SYSTEMS AND METHODS FOR THE TREATMENT OF BLADDER DYSFUNCTIONS USING NEUROMODULATION

FIELD OF THE INVENTION

This invention relates to systems and methods for stimulating nerves and/or muscles in animals, including humans, to treat bladder dysfunctions.

BACKGROUND OF THE INVENTION
I. Neuromodulation Stimulation

Neuromodulation stimulation (the electrical excitation of nerves to indirectly affect the stability or performance of a physiological system) can provide functional and/or therapeutic outcomes. While existing systems and methods can provide remarkable benefits to individuals able to be treated with neuromodulation stimulation, many limitations and issues still remain. For example, existing systems can often require the user to wear an external stimulator, which may provide a positive functional outcome, but may also negatively affect quality of life issues.

A variety of products and treatment methods are available for neuromodulation stimulation, including external and surgically implanted stimulators. As an example, neuromodulation stimulation has been used for the treatment of lower urinary tract dysfunctions, including bladder dysfunctions, which affects both men and women. In addition, a wide, range of other options exist for the restoration of bladder function. Treatments include everything from medications, devices such as catheters, and psychological counseling.

Both external and implantable devices are available for the purpose of neuromodulation stimulation for the restoration of bladder function. The operation of these devices typically includes the use of an electrode placed either on the external surface of the skin or a surgically implanted electrode. Although these modalities have shown the ability to provide a neuromodulation stimulation with some positive effects, they have received limited acceptance by patients because of their limitations of portability, limitations of treatment regimes, and limitations of ease of use and user control.

II. Bladder Function

In a healthy person, the lower urinary tract provides two functions: storage of urine (continence) and urination (micturition). During continence, the bladder is relaxed and fills with urine while the sphincter contracts to prevent leakage of urine. During micturition, the sphincter relaxes and the bladder contracts to expel urine through the urethra. Flow receptors along the urethra detect this flow of urine and send afferent (sensory) signals to the sacral spinal cord, which augments urination by decreasing (−) sphincter tone and increasing (+) efferent (motor) drive to the bladder detrusor muscle (see FIG. 1). This positive feedback continues until the urethral flow receptors no longer detect fluid flow and stop sending afferent signals to the spinal cord, resulting in relaxation of the bladder and the beginning of the next continence phase.

Continence may be restored through electrical stimulation of the dorsal genital nerve, which is a branch of the pudendal nerve. Similarly, micturition may be restored through electrical stimulation of urethra afferent nerves, which are also branches of the pudendal nerve (see FIGS. 2 and 3). Electrical stimulation of the urethral afferents can drive this positive feedback and activate the micturition circuitry in the sacral spinal cord, just as if the person was already in the process of urination. Just as in micturition in a healthy person, the sacral spinal cord would coordinate the process of urination by relaxing the sphincter and contracting the bladder to expel urine. This method has been used to empty the bladder in cats before and after spinal transection at T12 and achieve bladder contraction in humans after supra sacral spinal cord injury (SCI).

The conditions needed to evoke bladder emptying via activation of urethral afferents are known and include bladder volume, stimulation frequency, and neural circuitry. The bladder must contain more than a minimum threshold volume to initiate the micturition-like response, and the threshold volume varies markedly from individual to individual but on average is approximately 33 percent less than the volume at which the first distention-evoked contractions occur. Stimulation of the urethral afferents with frequencies between 1 and 50 Hz has been shown to evoke micturition-like responses in decerebrate and anesthetized animals. 33 Hz has been shown to be the stimulation frequency most effective in evoking sustained bladder contractions and voiding in cats, and stimulation frequencies of 20 to 40 Hz appear to be the most effective in eliciting micturition-like bladder contractions in persons with SCI. Furthermore, this frequency range has been shown to be identical to frequencies at which urethral afferents fire during urethral flow.

Stimulating urethral afferents at the appropriate frequency may evoke a micturition-like reflex if the starting bladder volume is above threshold. Electrical stimulation of urethral afferents may evoke micturition even if some of the neural circuitry is damaged or compromised (e.g., through disease or injury, including spinal cord injury). However, stimulation is more likely to be successful if the sacral spinal cord is intact because anatomical mapping and electrophysiology studies show that the sacral cord contains the spinal micturition circuitry. This is supported by observations of coordinated bladder-sphincter activity in humans with supra sacral injuries and confirmed by coordinated micturition-like activity evoked by electrical stimulation of urethra afferents before and after spinal transection (T10-T12) in cats.

III. Present Treatment Methods

The inability to empty the bladder is a significant problem that is not adequately addressed by present treatment options. Approximately 250,000 persons in the United States are living with a spinal cord injury (SCI), with approximately 10,000 more persons being spinal cord injured each year, and even more persons have damaged neural circuitry from disease or other injuries. In SCI persons, the SCI prevents the brain stem from communicating with the lower urinary tract, eliminating voluntary control of continence (urine storage) and micturition (urine evacuation). Bladder contractions become ineffective in emptying the bladder, leaving a high residual volume. The urinary system transformed by SCI typically results in additional complications such as ureteric reflux and obstruction, infection of the kidneys, long-term renal damage, episodes of autonomic dysreflexia with dangerous rises in blood pressure, bladder trabeculation, and frequent urinary tract infections.

For a person with SCI, the direct medical costs associated with urinary tract dysfunction may exceed $8,000 each year, making up a substantial component of the estimated $31,000 to $75,000 annual health care and living expenses of individuals with spinal injury. Furthermore, the loss of control of urinary function alters social relationships and can be personally demoralizing, and it can lead to depression, anger, poor self-image, embarrassment, frustration and can prevent persons from achieving their personal goals.

As previously identified, many techniques have been developed to treat lower urinary tract dysfunction brought about by SCI and other conditions. Presently, self-catheterization proves to be the best non-invasive method to care for lower urinary tract dysfunction, but many persons with lower urinary tract dysfunction sustain multiple infections per year, and persons with SCI often lack the physical ability to catheterize themselves. Alternative methods have been developed to empty the bladder by preventing the sphincter from closing the urethra, but most of them, including sphincterotomy, sphincter paralysis, and urethral stenting, leave the person incontinent and lead to further complications. Other techniques, such as balloon dilation, have a low (e.g., 15 percent) success rate, and presently, no techniques provide effective bladder emptying without the secondary consequences that limit widespread acceptance among the patient population.

There is a significant market need for providing bladder emptying with electrical stimulation. As previously stated, an estimated 250,000 persons with SCI in the United States suffer from urinary retention at an annual cost of $1.5 billion. VOCARE (FineTech Medical, UK) is the only commercially available neurostimulation system that provides bladder emptying, but it is used by less than one percent of eligible patients. It has been found that few people elect to receive the VOCARE system because it requires 1) a time-consuming (e.g., more than eight hours), invasive surgical procedure and 2) an irreversible nerve transection, resulting in the loss of sexual function and reflex defecation. The systems and methods of the present invention provide an alternative approach with several significant advantages over the VOCARE system.

The present novel invention addresses the need for a system that is simpler to implant and more acceptable to persons with bladder dysfunctions. Most potential VOCARE patients are unwilling to undergo the extensive surgery and extended inpatient hospital stay, and even fewer will consider sacrificing sexual function and reflex defecation in exchange for bladder control.

The present novel invention provides systems and methods for bladder control with a simple (e.g., less than two hour) outpatient procedure that may preserve all existing functions. Implantation of a VOCARE system requires the coordination of doctors from multiple disciplines, but the novel approach of the present invention allows the patient's regular Urologist to implant the system. Presently, it is difficult to determine how effective a VOCARE system may be prior to implantation. In comparison, the novel systems and methods include a stimulating catheter electrode (see FIG. 20A) adapted to be used as a quick (e.g., less than 15 minutes), minimally-invasive way to determine how well a patient may respond to the system before surgery. The stimulating catheter will be described further in section “V. Stimulating Catheter.” The novel systems and methods of the present invention combine bladder emptying through stimulation of urethral afferents and continence through stimulation of the dorsal genital nerve to provide complete bladder control with a simple surgical procedure that preserves all existing functions. This innovative approach may also benefit individuals with brainstem stroke or multiple sclerosis, who often do not have bladder control.

There remains a need for systems and methods that can treat lower urinary tract dysfunctions as a first line of treatment and for those who have not responded to conventional therapies, in a straightforward manner, without requiring drug therapy and complicated and irreversible surgical procedures.

SUMMARY OF THE INVENTION

The novel systems and methods of the present invention combine bladder emptying through stimulation of urethral afferents and continence through stimulation of the dorsal genital nerve to provide complete bladder control with a simple surgical procedure that preserves all existing functions.

Alternatively, at least one or more leads may activate selectively either the urethral afferent pathway to provide micturition or the genital afferent pathway to provide continence by changing stimulus parameters such as frequency, amplitude, and/or pulse width.

A stimulating catheter is provided to be used as a clinical screening tool. The stimulating catheter may be used to measure bladder pressures and stimulate the urethra at the same time.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view of sensory signals and the spinal circuitry activity that coordinates efferent and afferent nerve activity and produces bladder functions.

FIG. 2 is a lateral section view of a male pelvic girdle region.

FIG. 3 is a lateral section view of a female pelvic girdle region.

FIG. 4 is an anterior anatomic view of an exemplary embodiment of a system after implantation in a pelvic region for restoration of bladder functions.

FIGS. 5A and 5B are front and side views of one embodiment of the general purpose implantable pulse generator shown in FIG. 4, which may be powered by a primary or rechargeable battery.

FIGS. 6A and 6B are front and side views of an alternative embodiment of the general purpose implantable pulse generator as shown in FIG. 4, which may be powered by a primary or rechargeable battery.

FIG. 7 is a plane view of the implant system shown in FIG. 4, for restoration of bladder functions, showing implant depth and non-inductive wireless telemetry features.

FIGS. 8 and 9 are perspective views of the lead and electrode associated with the system shown in FIG. 4.

FIG. 10 is a side interior view of a representative embodiment of a lead of the type shown in FIGS. 8 and 9.

FIG. 11 is an end section view of the lead taken generally along line 11-11 in FIG. 10.

FIG. 12 is an elevation view, in section, of a lead and electrode of the type shown in FIGS. 8 and 9 residing within an introducer sleeve for implantation in a targeted tissue region, the anchoring members being shown retracted within the sheath.

FIG. 13 shows an anatomical view of an anterior approach for implanting a lead as part of the system shown in FIG. 4.

FIG. 14 shows a lateral section view of the anterior approach for implanting a lead, as shown in FIG. 13.

FIG. 15 shows an anatomical view of a perineal approach for implanting a lead as part of the system shown in FIG. 4.

FIG. 16 shows a lateral section view of the perineal approach for implanting a lead, as shown in FIG. 15.

FIG. 17 shows an anatomical view of a posterior approach for implanting a lead as part of the system shown in FIG. 4.

FIG. 18 shows a lateral section view of the posterior approach for implanting a lead, as shown in FIG. 17.

FIG. 19 is an anatomical view showing the implant system implanted in a pelvic region, and a clinical programmer within (or outside) the sterile field using non-inductive wireless telemetry to communicate with the implanted pulse generator.

FIG. 20A is a perspective view of a stimulating catheter adapted for urethral stimulation of both males and females.

FIG. 20A is a perspective view of stimulating catheter electrode adapted for urethral stimulation of both males and females.

FIG. 20B is a detailed plan view of an electrode secured to the catheter body of the stimulating catheter shown in FIG. 20A.

FIG. 20C is a perspective view of the stimulating catheter shown in FIG. 20A, except with an alternative configuration of electrode placement.

FIG. 21 is a cross-sectional view taken along lines 21-21 of FIG. 20A, showing a two lumen configuration used in conjunction with the stimulating catheter.

FIG. 22 is a cross-sectional view taken along lines 22-22 of FIG. 20A, showing an electrode used in conjunction with the stimulating catheter.

FIG. 23 is a lateral anatomical view showing the stimulating catheter of FIG. 20A positioned within the urethra of a human male to selectively stimulate urethral afferents.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention which may be embodied in other specific structures. While the preferred embodiment has been described, the details may be changed without departing from the invention.

I. Restoration of Bladder Function

The present novel invention provides systems and methods of bladder control to individuals with neurological disorders, including spinal cord injury (SCI), who do not have volitional control over their lower urinary tract. This lack of control results in incontinence and inability to urinate on demand, which frequently causes many serious adverse health effects. The only commercially available electrical stimulation product (VOCARE, FineTech Medical, UK) to restore full bladder control in persons with SCI includes an electrode placed on the sacral spinal motor nerves to empty the bladder. It also requires permanently severing sacral spinal sensory nerves (rhizotomy) to achieve continence.

Because this rhizotomy is irreversible and because it may result in loss of sexual function, VOCARE has not been widely accepted among the potential patient population.

The features and benefits of the present invention provide alternative neurostimulation systems and methods to restore bladder control that does not require electrode placement on the spinal nerve roots and does not require rhizotomy.

The pudendal nerve(s), their branches and/or their roots may be stimulated to restore lower urinary tract functions, including bladder emptying (urination) and/or storage (continence).

Electrical stimulation of the genital nerve(s) can provide continence, and electrical stimulation of the urethral sensory nerve(s) can provide micturition. Both of these pathways (genital and urethral) can, be activated at multiple locations and/or anatomical levels: at the most superficial level at and/or near the skin and/or urethra; at and/or near the respective urethral and/or genital nerve; at and/or near the pudendal nerve; and/or at and/or near the sacral nerve root(s).

Both the caudal and rostral portions of the urethra are innervated by urethral afferents in the cat, and both portions of the urethra are thought to be innervated by urethral afferents in the human (see FIGS. 1 to 3). One embodiment of the present invention may include stimulation of the caudal urethra because it contains the majority of the larger lamellated end-organs that act as urethral flow receptors. However, if stimulation of the caudal urethra is not effective to evoke bladder contractions, an alternative embodiment of the present invention may stimulate the rostral urethra because it is thought to contain a different type of flow receptors also known to evoke micturition-like responses in cats and humans after SCI. Or, both caudal and rostral portions of the urethra may be stimulated.

Combinations of lead placement may be used to restore bladder function. At least one or more lead(s) may activate the genital sensory pathway to produce urine storage (continence). At least one or more lead(s) may activate the urethral sensory pathway to provide bladder emptying (micturition). These lead(s) and functions may be combined to provide complete bladder control (storage and emptying) or used individually to provide either function (storage or emptying) as needed. Alternatively, at least one or more leads may activate selectively either the urethral afferent pathway to provide micturition or the genital afferent pathway to provide continence by changing stimulus parameters such as frequency, amplitude, and/or pulse width.

For example, electrical stimulation of pudendal nerve afferents differentially activates continence-like and micturition-like reflexes dependent on the frequency of stimulation. Different groups of pudendal nerve afferents can generate either inhibition or excitation of the bladder. Stimulation of genital and/or anal sensory pathways in the pudendal nerve inhibits the bladder by decreasing parasympathetic outflow in the pelvic nerve to the bladder detrusor muscle and by increasing sympathetic outflow in the hypogastric nerve. Bladder inhibition may be evoked by low frequency stimulation (e.g., 2 to 20 Hz) of pudendal nerve afferents; and inhibition may be lost during higher frequency (e.g., 35 Hz) stimulation.

Excitation of the bladder can be produced by stimulation of urethral sensory pathways over a range of stimulus frequencies. However, higher frequency (e.g., 20 to 40 Hz) stimulation may be more effective than 10 Hz stimulation at evoking bladder contractions, consistent with the firing rates of urethral afferents in response to urethral fluid flow that is capable of evoking bladder excitation.

The compound pudendal nerve contains both genital sensory (inhibitory) and urethral sensory (excitatory) pathways. Both excitatory and inhibitory pathways can be accessed at the level of the pudendal nerve and activated differentially according to stimulus frequency. Thus, it may be possible to control selectively both continence and micturition with a single electrode on a peripheral nerve (i.e. the pudendal nerve and/or its branches and/or its roots).

One embodiment of the present invention uses a lead and electrode placed in the pelvic region near pudendal urethral afferents to achieve urination and a lead and electrode placed in the pelvic region near the dorsal genital nerve to achieve continence (see FIG. 4). It is known that continence can be achieved with dorsal genital nerve stimulation. This embodiment includes a stimulator and two electrode leads adapted to combine techniques for bladder emptying and continence.

II. Implant System

An implant system may be used to provide electrical stimulation of a target nerve A and/or a target nerve B (e.g., the pudendal nerve and/or branches and/or roots, and/or the dorsal genital nerve, and/or urethral afferents), for the restoration of bladder function on demand and with a simple surgical procedure that preserves the existing anatomy. As used in this disclosure, it is to be appreciated that at least the terms “nerve”, “lead”, “electrode”, and “IPG” can include both the singular or plural meaning.

The electrical stimulation may be applied, with any type of electrical contact such as one or more leads having one or more electrodes placed in, on, around, or near any of the target nerves A and/or target nerves B named above. The lead may also include the ability to deliver medications or drugs as an adjunct to electrical stimulation. Note that the electrode may be in contact with the target nerve, or it may be some distance (on the order of centimeters) away because it does not have to be in contact with the target nerve to activate it.

Stimulation may be applied through a lead/electrode, such as a fine wire electrode, paddle electrode, intramuscular electrode, or adipose electrode, inserted via a needle introducer or surgically implanted in proximity of the target nerve. When proper placement is confirmed, as indicated by patient sensation or visible movement of related organ(s) such as the penis, scrotum, perineal muscle, perineal skin, and/or anal sphincter, (or clitoris for women), the needle may be withdrawn, leaving the electrode in place. Stimulation may also be applied through a penetrating electrode, such as an electrode array comprised of any number (e.g., greater than or equal to one) of needle-like electrodes that are inserted into the target nerve. In both cases, the lead may be placed using a needle-like introducer, allowing the lead/electrode placement to be minimally invasive.

Alternatively, stimulation may be applied through any type of nerve cuff (spiral, helical, cylindrical, book, flat interface nerve electrode (FINE), slowly closing FINE, etc.) that is surgically placed on or around a target nerve.

In all cases, the lead may exit through the skin and connect with one or more external stimulators, or the lead(s) may be routed subcutaneously to one or more implanted pulse generators (IPG), or they may be connected as needed to internal and external coils. The IPG may be located some distance (remote) from the electrode, or the IPG may be integrated with the electrode, eliminating the need to route the lead subcutaneously to the IPG.

Control of the stimulator and stimulation parameters may be provided by one or more external controllers. In the case of an external stimulator, the controller may be integrated with the external stimulator. The IPG external controller (i.e., clinical programmer) may be a remote unit that uses non-inductive radio frequency (RF) wireless communication to control the IPG. The external or implantable pulse generator may use regulated voltage (e.g., 10 mV to 20 V), regulated current (e.g., 10 μA to 50 mA), and/or passive charge recovery to generate the stimulation waveform.

The pulse may by monophasic, biphasic, and/or multi-phasic. In the case of the biphasic or multi-phasic pulse, the pulse may be symmetrical or asymmetrical. Its shape may be rectangular or exponential or a combination of rectangular and exponential waveforms. The pulse width of each phase may range between e.g., 10 μsec and 10 to the sixth power μsec.

Pulses may be applied in continuous or intermittent trains (i.e., the stimulus frequency changes as a function of time). In the case of intermittent pulses, the on/off duty cycle of pulses may be symmetrical or asymmetrical, and the duty cycle may be regular and repeatable from one intermittent burst to the next or the duty cycle of each set of bursts may vary in a random (or pseudo random) fashion. Varying the stimulus frequency and/or duty cycle may improve and/or optimize the response, and assist in preventing fatigue, warding off habituation, lessening the effects of long term potentiation or long term de-potentiation, because of the stimulus modulation.

The stimulating frequency may range from e.g., 1 to 300 Hz, and the frequency of stimulation may be constant or varying. In the case of applying stimulation with varying frequencies, the frequencies may vary in a consistent and repeatable pattern or in a random (or pseudo random) fashion or a combination of repeatable and random patterns that may be cycles through.

The stimulation pulses could be applied to a left target nerve and a right target nerve with different parameters, or the stimulation pulses could be applied to different branches of the same target nerve at different parameters, such as different frequencies, to provide the best response. For example, the left target nerve A could be stimulated at 25 Hz, and the right target nerve A could be stimulated at 30 Hz.

By way of an additional non-limiting example, 20 Hz may be used for all stimulation or 10 Hz may be used for target A stimulation and 40 Hz may be used for target B stimulation, and, target A may be stimulated at 2 mA and target B may be stimulated at 0.050 mA or vice versa, or both target A and target B may be stimulated at the same amplitude.

FIG. 4 shows an exemplary embodiment of an implant system 10 for the restoration of bladder function in animals, including humans. It is to be appreciated that multiple implant system configurations are possible. As non-limiting examples, a single IPG 18 may be coupled to a single lead 12 to unilaterally stimulate a single target nerve (either A or B); or a single IPG may be coupled to two leads to bilaterally stimulate a single target nerve (either A or B); or a single IPG may be coupled to two leads to unilaterally stimulate a target nerve A and target nerve B; or two IPGs may be implanted, each being coupled to a single lead to bilaterally stimulate a single target nerve (either A or B); or two IPGs may be implanted, each being coupled to a single lead to unilaterally stimulate a target nerve A and target nerve B; or two IPGs may be implanted, each being coupled to two leads to bilaterally stimulate a target nerve A and a target nerve B. It is to be appreciated that additional system configurations exist.

Referring to FIG. 4, the system 10 includes at least one implantable lead 12 having a proximal end and a distal end, the distal end being coupled to an implantable pulse generator or IPG 18. The lead 12 and the implantable pulse generator 18 are shown implanted within a pelvic region of a human or animal body, although other implant sites are possible.

In the embodiment shown, the distal end of the lead 12 includes at least one electrically conductive surface, which will in shorthand be called an electrode 16. The electrode 16 may be implanted in electrical conductive contact with at least a target nerve A and/or a target nerve B. The implantable pulse generator 18 includes a connection header 14 that desirably carries a plug-in receptacle 15 (connector) for the distal end of the lead 12 (see FIGS. 5A and 5B). In this way, the lead electrically connects the electrode 16 to the implantable pulse generator 18.

The implantable pulse generator 18 may be sized and configured to be implanted subcutaneously in tissue, desirably in a subcutaneous pocket, which can be remote from the electrode 16, as FIG. 4 shows. Desirably, the implantable pulse generator 18 may be sized and configured to be implanted using a minimally invasive surgical procedure.

The lead 12 and electrode 16 are sized and configured to be implanted percutaneously in tissue, and to be tolerated by an individual during extended use without pain or discomfort. The comfort is both in terms of the individual's sensory perception of the electrical waveforms that the electrode applies, as well as the individual's sensory perception of the physical or mechanical presence of the electrode and lead. In the case of the mechanical presence, the lead 12 and electrode 16 are desirably “imperceptible.”

In particular, the lead 12 and electrode 16 are sized and configured to reside with stability in the lower pelvic region of the body (see FIG. 4). It has been discovered that, when properly placed in this region, one or more lead/electrode(s) are uniquely able to deliver electrical stimulation current to a target nerve A and/or a target nerve B to treat bladder dysfunction.

FIGS. 5A and 5B, and 6A and 6B, show multiple embodiments of an implantable pulse generator 18 of the present invention, and will be described in greater detail later. The implantable pulse generator 18 includes a circuit 20 that generates electrical stimulation waveforms. An on-board, primary or rechargeable battery 22 desirably provides the power. The implantable pulse generator 18 also desirably includes an on-board, programmable microcontroller 24, which carries embedded code. The code expresses pre-programmed rules or algorithms under which the desired electrical stimulation waveforms are generated by the circuit 20. The implantable pulse generator 18 may also include an electrically conductive case 26, which can also serve as the return electrode for the stimulus current introduced by the lead/electrode when operated in a monopolar configuration.

The pulse generator 18 may be sized and configured to be implanted subcutaneously in tissue at an implant depth of between about five millimeters and about twenty millimeters, desirably in a subcutaneous pocket remote from the electrode 16 (see FIG. 7) and using a minimally invasive surgical procedure. This implant depth may change due to the particular application, or the implant depth may change over time based on physical conditions of the patient. As shown in FIG. 4, the implantation site can comprise a more medial tissue region in the lower abdomen. There, the pulse generator 18 can reside for extended use without causing pain and/or discomfort and/or without effecting body image. Alternatively, the implantation site can comprise a tissue region on the posterior hip, for example.

The implant system 10 may include an external patient controller 80 (or controller-charger when a rechargeable battery is used). The patient controller 80 may be sized and configured to be held or worn by the individual to transcutaneously activate and deactivate and/or modify the output of the pulse generator 18. The patient controller 80 may, e.g., be a simple magnet that, when placed near the site where the pulse generator 18 is implanted, toggles a magnetic switch within the implantable pulse generator 18 between an on condition and an off condition, or advances through a sequence of alternative stimulus modes pre-programmed by the clinician into the implantable pulse generator 18.

Alternatively, and as can be seen in FIGS. 4 and 7, the patient controller 80 may comprise more sophisticated circuitry that would allow the individual to make these selections through RF (Radio Frequency) wireless telemetry communications (rather that an inductively coupled telemetry) that passes through the skin and tissue within an arm's length distance from the implanted pulse generator, e.g., the controller 80 may be capable of communicating with the pulse generator 18 approximately three to six feet away from the implanted pulse generator (and the pulse generator may be able to communicate with the controller).

The wireless telemetry 82 provides reliable, bidirectional communications with a patient controller-charger and a clinical programmer, for example via an RF link in the 402 MHz to 405 MHz Medical Implant Communications Service (MICS) band per FCC 47 CFR Part 95, or other VHF/UHF low power, unlicensed bands.

With the use of the patient controller 80, the wireless link 82 allows a patient to control certain parameters of the implantable pulse generator within a predefined limited range. The parameters may include the operating modes/states, increasing/decreasing or optimizing stimulus patterns, or providing open or closed loop feedback from an external or internal sensor or control source. The wireless telemetry 82 also desirably allows, the user to interrogate the implantable pulse generator 18 as to the status of its internal battery 22 (either primary or rechargeable). The full ranges within these parameters may be controlled, adjusted, and limited by a clinician, so the user may not be allowed the full range of possible adjustments.

In one embodiment, the patient controller 80 may be sized and configured to couple to a key chain. It is to be appreciated that the patient controller 80 may take on any convenient shape, such as a ring on a finger, or a watch on a wrist, or an attachment to a belt, for example. The patient controller may also use a magnetic switch to enable the user to turn the IPG on/off.

The clinical programmer 52 may be used by a clinician to program the pulse generator 18 with a range of preset stimulus parameters. The user may then turn the implant system On/Off using the wireless patient controller 80. The patient controller 80 may be then programmed by the pulse generator, i.e., the range of or a subset of the preset stimulus parameters previously downloaded by the clinical programmer 52 may be uploaded to the controller 80. This range of preset stimulus parameters allows the user to make adjustments to the stimulus strength within the preset range. Stimulation may be delivered at a level that may be initially set at or above the sensory threshold of the user, but is not uncomfortable. The user may get accustomed to the stimulation level, and may adjust the stimulation up or down within the preset range.

According to its programmed rules, when switched on, the implantable pulse generator 18 generates prescribed stimulation waveforms through the lead 12 and to the electrode 16. These waveforms stimulate a target nerve A and/or a target nerve B in a manner that achieves the desired physiologic response.

Using the controller 80, the individual may turn on or turn off the bladder function control waveforms at will or adjust the waveforms to achieve the desired functional restoration result. As previously discussed, bladder function is just one example of a functional restoration result. Additional examples of desirable therapeutic (treatment) or functional restoration indications will be described in section “VI. Representative Indications.”

The system 10 desirably includes means for selectively varying the frequency or range of frequencies for a variable duration at which the stimulation waveforms are applied by the one or more electrodes 16. By modulating the frequency and/or duration of the stimulation waveform, the same system components and placement of electrodes can serve to achieve markedly different physiologic responses, and in addition, reduce habituation.

The shape of the pulse waveform can vary as well. It can, e.g., be a typical square pulse, or possess a ramped shape, rectangle, exponential, and/or some combination. The pulse, or the rising or falling edges of the pulse, can present various linear, exponential, hyperbolic, or quasi-trapezoidal shapes. The stimulation waveform can be continuous, or it can be variable and change cyclically or in step fashion in magnitude and waveform over time.

In a non-limiting exemplary embodiment, the stimulus waveforms may include a variable frequency for a variable duration (e.g., a first stimulation at 20 Hz for 2 seconds, then 30 Hz for 3 seconds, then 25 Hz for 1 second, and so on), intermittent stimulation (apply stimulation in bursts separated by pauses in stimulation (e.g., stimulation for 3 seconds, rest for 2 seconds, repeat, and so on). The stimulus waveforms may also include a continuously or intermittently applied duty cycle of pulses. This may be considered the same as changing the frequency but it also refers to 1) the duration of bursts of stimulation and 2) the duration of pauses between the bursts. For example, a variable duty cycle for intermittent pulses may include stimulation with 10 pulses, then off for 500 milliseconds, stimulation with 15 pulses, then off for 750 milliseconds, stimulation with 5 pulses, then off for 2 seconds, and it could keep going in this variable pattern.

The stimulus waveforms may also include stimulation at different amplitudes and different frequencies. Thus, amplitude and/or frequency modulation may be used to control and/or improve the response. Varying the amplitude may also provide another form of anti-habituation control, allowing a bladder function (e.g., micturition) to be more complete than if a target nerve was stimulated at a constant amplitude. Amplitude modulation may also more realistically recreate the varying level of fiber activation that occurs during urination.

The patient controller 80 and/or a clinical programmer 52, for example, may include a manual-actuated switch or control knob which an operator operates or tunes to acquire a desired waveform frequency, given the desired physiologic response.

As previously described, FIG. 4 shows an exemplary embodiment of a system 10 adapted for the functional restoration of bladder function. The assembly includes at least one implantable lead 12 and electrode 16 coupled to at least one implantable pulse generator or IPG 18. The lead 12 and the implantable pulse generator 18 are shown implanted within a pelvic region of a human or animal body.

Desirably, the components of the implantable pulse generator 18 are sized and configured so that they can accommodate several different indications, without major change or modification (see FIGS. 5A to 6B). Examples of components that desirably remain unchanged for different indications include the case 26, the battery 22, the microcontroller 24, much of the software (firmware) of the embedded code, the power management circuitry 40, and the stimulus power supply, both of which are part of the circuitry 20. Thus, a new indication may require only changes to the programming of the microcontroller 24. Most desirably, the particular code may be remotely embedded in the microcontroller 24 after final assembly, packaging, and sterilization of the implantable pulse generator 18.

Certain components of the implantable pulse generator 18 may be expected to change as the indication changes. For example, due to differences in leads and electrodes, the connection header 14 and associated receptacle(s) for the lead may be configured differently for different indications. Other aspects of the circuit 20 may also be modified to accommodate a different indication; for example, the stimulator output stage(s), sensor(s) and/or sensor interface circuitry. In addition, the case size may change due to a different header configuration and/or a desire to increase or decrease the battery size or capacity (compare FIGS. 5A and 5B to 6A and 6B).

In this way, the implantable pulse generator 18 accommodates implanting in diverse tissue regions and also accommodates coupling to at least one lead 12 and an electrode 16 having diverse forms and configurations, again depending upon the therapeutic or functional effects desired. For this reason, the implantable pulse generator can be considered to be general purpose or “universal.”

The implantable pulse generator 18 may be of the type described in co-pending U.S. patent application Ser. No. 11/517,056, filed Sep. 7, 2006, and entitled “Implantable Pulse Generator Systems and Methods for Providing Functional and/or Therapeutic Stimulation of Muscles and/or Nerves and/or Central Nervous System Tissue,” which is incorporated herein by reference. The pulse generator 18 includes a circuit that generates electrical stimulation waveforms. An on-board battery 22 (primary or rechargeable) provides the power. The pulse generator 18 also includes an on-board, programmable microcontroller 24, which carries embedded code. The code expresses pre-programmed rules or algorithms under which the desired electrical stimulation waveforms are generated by the circuit. The small metal case (e.g., titanium and/or titanium 23) of the pulse generator may also serve as the return electrode for the stimulus current introduced by the lead/electrode when operated in a monopolar configuration.

The functional elements of the implantable pulse generator 18 (e.g., circuit 20, the microcontroller 24, the battery 22, and the connection header 14) are integrated into a small, composite case 26. Referring to FIGS. 5A and 5B, the case of the pulse generator 18 defines a small cross section; e.g., desirably about (5 mm to 10 mm thick)×(15 mm to 40 mm wide)×(40 mm to 60 mm long), and more desirably about (7 mm to 8 mm thick)×(25 mm to 35 mm wide)×(45 mm to 55 mm long). The pulse generator also defines a generally pear-shaped case. The generally pear-shaped case can be described as including a bottom portion defining a curved surface having a radius, inwardly tapering sides, and a top portion being generally flat, as shown in FIGS. 5A and 5B. This geometry provides a case including a larger end (bottom portion) and a smaller end (top portion) and allows the smaller end of the case to be placed into the skin pocket first, with the larger end being pushed in last. The shape and dimensions of the pulse generator 18 produce a volume of approximately seven to nine cubic centimeters, and more desirably about eight cubic centimeters, and a weight of approximately seventeen grams.

In an alternative embodiment seen in FIGS. 6A and 6B, the case of the pulse generator 18 defines a small cross section; e.g., desirably about (7 mm to 13 mm thick)×(45 mm to 65 mm wide)×(30 mm to 50 mm long), and more desirably about (9 mm to 11 mm thick)×(50 mm to 60 mm wide)×(35 mm to 45 mm long). The pulse generator also defines a generally oval-shaped case. The generally oval-shaped case can be described as consisting generally of two congruent semicircles and two equal and parallel lines. The shape and dimensions of the pulse generator 18 produce a volume of approximately fifteen to nineteen cubic centimeters, and more desirably about seventeen cubic centimeters, and a weight of approximately twenty-seven grams.

The pulse generator 18 can deliver a range of stimulation parameters to the lead 12 and electrode 16, e.g., output current ranges of about 0.1 mA to about 20 mA, pulse duration ranges of about 0.1 microseconds to about 500 microseconds, frequency ranges of about one pulse per second to about 130 pulses per second, and duty cycle ranges from about zero to about 100 percent. The delivered stimulus may be an asymmetric biphasic waveform with zero net DC (direct current).

The implantable pulse generator 18 desirably incorporates circuitry and/or programming to assure that the implantable pulse generator 18 may suspend stimulation, and perhaps fall-back to only very low rate telemetry, and eventually suspends all operations when the battery 22 has discharged the majority of its capacity (i.e., only a safety margin charge remains). Once in this dormant mode, the implantable pulse generator may provide limited communications and may be in condition for replacement if a primary battery is used, or it must be recharged.

When a rechargeable battery is used, the battery desirably has a capacity of as small as 30 mA-hr and up to about 120 mA-hr or more, and recharging of the rechargeable battery may be required less than weekly. When the rechargeable battery has only a safety margin charge remaining, it can be recharged in a time period of not more than six hours.

The patient controller 80 may also be belt or clothing worn and used to charge the rechargeable batteries of the pulse generator 18 as needed. Charging may be achieved via an inductive RF link using a charge coil on or near the skin in close proximity to the IPG. The patient controller 80 may also be configured to provide the user with information on pulse generator battery status and stimulus levels.

The implantable pulse generator 18 desirably includes a lead connection header 14 (see FIGS. 5A to 6B), for connecting the lead(s) 12 that may enable reliable and easy replacement of the lead/electrode, and includes a small antenna 27 for use with the wireless telemetry feature.

The connection header (top header) 14 may be easy to use, reliable, and robust enough to allow multiple replacements of the implantable pulse generator after many years (e.g., more than ten years) of use. The surgical complexity of replacing an implantable pulse generator is usually low compared to the surgical complexity of correctly placing the implantable lead 12/electrode 16 in proximity to the target nerve/tissue and routing the lead 12 to the implantable pulse generator. Accordingly, the lead 12 and electrode 16 desirably has a service life of at least ten years with a probable service life of fifteen years or more. Based on the clinical application, the implantable pulse generator may not have this long a service life. The implantable pulse generator service life may largely be determined by the power capacity of the Lithium Ion battery 22, and is likely to be three to ten years, based on the usage of the device. Desirably, the implantable pulse generator 18 has a service life of at least three years.

As described above, the implantable pulse generator preferably uses a laser welded titanium case. As with other active implantable medical devices using this construction, the implantable lead(s) 12 connect to the implantable pulse generator through a molded or cast polymeric connection header 14. Metal-ceramic or metal-glass feed-thrus maintain the hermetic seal of the titanium capsule while providing electrical contact to the electrical contacts of the lead 12/electrode 16.

The standard implantable connectors may be similar in design and construction to the low-profile IS-1 connector system (per ISO 5841-3). The IS-1 connectors have been in use since the late 1980s and have been shown to be reliable and provide easy release and re-connection over several implantable pulse generator replacements during the service life of a single pacing lead. Full compatibility with the IS-1 standard, and mating with pacemaker leads, is not a requirement for the implantable pulse generator.

The implantable pulse generator connection system may include a modification of the IS-1 connector system, which shrinks the axial length dimensions while keeping the format and radial dimensions of the IS-1. For application with more than two electrode conductors, the top header 14 may incorporate one or more connection receptacles each of which accommodate leads with typically four conductors. When two or more leads are accommodated by the header, these leads may exit the connection header in opposite directions (i.e., from opposite sides of the header), as seen in FIGS. 6A and 6B.

These connectors can be similar to the banded axial connectors used by other multi-polar implantable pulse generators or may follow the guidance of the draft IS-4 implantable connector standard. The design of the implantable pulse generator housing and header 14 preferably includes provisions for adding the additional feed-thrus and larger headers for such indications.

The inclusion of the antenna 27 for the wireless telemetry inside the connection header 14 may be necessary as the shielding offered by the titanium case may severely limit (effectively eliminate) radio wave propagation through the case. The antenna 27 connection may be made through a feed-thru similar to that used for the electrode connections. Alternatively, the wireless telemetry signal 82 may be coupled inside the implantable pulse generator onto a stimulus output channel and coupled to the antenna 27 with passive filtering/coupling elements/methods in the connection header 14.

III. Features of the Lead and Electrode

A. Implantation in Pelvic Region

The lead 12 and electrode 16 are sized and configured to be inserted into and to rest in the targeted tissue region in the lower pelvic region without causing pain or discomfort or impact body image. Desirably, the lead 12 and electrode 16 can be inserted using the small (e.g., smaller than 16 gauge) introducer sleeve 32 with minimal tissue trauma. The lead 12 and electrode 16 are formed from a biocompatible and electrochemically suitable material and possess no sharp features that can irritate tissue during extended use. Furthermore, the lead 12 and electrode 16 possess mechanical characteristics including mechanical compliance (flexibility) along their axis (axially), as well as perpendicular to their axis (radially), and unable to transmit torque, to flexibly respond to dynamic stretching, bending, and crushing forces that can be encountered in this body region without damage or breakage, and to accommodate relative movement of the pulse generator coupled to the lead 12 without imposing force or torque to the electrode 16 which tends to dislodge the electrode.

Furthermore, one embodiment of a lead 12 and electrode 16 may also include an anchoring means 70 for providing retention strength to resist migration within or extrusion from the targeted tissue region in response to force conditions normally encountered during periods of extended use (see FIGS. 8 and 9). In addition, the anchoring means 70 is desirably sized and configured to permit the electrode 16 position to be adjusted easily during insertion, allowing placement at the optimal location where unilateral or bilateral stimulation of a target nerve A and/or a target nerve B occurs. The anchoring means 70 functions to hold the electrode at the implanted location despite the motion of the tissue and small forces transmitted by the lead due to relative motion of the connected pulse generator due to changes in body posture or external forces applied to the abdomen. However, the anchoring means 70 should allow reliable release of the electrode 16 at higher force levels, to permit withdrawal of the implanted electrode 16 by purposeful pulling on the lead 12 at such higher force levels, without breaking or leaving fragments, should removal of the implanted electrode 16 be desired.

B. The Lead

FIGS. 8 to 11 show a representative embodiment of a lead 12 that provide the foregoing features. The implantable lead 12 comprises a molded or extruded component 72, which encapsulates one or more stranded or solid wire elements 74, and includes the connector 62 (shown in FIG. 12). The wire element may be bifilar, as shown in FIG. 11, and may be constructed of coiled MP35N nickel-cobalt wire or wires that have been coated in polyurethane. In a representative embodiment with two electrically conductive surfaces 16 (as described below), one wire element 74 may be coupled to the distal electrode 16 and the pin 62A of the connector 62. A second wire element 74 may be coupled to the proximal electrode 16 and the ring 62B on the connector 62. The molded or extruded lead 12 can have an outside diameter ranging between about 0.05 mm to about 5.0 mm, and as small as about one (1) mm, and desirably about 1.9 mm. The lead 12 may also include an inner lumen 13 having a diameter about 0.2 millimeters to about 0.5 millimeters, and desirably about 0.35 millimeters. The lead 12 may be approximately 10 cm to 40 cm in length, although the lead may be shorter or longer, depending on the target nerve to be stimulated and the anatomy of the patient. The lead 12 provides electrical continuity between the connector 62 and the electrode 16.

The coil's pitch can be constant or, as FIG. 10 shows, the coil's pitch can alternate from high to low spacing to allow for flexibility in both compression and tension. The tight pitch may allow for movement in tension, while the open pitch may allow for movement in compression.

A standard IS-1 or similar type connector 62 at the proximal end provides electrical continuity and mechanical attachment to the pulse generator 18. The lead 12 and connector 62 all may include provisions (e.g., lumen 13) for a guidewire that passes through these components and the length of the lead 12 to the conductive electrode 16 at the distal end.

C. The Electrode

The electrode 16 may comprise one or more electrically conductive surfaces. Two conductive surfaces are show in FIGS. 8 and 9. The two conductive surfaces can be, used either A) as one two individual stimulating (cathodic) electrodes in a monopolar configuration using the metal case of the pulse generator 18 as the return (anodic) electrode or B) either the distal or proximal conductive surface as a individual stimulating (cathodic) electrode in a monopolar configuration using the metal case of the pule generator 18 as the return (anodic) electrode or C) in bipolar configuration with one electrode functioning as the stimulating (cathodic) electrode and the other as the return (anodic) electrode.

In general, bipolar stimulation is more specific than monopolar stimulation—the area of stimulation is much smaller—which may be good if the electrode 16 is close to the target nerve. But if the electrode 16 is farther from the target nerve, then a monopolar configuration could be used because with the pulse generator 18 acting as the return electrode, activation of the nerve may be less sensitive to exact placement than with a bipolar configuration.

In use, a physician may first attempt to place the electrode 16 close to the target nerve so that it could be used in a bipolar configuration, but if bipolar stimulation failed to activate the target nerve, then the electrode 16 could be switched to a monopolar configuration. Two separate conductive surfaces on the electrode 16 provide an advantage because if one conductive surface fails to activate the target nerve because it is too far from the nerve, then stimulation with the second conductive surface could be tried, which might be closer to the target nerve. Without the second conductive surface, a physician would have to reposition the electrode to try to get closer to the target nerve.

The electrode 16, or electrically conductive surface or surfaces, can be formed from PtIr (platinum-iridium) or, alternatively, 316L stainless steel. Each electrode 16 possess a conductive surface of approximately 10 mm²-20 mm²and desirably about 16.5 mm². This surface area provides current densities up to 2 mA/mm²with per pulse charge densities less than about 0.5 μC/mm². These dimensions and materials deliver a charge safely within the stimulation levels supplied by the pulse generator 18.

Each conductive surface has an axial length in the range of about three to five millimeters in length and desirably about four millimeters. When two or more conductive surfaces are used, either in the monopolar or bipolar configurations as described, there may be an axial spacing between the conductive surfaces in the range of 1.5 to 2.5 millimeters, and desirably about two millimeters.

D. The Anchoring Means

In the illustrated embodiment (see FIGS. 8 and 9), the lead may be anchored by anchoring means 70 specifically designed to secure the electrode 16 in tissue in electrical proximity to the target nerve, with or without the support of muscle tissue. The anchoring means 70 takes the form of an array of shovel-like paddles or scallops 76 proximal to the proximal-most electrode 16 (although a paddle 76 or paddles could also be proximal to the distal most electrode 16, or could also be distal to the distal most electrode 16). The paddles 76 as shown and described are sized and configured so they may not cut or score the surrounding tissue. It is to be appreciated that anchoring means are not a requirement for the present invention.

The paddles 76 are desirably present relatively large, generally planar surfaces, and are placed in multiple rows axially along the distal portion of lead 12. The paddles 76 may also be somewhat arcuate as well, or a combination of arcuate and planar surfaces. A row of paddles 76 comprises two paddles 76 spaced 180 degrees apart. The paddles 76 may have an axial spacing between rows of paddles in the range of six to fourteen millimeters, with the most distal row of paddles 76 adjacent to the proximal electrode, and each row may be spaced apart 90 degrees. The paddles 76 are normally biased toward a radially outward condition into tissue.

In this condition, the large surface area and orientation of the paddles 76 allow the lead 12 to resist dislodgement or migration of the electrode 16 out of the correct location in the surrounding tissue. In the illustrated embodiment, the paddles 76 are biased toward a proximal-pointing orientation, to better resist proximal migration of the electrode 16 with lead tension. The paddles 76 are desirably made from a polymer material, e.g., high durometer silicone, polyurethane, or polypropylene, bonded to or molded with the lead 12.

The paddles 76 are not stiff, i.e., they are generally pliant, and can be deflected toward a distal direction in response to exerting a pulling force on the lead 12 at a threshold axial force level, which may be greater than expected day-to-day axial forces. The paddles 76 are sized and configured to yield during proximal passage through tissue in result to such forces, causing minimal tissue trauma, and without breaking or leaving fragments, despite the possible presence of some degree of tissue in-growth. This feature permits the withdrawal of the implanted electrode 16, if desired, by purposeful pulling on the lead 12 at the higher axial force level.

Desirably, and as previously described, the anchoring means 70 may be prevented from fully engaging body tissue until after the electrode 16 has been deployed. The electrode 16 may not be deployed until after it has been correctly located during the implantation (installation) process.

More particularly, and as previously described, the lead 12 and electrode 16 are intended to be percutaneously introduced through the sleeve 32 shown in FIG. 12. As shown, the paddles 76 assume a collapsed condition against the lead 12 body when within the sleeve 32. In this condition, the paddles 76 are shielded from contact with tissue. Once the location is found, the sleeve 32 can be withdrawn, holding the lead 12 and electrode 16 stationary. Free of the sleeve 32, the paddles 76 spring open to assume their radially deployed condition in tissue, fixing the electrode 16 in the desired location. In the radially deployed condition, the paddles have a diameter (fully opened) of about four millimeters to about six millimeters, and desirably about 4.8 millimeters.

The lead has two ink markings 54, 55 to aid the physician in its proper placement. The most distal marking 20 (about 11 cm from the tip) aligns with the external edge of the introducer sleeve 32 when the tip of the lead is at the tip of the sleeve 32. The more proximal marking 21 (about 13 cm from the tip) aligns with the external edge of the sleeve 32 when the introducer has been retracted far enough to expose the tines 76. A central lumen 13 allows for guidewire 94 insertion and removal to facilitate lead placement. A funnel 95 may be included to aid in inserting the guidewire 94 into the lumen 13 in the lead 12.

The anchoring means 70 may be positioned about 10 millimeters from the distal tip of the lead, and when a second anchoring means 70 is used, the second anchoring means 70 may be about 20 millimeters from the distal tip of the lead.

The position of the electrode 16 relative to the anchoring means 70, and the use of the sleeve 32, allows for both advancement and retraction of the electrode delivery sleeve 32 during implantation while simultaneously delivering test stimulation. The sleeve 32 can be drawn back relative to the lead 12 to deploy the anchoring means 70, but only when the physician determines that the desired electrode location has been reached. The withdrawal of the sleeve 32 from the lead 12 causes the anchoring means 70 to deploy without changing the position of electrode 16 in the desired location (or allowing only a small and predictable, set motion of the electrode 16). Once the sleeve 32 is removed, the flexible, silicone-coated or polyurethane-coated lead 12 and electrode 16 are left implanted in the tissue.

IV. Implantation Methodology

There are at least three alternative methods for placing one or more lead/electrode(s) near one or more target nerves, and each are described below. The patient may undergo monitored anesthesia care (MAC), which is a planned procedure during which the patient undergoes local anesthesia together with sedation and analgesia. During MAC, the patient is sedated and amnestic but always remains responsive when stimulated to do so. Local anesthesia—e.g., 1% Lidocaine (2-5 ccs) or equivalent—may be injected prior to making the anticipated lead 12 incision site 60. The patient preparation may be the same for all implantation methods. Although the lateral views show the male anatomy, similar approaches may also be used in the female.

A. Anterior Approach

Referring the FIGS. 13 and 14, the site for the lead insertion 60 is desirably located midline or near-midline, over the pubic symphysis aiming toward the clitoris (or the base of the penis in males).

Once local anesthesia is established, a needle/introducer may be advanced percutaneously into the anesthetized site 60 to a depth of about five centimeters to about seven centimeters necessary to reach the target site between the pubic symphysis and the clitoris in females, or the base of the penis in males, to stimulate a target nerve(s) (e.g., dorsal genital nerves). The needle/introducer may then be replaced with a lead 12 threaded through the initially inserted sheath or needle. It is to be appreciated that this approximate insertion depth may vary depending on the particular anatomy of the patient. The physician may use one hand to guide the lead 12 and the other hand to hold surrounding tissue to stabilize the area. Once the lead 12 is positioned, it may be coupled to a test stimulator to apply stimulation waveforms through the lead 12 and electrode 16 concurrent with positioning of the electrode 16 to confirm the desired location.

B. Perineal Approach

Referring to FIGS. 15 and 16, the site for the lead insertion 60 may be perpendicular to the skin into the anesthetized site 60 located behind the scrotum as shown or lateral to the scrotum or near the base of the penis (e.g., lateral or posterior to the penis base). A similar approach may also be used in the female.

Once local anesthesia is established, a needle/introducer may be advanced percutaneously into the anesthetized site 60 to a target depth necessary to reach the target site along the urethra to stimulate a target nerve(s) (e.g., urethral afferents). The needle/introducer may then be replaced with a lead 12 threaded through the initially inserted sheath or needle. It is to be appreciated that insertion depths may vary depending the particular anatomy of the patient. The physician may use one hand to guide the lead 12 and the other hand to hold surrounding tissue to stabilize the area. Once the lead 12 is positioned, it may be again coupled to a test stimulator to apply stimulation waveforms through the lead 12 and electrode 16 concurrent with positioning of the electrode 16 to confirm the desired location.

C. Posterior Approach

The user may be placed in a lateral decubitus position with their back, hips and legs flexed. Referring the FIGS. 17 and 18, the site for the lead insertion 60 may be approximately 2 cm lateral and 2 cm caudal to the midpoint of a line defined between the posterior superior iliac spine and the ischical tuberosity.

Once local anesthesia is established, a needle/introducer may be advanced percutaneously into the anesthetized site 60 to a target depth necessary to reach the target site (e.g., at, along side of, and/or near Alcock's canal) to stimulate a target nerve(s) (e.g., pudendal nerves). The proximity of the needle tip to the pudendal nerve may be minimized through successively finer adjustments of the stimulus amplitude (e.g., an initial current of 3 mA, a pulse width of 0.1 sec. and a frequency of 2 Hz, for example), and electrode tip position, until external anal sphincter twitches can be evoked with stimuli less than 1 mA, for example. The needle/introducer may then be replaced with a lead 12 threaded through the initially inserted sheath or needle. It is to be appreciated that insertion depths may vary depending on the particular anatomy of the patient. The physician may use one hand to guide the lead 12 and the other hand to hold surrounding tissue to stabilize the area. Once the lead 12 is positioned, it may be again coupled to a test stimulator to apply stimulation waveforms through the lead 12 and electrode 16 concurrent with positioning of the electrode 16 to confirm the desired location.

V. Stimulating Catheter

A stimulating catheter 150 may be used as a clinical screening tool to identify appropriate candidates for the bladder function restoration system (see FIGS. 20A through 23). If a subject's stimulating catheter test demonstrates that urethral stimulation may be able to empty the bladder, then a fine wire lead known in the art (or a lead 12 as shown and described) would be implanted near the urethra in close proximity to the urethral afferents using one of the described approaches. Similarly, another fine wire lead (or a lead 12 as shown and described) may be placed near the dorsal genital nerve. After implantation of one or more leads, the subject would be sent home for a predetermined test period (e.g., a week) with the percutaneous leads connected to an external pulse generator (not shown).

For this test period, an external pulse generator can be used of the type described in U.S. Pat. No. 7,120,499, issued Oct. 10, 2006, and entitled “Portable Percutaneous Assemblies, Systems, and Methods for Providing Highly Selective Functional or Therapeutic Neurostimulation,” which is incorporated herein by reference. Optionally, an external pulse generator can be used of the type described in co-pending U.S. patent application Ser. No. 11/595,556, filed Nov. 10, 2006, and entitled “Portable Assemblies, Systems, and Methods for Providing Functional or Therapeutic Neurostimulation,” which is also incorporated herein by reference.

If the home trial provides functional results, e.g., prevents the patient from leaking between voids, and achieves a residual post-void bladder volume of a predetermined amount (e.g., less than 50 ml), then the patient may proceed to receive a fully implanted system, including an implantable pulse generator (IPG) to evaluate continence and emptying in the home environment over a longer period (e.g., 3 to 6 months). In contrast to the implantation of the VOCARE system on the sacral spinal roots which requires a time consuming and invasive laminectomy, the present systems and methods may allow urologists to place the lead/electrode(s) near the target nerve(s) easily and reliably because the urethra and genitals are an area in which urologists are comfortable and familiar.

During the first period of stimulation, the subjects may be in “continence mode” as their bladder fills, using dorsal genital nerve stimulation via a first lead to remain dry. When they are ready to urinate, they may press a button on their external controller to switch into “micturition mode” to empty their bladder with urethral afferent stimulation via a second lead. When they are finished urinating, they may press the other button on the external stimulator to switch back into “continence mode.”

The idea of stimulating the urethra is known, but the stimulating catheter 150 provides a unique combination of features. The stimulating catheter 150 is adapted to be used to measure bladder pressures and stimulate the urethra at the same time. Previously, bladder pressure was measured with one catheter, and another catheter-like lead, similar to a deep brain stimulation lead, which was placed alongside it to provide the stimulation. This arrangement is cumbersome for clinicians and provides less accurate information about the location of stimulation because the stimulating lead can move relative to the urethra.

As can be seen in FIG. 20A, the novel stimulating catheter 150 has a balloon 152 that may be inflated in the bladder neck that secures the catheter and one or more stimulating electrodes 154 in place so it does not move within the urethra. The stimulating catheter 150 as shown has multiple electrodes 154 along its length (e.g., 17 electrodes are shown) that can stimulate the urethra. This means once the catheter 150 is in place, it does not have to be moved again until it is removed. This is a crucial feature because movement inside the urethra can activate urethral afferents, which are the very fibers that need to be screened. Thus, movement of the stimulating catheter 150 along the urethra can confound the screening and also lead to unwanted elicitation of reflexes such as a reflex bladder spasm or contraction.

Multiple stimulating electrodes 154 placed along the catheter body 160 allow the stimulating catheter 150 to be able to stimulate different portions of the urethra without having to move the catheter inside the urethra once the catheter 150 is in place. Each electrode 154 may be secured to the catheter body with an adhesive 155 (see FIG. 20B), which also serves to provide a smooth transition from the catheter body 160 to an edge of an electrode 154. The electrodes 154 near the proximal portion 162 of the catheter body 160 are generally spaced about 1.0 cm to 2.0 cm apart, and more desirably about 1.5 cm apart, and the electrodes 154 near the distal portion 164 are generally spaced about 0.1 cm to 1.0 cm apart, and more desirably about 0.5 cm apart.

FIG. 20C shows an alternative configuration of electrodes 154. More than one configuration provides for flexibility depending on the patients anatomy. In FIG. 20C, fifteen electrodes 154 are shown. The electrodes 154 near the proximal portion 162 of the catheter body 160 are generally spaced about 1.0 cm to 2.0 cm apart, and more desirably about 1.5 cm apart, and the electrodes 154 near the distal portion 164 are generally spaced about 0.1 cm to 1.0 cm apart, and more desirably about 0.5 cm apart. An electrode free gap 156 may be provided between the higher concentration of electrodes near the distal portion 164 and the electrodes near the proximal portion 162. The gap 156 may be about 5 cm to 7 cm, and more desirably about 6 cm.

The multiple electrodes 154 are adapted to enable urethral stimulation to elicit bilateral activation of the urethral afferents. The multiple electrodes permit bipolar stimulation and ensure that one electrode may be located within a short distance (e.g. one cm or less) of the portion of the urethra most sensitive to electrical stimulation. Animal studies have shown the caudal urethra to be the most sensitive because electrical stimulation of the caudal urethra evoked the largest compound nerve action potentials in urethral afferents and sustained bladder contractions most consistently with the lowest stimulation amplitudes compared to other urethral locations.

The stimulating catheter 150 may also be used in both men and women. The higher concentration of electrodes 154 near the distal portion 164 of the catheter body 160 serves to most effectively stimulate the shorter urethra in women (generally about two to four cm long), and a large number of electrodes 154 along the length of the catheter body 160 are designed to accommodate urethras of longer lengths, and the higher concentration of electrodes 154 may be placed to stimulate the most well innervated portions of the urethra in either a man or a woman.

The balloon 152 may also be wedge shaped which may help prevent leakage around the balloon and may allow iso-volumetric measurements. This feature allows the stimulating catheter 150 to be used to analyze bladder contractions at the same volume without having to re-fill the bladder after each bladder contraction. This may be beneficial for at least two reasons: 1) it takes time to fill the bladder, and in order to make the procedure of analyzing responses to urethral stimulation a practical out-patient procedure, the total time needs to be kept down to about one to two hours, and having to re-fill the bladder after each bladder contraction would take too long (e.g., more than two hours), and 2) it makes the screening more robust and the results simpler and easier to analyze because the bladder reflexes are time and, history dependent. This means that every fill has an effect on each of the following bladder contractions, meaning that evoking bladder contractions and filling between bladder contractions to replace the leaked volume is not the same as evoking iso-volumetric bladder contractions without filling between each contraction.

Additionally, the stimulating catheter has a coude (curved) tip 158 which enables it to be inserted in men with enlarged prostates (see FIG. 20A). Without the curved tip 158, it would be nearly impossible to place the stimulating catheter in most men with enlarged prostates. The stimulating catheter body 160 may be small in diameter (e.g., twelve Fr), meaning that after the balloon 152 is deflated in the bladder neck, the rest of the catheter body 160 may not obstruct the urethra and may allow for voiding (around the catheter body) to be monitored.

The catheter body 160 is desirably a dual lumen body having a proximal portion 162 and a distal portion 164. The first lumen 166 extends from a fitting 168 near the proximal end 162 to the balloon 152 near the distal end 164, and carries an insulated solid or stranded wire element 170 for each electrode 154 (see FIGS. 21 and 22). The first lumen 166 also serves as a path for fluid flow (i.e., saline or distilled water) to fill and drain the balloon 152. The fitting 168 may be adapted to be connected to a fluid pump. Alternatively, a third lumen may be provided to serve as the balloon fill lumen.

The wire elements 170 for each electrode 154 are carried in an extension 176 which extends from the first lumen 166 to a connector 178. The connector 178 then couples to a computer system or external pulse generator, for example, to provide selective stimulation to the multiple electrodes 154.

The second lumen 172 extends from a fitting 174 near the proximal end 162 to an opening 176 near the catheter body tip 158, and serves as a path for fluid flow to fill the bladder, and to measure fluid pressure. The fitting 174 may be adapted to be connected to a fluid pump and pressure transducer. The bladder is typically filled with a saline solution, and the solution may contain a contrast medium to allow viewing of the bladder filling using fluoroscopy.

VI. Representative Indications

Due to its technical features, the implant system 10 can be used to provide beneficial results in diverse therapeutic and functional restorations indications.

For example, in the field of urology or urologic dysfunctions, possible indications for use of the implant system includes the treatment of (i) urinary and fecal incontinence; (ii) micturition/retention; (iii) restoration of sexual function; (iv) defecation/constipation; (v) pelvic floor muscle activity; and/or (vi) pelvic pain.

The foregoing is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described. While the preferred embodiment has been described, the details may be changed without departing from the invention.

Number	Date	Country
60931263	May 2007	US
60578742	Jun 2004	US
60578742	Jun 2004	US
60599193	Aug 2004	US
60680598	May 2005	US

	Number	Date	Country
Parent	11891074	Aug 2007	US
Child	12601195		US

	Number	Date	Country
Parent	11149654	Jun 2005	US
Child	11891074		US
Parent	11150418	Jun 2005	US
Child	11891074		US
Parent	11290268	Nov 2005	US
Child	11891074		US
Parent	11729333	Mar 2007	US
Child	11290268		US

SYSTEMS AND METHODS FOR THE TREATMENT OF BLADDER DYSFUNCTIONS USING NEUROMODULATION

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CPC

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Abstract

Description

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RELATED APPLICATION

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

PCT Information

Provisional Applications (5)

Continuations (1)

Continuation in Parts (4)