Novel personalized treatment strategy for patients with chronic stroke with severe upper-extremity impairment: The first patient of the AVANCER trial.

BACKGROUND: Around 25% of patients who have had a stroke suffer from severe upper-limb impairment and lack effective rehabilitation strategies. The AVANCER proof-of-concept clinical trial (NCT04448483) tackles this issue through an intensive and personalized-dosage cumulative intervention that combines multiple non-invasive neurotechnologies. METHODS: The therapy consists of two sequential interventions, lasting until the patient shows no further motor improvement, for a minimum of 11 sessions each. The first phase involves a brain-computer interface governing an exoskeleton and multi-channel functional electrical stimulation enabling full upper-limb movements. The second phase adds anodal transcranial direct current stimulation of the motor cortex of the lesioned hemisphere. Clinical, electrophysiological, and neuroimaging examinations are performed before, between, and after the two interventions (T0, T1, and T2). This case report presents the results from the first patient of the study. FINDINGS: The primary outcome (i.e., 4-point improvement in the Fugl-Meyer assessment of the upper extremity) was met in the first patient, with an increase from 6 to 11 points between T0 and T2. This improvement was paralleled by changes in motor-network structure and function. Resting-state and transcranial magnetic stimulation-evoked electroencephalography revealed brain functional changes, and magnetic resonance imaging (MRI) measures detected structural and task-related functional changes. CONCLUSIONS: These first results are promising, pointing to feasibility, safety, and potential efficacy of this personalized approach acting synergistically on the nervous and musculoskeletal systems. Integrating multi-modal data may provide valuable insights into underlying mechanisms driving the improvements and providing predictive information regarding treatment response and outcomes. FUNDING: This work was funded by the Wyss-Center for Bio and Neuro Engineering (WCP-030), the Defitech Foundation, PHRT-#2017-205, ERA-NET-NEURON (Discover), and SNSF (320030L_197899, NiBS-iCog).

A Novel Patient-Tailored, Cumulative Neurotechnology-Based Therapy for Upper-Limb Rehabilitation in Severely Impaired Chronic Stroke Patients: The AVANCER Study Protocol.

Effective, patient-tailored rehabilitation to restore upper-limb motor function in severely impaired stroke patients is still missing. If suitably combined and administered in a personalized fashion, neurotechnologies offer a large potential to assist rehabilitative therapies to enhance individual treatment effects. AVANCER (clinicaltrials.gov NCT04448483) is a two-center proof-of-concept trial with an individual based cumulative longitudinal intervention design aiming at reducing upper-limb motor impairment in severely affected stroke patients with the help of multiple neurotechnologies. AVANCER will determine feasibility, safety, and effectivity of this innovative intervention. Thirty chronic stroke patients with a Fugl-Meyer assessment of the upper limb (FM-UE) <20 will be recruited at two centers. All patients will undergo the cumulative personalized intervention within two phases: the first uses an EEG-based brain-computer interface to trigger a variety of patient-tailored movements supported by multi-channel functional electrical stimulation in combination with a hand exoskeleton. This phase will be continued until patients do not improve anymore according to a quantitative threshold based on the FM-UE. The second interventional phase will add non-invasive brain stimulation by means of anodal transcranial direct current stimulation to the motor cortex to the initial approach. Each phase will last for a minimum of 11 sessions. Clinical and multimodal assessments are longitudinally acquired, before the first interventional phase, at the switch to the second interventional phase and at the end of the second interventional phase. The primary outcome measure is the 66-point FM-UE, a significant improvement of at least four points is hypothesized and considered clinically relevant. Several clinical and system neuroscience secondary outcome measures are additionally evaluated. AVANCER aims to provide evidence for a safe, effective, personalized, adjuvant treatment for patients with severe upper-extremity impairment for whom to date there is no efficient treatment available.