CR will focus on neurodevelopmental techniques with emphasis on functional tasks when possible. The functional training will be designed based on patients' motor capacity and include gross motor and fine motor dexterity training, and transitive and intransitive training. Stretching of the more affected limb, passive and active range of movements, and normalizing muscle tone by applying reflex inhibition patterns, inhibiting abnormal patterns, weight bearing with the affected limb will be applied to assist in functional task practice.

The Myoton is a hand-held device measure of three mechanical properties of muscle: tone, stiffness and elasticity. Three measurement parameters in the Myoton: F - Frequency, Hz, characterizes muscle tone; D - Decrement, characterizes muscle elasticity; S - Stiffness, N/m, characterizes muscle stiffness. There have been several prototypes of Myoton. Present study will use MyotonPRO; the basic principle is the same in all prototypes but the MyotonPRO has several updates such as a triaxial accelerometer. Comparing with the single axis accelerometer in the earlier prototypes, MyotonPRO makes it more feasible for application.

Muscle metabolic dysfunction will be measured by the near-infrared ray spectroscopy (NIRS). The NIRS will be applied to both the affected and the unaffected arms. The NIRS sensor will be fixed on the targeted muscle of one of the forearms and a cuff is placed on the upper arm of the same side. The artery occlusion will be applied by inflating the cuff to a pressure of at least 60 to 80 above systolic pressure to block both venous outflow and artery inflow. The artery occlusion will last approximate 30 seconds then the cuff pressure is released. The decrease rate of oxyhemoglobin and the increase rate of deoxyhemoglobin during artery occlusion can reflect muscle's anaerobic metabolism during vasoconstriction. The hyperaemic response of the muscle during recovery phase can be characterized by reoxygenation rate and recovery time.

The BBT will be used as a test of manual dexterity. There are 150 blocks in a test box. When testing begins, the subject should grasp one block at a time with dominant hand, transport the block over the partition, and release it into the opposite compartment. Instruction of this test is "I want to see how quickly you can pick up one block at a time with your right (or left) hand [point to the hand]. Carry it to the other side of the box and drop it. Make sure your fingertips cross the partition." The testing time is one minute. Then, the procedure will be repeated with the nondominant hand. After testing, the examiner should count the blocks. The score is the number of blocks carried from one compartment to the other in one minute. Score for each hand will be separately calculated.

The changes on somatosensory function will be determined by the RNSA. This is a standardized tool with good reliability to measure sensory function in the stroke population.The RNSA includes 3 major types of sensation: tactile sensation, proprioception, and stereognostic sense. For the purpose of this study, the regions of upper limb will be selected to be assessed.

The FIM consists of 18 items grouped into 6 subscales measuring self-care, sphincter control, transfer, locomotion, communication, and social cognition ability. Each item is rated from 1 to 7 (maximum score 126) based on the required level of assistance to perform the tasks (e.g., 1-complete assistance and 7-complete independence). A low score on any subscale indicates a more severe disability.

The MAL will be used to capture the level of use of affected upper limb in daily living. The MAL is a semi-structured interview assessing the amount of use (AOU) and quality of movement (QOM) of the affected arm in 30 main daily activities. It scores 0-5 for each activity. Higher score means better performance of the affected arm.

The ABILHAND Questionnaire will be used to evaluate the ability of upper limb in bimanual activities. There are 23 bimanual activities to measure subjectively perceived difficulty of patients in performing some common activities in daily living, such as buttoning, cutting nails, and opening a bottle. It scores on a scale of 0-3 (0-cannot perform, 1-performs partially or with great difficulty, 2-performs with some difficulty, 3-performs fully). Its reliability and construct validity has been confirmed.

The AAP will be applied to indicate the level of participation in household and community activities. This profile includes 21 activities in the four areas: domestic chores, household maintenance, service to others, and social activities. It scores on a scale of 0-3, with higher score indicating more frequent participation.

The EQ-5D-5L is an instrument for measuring health status. It consists of the descriptive system and the EQ visual Analogue scale (EQ VAS). The descriptive system comprises the same 5 dimensions (mobility, self care, usual activities, pain/discomfort, and anxiety/depression). There are 5 levels for each dimension: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'.

The activity monitors (i.e. accelerometers) will be used to provide a direct and objective measure of the amount of the impaired arm movement outside the laboratory. This measure, quantitatively recording the amount of activity in free-living conditions, will be used to reflect increase in the amount of affected arm use over time. The participants will be asked to wear an accelerometer on each arm for 3 consecutive days to measure what they actually do. The accelerometers to be used will be wireless plastic units about the size and weight of a large wristwatch that will be worn proximal to the wrist on terrycloth bands.

Participants will receive fMRI scanning before and after the intervention on a 3T clinical MRI scanner at Chang Gung Memorial Hospital in Linkou. During the scanning sessions, the head and the unaffected hand of the participants will be restrained and stabilized in a head coil and by a customized splint mask and a wooden apparatus with straps, respectively. Both of their upper limbs will be posited by their torsos. During the two sessions of examination, the relative activity time courses of the blood oxygenation level-dependent (BOLD) response will be collected for further analysis.

The kinematic analysis will involve unilateral and bilateral tasks, in which the participants will be asked to perform by using the affected upper limb or both upper limb simultaneously. A motion analysis system with 7 cameras (VICON MX 30d, Oxford Metrics Inc., Oxford, UK) will be used to capture the motion of arm (s) in kinematic testing. The markers will be attached on the styloid processes of the ulna. Depending on the unilateral or bilateral tasks, the makers will be placed on the affected arm or the both arms, respectively.

Proinflammatory markers and anti-inflammatory markers will be used to reflect the changes on inflammation. Proinflammatory markers include C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, soluble intercellular adhesion molecule (sICAM), and matrix metalloproteinase 9 (MMP 9). Anti-inflammatory markers include IL-10 and IL-1 receptor antagonist.

Oxidative stress markers and antioxidative markers will be used to reflect the changes on oxidative stress. Oxidative stress makers include malondialdehyde (MDA), 8-Hydroxy-2-deoxyguanosine (8-OHdG), and immunoglobulin G (IgG), whereas antioxidants include superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase.

The Elongation Index (EI) will be used to determine the red blood cell deformability, which is based on an isointensity curve in the diffraction pattern by using an ellipse-fitting program. EI is calculated by (L-W)/(L+W), where L and W are the major and minor axes of the ellipse, respectively. The deformability index (δ) is defined as the ratio of the major to the minor axis length (L/W).

To investigate the relationships between blood glucose levels and functional outcomes, we will also test the level of glucose and HbA1C for the participants before and after rehabilitation intervention.