Selective neural electrical stimulation restores hand and forearm movements in individuals with complete tetraplegia.

BACKGROUND: We hypothesized that a selective neural electrical stimulation of radial and median nerves enables the activation of functional movements in the paralyzed hand of individuals with tetraplegia. Compared to previous approaches for which up to 12 muscles were targeted through individual muscular stimulations, we focused on minimizing the number of implanted electrodes however providing almost all the needed and useful hand movements for subjects with complete tetraplegia. METHODS: We performed acute experiments during scheduled surgeries of the upper limb with eligible subjects. We scanned a set of multicontact neural stimulation cuff electrode configurations, pre-computed through modeling simulations. We reported the obtained isolated and functional movements that were considered useful for the subject (different grasping movements). RESULTS: In eight subjects, we demonstrated that selective stimulation based on multicontact cuff electrodes and optimized current spreading over the active contacts provided isolated, compound, functional and strong movements; most importantly 3 out of 4 had isolated fingers or thumb flexion, one patient performed a Key Grip, another one the Power and Hook Grips, and the 2 last all the 3 Grips. Several configurations were needed to target different areas within the nerve to obtain all the envisioned movements. We further confirmed that the upper limb nerves have muscle specific fascicles, which makes it possible to activate isolated movements. CONCLUSIONS: The future goal is to provide patients with functional restoration of object grasping and releasing with a minimally invasive solution: only two cuff electrodes above the elbow. Ethics Committee / ANSM clearance prior to the beginning of the study (inclusion period 2016-2018): CPP Sud Méditerranée, #ID-RCB:2014-A01752-45, first acceptance 10th of February 2015, amended 12th of January 2016. TRIAL REGISTRATION: (www.clinicaltrials.gov): #NCT03721861, Retrospectively registered on 26th of October 2018.

Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes.

Vagus nerve stimulation can ameliorate autoimmune diseases such as rheumatoid arthritis by modulation of the immune system. Its efficacy for the treatment of type 1 diabetes has not been explored, in part because the nerves projecting to the pancreatic lymph nodes (pLNs) in mice are unmapped. Here, we map the nerve projecting to the pancreas and pLNs in mice and use a minimally invasive surgical procedure to implant micro-cuff electrodes onto the nerve. Pancreatic nerve electrical stimulation (PNES) resulted in ß-adrenergic receptor-mediated-accumulation of B and T cells in pLNs and reduced production of pro-inflammatory cytokines following lipopolysaccharide stimulation. Autoreactive T cells showed reduced proliferation in pLNs of mice receiving PNES as compared to sham controls. In a spontaneous mouse model of autoimmune diabetes, PNES inhibited disease progression in diabetic mice.

Development of a neurotechnological system for relieving phantom limb pain using transverse intrafascicular electrodes (TIME).

Phantom limb pain (PLP) is a chronic condition that develops in the majority of amputees. The underlying mechanisms are not completely understood, and thus, no treatment is fully effective. Based on recent studies, we hypothesize that electrical stimulation of afferent nerves might alleviate PLP by giving sensory input to the patient if nerve fibers can be activated selectively. The critical component in this scheme is the implantable electrode structure. We present a review of a novel electrode concept to distribute highly selective electrode contacts over the complete cross section of a peripheral nerve to create a distributed activation of small nerve fiber ensembles at the fascicular level, the transverse intrafascicular multichannel nerve electrode (TIME). The acute and chronic implantations in a small animal model exhibited a good surface and structural biocompatibility as well as excellent selectivity. Implantation studies on large animal models that are closer to human nerve size and anatomical complexity have also been conducted. They proved implant stability and the ability to selectively activate nerve fascicles in a limited proximity to the implant. These encouraging results have opened the way forward for human clinical trials in amputees to investigate the effect of selective electrical stimulation on PLP.

An implantable neuroprosthesis for standing and walking in paraplegia: 5-year patient follow-up.

We present the results of a 5-year patient follow-up after implantation of an original neuroprosthesis. The system is able to stimulate both epimysial and neural electrodes in such a way that the complete flexor-extensor chain of the lower limb can be activated without using the withdrawal reflex. We demonstrate that standing and assisted walking are possible, and the results have remained stable for 5 years. Nevertheless, some problems were noted, particularly regarding the muscle response on the epimysial channels. Analysis of the electrical behaviour and thresholds indicated that the surgical phase is crucial because of the sensitivity of the functional responses to electrode placement. Neural stimulation proved to be more efficient and more stable over time. This mode requires less energy and provides more selective stimulation. This FES system can be improved to enable balanced standing and less fatiguing gait, but this will require feedback on event detection to trigger transitions between stimulation sequences, as well as feedback to the patient about the state of his lower limbs.

Original electronic design to perform epimysial and neural stimulation in paraplegia.

This paper presents an original electronic architecture to manage epimysial and neural stimulation using the same implantable device. All the muscles needed to achieve lower limb movements such as standing and walking can thus be activated. Mainly for surgical reasons, some muscles need to be stimulated through different inputs: epimysium or motor nerve. We developed an electronic solution, including the design of an application-specific integrated circuit, to meet the requirements of both types of stimulation. Five years after the successful implantation of the system, we were able to evaluate the system's performance. The patient is still using the system at home and no failure occurred during this 5-year period. We conclude that the electronic design not only provides a unique investigative tool for research, but that it can also be used to restore the motor function of the lower limb. This technology has an advantage over external stimulation because the patient can safely use the system at home. However, improvements such as lower power consumption, and thus greater autonomy, are needed. We further conclude that the modelling of the electrical behaviour of the electrodes is reliable and the estimated parameter values are homogeneous and consistent for the same type of electrode. Thus, the three parameters of the first-order model can be identified from an acute animal experiment and provide a means to optimize the design of the output stage of implanted stimulators.