Patent ID: 12251558

While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the invention are directed to a retaining device, such as a carrier or cuff, which positions active contacts, i.e. electrodes, of a stimulation device against the targeted nerve directing the current from the electrodes into the nerve. The retaining device also inhibits or prevents the current from flowing out to the surrounding tissue.

Referring toFIG.1, one example of a nerve cuff100adapted for holding a stimulation device is coupled to a nerve102. Nerve102can comprise any nerve in the human body targeted for therapeutic treatment, such as, for example, the vagus nerve. Nerve cuff adapter100generally comprises an outer carrier or cuff104body that can comprise any of a variety of medical grade materials, such as, for example, Silastic™ brand silicone elastomers, or Tecothane™ polymer.

In general, a nerve cuff including a cuff104body having (or forming) a pouch or pocket106for removably receiving an active, implantable stimulation device108having one or more integrated, leadless electrodes110on a surface of stimulation device108proximate nerve102. As illustrated inFIGS.1and1A, nerve cuff100wraps around nerve102such that electrodes110are positioned proximate nerve102.

Contacts or electrodes110can be positioned directly against nerve102, as illustrated inFIG.1A, or in close proximity to nerve102, as illustrated inFIG.1B. Referring specifically toFIG.1B, close proximity of electrodes110and nerve102will leave a gap or space112that may naturally be filled with fluid or connective tissue. In one embodiment of the invention, electrodes110and/or the inner surface of cuff body104can include optional steroid coatings to aid in reducing the local inflammatory response and high impedance tissue formation.

In one embodiment, the pocket106for containing the stimulation device108is defined by the open space between the nerve102and the inner surface of the cuff body104. Stimulation device108can be passively retained within pocket106by the cuff body104, or can be actively retained on cuff body with fastening means, such as, for example, sutures. In other embodiments, pocket106can comprise a pouch-like structure attached to cuff body104into which stimulation device108can be inserted. Stimulation device108can be passively retained within a pouch-like pocket by simply inserting the device108into the pocket or can be actively retained with fastening means. A pouch-like pocket can be positioned either in the interior or on the exterior of cuff body104. Pouch-like pocket106and/or cuff body104can include access openings to allow electrodes to be positioned directly proximate or adjacent to nerve102.

Cuff body104can have a constant thickness or a varying thickness as depicted inFIGS.9A and9B. The thickness of cuff body104can be determined to reduce the palpable profile of the device once the stimulation device is inserted. In one embodiment, the thickness of cuff body can range from about 1 to about 30 mils, or from about 5 to about 20 mils. In one embodiment shown inFIG.9B, cuff104can have a greater thickness at a top and bottom portion of the cuff and a smaller thickness in a middle portion where the stimulation device is contained.

A key obstacle to overcome with implanting stimulation devices proximate nerves or nerve bundles is attaching a rigid structure that makes up the stimulation device along a fragile nerve in soft tissue. In one embodiment of the invention, this issue is resolved by encasing nerve102and device108in a cuff body104that comprises a low durometer material (e.g., Silastic™ or Tecothane™) as described above, that conforms around nerve102. Further, as illustrated inFIG.2, cuff body104can comprise strain reliefs114on its ends that reduce or prevent extreme torsional rotation and keep nerve102from kinking. Strain reliefs114can coil around nerve102, and are trimmable to a desired size, such as the size of nerve102. Further, strain relief114can be tapered. In some variations, the lateral ends of the nerve cuff, forming the channel into which the nerve may be place, are tapered and have a tapering thickness, providing some amount of support for the nerve. In some variations, the channel through the nerve cuff in which the nerve may sit, is reinforced to prevent or limit axial loading (e.g., crushing) of the nerve or associated vascular structures when the nerve is within the cuff.

Given the design or architecture of cuff body104, any vertical movement of cuff body104on nerve102is not critical to electrical performance, but can result in friction between device108and nerve102that could potentially damage nerve102. For that reason, device108should readily move up and down nerve102without significant friction while being sufficiently fixated to nerve102so that eventually connective tissue can form and aid in holding device108in place. The challenge is stabilizing device108so that it can be further biologically stabilized by connective tissue within several weeks.

Nerve cuff100should not be stabilized to surrounding muscle or fascia that will shift relative to the nerve. Therefore, referring toFIGS.3and4, nerve cuff100can further comprise connection devices, such as suture holes or suture tabs, for coupling and stabilizing cuff body104with device108to at least one of the nerve bundle or nerve102, and the surrounding sheath that contains nerve102. In one embodiment of the invention, for example, as shown inFIG.3, cuff body104can comprise suture holes116that can be used with sutures to couple cuff104body with device108to the surrounding nerve sheath. In an alternative embodiment of the invention, shown inFIG.4, suture tabs118with suture holes116extend from one or both sides of cuff body104.

Several stabilizing mechanisms can be used, including suture tabs and holes, staples, ties, surgical adhesives, bands, hook and loop fasteners, and any of a variety of coupling mechanisms.FIGS.3and4, for example, illustrates suture tabs and holes that can be fixed to the surrounding sheath with either absorbable sutures for soft tissue or sutures demanding rigid fixation.

FIG.5illustrates sutures120that clamp or secure cuff body104with device108to a surgeon-elected tension. Sutures120can be tightened or loosened depending on the level of desired stability and anatomical concerns. As shown inFIG.5, a gap122can be present so long as cuff adapter100is sufficiently secured to nerve102, with a limit set to a nerve diameter to prevent compression of the vasculature within nerve102. Surgical adhesives (not shown) can be used in combination with sutures120on surrounding tissues that move in unison with the neural tissue.

Muscle movement against cuff adapter100can also transfer undesired stresses on nerve102. Therefore, in an embodiment of the invention, low friction surfaces and/or hydrophilic coatings can be incorporated on one or more surfaces of cuff body104to provide further mechanisms reducing or preventing adjacent tissues from upsetting the stability of nerve cuff100.

FIG.6illustrates a nerve cuff100with a stimulator device removably or marsupially secured within pocket or pouch106of cuff body104. By the use of recloseable pouch106, active stimulator device108can be removed or replaced from cuff body104without threatening or endangering the surrounding anatomical structures and tissues. Device108can be secured within cuff body104by any of a variety of securing devices124, such as, for example, sutures, staples, ties, zippers, hook and loop fasteners, snaps, buttons, and combinations thereof. Sutures124are shown inFIG.6. Releasing sutures124allows access to pouch106for removal or replacement of device108. Not unlike typical cuff style leads, a capsule of connective tissue can naturally encapsulate nerve cuff100over time. Therefore, it will most likely be necessary to palpate device108to locate device108and cut through the connective tissue capsule to access sutures124and device. The removable/replaceable feature of nerve cuff100is advantageous over other cuff style leads because such leads cannot be removed due to entanglement with the target nerve and critical vasculature.

As discussed supra, compression of nerve102must be carefully controlled. Excess compression on nerve102can lead to devascularization and resulting death of the neural tissue. Compression can be controlled by over-sizing or rightsizing nerve cuff100, so that when pocket sutures124are maximally tightened, the nerve diameter is not reduced less that the measured diameter. Cuffs formed from Silastic™ or Tecothane™ materials are relatively low cost, and therefore several sizes can be provided to the surgeon performing the implantation of nerve cuff100to better avoid nerve compression.

Miniature stimulators, such as device, are still large enough to be felt and palpated by patients as are state-of-the-art commercial cuff systems. Referring toFIG.7, to avoid such palpation, nerve cuff100can further comprise a protecting shield126conforming to the shape of the anatomical structures, such as in the carotid sheath. In this embodiment, nerve cuff100is secured around the vagus nerve, while isolating device108from contact with both the internal jugular vein (IJV)132, and common carotid artery134. Shield126then further isolates device108from other surrounding tissues. It is critical to minimize the profile of the entire cuff adapter100while maintaining the compliance of such materials as Silastic™ or Tecothane™. In one embodiment of the invention, protective shield126is formed from a PET material, such as Dacron®, optionally coated with Silastic™ or Tecothane™ forming a thin and compliant structure that will allow for tissue separation when required.

When a nerve does not provide sufficient structural strength to support nerve cuff adapter100, collateral structures can be included in or on cuff body104. Because of a high degree of anatomical variance such a scheme must demand the skill of the surgeon to utilize a highly customizable solution.FIG.8aillustrates a variable size nerve cuff100with a wrappable retainer portion128extending from cuff body104. As shown inFIG.8c, cuff body104is secured around nerve102, while retainer portion128is secured around the sheath or other surrounding anatomical structures, such as the IJV132and/or carotid artery134. As shown inFIG.8b, wrappable retainer portion128can include securing devices130, such as suture holes, for securing the entire nerve cuff100around the desired anatomical structures. This configuration allows for access to device108through pocket106as in previous embodiments, while adapting to a multitude of anatomical variations to obtain the desired stability of nerve cuff100on nerve102.

FIGS.10A-10Dillustrate a variation of a nerve cuff that includes a cuff body forming a channel (into which a nerve may be fitted) and an slit formed along the length of the nerve cuff body. In this example, the nerve cuff body also includes a pocket region within the cuff body positioned above the nerve channel. The top of the body (opposite from the nerve channel) includes a long slit1003along its length forming on opening. The cuff body may be along the slit by pulling apart the edges, which may form one or more flaps. In the example shown inFIG.10A, the slit may be split open to expose the inside of the nerve cuff and allow the nerve to be positioned within the internal channel, so that the cuff is positioned around the nerve. The same split may be used to insert the microcontroller as well. In some variations a separate opening (slit or flap) may be used to access the pocket or pouch for the microcontroller.

FIG.10Bshows a perspective view of the nerve cuff holding a microcontroller after it has been inserted onto a nerve (e.g., the vagus nerve).FIG.10Cshows a side view of the same.FIG.10Dshows a section though the view ofFIG.10C, illustrating then nerve within the channel formed through the nerve cuff, and a microstimulator held snugly within the nerve cuff so that the microstimulator is in electrical communication with the nerve via a shared surface between the two. In some variations, as discussed below, the microstimulator is held in a separate, possibly isolated, compartment and electrical contact with the nerve is made by one or more internal leads that couple the microstimulator with the nerve through an internal contact.

The exemplary cuff shown inFIGS.10A-10Dhas a conformal configuration, in which the wall thickness is relatively constant, as can be seen from the sectional view inFIG.10D. In contrast,FIGS.11A-11Dillustrate a variation of a nerve cuff in which the wall thickness varies along the perimeter. This non-uniform thickness may effectively cushion the device relative to the surrounding tissue, even as the patient moves or palpitates the region. This may have the added benefit of preventing impingement of the nerve. Similarly, the variable thickness may enable smooth transitions and help conform the cuff to the surrounding anatomy.

For Example,FIG.11Ashows an end view (with exemplary dimensions illustrated). It should be noted that in any of the figures or examples provided herein, the dimensions shown or described are for illustration only. In practice the dimensions may be +/− some percentage of the values shown (e.g., +/−5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, etc.). The section through the device shown inFIG.11Dillustrates the non-uniform thickness of the walls.

Both nerve cuff variations shown inFIGS.10A-10DandFIGS.11A-11Dare substantially rounded or conforming, and have non-traumatic (or atraumatic) outer surfaces. As mentioned, this relatively smooth outer surface may enhance comfort and limit encapsulation of the nerve cuff within the tissue.

As can be seen fromFIGS.10D and11D, the microstimulator typically rests above (in the reference plane of the figure) the length of the nerve when inserted into the nerve cuff. In some variations, the microstimulator includes a contoured outer surface onto which one or more contacts (for contacting the nerve or an internal conductor within the nerve cuff) are positioned. For example,FIG.12illustrates one variation of a microstimulator1201. In this example, the microstimulator includes one or more contacts on its outer surface with which to provide stimulation to a nerve.FIG.13Ashows another variation of a microstimulator1301in which the outer surface (the bottom inFIG.13A) is curved to help form a channel surrounding the nerve when the microstimulator is inserted into the nerve cuff.FIG.13Bshows an end view, illustrating the channel concavity1303extending along the length of the microstimulator, andFIG.13Cshows a bottom view, looking down onto the channel region. In practice, the microstimulator shown may be placed within the nerve cuff and be held in position at least partially around the nerve. Thus, the microstimulator may help protect the nerve, which may lie within this channel. As mentioned above, and described in greater detail below, it is not necessary that the nerve lie against the contacts, as current may be conducted to the nerve from within the nerve cuff, which may be insulated sufficiently to prevent excessive leak or spillover of the current even when the cuff is oversized and only loosely surrounds the nerve. Furthermore, the nerve cuff may include one or more internal contacts allowing the current from the microstimulator to be distributed to the nerve via one or more internal contacts or leads, including circumferentially around the nerve.

FIGS.14A and14Bshow another variation of a nerve cuff. In this example, the slit forming the opening is positioned on the upper surface (opposite to the nerve channel) along the length of the device. The slit is formed in an interlocking pattern. InFIG.14a, the slit forms a zig-zag pattern, although other interlocking patterns may be used. For example, a sinusoidal or square-wave pattern may be used. The interlocking pattern may distribute the strain of closing the cuff around the nerve and microstimulator, and may make it easier to close the cuff once it has been positioned and the microstimulator has been inserted.FIG.14Bshows an end view of the same cuff shown inFIG.14A.

FIGS.15A-15Cshow a similar cuff to the one shown inFIG.14Afrom top and side views, connected to a nerve. In these example, the nerve extends through the internal channel and out the openings (which may be oval shaped, as shown inFIG.14B) at either end. InFIG.15C, a section through the length of the device shows that the microstimulator is positioned in the pouch (cavity) above the nerve. The microstimulator may be held in place by the walls of the cuff. A conforming microstimulator (such as the one shown inFIG.13A-13C) may be used, as illustrated in the cross-sectional view shown inFIG.15D. The contacts1503of the conforming microstimulator are positioned on the bottom of the device.

As mentioned briefly above, in some variations of the nerve cuff, the inner surface of the cuff body includes one or more internal contacts configured to couple with the microstimulator held within the pouch, and transmit any applied energy to the nerve (or receive energy from the nerve) positioned within the channel through the nerve cuff. The internal lead may be positioned so that it applies current to the underside (along the bottom region of the channel), or around the sides of the nerve as it sits within the channel. In some variations the internal conductor or lead is configured around the channel so that the nerve may be circumferentially stimulated, optimizing the applied stimulation.FIG.17is a long section though a nerve cuff, showing the inside of the cuff, and illustrates a variation of a nerve cuff having an internal lead1703that may apply stimulation to the underside of the nerve. This internal lead may be formed of any biocompatible conductive material, including medals, conductive plastics, or the likes. The internal lead may include exposed electrode surfaces1703for making contact with the nerve. Electrodes may be active contacts, also formed of any appropriate conductive material (e.g., metals, conductive polymers, braided materials, etc.). In some variations, the internal lead is coated or treated to help enhance the transfer of energy between the microstimulator and the nerve. Circumferential stimulation or conduction around the lead may reduce the impedances and assure uniform cross-sectional stimulation of the nerve bundle.

FIG.19shows another variation of a nerve cuff as described herein. In this example, the nerve cuff includes slit1903along one side of the device, adjacent to the nerve channel, which can be opened (e.g., by pulling apart the flaps or sides of the cuff) to expose nerve channel and the pocket for the microstimulator.

Many of the nerve cuff variations described herein may be opened and positioned around the nerve, for example, by splitting them open along a slit or hinge region. The device may be configured so that they have sufficient resiliency to close themselves, or remain closed if the edges of the slit region are brought together. Thus, the device may have a shape memory property that encourages them to close. In some variations, as already mentioned, it may be useful to hold them closed, at least temporarily, once they have been positioned over a nerve and the microstimulator has been positioned within the pocket. Thus, the device may include one or more closure elements. For example, the device may include a suture hole or passage for suturing the device closed. In some variations the nerve cuff includes a button or other fastener element. In some variations, as illustrated inFIGS.6and18, the device may be sutured close with a dissolvable suture. A few weeks or months after insertion, the nerve cuff may be encapsulated or engulfed by the surrounding tissue, and will be held closed by this encapsulation. Thus, the dissolvable sutures merely keep the cuff closed for initial anchoring before biointegration and encapsulation occurs.

Any of the nerve cuffs described herein may also include one or more external leads or contacts facing the outside of the nerve cuff body, which may be used to stimulate tissues outside of the nerve cuff, and not just the nerve within the channel through the cuff.FIG.21illustrates one variation of a nerve cuff having external leads. In this example, the nerve cuff includes two external contacts2103that are connected (through the wall of the nerve cuff body) to the microstimulator held within the nerve cuff pocket. Such external leads may be used for sensing in addition to (or instead of) stimulation. For example, these electrical contacts may be used to sense other physiological events such as muscle stimulation and/or cardiac function. These signals can be applied to aid synchronization of target nerve stimulation to minimize artifacts of target stimulation. Such signals may be too faint for reliable remote sensing, however the position of the microstimulator (insulated within the housing of the nerve cuff) may allow accurate and reliable sensing.

A nerve may sit within a supported channel through the nerve cuff. As illustrated inFIG.20, the channel2003may be formed having generally smooth sides, so as to prevent damage to the nerve and associated tissues. In some variations the nerve channel though the cuff is reinforced to prevent the cuff from pinching the device or from over-tightening the device when closed over the nerve. Supports may be formed of a different material forming the nerve cuff body, or from thickened regions of the same material. Although multiple sizes of nerve cuff may be used (e.g., small, medium, large), in some variations, an oversized nerve cuff may be used, because the insulated cuff body will prevent leak of current from the microstimulator to surrounding tissues.

In general, the nerve cuff body may be electrically insulating, preventing leakage of charge from the microstimulator during operation. In some variations the nerve cuff includes shielding or insulation sufficient to electrically insulate the microstimulator within the nerve cuff body. Shielding material may particularly include electrically insulative materials, including polymeric insulators.

It may be shown mathematically using an equivalent circuit of the microstimulator, as shown inFIG.23, that the current from a microstimulator is not appreciably passed out of even a loosely applied nerve cuff. This allows for the use of oversized nerve cuffs, rather than requiring rigorous sizing, or risking constricting the nerve.

For example, assuming a nerve with a cross section of Nareais surrounded by a column of fluid Fareaenclosed by the nerve cuff, where contacts on the inside the microstimulator are spaced Espacingapart (center to center) and have a width Ewidthand circle around the column of fluid and nerve Edegrees, it can be shown that the current will leak out the ends through a distance between the center of the electrode and the end of the nerve cuff that is defined by a distance Dguard.

The electrical model (illustrated inFIG.23) consists of a current source that drives through DC isolation capacitors (Ciso2optional), through the capacitance of each electrode (Cdl1and Cdl2). From the electrodes, the current passes through either path RSor Rlp1+Rb+Rlp2. Whereas a portion of the current passing through Rsprovides useful work and the current passing through Rlp1+Rb+Rlp2passes outside of the device and may cause undesirable effects.

If the nerve has a tight fit, then all the current passing through Rswould contribute towards stimulation, but only a portion of the current can activate the nerve in the case of a loose fit. Based on this model, it can be shown that (assuming that the nerve and fluid columns form an ellipse defined by the major and minor axis a and b, and the pulse width is short and capacitances are large) just the real impedance and efficiency can be estimated.

The electrode surface area is determined to estimate the complex portion of the impedance: Farea=π*aF*bFand Narea=π*aN*bN.

Assuming the impedance of the cuff contained fluid and nerve has a similar conductance ρ and electrodes are spaced at Espacingthen the real resistance of the conduction volume is: Rworking=Espacing*ρ/Farea, where the wasted resistance that should be maximized is calculated by: Rwasted=2*Dguard*ρ/Farea+Rbulk, where Rbulkis defined as the free field resistance between the two ends of the cuff.

So the efficiency (η) of the real current delivered in the POD is Rwasted(Rworking+Rwasted), and for the case of an undersized nerve assuming the conductivity of tissue and the fluid column is about equivalent then the stimulation efficiency is defined as ηT=η*Narea/Farea.

Methods of Insertion

In operation, any of the devices described herein may be positioned around the nerve, and the microstimulator inserted into the nerve cuff, in any appropriate manner.FIGS.22A-22Hillustrate one variation of a method for applying the nerve cuff around the nerve and inserting a microstimulator. In this example, the patient is prepared for application of the nerve cuff around the vagus nerve to hold a microstimulator device securely relative to the nerve (FIG.22A). An incision is then made in the skin (≈3 cm) along Lange's crease between the Facial Vein and the Omohyoid muscle (FIG.22B), and the Sternocleidomastoid is retracted away to gain access to the carotid sheath (FIG.22C). The IJV is then reflected and <2 cm of the vagus is dissected from the carotid wall.

In some variations, a sizing tool may be used to measure the vagus (e.g., diameter) to select an appropriate microstimulator and cuff (e.g., small, medium, large). In some variations of the method, as described above, an oversized cuff may be used. The nerve cuff is then placed under the nerve with the opening into the nerve cuff facing the surgeon (FIG.22D), allowing access to the nerve and the pocket for holding the microstimulator. The microstimulator can then be inserted inside cuff (FIG.22E) while assuring that the microstimulator contacts capture the vagus, or communicate with any internal contacts/leads. The nerve cuff may then be sutured shut (FIG.22F). In some variations, the microstimulator may then be tested (FIG.22G) to confirm that the device is working and coupled to the nerve. For example, a surgical tester device, covered in a sterile plastic cover, may be used to activate the microstimulator and perform system integrity and impedance checks, and shut the microstimulator off. If necessary the procedure may be repeated to correctly position and connect the microstimulator. Once this is completed and verified, the incision may be closed (FIG.22H).

The invention may be embodied in other specific forms without departing from the essential attributes thereof; therefore, the illustrated embodiments should be considered in all respects as illustrative and not restrictive. The claims provided herein are to ensure adequacy of the present application for establishing foreign priority and for no other purpose.