NeuroStep, a wearable neuroprosthesis for peripheral neuropathy

Aims: The actual treatments of peripheral neuropathy (PN) do not counteract sensory loss, but only partially manage its consequences. Electrical neural stimulation holds promise to restore sensations; however, it remains unknown if neurostimulation on damaged nerves in PN patients can elicit perceivable sensations and whether such stimulation could lead to health, pain, or functional benefits in daily activities. Thus, the objective of the study was to evaluate the responses of the PN-damaged nerves to the injected charge in terms of perceptual threshold and sensitivity to stimulation via psychometric measurements and compared them to measurements in healthy individuals.

Methods: The NeuroStep was preliminary evaluated during a one-day study in PN participants (N=14) and compared to healthy individuals (N=22). Anthropometric measures for key areas of the foot and ankle and specifications for array design with final number and position of electrodes were taken. Electrical stimulation paradigms were calibrated, and appropriate active sites were personalised to achieve targeted sensory restoration. NeuroStep targeted 3 lower-limb nerves: peroneal, posterior tibial (medial plantar, lateral plantar and medial calcaneal branches) and sural. Quantitative Sensory Testing was performed with a brush, light touch, and a 10 g monofilament to evaluate the sensory loss of PN participants. Neuropathic pain was evaluated through the Neuropathic Pain Symptom Inventory questionnaire (NPSI) taken before the day of targeted neurostimulation intervention and 24 hours later. Next, to investigate the somatosensory processing of restored sensations, healthy (N=12) and PN (N=5) participants underwent 3 Tesla functional MRIs, while they were neurostimulated.

Results: The system partially restored lost sensations in all participants through a purposely calibrated neurostimulation, despite PN nerves being less sensitive than healthy nerves. A restored sensation (over the area of sensory loss) of 27.0±3.2%, on the dorsal and plantar sides of the foot was elicited. Different type of sensations, including physiologically plausible ones, were elicited. The most common reported sensations were vibration and tingling (26% and 44% respectively), followed by electricity (9%) and touch (6%). Participants improved cadence and functional gait and reported a decrease of neuropathic pain.  On the day after the intervention, a clinically significant decrease of 30.4±9.2% of overall NPSI score in the 12 participants who reported pain has occurred. The dimensions of NPSI mainly responsible for the decrease in pain was burning, paroxysmal pain, and paraesthesia, found to clinically decrease by 37.7±11.2%, 48.1±13.3%, and 31.8±14.1% respectively. Restored sensations activated cortical patterns resembling naturally located foot sensations, supporting somatotopic stimulation as a valid physiologically accurate alternative to provide foot sensations.

Conclusions: NeuroStep restores real-time intuitive sensations in PN showing the potential to tackle functional, health and pain drawbacks of PN and pave the way for further long-term investigations.

Comments: This work showed the design and validation of a wearable somatosensory neuroprostheses to target various neuropathic symptoms. The device seems to be the prototype of the AI-driven neuroprosthetic smart sock which was among the winners of the Innovation Challenge at ADA 2025. The primary limitations of this work are its short-term duration and follow-up, which make it challenging to draw definitive conclusions.  Functional improvements should be evaluated depending on the disease severity to identify the participants who could benefit most. In a larger cohort, confounding factors beyond PN severity, such as patient characteristics (e.g., age, gender), should be controlled and their effects evaluated to ensure accuracy. In addition, the expert-guided calibration, needed to successfully target nerves that innervate the foot at a proximal level, is currently very time-intensive and can be automatised to make long-term testing more feasible. Overall, a long-term clinical trial comparing multiple sessions of targeted neurostimulation to a control group is crucial to validate the current findings on functional, sensory, and clinical outcomes.

Carla Greco

Reference: Gozzi N, Chee L, Odermatt I, Kikkert S, Preatoni G, Valle G, Pfender N, Beuschlein F, Wenderoth N, Zipser C, Raspopovic S. Wearable non-invasive neuroprosthesis for targeted sensory restoration in neuropathy. Nat Commun. 2024 Dec 30;15(1):10840. doi: 10.1038/s41467-024-55152-7. PMID: 39738088; PMCID: PMC11686223.

🔗 https://www.nature.com/articles/s41467-024-55152-7