Electrical stimulation system and method for pelvic disorder rehabilitation and treatment

Abstract

An implantable stimulation system is provided having a stimulation unit coupled to a programmable controller, a stimulation circuit, and an electrode array disposed on a pair of flexible blades for selectively stimulating at least one pelvic nerve, such as a cavernous nerve. The implantable stimulation system may be programmed to run a first sequence of stimulation pulses, the first stimulation pulse sequence corresponds to a first pattern for inducing a rapid erection reaction to achieve sexual behavior and potential ejaculation, a second pattern for inducing a rapid erection reaction sufficient to facilitate a medical procedure, such as applying a catheter, a third neurological rehabilitation stimulation pattern for restoring neurotransmission to treat urinary incontinence and / or intestinal dysfunction, and / or a fourth penis rehabilitation pattern for reducing penis fibrosis. A method of operating the system is also provided.

Description

[0001] Cross Reference to Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 487,859, filed March 1, 2023, the entirety of which is incorporated herein by reference. This application is also related to U.S. Patent Application No. 18 / 264,753, filed August 8, 2023, which claims priority to PCT / IB2022 / 051127 (Publication No. WO2022 / 172157), filed February 8, 2022, which claims priority to U.S. Patent Application No. 17 / 450,392, filed October 8, 2021, U.S. Patent Application No. 17 / 174,033, filed February 11, 2021, now U.S. Patent No. 11,141,590, and U.S. Patent Application No. 17 / 174,021, filed February 11, 2021, now U.S. Patent No. 11,141,589, the entirety of each of which is incorporated herein by reference. TECHNICAL FIELD

[0003] The present invention relates to an improved implantable electrical stimulation system and method for treating and preventing pelvic disorders such as sexual disorders, for example, erectile dysfunction, erectile dysfunction after prostatectomy, and erectile dysfunction associated with spinal cord injury. The present system can also be used for cavernous nerve rehabilitation, reducing penile fibrosis, treating urinary incontinence, and / or treating intestinal dysfunction. BACKGROUND

[0004] Sexual disorders (e.g., sexual dysfunction, sexual dysfunction) are complications experienced by an individual (male or female) or couple during any phase of normal sexual activity, including erection, physical gratification, desire, preference, sexual arousal, or orgasm. Sexual dysfunction often has a profound impact on an individual’s quality of life. The most common sexual disorders are erectile dysfunction (ED) and female sexual arousal disorder (FSAD).

[0005] Penile erection is a coordinated neurovascular response. See Dean RC and Lue TF, "Physiology of penile erection and pathophysiology of erectile dysfunction" (Urol Clin North Am., Nov 2005; 32(4): 379-95). In the flaccid state, the penile smooth muscle is in tonic contraction, allowing only a small amount of blood flow for nutritional purposes. When sexual stimulation triggers the release of neurotransmitters (primarily nitric oxide) from the cavernosal nerve endings, the penis becomes erect. The neurotransmitters cause relaxation of the smooth muscle cells in the cavernosal arterioles and sinuses, resulting in an increase in blood flow into the penis. This causes the cavernosal sinuses to fill with blood and expand against the tunica albuginea, partially occluding the venous outflow, resulting in an erection.

[0006] ED is a multi-factorial disease with multiple etiologies and can be psychogenic, vasculogenic, hormonal, or neurogenic in origin. However, studies have shown that neurogenic and vasculogenic causes are the most prevalent. Generally, the primary mechanisms leading to ED are either a failure of neuronal response (e.g., prostatectomy, cystectomy, abdominoperineal resection, spinal cord injury, or diabetes) or an increase in smooth muscle tone and / or contractility within the cavernosal and penile arteries (e.g., hypertension, atherosclerosis, and diabetes). See Sadeghi-Nejad H. "Penile prosthesis surgery: a review of prosthetic devices and associated complications" (Sex Med., Mar 2007; 4(2): 296-309).

[0007] Prostatectomy is known to cause severe ED. This important surgical procedure is often used to treat prostate cancer, but it often results in ED because the neural pathways for erectile function are inevitably disrupted. These endometrial nerves are located around the prostate and can be damaged during the procedure. Currently, surgeons attempt to perform nerve-sparing procedures; however, in real-world scenarios, it is shocking that 70% of patients who undergo prostatectomy will experience ED. See Penson DF, McLerran D, Feng Z, Li L, Albertsen PC, Gilliland FD, Hamilton A, Hoffman RM, Stephenson RA, Potosky AL, Stanford JL. "5-year urinary and sexual outcomes after radical prostatectomy: results from the Prostate Cancer Outcomes Study" (J Urol. 2008 May; 179(5 Suppl):S40-4).

[0008] Current drug treatments are available for ED. These drugs (e.g., sildenafil, (Viagra); tadalafil, (Cialis) or vardenafil, (PDE-5) to enhance the effects of the neurotransmitter nitric oxide. See Rotella DP. "Phosphodiesterase 5 inhibitors: current status and potential applications" (Nat Rev Drug Discov., 2002 Sep; 1(9): 674-82). PDE-5 is an enzyme responsible for the breakdown of intracellular second messenger cGMP, which is generated in response to NO stimulation. cGMP is involved in the regulation of some protein-dependent kinases that can relax smooth muscle cells and facilitate erection. Thus, patients with impaired erectile neurologic response do not respond well to such drugs. An alternative for these patients is the intracavernosal injection of vasodilators, which can produce direct erections independent of the neural pathway. See Leungwattanakij S, Flynn V Jr, Hellstrom WJ "Intracavernosal injection and intraurethral therapy for erectile dysfunction" (Urol Clin North Am., 2001 May; 28(2): 343-54) and Harding LM, Adeniyi A, Everson R, Barker S, Ralph DJ, Baranowski AP "Comparison of a needle-free high-pressure injection system with needle-tipped injection of intracavernosal alprostadil for erectile dysfunction" (Int J Impot Res., 2002 Dec; 14(6): 498-501). Alprostadil (prostaglandin E1, PGE1) is the most commonly used vasodilator for ED. See Harding and Eardley I, Donatucci C, Corbin J, El-Meliegy A, Hatzimouratidis K, McVary K, Munarriz R, Lee SW "Pharmacotherapy for erectile dysfunction" (J Sex Med., 2010 Jan; 7(1 pt 2): 524-40).Vasodilators can be injected into the corpora cavernosa with a needle and are effective in more than 80% of patients. See Harding. Common side effects of intracavernous injection are penile pain, bleeding, hematoma, penile priapism, and penile fibrosis, which can lead to permanent ED. See Leungwattanakij.

[0009] Another option for these patients is penile implants, which consist of a pair of malleable or inflatable rods implanted surgically into the penile erectile chambers. See Sadeghi-Nejad. Penile prostheses are of different types (rigid, semi-rigid, or inflatable) and all of these prostheses usually require irreversible, destructive surgery with the risk of intra- and post-operative complications. This prosthesis often requires surgical repair. However, due to the lack of better treatment options, prosthesis implantation is a common surgery. Therefore, it is clear that there is a need for better therapeutic strategies to treat ED caused by nerve pathway failure, such as post-prostatectomy ED, providing a painless, safe, easier, non-invasive, and more effective alternative.

[0010] A number of studies have shown that stimulation of the cavernous nerve can induce and maintain erection in animals and men. See Lue TF, Schmidt RA, Tanagho EA "Electrostimulation and penile erection" (Urol Int., 1985; 40(1): 60-4); Shafik A, Shafik AA, Shafik IA, El Sibai 0. "Percutaneous perineal electrostimulation induces erection: clinical significance in patients with spinal cord injury and erectile dysfunction" (J Spinal Cord Med., 2008; 31(1): 40-3); and Shafik A, el-Sibai 0, Shafik AA "Magnetic stimulation of the cavernous nerve for the treatment of erectile dysfunction in humans" (Int J Impot Res., 2000 Jun; 12(3): 137-41). Since then, electrical nerve stimulation for erectile response has been considered an option for patients undergoing prostatectomy. However, an obstacle to the development of this technology is the complex anatomy of the human cavernous nerve. See Klotz L. "Intraoperative cavernous nerve stimulation during nerve sparing radical prostatectomy: how and when?" (Curr Opin Urol., 2000 May; 10(3): 239-43) and Ponnusamy K, Sorger JM, Mohr C. "Nerve mapping for prostatectomies: novel technologies under development" (J Endourol., J Endourol. 2012 Jul; 26(7): 769-77). It is difficult to locate the optimal site for electrical nerve stimulation because the human cavernous nerve reaches the penis from the pelvic plexus through a complex anastomosis. Furthermore, there is significant anatomical variation in the location of the cavernous nerve; the pelvic plexus is a transparent veil with tiny nerves, and the distribution of the cavernous nerve is not uniform in every man. Furthermore, the anatomy, stage of disease, and location of the cancer are unique for each patient.Overall, these obstacles make it extremely difficult to identify the cavernous nerve segments for selective stimulation.

[0011] In some previously known systems, the localization and identification of the cavernous nerve is performed during the implantation procedure. For example, U.S. Patent No. 4,585,005 to Lue claims to identify and isolate the cavernous nerve prior to implantation. U.S. Patent No. 7,328,068 to Spinelli describes a method for stimulating penile nerve pathways that requires precise positioning of the implant for optimal stimulation. In Spinelli, neurophysiological monitoring assessment can be used as a method to locate the optimal stimulation site prior to implantation. U.S. Patent No. 7,330,762 to Boveja discloses a system for electrical nerve stimulation of the cavernous nerve, including different types of electrodes such as spiral electrodes, cuff electrodes, steroid-eluting electrodes, wrap-around electrodes, and hydrogel electrodes. Again, the Boveja system requires determination of the optimal stimulation site prior to implantation. U.S. Patent No. 7,865,243 to Whitehurst describes a system and method for stimulating the cavernous nerve; however, anatomical identification of the pudendal nerve and / or other nerves to be stimulated must be performed prior to implantation.

[0012] Recently, significant progress has been made in implementing a practical neuroelectrical stimulation system for treating ED that enables post-implantation localization and identification of the cavernous nerve. For example, U.S. Patent No. 9,821,163 and U.S. Patent No. 10,300,279 to Fragada Silva et al., invented by the inventors of the present application, describe a neuroelectrical stimulation system in which electrodes are stimulated post-implantation to empirically determine a preferred electrode excitation configuration to achieve sexual arousal. While the inventions described in these patents represent significant progress in using neuroelectrical stimulation to treat ED, it would be desirable to provide a method for reliably determining an electrode excitation configuration for producing arousal, in which the electrode excitation configuration can be determined by an automated process.

[0013] After bilateral nerve-sparing radical prostatectomy, some patients can recover from erectile dysfunction, especially younger patients without a history of ED or related risk factors. However, even if the individual regains erectile function, it often takes a long period of time, possibly years. During the recovery period, permanent penile injury can occur, resulting in some permanent ED.

[0014] Recent advances in the understanding of the pathophysiology of post-prostatectomy ED have fueled debate about the management of this condition, leading to the emergence of the concept of penile rehabilitation after prostatectomy ENREF_30. See, e.g., Wang, R. “Penile rehabilitation after radical prostatectomy: where do we stand and where are we going?” (J Sex Med, 2007, 4(4 Pt 2): 1085-97); Segal, R. L. et al. “Current penile-rehabilitation strategies: Clinical evidence,” (Arab J Urol, 2013, 11(3): 230-6); Gandaglia, G. et al. “Penile rehabilitation after radical prostatectomy: does it work?” (Transl Androl Urol, 2015, 4(2): 110-23); Clavell-Hernandez, J. et al. “Penile rehabilitation following prostate cancer treatment: review of current literature” (Asian J Androl, 2015, 17(6): 916-22). The rationale for this approach is that long-term inability to achieve an erection leads to fibrosis in the body, deterioration of the penile structure, and progressive worsening of ED, leading to a permanent state of ED.

[0015] As discussed in the aforementioned literature references, the regular cycle of penile erection is essential for the maintenance of penile function and tissue oxygenation in healthy men. In fact, physiologic nocturnal penile tumescence and spontaneous erections during sleep play a crucial role in maintaining organ oxygenation and function. Conversely, as described in Gandaglia; Muller, A. et al. “The effect of hyperbaric oxygen therapy on erectile function recovery in a rat cavernous nerve injury model” (J Sex Med, 2008, 5(3):562-70), long-term inability to achieve erection leads to chronic penile hypoxia and, in turn, fibrotic cytokines. This adverse local penile environment leads to increased apoptosis and collagen production, altering the cavernosal architecture. See, e.g., Gandaglia; Moreland, R. B. “Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence” (Int J Impot Res, 1998, 10(2): 113-20).

[0016] As further discussed in the literature references above, penile rehabilitation is defined as the use of any medical intervention or combination of interventions at or after prostatectomy with the goal of increasing penile blood flow and improving oxygenation in the body to avoid or reduce fibrosis until the ability to achieve natural erectile function is restored. The penile rehabilitation treatment preferably should be applied until neuroregeneration is achieved, which can take 12-18 months or even years after prostatectomy. Currently, the most advanced techniques require oral PDE5 inhibitors, in vivo injection therapies (e.g. alprostadil), vacuum erection devices or a combination of these treatments. See Mulhall, J.P. et al. “Standard operating procedure for the preservation of erectile function outcomes after radical prostatectomy” (J Sex Med, 2013, 10(1): 195-203); and Fode, M. et al. “Penile rehabilitation after radical prostatectomy: what the evidence really says” (BJU Int, 2013, 112(7): 998-1008). Overall, clinical trials reports using these methods show little or no improvement. See Clavell-Hernandez; Fode.

[0017] Furthermore, the reproductive capacity of patients with spinal cord injury (SCI) is considered lost or severely impaired. See Beretta, G. et al. "Reproductive Aspects in Spinal Cord Injured Males" (Paraplegia 27 (1989): 113-18). Paraplegic male infertility is determined by two main factors: (1) most SCI patients are unable to ejaculate; and (2) even if ejaculation is possible, the characteristics of the semen are always abnormal. Most SCI males have severely impaired fertility, characterized by erectile dysfunction (ED), ejaculatory dysfunction, and semen abnormalities. See Brackett, N.L. et al. "Treatment of Infertility in Men with Spinal Cord Injury" (Urology 7 (2010): 162-72). Specifically, the semen of SCI males has a unique semen profile characterized by normal sperm count but abnormally low motility and viability. Despite the abnormalities, the sperm of SCI males can successfully induce pregnancy. For some couples, a simple intra-vaginal insemination method is a viable option. Another option is intrauterine insemination (IUI), which effectiveness increases with the total number of motile sperm. In cases of very low total number of motile sperm, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are yet another option. For SCI males, penile vibratory stimulation (PVS) is recommended as a first-line treatment method for inducing ejaculation because it is simple to operate and safe enough to be used at home after a short training period. Patients who fail PVS can be considered for electro-stimulated ejaculation, in which a probe is inserted into the rectum and an electric current is delivered through the probe to induce ejaculation. If this method is not feasible, the physician can perform a prostate massage, trying to mechanically push the sperm out through the ejaculatory duct system by inserting a finger into the rectum to press the prostate and seminal vesicles. As a last resort, when other methods fail, surgical sperm retrieval can be considered. Therefore, methods of assisted ejaculation should be used before methods that bypass ejaculation because the former are less invasive and produce a higher total number of motile sperm than the latter. Higher total number of motile sperm production expands the options for assisted conception methods.

[0018] The drawback of using surgical retrieval as the first option is that it requires the couple to undergo IVF / ICSI, which is the most invasive and expensive of all assisted reproduction treatments. In contrast, the semen of SCI men usually has sufficient numbers of motile sperm to consider the option of IUI or even intra-vaginal insemination. It is recommended to consider intra-vaginal insemination or IUI before proceeding to assisted reproduction techniques such as IVF / ICSI. The reality of having a very high chance of becoming a biological father can have a positive impact on the couple’s relationship and improve the quality of life. See Ibrahim, E. et al. “Male Fertility Following Spinal Cord Injury: An Update” Andrology 4 (2016): 13-26. Comparing baseline semen characteristics with those after 3 months of PVS repeated once a week, higher sperm concentration, stronger forward motility, and decreased abnormal sperm morphology were found. See Trofimenko, V. et al. “Fertility Treatment in Spinal Cord Injury and Other Neurologic Disease” Translational Andrology and Urology 5(1) (2016): 102-116. Another study conducted on SCI patients showed that patients with antegrade ejaculation had improved sperm penetration ability, semen volume, and fructose content in the seminal plasma after receiving PVS once a week for 4-6 months, which suggested an improvement in the function of the seminal vesicles and prostate. While the above semen retrieval methods represent a significant improvement in the fertility of SCI men, there is still a need to find a method for inducing ejaculation and improving sperm motility to enhance the chances of SCI men becoming biological fathers and improving their quality of life.

[0019] Another complication that can occur after prostatectomy or after spinal cord injury is urinary incontinence due to injury to one or more nerves that control the lower urinary tract (pelvic parasympathetic, hypogastric sympathetic, and pudendal nerves). Electrical stimulation can be used to treat neurogenic bladder dysfunction. The following techniques are used: transrectal / transvaginal electrical stimulation, transcutaneous electrical nerve stimulation (TENS), and sacral neuromodulation. Electropelvic floor stimulation (EPFS) can improve urinary incontinence. Early EPFS was performed with external stimulation devices such as anal and / or vaginal electrodes, but these devices had several side effects, including current leakage from the device to the applied mucosa, which could cause pain or mucosal damage during stimulation.

[0020] The primary cause of urinary incontinence after prostatectomy has been described as due to sphincter insufficiency. Currently, pelvic floor muscle training (PFMT) is the most widely recommended non-invasive method for preventing post-radical prostatectomy urinary incontinence. However, it can take several months of time to recover from incontinence and some patients can continue to have incontinence despite continued rehabilitation. "Electrical stimulation of the pudendal nerve and its branches can produce direct reflex responses of the urethra and the pelvic floor striated muscles." Yamanishi, T. et al., "Pelvic floor electrical stimulation in the treatment of stress incontinence: an investigational study and a placebo controlled double-blind trial" (The Journal of urology vol., 158, 6 (1997): 2127-31). Studies have shown that low intensity electrical stimulation of the pelvic floor can promote nerve regeneration and thus help improve urinary function after radical prostatectomy.See Yamanishi, Tomonori, et al. "Randomized, placebo controlled study of electrical stimulation with pelvic floor muscle training for severe urinary incontinence after radical prostatectomy." The Journal of urology vol. 184, 5 (2010): 2007-12; Mariotti, Gianna, et al. "Early recovery of urinary continence after radical prostatectomy using early pelvic floor electrical stimulation and biofeedback associated treatment." The Journal of urology vol. 181, 4 (2009): 1788-93; Yokoyama, Teruhiko, et al. "Comparative study of effects of extracorporeal magnetic innervation versus electrical stimulation for urinary incontinence after radical prostatectomy." Urology vol. 63, 2 (2004): 264-7. Spinal cord injury patients also typically face bowel function issues.

[0021] In view of the foregoing shortcomings of previously known systems and methods, there is a need for systems and methods that can be used to identify the location of the cavernous nerves in an organized manner during implantation and / or after implantation and to determine optimal parameters for different activation patterns. There is also a need for systems and methods that can be used after prostatectomy to increase tissue oxygenation and maintain penile function to reduce fibrosis and to regenerate the cavernous nerves. There is also a need for systems and methods that can be used to treat other pelvic diseases such as urinary incontinence. SUMMARY

[0022] The present disclosure provides neuroelectrical stimulation systems and methods for treating sexual disorders, including patients who are unable to spontaneously obtain penile erection (e.g., erectile dysfunction (ED), including ED associated with neuronal response failure, such as post-prostatectomy ED) and patients with female sexual arousal disorder (FSAD), wherein optimization of electrode excitation configuration and stimulation parameters is achieved without extensive empirical testing.

[0023] Electrical stimulation systems for treating sexual disorders (e.g., ED) in patients can include an implantable stimulation unit, an external patient controller, and an external physician controller, as described in U.S. Patent Nos. 9,821,163 and 10,300,279. The entire contents of which are incorporated herein by reference. The implantable stimulation unit includes an electrode array disposed on an implantable plate and a power source, which can be rechargeable.

[0024] In accordance with the principles of the present invention, the programmable controller of the implantable stimulation unit is preprogrammed with a routine for optimizing the selection of a subset of the excitation electrode array and stimulation parameters to be applied to generate a fast erectile response, to restore nerve transmission in the corpora cavernosa after implantation, and / or to reduce penile fibrosis. The preprogrammed routine can also be subsequently activated after tissue healing following the implantation procedure to re-optimize the selection of the excitation electrode subset and / or adjust the stimulation parameters employed in a first fast response mode, a second neuro-rehabilitation mode, or a third penile rehabilitation mode.

[0025] In a preferred embodiment, the implantable stimulation unit includes an electrode array disposed on a pair of flexible paddles sized and shaped to be implanted at the pelvic plexus for selectively stimulating at least one of the cavernosal nerves. The electrode array on each of the pair of paddles is coupled to a programmable controller including a stimulation circuit, a non-volatile memory, and a microprocessor coupled to the stimulation circuit and the non-volatile memory. In accordance with an aspect of the present invention, the programmable controller is preprogrammed to execute an excitation electrode routine that selectively scans the electrode array on the paddles in at least two directions and in at least two regions with a series of directional currents to optimize the electrode selection for use in stimulating the cavernosal nerves of the patient.

[0026] Once the electrode selection configuration process is complete, the identification of the preferred subset of the electrode array ("excitation electrodes") is defined and stored in the non-volatile memory of the programmable controller. Thereafter, the stored electrode configuration and optimized stimulation parameters are employed to stimulate one or more nerves of the pelvic plexus, such as at least one of the cavernosal nerves, sufficient to elicit sexual arousal, such as an erection. The stimulation regimen can be composed of stimulation parameters including pulse duration, frequency, voltage, and current, and can be adjusted post-implantation by the external physician controller and / or the external patient controller.

[0027] In a preferred embodiment, the programmable controller initiates a preprogrammed electrode configuration process to cause the stimulation circuit to selectively activate a first series of electrode pairs of the electrode array to generate a first current flow between the first series of electrode pairs in a first direction to stimulate the cavernous nerves and elicit a first erectile response. Subsequently, the electrode configuration process selectively activates a second series of electrode pairs of the electrode array to generate a second current flow between the second series of electrode pairs in a second direction, which can be different from the first direction and oblique with respect to the first direction, to stimulate the cavernous nerves and elicit a second erectile response. The first and second erectile responses are then compared, for example by a physician, to select which of the first and second directional current flows provides a more favorable erectile response to determine a preferred current flow direction, which can be stored in the non-volatile memory for future stimulation. The programming instructions can identify the preferred erectile response in response to input generated by a sensor system associated with the programmable controller or in response to input provided by an external patient controller or an external physician controller.

[0028] Next, the programmable controller causes the stimulation circuit to selectively activate a subset of the electrode array using the previously determined preferred current flow direction to stimulate the cavernous nerves in at least a first region and a second region. Specifically, a first subset of the electrode array in the first region is stimulated to generate a first region response, and a second subset of the electrode array in the second region, which is different from the first region, is stimulated to generate a second region response. The first region response and the second region response are compared to determine which response is more favorable, and those corresponding regions of the electrodes are selected as preferred stimulation regions and stored in the non-volatile memory for future stimulation.

[0029] The programmable controller then causes the stimulation circuit to sequentially activate subsets of the electrodes within the preferred stimulation regions using the previously determined preferred current flow direction to elicit a series of erectile responses. The series of erectile responses are compared to determine which response is more favorable, and those corresponding subsets of the electrodes are selected as preferred stimulation electrodes and stored in the non-volatile memory for future stimulation.

[0030] Once the preferred stimulation region, including the preferred stimulation electrode with a directed current flow, is determined, the programmable controller selectively activates the stimulation circuitry to define at least a first stimulation mode in which the applied electrical stimulation elicits a rapid erectile response. Specifically, the programmable controller causes the stimulation circuitry to successively apply first and second stimulation protocols with different stimulation parameters, thereby eliciting first and second stimulation responses. The patient physician or patient can then compare the first response to the second response to determine which stimulation protocol produces a stronger and / or faster erectile response, and select that stimulation protocol as the preferred first stimulation mode and store it in the non-volatile memory. In a preferred embodiment, the system of the present application can include an external controller that the patient can actuate, e.g., by pressing a button, in a "on-demand" mode to activate the implantable stimulation unit to elicit a rapid erectile response.

[0031] According to another aspect of the present application, the programmable controller can also determine a second neuro-rehabilitation stimulation mode that corresponds to a lower current intensity than the first stimulation mode. For example, the neuro-rehabilitation stimulation mode can have a set of stimulation parameters that apply a current amplitude in the range of 0.1 to 2 mA at a frequency between 10 to 48 Hz and a pulse width between 0.01 to 1.0 msec, while the first stimulation mode can be a set of stimulation parameters that apply a current amplitude in the range of 0.5 to 25 mA at a frequency between 10 to 48 Hz, a pulse width between 0.1 to 1.0 msec. The neuro-rehabilitation stimulation mode is designed to improve the transmission of neural activity along the at least one cavernosal nerve. The programmable controller can be programmed to automatically execute the neuro-rehabilitation stimulation pulse sequence at least once a day, and more preferably at one or more specified times (e.g., just prior to the patient waking up).

[0032] According to another aspect of the present application, the programmable controller can also provide a third penile rehabilitation stimulation mode that corresponds to a higher current intensity than the second stimulation mode. For example, the penile rehabilitation stimulation mode can have a set of stimulation parameters that apply a current amplitude in the range of 0.5 to 25 mA at a frequency between 10 to 48 Hz, a pulse width between 0.1 to 1.0 msec. The penile rehabilitation mode is designed to induce at least partial penile tumescence to increase tissue oxygenation and reduce the risk of penile fibrosis. The programmable controller can be coupled to a sensor that monitors the degree of penile tumescence, and the programming instructions can store the set of stimulation parameters that generate the highest degree of penile tumescence as the optimal set of stimulation parameters. The programmable controller can be programmed to automatically execute the penile rehabilitation stimulation pulse sequence at least once a day, and more preferably at one or more specified times (e.g., just prior to the patient waking up). The neuro-rehabilitation stimulation mode and the penile rehabilitation stimulation mode can be automatically and separately executed at least once a day following prostatectomy.

[0033] In addition, in accordance with the principles of the present application, the programmable controller can be programmed to reactivate the recruitment electrode configuration process and optionally select the first, second, and / or third stimulation modes weeks or months after the implantation procedure is completed. In this manner, the selection of the preferred recruitment electrodes and / or stimulation protocol can be re-optimized to account for healing responses of the tissue surrounding the implantable stimulation unit, for example, to address tissue encapsulation. In addition, such re-optimization programming can allow the system of the present application to capture improvements in neural transmission achieved by the neuro-rehabilitation stimulation mode, such as to elicit a rapid erectile response at a lower current intensity than initially required after implantation. Such adjustments can be made under the control of the physician or the patient. Alternatively, at least one of machine learning or other forms of artificial intelligence can be used to make adjustments to the recruitment electrode configuration and / or stimulation protocol of the first, second, and / or third stimulation modes.

[0034] The external patient controller can be configured to selectively activate the implantable stimulation unit to actuate the recruitment electrode configuration process in response to patient input, and / or to refine the stimulation protocol employed in the first, second, and / or third stimulation modes to selectively actuate the first stimulation mode as needed, and to set parameters such as activation time(s) and duration of the rehabilitation stimulation mode. The external physician controller is configured to provide similar capabilities, including selectively activating the recruitment electrode configuration process to revise and / or re-optimize the electrode configuration and stimulation protocol stored in the non-volatile memory. The external physician controller preferably also provides the ability to interrogate the implantable stimulation unit to recover other operational data regarding the status and use of the implantable stimulation unit.

[0035] The implantable stimulation unit and the external patient controller preferably communicate wirelessly. Thus, the implantable stimulation unit can include a first transceiver and the external patient controller can include a second transceiver. The first and second transceivers can employ IEEE 802.11 or BLUETOOTH TM communication protocols. The wireless communication between the first and second transceivers can be encrypted. The external patient controller can be specifically designed for communication with the implantable stimulation unit, or can be a smartphone, laptop, tablet, or smartwatch that is programmed to communicate with the implantable stimulation unit.

[0036] The implantable stimulation unit and the external physician controller also preferably communicate wirelessly, and the external physician controller can include a third transceiver. The first and third transceivers can employ IEEE 802.11 or BLUETOOTH TMThe communication scheme, and the wireless communication between the first and third transceivers, can be encrypted. The external physician controller can be specifically designed for communication with the implantable stimulation unit, or can be a smartphone, laptop, tablet, or desktop computer programmed to communicate with the implantable stimulation unit.

[0037] The flexible paddles carrying the electrode arrays are preferably sized and shaped to conform to the anatomical shape of a portion of the pelvic plexus, and more preferably are implanted via laparoscopy. In one embodiment, each flexible paddle has a hemispherical shape that conforms to one half of the pelvic plexus to provide bilateral stimulation. Each paddle includes an array of at least two rows and two columns of individually addressable electrodes. Each paddle can also include one or more features, such as suture holes or anchors, configured to maintain the paddle in contact with the pelvic plexus after a radical prostatectomy. The anchors can be sutures or biocompatible glue, for example. Alternatively or additionally, each flexible paddle can include at least one opening designed to allow connective tissue to grow in and / or through the paddle to anchor the paddle near the pelvic plexus.

[0038] Methods for implanting the implantable stimulation unit, methods for programming the implantable stimulation unit to configure the preferred stimulating electrodes, electrode regions, current directions, and stimulation schemes to cause a rapid erectile response, restore neural transmission, or reduce penile fibrosis, and methods for using the system are also provided herein. The implantable stimulation unit and the flexible paddles can be sized and shaped for implantation using a robotic guided surgery system or laparoscopically.

[0039] According to another aspect of the present invention, the system can be used to treat urinary incontinence by, for example, electrically stimulating one or more nerves of the lower urinary tract. Electrical stimulation of the pelvic floor can promote nerve regeneration and thus aid in improving urinary function after a radical prostatectomy. In particular, low intensity stimulation can reestablish neural function by promoting axonal regeneration and reinnervation.

[0040] The programmable controller can cause the stimulation circuit to activate a pair of electrodes in the electrode array to stimulate at least one nerve associated with control of the bladder sphincter muscle, such as the pudendal nerve, hypogastric sympathetic nerve, or pelvic parasympathetic nerve, to promote rehabilitation of the nerve. The bladder nerve rehabilitation stimulation pattern can have a set of stimulation parameters that apply a current amplitude in the range of 0.1 to 2 mA, a frequency in the range of 10 to 48 Hz, and a pulse width in the range of 0.01 to 1 millisecond, and can be automatically performed for at least one hour per day after a prostatectomy.

[0041] The flexible paddle can also include a second array of electrodes disposed on a second side opposite the first side. The programmable controller can cause the stimulation circuit to activate a pair of electrodes in the second array of electrodes to stimulate at least one nerve associated with control of the urinary sphincter muscle.

[0042] Also provided herein are methods of treating urinary incontinence using the above-described systems. For example, the method can include implanting a flexible paddle having a first array of electrodes disposed on a first side and a second array of electrodes disposed on a second side adjacent to the pelvic plexus, coupling a programmable controller to the arrays of electrodes, and executing programming instructions stored in the memory to cause the stimulation circuit to activate a pair of electrodes on the first and / or second array of electrodes to stimulate at least one nerve associated with control of the urinary sphincter muscle.

[0043] According to another aspect of the present disclosure, an implantable system for treating a pelvic disorder is provided. The system can include a flexible paddle having an array of electrodes disposed on a first side, the flexible paddle configured to be disposed adjacent to a pelvic plexus of a patient, and a programmable controller including a stimulation circuit, a microprocessor, and a memory, the stimulation circuit operably coupled to the array, and the microprocessor configured to execute programming instructions stored in the memory to cause the stimulation circuit to activate at least one pair of electrodes in the array to stimulate at least one nerve, to promote healing of the at least one nerve. The programming instructions can cause the stimulation circuit to activate at least once per day.

[0044] For example, the microprocessor can be configured to execute programming instructions stored in the memory to cause the stimulation circuit to activate at least one pair of electrodes in the array to stimulate at least one nerve associated with control of a urinary sphincter muscle of the patient, to promote healing of the at least one nerve, to treat urinary incontinence. Additionally or alternatively, the microprocessor can be configured to execute programming instructions stored in the memory to cause the stimulation circuit to activate at least one pair of electrodes in the array to stimulate at least one nerve associated with control of a lower intestinal tract of the patient, to promote healing of the at least one nerve, to treat an intestinal tract disorder. BRIEF DESCRIPTION OF DRAWINGS

[0045] These and other features, aspects, and advantages of the present disclosure will become evident to those skilled in the art from the following description, the accompanying claims, and the appended drawings.

[0046] Figure 1 is a schematic diagram of an exemplary electrical stimulation system configured in accordance with the principles of the present disclosure.

[0047] Figure 2A and Figure 2Bare plan views of an exemplary flexible paddle suitable for use with the present invention and a plan view of the distal ends of two paddles arranged to be positioned against the patient's pelvic plexus, respectively.

[0048] Figure 3 is a plan view of an alternative embodiment of a flexible paddle suitable for use with the system of the present invention.

[0049] Figure 4A and Figure 4B are perspective views of the flexible paddle of FIG. 2 and Figure 3 are side cross-sectional and perspective line drawings of different electrode shapes for use in the flexible paddle of FIG. 2, while Figures 4C-4E depicts Figure 4A and Figure 4B depicts the charge distribution on the various electrode shapes depicted in

[0050] Figure 5 depicts a generalized block diagram of an exemplary programmable controller of an implantable stimulation unit of the stimulation system of Figure 1

[0051] depicts a generalized block diagram of an exemplary external patient controller of the stimulation system of Figure 6 Figure 1 is a block diagram of the functional components of an exemplary software-based programming system configured to run on an external physician controller of the stimulation system of

[0052] Figure 7 Figure 1

[0053] Figure 8A and Figure 8B are perspective views showing the placement of the flexible paddle of FIG. 2 positioned on the patient's prostate and pelvic plexus, respectively, with inset details.

[0054] Figure 9A and Figure 9B are plan views showing alternative placements of the flexible paddle of the present invention relative to the patient's urethra, respectively.

[0055] Figures 10A-10C depicts various directional currents between pairs of adjacent electrodes disposed on the flexible paddle of Figure 2A

[0056] Figures 11A-11C depicts illustrative regions within the electrode array of the flexible paddle of Figure 2A

[0057] depicts the selection of preferred electrode pairs within the various electrode regions according to the present invention. Figures 12A-12C

[0058] Figure 13 ​​​​​An exemplary method of delineating preferred stimulating electrodes and areas for use in electrical nerve stimulation to obtain sexual arousal is depicted.

[0059] Figure 14 A method of intraoperatively sequentially scanning adjacent electrode pairs according to the principles of the present invention is depicted.

[0060] Figure 15 is a flow chart showing steps of an exemplary method for configuring a subset of an electrode array for stimulation to induce optimal sexual arousal according to the principles of the present invention.

[0061] Figure 16 is a flow chart showing steps of an exemplary method for determining optimal placement of an implanted flexible paddle according to the principles of the present disclosure.

[0062] Figure 17 is a flow chart showing steps of an exemplary method for determining optimal stimulation protocols to induce erection, stimulation protocols for rehabilitation of at least one cavernosal nerve, and / or stimulation protocols for penile rehabilitation to reduce penile fibrosis.

[0063] Figure 18 is a flow chart showing steps of an exemplary method for adjusting optimal patterns of rehabilitation after a post-implantation interval.

[0064] Figures 19A-19E Results of a Qualiveen questionnaire provided by a patient with a spinal cord injury and a urological disorder are shown.

[0065] Figure 20 is a schematic representation of the local anatomy of the pelvic region of a male.

[0066] Figure 21A and Figure 21B is a cross-sectional side view of an exemplary flexible paddle.

[0067] Figure 21C and Figure 21D are perspective views with inset details showing placement of the flexible paddle Figure 21A and Figure 21B positioned on the pelvic plexus of a patient.

[0068] Figure 22 is a plan view of another alternative embodiment of a flexible paddle suitable for use with the electrical stimulation system of the present invention. DETAILED DESCRIPTION

[0069] The systems and methods described herein can be used to treat pelvic disorders, such as sexual disorders, for example, erectile dysfunction (ED), including ED associated with neuronal response failure (caused by, for example, prostatectomy, cystectomy, abdominoperineal resection, spinal cord injury, and / or diabetes) and ED associated with increased smooth muscle tone and / or contractility in the corpora cavernosa and penile arteries (caused by, for example, hypertension, atherosclerosis, and / or diabetes) as well as female sexual arousal disorder (FSAD) and other pelvic disorders such as urinary incontinence and intestinal dysfunction.

[0070] The systems and methods described herein contemplate restoring the function of denervated penises by, for example, electrically stimulating the terminal ends of the cavernosal nerves. The neuronal pathway that triggers the erectile response is parasympathetic input from the pelvic splanchnic plexus. The pelvic splanchnic plexus is composed of branches of the second, third, and fourth sacral nerves that intermingle with the hypogastric plexus, forming a neural network in the pelvis. The cavernosal nerves originate from the pelvic splanchnic nerves, travel along the prostatic plexus, lie almost around the prostate, and supply parasympathetic fibers to the corpora cavernosa and the corpus spongiosum of the penis. Thus, it is difficult to locate the optimal site for electrical nerve stimulation because the human cavernosal nerve reaches the penis from the pelvic plexus through a complex anastomosis. In addition, there is significant anatomical variation in the location of the cavernosal nerves. The anatomy, stage of disease, and / or cancer location of each patient is unique. The pelvic plexus is a transparent veil with tiny nerves, and the distribution of the cavernosal nerves is not uniform on every man. Thus, these obstacles make it extremely difficult to identify the cavernosal nerve segment for selective stimulation. Systems and methods for overcoming these obstacles are provided herein.

[0071] Referring to Figure 1 , an overview of an exemplary electrical stimulation system constructed in accordance with the principles of the present disclosure is provided. In Figure 1 , the components of the system are not depicted in relative or absolute scale. The electrical stimulation system 100 can include an implantable stimulation unit 200 with a programmable controller 300, an external patient controller 400, an external physician controller 500, and an external charger 600.

[0072] Referring now to Figure 2A and Figure 2BThe implantable stimulation unit 200 includes at least one flexible paddle, exemplarily a first flexible paddle 202a and a second flexible paddle 202b, each including an array of electrodes 204 and suture holes 206, a cable 208, and a programmable controller 300. Each electrode 204 can be individually selected to emit electrical energy to stimulate tissue. Preferably, the electrodes 204 are selected in one or more pairs by the programmable controller of the implantable stimulation unit 200 to cause stimulation of the erectile tissue when activated by a user or physician, for example, using an external patient controller 400 or physician controller 500. The electrodes 204 can be uniformly arranged and / or disposed in different spatial configurations. For example, the electrodes 204 can be spaced apart by about 0.05 mm to about 5.0 mm, and more preferably by about 0.5 mm to about 1.5 mm. Illustratively, the electrodes 204 are arranged in multiple rows and columns, and the number of electrodes 204 can vary between about 10 to more than 50 electrodes as needed. The electrodes 204 can apply bipolar stimulation such that electrical current passes from one electrode to another to stimulate a nerve or set of nerves disposed therebetween. The electrode array 204 can have a tissue-friendly shape designed to reduce adverse tissue reactions that can lead to fibrotic encapsulation formation. For example, the size and shape of the electrodes 204 can be determined such that convex, spherical, or flattened portions are exposed on the flexible substrate, thereby avoiding sharp surfaces that can damage or irritate tissue. The electrodes 204 can be made of platinum, gold, or other conductive implantable materials suitable for neural electrical stimulation.

[0073] The size and shape of the flexible paddles 202 are preferably determined to abut at least a portion of the pelvic plexus of the patient. As shown in Figure 2A and Figure 2B The first flexible substrate 202a is configured to conform to a first half of the pelvic plexus, and the second flexible paddle 202b is configured to conform to a second half of the pelvic plexus, as shown in

[0074] Referring again to Figure 1The implantable stimulation unit 200 includes a first array of electrodes 204 disposed on the first flexible paddle 202a and a second array of electrodes 204 disposed on the second flexible paddle 202b. The programmable controller 300 is preferably programmed to activate the stimulation circuit to cause one or more electrodes 204 disposed on the first flexible paddle 202a and one or more electrodes 204 disposed on the second flexible paddle 202b to simultaneously apply bilateral electrical stimulation to the patient's erection.

[0075] The implantable stimulation unit 200 can include at least one anchor, preferably individually coupled to the flexible paddles, to maintain the flexible paddles in contact with the pelvic plexus. The anchors can be composed of sutures, biocompatible matrices, biocompatible glue, or some combination thereof. In one preferred embodiment, each flexible paddle includes one or more suture holes 206 through which sutures can anchor the flexible paddles to the pelvic plexus. The implantable stimulation unit 200 can be encapsulated in one or more biocompatible materials suitable for long-term implantation (e.g., titanium cages, silicone gel cages). In one embodiment, the flexible paddles 202 can include one or more cavities disposed between the electrodes 204 or within specific regions of the paddles to allow connective tissue to grow in and / or through the paddles, thereby enhancing anchoring and fixation in the pelvic cavity.

[0076] Cables 208 electrically couple the electrodes 204 of the flexible paddles 202a and 202b to the programmable controller 300. The cables 208 can be insulated multi-conductor cables having a separate wire for each electrode 204. The cables 208 can include branches, as illustrated, to allow connection with the flexible paddles. In one embodiment, more than one cable 208 can be coupled to each of the arrays of electrodes 204 of the first flexible paddle 202a and the second flexible paddle 202b.

[0077] The programmable controller 300 can be implanted in the lower side abdomen between the umbilical line and the iliac crest line and includes circuitry configured to store stimulation routines and cause the stimulation circuit to provide electrical stimulation to selected subsets of electrodes 204 with parameters defined by a stimulation protocol. The parameters employed in such stimulation protocols can include the pulse duration of the stimulation, the frequency of the alternating current, the voltage, the current, and the time period.

[0078] The programmable controller 300 can be controlled by and optionally powered by an external patient controller 400. The external patient controller 400 preferably includes a user interface 402 that allows a user (e.g., a patient, a physician, a caregiver) to adjust a limited number of operating parameters of the programmable controller 300, including starting and stopping a stimulation session. The programmable controller 300 communicates with the external patient controller 400 via respective communication units, which can each include an inductive coil and / or an RF transceiver to communicate information in a bidirectional manner on the patient's skin and optionally to transfer power to the programmable controller 300. For example, the external patient controller 400 can selectively activate the programmable controller 300 in response to user input received at the user interface 402 via respective telemetry (or RF) systems in the programmable controller 300 and the external patient controller 400.

[0079] In preferred embodiments, a limited number of stimulation parameters can be adjusted at the user interface 402 to reduce the opportunity for harm from inappropriate adjustments made by a non-physician user. In alternative embodiments, the external patient controller 400 can also send adjustments to stimulation parameters (e.g., electrodes used to apply stimulation, pulse duration of stimulation, frequency, voltage, current, and time period of alternating current) to the programmable controller 300 in response to user input received at the user interface 402. In one embodiment, the external patient controller 400 can activate a preprogrammed routine stored in the programmable controller 300 to identify a preferred set of stimulating electrodes and store the identification of these electrodes in non-volatile memory, as described below.

[0080] The external patient controller 400 can be specifically designed for use with the implantable stimulation unit 200 and the programmable controller 300. Alternatively, the external patient controller 400 can be a smartphone, laptop, tablet, smartwatch, or the like that is programmed to communicate with the implantable stimulation unit 200 via an application or "app" downloaded from an app store. In either case, the external patient controller 400 is programmed to interface with the implantable stimulation unit 200 and / or the external physician controller 500 and can use a cellular, 802.11 WiFi, Zigbee, and / or BLUETOOTH TM chipset to communicate with those devices. In particular, the external patient controller can be programmed to selectively activate the programmable controller 300 in response to patient input.

[0081] The external physician controller 500 is programmed to communicate with the programmable controller 300 directly or via the external patient controller 400. As Figure 1As shown in FIG. 5, the external physician controller 500 illustratively can be a computer having a non-transitory computer readable medium programmed with instructions that, when executed on the computer, cause the computer to provide programming to the programmable controller 300. The external physician controller 500 can be wirelessly coupled to the programmable controller 300 and / or the external patient controller 400 so that the external physician controller 500 can download data stored on the programmable controller 300 and / or the external patient controller 400 for review. The external physician controller 500 can also transmit programming data to the programmable controller 300 to reprogram stimulation parameters programmed into the programmable controller 300. For example, the external physician controller 500 can be used to program and adjust parameters such as electrode pair(s) used for stimulation, pulse duration of stimulation, frequency of alternating current, voltage, current, and time period. The external physician controller 500 can also be programmed to upload and store data retrieved from the programmable controller 300 to a remote server for later access by a physician. In one embodiment, the external physician controller 500 can selectively activate a desired subset of electrodes 204 and cause the non-volatile memory of the programmable controller 300 to store the identification of those electrodes and a stimulation routine sufficient to cause sexual arousal, e.g., sufficient to achieve sexual intercourse and potential ejaculation, to facilitate a medical procedure such as the application of a urinary catheter, or penile rehabilitation, as further described below.

[0082] The external physician controller 500 can selectively activate the programmable controller 300 to execute a scan protocol stored in the non-volatile memory that, when activated, determines preferred electrode pairs, current flow directions, and electrode regions that cause a rapid erectile response, achieve neural rehabilitation, and / or reduce penile fibrosis, and stores the identification of these electrodes in the non-volatile memory of the programmable controller 300. More specifically, the scan protocol can cause the microprocessor of the programmable controller 300 to supply electrical stimulation via the stimulation circuit by selectively activating electrodes 204 in the array in a predetermined manner to determine a preferred current flow direction, a preferred electrode region when stimulating in the preferred direction of current flow, preferred electrode pairs within the preferred electrode region, and preferred stimulation parameters to be applied to those preferred electrodes, as described below. The scan protocol can be used to determine at least one of a stimulation pulse sequence corresponding to an erectile activation pattern for causing an erection sufficient to achieve sexual intercourse including, e.g., an ejaculation response, a stimulation pulse sequence corresponding to an erectile activation pattern for causing an erection sufficient to facilitate a medical procedure such as the application of a urinary catheter, a neural rehabilitation stimulation pulse sequence corresponding to a rehabilitation activation pattern for rehabilitating at least one cavernosal nerve, and / or a penile rehabilitation stimulation pulse sequence corresponding to a rehabilitation activation pattern for inducing at least partial penile tumescence ice reduction of penile fibrosis.

[0083] In one embodiment, the external physician controller 500 can be used during post-surgery (e.g., prostatectomy) to determine preferred electrode pairs and preferred stimulation parameters that produce a favorable rapid erection response or for nerve or penile rehabilitation. The external physician controller 500 can be used to cause the non-volatile memory of the programmable controller 300 to store a first stimulation protocol that, when activated on demand by the external patient controller 400, causes a rapid erection response (e.g., sufficient to enable sexual intercourse), a second stimulation protocol that, when activated on demand by the external patient controller 400, causes a rapid erection response (e.g., sufficient to facilitate a medical procedure such as the application of a urinary catheter), and / or a third stimulation protocol that is activated automatically by the programmable controller 300 at a preset time or via the external patient controller 400 to provide a lower current intensity to restore nerve transmission via the at least one cavernosal nerve. The stimulation protocols are stored within the memory of the programmable controller 300 so that the parameters can be used at a later time to achieve an erection, e.g., in response to user input at the external patient controller 400.

[0084] The external physician controller 500 can be specifically designed for use with the implantable stimulation unit 200. Alternatively, the external physician controller 500 can be a smartphone, laptop, tablet, desktop computer, etc. that is programmed to communicate with the implantable stimulation unit 200. Thus, for example, the external physician controller 500 can use software such as an application or "app" downloaded from an app store to interface with the implantable stimulation unit 200 and / or the external patient controller 400 and can use cellular, 802.11 WiFi, Zigbee, and / or BLUETOOTH TM chipset to communicate with those devices. The external physician controller 500 can communicate directly with the implantable stimulation unit 200 or via the external patient controller 400.

[0085] The external charger 600 can be in electrical communication with the programmable controller 300 and transcutaneously charge the programmable controller 300 via a respective pair of induction coils. The external charger 600 can generate an alert via an indicator LED, a sound alarm, or a vibrating motor when the power level of the programmable controller 300 is below a threshold power level.

[0086] Referring now to Figure 2A , Figure 2B and Figure 3, shows an exemplary paddle design for an implantable stimulation unit. The implantable stimulation unit 200 may include at least one flexible paddle 202 having an electrode array 204 and suture holes 206. The flexible paddle 202 may be operably coupled to the programmable controller 300 via a cable 208 having leads 210. The cable 208 may be an insulated multi-conductor cable having separate wires for each electrode 204. Figure 2A An embodiment is depicted in which a single cable 208 couples the flexible paddle 202 to the programmable controller 300. Alternatively, as Figure 3 As shown in , two or more cables 208 may be provided to couple the flexible paddle 202 to the programmable controller 300. Figure 3 In an embodiment, one of the cables 208 can electrically couple a first subset of the electrode array 204 (e.g., six electrodes) to the programmable controller 300, and another cable 208 can electrically couple a second subset of the electrode array 204 (e.g., the remaining six electrodes) to the programmable controller 300. Thus, the programmable controller 300 can include multiple ports for receiving the cables 208.

[0087] The flexible paddle 202 can be curved, for example, in an arcuate shape, and can be implanted (for example, during a prostatectomy) to contact the pelvic plexus. Preferably, the flexible paddle 202 can conform to the anatomical shape of a portion of the pelvic plexus. The flexible paddle 202 can include at least two rows and at least two columns of electrodes 204. Figure 2B In the preferred embodiment depicted in , the electrode array 204 can include 12 electrodes on each of the first flexible paddle 202a and the second flexible paddle 202b. The flexible paddle 202 can have a substantially hemispherical shape, including a protrusion 203 extending from the corner of the flexible paddle farthest from the cable 208. The hemispherical shape is selected to avoid damaging soft tissue, minimize trauma, and reduce fibrotic encapsulation that can hinder the transmission of stimulation pulses from the electrode to the nerve. The protrusion 203 also allows the flexible paddle to be placed near the cavernous nerve while adapting to the anatomy of the area, as described below with respect to Figure 8A and Figure 8B At least one electrode 204 may be provided on the protruding portion 203 of the blade.

[0088] See also Figure 2B , describes an embodiment with two paddles. In this embodiment, the stimulation unit 200 (see Figure 1) includes first and second flexible paddles 202a and 202b, each having an electrode array 204 and a suture hole 206. Each of the first and second flexible paddles 202a and 202b is coupled to the programmable controller 300 via a cable 208. Alternatively, a single cable 208 can include branches that couple the paddles 202a and 202b to the programmable controller 300. Because the pelvic plexus generally has two nerve groups, the first and second flexible paddles 202a and 202b can each cover part or the entire area of one nerve group, such that at least one of the electrode arrays 204 is in contact with the cavernosal nerves. For example, the first and second flexible paddles 202a and 202b can be implanted in a patient such that the protruding portions 203 of each hemi-spherical paddle face each other, as shown in Figure 2B . Thus, the protruding portions 203 can allow the flexible paddles to be placed around the urethra, as shown in Figure 9A and Figure 9B , as described below. In a preferred embodiment, each flexible paddle 202 has a thickness of about 2 mm, a length of about 32.5 mm, and a width of about 18 mm, except that the protruding portions 203 extend to a width of about 22 mm. The first and second flexible paddles 202a and 202b can have the same or different dimensions. When implanted, the distance between the two paddles can be between about 0.5 mm and about 8 cm.

[0089] Referring now to Figure 4A and Figure 4B , example electrode shapes for use in the implantable stimulation unit 200 are described. The electrodes 204a, 204b, and 204c each have a tissue-friendly shape that is configured to reduce adverse tissue reactions that can lead to fibrotic formation around the electrodes. The electrode 204a has a bulbous portion that extends from a flexible base portion 212 and is independently coupled to the circuitry of the programmable controller 300 by an electrical wire 214a of the cable. The electrode 204b has a flat portion that extends above the height of the flexible base portion 212 and is independently coupled to the circuitry of the programmable controller 300 by an electrical wire 214b of the cable. The electrode 204c is flat and flush with the surface of the flexible base portion 212 and is independently coupled to the circuitry of the programmable controller 300 by an electrical wire 214c of the cable. Advantageously, each electrode shape does not have a sharp surface that can damage or irritate tissue. Those skilled in the art will also appreciate that the electrode array 204 can use one, two, or three of these electrode shapes or other suitable tissue-friendly shapes.

[0090] Referring now to Figures 4C-4E , example electrode shapes are further described. Figures 4C-4E The surface charge density of each electrode shape is depicted. AsFigure 4C As shown in FIG. 2A, the hemispherical shape of electrode 204a allows for uniform charge distribution across the electrode surface, providing efficient energy delivery from the electrode to the cavernous nerves without damaging surrounding tissue. In contrast, as shown in FIG. 2B, the charge distribution of flat disc electrodes 204b and 204c exhibits a large accumulation of charge at the electrode periphery, which can impede energy delivery and can cause tissue damage. Figure 4D and Figure 4E As shown in FIG. 2A, the hemispherical shape of electrode 204a allows for uniform charge distribution across the electrode surface, providing efficient energy delivery from the electrode to the cavernous nerves without damaging surrounding tissue. In contrast, as shown in FIG. 2B, the charge distribution of flat disc electrodes 204b and 204c exhibits a large accumulation of charge at the electrode periphery, which can impede energy delivery and can cause tissue damage.

[0091] With respect to Figure 5 A generalized schematic of the internal functional components of programmable controller 300 is now described. Programmable controller 300 is programmed to cause stimulation of the preferred energizing electrodes in accordance with a stimulation program stored in the memory of programmable controller 300. Programmable controller 300 preferably includes a microprocessor 302, non-volatile memory 304, a communication unit 306, system sensors 308, a power source 310, a stimulation circuit 312, and a demultiplexer 314.

[0092] Microprocessor 302 is electrically coupled to and controls the functional components of programmable controller 300. Microprocessor 302 can comprise a commercially available microcontroller unit that includes a programmable microprocessor, volatile memory, non-volatile memory 304 such as EEPROM for storing programming, and non-volatile storage such as flash memory for storing firmware as well as logs of system operating parameters and patient data. The memory of microprocessor 302 stores program instructions that, when executed by microprocessor 302, cause the processor and functional components of programmable controller 300 to provide the functionality attributed to them herein. Preferably, microprocessor 302 is programmable such that programming data (e.g., stimulation programs, identification of energizing electrodes, stimulation parameters, etc.) is stored in non-volatile memory 304 of microprocessor 302 and can be adjusted using external patient controller 400 and / or external physician controller 500.

[0093] The microprocessor 302 can be programmable to allow electrical stimulation of any selected combination of electrodes 204 on the array, providing a simple bipolar configuration. The microprocessor 302 can also be programmed with routines to selectively activate a desired subset of the electrode array 204 to determine one or more stimulation programs and subsets of the electrode array that provide a beneficial stimulation and store that information in the non-volatile memory 304 for subsequent use by the microprocessor 302. As used in this disclosure, the term "excitation electrodes" refers to a subset of electrodes determined to provide a preferred erectile response for a preferred current flow direction. Further, as used in this disclosure, the term "stimulation program" refers to a set of stimulation parameters judged by the patient or physician to elicit a beneficial rapid erectile response or to provide stimulation determined by the patient or physician to be beneficial for restoring or strengthening neural transmission via at least one cavernosal nerve.

[0094] For example, the microprocessor 302 can use the demultiplexer 314 to direct the power source 310 to send electrical signals to the excitation electrode set 204 via the stimulation circuit 312. The stimulation program used by the microprocessor 302 provides electrical stimulation to the at least one cavernosal nerve via the stimulation circuit 312 and the plexus sufficient to cause sexual arousal (e.g., erection), sufficient to enable sexual intercourse, or sufficient to facilitate a medical procedure such as the application of a urinary catheter or for nerve or penile rehabilitation. The routine can activate the identified and stored subset of electrodes automatically and / or in response to user input at the external patient controller 400 and / or the external physician controller 500. Further, as described below, the non-volatile memory 304 stores preprogrammed routines for scanning the electrode array to enable identification of stimulation parameters and the excitation electrode set for a preferred stimulation program both at an initial time after implantation of the implantable stimulation unit 200 and at a later time after implantation, which can be directed to the external patient controller 400 or the external physician controller 500. The excitation electrode set produces the best erectile response, e.g., for enabling sexual arousal or for facilitating a medical procedure such as the application of a urinary catheter and is stored in memory. The identification of the excitation electrode set is stored for later stimulation and can also be transmitted to the external patient controller 400 and / or the external physician controller 500.

[0095] Stimulation parameters are selected to provide sexual arousal, promote nerve regeneration, and / or improve nerve regeneration to treat sexual disorders, such as erectile dysfunction and female sexual arousal disorder. For example, stimulation can induce and maintain an erection, and can promote and / or improve nerve (e.g., pelvic plexus nerve(s) and / or cavernous nerve(s)) regeneration over time. As an example, pulse duration can be programmed to be between about 0.5 milliseconds to about 10 milliseconds, about 0.5 milliseconds to about 5 milliseconds, about 1 millisecond to about 4 seconds, or about 1 millisecond to about 3 milliseconds. The frequency of alternating current can be programmed to be between about 10 Hz to about 30 Hz, about 10 Hz to about 25 Hz, about 10 Hz to about 20 Hz, or about 15 Hz to about 25 Hz. Voltage can be programmed to be between about 1 V to about 15 V, about 5 V to about 10 V, about 1 V to about 5 V, or about 10 V to about 15 V. Current can be programmed to be between about 1 milliamp to about 100 milliamps, about 1 milliamp to about 50 milliamps, about 1 milliamp to about 20 milliamps, about 20 milliamps to about 50 milliamps, about 50 milliamps to about 100 milliamps, or about 75 milliamps to about 100 milliamps. Stimulation sessions can be programmed to automatically stimulate during a predetermined time, or can be stimulated in response to user input, e.g., at user interface 402. For example, stimulation can be maintained during a portion of or the entire time period in which an erection is desired. For nerve regeneration, it is preferable to stimulate at predetermined intervals over time. For example, automatic stimulation can occur as follows: every hour, once a day, twice a day, three times a day, four times a day, every other day, every three days, or once a week for a period of 10 minutes to 2 hours, 10 minutes to 1 hour, 10 minutes to 30 minutes, 10 minutes to 20 minutes, or 1 hour to 2 hours. Preferably, oscillating current or low frequency electrical stimulation is used to stimulate nerve regeneration.

[0096] The microprocessor 302 is coupled to a communication unit 306 having circuitry configured to communicate with the external patient controller 400 and / or the external physician controller 500. The communication unit 306 allows for the transmission of stimulation commands, and optionally power, between the programmable controller 300 and the external patient controller 400, such that the programmable controller 300 can be powered, programmed, and / or controlled by the external patient controller 400. For example, in response to a stimulation command received from a corresponding communication unit (e.g., an inductive unit having a telemetry system and coil and / or an RF unit having a transceiver and antenna) of the external patient controller 400, the microprocessor 302 can begin or stop a stimulation session or implement an evaluation to determine a preferred subset of the electrode array 204. The communication unit 306 also allows for the transmission of programming data, and optionally power, between the programmable controller 300 and the external physician controller 500, such that the programmable controller 300 can be powered, programmed, and / or controlled by the external physician controller 500. For example, in response to programming data received from a corresponding communication unit (e.g., an inductive unit having a telemetry system and coil and / or an RF unit having a transceiver and antenna) of the external physician controller 500, the microprocessor 302 can direct changes to the electrodes included in the set of energizing electrodes used for stimulation and the preferred stimulation regimen, including the pulse duration of the stimulation, the frequency of the alternating current, the voltage, the current, and / or the time period.

[0097] The communication unit 306 can include a telemetry system electrically coupled to an inductive coil. Techniques for telemetry systems and coils are well known to those skilled in the art and can include a magnet, a short-range telemetry system, a longer-range telemetry system such as using MICS RF telemetry available from Zarlink Semiconductor of Ottawa, Canada, or similar to a pacemaker programmer. Alternatively, the coil can be used only for the transmission of power, and a separate radio frequency transmitter can be provided in the programmable controller 300, the external patient controller 400, and / or the external physician controller 500 for establishing bidirectional or unidirectional data communication.

[0098] The communication unit 306 can also include communication circuitry (with or without telemetry systems and coils) employing a transceiver coupled to an antenna (which can be internal or external to the sealed housing). The transceiver preferably includes a radio frequency (RF) transceiver and is configured for bidirectional communication via the antenna with similar transceiver circuitry disposed in the external patient controller 400 and / or the external physician controller 500. For example, the transceiver can receive stimulation commands from the external patient controller 400 and programming data from the external physician controller 500. In response to programming data and / or stimulation commands received via the antenna and transceiver of the communication unit 306 from the corresponding transceiver and antenna of the external patient controller 400 and / or the external physician controller 500, the microprocessor 302 can direct changes to the electrodes included in the set of electrodes used for stimulation and the preferred stimulation regimen, including the pulse duration of the stimulation, the frequency of the alternating current, the voltage, the current, and / or the time period, can start or stop a stimulation session, and / or can implement an evaluation to reassess the preferred subset of electrodes. The transceiver can also include a low power mode of operation such that it periodically awakens to listen for incoming messages and only responds to those messages that include a unique device identifier assigned to that programmable controller. Additionally, the transceiver can employ encryption routines to ensure that messages sent from or received by the programmable controller 300 cannot be intercepted or falsified. The communication unit 306 can include a wireless chipset; e.g., WiFi, BLUETOOTH TM , cellular, Zigbee, etc.; such that the programmable controller 300 can wirelessly communicate with the external patient controller 400 and / or the external physician controller 500.

[0099] The system sensors 308 can include one or more sensors that monitor the operation of the system of the programmable controller 300 and log data related to system operation and system malfunctions, which can be stored in a log for later retrieval using the external physician controller 500. The microprocessor 302 can be programmed to receive sensor signals from the system sensors 308 and adjust stimulation parameters based on the sensor signals. The sensors 308 can include, for example, a humidity sensor to measure the humidity within the housing of the programmable controller 300, which can provide information related to the status of the electronic components, and / or a temperature sensor, e.g., to measure the battery temperature during charging to ensure safe operation of the battery. Data from the system sensors can be logged by the microprocessor 302 and stored in the non-volatile memory 304 for later transmission to the external physician controller 500.

[0100] Power source 310 powers the electronic components of programmable controller 300 and can include a primary battery or battery pack, a secondary (rechargeable) battery or battery pack, or a combination of both. Alternatively, power source 310 can not include a battery or battery pack, but rather a capacitor that stores energy transferred through the skin via a transcutaneous energy transfer system (TET), for example by inductive coupling. In a preferred embodiment, power source 310 includes a lithium-ion battery pack.

[0101] Stimulation circuit 312 is configured to use energy supplied from power source 310 to send pulses to electrodes 204 such that the selected electrode(s) supply electrical stimulation at the desired parameters.

[0102] Microprocessor 302 can also be coupled to a demultiplexer 314 such that any subset of electrode array 204 can be selectively coupled to stimulation circuit 312. In this way, the appropriate set of electrodes can be picked from the entire selection of electrodes implanted in the patient to achieve the ideal therapy effect. Demultiplexer 314 preferably operates at high speed, allowing successive stimulation pulses to be applied to different combinations of electrodes.

[0103] With respect to Figure 6 A generalized schematic of the internal functional components of external patient controller 400 is now described. External patient controller 400 can include a user interface 402, a programmable microprocessor 404, a communication unit 406, a power source 408, and input and output circuitry (I / O) 410. As explained above, external patient controller 400 can be specifically designed for use with implantable stimulation unit 200 or alternatively can be a multi-purpose smartphone, laptop, tablet, smartwatch, etc. that is programmed to communicate with implantable stimulation unit 200 and / or external physician controller 500. In the latter case, user interface 402, programmable microprocessor 404, communication unit 406, power source 408, and I / O 410 can be hardware previously installed on the smartphone, laptop, tablet, smartwatch, etc.

[0104] The microprocessor 404 is electrically coupled to and configured to control the internal functional components of the external patient controller 400. The microprocessor 404 can comprise a commercially available microcontroller unit including a programmable microprocessor, volatile memory, non-volatile memory such as EEPROM for storing programming, and non-volatile storage such as flash memory for storing firmware and logs of system operating parameters and patient data. The memory of the microprocessor 404 can store program instructions that, when executed by the processor of the microprocessor 404, cause the processor and functional components of the external patient controller 400 to provide the functionality attributed to them herein. Preferably, the microprocessor 404 is programmable and programmed to store changes to the electrodes included in the set of stimulating electrodes used for stimulation and the preferred stimulation regimen, including the pulse duration of the stimulation, the frequency of the alternating current, the voltage, the current, and / or the time period, in response to user input received at the user interface 402 and / or at the external physician controller 500 and transmit the stimulation commands and programming data to the programmable controller 300 via the communication unit 406.

[0105] The microprocessor 404 can be coupled to a communication unit 406 that can communicate with the programmable controller 300 and the external physician controller 500. The communication unit 406 can include an inductive unit with a telemetry system and coil and / or a transceiver with a wireless chipset and antenna; e.g., WiFi, BLUETOOTH TM , cellular, Zigbee, etc.; thereby enabling the external patient controller 400 to wirelessly communicate with the programmable controller 300 and / or the external physician controller 500 and, optionally, power the programmable controller 300.

[0106] The user interface 402 receives user input and displays information to the user. The user interface 402 can include buttons, LEDs, displays, touchscreens, keypads, microphones, speakers, trackballs, etc. for receiving user input and / or displaying information to the user. For example, the user interface 402 can display the current stimulation parameters and allow the user to adjust the stimulation parameters. In preferred embodiments, a limited number of stimulation parameters can be adjusted at the user interface 402 to reduce the chance of injury caused by adjustments made by a non-physician user. For example, the user interface 402 can only allow the user to start or stop a stimulation session, such as a first stimulation pulse sequence, corresponding to a first erection mode for causing a rapid erection response to cause sexual arousal to enable sexual intercourse, a second erection mode for causing a rapid erection response to cause an erection sufficient to facilitate a medical procedure such as the application of a urinary catheter, a third neuro-rehabilitation stimulation mode for selecting for restoration of neural transmission in the cavernosal nerve, or a fourth penile rehabilitation mode for selecting to reduce penile fibrosis.

[0107] The power source 408 provides power to the electronic components of the external patient controller 400 and may include a primary battery or battery pack, an auxiliary (rechargeable) battery or battery pack, or a combination of both. Alternatively, the power source 408 may be a port that allows the external patient controller 400 to be plugged into a conventional wall outlet to power the components.

[0108] The input and output circuitry (I / O) 410 may include ports for data communications (such as wired communications with a computer) and / or a port for receiving removable memory (e.g., an SD card) on which program instructions or data related to the use of the external patient controller 400 may be stored.

[0109] See also Figure 7 , we will now describe the software implemented on the external physician controller 500. This software includes several functional blocks, such as Figure 7 , including a main block 502, an event log block 504, a data download block 506, a configuration setting block 508, a user interface block 510, an alarm detection block 512, a sensor calibration block 514, a firmware upgrade block 516, a device identifier block 518, and a status information block 520. The software is preferably written in C++ and uses an object-oriented format. In a preferred embodiment, the software is configured to run on Microsoft (a registered trademark of Microsoft Corporation of Redmond, Washington) or a Unix-based operating system, such as those commonly used on desktop and laptop computers. As discussed above, the computer may include a transceiver, antenna, and wireless card; for example, IEEE 802.11, cellular, BLUETOOTH, TM , Zigbee, etc.; thereby enabling the programmable controller 300 and / or the external patient controller 400 to wirelessly communicate with the external physician controller 500.

[0110] The main block 502 preferably comprises the main software routine that executes on the physician's computer and controls the overall operation of the other functional blocks. The main block 502 enables the physician to download event data and alarm information stored on the programmable controller 300 and / or the external patient controller 400 to his office computer, and also allows the external physician controller 500 to directly control the operation of the programmable controller 300. The main block 502 also enables the physician to upload firmware updates and configuration data to the programmable controller 300.

[0111] The event log block 504 is a record of operational data downloaded from the programmable controller 300 and can include, for example, treatment session start and stop times, current stimulation parameters, stimulation parameters from previous treatment sessions, sensor data, battery current, battery voltage, battery status, and the like. The event log can also include occurrences of events such as alarms or other abnormal conditions.

[0112] The data download block 506 is a routine that commands the programmable controller 300 to transfer data to the external physician controller 500 for download after the programmable controller 300 is coupled to the external physician controller 500. The data download block 506 can initiate the download of data stored in the event log automatically or at the physician's behest via the user interface block 510.

[0113] The configuration settings block 508 is a routine that configures parameters stored within the programmable controller 300 that control the operation of the programmable controller 300. An interval timing parameter can determine, for example, how long the processor remains in a sleep mode before being awakened to listen for radio communications or to control the operation of the programmable controller 300. An interval timing parameter can control, for example, the duration of a stimulation session. The interval timing setting transmitted to the programmable controller 300 can also determine when and at what frequency event data is written to the memory in the microprocessor 302. In embodiments where the external physician controller 500 is also configured to transfer data to the external patient controller 400, the external physician controller block 500 can also be used to configure timing parameters used by the firmware executed by the microprocessor 404 of the external patient controller 400. The block 508 can also be used by the physician to configure parameters stored within the memory of the microprocessor 302 related to limits on the operation of the microprocessor 302. These values can include the times at which the programmable controller 300 can and can not operate, among others.

[0114] The block 508 can also configure parameters stored within the memory of the microprocessor 302 related to the control of the operation of the programmable controller 300. These values can include stimulation parameters.

[0115] The user interface block 510 handles the display of information retrieved from the programmable controller 300 and / or the external patient controller 400 and the data download block 506 and presents the information in an intuitive, easy-to-understand format for viewing by the physician. Such information can include the status of the programmable controller 300, treatment session start and stop times, current stimulation parameters, stimulation parameters from previous treatment sessions, sensor data, battery status, and the like. The user interface block 510 also generates user interface screens that allow the physician to enter information to configure treatment session timing, stimulation parameters, and requests to determine or re-determine the subset of energized electrodes, among others.

[0116] The alarm detection block 512 can include routines for evaluating data retrieved from the programmable controller 300 and flagging abnormal conditions for the attention of the physician. For example, the alarm detection block 512 can flag when a parameter measured by a system sensor 308 is above or below a predetermined threshold.

[0117] The sensor calibration block 514 can include routines for testing or measuring the drift of system sensors 308 employed in the programmable controller 300, for example, due to aging or humidity changes. The block 514 can then calculate an offset value for correcting the measured data from the sensors and transmit this information to the programmable controller 300 for storage in the non-volatile memory of the microprocessor 302.

[0118] The firmware upgrade block 516 can include routines for checking the version number of the controller firmware installed on the programmable controller 300 and / or the external patient controller 400 and identifying if there is an upgrade firmware. If so, the routines can notify the physician and allow the physician to download the revised firmware in the non-volatile memory to the programmable controller 300 and / or the external patient controller 400.

[0119] The device identifier block 518 can include a unique identifier of the programmable controller 300 stored in the non-volatile memory 304 of the microprocessor 302 and routines for reading this data when the external physician controller 500 is coupled to the programmable controller 300. The device identifier can also be used by the programmable controller 300 to confirm that communications received from the external patient controller 400 and / or the external physician controller 500 are intended for that particular programmable controller. Likewise, this information is employed by the external patient controller 400 and / or the external physician controller 500 to determine if the received message was generated by a programmable controller associated with the system. Finally, the external physician controller 500 can employ the device identifier information to confirm that the external patient controller 400 and the programmable controller 300 make up a matched set.

[0120] The status information block 520 includes routines for interrogating the programmable controller 300 to retrieve current status data from the programmable controller 300. Such information can include, for example, battery status, stimulation parameters, date and time on an internal clock of the treatment session, version control information for the firmware and hardware currently in use, and sensor data.

[0121] Figure 8A And Figure 8B Figures 1 1 and 12 illustrate the flexible paddles 202a and 202b positioned over the prostate and the pelvic plexus, respectively. As above with respect to Figures 9 and 10, the flexible paddles 202a and 202b are shown in a deployed position. The flexible paddles 202a and 202b are shown in a deployed position in Figures 1 1 and 12, respectively. Figure 2A And Figure 2BAs described, each of the flexible paddles 202a and 202b carries an electrode array 204 and suture holes 206, and is coupled to a programmable controller 300 via one or more cables 208. The system can be implanted laparoscopically, for example, by folding the flexible paddles so as to pass the flexible paddles through a trocar. Figure 8A and Figure 8B The illustrations in Figure 8A show the flexible paddles 202 positioned against the prostate. Alternatively, the flexible paddles 202 can be positioned against the pelvic plexus, so that the paddles 202 surround the urethra, as shown in Figure 8B For patients who have undergone prostatectomy, in which the prostate was partially or completely removed, implantation on the pelvic plexus can be more suitable.

[0122] Referring now to Figure 9A and Figure 9B , the positioning of the flexible paddles 202 is described. As described above with respect to Figure 2A and Figure 2B , each flexible paddle 202 preferably has a substantially hemispherical shape, with the protruding portions 203 extending from the corners of the flexible paddle that are farthest from the cables 208. The first and second flexible paddles 202a and 202b can be positioned so that the flexible paddles have a side with exposed electrodes that contact the pelvic plexus, and the flexible paddles surround the urethra and the protruding portions 203 face each other. The flexible paddles 202 include suture holes 206 through which sutures can be passed to anchor the flexible paddles to the pelvic plexus. In Figure 9A , a first position is illustrated, so that the protruding portions 203 of the paddles are close to each other. In Figure 9B , a second position is illustrated, in which the protruding portions 203 of the paddles are far from each other, which can be advantageous if the patient's cavernous nerves are located farther from the urethra.

[0123] The programmable controller 300, which is operatively coupled to the electrode arrays, can be programmed to selectively activate the electrodes 204 during implantation of the paddles to determine an optimal position (e.g., the first position or the second position, as shown in Figure 9A and Figure 9B ) to implant the flexible paddles. For example, the flexible paddles can be placed at a first position adjacent to the pelvic plexus and close to at least one of the cavernous nerves (e.g., Figure 9A ). The programmable controller can then cause the stimulator circuit to activate the electrodes 204 at the first position to generate a first position response. For example, penile plethysmography can be used to measure penile diameter or circumference changes and penile tumescence, thereby measuring activation of the cavernous nerves.

[0124] The flexible paddle can then be moved to a second position different from the first position, adjacent the potted cluster, and proximate to the at least one cavernous body nerve (e.g., Figure 9B ). The programmable controller can again selectively activate the electrodes 204 at the second position to generate a second position response. The programmable controller can also compare the first and second position responses to determine a position that elicits an erection response via feedback from the sensor system 308 or in response to input from the external patient controller 400 or the external physician controller 500. If more than one position elicits an erection response, the position that elicits the strongest or fastest erection response without causing significant discomfort or side effects can be selected as the preferred paddle placement position.

[0125] Referring now to Figures 10A-10C , a process is described for evaluating tissue stimulation with sequentially varying current flow directions within the electrode array 204. As explained above, each electrode 204 on the flexible paddles 202a and 202b can be individually accessed to function as a source or sink to allow current flow in multiple directions, as indicated by the arrows between the electrodes 204 in Figures 10A-10C . In Figure 10A , a first direction of current flow is indicated by arrows 220a in a diagonal direction toward the other flexible paddle. For example, current flows from electrode 1 to electrode 2, but not between electrode 1 and electrodes 3 or 4. Figure 10B a second direction of current flow 220b is shown, in which current flows between the electrodes 204 in each flexible paddle in a diagonal direction away from the other flexible paddle. As shown in Figure 10B , the second direction of current flow is preferably oblique with respect to the first direction of current flow, so as to increase the likelihood that activation of a pair of electrodes will stimulate a nerve and thereby elicit a response. As depicted in Figure 10B , current flows from electrode 1 to electrode 3, but not between electrode 1 and electrodes 2 or 4. Figure 10C a third direction of current flow 220c is shown, in which current flows between the electrodes 204 in each flexible paddle in a downward direction. For example, current can flow from electrode 1 to electrode 4, but not from electrode 1 to electrodes 2 or 3. As will be appreciated by those of ordinary skill in the art, the direction of current flow can be different than shown in Figures 10A-10C , depending on the number and arrangement of the electrode array 204.

[0126] With respect to Figures 11A-11C , the electrodes 204 are described as being grouped into exemplary zones. Figures 11A-11C corresponding to Figures 10A-10CThe first electrode region 222a in Figure 11A may include electrodes 1-5, while the second electrode region 222b in Figure 11B may include electrodes 1-4 and 6, and the third electrode region 222c in Figure 11C may include electrodes 1, 3, 4, 6, 7, 10, and 11.

[0127] Referring now to Figures 12A-12C , the selection of preferred electrode pairs within an electrode array is shown. Figures 12A-12C Each of the electrode regions 222a, 222b, 222c in Figures 10A-10C corresponds to the directional current flow depicted in Figures 11A-11C and to the electrode regions depicted in Each electrode array 204 has at least one electrode pair within each electrode region 222, each electrode pair including two electrodes 204 from the electrode array. Each electrode region 222 can have the same or different number of electrodes 204 and electrode pairs as the other electrode regions 222.

[0128] Referring to Figure 13 , a programming method for identifying a subset of energizing electrodes is described, where the preferred direction of current flow, electrode regions, and preferred electrode pairs are determined. Following this electrode selection process, a programming method to determine parameters for a preferred stimulation protocol to elicit a favorable erection response is completed. According to an aspect of the present application, a programmable controller 300 is operatively coupled to the electrode array and programmed to selectively activate the electrodes 204 to determine the energizing electrodes and the preferred stimulation protocol.

[0129] More specifically, the programmable controller 300 is programmed to selectively activate the electrodes 204 within the electrode array in at least two current flow directions, for example, as shown in Figures 10A-10CThe erectile response can be measured by measuring activation of the cavernosal nerves, for example using a penile plethysmograph to measure penile diameter or circumference changes and penile tumescence. For each electrode array, the current flow direction that elicits an erectile response can be selected as the preferred current flow direction. If more than one current flow direction on each electrode array elicits an erectile response, the current flow direction that elicits the strongest erectile response without causing significant discomfort or side effects can be selected as the preferred current flow direction. For example, Figure 13 The second current flow direction 220b is shown selected as the preferred current flow direction for each electrode array. As will be appreciated by one of ordinary skill in the art, the preferred current flow direction on the first flexible paddle can be the same or different than the preferred current flow direction on the second flexible paddle.

[0130] The programmable controller 300 can also be programmed to activate electrodes 204 within the electrode array selectively by region using the preferred current flow direction from the previous process. For example, if the second current flow direction 220b is the preferred current flow direction, then the electrode region corresponding to the preferred current flow direction can be activated, as shown in Figure 11B The erectile response to each region stimulation can be measured using the same methods as described above. For each electrode array, the electrode region that elicits an erectile response can be selected as the preferred electrode region. If more than one electrode region elicits an erectile response, the electrode region that elicits the strongest erectile response without causing significant discomfort or side effects can be selected as the preferred region. For example, Figure 13 The second electrode region 222b on the first flexible paddle plate and the third electrode region 222c on the second flexible paddle plate are depicted selected as the preferred regions.

[0131] Next, the programmable controller 300 selectively activates electrodes 204 within the electrode array in the preferred current flow direction and in the preferred region. For example, Figure 13The second current flow direction 220b is depicted as the preferred current flow direction, and the second electrode region 222b on the first flexible paddle and the third electrode region 222c on the second flexible paddle are the preferred regions. Sequential stimulation can be applied between each electrode pair on the electrode array in the preferred current flow direction and in the preferred regions, and the erectile response can be measured using the same methods as described above. For each electrode array, the electrode pair or pairs that elicit an erectile response can be selected as the preferred electrode pair. If more than one electrode pair elicits an erectile response, the electrode pair or pairs that elicit the strongest erectile response without causing significant discomfort or side effects can be selected as the preferred electrode pair. In Figure 13 In the example shown in FIG. 2, three preferred electrode pairs 224 are identified as the excitation electrode subset. As will be appreciated by one of ordinary skill in the art, the number of preferred electrode pairs on the first flexible paddle can be the same as or different from the number of preferred electrode pairs on the second flexible paddle.

[0132] After the preferred electrode pairs 224 are determined, a plurality of stimulation parameters having unique combinations of frequency and amplitude of intensity can be applied to the preferred electrode pairs. Stimulation pulse sequences for different uses can be determined by comparing the responses generated by activating the preferred electrode pairs in different patterns having different stimulation parameters. For example, stimulation pulse sequences corresponding to activation patterns of one or more levels of erection can be determined. For example, a stimulation protocol for producing an erection (e.g., a full erection for sexual intercourse) can apply a current amplitude in the range of 0.5 to 25 mA, a frequency in the range of 10 to 48 Hz, and a pulse width in the range of 0.1 to 1 msec. Patients subjected to such stimulation not only exhibit a full erection for sexual intercourse, but also produce an ejaculation response. This ejaculation response (e.g., for men with spinal cord injuries who can not be able to ejaculate due to sexual arousal) is expected to improve the fertility outcome for such patients. For example, the ejaculation response achieved by the electrical stimulation described herein is expected to improve the quality of the semen (e.g., motility) over time and / or increase the success rate because it is possible to perform natural insemination for reproduction.

[0133] Alternatively or additionally, an erection level lower than a full erection can be needed to facilitate medical procedures that can require a non-flaccid penis. For example, for some men, partial or full erection can facilitate the application of a urinary catheter. A stimulation protocol for producing such an erection (e.g., an erection sufficient to facilitate a medical procedure such as insertion of a urinary catheter) can include stimulation parameters having a lower current intensity than the stimulation protocol for producing a full erection for sexual arousal and sexual intercourse. For example, the stimulation protocol can apply a current having an amplitude in the range of 1 to 6 mA, preferably 3 mA, a frequency in the range of 6 to 100 Hz, preferably 12 Hz, and a pulse width in the range of 0.1 to 1 msec, preferably 1 msec.

[0134] Alternatively or additionally, the device can be used to repair at least one cavernous nerve and determine a neurorehabilitation stimulation protocol corresponding to an activation pattern for neurorehabilitation. The neurorehabilitation stimulation protocol can include stimulation parameters having a lower current intensity than a stimulation protocol for producing an erection. For example, the neurorehabilitation stimulation protocol can apply a current with an amplitude in the range of 0.1 to 2 mA, a frequency in the range of 10 to 48 Hz, and a pulse width in the range of 0.01 to 1 millisecond. The neurorehabilitation stimulation protocol can be programmed to be automatically executed at least once a day.

[0135] Alternatively, the device can be used to determine a penile rehabilitation stimulation program corresponding to a penile rehabilitation activation pattern. After prostatectomy, if the cavernous nerves are damaged or completely severed, a penile rehabilitation stimulation program can be used to induce at least partial penile swelling to increase tissue oxygenation and maintain penile function, thereby reducing penile fibrosis. This stimulation program can be performed at least once a day while the cavernous nerves rebuild naturally, or reconnect and regenerate with the help of a neurorehabilitation stimulation program. The penile rehabilitation stimulation program may include stimulation parameters with a higher current intensity than the neurorehabilitation stimulation program and a lower current intensity than the stimulation program used to produce an erection. For example, the penile rehabilitation stimulation program may apply a current amplitude in the range of 0.5 to 25 mA, a frequency in the range of 10 to 48 Hz, and a pulse width in the range of 0.1 to 1 millisecond. The penile rehabilitation stimulation program can be programmed to be automatically executed at least once a day, and such actuation can occur at a different time from the neurorehabilitation program.

[0136] Preferably, the current flow direction, electrode areas, electrode pairs, and stimulation parameters may be stored in a non-volatile memory of the programmable controller 300, the external patient controller 400, and / or the external physician controller 500. A variety of stimulation protocols may also be stored in the memory of the programmable controller 300, the external patient controller 400, and / or the external physician controller 500, such that the programmable controller may be selectively activated in response to patient or physician input. For example, a patient may selectively activate a stimulation protocol to produce one or more levels of erection. Alternatively, if so programmed, the programmable controller may automatically execute the neurorehabilitation stimulation protocol and / or the penile rehabilitation stimulation protocol at least once per day after prostatectomy, preferably for one hour for each rehabilitation stimulation protocol.

[0137] about Figure 14FIG. 6, a schematic diagram depicting the operation of an intraoperative scanning procedure is described. Sequential stimulation will be applied between each electrode pair within each electrode array. Stimulation of each electrode pair will be applied automatically during the inter-pulse period of the other electrode pairs. Intraoperative stimulation can activate the cavernosal nerves, which are detected by the penile plethysmograph to measure penile diameter or circumference changes and penile tumescence. During the scanning procedure, each configuration can require 1 to 2 minutes of stimulation period for proper measurements. There can be a 5 minute rest period between each stimulation to maintain stability and avoid the refractory effect of detumescence.

[0138] In Figure 15 which an exemplary method for determining a subset of an electrode array positioned to provide electrical stimulation to at least one cavernosal nerve via the pelvic plexus to induce sexual arousal, e.g., erection, preferably after implantation, is described. In the method 700, at 702, stimulation parameters are set, which can include the electrode pair(s) 204 in the array to be used, the pulse duration of the stimulation, the frequency of the alternating current, the voltage, the current, and the period. The stimulation parameters can be set at the external patient controller 400, but preferably are set at the external physician controller 500. At 704, electrical stimulation is supplied to the tissue between the selected electrode pairs in the array, e.g., the pelvic plexus, at the set stimulation parameters. The selected array electrode pairs at the set stimulation parameters can be selected by the physician via the external physician controller 500 and / or determined as a result of the scanning protocol described above. At 706, it is observed whether sexual arousal, e.g., erection, is achieved. If not, the stimulation parameters can be reset for the selected electrode pair(s), or a different electrode pair(s) can be selected for stimulation at the same or adjusted parameters. If sexual arousal is achieved, the stimulation parameters including the electrode pair(s) are stored in memory at the programmable controller 300, the external patient controller 400, and / or the physician controller 500.

[0139] Optionally, even after achieving sexual arousal, at 710, additional stimulation can be implemented at the electrode pair(s) using the adjusted stimulation parameters, or a different electrode pair(s) can be selected for stimulation at the same parameters or at adjusted parameters to determine whether stronger sexual arousal can be achieved at 712. If not, stimulation can be repeated with different configurations at 710, or the test can end and the parameters stored at 708 can be used. If stronger sexual arousal is achieved, at 708, the stimulation parameters of the electrode pair(s) are stored as the preferred parameters in the memory at the programmable controller 300, the external patient controller 400, and / or the physician controller 500, and the previously stored parameters can be overwritten. Optionally, even after achieving stronger sexual arousal, at 710, additional stimulation can be implemented at the electrode pair(s) using the adjusted stimulation parameters, or a different electrode pair(s) can be selected for stimulation at the same parameters or at adjusted parameters to determine whether even stronger sexual arousal can be achieved at 712.

[0140] Once the user is satisfied with the determined preferred parameters, or because all electrode pairings in the array have been tested or because suitable sexual arousal has been achieved, the preferred parameters are stored. In this way, the patient external controller 400 and / or the external physician controller 500 can initiate a stimulation routine at a later time (e.g., minutes, hours, days, months, years later) with the preferred parameters; thereby causing sexual arousal, e.g., erection.

[0141] Referring now to Figure 16 An exemplary method for determining the optimal positioning of a flexible paddle is described. In the method 800, at step 802, an electrode array is placed at a first location proximate the pelvic plexus and near at least one cavernosal nerve. At least one electrode pair is selectively activated to stimulate the at least one cavernosal nerve and generate a first location response. At step 804, the same process is repeated at a second location different from the first location, proximate the pelvic plexus, and near the at least one cavernosal nerve. Specifically, at least one electrode pair is selectively activated to stimulate the at least one cavernosal nerve and generate a second location response. At step 806, the first location response and the second location response are compared to determine which response elicits a stronger location erection response. If more than one location elicits an erection response, the location that elicits the strongest erection response without causing significant discomfort or side effects can be selected as the optimal location. The process can be repeated at a third location to further determine the optimal location for implanting a flexible paddle.

[0142] Referring now to Figure 17, exemplary methods for determining a preferred stimulation protocol that elicits one or more levels of erection and optionally for neurorehabilitation and / or for penile rehabilitation are described. In the method 900, at step 902, at least one electrode pair in the array is selectively activated to stimulate at least one cavernosal nerve. The at least one electrode pair can be selectively activated in a first direction and a second direction to generate a first direction response and a second direction response, respectively. At step 904, a current flow direction that elicits a first erection response can be determined by comparing the first direction response and the second direction response. At step 906, at least one electrode pair in the array is selectively activated in a preferred direction to stimulate at least one cavernosal nerve. The at least one electrode pair in a first region and the at least one electrode pair in a second region can be selectively activated in the preferred direction to generate a first region response and a second region response, respectively.

[0143] At step 908, an electrode region that elicits a second erection response can be determined by comparing the first region response and the second region response. The process is then repeated to determine a preferred electrode pair. At step 910, at least one electrode pair in the array is selectively activated in the preferred direction and within the preferred region. The first electrode pair and the second electrode pair within the preferred region can be selectively activated in the preferred direction to generate a first pair response and a second pair response, respectively. At step 912, one or more electrode pairs that elicit a third erection response can be determined by comparing the first pair response and the second pair response.

[0144] At step 914, the preferred electrode pair(s) can be selectively activated at different frequencies and current intensities. The preferred electrode pair(s) can be selectively activated in a first mode with a first stimulation protocol and a second mode with a second stimulation protocol to generate a first response and a second response, where the second stimulation protocol employs different stimulation parameters than the first stimulation protocol. Optionally, at step 916, an activation mode for a full erection for sexual activity can be determined by comparing the first mode response and the second mode response. Optionally, at step 918, an activation mode for an incomplete erection can be determined by comparing the first mode response and the second mode response, for example for assisting in a medical procedure such as applying a urinary catheter. Optionally, at step 920, the comparison can be repeated to determine an activation mode for rehabilitating at least one cavernosal nerve. Optionally, at step 922, the comparison can be repeated to determine an activation mode for penile rehabilitation to reduce penile fibrosis. At step 924, the determined activation mode(s) can be stored in a memory of the programmable controller 300, the external patient controller 400, and / or the physician controller 500.

[0145] Referring now to Figure 18described above. In method 1000, steps 1002-1010 are similar to steps 914-918 in method 900. At step 1002, a preferred electrode pair can be selectively activated in a first mode with a first stimulation protocol to generate a first response. At step 1004, the preferred electrode pair can be selectively activated in a second mode with a second stimulation protocol to generate a second response. At step 1006, the first response and the second response can be compared. Optionally, at step 1008, a fast erection activation mode can be determined based on the comparison. Optionally, at step 1010, an activation mode to promote rehabilitation of at least one cavernous nerve based on the comparison. The nerve rehabilitation mode can supply a lower current intensity stimulation than the fast erection activation mode. Optionally, at step 1012, machine learning or other types of artificial intelligence can be used to adjust the nerve rehabilitation activation mode. In addition, the preferred electrodes can also be used to measure neural activity, and these measurements can be used in conjunction with artificial intelligence to adjust the rehabilitation activation mode to achieve more efficient or effective neural transmission. Alternatively, the method of FIG. 8 can be used to adjust a stimulation protocol for producing one or more levels of erection or a penile rehabilitation stimulation protocol for reducing fibrosis.

[0146] In addition to stimulation protocols that cause a fast erection response, restore neural transmission in the cavernous nerves, or reduce penile fibrosis, the systems and methods described herein can also be used to treat urinary incontinence by, for example, electrically stimulating one or more nerves of the lower urinary tract. As described above, electrical stimulation of the pelvic floor can promote neural regeneration and thus help improve urinary function after radical prostatectomy. In particular, low intensity stimulation can reestablish neural function by promoting axonal regeneration and reconnection. Such neural regeneration is expected to improve urinary function and quality of life for patients with spinal cord injuries and concomitant urological disease, as described in more detail below in the Figures 19A-19E Detailed Description.

[0147] Figures 19A-19E Results from Qualiveen questionnaires provided by spinal cord injury patients with urological disease who participated in a study using an implantable system described herein that applies a stimulation protocol to treat urinary incontinence (labeled CaverSTIM, n=2) are illustrated. The results are compared to published data for other therapies that treat urological disease to illustrate the improvement in quality of life for CaverSTIM patients, for example, as measured by the specific impact of urinary problems (SIUP), inconvenience, restriction, fear, and feeling. For example, Figure 19ACaverSTIM Qualiveen questionnaire data were compared to published data from the following studies: in a study in which patients were given a single dose of intrathecal infusion of expanded WJ-MSC or placebo, n=7 (designated Albu 2020); a study involving an exoskeleton training program for lower urinary tract function, n=4 (designated Williams 2021); in a study in which patients were given an intradetrusor injection of botulinum toxin A (OnabotA, n=28) at baseline and week 24 (designated Ferreira 2018 injection OnabotA); and in a study in which patients were given oral Oxybutynin (Oxy, n=3) at baseline and week 24 (designated Ferreira 2018 oral Oxy) to illustrate the reported change in SIUP after the respective intervention therapy, which measures the specific impact of urinary problems on the quality of life of patients with spinal cord injury. As shown in Figure 19A CaverSTIM patients reported a significant decrease in the specific impact of urinary problems on their quality of life after receiving an implantable system intervention (treatment of urinary incontinence with a stimulation regimen) compared to Ferreira 2018 oral Oxy patients, and especially compared to Albu 2020 patients and Willaims 2021 patients.

[0148] Figure 19B CaverSTIM Qualiveen questionnaire data were compared to published data from the following studies: in a study in which patients were given a single dose of intrathecal infusion of expanded WJ-MSC or placebo, n=7 (designated Albu 2020); and a study involving an exoskeleton training program for lower urinary tract function, n=4 (designated Williams 2021) to illustrate the reported change in inconvenience experienced by patients with spinal cord injury after the respective intervention therapy, which is measured by identifying the places and activities in which patients experience inconvenience related to their urinary problems. As shown in Figure 19B CaverSTIM patients reported a significant decrease in inconvenience related to urinary problems after receiving an implantable system intervention (treatment of urinary incontinence with a stimulation regimen) compared to Albu 2020 patients, and especially compared to Willaims 2021 patients.

[0149] Figure 19CCaverSTIM Qualiveen questionnaire data was compared to published data from a study in which patients were given a single dose of intrathecal infusion of expanded Wharton’s Jelly Mesenchymal Stromal Cells (WJ-MSC) or placebo, n=7 (labeled Albu 2020 Mean; Albu 2020), and a study involving an exoskeleton training program for lower urinary tract function, n=4 (labeled Williams 2021 Mean; Williams 2021), to illustrate changes in reported restrictions experienced by patients with spinal cord injury following the respective intervention, as measured by the frequency with which patients reduced outings or took precautions in performing activities. As shown in Table 2, CaverSTIM patients reported a significant reduction in restrictions related to voiding issues following intervention with the implantable system and treatment of urinary incontinence with the stimulation regimen, compared to Albu 2020 patients and Willaims 2021 patients. Figure 19C CaverSTIM Qualiveen questionnaire data was compared to published data from a study in which patients were given a single dose of intrathecal infusion of expanded Wharton’s Jelly Mesenchymal Stromal Cells (WJ-MSC) or placebo, n=7 (labeled Albu 2020 Mean; Albu 2020), and a study involving an exoskeleton training program for lower urinary tract function, n=4 (labeled Williams 2021 Mean; Williams 2021), to illustrate changes in reported restrictions experienced by patients with spinal cord injury following the respective intervention, as measured by the frequency with which patients reduced outings or took precautions in performing activities. As shown in Table 2, CaverSTIM patients reported a significant reduction in restrictions related to voiding issues following intervention with the implantable system and treatment of urinary incontinence with the stimulation regimen, compared to Albu 2020 patients and Willaims 2021 patients.

[0150] Figure 19D CaverSTIM Qualiveen questionnaire data was compared to published data from a study in which patients were given a single dose of intrathecal infusion of expanded Wharton’s Jelly Mesenchymal Stromal Cells (WJ-MSC) or placebo, n=7 (labeled Albu 2020 Mean; Albu 2020), and a study involving an exoskeleton training program for lower urinary tract function, n=4 (labeled Williams 2021 Mean; Williams 2021), to illustrate changes in reported restrictions experienced by patients with spinal cord injury following the respective intervention, as measured by the frequency with which patients reduced outings or took precautions in performing activities. As shown in Table 2, CaverSTIM patients reported a significant reduction in restrictions related to voiding issues following intervention with the implantable system and treatment of urinary incontinence with the stimulation regimen, compared to Albu 2020 patients and Willaims 2021 patients. Figure 19D CaverSTIM Qualiveen questionnaire data was compared to published data from a study in which patients were given a single dose of intrathecal infusion of expanded Wharton’s Jelly Mesenchymal Stromal Cells (WJ-MSC) or placebo, n=7 (labeled Albu 2020 Mean; Albu 2020), and a study involving an exoskeleton training program for lower urinary tract function, n=4 (labeled Williams 2021 Mean; Williams 2021), to illustrate changes in reported restrictions experienced by patients with spinal cord injury following the respective intervention, as measured by the frequency with which patients reduced outings or took precautions in performing activities. As shown in Table 2, CaverSTIM patients reported a significant reduction in restrictions related to voiding issues following intervention with the implantable system and treatment of urinary incontinence with the stimulation regimen, compared to Albu 2020 patients and Willaims 2021 patients.

[0151] Figure 19ECaverSTIM Qualiveen questionnaire data were compared to published data from a study in which patients were given a single dose of intrathecal infusion of expanded WJ-MSC or placebo, n=7 (labeled Albu 2020 Mean; Albu 2020), and a study involving an exoskeleton training program for lower urinary tract function, n=4 (labeled Williams 2021 Mean; Williams 2021), to illustrate the changes in the reported feelings experienced by patients with spinal cord injuries following the respective intervention, as measured by the negative impact on patient self-esteem of urinary issues such as shame, humiliation, and anxiety. Figure 19E As shown in

[0152] Notably, in an ongoing clinical trial involving patients with spinal cord injuries, using the implantable system disclosed herein to apply a stimulation regimen to treat urinary incontinence, significant improvements in urinary function and bowel function were observed. For example, one patient in the study reported needing 1 hour to defecate prior to device implantation and reported being able to defecate within 30 minutes after the intervention. Another patient in the study reported experiencing 10 to 20 days of constipation prior to device implantation and reported that the time to constipation was halved after the intervention. Thus, the implantable system described herein can modulate nerves that control the patient’s pelvic plexus of the lower bowel, which are in close proximity to the implanted electrodes.

[0153] Referring now to Figure 20 , a schematic representation of the local anatomy is shown. The nerves that control the lower urinary tract include the pelvic parasympathetic nerves, hypogastric sympathetic nerves, and pudendal nerves. The flexible paddle is preferably configured so that the pudendal nerves, which control the external sphincter, are stimulated. However, depending on the location of the implantation of the flexible paddle and the configuration of the electrodes, other nerves that are not in direct contact with the electrodes, including the hypogastric sympathetic nerves, can be rehabilitated.

[0154] Referring now to Figure 21A and Figure 21B , cross-sectional side views of exemplary flexible paddles are shown. Similar to Figure 2A and Figure 2BThe flexible paddle 202, such as those shown in FIGS. 1-3, can be used to treat urinary incontinence. In particular, an implantable stimulation unit can include a first flexible paddle 202 and a second flexible paddle 202, each including an array of electrodes 204 and suture holes, cables, and a programmable controller, as described above. The electrodes 204 can be arranged in multiple rows and columns, and can apply a bipolar stimulation such that current passes from one electrode to another to stimulate a nerve or set of nerves disposed therebetween. The flexible paddle 202 is preferably sized and shaped to abut at least a portion of a patient's pelvic plexus. The first flexible paddle is configured to conform to a first half of the pelvic plexus, and the second flexible paddle is configured to conform to a second half of the pelvic plexus. The flexible paddles can be curved to form an arc that conforms to the pelvic plexus, and can be implanted thereon, for example, during a prostatectomy procedure. Preferably, the flexible paddle 202 conforms to the anatomical shape of a portion of the pelvic plexus, and can cover a portion or the entire area of the pelvic plexus such that the electrodes 204 optimally contact the pudendal nerve. The flexible paddle can include a structural matrix of silicone or other flexible non-conductive material that allows for adaptation and molding to the local anatomy, thereby optimizing placement and minimizing tissue reaction. The flexible paddle can have a flat structure that is designed into a suitable shape (e.g., hemispherical, rectangular, square, oval, elliptical, or trapezoidal), and is dimensioned to better fit the anatomy and needs of each patient.

[0155] As Figure 21A shown in FIG. 4, the flexible paddle 212 can include a first plurality of electrodes 214a on a first surface of the paddle. As Figure 21B shown in FIG. 4, the flexible paddle 212 can additionally include a second plurality of electrodes 214b on a second surface of the paddle opposite the first surface. Figure 21B Embodiments of the present application can be particularly beneficial for treating urinary incontinence because the damaged nerves, such as the hypogastric sympathetic nerves, can not be proximate to the pelvic floor. Because low intensity stimulation is used to rehabilitate the one or more nerves that control the lower urinary tract, a larger portion of the pelvic plexus can be stimulated without producing adverse effects.

[0156] Figure 21C and Figure 21D are perspective views with inset detail showing placement of the flexible paddle 212 positioned on a patient's pelvic plexus. Preferably, the flexible paddle 212 is positioned against the pelvic plexus such that the paddle surrounds the urethra and is proximate to the pudendal nerve. Figure 21A and Figure 21B are perspective views with inset detail showing placement of the flexible paddle 212 positioned on a patient's pelvic plexus. Preferably, the flexible paddle 212 is positioned against the pelvic plexus such that the paddle surrounds the urethra and is proximate to the pudendal nerve. Figure 21D shows Figure 21BThe implantable flexible paddle of FIG. 1 has a first plurality of electrodes 214c and a second plurality of electrodes 214d on opposite surfaces of the paddle. The first plurality of electrodes 214c can be configured to stimulate nerves proximate to the pelvic floor, and the second plurality of electrodes 214d can be configured to stimulate nerves proximate to the bladder neck and internal sphincter. In particular, this configuration allows for stimulation of a larger area, which can result in rehabilitation and regeneration of the hypogastric sympathetic nerves or other nerves not in direct contact with the electrodes in addition to the pudendal nerve.

[0157] Low intensity stimulation can be designed to promote regeneration of damaged axons and reconnection of nerves, and preferably does not activate the nerves. Thus, the patient should not be able to perceive the stimulation and should not have a physiological response. In some embodiments, it is not necessary to determine the optimal electrode pair. Rather, preferably all electrodes on each flexible paddle are activated, which increases the area of the pelvic plexus that is stimulated and promotes regeneration of all nerves in the area. Alternatively, only one electrode pair or multiple electrode pairs on each flexible paddle can be activated.

[0158] Preferably, the bladder nerve rehabilitation stimulation pattern has a low current intensity, similar to the current intensity of the nerve rehabilitation stimulation pattern for rehabilitating at least one cavernous nerve. For example, the bladder nerve rehabilitation stimulation regimen can apply a current amplitude in the range of 0.1 to 2 mA, a frequency in the range of 10 to 48 Hz, and a pulse width in the range of 0.01 to 1 millisecond. The programmable controller can be programmed to automatically execute the bladder nerve rehabilitation stimulation pulse sequence at least once a day for at least one hour at one or more specified times, for example, just before the patient wakes up.

[0159] Referring now to Figure 22 Another exemplary flexible paddle for use with the electrical stimulation systems described herein is provided. In particular, without the implantable programmable controller 300, the programmable controller can be integrated with, for example, an external patient controller and / or an external physician controller (as described above) such that the proximal end of the electrical cable 208 can include a controller 1100 having an antenna for wireless communication with the external patient controller and / or the external physician controller. The antenna can be constructed using technology provided by Stimwave Technologies (Pompano Beach, FL). For example, as Figure 22As shown in FIG. 4, the patient controller 400 can be configured to transmit one or more commands to the controller 1100 via an antenna of the controller 1100 in a wireless transcutaneous manner to initiate and / or stop a stimulation session in any of the stimulation modes described above, and / or to adjust operational parameters of the controller 1100. In addition, the patient controller 400 can transmit power to the controller 1100 transcutaneously during a stimulation session. Thus, the controller 1100 can also include a memory for storing operational parameters, e.g., for selectively activating one or more electrode pairs in accordance with a stimulation session. For example, the controller 1100 can receive a command via the antenna to initiate a stimulation session and activate one or more preferred electrode pairs in accordance with operational parameters associated with the stimulation session. The controller 1100 can include a stimulation circuit, a microprocessor, and a memory (e.g., EEPROM) as described above, as well as antenna technology. In this manner, the microprocessor can execute programmed instructions stored in the memory that are related to the preferred stimulation electrodes in response to the transcutaneous signals from the patient controller 400.

[0160] In some embodiments, the system includes a wearable device, such as a belt or harness designed to hold the patient controller 400. In this manner, the patient controller 400 can be held in the wearable device throughout a stimulation session to provide power and stimulation protocols to the antenna of the controller 1100 transcutaneously. Once the session has ended, e.g., after sexual or medical activity is complete, the patient can remove the patient controller 400 and / or the wearable device.

[0161] As described above, the programmable controller can be controlled by an external patient controller. The external patient controller preferably includes a user interface that allows a user, e.g., a patient, physician, caregiver, to adjust a limited number of operational parameters of the programmable controller, including starting and stopping a bladder neurorehabilitation stimulation session. The external physician controller can be programmed to communicate with the external patient controller and the programmable controller. The external physician controller can be used to cause the non-volatile memory of the programmable controller to store a bladder neurorehabilitation stimulation protocol that controls the restoration of neural transmission in the nerves of the lower urinary tract when activated on demand by the external patient controller or automatically by the programmable controller at a preset time.

[0162] While various illustrative embodiments of the application have been described above, it will be apparent to one skilled in the art that many modifications and variations can be made therein without departing from the true scope of the application. The appended claims are intended to cover all such modifications and variations as falling within the true scope of the application.

Claims

1. A system for treating erectile dysfunction, the system comprising: a flexible paddle having an electrode array, the flexible paddle configured to be implanted proximate one or more cavernous nerves; as well as a programmable controller comprising a stimulation circuit operatively coupled to the electrode array, a microprocessor, and a memory, the stimulation circuit being configured to execute programmed instructions stored in the memory to: The stimulation circuit selectively activates a preferred set of excitation electrodes in the electrode array in a preferred current direction within a preferred area of ​​the electrode array according to preferred stimulation parameters stored in the memory to stimulate the one or more cavernous nerves, thereby inducing an erectile response.

2. The system of claim 1 , wherein the programmable controller is disposed within an implantable pulse generator configured to be operably coupled to the electrode array via one or more leads.

3. The system of claim 2, wherein the programmable controller is configured to cause the stimulation circuit to selectively activate the preferred set of stimulation electrodes in response to a command received from at least one of an external patient controller or an external physician controller.

4. The system of claim 1 , wherein the programmable controller is disposed within at least one of an external patient controller or an external physician controller, and wherein the flexible paddle comprises an antenna configured to communicate with at least one of the external patient controller or the external physician controller.

5. The system of claim 4, wherein the flexible paddle comprises a controller, the controller comprising the antenna, the controller having a memory configured to store one or more operating parameters associated with the electrode array.

6. The system of claim 5, wherein the programmable controller is configured to cause the stimulation circuit to cause the controller to selectively activate the preferred set of stimulation electrodes in response to user input received by at least one of the external patient controller or the external physician controller.

7. The system of claim 1 , wherein the erectile response comprises an erection sufficient to enable sexual intercourse.

8. The system of claim 1 , wherein the erectile response comprises an ejaculatory response.

9. The system of claim 8, wherein the current applied by the stimulation circuit has an amplitude in the range of 0.5 mA to 25 mA, a frequency between 10 Hz to 48 Hz, and a pulse width between 0.1 milliseconds to 1.0 milliseconds.

10. The system of claim 1, wherein the erectile response comprises an erection sufficient to perform a medical procedure.

11. The system of claim 10, wherein the medical procedure comprises application of a urinary catheter.

12. The system of claim 10, wherein the current applied by the stimulation circuit has an amplitude in the range of 1 mA to 6 mA, a frequency between 6 Hz and 100 Hz, and a pulse width between 0.1 milliseconds and 1.0 milliseconds.

13. The system of claim 1, wherein the erectile response promotes restoration of neurotransmission via the one or more cavernous nerves.

14. The system of claim 13, wherein the programmable controller is configured to automatically activate the stimulation circuit to selectively activate the preferred set of stimulation electrodes at least once a day to restore neural transmission.

15. The system of claim 1, wherein the erectile response induces at least a partial penile erection, thereby reducing the risk of penile fibrosis.

16. The system of claim 1 , wherein the microprocessor is configured to execute programmed instructions stored in the memory to: causing the stimulation circuit to selectively activate a first pair of electrodes in the electrode array to generate a first current in a first direction between the first pair of electrodes, the first current being configured to stimulate the cavernous nerve to induce a first erectile response; causing the stimulation circuit to selectively activate a second pair of electrodes in the array to generate a second current in a second direction between the second pair of electrodes, the second direction being different from the first direction, the second current being configured to stimulate the cavernous nerve to induce a second erectile response; identifying the first erectile response or the second erectile response as a first preferred erectile response; and An identification of the first direction or the second direction is stored as the preferred current direction.

17. The system of claim 16, wherein the microprocessor is configured to execute programmed instructions stored in the memory to: causing the stimulation circuit to selectively activate electrodes in a first region of the electrode array having the preferred current direction to generate a third erectile response; causing the stimulation circuit to selectively activate electrodes in a second region of the electrode array having the preferred current direction to generate a fourth erectile response; identifying the third erectile response or the fourth erectile response as a second preferred erectile response; and The identifier of the first area or the identifier of the second area is stored as the preferred area.

18. The system of claim 17, wherein the microprocessor is configured to execute programmed instructions stored in the memory to: causing the stimulation circuit to sequentially activate a subset of electrodes within the preferred region in the preferred current direction to elicit a series of erectile responses; identifying a favorable erectile response from the series of erectile responses; and An identification of at least a subset of electrodes within the preferred region is stored as the preferred stimulation electrode set.

19. The system of claim 18, wherein the microprocessor is configured to execute programmed instructions stored in the memory to: causing the stimulation circuit to selectively activate the preferred set of stimulation electrodes in the preferred current direction using a series of stimulation parameters to elicit an additional series of erectile responses; identifying the best response from among the additional series of erectile responses; and The stimulation parameters that elicit the best response are stored as the preferred stimulation parameters.

20. The system of claim 1, wherein the flexible paddle is configured to be implanted laparoscopically into the pelvic plexus.

21. An implantable system for treating a pelvic condition, the system comprising: a flexible paddle having an electrode array disposed on a first side, the flexible paddle configured to be disposed adjacent a patient's pelvic plexus; as well as a programmable controller comprising a stimulation circuit, a microprocessor, and a memory, the stimulation circuit being operatively coupled to the array, the microprocessor being configured to execute programmed instructions stored in the memory to cause the stimulation circuit to activate at least one pair of electrodes in the electrode array, thereby stimulating at least one nerve to promote rehabilitation of the at least one nerve, wherein the programming instructions cause the stimulation circuit to be activated at least once per day.

22. The system of claim 21 , wherein the microprocessor is configured to execute programmed instructions stored in the memory to cause the stimulation circuit to activate at least one pair of electrodes in the electrode array, thereby stimulating at least one nerve associated with control of the patient's bladder sphincter to promote rehabilitation of the at least one nerve, thereby treating urinary incontinence.

23. The system of claim 21 , wherein the microprocessor is configured to execute programmed instructions stored in the memory to cause the stimulation circuit to activate at least one pair of electrodes in the electrode array, thereby stimulating at least one nerve associated with control of the patient's lower intestine to promote rehabilitation of the at least one nerve, thereby treating intestinal dysfunction.

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