阅读说明：本技术 用于刺激脊髓的经硬膜电极装置 (Transdural electrode device for stimulating the spinal cord ) 是由 马修·A·霍华德三世 乔治·T·吉利斯 洛根·海兰德 罗伊斯·伍德罗夫 查尔斯·罗曼斯 索 于 2019-06-03 设计创作，主要内容包括：本发明的脊髓刺激装置被配置成用于植入患者体内,以便跨越围绕脊髓的硬膜。将装置放置在此位置使电极与靠近脊髓的脑脊液(CSF)直接接触。装置具有硬膜内部分和硬膜外部分,其将硬膜按压并密封在它们之间,从而将装置固定就位并防止CSF泄漏。它由植入的脉冲发生器以电子方式供电,该脉冲发生器产生一系列信号,以中断或以其他方式减弱疼痛介导神经信号通过脊髓的传输。一旦装置被植入患者体内,它就提供与目前可用的技术相比改善的刺激效率、降低的功率需求以及潜在改善的临床效果。(The spinal cord stimulation device of the present invention is configured for implantation within a patient so as to span the dura mater surrounding the spinal cord. The device is placed in this position with the electrodes in direct contact with the cerebrospinal fluid (CSF) near the spinal cord. The device has an epidural portion and an epidural portion that presses and seals the dura between them, securing the device in place and preventing CSF leakage. It is electrically powered by an implanted pulse generator that generates a series of signals to interrupt or otherwise attenuate the transmission of pain-mediated neural signals through the spinal cord. Once implanted in a patient, the device provides improved stimulation efficiency, reduced power requirements, and potentially improved clinical outcome compared to currently available techniques.)

1. A device for spinal cord stimulation configured to be secured to the dura surrounding the spinal cord of a subject, the device comprising the following components:

a plurality of electrodes;

a lead configured to electrically connect the electrode to the epidural signal source; and

means for securing the device to the dura mater such that the electrodes are in direct contact with cerebrospinal fluid (CSF) within the subdural space, but not with the spinal cord itself.

2. A device for spinal cord stimulation configured to span and be secured to the dura mater surrounding the spinal cord of a subject, the device comprising the following components:

a dura mater-passing portion;

an epidural component;

an epidural component;

a plurality of electrodes on the epidural portion and/or the epidural component; and

a lead connected to the electrode through the epidural portion;

the device being transitionable from an open position to a clamped position;

wherein the open position configures the device to be inserted through an incision in the dura mater to place the intra-dural portion within the dura mater;

wherein the clamping location secures the device to the dura mater by clamping the dura mater between the epidural component and the epidural component, wherein the electrodes are in direct contact with the cerebrospinal fluid.

3. A device for spinal cord stimulation configured for spanning and securing to the dura mater surrounding the spinal cord of a subject, the device comprising:

a dura mater portion comprising an outer surface and a longitudinal axis;

an epidural component conforming to an inner surface of the dura, wherein the epidural component is fixedly or slidably or rotatably connected to the dura portion and has a gripping portion extending or extendable to a position radially beyond the outer surface of the dura portion;

an epidural component conforming to an outer surface of the dura, wherein the epidural component is fixedly or slidably or rotatably connected to the epidural portion and has a grip portion extending or extendable to a position radially beyond the outer surface of the epidural portion; and

one or more electrodes contained in the epidural portion and/or the epidural component;

wherein the epidural and/or epidural component contains an aperture that is complementary to and surrounds the outer surface of the epidural portion, thereby configuring the respective components to slide over or around the outer surface of the epidural portion such that a space between the epidural component and the epidural component can narrow from an open position to a clamped position;

wherein, when in the open position in the device, the epidural component is configured to pass through a short incision in the dura surrounding the spinal cord, leaving the epidural component outside the dura, then sliding or rotating the epidural component and/or the epidural component on or around the outer surface of the epidural portion to narrow the distance therebetween, and securing the epidural component and the epidural component in the clamped position has the effect of clamping the dura between the epidural component and the clamped portion of the epidural component.

4. The device according to claim 2 or claim 3, wherein the epidural component is fixed to the epidural portion and the epidural component is configured to pass over the outer surface of the epidural portion towards the epidural component.

5. The device according to any one of claims 2 to 4, wherein the outer surface of the dura mater portion about the longitudinal axis is cylindrical.

6. The device of claim 4 or claim 5, wherein the epidural portion has external threads configured to receive a locking nut that tightens the epidural portion, thereby securing the epidural component to the epidural component.

7. The device according to claim 6, wherein the locking nut is a separate component of the device from the epidural portion or the epidural portion.

8. The device according to any one of claims 2 to 5, comprising a securing member extending radially from the epidural component and spring loaded to prevent the epidural component from sliding away from the epidural component once the epidural component is in the clamped position.

9. The device of any one of claims 2 to 5, comprising a snap fastener configured to fasten the epidural component to the epidural portion, thereby securing the device in the clamped position.

10. The device according to any one of claims 2 to 9, wherein the epidural component is operable from a retracted position or an insertion position to a deployed position in which a gripping portion of the epidural component extends radially beyond the outer surface of the epidural portion.

11. The device of any one of claims 2 to 10, wherein the epidural component comprises a plurality of flanges, wherein at least one of the flanges is movable from an insertion position to a deployed position:

in the insertion position, the flanges are located below or inside the dural part, or are oriented parallel to each other;

in the deployed position, portions of each of the flanges extend radially beyond the outer surface of the dural portion in different directions.

12. The device according to any one of claims 2 to 10, wherein the epidural component includes both:

a circular member secured or connected to the dura mater portion with a clamp portion that extends radially to a location beyond the outer surface of the dura mater portion; and

at least three flanges, wherein at least two of the flanges are rotatably movable from an insertion position in which the flanges are parallel to each other to a deployed position in which each of the flanges extends away from the dura mater portion in a different direction.

13. The device according to any one of claims 2 to 12, wherein the epidural component and the epidural component are elliptical, ellipsoidal, rectangular or ellipsoidal so as to cover the incision between them and form a watertight closure when the device is in the clamped position.

14. The device according to any one of claims 2 to 13, comprising at least one electrode positioned on or near the longitudinal axis such that when the device is secured to the dura mater, the electrode is directionally located inside the dura mater towards the spinal cord.

15. The device of any one of claims 2 to 14, wherein the epidural component has a long axis, wherein a plurality of electrodes are arranged along the long axis.

16. The device according to any one of claims 2 to 15, wherein the epidural component is "T" shaped, with electrodes arranged along each arm or the "T".

17. The device of any one of claims 2 to 16, comprising a plurality of leads connected to the electrodes through the epidural portion.

18. The apparatus according to any one of claims 2 to 17, wherein the epidural component further comprises one or more electrodes, thereby configuring the apparatus to provide electrical stimulation both intraddurally and extradurally.

19. The device according to any one of claims 2 to 18, wherein the shape of the epidural component is spiral or hollow circular so as to be rotatably insertable through a narrow incision.

20. The apparatus according to claim 19, wherein the epidural component is circular and has a perimeter that aligns with a perimeter of the epidural component.

21. The device of any one of claims 1-20, wherein the epidural component is configured to pass through an incision that does not exceed 0.5, 1.0, or 1.5cm when in the open position in the device.

22. The device of any one of claims 1 to 21, further comprising a sleeve or coupler configured for reversibly securing the device to a positioning tool such that the device can be manipulated to place the epidural component within the dura and then the positioning tool can be removed from the sleeve or coupler.

23. A positioning tool configured for clamping the device according to any one of claims 2 to 22 to the dura mater of the spinal cord of a subject, the positioning tool comprising a housing, a holding device reversibly fixing the insertion tool to the device, and a clamping device sliding the epidural component of the device along the epidural portion towards the epidural component, thereby reducing the distance therebetween and clamping the device to the dura mater.

24. A combination for preparing a subject for spinal cord simulation, the combination comprising:

the spinal cord stimulation device according to any one of claims 1 to 22; and

a positioning tool reversibly connectable to the device such that the device can be manipulated to place the epidural component inside the dura and then the positioning tool can be removed from the device.

25. A combination according to claim 24, wherein the positioning tool is configured to change the device from an open position for surgically adapting the device to span the dura of the subject's spinal cord to a clamped position in which the device is secured to the dura.

26. A combination according to claim 24 or claim 25, wherein the positioning tool is configured to tighten a locking nut along the epidural component, thereby clamping the epidural component to the epidural component in order to fix the device to the dura mater.

27. A combination for spinal cord stimulation in a subject, comprising:

the spinal cord stimulation device according to any one of claims 1 to 22;

a signal source configured and programmed to deliver electrical stimulation to the spinal cord of a subject by the device, wherein the electrical stimulation is sufficiently high to cause stochastic depolarization and/or reduce frequency variations or fluctuations in pain transmission through the spinal cord;

a lead configured to electrically connect the device to the signal source when the device and the signal source are implanted in the subject.

28. A combination for spinal cord stimulation in a subject, comprising:

the spinal cord stimulation device according to any one of claims 1 to 22;

a signal source configured and programmed to deliver electrical stimulation to the spinal cord of a subject by the device, wherein the electrical stimulation varies or fluctuates at a frequency of at least 200 or 500 Hz; and

a lead configured to electrically connect the device to the signal source when the device and the signal source are implanted in the subject.

29. The device or combination of any one of claims 1-28, wherein the plurality of electrodes are spaced to selectively target fibers selected from large, medium, or all fibers within the spinal cord.

30. The device or combination of any one of claims 1-28, wherein the plurality of electrodes are spaced apart such that they are in a T-shaped epidural electrode array configuration.

31. A method of preparing a subject for treatment of pain, the method comprising:

(a) obtaining a surgical access to the dura mater surrounding the spinal cord of the subject;

(b) making a short incision in the dura mater;

(c) obtaining a spinal cord stimulation device comprising a dural portion, one or more electrodes, an epidural component, and an epidural component;

(d) positioning the device such that the epidural component is inside the dura mater, the epidural portion reaching from inside the dura mater to outside the dura mater; and the epidural component is external to the dura mater;

(e) narrowing the distance between the epidural component and the epidural component to a clamped position; and

(f) securing the epidural component and/or the epidural component in place to maintain the clamping position, thereby securing the device to the dura mater, preferably sealing the dura mater, to prevent leakage of cerebrospinal fluid into the epidural compartment or epidural outflow into the epidural compartment.

32. The method of claim 31, wherein the narrowing comprises tightening a locking nut along a durally covered portion of the device.

33. The method of claim 31 or claim 32, further comprising electrically connecting the device to a signal source configured and programmed to deliver electrical stimulation to the spinal cord of the subject through the device.

34. A method of preparing a subject for treatment of pain comprising securing a device according to any one of claims 1 to 22 to the dura mater surrounding the spinal cord of the subject.

35. A method of treating pain in a subject comprising delivering electrical stimulation to the spinal cord of the subject by a device according to any one of claims 1 to 22, the device having been secured to the dura mater of the spinal cord of the subject, thereby alleviating the pain without stimulating dorsal nerve roots.

36. The method of claim 35, comprising monitoring transmission of a simultaneous action potential through the spinal cord and/or transmission of pain experienced by the subject, and then modulating an electrical stimulus so as to further inhibit or otherwise modulate transmission of a simultaneous action potential through the spinal cord and/or reduce perception of the pain by the subject.

37. A method of treating spasticity in a subject, comprising delivering electrical stimulation to the spinal cord of the subject by a device according to any one of claims 1 to 22, said device having been secured to the dura mater of the spinal cord of the subject.

38. The method of any one of claims 31 to 37, wherein the electrical stimulation varies or fluctuates at a frequency of at least 200 or 500 Hz.

39. The device or combination according to any one of claims 1 to 30 for use in the treatment of pain.

40. A device or combination according to any one of claims 1 to 30 for use in the treatment of spasticity.

Technical Field

The present invention relates generally to the field of medical devices for managing conditions that are at least partially due to the deleterious transmission of nerve impulses through the spinal cord. In particular, it provides improved devices and their use in applying electrical stimulation to the spinal cord.

Background

Both intractable pain and spinal cord injury are major public health problems. Pain may be the result of failed back surgery, complex local pain syndrome, neurodegeneration and trauma. Over one million patients are not treated properly in the united states alone, and midline spinal pain is a leading cause of unemployment and disability in americans. Almost 300,000 patients suffer from Spinal Cord Injury (SCI), including partial or total loss of motor, sensory, and autonomic (autonomic) function. These clinical conditions place a tremendous economic, clinical and emotional burden on the patient and their families, as well as the society as a whole.

There are some devices designed for Spinal Cord Stimulation (SCS) from within the dura mater (dura). Us patents 9,364,660 and 9,486,621 provide an electrode array that can be implanted directly against the spinal cord. Us patents 9,254,379 and 9,572,976 describe how such SCS devices can be fixed in place by components that are fixed to the vertebrae. US patents 9,403,008 and 9,950,165 and pre-grant publication (pre-grant publication) US 2018/0369577 a1 describe how these devices can be used to deliver (deliverer) high frequency stimulation to cause the propagation of action potential patterns (action potential patterns) that mediate pain sensations within the spinal cord. Us patent 10,071,240 describes floating electrodes that engage and accommodate spinal cord movement, as well as other aspects and configurations of intracranial SCS devices.

Nevro Corp (Redwood, California) developed an SCS device that provided high frequency stimulation from the epidural space. Aspects of the Nevro device are described in U.S. patents 8,170,675, 8,359,102, 8,712,533, 8,838,248 and 8,892,209. They are marked by trademarksAndand performing commercial distribution.

Early publication US 2013/0274846 a1(Lad) relates to methods and devices for stimulating the spinal cord. U.S. patent 6,319,241(King) relates to techniques for positioning a therapy delivery element within the spinal cord or brain. The early publication US 2006/0173522 a1(Osorio) contemplates anchors for medical device components near the dura mater of the brain or spinal cord. Us patent 3,724,467(Avery) proposes an electrode implant for nerve stimulation of the spinal cord. In unrelated work, US 2010/0057115 a1(Rao) proposes a surgical method and clamping device for repairing dural or vessel wall defects.

Early publication US 2006/0052835 a1(Kim) proposed a method of stimulating the spinal cord and nervous system. Us patent 9,630,012(Carroll) proposes a technique for spinal cord stimulation using inferred currents. Us patent 9,937,349(Grandhe) outlines a system for programming a neuromodulation system. Us patent 9,937,348(Bradley) proposes a system for selecting low power efficient signal delivery parameters for an implanted pulse generator. Us patent 6,999,820(Jordan) proposes a winged electrode body for spinal cord stimulation. US patent 8,2224,453(De rider) and early publication US 2005/0055065 a1 discuss spinal cord stimulation to treat pain.

Other prior publications include U.S. Pat. No. 4,633,889 (Talallal), U.S. Pat. No. 7,107,104(Keravel), U.S. Pat. No. 7,333,857(Campbell), U.S. Pat. No. 7,697,995(Cross), U.S. Pat. No. 7,962,218(Balzer), U.S. Pat. No. 8,346,366(Arle), U.S. Pat. No. 9,179,875(Hua), U.S. Pat. No. 9,386,934(Parker), U.S. Pat. No. 10,278,600(Parker), U.S. Pat. No. 2007/0010862A 1(Osypka), and U.S. Pat. No. 9,586,039A 1 (Bornzin).

Medical and surgical therapies currently used clinically to treat back pain, movement disorders, spinal cord injury and spasticity are suboptimal. Many patients fail to respond to Spinal Cord Stimulation (SCS) using currently available medical devices, fail to fully alleviate it, or only respond temporarily and return to a painful, debilitating or immotile condition. The introduction of new safe and effective therapeutic means and methods is an important medical, ethical and economic desideratum.

Disclosure of Invention

The electrode device of the present invention is configured for implantation in the dura mater (dura mater) surrounding the spinal cord. The device is placed in this position with the electrodes in direct contact with the cerebrospinal fluid (CSF) near the spinal cord. The device has an epidural portion and an epidural portion that compress and seal the dura between them, thereby securing the device in place and preventing CSF leakage. The device can be powered by an implanted pulse generator that generates a series of signals to interrupt or otherwise attenuate the transmission of pain-mediated neural signals through the spinal cord. Optionally, the device is configured to sense endogenous neural activity and/or evoked potentials that occur in response to the stimulus. The device can be programmed to respond to such neural activity by: delivering a dose of stimulation, an aliquot of stimulation, a continuous stimulation, or a stimulation pulse, and any suitable combination of parameters including frequency, width, amplitude, duty cycle, polarity, charge balance, chirp (chirp), and/or burst (burst), with or without dc offset. Stimulation may be delivered automatically without clinical intervention, providing a customized stimulation pattern that is dependent on individual patient response. The device can be implanted using Minimally Invasive Surgery (MIS), optionally with robotic assistance or using reality-based imaging.

Certain features of the invention are set forth in the appended claims. Other features are mentioned in the following description. The features described in this disclosure can be selected to use a device or system according to the invention in any operable combination.

Drawings

Fig. 1 and 2 show an exemplary SCS device according to the invention with an epidural component 6, via epidural parts 11 and 12, epidural components 7, 8 and 10 and a lock nut 14 clamping the epidural and epidural components on the dura mater 18 of the spinal cord.

Fig. 3 shows a positioning tool physically coupled to the device (below) for surgical implantation of an SCS device onto the dura mater of the spinal cord.

Fig. 4 shows details of the lower part 5, 9 of the positioning tool coupled to the epidural components 7, 8 and 10 of the SCS device.

Fig. 5A (side view) and 5B (craniocaudal view) show close-ups of a mechanical stabilization device for securing the epidural element of an implant in a patient.

Fig. 6 shows the T-shaped geometry of an exemplary epidural electrode array 20 mounted on the distal side of the epidural compression plate 6.

Fig. 7 shows a combined stimulation system for achieving extended coverage of the spinal cord with improved targeting of critical structures and avoidance of non-target structures. The epidural array 20 is shown in place inside the dura mater 18 suspended above the spinal cord 20 by means of the present invention. The device is configured to provide epidural stimulation through electrodes on the epidural component 5. Simultaneously or alternatively, the device can also provide epidural stimulation through electrodes located on the base plate 10 of the epidural component and facing outward.

Figures 8A, 8B, 9 and 10 show suitable dimensions for the positioning tool, epidural component and epidural component, respectively.

Fig. 11A, 11B and 11C show another SCS device according to the invention with an epidural component 11, a epidural part 31 and an epidural component 21. The epidural component has a flange 15 that can be deployed under the dura mater. The flange clamps against the clamping surface 23 of the epidural pad 22, securing the device to the dura and stabilizing it for long term use.

Fig. 12A to 12E illustrate the use of an insertion tool 40 to insert and clamp the device of fig. 11A onto the dura mater of the spinal cord.

Fig. 13A to 13C show the electrode device insertion tool alone.

Fig. 14 shows the device according to fig. 11A coupled to an insertion tool by a positioning rod 44.

Fig. 15A to 15C illustrate the operation of the insertion tool to transition the device from the open position to the clamped position.

Fig. 16A and 16B show an SCS device according to the present invention with a long flange arm 15B, the flange arm 15B having a linear array of electrodes 14a, 14B, and 14 c.

Fig. 17A to 17C show a device with three long flanged arms providing a two-dimensional array of seven electrodes.

Fig. 18A, 18B and 18C illustrate an SCS device according to the present invention having ellipsoidal (elliptical shaped) intradural and epidural components designed to be clamped together to seal an incision for insertion of the epidural component through the dura mater.

Figures 19A to 19D and 20A to 20D provide a procedure for inserting and securing the ellipsoid device to the dura mater.

Fig. 21A, 21B, 22A, 22B, 23A and 23B show another SCS device according to the invention with an epidural component 11, which epidural component 11 is shaped as a hollow circle to facilitate insertion through a narrow incision in the dura mater. Epidural component 22 is circular with a complementary gripping surface.

Fig. 24 shows the insertion of the device through a very narrow incision.

Fig. 25 and 26A-26F depict a surgical procedure in which the spinal cord of a subject is exposed and an SCS device according to the present invention is inserted and fixed in place through an incision in the dura mater for SCS therapy.

Fig. 27A-27F illustrate an electrical simulation device of the present disclosure designed to function as a port. The device contains one or more openings in fluid connection with the CSF and the epidural space, allowing fluid to be transferred from the epidural space to the CSF.

Fig. 28 shows a schematic diagram of an epidural stimulation system with one (or more) auxiliary epidural leads.

Fig. 29A and 29B are three-dimensional illustrations of prototypes of an epidural stimulator implantation tool and a T-shaped epidural electrode array on the distal end of the implantation tool prior to insertion, respectively.

Fig. 30 shows the geometric configuration and electrical parameters of the spinal cord and T-shaped electrode arrays used in the modeling study described in example 2 below.

Fig. 31A is a representation of the pia mater (pia) covering of white matter as a cross-section of white and gray matter across the spinal cord when viewed from below. The potentials due to current drive on six electrodes located in the epidural space, at the intersection of the T-array, are shown for the electrode site itself (lower scale) and projected on the pia surface and white matter cross-section (upper scale). In this example, the maximum and minimum voltages of these potentials are in each case displayed on the right and left side of the scale, respectively. The five lines drawn through the white matter represent the locations where the voltage within the brain parenchyma was sampled.

Fig. 31B is a plot of stimulation potential in millivolts versus axial distance along the spinal cord for the positions along the five position sampling lines shown in fig. 31A. These potentials are generated by currents driven by 6 electrodes at the intersection of a T-array within the dura as shown in figure 31A, positioned such that the electrode surfaces protrude approximately 0.3mm below the underside of the dura. The negative peaks of these spatial waveforms represent positive second-order spatial derivatives or differences surrounded by smaller negative spatial second-order derivatives. These are examples of computational results produced by finite element modeling of epidural spinal cord stimulation.

Fig. 32 provides the results of calculations generated by finite element modeling of the epidural spinal cord stimulation. The top of the left side shows a T-shaped arrangement of 12 electrodes of the epidural array. TC denotes the "top" electrode at the intersection of T. Likewise, CC represents the "center" electrode at the intersection of T, while BC represents the "bottom" electrode on the vertical component of T. The left side shows the gray scale range of the nerve fiber size excited within the white matter. Four examples of curved equipotential lines resulting from the stimulation parameters are shown on the right (where the intensity of each potential is marked in mV), the magnitude of the stimulation parameters for each case being shown only on the left side of each graph (plot). These stimulation parameters are the currents driven from the TC, CC and BC sites, and the resulting power consumption. The graph shows the depth of the isoelectric lines compared to the lateral position (both in mm) and reveals that their shape is restricted to white matter regions located within the dorsal horn gray matter boundaries. The gray points between the equipotentials show some locations in the white matter where different sized fibers are excited according to the gray scale range of sizes shown at the bottom of the left. These examples show precise control of the depth of stimulation within the white matter with little to no stimulation of non-target gray matter.

Fig. 33 provides the results of calculations generated by finite element modeling of the epidural spinal cord stimulation. The top of the left shows the electrodes of the T-array and gives an example of the current variation driven by those electrodes at the intersection of the T-shape. The current of the central two electrodes varied between 0 and-3 mA, while those of the other four electrodes varied between 0 and 1.4mA simultaneously. For the purposes of this example, the arrows indicate the direction of current change from positive to negative or negative to positive. The right side shows a graph of equipotential lines, where the intensity of each equipotential line is represented in mV, and shows their position in the white matter as the exemplary electrode current changes in five equal steps over its range from one pole to the other. The gray scale range of the size of the nerve fibers excited within the white matter is the same as those defined in fig. 32. The power consumption (in μ W) generated in each of the five cases is shown next to each graph. The graph shows the depth of the isoelectric line versus the lateral position (both in mm) and reveals that within the white matter within the dorsal horn gray matter boundary, its circumferential stimulation pattern can be controlled in a substantially linear manner. These examples show precise control over the circumferential course of the intraparenchymal stimulation with little to no stimulation of non-target gray matter.

Fig. 34A is a plot of millivolts versus milliseconds for an example of a set of action potentials generated at a node of a neuron targeted by a stimulation pulse from an epidural electrode array. In the trace under the graph, in this example case, the "stimulation" segment constitutes the ≈ 200 μ s cathodic depolarization component of the phase, while the "recovery" segment constitutes the ≈ 750 μ s anodic component of the phase. Individual action potentials occur within a specified time frame as governed by the electrophysiology of the neuron.

Fig. 34B is a plot of milliseconds versus millivolts of varying stimulation, with the center electrode of the T-array delivering an anodic first component ≈ 200 μ s, to show the ability to obtain the focusing effect required to avoid stimulating off-target tissue. It constitutes an example of a well-designed pulse that does not cause off-target action potentials, as indicated by the low amplitude of the peak in the recovery portion of the phase, and therefore does not stimulate off-target neurons. Fig. 34C is a plot of millivolts versus milliseconds demonstrating that if the recovery (cathodic) segment following the anodic first segment has the same pulse area, but is of greater amplitude, accidental discharge and propagation may occur in non-target tissue, as indicated by the high amplitude action potential occurring after the recovery component of this phase. These are further examples of the computational results produced by finite element modeling of the epidural spinal cord stimulation.

FIG. 35A is a millivolt versus time millisecond plot of stimulation drive voltage and average interface voltage at a circular electrode site having an area of ≈ 1.8mm²And driven by a 2mA cathodic pulse at 200 μ s, followed by a 50 μ s dwell and a 1mA charge balance phase at 400 μ s. The drive and interface voltages show a step at the beginning of the pulse and then gradually decrease until the end of the cathodic pulse. The average interface voltage increases because the current distribution efficiency is lower late in the pulse. The difference between the drive voltage and the interface voltage is caused by the charge accumulated on the surface of the electrode site and the difference in current distribution over the period.

Fig. 35B is a graph of the distribution of interface current (mA) versus radial distance (mm) across the electrode site from just before the start of the cathodic pulse to just before its end. At the start of the pulse, the current at the edge of the site (i.e., at a radial distance of 0.7 to 0.8 mm) spikes to a level well above the center of the electrode. Over time, the current distribution will become more uniform. Fig. 35C is a graph of the distribution of interface voltage (mV) versus radial distance (mm) across the electrode site over the same time as fig. 35B. It can be seen that this negative potential increases in magnitude, but is also lower at the edges due to the accumulated charge.

Fig. 36 is a diagram of a spatial model of the spinal cord showing the current distribution on the electrode sites of the white matter and the pia mater surface at the instant of the cathodal stimulation phase starting ≈ 200 μ s. The current density at the edge of the electrode site (upper scale) is very large relative to the average current, but this disappears quickly as the site charging progresses. Due to the shunting effect of cerebrospinal fluid, the current in and out of white matter (lower scale) is much smaller than at the electrode site. In this example, the total current at the cathodic site totals 4mA, while the total current into the white matter is only 0.13mA or 3.25%. The maximum and minimum values of the current density are shown on the right and left sides of the scale, respectively.

Detailed Description

The present invention provides a new technology for managing pain and other conditions by stimulating the spinal cord in a manner that disrupts, interferes with, and/or inhibits the transmission of harmful or unwanted sensory inputs. Such stimulation alleviates the symptoms and signs of pain while inhibiting or minimizing the risk of side effects such as paresthesia and potentially minimizing any side effects on basic nervous system processes such as motor neuron transmission and proprioception.

The techniques provided in the present disclosure can be used for any type of Spinal Cord Stimulation (SCS) that is beneficial to a patient. The present device is suitable for the administration of SCS at low as well as high frequencies. As described herein, the present device can be configured to sense action potentials and deliver a customized dose of stimulation in a closed-loop manner. The size and ease of implantation of the disclosed devices enables the devices to be used in a variety of therapeutic applications. These features allow for the manufacture of multiple implants in an individual patient, each potentially including an electrode array having various configurations. Any of the devices described or claimed below may be configured to be placed within the dura mater such that the electrodes are in direct contact with the CSF, but not with the spinal cord itself.

One of the advantages associated with high frequency stimulation is that patients typically do not experience paresthesia. When high frequency SCS is used, the specific location of the stimulation electrode within the epidural space of the spinal canal may be less important in its impact on clinical efficacy. This is significantly different from standard SCS methods and devices, where the location of the electrodes within the epidural space is critical due to the need to focus or align the current. A significant limitation of standard SCS approaches is that accidental movement of the implanted epidural lead often results in reduced or no clinical efficacy of subsequent stimulation due to, for example, failure of the anchoring mechanism.

Advantages of the devices and methods described herein include the ability to provide stimulation through direct contact with CSF, which avoids problems caused by providing stimulation within the epidural space. For example, to provide an effective amount of stimulation to the spinal cord from the epidural space, a sufficiently strong current must be used, and in some cases, such current can cause undesirable off-target stimulation. As described herein, the devices and methods are capable of delivering high frequency stimulation, e.g., about 2-10kHz or low frequency stimulation, e.g., less than 2kHz, less than 1kHz, or less than 500Hz, to the CSF.

The invention described and claimed herein overcomes many of the limitations of epidural placed electrodes by making it possible to stimulate neural structures deep in the spinal cord at specific target locations without stimulating non-target structures such as the dorsal rootlets.

Other advantages of the invention

A disadvantage of the SCS systems currently on the market is that frequent battery charging is required due to high power requirements. This limits not only their use, but also their effectiveness. We believe that the primary factor contributing to this high power requirement is that the delivery of stimulation from the epidural space must cross the electrical resistance barrier of the dura mater in order to drive therapeutic levels of current density through the CSF and into the target region of the spinal cord. We estimate that the presence of the dura mater between the stimulation electrode and the CSF layer increases the power requirements by five to ten times.

The new epidural SCS devices described in this disclosure are designed to overcome this limitation by placing one or more SCS electrodes inside the dura mater without substantially increasing the complexity, duration, or risk associated with epidural SCS. The clinician can use the device of the present invention to place the electrode in a stable position within the epidural space of the spinal canal so as to be in direct electrical contact with the CSF. The placement of the electrodes can be used to control the relative distance from the electrodes to the spinal cord itself, and in some applications it is useful to position the electrodes at a location about 0.05-3mm or about 3-8mm from the surface of the spinal cord.

Depending on the implementation, the main advantage of this approach is the potential to reduce the power requirements by a factor of 5 to 10 or more. This in turn reduces the battery charging requirements, resulting in a more generous time interval before the battery needs to be replaced. In addition, clinical efficacy is also expected to be improved due to good electrical coupling between the electrodes and the CSF, as well as proximity to the spinal cord. Other advantages include reducing the occurrence of off-target stimulation, such as adverse stimulation of surrounding tissue (e.g., dorsal rootlets).

Another advantage of the present invention is that the neurosurgeon can easily implant the device at an effective location within the subject's body, thereby minimizing the risk of damage caused by surgery or manipulation of the device, thereby improving patient safety. The dorsal surface of the dura mater of the spinal cord is exposed in a manner similar to that currently used to implant SCS devices into the epidural space. After dura mater exposure, the device is placed through an incision in the dura mater by a Minimally Invasive Surgical (MIS) procedure that requires only a few minutes. The electrode leads are then connected to a pulse generator that is implanted elsewhere in the patient's body using standard surgical methods.

The SCS device of the present invention reduces the risk of lead migration, which can be a substantial problem for leads of devices placed outside the dura. Since the electrodes distal to the lead beams are fixed to the inner wall of the dura mater (dura mater) they do not drift or move from near the anatomical location where they are implanted. The SCS devices of the present invention also avoid the epidural mass effects caused by large epidural devices that can limit the thickness of the CSF-filled space, limit the natural flow of CSF, and potentially tie the pia mater surface of the spinal cord.

Other advantages of the present technology are detailed elsewhere in this disclosure and will be apparent to the reader when used in the clinic. All of these advantages combine to provide superior, more focused and sustained therapeutic effects for the subject being treated.

Technical platform

In summary, the present invention provides a device for spinal cord stimulation configured for fixation to the dura mater of a subject's spinal cord. It contains one or more electrodes and a means of securing the device to the dura mater such that the electrodes are in direct contact with the cerebrospinal fluid within the spinal canal, but not with the spinal cord itself.

A fixation device may be passed through the dura mater to clamp the apparatus to the dura mater. Alternatively or additionally, the device may be secured to another anatomical structure outside of the dura, to the inner surface of the dura, or otherwise securely suspend the electrodes above the spinal cord in direct electrical contact with the cerebrospinal fluid. Typically, the securing device secures the electrode assembly in the desired position with sufficient durability such that it is typically reliably held in place on a chronic, long-term basis (at least weeks, months, or years).

When the device is configured for spanning and securing to the dura surrounding the spinal cord of a subject, the device may include a epidural portion, an epidural component, and one or more electrodes on the epidural portion and/or the epidural component. To assist in securing the device to the dura mater, it is often converted from an "open" position to a "clamped" position. In the open position, the device is inserted through an incision in the dura mater to place the epidural portion within the dura mater. By clamping the dura between the epidural and epidural components, the device is secured to the dura in a leak-free manner with the electrodes in direct contact with the cerebrospinal fluid.

In more detail, the epidural portion may contain an outer surface and a vertical or longitudinal axis, which is located perpendicular to the surface of the dura mater after implantation. The epidural component is generally aligned and conformed to the inner surface of the dura mater (conform to). It is fixedly or slidably or rotatably connected to the dural part. It has a gripping portion that extends or is extendable radially beyond the outer surface of the dural part. This means that, when implanted, the gripping portion extends in one or more directions perpendicular to the longitudinal axis, either linearly along the anterior-posterior axis, curvedly along the cephalad-caudal axis (rostral caudal axes) to conform to the inner surface of the dura mater, or both, such that the gripping surface of the intra-dural portion is in contact with the inner surface of the dura mater.

Similarly, an epidural component is affixed to the outer surface of the dura mater, wherein the epidural component is fixedly or slidably or rotatably connected to the epidural portion. The gripping portion of the epidural component extends or is extendable to a position radially beyond the outer surface of the epidural portion. This means that, when implanted, the gripping portion extends in one or more directions perpendicular to the longitudinal axis, either linearly along the anterior-posterior axis, curvedly along the cephalad-caudal axis to conform to the outer surface of the dura mater, or both, such that the gripping surface(s) of the epidural portion are in contact with the outer surface of the dura mater. Additionally, one or more electrodes are included in the epidural portion, the epidural component, or a combination thereof.

To enable the epidural component and the epidural component to be closed together, one or both of them will contain an aperture that is complementary to and surrounds the outer surface of the epidural portion. This configures the respective components to slide over or around the outer surface of the epidural portion so that the spacing between the epidural component and the epidural component can narrow from the open position to the clamped position. Typically, the epidural component is configured to pass through a short incision in the dura surrounding the spinal cord when the device is in the open position, leaving the epidural component outside the dura, and then sliding or rotating the epidural component and/or the epidural component over or around the outer surface of the epidural portion to narrow the distance therebetween and fix the epidural and epidural components in the clamped position has the beneficial effect of clamping the dura between the clamped portions of the epidural and epidural components.

Illustratively, the device shown in fig. 1 and 2 has an epidural component 6 secured to epidural sections 11 and 12. The epidural components 7, 8 and 10 are configured to slide over the outer surface of the epidural portions 11 and 12 towards the epidural component 6. The outer surface of the epidural portion around the longitudinal axis can be cylindrical or any other shape that allows the epidural component to face the epidural component and be secured to the epidural portion at the clamped location. In this illustration, a portion of the dural portion 12 is threaded to receive and retain the locking nut 14.

In some implementations of the invention (illustrated in fig. 1,2, 8A, and 8B), the base of the epidural component 6 and the base of the epidural component 10 are elliptical (oval), ellipsoidal (ellipsoid), rectangular, or ellipsoidal in shape. When the device is in the clamped position, the surgical incision made during implantation of the device is blocked within the dura mater and between the epidural components. Multiple electrodes may be arranged along the long axis of the ellipsoid of the epidural component. In other implementations of the invention (illustrated in fig. 11A and 11B), the shape of the epidural component is a spiral or hollow circle so as to be rotatably insertable through a narrow incision. The epidural component is circular and has a periphery that aligns with the periphery of the epidural component so that they can clamp the dura between them. In various implementations of the invention, the number of electrodes present may be at least one, two, four, seven, or ten or more arranged in a one-dimensional, two-dimensional, or three-dimensional array along the epidural component, the epidural portion, the flange arm, or a combination thereof.

To secure the epidural component in place at the clamping location, any suitable securing device may be used that holds the epidural clamping surface and the epidural clamping surface close enough to secure the device to the dura mater.

An exemplary device for clamping an epidural component to an epidural component is shown in fig. 2. In this configuration, the epidural parts 11 and 12 are attached to the epidural part 6. The epidural portion 10 has an opening that is circumscribed (circumscript) across and slides over the epidural portion, clamping the dura mater 18 against the epidural portion 6. The lock nut 14 is threaded along external threads on the epidural part 12 to secure the epidural part to the epidural part in the clamp part and reversibly fix it in place.

Other options for clamping the epidural component to the epidural component include one or more prongs (prong) or retaining snaps that extend radially outward from the circumferential outer periphery of the epidural component, optionally spring-loaded. Such a pin or snap is shown as part 34 in fig. 14. The epidural pad slides down along or over the epidural portion to a position beyond the prongs or catches, which thereafter prevent the pad from sliding up the epidural portion.

Another option is a snap in the form of a snap button (snap button) with a male component on the epidural pad and a corresponding female component on the epidural portion (or vice versa). Another option is a tongue and groove system, such as a bayonet-style connector (bayonet-style connector), in which a tongue on the epidural component, and a corresponding groove on the epidural component (or vice versa) engage when the epidural component is sufficiently close to the epidural component to apply a fixation force to the dura between the clamping surfaces. For example, a tongue on the epidural component may slide along a groove in the epidural part so the epidural component can be rotated around the epidural part to a position that locks the epidural component in place in the clamped position.

Another option is to have complementary threads on the epidural component and the epidural portion. In this configuration, the epidural component is rotated around the epidural portion so as to screw it down, closing the distance between the clamping surfaces. Thus, the fixation device on the dural part may comprise one or more elements selected from the group consisting of: pins, male or female portions of a snap, male or female portions of a tongue and groove system, ratchet-shaped couplers, or a threaded system that interacts with a corresponding member on an epidural device. Suitable lubricants may be used to facilitate implantation of the device component, and suitable adhesives may be used to facilitate fixation of the device component and the dural seal.

When the device is implemented such that the epidural component is slidably or rotatably connected to the epidural portion, it can be moved towards the epidural component and fixed in place using the same features as the epidural component with the necessary modifications.

Deployable intradural components

In some implementations of the invention, the epidural component of the device is also deformable: in particular, from an insertion or retracted position to a deployed position in which the gripping portion of the epidural component extends radially beyond the outer surface of the epidural portion. Where the epidural component can be deployed in this manner, the epidural component can be configured to contain multiple flanges, where at least one of the flanges is movable from a retracted position or an insertion position. When the epidural component is in the insertion position, the flanges are below or inside the epidural portion, or parallel to each other so they can be stacked on top of each other. When they are in the deployed position, a portion of each flange extends radially beyond the outer surface of the epidural portion in a different direction.

Figures 11B and 11C illustrate an example in which the epidural component includes the following two items: a circular member secured to or connected to the dura mater portion with a gripping portion extending radially to a location beyond an outer surface of the dura mater portion; and at least three flexible flanges, wherein at least two of the flanges are rotatably movable from an insertion position (wherein the flanges are parallel to each other) to a deployed position (wherein each of the flanges extends away from the dural portion in a different direction). One or more of the flanges may comprise a flange arm that extends radially at least 1cm beyond the dural portion. One or more of the flange arms may contain two or more separate electrodes arranged along the length of the arm.

To facilitate deployment of the flexible flanges during implantation, each of the rotatably deployable flanges may be connected to a shaft that passes through the dural portion in a longitudinal axis direction to an opposing or outwardly facing surface of the dural portion such that rotating the shaft from the opposing surface moves the flange from the insertion position to the deployed position.

Additional features

The device can have at least one electrode positioned on or near the longitudinal axis such that when the device is secured to the dura mater, the electrode is oriented within the dura mater, toward the spinal cord. Alternatively or additionally, one or more electrodes may be arranged on the epidural component. The device may also have a sleeve or coupler (e.g., with a threaded or tongue and groove locking system) for reversibly securing the device to a positioning tool, such that the device can be manipulated to place the epidural component within the dura mater, and then the positioning tool can be removed from the sleeve.

The invention comprises such a device in combination with a signal source by which electrical stimulation is delivered to the subject's spinal cord. The signal source may be contained within the device itself, but is typically implanted elsewhere in the subject. Power may be transferred from the signal source to the device wirelessly or through a line connecting the two. When the device is used for high frequency stimulation, the electrical stimulation provided by the signal source may vary or fluctuate at a frequency that is sufficiently high to cause random depolarization and/or reduce transmission of pain through the spinal cord. This may be a frequency of at least about 200 or 500Hz, or as explained in more detail below.

By obtaining surgical access to the dura surrounding the spinal cord of a subject, making a short cut in the dura, positioning the device of the present invention such that the epidural component is inside the dura, passing from inside the dura to outside the dura through the dura portion, and the epidural component is outside the dura, reducing the distance between the epidural component and the epidural component to a clamped position, and securing the epidural and/or epidural component in place so as to maintain the clamped position, thereby securing the device stably on the dura, enabling the subject to be prepared for treating pain, movement disorders, spasticity, or other indications. When the epidural component contains multiple flanges that are retracted or oriented in parallel below or inside the epidural portion, the mounting of the device involves rotating at least one of the flanges to a deployed position, thereby orienting each flange in a different direction before narrowing the distance between the epidural and epidural components.

According to this arrangement, the clamping portion of the epidural and epidural components may seal the dura to prevent cerebrospinal fluid from leaking into the epidural compartment or epidural outflow into the epidural compartment. The surgical surgeon can use sutures, stapled wires (staples), glue, or any other suitable closure material to repair any voids or leaks. The surgeon then connects the device to a suitably programmed and equipped signal source.

The present invention also provides various configurations of positioning or insertion tools for clamping the device of the present invention to the dura mater surrounding the subject's spinal cord. The nature and operation of the tool will be described in more detail in the sections below.

The invention is realized by locking nut clamping equipment

In the implementation of the invention shown in fig. 1 to 10, the general numbering scheme for the various components is as follows:

positioning a tool:

an electrode assembly:

other components:

anatomical and surgical features:

fig. 1 shows details of a pressing plate 6 of an epidural component, which pressing plate 6 serves as a substrate for an electrode array configured for positioning in an epidural space. In this implementation of the invention, the epidural portions 11 and 12 are fixed directly to the epidural component 6. The upper part 12 (axial extension of the distal base bushing 11) has an external thread which engages with a locking nut 14. In this example, the profile of the epidural compression plate 6 is T-shaped with the cross-bar of the T on the opposite side (as shown on the right). The distal hub 11 has laterally and contralaterally extending tabs, each of which serves as a position marker to ensure alignment of the compression plate 10 of the epidural component.

This arrangement ensures that the long axis of the epidural compression plate 10 is located directly above the long axis of the epidural compression plate 6 so that there is a precise overlap of the padding material 15 between these plates. This helps to maximize the cushion coverage of the dura sandwiched therebetween. The distal bushing 11, stud fitting 12 and central shaft distal end 13 are hollow on the inside. This serves to accommodate electrical leads connected to the electrode array on the distal surface of the epidural compression plate 6. The lead extends from the connector through the length of the assembly and eventually exits the aperture at the proximal end of the central shaft. The device components, except for the electrode array, its connectors and leads, and the press pad, are typically made of a biocompatible polymer such as Polyetheretherketone (PEEK).

The cushion 15 can be attached to the press plate using an adhesive, a mechanical clamping mechanism, or a combination thereof. In fig. 2, the cushion 15 is shown as a layer of a component sandwiched between the hard coat 18 and the pressing plates 10 and 6. In this particular illustration, the size and shape of the pad at the press plates 6 and 10 are substantially the same. Optionally, the pad extends beyond the edge of one or more press plates or pads (whose surface area is less than the surface area of the press plates). Alternatively, the single or multi-layer liner does not adhere to the compression plate, but forms a seal to prevent leakage of CSF when the device is implanted and secured around the dura mater. To this end, the gasket can be made of a biocompatible material that can form a seal and prevent leakage of CSF. Suitable materials may include polyurethane, polyamide-polyurethane, collagen dura, poly (lactide-co-glycolide), polyethylene glycol hydrogel, silicone rubber, silicone caulk, silicone, polysiloxane, and low durometer elastomer, combinations thereof, and combinations comprising one or more of these materials as ingredients.

Fig. 2 shows the lock nut 14 after being rotationally driven into place on the threaded adjustment fitting 12 (which results in optimal positioning of the epidural pressing plate 10 directly over the epidural pressing plate 6). The profile of the epidural compression plate 6 is T-shaped with the cross-bar of the T on the opposite side (as shown on the right). The epidural component contains contralateral interlocking notch mechanisms 7 and 8 that reversibly engage corresponding notch mechanisms on the positioning tool.

Once the locking nut 14 is fixed in place on the stud, the dura mater present between the pressing plates is pressed on the proximal and distal surfaces by a cushion positioned between the distal side of the epidural pressing plate 10 and the proximal side of the epidural pressing plate 6. The gasket ensures a water-tight seal to prevent CSF from leaking through the epidural space or via any other path between the intrathecal cavity and the epidural space. The padding material may be bioabsorbable so as to fuse with the dura over time to form a fully remodeled (re-remodeled) anatomical membrane having substantially the same biomechanical properties as the natural dura.

In addition to the electrode array and its connectors and leads and the press pads, other device components are often made of biocompatible polymers such as PEEK. The sealing effect achieved by pressing the liner may be enhanced by a tissue sealant film layer applied to the liner prior to implantation, and/or by auxiliary sutures, glues, adhesives, blood patches, or other materials.

Fig. 3 shows a full side view of a pre-deployed configuration, where the combined epidural component 6 and epidural component are attached to the positioning tools 1 to 5. The positioning tool is a surgical instrument for placing and securing the combined assembly in place at a selected location on the dura mater of the spinal cord. During the implantation procedure, the assembly is reconfigured from an open position to a clamped position using a positioning tool where it is secured in the dura by a locking nut. The positioning tool is then removed from the surgical site for reuse or for disposal, allowing the surgeon to close the wound with the electrode assembly in place.

The positioning tool has a proximal end (top) and a distal end (bottom). It extends longitudinally down through the device and terminates in a fixture in the distal hub assembly 5. Electrical leads from the intracorporeal electrode array 6 at the distal end of the positioning tool traverse the length of the central axis and exit from the proximal port thereof. The upper swivel hub 3 is used to twist the cylindrical housing shaft 4 about the longitudinal axis of the tool in order to tighten the lock nut onto the threaded shaft of the connector housing, both inside the distal hub assembly 5. This pulls the epidural compression plate 6 and the epidural compression plate 10 together so that the cushion between them is forced against the dura and sandwiched between them to form a water tight seal, preventing leakage of cerebrospinal fluid.

The knurled upper fixture fitting 2 serves to hold the components 3, 4 and 5 in axial order as shown and ensures continuous rotation 4 in response to manually applied twisting of the 3. When the fitting 2 is loosened and removed, the components 3, 4 and 5 can be removed from the assembly, leaving only the distal intradural and epidural components in place along with the epidural portion. All device components, except the electrode array and its connectors and leads and the press pads, are typically made of a biocompatible polymer such as Polyetheretherketone (PEEK).

Fig. 4 shows the epidural and epidural components at the distal tip of the positioning device. The cylindrical housing shaft 4 enters the proximal end of a distal hub assembly 5, which distal hub assembly 5 surrounds a rotary coupler 9 for an epidural lock nut 14. The distal hub assembly 5 mates with the epidural compression plate 10 through lateral and contralateral interlocking notches 7 and 8, respectively. Rotation of the coupler 9 pulls the stud housing proximally attached to the epidural compression plate 6 upward to compress the pad integral with the distal side of 10 and the proximal side of 9 onto the dura mater traversed by the stud housing, forming a leak-free seal preventing CSF from entering the epidural space from within the sheath capsule.

The profile of the epidural compression plate 6 is T-shaped with the cross-bar of the T on the opposite side (as shown on the right). The device components, except for the electrode array and its connectors and leads and the compression pads, are typically made of a biocompatible polymer such as PEEK. The padding can be made of known materials used in dural replacement surgery. The thickness of the pad may be in the range of 0.1mm to 0.7mm to suit the size of the implant and the thickness of the patient's dura mater. The liner may be coated with a hard-coat sealant film or membrane to help achieve a leak-free closure of the hard coat. Over time, the seal is naturally enhanced, usually by scar tissue that forms in response to the presence of the epidural component.

Fig. 5A (side view) and 5B (craniocaudal view) show close-ups of a mechanical stabilization device for securing the epidural element of an implant in a patient. The device shown here contains a retracted suture 16 threaded through lateral and contralateral eyelets 17 extending proximally from the epidural compression plate 10. After the epidural compression plate 10 is tightened against the epidural compression plate 6 using the lock nut 14, securing the dura mater 18 therebetween, the retracted suture 16 is threaded into place as shown. The proximal end is fixed directly to the epidural fascia tissue, ensuring a stable suspension of the implant above the spinal cord, providing stress relief for the electrical lead 19 connecting the epidural electrode array below the distal compression plate to the pulse generator implanted inside the patient's body.

Fig. 6 shows a possible geometry of an epidural electrode array 20 mounted on the distal side of an epidural compression plate 6. In this example, the array 20 is fabricated in the shape of the letter "T". Electrodes along the long (cranio-caudal) axis of the intradural compression plate 6 help stimulate nerve fibers in the dorsal column of the spinal cord. Electrodes along the short (transverse) axis of the epidural compression plate 6 help guide the stimulation field to achieve selective activation of target structures elsewhere in the spinal cord without inadvertently activating the dorsal nerve rootlets or other off-axis structures that may cause discomfort, pain, or paresthesia in the patient. To create nano-and micro-patterned structures to increase their active surface area by, for example, 2-fold, 5-fold, or more, individual electrodes may be treated by laser etching or some other suitable method to generate a current density at the electrode-CSF interface that maximizes the therapeutic response of the treatment while minimizing the risk of neurotoxicity due to electrolysis and excessive charge density.

Electrical leads from the electrode array may be attached to the intermediate body inside the epidural component of the device. This may provide an interface structure for stress relief of very thin wires or conductors leading from the thin film electrode array. Alternatively, the leads from the electrode array are connected directly to a bundle of leads that extend proximally from the connection point to the exterior of the epidural component of the implant, at which point the bundle of leads is secured to the body tissue.

Fig. 7 shows the combination of an epidural component with an epidural component to achieve extended coverage of the spinal cord with improved targeting of critical structures and avoidance of non-target structures. The epidural array 20 is internal to the dura mater 18 and suspended above the spinal cord 20. The electrical leads 19 from the epidural array 20 interface with a separate channel 27 of the implantable pulse generator 25. Also shown is a standard cylindrical, low profile epidural stimulator implant lead 23, which is positioned in the epidural space cranially of the epidural implant. The electrical connector 24 from the epidural stimulator implant lead 23 interfaces with another independent channel 26 of an implantable pulse generator 25.

This arrangement allows the clinician to use a combination of epidural and epidural stimulation to obtain the best clinical result for the patient, and also allows combined epidural and epidural sensing of evoked compound action potentials for use in a closed-loop stimulation algorithm. For example, the epidural stimulator array may be inserted first, and then the epidural lead is slid into the epidural space beginning and ending with the epidural array. The electrical leads of both the epidural and epidural implants are then connected to the implantable pulse generator 25. This arrangement allows for exhaustive and rigorous testing of key neurophysiological assumptions. For example, a user may directly compare epidural to epidural stimulation of the same subject and test a combination of epidural and epidural contacts in various montages with the goal of identifying, implanting, and achieving the optimal configuration of the device for the patient's needs.

Figures 8A, 8B, 9 and 10 illustrate possible geometries and measurements for the electrode assembly and positioning tool shown in figures 1 to 4. The shape of the epidural plate 10 and the epidural plate 6 is about 1.5cm × 0.5 cm. They are attached to a positioning tool of 18.5cm in length by a 1.0cm sleeve.

The epidural compression plate 6 is thin (0.5 to 1.5mm) in order to minimize the risk of obstructing the flow of CSF through the space between the plate and the underlying spinal cord. The plate here is shown as oval, which helps seal the incision in the dura mater when positioned parallel to the spinal cord. The peripheral edges of the plate are generally smooth, without burrs or other manufacturing artifacts (artifacts) that may risk tearing or scarring of the hard film. The flat surface is smooth to ensure optimal contact with the gasket used to seal the dura against the plate.

Implementation of the invention with other clamping devices

In the implementation of the invention shown in fig. 11A to 26F, the general numbering scheme for the components is as follows:

epidural component: 21

Epidural pad 22

Epidural clamping surface 23

Figures 11A, 11B and 11C illustrate an implementation of the device using a flexible flange arm as part of an epidural component. Fig. 11A is a side view showing a epidural portion 31 having a lead or lead bundle 32 for connection to a signal source (not shown). The epidural component 11 comprises one or more electrodes 14 and a rotatable flange 15 having an epidural clamping surface 13. The epidural component 21 contains an epidural pad 22 having an epidural clamping surface 23. The epidural component is configured to slide down the outer surface of the epidural portion 31 until it is held in place by the fixation member 34. This secures the epidural pad 22 in place adjacent to the flange 15, leaving just enough space to clamp or secure the device to the dura. Also shown is a sleeve or receiving member 33 for reversibly securing the device to a locating tool. This allows the device to be manipulated to place the epidural component inside the dura, after which the locating tool can be removed from the sleeve. The flange rotator 35 passes through the dural portion from each of at least some of the flanges so that the flanges can be rotated from outside the dura to a deployed position.

The diameter of the epidural component may be in the range of 5 to 9mm, depending on the purpose of construction and care. In this illustration, the length of the flange arm is in the range of 0.5 to 2cm, with a thickness of 1 to 2 mm. The flange and flange arms can be made of a soft polymer (such as silicone) where stiffening elements (such as wires or rigid polymer materials) may be inserted inside the flange arms to give them axial stiffness while still maintaining torsional compliance that adapts to the curved surface of the hard film during flange rotation without risk of cracking, tearing or scratching. The epidural pad can also be made of a soft polymer (e.g., silicone) as long as it has sufficient rigidity to keep the dura mater sealed around the original incision. The actual electrode itself may have any suitable holding shape and configuration, such as a small flat disc, "spherical cap" (part hemisphere) or half moon shape. They can be made of platinum or platinum-iridium alloys. Each electrode typically has an electrical lead that is soldered or otherwise in permanent, strong, low resistance ohmic contact with its proximal side.

Fig. 11B shows the flange 15 in a substantially parallel orientation from below the dural part 31. This is the retracted or insertion position whereby the surgeon may insert the flanges together through an incision in the dura mater. Figure 11C shows the flange 15 rotated to the deployed position, anchoring the epidural component underneath the dura mater.

Fig. 12A to 12E show how the device can be secured to the dura mater of a subject. In fig. 12A, the dorsal surface of the dura mater is accessed using standard surgical methods. The amount of exposure achieved using Minimally Invasive Surgical (MIS) devices and methods is sufficient for this purpose. In preparation for a small puncture incision through the dura, the dura is "held up" (further elevated above the surface of the spinal cord) using a suture or a miniature hook instrument. Custom blades can be used to create an epidural incision of the exact length desired.

Fig. 12B shows an insertion tool 40 (described further below) for securing the device. As shown, the apparatus has: an epidural pad in the open position, electrodes 14 directed towards the spinal cord inside the dura, and a flange 15 at the insertion site. During the implantation procedure, and in order to control the angle of the flanges 15 protruding from the bottom surface of the device, the insertion tool can be configured such that one of the flanges 15 is firmly fixed to the epidural portion without a position controller attached thereto. The rotational position of the other two inner flanges 15 is each controlled by its own flange rotator 16, and this flange rotator 16 is in turn manipulated using a flange control rod passing through the body of the insertion tool, as described below.

In the inserted or retracted position, the flanges 15 are oriented substantially parallel to each other, with the tip of each flange facing in substantially the same direction. This effectively creates a thin right angle dura mater separator (an instrument used to open the dura mater during neurosurgical procedures) protruding in a single direction from the lower surface of the combined electrode & insertion tool. This is another advantage of the present invention because the surgeon can push the parallel flanges into the subdural space through the epidural incision without risking the underlying spinal cord. The neurosurgeon lifts the dura slightly from the underlying spinal cord and then cuts the dura under direct visualization. The device with the flange at the insertion site acts as a blade for the dural separator, allowing its introduction into the subdural space, bringing the flange flush with the dura, thus applying upward pressure to the dura to raise the membrane away from the spinal cord.

Fig. 12C shows the flange 15 rotated to the deployed position, anchoring the device under the dura mater. The surgeon can independently rotate the two flanges 15 using the flange rotors in the epidural portion, respectively. The surgeon controls the rotational position or angle of the two flanges by means of a flange control rod extending from the other end of the insertion tool 30 (the portion closest to the surgeon's hand). By rotating the two movable flanges 15 into the deployed configuration, the entire incised incision edge of the dural opening is displaced above (superficially on) the flanges. The epidural edge is now located in the space between the flange 15 and the epidural pad 22, shown here in the up or open position. The gripping surface of the pad can be made of an artificial hard film material. The outer surface of the liner and the remainder of the device can be made of a rigid, biocompatible polymeric compound that can be MRI compatible.

Fig. 12D shows the epidural pad 22 pressed down against the flange 15 by the insertion tool 40. After properly positioning the device within the epidural opening, the surgeon slides the epidural pad pressing cylinder down the assembly 40 toward the dura mater, thereby pushing the epidural pad 22 through the securing clasp 34 to achieve a tight, water-tight closure on the dura mater. The use of an artificial dural-type substrate to make the lower surface of the pad facilitates rapid tissue fusion of the pad with the dura: for example, by absorbing dural substitute at the interface with the dura mater. The securing catch 34 locks the gasket in a fixed position.

Fig. 12E shows the electrode device secured to the membrane with the insertion tool removed. The epidural pad assembly 22 clamps the dura against the flange 15, thereby positioning the electrode 14 such that it protrudes downwardly from the dura towards the spinal cord.

Positioning tool

Fig. 13A, 13B and 13C depict another inserter assembly or insertion tool suitable for implanting the electrode assembly of the present invention in a subject. In this illustration, the insertion tool is adapted to operate a device having a movable flanged arm as shown in FIGS. 11A, 11B and 11C. The electrode arrangement itself is not shown.

Fig. 13A depicts a side view. Three control elements extend from the top of the device and are controlled by the surgeon. In particular, two flange control levers 46 are used to control and adjust the position of two movable flanges that are part of the electrode arrangement. The positioning rod 44 reversibly connects the insertion tool to the electrode device. The epidural pad pressing cylinder 42 is shown in an upward position around the inner housing 41. Four cross-sectional images are shown depicting the internal structure of the device. In the two cross-sectional views below, a groove 45 is shown, which groove 45 is adapted to place an electrical lead on the device.

Fig. 13B is a front view of the insertion tool itself. This provides a view of the lead receiving groove 45. Fig. 13C is a front view of the epidural pad pressing cylinder 42 in the downward position. To install a device without a rotatable flange, a flange lever is not required. The outer surface of the insertion tool may conform to an elliptical or ellipsoidal shape, rather than a circular shape, and is generally complementary to the outer surface of the epidural component.

Fig. 14 shows an electrode assembly coupled to an insertion tool. In this figure, the electrode device is aligned with the housing 41 of the insertion tool, which means that the cross-sectional shape or diameter of the surface of the dura mater portion 31 of the device is substantially the same as the housing 41. The device is held in place at the bottom of the housing by inserting the positioning rod 44 into the sleeve 33 of the epidural portion. In this figure, the insertion tool has a recess 45 to accommodate the lead 32 that ultimately connects the electrode 14 to an external signal source. There are two flange levers 46 that control the two movable flanges 15 of the device. Each flange lever 46 is connected to the reversible interface 36 at the top of a flange rotator 35 housed in the dura mater portion 31 of the device, the flange rotator 35 being used to rotate the respective flange 15 to adjust the angle or intradural orientation. Interface 36 is depicted here as a dome with a slotted head. In the alternative, the interface may be cross-shaped or hexagonal so as to match a corresponding pattern in the flanged control rod 46 of the insertion tool.

The insertion tool has a locating rod 44 which passes from the top of the inserter protruding from the device, down through the insertion tool to the opposite surface of the insertion tool to abut the electrode device. The positioning rod 44 is reversibly interconnected with the sleeve 33, which is shown here with a threaded interface, to secure the electrode device to the bottom of the insertion tool. After the electrode assembly is implanted in place in the patient (after the epidural pad 22 has been locked in the downward position), the positioning rod 44 is detached from the electrode device by rotation, thereby releasing the insertion tool from the electrode device and allowing it to be removed from the surgical field.

Fig. 15A, 15B and 15C depict the operation of the insertion tool in combination with an electrode device. Once the combination is inserted through the incision in the dura as shown in fig. 15A, the surgeon controls the rotational position of the flange 15 using the flange control rod 46 of the insertion tool, thereby deploying the flange 15 into different orientations as shown in fig. 15B and anchoring the epidural component beneath the dura. The surgeon then slides the pressing sleeve 42 down the housing 41 of the insertion tool, thereby sliding the pad 22 down the epidural portion 31 of the electrode device to a position where it is secured by the snap 34. As a result, the edge of the epidural incision is firmly pressed between the pad 22 and the flange 15, thereby preventing CSF leakage. The insertion tool is then released, thereby securely securing the electrode assembly stabilizing AMD to the dura mater.

Electrode placement on an epidural component

To obtain some of the efficiency benefits of the present invention, at least one anode and at least one cathode are positioned on or around the epidural component or the epidural portion to complete the entire electrical circuit within the epidural space. Due to the advantageous location of the intra-dural electrodes, efficiencies can also be obtained on currently available SCS systems by using combined electrode arrays or epidural and intra-dural electrodes.

The electrode arrangement can be designed to have a larger distance between the electrodes depending on the target tissue and the clinical condition to be addressed. For example, the plurality of electrode contacts can be positioned in a linear configuration parallel to the long axis of the spinal cord. Alternatively or additionally, multiple electrodes can be positioned along the inner surface of the dura mater, making it possible to deliver stimulation using an electrode montage having a spatial orientation that is perpendicular or at an angle of at least 45 or 60 degrees relative to the long axis of the spinal cord. By positioning the positive and negative electrode contacts in left and right positions within the sheath capsule, the targeted nerve tissue (dorsal rootlet, dorsal rootlet entry zone, and dorsal column) is optimally located in the space between the contacts on either side.

Referring to fig. 16A through 17C, the flange arm of the epidural component is constructed longer, thus providing a greater electrode spacing. The flange arms intended to be wrapped against the dura at least partially around the spinal cord are typically made of a semi-rigid flexible material that is able to conform to the inner surface of the dura without risk of rupture, tearing or abrasion. The entire flange can be made of the same material, or the portion of the flange near the flanged rotor can be made of a more rigid material, further connected along its length with a more flexible material. Each flange arm can be lined with a plurality of electrodes, optionally arranged in a pattern of linear, non-linear or fractal configuration, and having a nano-or micro-patterned surface to increase its effective area relative to the nominal geometric area. The electrode array on each flange arm bends and conforms to the inner arc of the dura mater as needed during the insertion process. After implantation, the compliance of the flange arms accommodates changes in the sheath capsule (dural lining) that accompany the subject's normal movements.

Fig. 16A is an oblique top view of an electrode assembly having an array of electrodes 14 along one of the flange arms 15. Fig. 16B is a bottom oblique view of the electrode device. On the bottom of the dural part 31 is an electrode 14 a; on the inside of the flange arm 15a near the dural part 31 is a second electrode 14 b; and a third electrode 14c on the distal or outermost end 15b of the flange arm.

Figure 17A shows the insertion of the electrode device through a small epidural incision. The distal part of the flange arm 15b with the outermost electrode is first inserted into the opening, after which the proximal part 15a is brought near the epidural part. As depicted here, the implanted electrodes 14a, 14b and 14c form a one-dimensional epidural array.

FIG. 17B depicts another form in which all three flanges are extended and carry an array of electrodes. In the inserted position, the three flanges are oriented parallel and stacked on top of each other. They are introduced into the subdural space as a beam. After the epidural component is properly positioned within the dura opening and secured to the dura, two of the flanges are rotated to the deployed position. Thereby sliding the electrode back along the inner surface of the dura to the position shown.

Fig. 17C is a cross-sectional schematic depicting the location of the contacts on the electrode array that has been rotated to a lateral position along the lower surface of the hard mask. With this configuration, it is possible to select montages of various stimulation geometries: for example, the dorsal half of the spinal cord, where all target structures are contained, is positioned in the space between two active contacts on either side of the spinal cord.

Other configurations of the epidural component

The electrode device of the present invention may also be configured without a rotatable flange on the epidural component. As an alternative or in addition to the flange, there is a fixed-shape epidural lining pad with an epidural clamping surface oriented upwards in the direction of the epidural part. The following options can be combined with any features mentioned elsewhere in this disclosure with respect to other components of the device. By substantially matching the outer perimeter of the epidural pad to the epidural pad, the spatial gap around the entire circumference of the epidural opening is minimized. When the epidural compression pad is moved to the clamped position, a substantially uninterrupted water-tight seal is formed around the entire circumference of the implant device.

Fig. 18A to 20D show Asymmetric Linear Arrays (ALA). The intracranial and epidural components have an elongated shape in an ellipsoidal or ellipsoidal manner, are eccentric with respect to the epidural portion of the device, have long and short arms. This configuration is beneficial because it spans the incision made on the dura during implantation, thereby providing an excellent seal.

Fig. 18A and 18B are diagrams of the epidural component and the dural part of an ALA device. The long arm of the epidural component can have any suitable length and accommodate any suitable number of electrodes in a linear, two-dimensional, or fractal array. In a typical implantation procedure, the long arm 11a is inserted through the epidural space opening in a manner that provides a right angle dural separator for accessing the subdural space. The short arm 11b of the epidural component extends from the epidural portion 31a sufficient distance to provide a sufficient gripping area to grip the device towards the superior outer liner.

Fig. 18C depicts an insertion tool suitable for implantation of an ALA device. The positioning rod 44 is used to reversibly attach the insertion tool to the device. The pressing cylinder 42 is shown in an upward position relative to the inner housing 41. To operate the insertion tool, the surgeon presses the epidural pad 22 onto the electrode device assembly by moving the pressing cylinder 42 downward, pushing the epidural pad 22 past the fixed catch 34. The electrode lead 32 is positioned within the space formed by the aligned grooves 45 in the housing 41 and the press cylinder 42 of the insertion tool. The insertion tool does not have a flanged lever. As depicted here, the surface of the housing 41 (as viewed in cross-section) is elliptical rather than circular, and the pressing cylinder 42 has substantially the same asymmetric cross-section as the ALA device itself. In the clamped position, the external pressure cylinder fits tightly over the entire surface of the epidural ALA device-thereby securing the clamping surface 23 of the epidural component adjacent to the clamping surface 13 of the epidural component.

Fig. 19A to 19D provide a top or surgeon eye view of an exemplary ALA device insertion procedure. A linear incision is created in the dura mater. The incision is long enough for placement of the epidural component, but no longer (fig. 19A). The long arm 11a of the epidural component is inserted into the subdural space using a right angle epidural separator dissection technique (fig. 19B). Next, the inner hard film liner is lifted and the hard film is stretched so that the short end 11b of the inner hard film liner slides into the lower hard film cavity, similar to inserting a button through an eyelet or passing the head of a rivet through its mating part (fig. 19C). The surgeon positions the epidural component so that the cutting edge of the dura abuts the dura mater portion 31 immediately adjacent the short arm 11 b. This results in the epidural space being positioned over the long arm 11a of the epidural component. There is more surface area on the long arm 11a available for pressing the dura mater margin. In the final step of the procedure, the surgeon slides the epidural pad 22 down the epidural portion 31 where it is held in place by the snap 34. She then disconnects the insertion tool from the electrode device, securing the implanted electrode to the dura mater in a watertight or leak-free manner (fig. 9D).

Fig. 20A to 20D show the steps of an ALA device implantation procedure from a side view. The linear epidural incision (fig. 20A) was much shorter than the length of the ALA device. The long arm 11a of the epidural component is inserted first (fig. 20B), and then the short arm 11B is inserted. As shown in fig. 20C, the device is positioned in the incision such that the gap extending beyond the dural portion 31 is above the long arm 11a of the epidural component. The epidural pad 22 is then depressed using the pressing cylinder 42 until it is secured in place against the dura mater due to the snap 34. Depending on the circumstances, it may be possible to perform the electrode implantation portion of the procedure in a few minutes or less after the surgeon has exposed the dura using minimally invasive surgical techniques.

Fig. 21A to 24 show a device labelled W2 that contains another possible shape for an epidural component: in particular a spiral, or a hollow circle or ellipse. This shape helps the surgeon insert the epidural component through a very narrow incision in the dura mater.

Fig. 21A and 21B show top and bottom views of the W2 device without an epidural component. A plurality of electrodes 14 are arranged around the inner assembly 11 by routing through the dura portion 31 to a lead bundle 32. Fig. 22A and 22B show side and oblique views of the W2 device without an epidural component. In fig. 22A, a thin linear attachment 36 connects the epidural component 11 to the epidural portion 31. The appendage 36 fits tightly in a small linear dura mater opening. As previously described, the epidural portion can be reversibly connected to an insertion tool to assist the surgeon in implanting the device into the subject. The insertion tool has a shape that corresponds or conforms to the altered shape of the epidural component.

Fig. 23A and 23B show the configuration of the W2 device after insertion. The dura is pressed between the epidural component 11 and the epidural pad 21. An almost continuous circumferential epidural compression surface area is created by the epidural component. The epidural component is typically rigid such that the edges of the epidural component on either side of the epidural incision remain well aligned during insertion. This ensures that the epidural pad across the gap is held in a sufficiently stable position to achieve a watertight or leak-free closure after the epidural pad 22 has been moved down to the clamped position.

Fig. 24 depicts a possible W2 insertion process. A small linear incision is made in the dura mater just long enough to accommodate the thin linear attachment feature 36 by connecting the circular electrode array to the electrode housing. The anterior or free end of the epidural component is pushed into the subdural space under direct visualization using right angle epidural separator dissection techniques. The surgeon continues to push and rotate W2 until it is in the final fully inserted position and is properly seated. The epidural pad is then lowered onto the dura mater to achieve a water-tight or leak-free seal, and the device is then disconnected from the insertion tool.

Fig. 27A to 27F depict devices designed to function as ports. The device contains one or more openings in fluid connection with the CSF and the epidural space, allowing fluid to be transferred from the epidural space to the CSF. The opening(s) can be positioned in a variety of positions and configurations substantially the same as depicted elsewhere in this disclosure. For example, an array of openings can be contained, or alternatively, a single opening can be contained. One or more valves can be contained within the fluid conduit. The valve(s) can be positioned anywhere within the fluid conduit system, for example, at the location of the one or more openings or near the reservoir. In some devices, the valve(s) are one-way to prevent CSF from migrating out of the epidural space.

The device can be used to deliver a variety of substances, such as active pharmaceutical ingredients, e.g., antibiotics, analgesics, cancer therapeutics, biologies, and combinations thereof. Delivery can be passive or active. For example, various permselective membranes can be used to achieve passive delivery, or pressure differentials (e.g., an epidural syringe, a pressurized reservoir, or a reservoir associated with an active pump) can be used to achieve active delivery.

Implantation procedure

The surgical protocol for implantation, testing, commissioning and use of the present invention may be as follows. A Magnetic Resonance (MR) scan of the thoracic vertebrae of a patient determined to be a candidate for intradural spinal cord stimulation is obtained. The MR scan is reviewed by a clinician to determine the implantation site of the device. Under standard clinical protocols, an epidural is performed using minimally invasive surgical techniques, and the device is implanted and then secured such that the electrode array is positioned on the inner wall of the dura in a leak-free manner. The electrode leads are connected to an Implantable Pulse Generator (IPG) and the surgical site is then closed in a standard manner. The IPG is then programmed using standard wireless technology.

The following description shows how an electrode device according to the invention may be implanted in a subject. This is provided by way of example for implanting the device according to fig. 11A to 11C. The procedure can be adjusted as necessary to be modified for implantation of other working models of the present invention.

The implantation procedure is typically performed under general anesthesia. As shown in figure 25, the patient is lying prone and an incision of about 2-3cm is made in the skin above the level of the spine to be implanted. These figures depict the device implanted at the level of T8-T9.

FIGS. 26A and 26B show how the surgeon can gain access to the T8-T9 lamina using standard exposure techniques. The access obtained using standard Minimally Invasive Surgery (MIS) is usually sufficient. After the retractor system is in place flush with the lamina, the surgeon removes a portion of the caudal layer of the T8 lamina, the head portion of the T9 lamina, and the ligamentum flavum spanning the gap between the two laminae using standard MIS techniques. This results in exposure of the underlying dura mater.

Fig. 26C to 26F continue the process. In fig. 26C, the surgeon lifts the dura using a sharp microdissector and creates a small epidural opening using a custom-made sharp instrument (which ensures the dura opening is correctly sized). In fig. 26D, the surgeon slides the flange lever 46 of the insertion tool 41 into the dura opening. The flange levers are in the insertion orientation, meaning parallel and flush with each other, with the blades all facing in the same direction, corresponding to the insertion or retraction configuration of the device itself. The surgeon manipulates the insertion tool using the same technique as the right angle dural separator to gain safe access to the dural cavity.

In fig. 26E, the surgeon orients the insertion tool perpendicular to the spinal canal and rotates the two flange position controls to move the flange arms to the deployed position. This action positions the incised dural edge tightly around the entire circumference of the device. The surgeon then slides the handle 43 of the epidural pad pressing cylinder 42 down the insertion tool until the pad snaps into place, thereby securing the device to the dura and substantially sealing the epidural space. After securing the device to the dura mater, the surgeon rotates the positioning rod 44 to unscrew and loosen the electrode device from the insertion tool. The insertion tool is then withdrawn and removed from the field as shown in fig. 26F.

The robotic system may be under the remote control of a medical professional for performing some or all of these surgical steps.

Numerical control signal source

After implantation, the device is connected to a power or signal source configured and programmed to deliver electrical stimulation to the subject's spinal cord through the device. Any suitable signal source that provides the desired stimulation intensity, frequency and duration when electrically connected to the electrodes can be used. The stimulation is typically controlled by suitably programmed digital circuitry, typically located in the signal source assembly.

The "signal source" referred to in this disclosure is both an electrical power source and a digital device for adjusting the waveform of electrical power fed to the electrodes of the device via the leads in order to deliver spinal stimulation (SCS) at a desired frequency or pattern. The digital control device can be, for example, a microprocessor, microcontroller, digital signal processor or other electronic signal synthesizing and controlling means suitable for the purpose.

Optionally, the device can be configured to receive energy wirelessly from a power source. The device may include a receptacle disposed along the backing of the electrode assembly. Energy can be received, for example, from a signal generator and transmitter implanted at the epidural location.

By way of illustration, the signal source can be an implantable and externally programmable pulse generator with an integrated external rechargeable battery. The subject can be given a handheld control unit that can program the pulse generator and charge the battery via a wireless telemetry link. The signal source is typically located away from the spinal cord, for example in the musculature of the lower back (mistleture). The epidural implant can in principle be connected to a signal source wirelessly or using an electrical lead bundle. By way of illustration, the pulse generator can be configured and programmed to deliver any one or more of: tunable mode (tonic mode) stimulation (standard low frequency <1kHz), high frequency stimulation (>1kHz), burst mode stimulation (a sequence of chirped pulses or a combination of frequencies), pulse trains, noise signals, discontinuous waveforms (e.g. square and triangular waves) and smooth waveforms (e.g. sine waves), any one or more of these with an amplitude in the range of 10mV or less to 10V or more.

A signal source adapted to provide an electrical signal to a subject by a device configured to be implanted in the dura mater according to the present invention can be sold with the device and implanted separately or together in the subject.

Use of implanted devices for stimulating the spinal cord and treating pain

Once in place, the device can be used to deliver electrical stimulation to a target area of the spinal cord. Electrical stimulation typically includes a pattern of electrical pulses that has been predetermined or empirically determined to provide a desired benefit to the patient. The stimulus may be applied to inhibit pain, or to inhibit symptoms or sensory inputs that are undesirable or disruptive to the patient, including those resulting from spasticity caused by spinal cord injury or morbidity, such as Parkinson's disease, multiple sclerosis, congestive heart failure, or visceral pain. The stimulus may be provided to the spinal cord by the device based on an on a consistent basis, automatically in response to feedback data, by remote control by a managing clinician, or it may also be subject to voluntary control by the patient.

Electrical stimulation can be performed in any effective form for any valuable clinical purpose without limitation. In particular, the spinal cord is stimulated to inhibit pain transmission by applying electrical stimuli directly to the spinal cord that desensitize sensory neurons to the transmission of synchronous action potentials evoked within the spinal cord. This suppresses pain caused by sensory input sensed locally, and side effects such as paresthesia that may be induced during local treatment. Electrical stimuli are thought to promote random depolarization of sensory neurons within the spinal cord, thus causing a state of nerve quiescence. As one example, stimulation may be used to reduce visceral pain through targeted reversible neuromodulation of the postsynaptic dorsal column pathway within the spinal cord.

Different stimulation algorithms can be used depending on the needs of the patient. They may include tunable (standard low frequency) stimulation, high frequency stimulation, burst mode stimulation, random waveform stimulation, and methods using special patterns or combinations of frequencies. Feedback can be used to monitor the excitation of target neural structures, track vital signs of the patient, and synthesize measurements or observations of the patient's posture and motor activity. The state of the device and its impact on the patient can optionally be monitored by a physician or other hospital staff or caregiver via telemedicine techniques, connecting the stimulator directly to the internet or telephone network (wired or wireless), or by any other means suitable for unidirectional or bi-directional delivery of stimulation parameters and settings, as well as the patient's reactions and conditions.

The sensation of neural activity due to stimulation can be used, for example, to optimize response to treatment via measurement of evoked compound action potentials (U.S. Pat. No. 9,386,934; M.Russo et al, neuro-stimulation, 21:38-47,2018). The data obtained in this way is recorded in the epidural space and is therefore far-field in nature. However, by placing the electrode array within the hard film according to the means and method of the present invention, the induction of the evoked compound action potentials becomes substantially more near field. This has a number of potential advantages, including less uncertainty in the isolation and identification of the target neuron, less risk of movement of the sensing electrode relative to the target neuron, and improved signal-to-noise ratio.

The therapeutic dose of current density into the target neural structure can be titrated, ramped, or otherwise made adjustable for the purpose of optimizing the therapeutic benefit to the patient. Any level of current density approved by the U.S. Food and Drug Administration (FDA) for safe and effective delivery of SCS therapy can be used.

The device is configured to enable the treating clinician to apply spinal cord stimulation at high frequency alternating voltages according to his choice. Regardless of the manner in which the potential changes over time, the frequency can be calculated by determining the number of positive and negative changes per unit time. The effective frequency range depends on the anatomical placement of the electrode array, the characteristics of the array, the nature, health and electrophysiological properties of the tissue in which the array is placed, and the therapeutic objectives. The general purpose is to cause spinal cord refractory to transmit harmful signals or locally triggered synchronous depolarization events. This can be adjusted empirically by determining neural activity and recording the symptoms experienced by the patient.

Depending on the purpose of the treatment and the manner of deployment of the technique, the effective pulse repetition rate or frequency may be equal to or higher than 100Hz (pulses per second), 200Hz, 500Hz, 2,000Hz or 5,000 Hz; a frequency of about 1,000Hz, 4,000Hz, or 10,000 Hz; or a frequency range of about 500 to 50,000Hz, 1,000 to 9,000Hz, 3,000 to 8,000Hz, 2,000 to 20,000Hz, or 5,000 to 15,000 Hz.

The electrical stimulus may be adjusted in frequency or other waveform parameters and application patterns to minimize the effect on transmission of essential nervous system components (essential neurological interfaces), including motor neuron activity, and nerves involved in proprioception, motor sensation, and cognitive control or autonomic body function. Optionally, an input device may be provided to the clinician or user to select a mode, adjust frequency and adjust intensity based on perceived symptoms and practice criteria.

The potential may vary at a regular frequency of a sinusoidal or square waveform. Alternatively, the waveform may be a more complex charge balance pattern, in which pulses occur at varying intervals and intensities according to a calculated, repetitive or random pattern. Such patterns include pulse trains that generate substantially continuous activation of nerves within the spinal cord, and may incorporate irregular pulse intervals, irregular pulse amplitudes, various waveforms (e.g., monophasic, biphasic, rectangular, sinusoidal, and asymmetric or irregular waveforms), or any combination thereof. In the digital circuit of the signal source, the potential can also create pulses of essentially broadband noise, which vary in random or essentially random intervals and intensities, under the influence of a suitable calculation algorithm or automatic control program.

The electrodes through which the high frequency stimuli are delivered are typically arranged on a flexible background made of a material and shaped to allow it to conform directly to the morphology of the spinal cord. Optionally, the technique can be configured to apply different stimuli via different electrodes of the device and actively control the polarity of the individual electrodes in the array.

Treating pain according to the present disclosure can include applying an electrical stimulus to the spinal cord, monitoring transmission of a synchronous action potential through the spinal cord and/or pain experienced by the subject, and then adjusting the electrical stimulus to further inhibit or otherwise adjust transmission of the synchronous action potential through the spinal cord. The target may be anything that is clinically valuable, such as reducing a subject's perception of pain (particularly back pain), such as may occur during spinal cord injury, spinal cord disease or strain, parkinson's disease, osteoarthritis, or congestive heart failure.

Use of implanted devices in the treatment of spasticity

68% to 78% of spinal cord injured patients suffer from spasticity-approximately 200,000 in the United states alone. Spasticity can also be caused by upper motor neuron syndromes, such as multiple sclerosis and stroke: in the united states, this is the major cause of disability, with an estimated 540 million affected patients. About 50% of patients who have experienced a stroke suffer from long-term disability and require assistance from care givers in daily life. Between 30 and 500 people in every 10 million have a history of stroke, about one third of which have lower limb spasms, many of which require medical intervention.

Disorders characterized primarily by spasticity include cerebral palsy, Multiple Sclerosis (MS), ischemic or hemorrhagic stroke, brain injury, and Spinal Cord Injury (SCI). Patients with long-term spasticity are limited by pain and contractures that interfere with activities of daily living and impede rehabilitation efforts. Although drugs and surgical therapies are available to reduce the burden of symptoms, these therapies are neither curative nor restorative, providing only partial or no selectivity at all. Although initial attempts to treat spasticity using epidural spinal cord stimulation have been made, the results are not clear due to limitations of this technique.

The present invention encompasses direct SCS as an alternative to standard epidural spinal cord neuromodulation. It is superior to the technology currently used commercially because it directly activates the neural circuits that regulate spinal motor neurons. By placing the electrode array within the dura mater, greater targeting selectivity of neural structures can be achieved. This is possible even at much lower stimulation amplitudes. The SCS devices of the present invention can be mated (co-opt) and electrically integrated with a target region of the spinal cord to modulate a limited number of selected motor neurons, such as those around the L3 segment. The stimulus-interference paradigm may also work. Once the therapeutic effect is established in each patient, the treating physician can selectively switch the stimulation control to treat the spasm first, and then expand with more complex programming.

Treating spasticity according to the invention can comprise applying an electrical stimulus to the spinal cord, monitoring transmission of a synchronous action potential through the spinal cord and/or symptoms of spasticity experienced by the subject, and then adjusting the electrical stimulus to further inhibit or otherwise modulate transmission of the synchronous action potential and/or excessive velocity-dependent muscle contraction signal through the spinal cord that causes symptoms of spasticity. In a closed loop configuration of the type proposed herein, the therapeutic response will be optimized by the intracranial location of the stimulator electrode array, and also by measuring evoked compound action potentials related to the response to the stimulus using a combined epidural/epidural sensing method.

Dose of stimulation

The techniques of the present disclosure can be used to cause interruption of a synchronous firing (fire) of an axon or a portion of an axon within a nerve bundle. The destructive power can be controlled by increasing or decreasing the frequency and/or power of the stimulation. High frequency stimulation can be used to cause spurious spontaneous discharges (random axonal discharges usually associated with non-sensory stimulation states), thereby making the patient unable to perceive pain. In some of the methods described herein, the frequency can be set such that stimulation is provided at a frequency that does not allow some or all of the axons in the nerve bundle sufficient time to reestablish their membrane potential.

The frequency and power used to provide therapeutic benefit will vary from patient to patient and the devices disclosed herein can be adjusted using feedback from the patient or sensors included to identify and subsequently generate and control the optimal stimulation. By way of illustration, the patient can first begin with one therapeutic stimulation dose or regimen and, over time, as the patient adapts to the dose, a new dose or regimen is prescribed and applied.

Using the principle of high-frequency stimulation

The following discussion is provided from the perspective of a instructor and to facilitate technical improvements. They should not be construed as imposing any limitations upon the practice of the present invention unless explicitly stated or otherwise required. The reader may implement and modify the apparatus and methods of the present invention without understanding or justifying any of the phenomena set forth herein.

High frequency stimulation of the spinal cord can benefit patients by causing a state of pseudo spontaneous axonal discharge. It is believed that sensory axonal bundles will randomly discharge when they do not transmit sensory stimuli. When a sensory stimulus is present, the vast majority of axons in the bundle or pathway discharge in a synchronous manner-approximately simultaneously with axonal potential discharge. This results in sensory input being transmitted along axons in the bundle so that the subject can experience a sensation. In other words, the absence of sensation is encoded by the random timing of axonal discharge in the bundle, while sensory perception is encoded by the simultaneous discharge of axonal populations.

The present disclosure assumes that patients with leg and back pain have axonal bundles that spontaneously discharge in a synchronized manner (or some other non-random manner) rather than the normal random discharge pattern. The electrical pulse is accompanied by axonal discharge. A single pulse delivered to the axonal bundle will cause all of them to discharge synchronously. If the time interval between each electrical shock in the pulse train is longer than the refractory period of the axons in the bundle, then each subsequent shock will also activate all axons simultaneously and the patient will experience a sensation. Low frequency alternating current (50Hz) applied to the back can be effective in reducing the perception of pain, but the stimulation can produce neurological side effects such as unwanted paresthesia (tingling or numbness).

High frequency electrical stimuli (e.g., about 5,000Hz) have spaced gaps that are shorter than the refractory period of the axon. A single axon cannot discharge again in response to a second impact until its membrane potential recovers from the effect of the first impact, which takes time. Different axons have different refractory periods. By delivering electrical pulses at high frequencies, the relative timing of individual axon discharges in the axon bundle is nearly random, with different axons becoming excitable again at different times.

Application of high frequency pulses to the spinal cord can be used to restore an active resting state of sensory nerves across the spinal cord. This can inhibit the transmission of unwanted signals (e.g., painful sensations in the spinal cord or limbs, or excessive muscle contraction signals that cause spasticity) through the spinal cord.

Definition of

The "electrode assembly" of the present invention may be referred to variously and interchangeably as an electrode assembly or a button electrode assembly, and may be referred to by the designation I-Patch^TMOr I-batch 2.0^TMAnd (4) indicating. These terms refer to a medical device configured to be implanted in the dura of a subject in an open or clamped position, with or without an insertion tool. The flange or other deployable feature (if present) may be in an insertion position or in a deployed position. Unless otherwise stated or implied, the signal source and the insertion tool are referred to and characterized separately when used alone or in combination.

When there is an "epidural component", and "epidural portion" of a device, it refers to the component of the device that has this structure and performs its defined action. They need not be located in any particular physical space before or after implantation. After implantation, unless explicitly stated or otherwise required, the epidural component is not required to be positioned completely below the dura mater, the epidural component is not required to be passed completely through the dura mater, and the epidural component is not required to be positioned completely outside the dura mater. Similarly, only a "gasket" is required to perform the indicated function, and may be made of any suitable material.

The terms "positioning tool" or device and "insertion tool" or device are used interchangeably to refer to a device or portion of a device that a surgeon uses when implanting the combined electrode assembly into a patient and then removes it from the surgical field for reuse or disposal, leaving the electrode assembly in place. The positioning tool need not be included with the electrode assembly of the present invention, as claimed. For industrial applicability, the positioning tool may be provided in combination with the electrode assembly, or it may be provided separately and combined with the electrode assembly in the operating room. The electrode assembly of the present invention may be implanted using the positioning tool of the present invention or any other device deemed appropriate by the surgeon.

The term "quiescence" as used in this disclosure with respect to a bundle of axons refers to the state of random depolarization or discharge of axons inside the bundle. In the natural state, the nervous system can actively signal that the entire tract has no sensory input to transmit. As described herein, this can be caused by pseudo-spontaneous nerve stimulation by applying an effective pattern of high frequency electrical pulses in an appropriate manner.

When describing the shape (e.g., cylindrical, circular, or elliptical) or position (e.g., parallel or perpendicular) relative to another component of a device or tool of the present invention, or making a comparison (e.g., having the same shape or being complementary), such terms are approximate unless otherwise specifically indicated. The actual shape or position may deviate from the exact shape or position mentioned within the functional tolerances of the arrangement without departing from the scope described or claimed. This is done to aid the reader in orienting when referring positionally to various components (e.g., vertical or longitudinal axes) of the device or tool of the present invention: this does not impose any particular position or orientation requirements on the device when sold or in vivo.

Examples

Example 1: testing various pads for use with an epidural stimulator

To test the usability of the gasket as a sealing mechanism to prevent CSF leakage, compression of a prototype epidural stimulator of the type shown in fig. 1 to 4The plate and shell are implanted into a simulated epidural incision that has been cut into the simulated sheath capsuleIn the tube. A thin, smooth strip of polyethylene is used instead of the hard film to ensure that any leak path is associated only with the liner, regardless of the porosity of the hard film replacement. The cushion between the compression plates is replaced by a dura mater commonly used for dura mater closure and sealingAnd (4) preparing. The pad is nominally 0.5mm thick and is oval in shape, with its length and width matching the size of the hard disk, as shown in fig. 10.

Connecting the syringe toOne end of the tube and the other end is closed. The tube was filled with water and the hydrostatic pressure was manually controlled by the force acting on the syringe plunger. The hydrostatic pressure within the tube, which can be increased to an supraphysiological level, is monitored using a pressure gauge. A dural incision was made in a polyethylene test strip and the stimulator assembly was implanted, placing a membrane on either side of the stripA liner. The compression nut is then gently tightened to pull the epidural inner and outer plates toward each other and create a closure to the epidural incision, and then the hydrostatic pressure is raised using a syringe. The seal created by the cushion remains leak-free at a maximum applied pressure of approximately 250mm Hg, which is several times the peak intrathecal pressure observed in the patient during postural changes. This demonstrates the usefulness of the gasket as a seal to prevent potential post-implantation CSF leakage.

Another concern relates to the dynamics of the prototype sealing mechanism. The surface area A of each pad was approximately 25x10^{- 6}m²And according to a standard engineering modelModel, we estimate that the closing tension F exerted on the gasket by the pressing nut is approximately 1.1N. Thus, the pressure P acting on the gasket within the assembly will be P ═ F/a ═ 1.1N/(25x 10)^-6m²)＝4.4x10⁴Pa ≈ 330mm Hg. This pressure was 33% greater than the peak pressure exerted on the liner in our test, roughly 15 times the normal intrathecal pressure, thus further understanding the leak-free performance of the seal as observed in our experiments.

Example 2: t-shaped electrode modeling and selective fibrous stimulation

The modeling described herein demonstrates that the epidural stimulation device can be effectively used to selectively modulate target neurons within the spinal cord, while not affecting non-target structures. Furthermore, modeling such as described in this example 2 can be used to determine additional configurations of the epidural stimulation electrode array that can be used to selectively stimulate neural structures (e.g., large fibers, small fibers, medium fibers, and combinations thereof). On the most basic level, this means controlling or directing the electric field generated by the current delivered from the electrode contacts; this typically involves spatial and temporal control properties. The spatial distribution of field strength and gradient determines which neurons are affected. Currents entering these fields through axons may be susceptible to depolarization triggered by external sources. The temporal pattern of the field will also affect axonal action potentials. From this combined response to field strength and time application, a "selective" and desired modulation of neural activity occurs.

Using COMSOL(a general simulation software available from COMSOL, inc. of burlington, ma for modeling designs, devices, and procedures) to solve the electric fields and currents on the axial and transverse sections of the spinal cord deep in the dura mater. Deriving data and graphics for basing onThe procedure of (a) is described and used, which reconstructs complex fields and simulates field to axons of various sizes within the dorsal columnInfluence.

Fig. 28 is a schematic diagram of an epidural stimulation system with one (or more) auxiliary epidural leads. Fig. 29A and 29B are illustrations of an implantation tool and an exemplary version of an epidural stimulator. After opening the dura, the surgeon uses the tool to insert the electrode array into the sheath capsule. The inner shaft of the tool gently tightens the closure nut onto the surface of the epidural compression plate. This sandwiches the dura between the padding material on either side of the compression plate and holds the electrode array in place. The outer shaft of the implantation tool is then rotated to release and remove it from the opposing tongue and groove junction on the epidural plate. The lead bundle is connected to one channel of the pulse generator and, as schematically shown in fig. 28, a simultaneously implanted auxiliary epidural cylindrical lead is connected to the other channel, completing the procedure.

The size and contour of the intracranial electrode array matches that of the adult spinal cord. For example, there can be a concave side and a convex side, and the electrode in contact with the CSF can be mounted on the convex side, while the concave side is directly or indirectly adjoined to the intradural membrane by another layer. For computational purposes, the features of the human spinal cord captured in geometry are shown in fig. 30. For our simulations, these contained (1) a gray matter core, (2) white matter surrounding gray matter, (3) a CSF layer bounded by the spinal cord and dura mater, and (4) the dura mater itself, the outer layer of the model. Also according to fig. 30, conductivity is assigned to each volume and to the dural interface with the external ground. All conductivities are scalar except for those of white matter, which has different longitudinal and radial conductivities. Electrical continuity between each volume is assumed. It is further assumed that electrical activity outside the dura is small relative to internal activity. Over a simulated 80mm marrow, the cross-section of the marrow remained constant. A substrate with twelve sites was positioned just below the dura and protruded 0.3mm below the dura.

Internal physical and boundary conditions

The continuity condition for zero charge creation is maintained anywhere inside the modelAll surfaces of the medullary end have zero potential (V ═ 0), indicating that the outer ellipsoidal surface of the dura mater is at zero reference voltageOn, and the locus is a current source such that:the actual distribution of current at each site is determined by the surrounding electrical environment. V is a dependent variable representing the internal scalar potential voltage, σ is the conductivity scalar or tensor, d_sIs the hard film thickness, and J is the current vector

The geometry and boundary conditions are used to solve for the electric field. This is done by using a volume of a discrete model of the tetrahedral mesh, followed by a finite element method, both of which areTo be implemented in (1).

Field assessment

Several post-processing methods are available in COMSOL to produce significant data products from the field solution. There is a visualization of the fields and currents superimposed on the geometry, the computation of quantiles (e.g., maxima, minima, averages, integrals, etc.) on points, lines, surfaces, or volumes, and the output of any product.

Basis function method for field reconstruction

When performing many serial calculations on fields under different driving conditions, it is convenient to use the underlying method to reconstruct each new field indicated by the new boundary conditions. This is done by solving for the model with only a uniform current (1mA) excitation for each site and the other sites set to zero. By superimposing the basic field scaled by the current at that site, the complex field generated by several sites with different currents can be approximated accurately. This approach is used when performing calculations such as neural simulations using a MATLAB platform external to COMSOL. The fact that the model is linear justifies this approach.

Nerve model

There are many variations of the model of the propagation of nerve spikes in myelin axons and how electric field potentials trigger nerve spikes. The smallest configuration is a string of nodes consisting of a capacitive membrane consisting of simulators of different voltage controlled channel species of sodium and potassium held at equilibrium potential by diffusion potential. When the membrane is sufficiently depolarized, the node is then provided with an action potential. When nodes are connected internally by conductive and fully insulated axons, it is possible to drive current through the action potential to depolarize adjacent nodes, thereby propagating the action potential from one node to another.

The trigger mechanism is as follows. The electrical stimulus causes actuation of the first action potential by a positive second potential difference external to the node. This will drive the current to cause depolarization of a single node or a group of nodes within the influence range of the second difference, which is strong enough. Thus, both field strength and field shape are important for initiating the action potential. For example, a constant field potential or constant potential gradient cannot initiate an action potential in the axon. Fig. 31A is a view from below the pia mater surface. Pia mater and cross sections are colored with a representation of the potential field. In addition, a line parallel to the medullary axis is inserted to mark the position of the waveform sample shown in fig. 31B. These spatial waveforms clearly show the positive second order spatial derivative or difference.

From this minimal complexity axon model, several functions can be added that improve simulation fidelity. These include better models of myelin axons by adding segmented cable properties to conducting segments and adding finer channel groups to nodes, etc. For example, the McIntyre-Richardson-Grill (MRG) model connects membrane/myelin lumped circuits in series with myelin leakage and capacitance to membrane leakage and capacitance (McIntyre CC, et al, J Neuropysiol 2002; 87(2): 995-1006). In addition, conductive spaces are added between the membrane and myelin, and the network is typically distributed in multiple networks along the internodes. The model adds two differential equations for each inter-node network, which can be repeated up to ten times.

Illustration of the drawings

Fig. 32 shows the equipotentiality in white matter where fibers of different fiber size classes were excited. As the current increases from top to bottom and the proportion of current required at the tip site increases, the contour lines become more curved and axon excitation extends to greater depths.

Fig. 33 shows that in the right image from top to bottom almost the same stimulus distribution is seen across the entire marrow in the image. At the top, 1.4, 0, -3, 0, 1.4, 0 current patterns are shown. The pattern of stimulation proceeds linearly until the current program is achieved at the bottom [0, 1.4, 0, -3, 0, 1.4 ]. The power (P) for each case is displayed.

Fig. 34A-34C show that during a stimulation pulse, an electrode site on the intended target delivers a cathodal depolarization pulse, sending some nodes of the neuron into an action potential, which then propagates the action potential in both directions. In the recovery phase, longer duration and reduced amplitude anodic pulses perform the required charge balancing. To obtain a focusing effect to avoid stimulating off-target tissue, an anodal first pulse is delivered to the periphery of the central electrode site. The well-designed pulse (b) prevents diffusion of the target region and does not cause off-target action potential. If the recovery (cathodic) portion of the anodic first pulse has too large an amplitude (c), accidental discharge and propagation may occur.

Figures 35A to 35C show a circular electrode site with the same area as the site used in the device, with a 200 mus cathodic pulse followed by a 50 mus dwell and a 400 mus charge balance phase to drive a similar interface impedance. (a) The drive and interface voltages show a step at the beginning of the pulse and then gradually decrease until the end of the cathodic pulse. The average interface voltage increases because the current distribution efficiency is lower late in the pulse. The difference between the driving voltage and the interface voltage is caused by the charge accumulated on the surface of the site and the difference in current distribution as the phase progresses. (b) Shown is the current distribution from the point just before the start of the cathodic pulse to the point just before its end. At the start of the pulse, the current peaks at the edges of the site rise to a level well above the center of the site. The current distribution becomes more uniform over time. (c) The display time of the interface voltage is the same as (b). As explained above, the magnitude of this negative potential increases, but it is also lower at the edges due to the accumulated charge.

Fig. 36 shows the current distribution to the site of white matter and the leptomeningeal surface at the instant the cathodal stimulation phase was initiated. The current on the edge of the site is very large relative to the average current, but this disappears quickly as the site charging progresses. Due to the shunting effect of CSF, the current flow into and out of the white matter is much less than the current flow at the site. Although the total current at the cathode site was 4mA, the current into the white matter was only 0.13mA or 3.25%.

As a result: tissue targeting and selectivity

The current from any single site on the implant will diffuse preferentially in the CSF because it has the highest conductivity of any medium in the model, e.g., -20 times the lateral component of the white matter conductivity tensor. The isoelectric lines seen in the gray and white matter of the spinal cord tend to be straight lines, thus transecting not only the white matter, but also the gray matter, resulting in accidental stimulation of cells in the gray matter. The term T-electrode or T herein refers to an electrode having an array comprising electrodes that can be used in a T-shape as shown in fig. 29B. The solution is to excite the central site of the implant with cathodic potential, while exciting the lateral sites of the T-tips with anodic potential. This limits the lateral diffusion of the cathode potential and thus the loss of the grey matter back angle. Fig. 32 shows the case for four different current levels in the central two sites of T. For larger central cathode currents, a larger proportion of the anode current from the tip site is required, resulting in an approximately squared increase in power consumption.

With greater stimulation depth achieved, the current from the site on T can be manipulated to move the effective stimulation area horizontally across the entire medulla. Fig. 33 shows how the sweep of the current source across T can locate the center of the stimulus with high spatial resolution. Four steps are shown, but more instances can be placed in progress, creating a higher position resolution. By deviating from the symmetry of the montage practiced in the examples, the linear stepping method used to achieve progression of the stimulation center across the medulla can be significantly diversified to obtain greater depth, and possibly greater off-normal patterns.

When shaping the stimulation field, we will confine the cathodic pulse to the target area, but the electrochemical requirements of the electrode site have a recovery phase of the stimulus waveform that balances the net stimulation charge to zero. This means that a volume of tissue not contained in the target will receive a cathodic current during the recovery phase that may excite an unintended volume of neurons. The commonly used method makes the recovery current much smaller than the stimulation phase over a longer period of time. In some cases, the requirements for this factor in the stimulus design may limit the depth and selectivity strategy. Fig. 34A to 34C illustrate this challenge.

The epidural electrical bypass thus saves 75% of the large amount of electrical energy due to the large impedance relative to the subdural structures. This function can extend battery life. In addition, the subdural device extends slightly into the CSF space, bringing the electrode sites closer to the excitable element of the white matter, so that the current spreads less within the CSF. This better proximity improves the ability to direct or focus the potential in the white matter. Independent of the reduced impedance barrier and improved proximity curve of the equipotential needed to obtain selectivity and improved depth. Fig. 32 shows the improved depth by having more current flow through the center and tip sites of the T-intersection. To improve the depth obtained from no tip penetration to maximum tip penetration, the power was increased by 1800%, which places stress on the site electrochemically and in the tissue directly under the pia mater. To determine the limits, a safety analysis needs to be performed: the resistance to current density and total charge per pulse phase is organized and electrode failure is prevented.

Corrosion of the site can lead to device failure and target tissue poisoning. The electrode sites used in IP 2.0 are small according to the criteria of the dorsal column stimulation device. This is evidenced by the proximity of the site to the target tissue and the absence of the impedance and distance barriers presented by the dura mater. The area of these sites was 1.72mm²Safe charge per phase of platinum acceptanceThe delivery amount was 50. mu.C/cm²The charge limit per phase for the T-array site was found to be 0.86 μ C. 50 μ C/cm₂The value of (b) is the threshold for the onset of damage to nervous system tissue. Thus, for a 200 μ s pulse, the maximum current allowed is 4.3 mA. It is also assumed that the capacitance of the site surface is 0.45F/m²Although it may be assumed that materials with higher effective capacitance may also be used for this application.

An example pulse sequence consisting of a 200 μ s cathode phase at 2mA followed by a 400 μ s anode phase at 1mA uses about half the capacity of the site. The voltages required to perform this charge balancing pulse sequence are shown in fig. 35A for the circular locus of the same locus region used in the global model. When the sequence begins, the average interface voltage and the drive voltage are equal, but differ as the site is charged. In the anionic phase, the curve converges again when charge balance is reached. Details of how the electrode current and charge distribution change with time and radius are shown in fig. 35B and 35C. As the sequence begins, the drive voltage jumps to overcome the spreading resistance and then gradually decreases due to (1) an increase in average charge across the site, and (2) a decrease in charge transfer efficiency as a result of an increase in peripheral charge.

This rapid accumulation of charge at the site edges is due to the current increase there, as shown in fig. 35B. If the site and pulse regime is not designed to control the edge current, site corrosion can occur. During the first few microseconds of the pulse, the imbalance between center and edge currents is somewhat extreme, but over time the current density becomes more uniform throughout the site. At the end of the cathode phase, the potential difference due to the extra charge at the edges is about 100 mV. The magnitude of the edge current at the beginning of the pulse can be reduced in several ways. (1) It is important to keep the curvature of the perimeter of the site to a minimum. The circular sites are most efficient when used alone. (2) Shaping the leading edge of the pulse to have a longer rise time allows charge to accumulate more slowly, thereby reducing the maximum current density at that edge. (3) Preventing adjacent sites from having extreme polarity differences will prevent large currents from flowing directly between the sites. The parallel edges of adjacent sites promote uniformity of current flow. This is another cost of target selectivity. (4) Adding a resistive layer at a location forces current flow, thereby making the distribution more uniform, but at the expense of increased power due to resistive voltage drops and less efficient current flow into the medium.

Fig. 36 shows an example of the current distribution at the site of transient white matter and the leptomeningeal surface during the cathodal stimulation phase. Due to the gap between the site and the target, the distribution of current density on the surface of the pia mater changes minimally on the charge injection pulse, but as mentioned above, the current distribution on the site changes greatly.

None of the examples used in this example 2 exceeded 50 μ C/cm²The limit of (c). Also, there are limits to the current density that neural tissue can tolerate. The maximum current density seen in our maximum depth of excitation map was 1.33mA/cm²For a 200. mu.s pulse, the current density was 0.266. mu.C/cm²Well below 30 μ C/cm²Is acceptable boundary.

* * * * * * * * *

Prior U.S. patents 9,364,660,9,486,621,9,254,379,9,572,976,9,403,008 and 9,950,165 are incorporated herein by reference in their entirety for all purposes, including but not limited to the description and detailed description of SCS device components that may be included or excluded in any embodiment of the SCS devices and uses thereof described and claimed herein.

Each publication and patent document cited in this disclosure is incorporated by reference in its entirety for all purposes to the same extent as if each such publication or document were specifically and individually indicated to be incorporated by reference.

Although the invention has been described with reference to specific examples and illustrations, it is recognized that departures can be made therefrom within the scope of routine development and optimization and that equivalents can be substituted for elements thereof without departing from the scope of the claims, which are intended to be encompassed by the invention.