Cross Education for Upper Extremity Motor Function and Strength in Stroke

Stroke is the leading cause of disability and mortality worldwide. The impact of stroke on the upper extremity functions is a common and important cause of long-term disability. Indeed, six months after the stroke, a considerable amount of patients are still unable to incorporate the affected upper limb into their daily activities. On the other hand, weaknesses are also observed in the "apparently normal" ipsilateral side of the lesion due to the presence of corticospinal fibers that do not cross to the contralateral side of the medulla.

This study aims to investigate the effects of cross-education (CE) using robotic rehabilitation on upper extremity motor function and strength in patients with stroke. Secondary objectives include assessing quality of life and activities of daily living.

Researchers will compare CE using robotic rehabilitation to the control group (CON) that received lower extremity-focused exercises to see if CE works to enhance rehabilitation outcomes.

Participants will receive 20 min, twice weekly CE (to the less affected upper limb) or CON before the RR intervention included in the PT intervention administered 5 days in a week for 5 weeks. They will be evaluated using the relevant outcomes at the beginning and the end of the study (5th week).

After a stroke, upper extremity strength and skill deficits are predominant on the paretic side. In the chronic phase of stroke, patients with moderate to severe impairment also experience functional deficits on the less affected side, increasing dependence on this extremity during daily living activities. This situation highlights the necessity of incorporating the non-affected side into rehabilitation. Current rehabilitation approaches focus on intensive, highly repetitive, and task-oriented training. The aim within this framework is to induce neuroplasticity in the lesioned hemisphere to promote motor recovery. Techniques such as constraint-induced movement therapy are effective for inducing neuroplastic changes but are not suitable for all patient populations. Therefore, alternative treatment strategies are needed to induce neuroplastic changes in patients with greater upper extremity disability.

As stated above, promoting lesional hemispheric reorganization is crucial for recovery; however, the role of the contralesional motor cortex in recovery remains debated. Rehabilitation strategies must be tailored to the severity of motor impairment in patients. Cross-education (CE) emerges as a novel alternative rehabilitation strategy for individuals with moderate to severe motor impairment on the affected side. CE refers to the improvement in strength or skill in the contralateral limb through unilateral motor training. For stroke patients, this can be defined as gains in the paretic extremity through the training of the less affected side. Two main hypotheses underlie CE: the "cross-activation" and "bilateral access". The cross-activation model posits that unilateral activity stimulates both ipsilateral and contralateral cortical motor areas, whereas the bilateral access model suggests that training one side leads to adaptation in the untrained muscle on the opposite side via communication between motor areas in both hemispheres. Evidence indicates that in stroke patients, the corticospinal excitability of the affected hemisphere increases with CE-induced gains. functional magnetic resonance imaging (fMRI) studies in healthy individuals show that CE results in expanded activation areas in the contralateral sensorimotor cortex and the ipsilesional temporal lobe.

To date, studies on stroke involving CE have included strengthening exercises and task-oriented functional skill training, appearing effective in improving motor function and strength. Studies have shown that strength gains in stroke patients are greater compared to neurologically intact individuals. Robotic rehabilitation has proven effective in improving upper extremity motor functions and strength in stroke patients. However, no studies have investigated CE provided through unilateral robotic rehabilitation. This study aims to evaluate the effect of CE provided by an exoskeleton-type unilateral upper extremity robotic rehabilitation device on upper extremity motor function and strength.

Eligibility Criteria:
Inclusion Criteria:

* Chronic stroke more than 3 months of stroke onset
* History of first-ever unilateral ischemic or hemorrhagic stroke
* Upper extremity motor impairment; defined by an upper extremity score ≤42 on the Fugl Meyer upper extremity (FM-UE) assessment.
* No excessive spasticity in the affected arm (Modified Ashworth Scale ≤3)
* Having the ability to communicate and understand instructions (Mini-mental state examination ≥ 24)
* Being able to sit without needing any additional support and without leaning on a backrest

Exclusion Criteria:

* Cardiovascular instability (severe, uncontrolled hypertension, coronary artery disease, etc.)
* Other neurological or musculoskeletal problems that can affect upper extremity functions
* Severe upper extremity pain defined as \>7 on the Visual Analogue Scale
* Botox injections of the upper extremity within 3 months before enrollment