Neurostimulation Systems for Central Nervous System (CNS) and Peripheral Nervous System (PNS)

Abstract

PROBLEM TO BE SOLVED: To provide a neurostimulation system improving recovery after neurological disorders like spinal cord injury (SCI) after trauma, also adjusted to the progress of the rehabilitation of a patient, in the field of providing desired assistance in training and daily life for the patient.SOLUTION: The present disclosure relates to a neuromodulation and / or neurostimulation system 10 comprising at least the following components: at least one sensing unit 12; at least one control unit 14; at least one stimulation unit 16; at least one Central Nervous System (CNS) stimulation module 18; and at least one Peripheral Nervous System (PNS) stimulation module 20. At least one of the components of the neuromodulation and / or neurostimulation system 10 is implantable.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an active closed-loop medical system, in particular for neurostimulation, for example in the field of improving recovery after neurological disorders such as spinal cord injury (SCI), for example after trauma. [Background technology]

[0002] EP 2868343 A1 discloses a system for delivering adaptive electrical spinal cord stimulation to facilitate and restore locomotion after neuromotor dysfunction. Among other things, a closed-loop system for real-time control of epidural electrical stimulation is disclosed, comprising a means for neuromodulation of a subject with adjustable stimulation parameters, the means being operatively connected to a real-time monitoring component comprising a sensor for continuously acquiring feedback signals from the subject, the signals providing characteristics of the subject's movements, the system being operatively connected to a signal processing device for receiving the feedback signals and operating a real-time automatic control algorithm, the signal processing device being operatively connected to the means for providing new stimulation parameters to the means with minimal delay. This known system improves the consistency of gait in subjects with neuromotor dysfunction. A real-time automatic control algorithm is used that comprises a feedforward component using a single-input single-output model (SISO) or a multiple-input single-output (MISO) model. See also Wenger et al., Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury, in Science Translational Medicine, vol. 6, num. 255, 2014.

[0003] WO 2002 / 034331 discloses a non-closed loop implantable medical device system comprising an implantable medical device together with a transceiver device, which exchanges data with the patient, between the patient and the implantable medical device, and between a remote location and the implantable medical device. A communication device coupled to the transceiver device exchanges data with the transceiver device, through a receiver device, and between the transceiver device and the remote location, allowing two-way data transfer between the patient, the implantable medical device, the transceiver device and the remote location. A converter unit converts the transmission of data from a first telemetry format to a second telemetry format, and a user interface allows information to be exchanged between the transceiver device and the patient, between the implantable medical device and the patient through the transceiver device, and between the patient and the remote location through the transceiver device.

[0004] US Patent Application Publication No. 2002 / 0052539 describes a partially closed loop, non-continuous and non-real-time emergency medical information communication system and corresponding method. The system allows emergency alerts to be issued based on information sensed or processed by an implantable medical device (IMD) implanted in a patient's body. The IMD is capable of two-way communication with a communication module, mobile phone and / or personal digital assistant (PDA) located outside the patient's body. The communication module, mobile phone or PDA is capable of communicating emergency alerts generated by the IMD to a remote computer via the communication system. It may be determined at the remote computer system that emergency corrective action is required. The action is then performed remotely from the remote computer system in the IMD via the communication system.

[0005] US Patent No. 7,149,773 relates to a method, device and system for automatically generating an invoice when medical services are provided to a patient. The invoice is automatically generated by the system, for example, when monitoring of some aspects of the performance of an implantable medical device (IMD) implanted in the patient's body is initiated by the patient or remotely, or when delivery of a treatment to the patient through the IMD is initiated locally or remotely. The IMD is capable of two-way communication with a communication module, a mobile phone and / or a personal digital assistant (PDA) located outside the patient's body. The invoicing system may comprise an IMD, a communication module and / or a mobile phone and / or a PDA, a means for generating an invoice, a remote computer system, and a communication system capable of two-way communication. In the two-way communication, the communication module, the mobile phone and / or the PDA may receive information from the IMD or relay information to the IMD.

[0006] US Patent No. 6,878,112 discloses multiple coordinating and complementary software programs implemented in a web-enabled high-speed computer system to remotely monitor, manage and modify operational and functional parameters of multiple implantable medical devices (IMDs). The system utilizes a virtual electrophysiologist module (VEM), a chronic monitoring module (CMM) and a prescriptive program module (PPM) program to remotely, conditionally and on a real-time basis, perform specific therapeutic and diagnostic methods for managing the IMDs. The modules enable remote, continuous monitoring, management and maintenance of the IMDs by identifying critical medical events, determining optimal clinical settings and upgrading performance parameters based on prescriptive data. The modules are implemented in a data center having high-speed computers operating in a web-enabled environment. The modules and the IMDs communicate via a programmer or an interface medical unit (IMD) through a wireless communication system.

[0007] EP 2 652 676 A1 relates to gesture control for monitoring vital body signs and reuses the accelerometer, or more precisely the detected acceleration of a body sensor, for user control of the body sensor. This is achieved by detecting predefined patterns in the acceleration signal that are unrelated to other movements of the patient. These include tapping on / with the sensor, vibration and turning of the sensor. A new procedure is described that allows to reuse the acceleration detection for reliable gesture detection without causing many false positives due to non-gesture movements such as breathing, heartbeat, walking, etc. Similar solutions for user tapping detection are known from US Pat. No. 8,326,569 and US Pat. No. 7,742,037.

[0008] Known stimulation systems use central nervous system (CNS) stimulation, in particular epidural electrical stimulation (EES), or peripheral nervous system (PNS) stimulation, in particular functional electrical stimulation (FES).

[0009] Epidural Electrical Stimulation (EES) is known to restore motor control in animal and human models and has been specifically shown to restore locomotion after spinal cord injury by artificially activating neural networks responsible for locomotion below the spinal cord lesion (Capogrosso, M, et al., A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits, Journal of Neuroscience 4 December 2013, 33 (49) 19326-19340; Courtine et al., Transformation of nonfunctional spinal circuits into functional states after the loss of brain input, Nat Neurosci. 2009 Oct; 12(10): 1333-1342; Maraud et al, Mechanisms Underlying the Neuromodulation of Spinal Circuits for Correcting Gait and Balance Deficits after Spinal Cord Injury, Neuron Volume 89, Issue 4, p814-828, 17 February 2016). EES stimulates afferent sensory neurons before they enter the spinal cord, rather than directly stimulating motor neurons. In this way, the spinal neural circuits responsible for locomotion are indirectly recruited by these afferents, and locomotion movements are globally restored by activating the necessary muscle synergies. The movements generated are functional, but are less controllable due to relatively poor selectivity (neural network activation instead of selectively targeting key muscles), and imprecision prevents fluidity and full functionality in the potential space of movements.

[0010] Peripheral nerve stimulation (PNS) systems used so far in clinical practice are known as functional electrical stimulation (FES), which delivers electrical stimulation to target muscles by direct stimulation of the muscles with surface electrodes or by transcutaneous stimulation of peripheral nerves. The resulting muscle fatigue makes FES unsuitable for use in daily life. Furthermore, the cumbersome setup when using surface muscle stimulation, the unmet demands in terms of selectivity (when using transcutaneous nerve stimulation), and the lack of stability (it is not possible to move the electrodes and reproduce the exact electrode placement routinely when stimulating muscles due to clothing, sweat, etc.) have limited success. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] European Patent Application Publication No. 2868343 [Patent Document 2] International Publication No. 2002 / 034331 Brochure [Patent Document 3] US Patent Application Publication No. 2002 / 0052539 [Patent Document 4] U.S. Patent No. 7,149,773 [Patent Document 5] U.S. Patent No. 6,878,112 [Patent Document 6] European Patent Application Publication No. 2652676 [Patent Document 7] U.S. Patent No. 8,326,569 [Patent Document 8] U.S. Patent No. 7,742,037 [Patent Document 9] International Publication No. 2016 / 0279418 Brochure [Non-patent literature]

[0012] [Non-Patent Document 1] Wenger et al., Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury, in Science Translational Medicine, vol. 6, num. 255, 2014 [Non-Patent Document 2] Capogrosso, M, et al., A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits, Journal of Neuroscience 4 December 2013, 33 (49) 19326-19340 [Non-Patent Document 3] Courtine et al., Transformation of nonfunctional spinal circuits into functional states after the loss of brain input, Nat Neurosci. 2009 Oct; 12(10): 1333-1342 [Non-Patent Document 4] Maraud et al, Mechanisms Underlying the Neuromodulation of Spinal Circuits for Correcting Gait and Balance Deficits after Spinal Cord Injury, Neuron Volume 89, Issue 4, p814-828, 17 February 2016 [Non-Patent Document 5] X. Navarro, et al., A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems, J. Peripher. Nerv. Syst. 10 (3) (2005) 229-258 [Non-Patent Document 6] K. Yoshida, K. Jovanovic, RB Stein, Intrafascicular electrodes for stimulation and recording from puppy mud spinal roots, J. Neurosci. methods 96 (1) (2000) 47-55 [Non-Patent Document 7] J. Badia, et al., Comparative analysis of transverse intrafascicular multichannel, intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles, J. neural Eng. 8 (3) (2011) 036023 Summary of the Invention [Problem to be solved by the invention]

[0013] The object of the present invention is to improve neurostimulation systems, for example in the field of improving recovery after neurological diseases, such as spinal cord injury (SCI), for example after trauma, in particular in that neuromodulation and / or neurostimulation can be provided in a more individualized manner adapted to the needs of the patient, as well as providing the necessary support in the patient's training and daily life, tailored to the patient's rehabilitation progress. [Means for solving the problem]

[0014] This object is solved according to the invention by a neuromodulation and / or neurostimulation system having the features of claim 1. It therefore comprises at least the following components: at least one detection unit; at least a control unit; - at least one stimulation unit; - at least one central nervous system (CNS) stimulation module; - at least one peripheral nervous system (PNS) stimulation module; In particular, at least one of the components of the neuromodulation and / or neurostimulation system is implantable.

[0015] The present invention is based on the basic idea that a system can be used to provide neuromodulation and / or neurostimulation to the central nervous system (CNS) and peripheral nervous system (PNS). Both the CNS and the PNS can be stimulated simultaneously or can be stimulated intermittently or on demand. These two complementary stimulation paradigms can be combined into one strategy and made available to patients equipped with the system. For example, CNS neuromodulation and / or neurostimulation can be used to enhance and / or restore a patient's ability to move, particularly in such a way that the existing mode of transfer of physiological signals within the patient's body is supported, such that command signals for body movements etc. are still provided by the patient's nervous system and are simply supported and / or enhanced or transformed by the CNS stimulation module. Stimulation provided by the PNS module can be used to locally manipulate and direct stimulation signals to specific peripheral nerve structures to trigger specific movements and / or improve existing movements. Such PNS stimulation can be used to improve and / or complete the movement and / or movement capabilities of a patient wearing the system. For example, this can be used to complete, but is not limited to, bending, extending, lifting, turning, etc., of a patient's toes, fingers, arms, feet, legs, or any limb. This is done, for example, when it is recognized that the neuromodulation and / or neurostimulation provided by the CNS stimulation module is not sufficient to complete the patient's movement or intended state. Such movement or intended state can then be completed or supported by stimulation provided by the PNS stimulation system. PNS stimulation can also be used to reduce side effects and compensate for inaccuracies of CNS stimulation.

[0016] Such a combination of CNS and PNS stimulation can provide individualized stimulation and therapy for a patient.

[0017] The system may be fully implanted, partially implanted, or may be provided with essentially only non-invasive components.

[0018] The system can be used to provide treatments for, but not limited to, restoring or training a patient's movement, locomotion, standing and / or walking, reaching and / or grasping, the patient's cardiovascular signals such as blood pressure and / or pulse, tension, nerve stimulation, e.g., vagus nerve stimulation, enhancing the patient's immune system, body temperature, etc. Additionally, the patient's overall sensation and well-being (e.g., pain treatment) can also be improved.

[0019] The central nervous system (CNS) stimulation module may be or may comprise an epidural stimulation module capable of providing epidural stimulation, and / or a subdural stimulation module capable of providing subdural stimulation, and / or an intracortical stimulation module capable of providing intracortical stimulation, and / or an intrathecal stimulation module capable of providing intrathecal stimulation.

[0020] In particular, the epidural stimulation module can be an epidural electrical stimulation (EES) neurostimulator element.

[0021] EES stimulates afferent sensory neurons before they enter the spinal cord, rather than directly stimulating motor neurons. In this way, the spinal neural circuits responsible for locomotion are indirectly reinforced by these afferents, globally restoring locomotion movements by activating the necessary muscle synergies. The movements generated are functional, but are less controllable due to relatively poor selectivity (neural network activation instead of selectively targeting key muscles), and imprecision prevents fluidity and full functionality in the potential space of movements.

[0022] In the context of locomotion, EES can be additionally used to further improve the immediate effect and training-induced benefits when the solid receptor afferents are more selectively stimulated and coordinated with the different phases of the gait cycle. During walking, these phases consist of alternating stimulation of the extensor and flexor muscles of the right versus left leg. Using spatiotemporal EES, both the swing phase (flexion) and the load-bearing stance phase (extension) can be restored, whereas continuous EES may interfere with the limb.

[0023] In particular, the epidural stimulation module (epidural electrical stimulation (EES) neurostimulation element) can be positioned and configured as a spatially selective spinal implant configured to function based on a time-rigorous stimulation algorithm coordinated in a "closed-loop" manner with real-time motor feedback input as part of an active closed-loop medical system.

[0024] The peripheral nervous system (PNS) stimulation module can be a functional electrical stimulation (FES) module capable of providing functional electrical stimulation (FES) and electrical stimulation of peripheral nerves, thereby enhancing selective refinements to the movements produced.

[0025] During peripheral nervous system (PNS) stimulation, efferent motor neuron axons, and consequently muscles, are directly stimulated efferently from complex circuits in the spinal cord. Various types of interfaces with the periphery exist (see X. Navarro, et al., A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems, J. Peripher. Nerv. Syst. 10 (3) (2005) 229-258), which vary in terms of invasiveness, selectivity and reliability. Intraneural implants are the most suitable implants as they offer better stimulation selectivity, increased signal-to-noise ratio of recordings, and lower activation thresholds than extraneural or epimysial implants (see K. Yoshida, K. Jovanovic, RB Stein, Intrafascicular electrodes for stimulation and recording from mud puppy spinal roots, J. Neurosci. methods 96 (1) (2000) 47-55; J. Badia, et al., Comparative analysis of transverse intrafascicular multichannel, longitudinal intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles, J. neural Eng. 8 (3) (2011) 036023).

[0026] Stimulating peripheral nerves with intraneural electrodes provides direct, tightly localized control. However, artificial stimulation quickly fatigues muscles due to an unnatural sequence of reinforcement of neurons. Indeed, large diameter neurons, and therefore large diameter muscle fibers, are first reinforced with artificial electrical stimulation, while spinal cord stimulation reinforces afferent fibers before they enter the network in the spinal cord, thereby facilitating the natural reinforcement of motor neurons (small diameter neurons first). In contrast, while providing extremely tightly localized control, PNS stimulation results in an excitable state of the fiber type with rapid fatigue of the normal task, which is a major limitation to the functional use of this fiber type.

[0027] Thus, intraneural peripheral nerve stimulation very well addresses the demands in terms of increased selectivity, stability and reduced cumbersomeness, since such a system can be implemented with a single neural implant. The architecture of the peripheral nervous system allows for proximally interfacing intraneural fiber bundles with multiple channels, thereby targeting multiple agonist and antagonist muscles by selectively stimulating fibers that innervate more distal muscles. These types of implants are well anchored within the nerve, thus providing stability.

[0028] Intraneural PNS stimulation can directly target specific muscles, resulting in selective and controllable activation that allows for an expansion of the reachable space of movement. However, intraneural PNS stimulation is not efficient enough to generate powerful and consistent movements at any given time, because it reinforces motor axons and causes high muscle fatigue compared to spinal cord stimulation. Furthermore, the extreme selectivity caused by the direct projection from the nerve to the innervated muscle prevents the generation of functional, load-bearing movements. In fact, functional, multi-joint movements require the reinforcement of muscles innervated by two or more nerves, and stimulating one nerve is not sufficient to generate useful movements.

[0029] Therefore, the combination of both CNS, e.g., EES, and PNS, e.g., FES, stimulation types leverages the advantages of each stimulation paradigm to restore functional, complex, and fine movements after paralysis. Targeting the central and peripheral nervous systems is complementary, allowing the restoration of functional, weight-bearing movements.

[0030] Intraneural peripheral nerve stimulation certainly meets several of the above-mentioned demands in terms of increased selectivity, stability, and reduced cumbersomeness, since such a system can be implemented with a single neural implant. The architecture of the peripheral nervous system allows for targeting multiple agonist and antagonist muscles by proximally interfacing intraneural fiber bundles with multiple channels, thereby selectively stimulating fibers that innervate more distal muscles. These types of implants are well anchored within the nerve, thus providing selectivity and stability. However, direct reinforcement of motor axons also causes high muscle fatigue compared to muscle stimulation, and is therefore not efficient enough to generate powerful and coherent movements at any given time.

[0031] More recently discovered indirect EES methods build on a strong scientific foundation and have the potential to overcome most of the inherent limitations to FES, but so far lack extensive clinical experience.

[0032] The central nervous system (CNS) stimulation module may be at least partially implantable or at least partially implanted, allowing the CNS stimulation module to be positioned close to the side where stimulation is needed, and then highly effective therapy with the system can be provided to the patient.

[0033] The peripheral nervous system (PNS) stimulation module may be or may be at least partially implanted. Generally speaking, the PNS stimulation module may not be implanted, but may simply be attached in a suitable manner to the patient's skin. Nevertheless, by implanting the PNS stimulation module, the stimulation module can be located closer to the target structure to which stimulation is to be applied. Also, an implanted PNS stimulation module allows for more selective stimulation.

[0034] The components of a neuromodulation and / or neurostimulation system can, for example, form a closed loop system.

[0035] The closed loop system can be formed such that the control unit receives inputs from the sensing unit. Such inputs can relate to physiological signals, such as physiological electrical signals from a patient (i.e. a patient equipped with a neuromodulation and / or neurostimulation system). By using physiological feedback provided by the patient stimulated by the system, the stimulation can be better adapted to the patient's needs. Such physiological signals can relate to, but are not limited to, physiological signals related to the patient's gait cycle, locomotion, standing and / or walking, the patient's cardiovascular signals, such as blood pressure and / or pulse, tension, neural stimulation, e.g. vagus nerve stimulation, signals directly or indirectly related to the patient's immune system, body temperature, etc. Based on this signal, the controller can control the stimulation unit, and thus the CNS and PNS stimulation modules. The CNS and PNS stimulation modules can provide the necessary neuromodulation and / or neurostimulation signals. These signals and the patient's physiological responses can be sensed by the sensing unit, and the respective sensor signals can then be used as a further basis for the control provided by the control unit. This can provide a closed loop system.

[0036] It is also possible for the components of the neuromodulation and / or neurostimulation system to form an open-loop system. In that case, the required system and electronic components may be less sophisticated, thus providing a cheaper system. Also, the complexity of the system may be reduced, which may also allow the system to be more reliable with less effort. In particular, in the case of an open-loop system, for example, a predetermined stimulation protocol and settings may be provided to the patient. If changes are required, such changes can be introduced into the system by upgrading or installing additional stimulation routines. Thus, a very simple system layout may be achieved with the open-loop approach.

[0037] Furthermore, the control unit can be configured such that the control is performed in real time, which in particular can be understood as a delay between the sensing signal and the applied stimulation signal of not more than 30 ms, as already mentioned in WO 2016 / 0279418.

[0038] Real-time control in the sense of the present invention and its preferred embodiments, i.e. in particular that the delay between the sensing signal and the applied stimulation signal should not exceed 30 ms, is advantageous for an open-loop approach, but also for a closed-loop approach. It is very useful for a patient equipped with a system to have stimulation at or close to the time when advancement is required, e.g. with a desired movement.

[0039] Additionally, the peripheral nervous system (PNS) stimulation module may include at least one electrode having at least one fixation element for anchoring the electrode in or to a surrounding structure, thereby allowing the position of the electrode of the PNS stimulation module to be maintained near the structure to be stimulated or stimulated by the PNS stimulation module.

[0040] Further, the control unit may be configured to control the stimulation provided by the PNS stimulation module and / or the stimulation provided by the CNS stimulation module based on the obtained sensing signal provided by the sensing unit. - to at least partially align stimulation control signals provided by the control unit for controlling the PNS stimulation module and / or the CNS stimulation module with physiological signals associated with the subject's intention to move, the physiological signals being decoded from the subject's brain and / or nervous system; and / or - to at least partially align stimulation control signals provided by the control unit for controlling the PNS stimulation module and / or the CNS stimulation module with a desired kinematic trajectory; and / or - to at least partially align stimulation control signals provided by the control unit for controlling the PNS stimulation module and / or the CNS stimulation module with a desired force on a surface on which the subject is positioned or touching; and / or - to at least partially align stimulation control signals provided by the control unit for controlling the PNS stimulation module and / or the CNS stimulation module with muscle activation for a certain gait pattern and / or grip type and / or movement; It can be configured to be adjustable and / or adaptable.

[0041] By matching the stimulation control signals, very specific neuromodulation or stimulation can be provided. Furthermore, by detecting physiological signals related to the subject's intention to move, decoded from the brain and / or nervous system, very accurate neuromodulation and trigger detection of neuromodulation or neurostimulation can be obtained, and very accurate neuromodulation or neurostimulation can be provided by the system. By matching the stimulation control signals in relation to the desired kinematic trajectory, correction of undesired signals can be performed and the intended movement can be supported in an individually suitable manner. Furthermore, the stimulation control signals for controlling the PNS stimulation module and / or the CNS stimulation module can be matched with the intended and required force to be touched by the subject. Such support can be linked to the control of the patient's standing and walking, or hand or arm movements. It is also possible to match the stimulation control signals with physiological signals to detect, activate and control muscle activation for certain walking patterns and / or grip types and / or movements. By finding specific physiological trigger signals for such walking patterns or grip types and movements, the system can provide very specific support by neuromodulation and / or neurostimulation.

[0042] It is further possible that the control unit may be configured to be able to decode signals provided by the sensing unit and related to the subject's movements, in particular to be able to continuously decode signals related to the subject's movements and / or forces and / or EMG activity and / or kinematic trajectories. There may be an interaction of stimuli with physiological signals of the subject. This interaction of stimuli and physiological signals can be used to individually adapt the neuromodulation or neurostimulation provided by the system. In particular, a tonic or transient stimulation can be provided by the CNS stimulation module, and there may also be a transient stimulation in the PNS neurostimulation module, which can be triggered by a trigger event. Such a trigger event can be provided by the sensing unit and can utilize EEG or EMG or force signals or cortical signals, or can be from voice control or movement signals, etc. Here, external sensors such as accelerometers, force sensors, interactive sensors or even microphones for voice control can be used. Cameras, etc. can also be used to provide the respective signals. Also, there can be stimulation interactions to match stimulation control signals, the triggering event can be a particular movement or force or EMG profile, and the CNS and PNS stimulation can be tonic, episodic, or triggered by any other signal.

[0043] The control unit can be configured such that the stimulation provided by the PNS stimulation module and the stimulation provided by the CNS stimulation module are at least partially alternated, the particular stimulation being capable of supporting the motor output of the patient.

[0044] Furthermore, the control unit may be configured such that the stimulation provided by the PNS stimulation module and the stimulation provided by the CNS stimulation module may at least partially overlap, which may improve the effect of the stimulation.

[0045] Thus, the control unit may be configured such that stimulation provided by the PNS or CNS stimulation modules is used at least in part to compensate for stimulation provided by other stimulation modules to improve motor output. Such an approach may be used to support movements, compensate for movements and specific movements, and assist the patient in movements.

[0046] The control unit may be capable of independently controlling and switching on and off the PNS or CNS stimulation modules. This allows for the provision of only CNS stimulation or only PNS stimulation. Such functionality of the system also increases the manner in which the system can be used. Depending on the circumstances of the subject being equipped with the system, stimulation can be tailored to specific needs.

[0047] Furthermore, the present invention relates to a method of providing neuromodulation and / or neurostimulation, particularly by providing central nervous system (CNS) stimulation in combination with peripheral nervous system (PNS) stimulation, by using any of the above-described neuromodulation and / or neurostimulation systems.

[0048] Further in the context of the present disclosure there is disclosed the use of a neuromodulation and / or neurostimulation system as defined in any one of claims 1 to 14 for providing neuromodulation and / or neurostimulation by providing central nervous system (CNS) stimulation combined with peripheral nervous system (PNS) stimulation.

[0049] In connection with peripheral nervous system (PNS) stimulation, stimulation of the upper limb nerves can be provided, i.e., the radial nerve, the ulnar nerve, and / or the median nerve. Similarly, in connection with PNS stimulation, stimulation of the lower limb nerves, such as the sciatic nerve and / or the femoral nerve, can be provided. All PNS stimulation can be performed by targeting one of the above-mentioned nerves with an intraneural electrode (lateral or longitudinal) or a nerve sheath (cuff) electrode.

[0050] In relation to central nervous system (CNS) stimulation, the following neural structures can be stimulated: for upper limb movements, the cervical spinal cord or the hand / arm motor cortex can be stimulated by the CNS stimulation module; for lower limb movements, the lumbosacral spinal cord or the lower limb can be stimulated. All these nerves can be targeted by epidural, subdural or intrathecal / intracortical stimulation.

[0051] The sensing module can sense muscle activation (by surface or intramuscular EMG electrodes, one or several electrodes to construct a control signal). The patient's kinematics can be sensed by variables such as kinematic markers or IMUs. There can also be several sensors that detect forces on the skin or forces intended to be exerted by the subject, for example by pressure sensors in the foot insoles or gloves. Such sensors can also be wearable. Neural signals such as field potentials, multi-units, single spikes, etc. can be detected by EEG, ENG, ECoG, intracortical electrode arrays, patch clamp electrodes, or single penetrating power.

[0052] Both stimulation units can use a common IPG, which can be used to provide the necessary stimulation currents and signals for the CNS and PNS stimulation modules. It is also possible that two separate IPGs are provided, one IPG for the PNS stimulation module and one IPG for the CNS stimulation module.

[0053] Stimulation parameters for peripheral nervous system (PNS) stimulation and EES stimulation can be frequency, amplitude, pulse width, etc.

[0054] A suitable frequency range is, for example, about 30 Hz to 120 Hz.

[0055] The amplitude value can be selected from 20 μA to 1000 μA.

[0056] Pulse width values ​​can be selected between 0.040 msec and 1 msec. Preferred parameters are in the range of 50 μA to 300 μA for amplitudes with pulse widths between 40 μsec and 120 μsec.

[0057] The above values ​​of amplitude and pulse width depend, among others, on the interface used and the invasiveness it represents. For example, intraneural electrodes are more invasive than, for example, nerve sheath cuffs (both may be used in the system), and for this reason the stimulation charge required to reinforce the axon is lower. For these intraneural electrodes, this total injected charge (charge = amplitude x pulse width) per stimulation pulse should not be higher than 120 nC (limitations of the electrode itself, not the tissue - risk of delamination, etc.). Within this constraint, the amplitude can be between 20 μA and 1000 μA and the pulse width between 0.040 msec and 1 msec. The preferred parameters are in the range of 50 μA to 300 μA for amplitudes with pulse widths of 40 μsec to 120 μsec.

[0058] EES can be episodic or sustained, while selective PNS is always episodic. Phasic is defined as being anchored to a defined event in the sensed signal (decoded intent, sequential decoding, onset of muscle activation, initiation of movement), a defined event during movement (e.g. foot lift or foot contact during walking).

[0059] In relation to the closed loop system, the following functioning scheme is performed by the entire system:

[0060] Based on the sensed signal, stimulation in the PNS and / or CNS is performed in real time. - to align with the intent decoded from the brain, and / or - to continuously decode the motion, force or EMG from the signals, and / or - to conform to a predetermined kinematic trajectory, and / or - to match the desired force to the softness of the surface (of the ground or the grasped object); and / or - To align muscle activation for a given gait pattern / grasp type can be adjusted.

[0061] Further details and advantages of the invention will now be disclosed with reference to the drawings. [Brief description of the drawings]

[0062] [Figure 1] 1 is a schematic diagram of a layout of an embodiment of a neuromodulation and / or neurostimulation system according to the invention. [Diagram 2] 1 is a schematic diagram of an implantable system and a subject wearing the system. [Diagram 3] 1 is a schematic overview of a feasibility study performed on rats showing an example of a system for targeting lower limb movements according to the present invention. [Figure 4] FIG. 1 is a further schematic overview of a feasibility study carried out on a rat, showing an example of how CNS and PNS stimulation can be used based on the sensory signals recorded in the framework of restoring lower limb movement, for the system and method according to the present invention. [Diagram 5] 1 is a further schematic overview of a feasibility study performed with rats providing proof of concept of the system and method according to the present invention. [Figure 6] FIG. 13 is a further diagram of the walking patterns generated by CNS stimulation under the EES only form, as well as by combined PNS and CNS stimulation, where the PNS locally refines the generated patterns depending on the frequency of PNS stimulation used, illustrating the efficiency of the system for restoring improved lower limb movement according to the present invention. [Figure 7] 1 is a flow chart illustrating an example of how an embodiment of the present invention of a neuromodulation and / or neurostimulation system operates. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0063] FIG. 1 shows, in a schematic diagram, the layout of a neuromodulation and / or neurostimulation system 10 according to the present invention.

[0064] System 10 comprises several components: a sensing unit 12, a control unit 14, a stimulation unit 16, a central nervous system (CNS) stimulation module 18, and a peripheral nervous system (PNS) stimulation module 20.

[0065] The stimulation unit 16 includes one implantable pulse generator (IPG) 22 for the CNS stimulation module 18 and another IPG 24 for the PNS stimulation module 20 .

[0066] It is also possible that only one IPG is provided for both the CNS stimulation module 18 and the PNS stimulation module 20.

[0067] The system 10 is at least partially implantable, but also includes sensors, which are not implanted and are connected via wires to a connector and to a recording chamber, or by a wireless data transmission link to a control unit 14 (see FIG. 2).

[0068] As can be seen in Fig. 2, there are sensing units 12a and 12b implanted in the patient. These sensing units 12a, 12b are sensors, here sensing electrodes, that monitor and detect physiological signals.

[0069] A control unit 14 is also implanted in the patient P. It is also possible that this control unit is not implanted.

[0070] The control unit 14 comprises at least one memory M.

[0071] The memory provides storage capacity for data and, among other things, control instructions for controlling the system 10 .

[0072] Such instructions include, but are not limited to: how to align the stimulation control signals provided by the control unit 14 for controlling the PNS stimulation module 20 and / or the CNS stimulation module 18 with physiological signals decoded from the subject's brain and / or nervous system that are related to the subject's intention to move; and / or how to align the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and / or the CNS stimulation module 18 with the desired kinematic trajectory; and / or how to align the stimulation control signals provided by the control unit 14 for controlling the PNS stimulation module 20 and / or the CNS stimulation module 18 with a desired force on the surface on which the subject is positioned or touching, and / or - how to align the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and / or the CNS stimulation module 18 with muscle activation for certain gait patterns and / or grip types and / or movements;

[0073] These instructions may be part of the control routine or software, may be stored as a separate software module, or may be stored in memory as instruction data.

[0074] The link between the sensor signals and the instructions can be realised by providing the memory M with respective metadata that is stored separately, for example in a metadata memory portion or storage.

[0075] A CNS stimulation module 18 and a PNS stimulation module 20 are also implanted in the patient P.

[0076] To this end, each IPG 22 and 24 is also implanted in the patient P.

[0077] However, there are also sensors 12c and 12d that are not implanted but are attached to the skin of the patient P and provided as wearables. These can be attached to the skin of the patient P by gluing, or worn as a glove (see 12c), etc.

[0078] The central nervous system stimulation module 18 is, in the embodiment shown, an epidural stimulation module capable of providing epidural stimulation via electrodes 25 .

[0079] Generally, the central nervous system stimulation module 18 may be provided as a stimulation module capable of providing subdural or intracortical or intrathecal stimulation.

[0080] The PNS stimulation module 20 is a functional electrical stimulation module capable of providing electrical stimulation of peripheral nerves via electrodes 26.

[0081] As can be seen in FIGS. 1 and 2, the PNS stimulation module 20 includes an electrode 26 .

[0082] The electrode 26 is implanted and has fixation elements at the implanted side for anchoring the electrode 26 to the surrounding structure.

[0083] The control unit 14 receives signals from the various sensors of Figures 1 and 2 and uses the various actuators of Figures 1 and 2 to adjust stimulation parameters based on the received signals and instructions stored in the memory of the control unit 14.

[0084] The control unit 14 controls the stimulation provided by the PNS stimulation module 20 and / or the stimulation provided by the CNS stimulation module 18 based on the sensed signals provided and acquired by the detection unit 12. - to align stimulation control signals provided by the control unit 14 for controlling the PNS stimulation module 20 and / or the CNS stimulation module 18 with physiological signals decoded from the subject's brain and / or nervous system that are related to the subject's intention to move; and - aligning stimulation control signals provided by the control unit 14 for controlling the PNS stimulation module 20 and / or the CNS stimulation module 18 with a desired kinematic trajectory; and - to align the stimulation control signals provided by the control unit 14 for controlling the PNS stimulation module 20 and / or the CNS stimulation module 18 with a desired force on the surface on which the subject is positioned or touching, and - aligning stimulation control signals provided by the control unit 14 for controlling the PNS stimulation module 20 and / or the CNS stimulation module 18 with muscle activation for certain gait patterns and / or grip types and / or movements; It is configured to be adjustable and / or adaptable.

[0085] Furthermore, the control unit 14 is configured to be able to decode signals provided by the sensing unit 12 and related to the subject's movements, in particular to be able to continuously decode signals related to the subject's movements and / or forces and / or EMG activity and / or kinematic trajectories.

[0086] The system 10 functions in real time as a closed loop system.

[0087] In particular, the stimulation signals provided by the CNS stimulation module 18 and its electrodes 25, and the PNS stimulation module 20 and its electrodes 26, are monitored and recorded by the sensing units and sensors 12, 12a, 12b, 12c, 12d, along with the patient's respective responses.

[0088] Typically, system 10 is and can function as an open-loop system, in particular, there can be a pre-programmed set or pattern of stimuli to achieve a desired exercise result.

[0089] In particular, the sensing signal is used to affect the stimulation signal, which is again sensed by the sensing unit 12 and which again affects the control unit 14 .

[0090] This functioning method is controlled by a control unit 14 which is arranged so that the control takes place in real time.

[0091] The real-time control and function of the system 10 means that the control occurs with minimal delay, ie, within the range of about 0 ms to 30 ms.

[0092] The control unit 14 is configured to at least partially alternate between the stimulation provided by the PNS stimulation module 20 and the stimulation provided by the CNS stimulation module 18 .

[0093] Additionally, the control unit 14 may be configured such that the stimulation provided by the PNS stimulation module 20 and the stimulation provided by the CNS stimulation module 18 at least partially overlap.

[0094] By alternating or overlapping signals, stimulation can be tailored to the individual.

[0095] Furthermore, the control unit 14 is configured such that the stimulation provided by the PNS stimulation module 20 or the CNS stimulation module 18 is used, at least in part, to compensate for the stimulation effect provided by the other stimulation module in order to improve motor output.

[0096] Furthermore, the control unit 14 is capable of independently controlling and switching on and off the PNS stimulation module 20 or the CNS stimulation module 18. In other words, the PNS stimulation module 20 and the CNS stimulation module 18 can be controlled independently of each other.

[0097] Such control is performed by the control unit 14.

[0098] The functionality of the system 10 can be described as follows.

[0099] The system 10 provides a novel electrical stimulation paradigm for recovery or precise and controllable motor function targeting both the central and peripheral nervous systems in an improved neuroprosthetic rehabilitation for neuromotor disorders. As explained above, rather than using spinal cord stimulation or nerve stimulation alone, electrical stimulation of the central nervous system (spinal cord) can be combined in real time with intermittent electrical stimulation of peripheral nerves to establish a specific and more general stimulation approach.

[0100] It is possible to take advantage of the complementary advantages of both stimulation types.

[0101] For healthy individuals, motor output is constantly refined and adjusted based on information from the periphery (e.g. proprioceptive, sensory, visual...).

[0102] To achieve such precise tuning, the stimulation paradigm needs to selectively reinforce specific muscles to compensate for imprecision in the motor output produced by the central stimulation paradigm.

[0103] The system 10 can use information from the peripheral and central nervous systems to refine and adjust the required stimulation output via the CNS stimulation module 18 or the PNS stimulation module 20.

[0104] For this reason, there exists a combination of spinal cord and peripheral nerve electrical stimulation. The combination of both strategies results in a highly improved and much more efficient neuroprosthetic rehabilitation of motor control, with potential applications in both paraplegic and upper limb paraplegic paradigms.

[0105] In the paralytic framework, spinal cord stimulation reinforces the functional network below the lesion and activates muscle synergies that serve as building blocks for functional movements. While the movements resulting from the activation of movement-related muscle synergies are powerful, controlling and executing precise movements is a challenging task, and the movements generated and their inaccuracies impede fluidity and full functionality in the movement potential space.

[0106] Peripheral nerve stimulation can directly target specific muscles, resulting in selective and controllable activation that allows expanding the reachable space of movement. The bottleneck of this extreme selectivity caused by the direct projection from the nerve to the muscle it innervates is the inability to generate functional, load-bearing movements. In fact, functional, multi-joint movements require reinforcing muscles innervated by two or more nerves, and stimulating one nerve is not sufficient to generate useful movements.

[0107] Therefore, combining both stimulation types could exploit the advantages of each stimulation paradigm to restore functional, complex and precise movements after paralysis.

[0108] The feasibility of the above paradigm has been demonstrated in a rat model of paralytic spinal cord injury, as shown in Figures 3, 4, 5 and 6.

[0109] FIG. 3 shows a schematic diagram of an example of the implementation of the system 10' in a feasibility study conducted with a rat 100, aimed at restoring improved locomotion after a paralytic spinal cord injury.

[0110] Similar practices are possible in other mammals or in humans.

[0111] There is a CNS stimulation module 18' and a PNS stimulation module 20' that have the structural and functional characteristics as described above, but are adjusted to the size of the rat 100.

[0112] In this example, the spinal cord 102 of a rat 100 has been injured at the mid-thoracic level (approximately T8 / T9) by either a severe spinal cord contusion or a complete spinal cord transection (see the lower left portion of FIG. 3).

[0113] EMG signals from the ankle muscles 104 are recorded via bipolar wire electrodes 106 of a neural polyimide-based multi-channel implant 107 implanted within the muscle (see the lower right and upper left parts of FIG. 3).

[0114] The kinematics of the lower limb joints are recorded by reflective markers glued to the joints with double-sided tape by a recording system 101. CNS stimulation is delivered epidurally over the lumbosacral spinal cord 102 by two monopolar wire electrodes 108, 110 (see the upper right part of Figure 3) placed at levels L2 and S1, respectively.

[0115] 5HT7, 5HT2 and 5HT1a represent agents that can be used to support stimulation.

[0116] The recorded signals relate to the kinematics of the lower limb segments (i.e. stance, swing and drag), here as follows: - the crest, i.e. the kinematic crest signal K1, - hips, i.e. the kinematic hip signal K2, - the knee, i.e. the kinematic knee signal K3, the ankle joint, i.e. the kinematic ankle joint signal K4, and - Foot, i.e. the kinematic foot signal K5.

[0117] Additionally, EMG activity is recorded by the recording system 101, where EMG signals associated with the ankle joint, flexors and extensors are recorded.

[0118] The signals recorded by the recording system 101 may be stored in a memory of the recording system 101. They are also used by a control unit of the system 10' (not shown, but whose functions are described above in relation to the control unit 14).

[0119] PNS stimulation is applied via an intraneural polyimide-based multi-channel implant inserted into the proximal sciatic nerve 112 (above the bifurcation point where it splits into separate bundles) (see the bottom right portion of FIG. 3).

[0120] In this setup, the wires from the EMG electrodes and the epidural spinal electrodes are all routed subcutaneously to a common connector that is cemented to the rat's skull. An amplifier for the EMG signal and a stimulator feeding the spinal cord can be plugged into this connector. The wires from the intraneural electrodes are routed subcutaneously to a plug in the rat's lower back, and a stimulator can be plugged into this plug.

[0121] As shown in the upper left portion of FIG. 3, the kinematics (of the bone crest, hip, knee, ankle and foot) and the respective EMG activity (of the ankle, flexors and extensors) are recorded by sensors in the system 10'.

[0122] FIG. 4 shows how a system 10' such as that presented in FIG. 3 can be used in real time to generate functional and improved motion.

[0123] Epidural electrodes, i.e., two monopolar wire electrodes 108, 110 on the lumbosacral spinal cord 102 (see upper right portion of FIG. 3 and CNS stimulation module 18'), electrically stimulate the locomotor circuitry to generate a functional walking pattern.

[0124] The generated movements of the rat 100 on the treadmill 114 are monitored in real time by a camera 116, among other things, using reflective markers glued to the hind limb joints (bony crest, hip, knee, ankle, toe).

[0125] In this example, the control unit 14' (which may wirelessly control, among other things, the components of the system 10') compares the generated gait pattern with a model gait cycle in real time to recognise key events such as foot contact, toe off or maximum foot height and their timing in real time.

[0126] Also in this example, selective PNS is used at defined stages in the walking cycle to refine the generated gait if the generated gait does not match the desired model walking cycle.

[0127] Bilateral intraneural electrodes in the right and left sciatic nerves deliver transient electrical stimulation to correct inaccuracies found in the pattern and improve gait.

[0128] In this example, the intensity of the PNS was controlled by the frequency of the delivered pulses.

[0129] Figure 5 (top) shows preliminary results obtained using the system described in Figures 3 and 4. Ankle flexion was improved through selective sciatic nerve stimulation of the peroneal nerve bundle at the start of the swing phase, while ankle extension was improved through selective stimulation of the tibial branch of the sciatic nerve via a different activation site at the end of the stance phase.

[0130] Adding PNS to the CNS had a profound effect on the stimulated and contralateral legs, indeed resulting in a large increase in step height for the leg additionally stimulated by PNS.

[0131] Furthermore, foot-catching stimulated additionally by PNS was significantly reduced compared with CNS alone.

[0132] Applying peripheral nervous system (PNS) stimulation via the PNS stimulation module 20 on one leg had a significant effect on the other leg, for example, greatly increasing the stride length of that leg.

[0133] This improvement in walking enabled the rat 100 to walk on ground (bottom of FIG. 5) and climb stairs (see center part of FIG. 5 with stairs ST) with significantly reduced missteps and falls.

[0134] The present invention has great potential for restoring fine movement to people affected by paralysis.

[0135] In particular, in the case of upper limb paralysis, spinal cord stimulation has proven to have fairly limited success in being able to selectively activate muscles in the forearm or fingers.

[0136] Therefore, centrally activating reaching and grasping synergies and improving these peripherally has great potential to restore functional, improved and controllable movements of the upper limbs after paralysis.

[0137] Central neuromodulation in the form of spinal electrical stimulation generates motor synergies that result in functional movements, but these movements are spatially limited. By additionally stimulating the peripheral nerves with different stimulation frequencies in addition to central neuromodulation, i) gradually improving the generated movements; ii) locally expanding the reachable space in a highly controllable manner This makes it possible.

[0138] Figure 6 illustrates this concept in a paraplegic framework.

[0139] Foot trajectories T1, T1' (black) are obtained with central neuromodulation (electrical epidural stimulation of the lumbosacral spinal cord) and exhibit moderate step height and foot hooking. Superimposition of selective sciatic nerve stimulation allows further gradual modulation of the gait cycle, improving movement, for example by increasing the step height of the stimulated leg with higher frequencies (trajectory T2 at 30 Hz, trajectory T3 at 70 Hz) or reducing the hooking of the contralateral leg (trajectory T2' at 30 Hz and trajectory T3' at 70 Hz). Peripheral nerve stimulation with graded frequencies gradually improves the overall stepping pattern of both the stimulated and the contralateral leg, which, in combination with central neuromodulation, improves the recovery of controlled movement.

[0140] The lower part of FIG. 6 shows the foot trajectories for improved ipsilateral flexion, shown as trajectory T1 for FES stimulation only, and superimposed therewith, trajectory T3 for EES stimulation plus PNS.

[0141] PNS stimulation is performed in the range of 30 Hz (trajectory T2) to 70 Hz (trajectory T3).

[0142] The upper portion of FIG. 6 illustrates improved contralateral extension with foot trajectories shown as trajectory T1' for EES stimulation alone and superimposed trajectory T3' for EES stimulation plus PNS.

[0143] PNS stimulation is performed in the range of 30 Hz (trajectory T2') to 70 Hz (trajectory T3').

[0144] FIG. 7 relates to a flow chart illustrating an example of how a closed-loop embodiment of the neuromodulation and / or neurostimulation system 10 according to the present invention operates.

[0145] In step S1, physiological signals of a patient (or a rat, as shown in the mammalian example of FIGS. 3 to 6) are obtained and recorded. This is done by the sensing unit 12.

[0146] In step S2, the resulting signal is provided to the control unit 14.

[0147] In step S3, an initial stimulation parameter set is provided by the control unit 14.

[0148] In step S4, the control unit 14 matches the stimulation control signals provided to control the PNS stimulation module 20 and / or CNS stimulation module 18 with physiological signals decoded from the subject's brain and / or nervous system related to the subject's intention to move.

[0149] In step S5, the control unit 14 aligns the stimulation control signals provided to control the PNS stimulation module 20 and / or the CNS stimulation module 18 with the desired kinematic trajectory.

[0150] In step S6, the control unit 14 coordinates the stimulation control signals provided to control the PNS stimulation module 20 and / or CNS stimulation module 18 with the desired force on the surface on which the subject is positioned or touching.

[0151] In step S7, the control unit 14 coordinates the stimulation control signals provided to control the PNS stimulation module 20 and / or CNS stimulation module 18 with muscle activation for a certain gait pattern and / or grip type and / or movement.

[0152] Steps S4 to S7 can be performed consecutively or in parallel.

[0153] In step S8, the physiological signals are decoded. This is performed by the control unit 14. The control unit 14 is configured to be able to decode the signals provided by the sensing unit 12 and related to the subject's movements, in particular to be able to successively decode signals related to the subject's movements and / or forces and / or EMG activity and / or kinematic trajectories.

[0154] As can be seen from the flow chart, the system 10 functions in real time as a closed loop system.

[0155] Step S8 is followed by step S1.

[0156] It should be noted that the exemplary control and estimation routines included herein can be used with a variety of neuromodulation and / or neurostimulation system configurations. The control methods and routines disclosed herein can be stored as executable instructions in a non-transitory memory and executed by a control unit in combination with various sensors, actuators and other system hardware. The specific routines described herein can represent one or more of any number of processing strategies, such as event-driven, interrupt-driven, multitasking, multi-threading, etc. Thus, the various actions, operations and / or functions shown can be performed in the order shown, in parallel, or omitted in some examples. Similarly, the order of processing is not necessarily required to achieve the features and advantages of the exemplary embodiments described herein, but is provided for ease of illustration and description. One or more of the illustrated actions, operations and / or functions can be performed repeatedly depending on the particular strategy being used. Furthermore, the described actions, operations and / or functions can be represented diagrammatically as code programmed into a non-transitory memory of a computer-readable storage medium in a control unit, where the described actions are performed by executing instructions in a system including various hardware components in combination with an electronic control unit. [Explanation of symbols]

[0157] 10 Neuromodulation and / or Neurostimulation Systems 12 Detection unit 12a Detection unit 12b Detection unit 12c Sensor 12d Sensor 14 Control unit 16 Stimulation Units 18 Central Nervous System (CNS) Stimulation Module 20 Peripheral Nervous System (PNS) Stimulation Module 22 Implantable Pulse Generators (IPGs) 24 Implantable Pulse Generators (IPGs) 25 electrodes 26 electrodes 10' System 14' Control Unit 18' Central Nervous System (CNS) Stimulation Module 20' Peripheral Nervous System (PNS) Stimulation Module 100 rats 102 Spinal cord (rat) 104 Ankle Muscles 106 Bipolar Wire Electrode 107 Polyimide-based multi-channel neural implant 108 Unipolar Wire Electrode 110 Unipolar Wire Electrode 112 Sciatic Nerve 114 Treadmill 116 Cameras P patient K1 kinematic bone ridge signal K2 kinematic hip signal K3 kinematic knee signal K4 Kinematic ankle signal K5 kinematic foot signal M Memory ST stairs S1 Method step S1 S2 Method step S2 S3 Method step S3 S4 Method step S4 S5 Method step S5 S6 Method step S6 S7 Method Step S7 S8 Method step S8 T1 orbit (EES only) T2 orbit T3 orbit T1' orbit (EES only) T2' trajectory (EES and PNS with Hz) T3' orbit

Claims

1. A neuromodulation and / or neurostimulation system (10) comprising at least the following components: at least one sensing unit (12); at least one control unit (14); - at least one stimulation unit (16) including: (i) at least one central nervous system (CNS) stimulation module (18) with electrodes (25) for providing central nervous system (CNS) stimulation; and (ii) at least one peripheral nervous system (PNS) stimulation module (20) with electrodes (26) for providing peripheral nervous system (PNS) stimulation; Equipped with At least one of the components of the neuromodulation and / or neurostimulation system (10) is implantable; and wherein the control unit (14) is configured to adjust the PNS stimulation and the CNS stimulation based on the obtained detection signals provided by the sensing unit (12) so that stimulation control signals provided by the control unit (14) for controlling the PNS stimulation module (20) and the CNS stimulation module (18) are at least partially consistent with physiological signals associated with the subject's intention to move decoded from the brain and / or nervous system signals of the subject detected by the at least one detection unit, and promote the subject's intended movement. The neuromodulation and / or neurostimulation system (10).

2. 10. The system of claim 1, wherein the central nervous system (CNS) stimulation module is or comprises an epidural stimulation module capable of providing epidural spinal cord stimulation.

3. 3. The system (10) of claim 1 or 2, characterized in that the peripheral nervous system (PNS) stimulation module (20) is a functional electrical stimulation (FES) module capable of providing electrical stimulation of peripheral nerves.

4. The system (10) of any one of claims 1 to 3, characterized in that the central nervous system (CNS) stimulation module (18) is at least partially implantable or at least partially implanted and / or the peripheral nervous system (PNS) stimulation module (20) is at least partially implantable or at least partially implanted.

5. The system (10) according to any one of claims 1 to 4, characterized in that the components of the neuromodulation and / or neurostimulation system (10) form a closed loop system.

6. The system (10) according to any one of claims 1 to 4, characterized in that the components of the neuromodulation and / or neurostimulation system (10) form an open-loop system.

7. The system (10) according to any one of claims 1 to 6, characterized in that the control unit (14) is arranged such that the control is performed in real time.

8. The system (10) of any one of claims 1 to 7, characterized in that the electrode (26) of the peripheral nervous system (PNS) stimulation module (20) has at least one fixation element for anchoring the electrode (26) in or to a surrounding structure.

9. The control unit (14) controls the stimulation provided by the PNS stimulation module (20) and / or the stimulation provided by the CNS stimulation module (18) based on the obtained detection signal provided by the detection unit (12). - to at least partially align stimulation control signals provided by the control unit (14) for controlling the PNS stimulation module (20) and / or the CNS stimulation module (18) with signals corresponding to a desired kinematic trajectory; The system (10) according to any one of claims 1 to 8, characterized in that it is further configured to be adjustable and / or adaptable.

10. The system (10) according to claim 9, characterized in that the control unit (14) is configured to be able to decode signals related to the subject's movements from signals provided by the detection unit (12) and from the brain and / or nervous system of the subject, in particular to be able to continuously decode signals related to the movements of the subject and / or forces and / or EMG activity and / or kinematic trajectories.

11. The system (10) according to any one of claims 1 to 10, characterized in that the control unit (14) is configured to at least partially alternate between the stimulation provided by the PNS stimulation module (20) and the stimulation provided by the CNS stimulation module (18).

12. The system (10) of any one of claims 1 to 11, characterized in that the control unit (14) is configured such that the stimulation provided by the PNS stimulation module (20) and the stimulation provided by the CNS stimulation module (18) are at least partially overlapping.

13. The system (10) of any one of claims 1 to 12, characterized in that the control unit (14) is configured such that the PNS stimulation provided by the PNS stimulation module (20) is used for correction of the CNS stimulation provided by the CNS stimulation module (18) to improve motor output.

14. The system (10) according to any one of claims 1 to 13, characterized in that the control unit (14) is capable of independently controlling and switching on and off the PNS stimulation module (20) or the CNS stimulation module (18).

15. The system (10) of any one of claims 1 to 14, wherein the control unit (14) is configured to generate CNS stimulation through the CNS stimulation module and to generate PNS stimulation at a stimulation frequency of 30 to 120 Hz.

16. A method (10) for controlling a neuromodulation and / or neurostimulation system, said system comprising at least the following components: at least one sensing unit (12); at least one control unit (14); - (i) at least one central nervous system (CNS) stimulation module (18) that provides central nervous system (CNS) stimulation, and (ii) at least one peripheral nervous system (PNS) stimulation module (20) that provides peripheral nervous system (PNS) stimulation; Equipped with The method comprises: obtaining a detection signal by said detection unit (12); adjusting the PNS stimulation and the CNS stimulation based on the detection signals obtained by the sensing unit (12) such that stimulation control signals provided by the control unit (14) for controlling the PNS stimulation module (20) and the CNS stimulation module (18) are at least partially consistent with physiological signals associated with the subject's intention to move decoded from the brain and / or nervous system signals of the subject detected by the at least one detection unit and promote the subject's intended movement; A method for controlling the neuromodulation and / or neurostimulation system (10), comprising:

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