The present proposal aims to assess whether a combined rehabilitation approach using virtual reality based therapy with motivational feedback, levodopa for pharmacotherapy and standard rehabilitative occupational therapy and physiotherapy will lead to signifcantly better outcomes for stroke recovery.

It is a randomised controlled trial with blinding of the assessors only. It will be preceeded by a Phase 1 pilot trial of the VR physiotherapy and standard therapy only. Recruited in-patient rehabilitation ward patients who have recently suffered stroke will be randomized, through a computer-based random number generator, to either one of two treatment arms:

1. Control occupational therapy + pharmacotherapy for 2 weeks
2. Assisted Virtual-Reality physiotherapy + pharmacotherapy for 2 weeks

The study is designed as a single-blinded randomized controlled trial, preceeded by a Phase 1 pilot trial of the VR physiotherapy and standard therapy only.

Phase 1 will comprise of recruitment of up to 5 patients who have recently suffered a stroke who will be informed that they will receive ten 15- 30 minutes of VR therapy in addition to their standard stroke therapy. They will not receive any pharmacotherapy during this period. At the start and end of the VR phase, clinical assessment (Fugl-Meyer scores, Action Research Arm Test) will be made of each patient by a blinded clinician investigator.

From this data, calibration to the VR program will be made to ensure reproducibility of effectiveness of movements assessed.

Subsequently, for the main phase of the trial, recruited in-patients who have recently suffered stroke will be randomized, through a computer-based random number generator, to either one of two treatment arms:

1. Control occupational therapy + pharmacotherapy
2. Assisted Virtual-Reality physiotherapy + pharmacotherapy

Each patient will receive an initial functional Magnetic Resonace Imaging (fMRI) scan prior to the start of the study. The initial pilot single-centre study will be run in the Singapore General Hospital Rehabilitation Ward across a 2-week period, where participants will undergo daily 15-30 minute VR based therapy in addition to the physiotherapy/occupational therapy session they receive daily.

The VR therapy session consists of the subject interacting with a computer-based program in which they guide an avatar to gather items by using flexion and extension gestures of the affected upper limb. VR therapy sessions will last for 15-30 minutes depending on the subject's tolerance and participation. For patients who are unable to overcome gravity fully, they can still participate in this therapy by resting their arm on a table.

Patients will receive a single dose of 100mg levodopa in combination with benserazide 2-3 hours before an additional half an hour of occupational therapy to the weaker arm or VR therapy session, depending on the assigned group.

At the start and end of the trial, clinical assessment (Fugl-Meyer scores, Action Research Arm Test and Functional Independence Measure) will be made of each patient by a blinded clinician investigator. At the final (10th) session, patients will undergo the final fMRI scan. MRI scans will be analysed by blinded assessors.

Inclusion Criteria:

• Age: 25-99yrs
• Right-handed
• Cognitively coherent, able to provide informed consent (MMSE >25)
• Newly diagnosed, first episode ischemic stroke in the past 2-21 days
• Motor score: Strength of 2-3 out of 5 on affected side upper limb

Exclusion Criteria:

• Declined consent to participate in the study
• Cognitive impairment or significant aphasia with inability to understand study requirements and inability to participate in therapy
• Other neurological or physical ailments with pre-existing motor weakness
• Haemorrhagic stroke
• Patient due to undergo significant medical interventions such as carotid endarthrectomy
• Patients on neuroactive agents prior to the stroke such as antidepressants
• Hypersensitivity to benserazide, levodopa, sympathomimetics, or any component of the formulation
• Use of MAO inhibitors within the last 14 days
• Patients with clinical or laboratory evidence of uncompensated cardiovascular, endocrine, renal, hepatic, hematologic, or pulmonary disease
• Patients with decompensated endocrine, renal, hepatic, cardiac disorders, psychiatric disorders, narrow-angle glaucoma, or closed-angle glaucoma;
• Patients <25 years of age (due to possibility of skeletal abnormalities from benserazide)
• Pregnancy or use in women of childbearing potential without adequate contraception.