This randomized pilot clinical study aims to investigate the effects of trans-auricular vagus nerve stimulation (tVNS) on neuromotor recovery in patients in the subacute phase after stroke. Participants admitted for intensive rehabilitation at ICS Maugeri Centers (Montescano, Pavia, Nervi) will be randomized into four groups receiving either traditional or technological rehabilitation (Khymeia device), combined with active or sham tVNS.
The Parasym® device (CE 0197) delivers non-invasive stimulation of the auricular branch of the vagus nerve at the left ear for 60 minutes daily.
The primary outcome is the improvement in upper limb motor function, assessed by the Fugl-Meyer scale. Secondary outcomes include other clinical, cognitive, and psychological measures, as well as neurophysiological and cardiovascular autonomic parameters.
The study hypothesizes that coupling tVNS with rehabilitation enhances cortical plasticity and accelerates motor recovery. Adverse effects are expected to be minimal, with previous studies reporting only mild transient skin irritation. The results may provide new insights into the neurophysiological mechanisms of recovery and support the integration of non-invasive neuromodulation in post-stroke rehabilitation.
Patients with hemiplegia following ischemic or hemorrhagic stroke occurred within the previous 6 months, clinically stable
Age ≥ 18 years
Single cortical or subcortical lesion documented on neuroimaging, corresponding to the motor deficit
Cognitively able to understand and follow therapeutic instructions
Multiple brain lesions on neuroimaging
Severe spasticity (Modified Ashworth Scale 3-4)
Aphasia preventing comprehension of verbal instructions
Cognitive decline or behavioral disorders interfering with collaboration during training
Parallel
Active trans-auricular vagus nerve stimulation (tVNS)
DeviceActive tVNS with the Parasym® device (CE 0197). Electrode placed on the left tragus, 25 Hz, 250 μs, intensity to tolerance, 60 min/day, 5 days/week for 4 weeks.
Sham tVNS
DeviceSham tVNS using the Parasym® device with electrodes on the left earlobe (non-vagal area). Same schedule as active tVNS (60 min/day, 5 days/week for 4 weeks).
Khymeia robotic upper limb rehabilitation
DeviceRobotic-assisted rehabilitation for the upper limbs using the Khymeia system.
Traditional Rehabilitation
BehavioralStandard traditional physical therapy and rehabilitation protocols for upper limb recovery.
Upper limb motor recovery assessed by Fugl-Meyer Assessment (FMA-UE)
The FMA-UE is a scale used to measure sensorimotor impairment. Scores range from 0 to 66, where higher scores indicate better motor function.
Functional Independence Measure (FIM)
The FIM assesses the physical and cognitive disability of a patient. Total scores range from 18 to 126, where higher scores indicate greater independence in activities of daily living.
Barthel Index
The Barthel Index measures the extent to which a person can function independently and has mobility in activities of daily living (ADL). The total score ranges from 0 to 100, where higher scores indicate better performance and greater independence.
Mini-Mental State Examination (MMSE)
The MMSE is a 30-point questionnaire used to measure cognitive impairment. Scores range from 0 to 30, where higher scores indicate better cognitive function (scores ≥24 are typically considered normal).
Frontal Assessment Battery (FAB)
The FAB is a brief tool to assess frontal lobe functions (executive functions). Total scores range from 0 to 18, where higher scores indicate better executive performance.
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