ 1
* Recovering moderate motor impairment at the shoulder and elbow or hand such as:

  * Proximal UE voluntary activity indicated by a score of ≥ 3 on the upper arm item of the Motor Assessment Scale - wrist and finger movement is not required

or

* Manual Muscle Test (MMT) score of ≥ 2 on shoulder flexion or abduction and MMT score of ≥ 2 for any of the following: elbow flexion, elbow extension, wrist flexion, wrist extension, finger flexion or finger extension.

or

* Active range of motion (AROM) to at least 50% of range in gravity eliminated position for shoulder flexion or abduction, and for any of the following motions: elbow flexion, elbow extension, wrist flexion, wrist extension, finger flexion or finger extension.

  * Score of ≤ 8 on the Short Blessed Memory Orientation and Concentration Scale
  * Follows 2 step commands
  * No upper extremity injury or conditions that limited use prior to the stroke
  * Pre-stroke independence: Modified Rankin Score 0 or 1

Exclusion Criteria:

* Inability to give informed consent
* Prior stroke with persistent motor impairment or other disabling neurologic condition such as multiple sclerosis, parkinsonism, amyotrophic lateral sclerosis (ALS), dementia requiring medication
* Rapidly improving motor function
* Clinically significant fluctuations in mental status in the 72 hours prior to randomization
* Hemispatial neglect as determined by \>3 errors on the Mesulam Symbol Cancellation Test
* Not independent prior to stroke (determined by scores of \<95 on Barthel Index or \>1 on Modified Rankin Scale
* Dense sensory loss indicated by a score of 2 on NIHSS sensory item
* Ataxia out of proportion to weakness in the affected arm as described by a score of ≥ 1 on the NIHSS limb ataxia item
* Active or prior psychosis within 2 years
* Active or prior (within 2 years) substance abuse
* Not expected to survive 1 year due to other illnesses (cardiac disease, malignancy, etc)
* Received upper extremity botulinum toxin within 6 months (other medications do not exclude)