Electrical stimulation systems and methods for functional recovery and treatment of sexual dysfunction

Abstract

An implantable stimulation system having a stimulation unit coupled to a programmable controller, a stimulation circuit, and an array of electrodes disposed on a pair of flexible paddles is provided for selectively stimulating at least one pelvic (e.g., cavernous) nerve. The programmable controller is preprogrammed to activate an excitation electrode routine that selectively scans the electrode array with a sequence of directional current flow and optimizes electrode selection for use in stimulating the nerve. The implantable stimulation system can be programmed to activate a first stimulation pulse sequence for inducing a rapid erectile response corresponding to a first mode, a second nerve function restoration stimulation mode for restoring nerve conduction in the cavernous nerve, a third penile function restoration mode for reducing penile fibrosis, and / or a fourth bladder nerve function restoration mode for restoring nerve conduction in nerves controlling the lower urinary tract.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims priority to U.S. Patent Application No. 17 / 450,392, filed Oct. 8, 2021; U.S. Patent Application No. 17 / 174,033, filed Feb. 11, 2021 (currently U.S. Patent No. 11,141,590); and U.S. Patent Application No. 17 / 174,021, filed Feb. 11, 2021 (currently U.S. Patent No. 11,141,589), the entire contents of each of which are incorporated herein by reference.

[0002] (Field of the Invention) The present disclosure relates to improved implantable electrical stimulation systems and methods for treating and preventing sexual disorders such as erectile dysfunction, erectile dysfunction following prostatectomy surgery, and erectile dysfunction associated with spinal cord injury. The system of the present invention can also be used to restore the function of the cavernous nerves, reduce penile fibrosis, or treat urinary incontinence.

Background Art

[0003] Sexual disorders (e.g., sexual dysfunction, sexual abnormalities) are complications experienced by an individual male or female or couple during any stage of normal sexual activity, including erection, physical pleasure, desire, preference, excitement, or orgasm. Sexual dysfunction generally has a significant impact on an individual's quality of life. The most widely recognized sexual disorders are erectile dysfunction (ED) and female sexual arousal disorder (FSAD).

[0004] Penile erection is a coordinated neurocardiovascular response. See Dean RC and Lue TF, Physiology of penile erection and pathophysiology of erectile dysfunction, Urol Clin North Am. 2005 Nov;32(4):379-95. In a flaccid state, the penile smooth muscle is contracted tonically, allowing only a small amount of blood flow for nutritional purposes. Penile erection occurs when sexual stimulation triggers the release of neurotransmitters (primarily nitric oxide) from cavernous nerve endings. These neurotransmitters cause relaxation of the smooth muscle cells in the cavernous arterioles and sinuses, bringing increased blood flow into the penis. This fills the cavernous sinuses with blood, dilating them against the tunica albuginea and partially occluding the venous outflows, thus resulting in an erection.

[0005] Erectile dysfunction (ED) is a multi-cause disorder with diverse etiologies, and can be psychogenic, vascular, hormonal, or neurological. However, research indicates that neurological and vascular causes are the most widely recognized. Generally, the main mechanisms involved in ED are dysfunction in neuronal responses (e.g., prostatectomy, cystectomy, abdominoperineectomy, spinal cord injury, or diabetes) or increased tension and / or contraction of smooth muscle in the corpus cavernosum and penile arteries (e.g., hypertension, atherosclerosis, and diabetes). See Sadeghi-Nejad H., Penileprosthesis surgery: a review of prosthetic devices and associated complications, Sex Med. 2007 Mar;4(2):296-309.

[0006] Prostatectomy is known to cause severe erectile dysfunction (ED). Generally, this essential surgical procedure for treating prostate cancer often leads to ED due to the inevitable disruption of nerve pathways for erectile function. These endometrial nerves are located around the prostate and can be damaged during surgery. Currently, surgeons are attempting to perform nerve-sparing surgery. However, in actual scenarios, surprisingly, 70% of patients undergoing prostatectomy will develop 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.

[0007] Pharmacological treatments are currently available for erectile dysfunction (ED). These drugs (e.g., sildenafil, Viagra®, tadalafil, Cialis®, or vardenafil, Levitra®) are effective for the majority of ED patients. However, they show low efficacy for ED resulting from prostatectomy or other causes associated with dysfunction in neuronal responses. Such drugs work by enhancing the action of the neurotransmitter nitric oxide by inhibiting the enzyme phosphodiesterase type 5 (PDE-5). 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 involved in disrupting cGMP, a second intracellular messenger generated by NO stimulation. cGMP is involved in the regulation of several protein-dependent kinases, which relax smooth muscle cells and promote erection. Therefore, patients with impaired erectile nerve response do not respond well to such drug therapies. One alternative for these patients is intrapeneal injection of a vasodilator, which induces erection directly, independently of the nerve 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, Baranoski 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 erectile dysfunction. 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 corpus cavernosum using a needle and are effective in over 80% of patients. See Harding. Common side effects of intrapenile injection include penile pain, bleeding, hematoma, priapism, and penile fibrosis, which can lead to permanent ED. See Leungwattanakij.

[0008] Another option for these patients is a penile implant, which consists of a pair of malleable or inflatable rods surgically embedded in the erectile chamber of the penis. See Sadeghi-Nejad. Different types of penile prostheses exist (rigid, semi-rigid, or inflatable), and all of these prostheses typically require irreversible and destructive surgery with the risk of intraoperative and postoperative complications. Such prostheses frequently require corrective surgery. Nevertheless, implantation of prostheses is a common procedure due to the lack of better treatment options. Therefore, there is a clear need for better therapeutic strategies for treating ED resulting from nerve pathway dysfunction, such as post-prostatectomy ED, that offer a painless, safe, easier, non-traumatic, and more effective alternative.

[0009] Numerous studies have shown that cavernous nerve stimulation can induce and maintain erections 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, electroneural stimulation for erectile response has been considered an option for patients undergoing prostatectomy. However, a barrier to the development of such techniques is the complex biostructure 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. 2012 Jul;26(7):769-77. Identifying the optimal site for electroneural stimulation is difficult because the human cavernous nerve progresses through a complex network of anastomoses from the pelvic plexus to the penis.Furthermore, there is considerable anatomical variability in the location of the cavernous nerve. The pelvic plexus is a transparent veil of microscopic nerves, and the cavernous nerve is not uniformly distributed in everyone. Moreover, each patient's biostructure, disease stage, and cancer location are unique. Collectively, these barriers make the identification of cavernous nerve segments for selective stimulation extremely difficult.

[0010] In some known systems, the location and identification of the cavernous nerve are performed during the implantation surgery. For example, Lue's U.S. Patent No. 4,585,005 (Patent Document 1) requires prior identification and isolation of the cavernous nerve. Spinelli's U.S. Patent No. 7,328,068 describes a method for stimulating penile nerve pathways, requiring precise implant positioning to achieve optimal stimulation. In Spinelli, neurophysiological monitoring assessment may be used as a method for positioning the optimal stimulation site before implantation. Boveja's U.S. Patent No. 7,330,762 discloses a system for electroneurostimulation of cavernous nerves, including different types of electrodes such as spiral electrodes, cuff electrodes, steroid-eluting electrodes, wrap electrodes, and hydrogel electrodes. Again, the Boveja system requires identification of the optimal site for stimulation before implantation. Whitehurst's U.S. Patent No. 7,865,243 describes a system and method for stimulating cavernous nerves. However, anatomical identification of the pudendal nerve and / or other nerve pathways to be stimulated must be positioned before implantation.

[0011] Recently, significant progress has been made in achieving practical neuroelectric stimulation systems for the treatment of erectile dysfunction (ED) that enable the localization and identification of the cavernous nerve after implantation. For example, U.S. Patent No. 9,821,163 (Patent Document 2) and No. 10,300,279 by Fraga da Silva et al., invented by the present inventors, describe neuroelectric stimulation systems in which electrodes are stimulated after implantation to experimentally determine a preferred electrode excitation configuration for achieving sexual arousal. While the inventions described in those patents represent considerable progress in the use of neuroelectric stimulation for the treatment of ED, it would be desirable to provide a method for reliably determining an electrode excitation configuration to produce excitation, which can be determined by an automated process.

[0012] After bilateral nerve-sparing radical prostatectomy, some patients, particularly younger patients without a history of ED or associated risk factors, may recover from erectile dysfunction. However, even when individuals regain erectile function, it is typically a long process, sometimes lasting several years. During the recovery period, permanent penile damage may occur, which in some cases can lead to permanent ED.

[0013] Recent advances in understanding the pathophysiology of post-prostatectomy erectile dysfunction have stimulated discussions regarding the management of this condition and led to the emergence of the concept of penile function recovery after prostatectomy. For example, 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, RL et al., Current penile-rehabilitation strategies: Clinical evidence, Arab J Urol,2013. 11(3):230-6, Gandaglia, G., et al. 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 such treatment is the recognition that prolonged inability to achieve an erection can lead to internal fibrosis, deterioration of penile structure, and progressive worsening of ED, ultimately resulting in a permanent state of ED.

[0014] As discussed in the aforementioned references, the regular cycle of penile erection is essential for tissue oxygenation and maintenance of penile function in healthy men. Indeed, physiological nocturnal penile swelling and spontaneous erections during sleep play a crucial role in maintaining organ oxygenation and function. In contrast, prolonged inability to achieve erection leads to chronic penile hypoxia and the resulting fibrosis-inducing cytokine production, 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):p.562-70. This unfavorable local intrapenile environment can lead to apoptosis and increased collagen production, potentially altering the spongiform structure. For example, see Gandaglia; Moreland, RB, 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): pp. 113-1120.

[0015] As further discussed in the references above, penile function restoration is defined as the use of any medical intervention or combination of interventions during or after prostatectomy with the goal of increasing penile blood flow, improving intracellular oxygenation, and avoiding or reducing fibrosis, until the ability to achieve spontaneous erectile function is restored. Penile function restoration treatment should preferably be applied until nerve regeneration is achieved, which can take 12 to 18 months, and up to several years, after prostatectomy. Currently, state-of-the-art technologies require oral PDE5 inhibitors, intracellular injection therapies (e.g., alprostadil), vacuum erection devices, or combinations of these treatments. See Mulhall, JP, 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):p.998-1008. Collectively, clinical trials using these approaches have reported little to no improvement. See Clavell-Hern and ez; Fode.

[0016] Another complication that can occur after prostatectomy or spinal cord injury is urinary incontinence resulting from damage to one or more nerves that control the lower urinary tract, namely the pelvic parasympathetic nerve, the hypogastric sympathetic nerve, and the pudendal nerve. Electrical stimulation may be used to treat neurogenic bladder dysfunction. The following techniques have been used: transrectal / transvaginal electrical stimulation, transepidermal electrical nerve stimulation (TENS), and sacral nerve modulation. Electrical pelvic floor stimulation (EPFS) may improve urinary incontinence. Early EPFS was performed with external stimulation devices such as anal and / or vaginal electrodes, but these devices are associated with several side effects, including leakage of electrical current from the device to the mucous membrane to which it is applied, which can result in pain during stimulation or damage to the mucous membrane.

[0017] The primary cause of urinary incontinence after prostatectomy is explained as sphincter dysfunction. Currently, pelvic floor muscle training (PFMT) is the most widely recommended non-invasive method to prevent urinary incontinence following radical prostatectomy. Nevertheless, it can take several months to restore voluntary control, and some patients may have persistent incontinence despite continued attempts at functional recovery. "Electrical stimulation of the pudendal nerve and its branches can produce direct and reflex responses in the urethra and 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 may promote nerve regeneration and thus help improve urinary function following radical prostatectomy.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 63,2 (2004):264-7.

[0018] In light of the aforementioned shortcomings of systems and methods known to date, there is a need for systems and methods that can be used to systematically identify the location of the cavernous nerve during and / or after implantation and to determine the optimal parameters for different modes of activation. Furthermore, there is a need for systems and methods that can be used after prostatectomy to increase tissue oxygenation, maintain penile function, thereby reducing fibrosis and regenerating the cavernous nerve. Furthermore, there is a need for systems and methods that can be used to treat other pelvic disorders such as urinary incontinence. [Prior art documents]

Patent Document

[0019]

Patent Document 1

Patent Document 2

Summary of the Invention

Means for Solving the Problems

[0020] The present disclosure provides a neuroelectrical stimulation system and method for treating sexual disorders, including in patients who are unable to spontaneously achieve penile erection (e.g., erectile dysfunction (ED) associated with functional cessation in neuronal responses such as post-prostatectomy ED), and patients suffering from female sexual arousal disorder (FSAD). Optimization of the electrode excitation configuration and stimulation parameters can be achieved without extensive experimental testing.

[0021] An electrical stimulation system for treating sexual disorders, such as ED, in patients may 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 (which are hereby incorporated by reference in their entirety). The implantable stimulation unit may include an array of electrodes disposed on an implantable paddle and a power source that may be rechargeable.

[0022] According to the principles of the present invention, the programmable controller of an implantable stimulation unit is pre-programmed with routines for optimizing the selection of a subset of an array of excitation electrodes and stimulation parameters to be applied to generate a rapid erectile response, restore the function of cavernous nerve transmission after implantation, and / or reduce penile fibrosis. The pre-programmed routines are subsequently activated following the implantation process and also after tissue healing to re-optimize the selection of the subset of excitation electrodes and / or adjust the stimulation parameters employed in any of a first rapid response mode, a second nerve function restoration mode, or a third penile function restoration mode.

[0023] In a preferred embodiment, the implantable stimulation unit includes an array of electrodes disposed on a pair of flexible paddles sized and shaped to be implanted in the pelvic plexus to selectively stimulate at least one cavernous nerve. The array of electrodes 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. According to one aspect of the present invention, the programmable controller is pre-programmed to initiate an excitation electrode routine that optimizes electrode selection for use in selectively scanning an electrode array on the paddle with a series of directional current flows in at least two directions and in at least two regions to stimulate the patient's cavernous nerve.

[0024] Upon completion of the electrode selection configuration process, the identification of a preferred subset of the array of electrodes ("excitation electrodes") is defined and stored in the non-volatile memory of the programmable controller. Thereafter, the stored electrode configuration is employed using stimulation parameters optimized to sufficiently stimulate one or more nerves of the pelvic plexus, such as at least one cavernous nerve, to cause sexual arousal, e.g., an erection. The stimulation prescription regimen can consist of stimulation parameters including pulse duration, frequency, voltage, and current and can be adjusted by an external physician controller and / or an external patient controller after implantation.

[0025] In a preferred embodiment, a programmable controller initiates a pre-programmed electrode configuration process, causing a stimulation circuit to selectively activate a first set of electrode pairs of an electrode array, generating a first current flow between them in a first direction, stimulating the cavernous nerve and inducing a first erectile response. Subsequently, the electrode configuration process selectively activates a second set of electrode pairs of the electrode array, generating a second current flow between them in a second direction, different from the first direction and possibly oblique to it, stimulating the cavernous nerve and inducing 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 preferred erectile response, thereby determining the preferred current flow direction, which may be stored in non-volatile memory for future stimulation. The programmed commands may identify a preferred erectile response in response to inputs generated by a sensor system associated with the programmable controller, or in response to inputs provided by an external patient controller or external physician controller.

[0026] Next, the programmable controller selectively activates a subset of the electrode array in the stimulation circuit using a previously determined preferred current flow direction, stimulating the cavernous nerve in at least the first and second regions. Specifically designed, a first subset of the electrode array in the first region is stimulated to produce a first local response, and a second subset of the electrode array in a second region distinct from the first region is stimulated to produce a second local response. The first and second local responses are compared to determine which response is more preferable, and their corresponding regions of the electrodes are selected as preferred excitation regions and stored in non-volatile memory for future stimulation.

[0027] Next, the programmable controller sequentially activates a subset of electrodes within a preferred excitation region using a previously determined preferred current flow direction in the stimulation circuit, thereby inducing a series of erectile responses. The series of erectile responses are compared to determine which response is more preferred, and their corresponding subsets of electrodes are selected as preferred excitation electrodes and stored in non-volatile memory for future stimulation.

[0028] Once a preferred excitation region, including a preferred excitation electrode with directional current flow, is determined, the programmable controller selectively activates the stimulation circuit and defines at least a first stimulation mode in which the applied electrical stimulation induces a rapid erectile response. In particular by design, the programmable controller causes the stimulation circuit to sequentially apply first and second stimulation prescription plans employing different stimulation parameters, thereby inducing first and second stimulation responses. The patient's physician or the patient then compares the first and second responses to determine which stimulation prescription plan produces a stronger and / or faster erectile response, selects that stimulation prescription plan as the preferred first stimulation mode, and stores it in non-volatile memory. In a preferred embodiment, the system of the present invention may include an external controller that can be operated in "on-demand" mode by the patient, for example, by pressing a button to activate an implantable stimulation unit and induce a rapid erectile response.

[0029] According to another aspect of the present invention, the programmable controller may also determine a second neuronal function recovery stimulation mode corresponding to a lower current intensity than the first stimulation mode. For example, the neuronal function recovery stimulation mode may have a set of stimulation parameters that apply a current amplitude in the range of 0.1 to 2 mA with a pulse width of 0.01 to 1.0 milliseconds at a frequency of 10 to 48 Hz, while the first stimulation mode may have a set of stimulation parameters that apply a current amplitude in the range of 0.5 to 25 mA with a pulse width of 0.1 to 1.0 milliseconds at a frequency of 10 to 48 Hz. The neuronal function recovery stimulation mode is designed to improve the transmission of neural activity along at least one cavernous nerve. The programmable controller may be programmed to automatically execute the neuronal function recovery stimulation pulse sequence at one or more defined times, for example, at least once a day immediately before the patient wakes up.

[0030] According to another aspect of the present invention, the programmable controller may also provide a third penile function recovery stimulation mode corresponding to a higher current intensity than the second stimulation mode. For example, the penile function recovery stimulation mode may have a set of stimulation parameters that apply a current amplitude in the range of 0.5 to 25 mA with a pulse width of 0.1 to 1.0 milliseconds at a frequency of 10 to 48 Hz. The penile function recovery mode is designed to induce at least partial penile swelling, increase tissue oxygenation, and reduce the risk of penile fibrosis. The programmable controller may be coupled to a sensor that monitors the degree of penile swelling, and programmed commands may store a set of stimulation parameters that produces the highest degree of penile swelling as the optimal set of stimulation parameters. The programmable controller may more preferably be programmed to automatically execute the penile function recovery stimulation pulse sequence at one or more predetermined times, for example, at least once a day, immediately before the patient wakes up. Following prostatectomy, both the nerve function recovery stimulation mode and the penile function recovery stimulation mode may be performed automatically and separately at least once a day.

[0031] Furthermore, according to the principles of the present invention, the programmable controller can be programmed to reactivate the excitation electrode configuration process several weeks or months after the completion of the implantation procedure and to optionally select a first, second, and / or third stimulation mode. Thus, the selection of a preferred excitation electrode and / or stimulation prescription plan may be re-optimized to address, for example, tissue encapsulation, taking into account the healing response of the tissue surrounding the implantable stimulation unit. In addition, such re-optimization programming may allow the system of the present invention to capture improvements in neurotransmission achieved by a neurofunctional recovery stimulation mode, such as inducing a rapid erectile response using a lower current intensity than initially requested after implantation. Such adjustments may be made under the control of a physician or patient. Alternatively, adjustments to the excitation electrode configuration and / or stimulation prescription plan for the first, second, and / or third stimulation modes may be made using at least one of machine learning or other forms of artificial intelligence.

[0032] An external patient controller may be configured to selectively activate the implantable stimulator in response to patient input, to actuate the excitation electrode configuration process, and / or refine the stimulation prescription plan employed in the first, second, and / or third stimulation modes, to selectively actuate the first stimulation mode on demand, and to set parameters, such as activation time and duration for the functional recovery stimulation mode. An external physician controller may also be configured to provide similar capabilities, including selectively activating the excitation electrode configuration process and revising and / or re-optimizing the electrode configuration and stimulation prescription plan stored in non-volatile memory. Preferably, the external physician controller also provides the ability to query the implantable stimulator and retrieve other operational data regarding the status and usage of the implantable stimulator.

[0033] The implantable stimulation unit and the external patient controller preferably communicate wirelessly. Therefore, the implantable stimulation unit may include a first transceiver, and the external patient controller may include a second transceiver. The first and second transceivers may use IEEE 802.11 or Bluetooth®. TM A communication scheme may be employed. Wireless communication between the first transceiver and the second transceiver may be encrypted. The external patient controller may be specifically designed for communication with the implantable stimulation unit, or it may consist of a smartphone, laptop, tablet, or smartwatch programmed to communicate with the implantable stimulation unit.

[0034] The implantable stimulation unit and the external physician controller preferably communicate wirelessly, and the external physician controller may include a third transceiver. The first and third transceivers are IEEE 802.11 or Bluetooth®. TM A communication scheme may be employed, and wireless communication between the first transceiver and the third transceiver may be encrypted. The external physician controller may be specifically designed for communication with the implantable stimulation unit, or it may be a smartphone, laptop, tablet, or desktop computer programmed to communicate with the implantable stimulation unit.

[0035] Flexible paddles having electrode arrays are preferably shaped to conform to the anatomical shape of a portion of the pelvic plexus, and more preferably sized and shaped to be implanted laparoscopically. In one embodiment, each flexible paddle has a hemispherical shape that conforms to half of the pelvic plexus and provides bilateral stimulation. Each paddle includes an array of at least two rows and two columns of individually addressable electrodes. Each paddle may also include one or more features, such as suture holes or anchors, configured to hold the paddle in contact with the pelvic plexus following radical prostatectomy. The anchors may be, for example, sutures or biocompatible glue. Alternatively, or in addition, each flexible paddle may include at least one opening designed to allow connective tissue growth within and / or through the paddle and to position the paddle adjacent to the pelvic plexus.

[0036] Methods for implanting an implantable stimulation unit, programming the implantable stimulation unit and configuring a preferred excitation electrode, electrode area, current direction, and stimulation prescription plan to induce a rapid erectile response, restore function of nerve transmission, or reduce penile fibrosis, and methods for using the system are also provided herein. The implantable stimulation unit and flexible paddle may be sized and shaped for implantation using a robot-guided surgical system or laparoscopically.

[0037] According to another aspect of the present invention, the system may be used to treat urinary incontinence by, for example, electrically stimulating one or more nerves in the lower urinary tract. Electrical stimulation of the pelvic floor may help promote nerve regeneration and thus improve urinary function following radical prostatectomy. In particular, low-intensity stimulation may re-establish nerve function by promoting axonal regrowth and reconnection.

[0038] The programmable controller can activate a pair of electrodes in an electrode array in the stimulation circuit to stimulate at least one nerve associated with the control of the bladder sphincter, such as the pudendal nerve, hypogastric sympathetic nerve, or pelvic parasympathetic nerve, thereby promoting the recovery of nerve function. The bladder nerve function recovery stimulation mode may 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 executed for at least one hour per day following prostatectomy.

[0039] The flexible paddle may further comprise a second array of electrodes positioned on a second side opposite to the first side. A programmable controller may cause the stimulation circuit to activate a pair of electrodes in the second array of electrodes, thereby stimulating at least one nerve associated with the control of the bladder sphincter.

[0040] Methods for treating urinary incontinence using the system described above are also provided herein. For example, a method may include embedding a flexible paddle having a first array of electrodes positioned on a first side and a second array of electrodes on a second side at a position adjacent to the pelvic plexus; coupling a programmable controller to the array of electrodes; and executing a command in a stimulation circuit stored in memory which is programmed to activate a pair of electrodes on the first and / or second array of electrodes and stimulate at least one nerve associated with the control of the bladder sphincter. The present invention provides, for example, the following: (Item 1) An implantable system for treating erectile dysfunction, wherein the system is A flexible paddle having an array of electrodes, A programmable controller equipped with a stimulation circuit, a microprocessor, and memory. Equipped with, The stimulation circuit is operably coupled to the array, and the microprocessor is The stimulation circuit is configured to selectively activate a first pair of electrodes in the array and generate a first current flow between them in a first direction, wherein the first current flow is configured to stimulate the cavernous nerve and induce a first erectile response. The stimulation circuit is to selectively activate the second electrode pair of the array and generate a second current flow between them in a second direction, wherein the second direction differs from the first direction, and the second current flow is configured to stimulate the cavernous nerve and induce a second erectile response. Identifying either the first erectile response or the second erectile response as the first preferred erectile response, The system stores the identification of either the first direction or the second direction as the preferred current direction for subsequent stimulation of the cavernous nerve. An embeddable system configured to execute programmed instructions stored in the memory for performing the above. (Item 2) The implantable system according to item 1, wherein the programmed command identifies either the first erectile response or the second erectile response as the first preferred erectile response in response to an input generated by a sensor system associated with the programmable controller. (Item 3) The implantable system according to item 1, wherein the programmed instructions, in response to input provided by an external patient controller or an external physician controller, identify either the first erectile response or the second erectile response as the first preferred erectile response. (Item 4) The electrode array comprises a first region and a second region, and the microprocessor is The stimulation circuit is to selectively activate the electrodes in the first region with the preferred current direction, thereby generating a third erectile response. The stimulation circuit is to selectively activate the electrodes in the second region with the preferred current direction, thereby generating a fourth erectile response. Identifying either the third or fourth erectile response as a second preferred erectile response, A preferred area is one in which the identification of either the first area or the second area is stored. The embeddable system described in item 1, further configured to execute programmed instructions stored in the memory for performing the above. (Item 5) The implantable system according to item 4, wherein the programmed command identifies either the third erectile response or the fourth erectile response as a second preferred erectile response in response to an input generated by a sensor system associated with the programmable controller. (Item 6) The implantable system according to item 4, wherein the programmed instructions identify either the third erectile response or the fourth erectile response as a second preferred erectile response in response to input provided by an external patient controller or an external physician controller. (Item 7) The aforementioned microprocessor is The stimulation circuit is instructed to sequentially activate a subset of electrodes within the preferred region with the preferred current direction, thereby inducing a series of erectile responses. Identifying a preferred erectile response from the aforementioned series of erectile responses, The identification of a subset of at least one electrode within the preferred region as a preferred set of excitation electrodes for subsequent stimulation of the cavernous nerve, and The embeddable system described in item 4, further configured to execute programmed instructions stored in the memory for performing the above. (Item 8) The implantable system according to item 7, wherein the programmed command identifies the preferred erectile response from a set of erectile responses in response to an input generated by a sensor system associated with the programmable controller. (Item 9) The implantable system according to item 7, wherein the programmed instructions identify the preferred erectile response from the set of erectile responses in response to input provided by an external patient controller or an external physician controller. (Item 10) The aforementioned microprocessor is In the aforementioned preferred current direction, the stimulation circuit is instructed to selectively activate the preferred set of excitation electrodes using a series of stimulation parameters, thereby inducing a further series of erectile responses. Identifying the optimal response from the aforementioned series of further erectile responses, The preferred stimulus parameters include storing the stimulus parameters that induce the optimal response. The embeddable system described in item 7, further configured to execute programmed instructions stored in the memory for performing the above. (Item 11) The implantable system according to item 10, wherein the programmed command identifies the optimal response from a series of further erectile responses in response to an input generated by a sensor system associated with the programmable controller. (Item 12) The implantable system according to item 10, wherein the programmed command identifies the optimal response from a series of further erectile responses in response to input provided by an external patient controller or an external physician controller. (Item 13) The implantable system according to item 10, wherein the programmed command storing the preferred stimulation parameters stores stimulation parameters that induce a rapid erectile response. (Item 14) The implantable system according to item 10, wherein the programmed command storing the preferred stimulation parameters stores stimulation parameters that restore function of neurotransmission via the cavernous nerve. (Item 15) The implantable system according to item 10, wherein the programmed instructions determining the preferred current direction, the preferred region, the preferred set of excitation electrodes, and the preferred stimulation parameters are configured to be executed periodically in response to commands from an external patient controller or an external physician controller after the implantable system has been implanted. (Item 16) The implantable system according to item 10, wherein the programmable controller is configured to adjust the preferred stimulus parameters using at least one of machine learning or artificial intelligence. (Item 17) The implantable system according to item 13, wherein the programmable controller is configured to activate the stimulation circuit and apply the stimulation parameters that induce a rapid erectile response in response to a command received from an external patient controller. (Item 18) The implantable system according to item 14, wherein the programmable controller is configured to automatically activate the stimulation circuit at least once a day and apply the stimulation parameters to restore the function of neurotransmission. (Item 19) The implantable system according to item 1, wherein the flexible paddle is configured to be implanted in the pelvic nerve plexus via laparoscopic surgery. (Item 20) The implantable system according to item 1, wherein the flexible paddle has a hemispherical shape, and the electrode array comprises at least two electrode rows and at least two electrode columns. (Item 21) The embeddable system according to item 1, wherein the second direction of the second current flow is oblique to the first direction of the first current flow. (Item 22) A method for treating erectile dysfunction, wherein the method is: The method involves placing a flexible paddle at a first position adjacent to the pelvic plexus and close to the cavernous nerve, wherein the flexible paddle has an array of electrodes. Using a programmable controller, the first electrode pair of the array is selectively activated, and the cavernous nerve is stimulated using current flow in a first direction that induces a first erectile response. Using the programmable controller, the second electrode pair of the array is selectively activated, and the cavernous nerve is stimulated using current flow in a second direction that induces a second erectile response. The first erectile response and the second erectile response are compared to determine the preferred erectile response, The programmable controller stores either the first direction or the second direction as a preferred current direction for applying further stimulation using the programmable controller. Methods that include... (Item 23) The electrode array includes a first region and a second region, and the method is as follows: Using the programmable controller, the electrodes in the first region with the preferred current direction are selectively activated to generate a third erectile response. Using the programmable controller, the electrodes in the second region with the preferred current direction are selectively activated to generate a fourth erectile response. The third erectile response and the fourth erectile response are compared to determine the second preferred erectile response. A preferred region for applying further stimulation using the programmable controller is to store either the first region or the second region in the programmable controller. The method described in item 22, further including the method described in item 22. (Item 24) Using the programmable controller, a subset of electrodes within the preferred region with the preferred current direction is sequentially activated to induce a series of erectile responses. Identifying a preferred erectile response from the aforementioned series of erectile responses, For the application of further stimulation using the programmable controller, the programmable controller stores the identification of at least one subset of electrodes within the preferred region. The method described in item 23, further including the method described in item 23. (Item 25) Using the programmable controller, a subset of electrodes in the preferred current direction is selectively activated using a series of stimulation parameters to induce a series of erectile responses. Identifying the optimal response from the aforementioned series of erectile responses, In order to apply further stimulation using the aforementioned programmable controller, preferred stimulation parameters are stored in the programmable controller. The method described in item 22, further including the method described in item 22. (Item 26) The method according to item 25, further comprising storing preferred stimulation parameters in the programmable controller for inducing a rapid erectile response or restoring function of neurotransmission via the cavernous nerve. (Item 27) The method according to item 22, wherein the second direction of current flow is different from the first direction of current flow and is oblique to the first direction. (Item 28) An implantable system for reducing penile fibrosis following prostatectomy, wherein the system is A flexible paddle having an array of electrodes configured to be positioned adjacent to the patient's pelvic nerve plexus, A programmable controller equipped with a stimulation circuit, a microprocessor, and memory. Equipped with, The stimulation circuit is operably coupled to the array, and the microprocessor is configured to execute programmed instructions stored in the memory, the instructions causing the stimulation circuit to selectively activate a set of excitation electrodes in the array of electrodes, stimulating one or more nerves in the patient's pelvic plexus, thereby inducing at least partial penile swelling. An implantable system in which the programmed commands cause activation of the stimulation circuit at least once a day during the recovery period following prostatectomy, thereby reducing the risk of penile fibrosis. (Item 29) The implantable system according to item 28, wherein the programmed instructions cause the stimulation circuit to further excite the set of excitation electrodes using a series of stimulation parameters and to identify the optimal set of stimulation parameters for inducing penile swelling. (Item 30) The embedded system described in item 29 stores the optimal set of stimulus parameters in the programmed instructions. (Item 31) The implantable system according to item 30, wherein the programmable controller is coupled to a sensor that monitors the degree of penile swelling, and the programmed command further stores the set of stimulation parameters that produce the highest degree of penile swelling as the optimal set of stimulation parameters. (Item 32) The implantable system according to item 31, wherein the programmed instructions identify the optimal set of stimulation parameters in response to inputs provided by an external patient controller or an external physician controller. (Item 33) The implantable system described in item 32 applies a current amplitude in the range of 0.5 to 25 mA at a frequency of 10 to 48 Hz with a pulse width of 0.1 to 1.0 milliseconds. (Item 34) An implantable system for treating erectile dysfunction, wherein the system is A flexible paddle having an array of electrodes configured to be positioned adjacent to the patient's pelvic nerve plexus, A programmable controller equipped with a stimulation circuit, a microprocessor, and memory. Equipped with, The stimulation circuit is operably coupled to the array, and the microprocessor is The stimulation circuit is to activate a subset of electrodes in the array according to a first set of stimulation parameters in response to an "on-demand" input from an external patient controller or an external physician controller, thereby inducing an erection. At least daily, in response to a scheduled input from the external patient controller or the external physician controller, a subset of the electrodes in the array is activated using a second set of stimulation parameters to induce an erectile response that promotes penile function recovery. An embeddable system configured to execute programmed instructions stored in the memory for performing the above. (Item 35) The implantable system according to item 34, wherein the programmed instructions cause the stimulation circuit to further excite a subset of the electrodes using a set of stimulation parameters and to identify the optimal set of stimulation parameters for at least one of the first set of stimulation parameters and the second set of stimulation parameters. (Item 36) The programmed instructions store the optimal set of stimulus parameters in the embeddable system described in item 35. (Item 37) The implantable system according to item 36, wherein the programmable controller is coupled to a sensor that monitors the degree of penile swelling, and the programmed command further stores the set of stimulation parameters that produce the highest degree of penile swelling as the optimal set of stimulation parameters. (Item 38) The implantable system according to item 36, wherein the programmed instructions identify the optimal set of stimulation parameters in response to inputs provided by an external patient controller or an external physician controller. (Item 39) The implantable system according to item 35, wherein the first set of stimulation parameters and the second set of stimulation parameters apply a current amplitude in the range of 0.5 to 25 mA at a frequency of 10 to 48 Hz with a pulse width of 0.1 to 1.0 milliseconds. (Item 40) The implantable system according to item 35, wherein the programmed instructions cause the stimulation circuit to further activate a subset of electrodes in the array using a third set of stimulation parameters in response to a scheduled input from the external patient controller or the external physician controller at least daily, thereby inducing an erectile response that promotes the functional recovery of the cavernous nerve. (Item 41) The implantable system described in item 40, wherein the third set of stimulation parameters applies a current amplitude in the range of 0.1 to 2 mA at a frequency of 10 to 48 Hz with a pulse width of 0.01 to 1.0 milliseconds. (Item 42) A method for reducing penile fibrosis following prostatectomy, wherein the method is During the prostatectomy procedure, a flexible paddle with an array of electrodes is implanted adjacent to the patient's pelvic nerve plexus, During or after the prostatectomy procedure, a programmable controller comprising a stimulating circuit, a microprocessor, and a memory is coupled to the electrode array, wherein the microprocessor is configured to execute programmed instructions stored in the memory, and the instructions cause the stimulating circuit to selectively activate a set of excitation electrodes in the electrode array. At least once a day, during the recovery period following the prostatectomy procedure, the programmed instructions shall be executed. Includes, A method wherein the instruction causes activation of the stimulation circuit, stimulates one or more nerves of the patient's pelvic plexus, induces at least partial penile swelling, and thereby reduces the risk of penile fibrosis. (Item 43) The method according to item 42, further comprising executing the programmed instructions, the instructions further causing the stimulation circuit to excite a set of excitation electrodes using a set of stimulation parameters and to identify the optimal set of stimulation parameters for inducing penile swelling. (Item 44) The method according to item 43, further comprising storing the optimal set of stimulus parameters. (Item 45) The present invention provides a sensor coupled to the microprocessor, wherein the sensor is configured to monitor the degree of penile swelling. The optimal set of stimulation parameters is to store the set of stimulation parameters that produces the greatest degree of penile swelling. The method described in item 44, further including the method described in item 44. (Item 46) Identifying the optimal set of stimulation parameters is the method of item 44, which includes accepting inputs provided by an external patient controller or an external physician controller. (Item 47) The stimulation circuit is the method described in item 42, wherein a current amplitude in the range of 0.5 to 25 mA is applied at a frequency of 10 to 48 Hz with a pulse width of 0.1 to 1.0 milliseconds. (Item 48) An implantable system for treating urinary incontinence, wherein the system is A flexible paddle having an array of electrodes arranged on a first side, wherein the flexible paddle is configured to be positioned adjacent to the patient's pelvic nerve plexus, A programmable controller equipped with a stimulation circuit, a microprocessor, and memory. Equipped with, The stimulation circuit is operably coupled to the array, and the microprocessor is configured to execute programmed instructions stored in the memory, the instructions causing the stimulation circuit to activate at least one pair of electrodes in the array of electrodes, stimulate at least one nerve associated with the control of the bladder sphincter, and promote the functional recovery of the at least one nerve. An implantable system in which the programmed command causes activation of the stimulation circuit at least once a day. (Item 49) The implantable system described in item 48, wherein the stimulation circuit applies 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. (Item 50) The implantable system according to item 48, wherein the flexible paddle is configured to be implanted in the pelvic nerve plexus via laparoscopic surgery. (Item 51) The implantable system according to item 48, wherein the flexible paddle has a hemispherical shape, and the electrode array comprises at least two electrode rows and at least two electrode columns. (Item 52) The implantable system according to item 48, wherein the programmed instructions cause the activation of the stimulus for at least one hour per day. (Item 53) The implantable system according to item 48, wherein the at least one nerve associated with the control of the bladder sphincter is the pudendal nerve, the inferior gastrointestinal sympathetic nerve, or the pelvic parasympathetic nerve. (Item 54) The implantable system according to item 48, wherein the programmed instructions cause the stimulation circuit to further activate at least one pair of electrodes of an array of electrodes, stimulate the pudendal nerve, and promote the functional recovery of the pudendal nerve. (Item 55) The implantable system according to item 54, wherein the flexible paddle further comprises a second array of electrodes arranged on a second side opposite to the first side. (Item 56) The implantable system according to item 55, wherein the programmed instructions cause the stimulation circuit to further activate at least one electrode pair of the second array of electrodes, stimulate the pudendal nerve, and promote the functional recovery of the pudendal nerve. (Item 57) The implantable system according to item 56, wherein the programmed instructions cause the stimulation circuit to further activate at least one electrode pair of the second array of electrodes, stimulate the hypogastric sympathetic nerve, and promote the functional recovery of the hypogastric sympathetic nerve. (Item 58) A method for treating urinary incontinence, wherein the method is The method involves implanting a flexible paddle adjacent to the pelvic nerve plexus, wherein the flexible paddle has an array of electrodes positioned on the first side. The invention involves connecting a programmable controller, which includes a stimulation circuit, a microprocessor, and a memory, to the electrode array, wherein the microprocessor is configured to execute programmed instructions stored in the memory, and the instructions cause the stimulation circuit to activate at least one electrode pair of the electrode array. The programmed command is executed, causing activation of the stimulation circuit and stimulating at least one nerve associated with the control of the bladder sphincter. Methods that include... (Item 59) The flexible paddle is implanted during prostatectomy, as described in item 58. (Item 60) The method according to item 58, further comprising executing the programmed instruction at least once a day. (Item 61) The method according to item 60, wherein executing the programmed command at least once a day includes stimulating the nerve for at least one hour. (Item 62) The stimulation circuit applies 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, as described in item 58. (Item 63) The method of item 58, further comprising using an external patient controller or an external physician controller to adjust the programmed instructions. (Item 64) The method according to item 58, wherein the at least one nerve associated with the control of the bladder sphincter is the pudendal nerve, the inferior sympathetic nerve, or the pelvic parasympathetic nerve. (Item 65) The method according to item 58, wherein executing the programmed command and causing activation of the stimulation circuit causes stimulation of the pudendal nerve. (Item 66) The method according to item 65, wherein the flexible paddle further comprises a second array of electrodes arranged on a second side opposite to the first side. (Item 67) The method according to item 66, wherein the microprocessor is further configured to execute programmed instructions stored in the memory, the instructions causing the stimulation circuit to activate at least one pair of electrodes of a second array of electrodes. (Item 68) The method according to item 67, further comprising executing the programmed command, causing activation of the stimulation circuit, and stimulating the hypogastric sympathetic nerve. [Brief explanation of the drawing]

[0041] These and other features, aspects, and advantages of this disclosure will become apparent from the following description, the appended claims, and the accompanying exemplary embodiments shown in the drawings briefly described below.

[0042] [Figure 1] Figure 1 is a schematic diagram of an exemplary electrical stimulation system constructed in accordance with the principles of this disclosure.

[0043] [Figure 2] Figures 2A and 2B are plan views of an exemplary flexible paddle suitable for use with the present invention and plan views of the distal ends of two paddles positioned to be positioned relative to the patient's pelvic plexus, respectively.

[0044] [Figure 3] Figure 3 is a plan view of an alternative embodiment of a flexible paddle suitable for use with the system of the present invention.

[0045] [Figure 4-1] Figures 4A and 4B are side and oblique views, respectively, of different electrode shapes for use in the flexible paddles of Figures 2 and 3, while Figures 4C-4E depict the charge distribution across the various electrode shapes shown in Figures 4A and 4B. [Figure 4-2] Figures 4A and 4B are side and oblique views, respectively, of different electrode shapes for use in the flexible paddles of Figures 2 and 3, while Figures 4C-4E depict the charge distribution across the various electrode shapes shown in Figures 4A and 4B.

[0046] [Figure 5] Figure 5 depicts a generalized block diagram of an exemplary programmable controller for the implantable stimulation unit of the stimulation system shown in Figure 1.

[0047] [Figure 6]Figure 6 depicts a generalized block diagram of an exemplary external patient controller for the stimulation system shown in Figure 1.

[0048] [Figure 7] Figure 7 is a block diagram of the functional components of an exemplary software-based programming system configured to be launched on an external physician controller of the stimulation system shown in Figure 1.

[0049] [Figure 8] Figures 8A and 8B are perspective views with insertion detail diagrams showing the placement of the flexible paddles shown in Figure 2, positioned on the patient's prostate and pelvic nerve plexus, respectively.

[0050] [Figure 9] Figures 9A and 9B are plan views, respectively, showing alternative placement of the flexible paddle of the present invention in the patient's urethra.

[0051] [Figure 10] Figures 10A-10C illustrate various directional current flows between adjacent electrode pairs positioned on the flexible paddle in Figure 2A.

[0052] [Figure 11] Figures 11A–11C illustrate illustrative regions within the electrode array of the flexible paddle shown in Figure 2A.

[0053] [Figure 12] Figures 12A-12C illustrate the selection of preferred electrode pairs within various electrode regions according to the present invention.

[0054] [Figure 13] Figure 13 illustrates an exemplary method for defining preferred excitation electrodes and regions for use in electroneural stimulation to obtain sexual arousal.

[0055] [Figure 14] Figure 14 illustrates a method for sequentially scanning adjacent electrode pairs during surgery according to the principle of the present invention.

[0056] [Figure 15] Figure 15 is a flowchart illustrating the steps of an exemplary method for constructing a subset of electrode arrays for stimulation to induce optimal sexual arousal according to the principles of the present invention.

[0057] [Figure 16] Figure 16 is a flowchart illustrating the steps of an exemplary method for determining the optimal position for embedding a flexible paddle according to the principles of this disclosure.

[0058] [Figure 17] Figure 17 is a flowchart illustrating the steps of an exemplary method for determining an optimal stimulation prescription plan to induce an erection, a stimulation prescription plan for restoring the function of at least one cavernous nerve, and / or a stimulation prescription plan for restoring penile function to reduce penile fibrosis.

[0059] [Figure 18] Figure 18 is a flowchart illustrating the steps of an exemplary method for adjusting the optimal mode for functional recovery after a certain time interval following implantation.

[0060] [Figure 19] Figure 19 is a schematic diagram of the local biological structure in the pelvic region of a male.

[0061] [Figure 20-1] Figures 20A and 20B are cross-sectional side views of an exemplary flexible paddle.

[0062] [Figure 20-2] Figures 20C and 20D are perspective views with insertive detail diagrams showing the placement of the flexible paddles shown in Figures 20A and 20B, respectively, on the patient's pelvic plexus. [Modes for carrying out the invention]

[0063] The systems and methods described herein may be used to treat not only erectile dysfunction (ED), including ED associated with a cessation of neuronal response (e.g., resulting from prostatectomy, cystectomy, abdominoperineectomy, spinal cord injury, and / or diabetes), and ED associated with increased tension and / or contractility of smooth muscle in the corpus cavernosum and penile arteries (e.g., resulting from hypertension, atherosclerosis, and / or diabetes), as well as sexual disorders such as sexual arousal disorder (FSAD) in women, and pelvic disorders such as urinary incontinence.

[0064] The systems and methods described herein are expected to restore the function of a denervated penis, for example, by electrically stimulating the terminal ends of the cavernous nerve. The neuronal pathway that induces the erectile response is the parasympathetic input originating from the pelvic splanchnic plexus. The pelvic splanchnic plexus consists of branches from the second, third, and fourth sacral nerves, which are confounded with the inferior hypogastric plexus and form a network of nerves within the pelvis. The cavernous nerve originates from the pelvic splanchnic nerves and proceeds along the prostatic plexus, which is located almost around the prostate, supplying parasympathetic fibers to the clitoral and urethral corpora cavernosa of the penis. Therefore, locating the optimal site for electrical nerve stimulation is difficult because the human cavernous nerve proceeds from the pelvic plexus to the penis through a complex network of anastomoses. Furthermore, there is considerable anatomical variability in the location of the cavernous nerve. Each patient's biostructure, disease stage, and / or cancer site are unique. The pelvic plexus is a transparent veil of microscopic nerves, and the cavernous nerves do not follow uniform localization in all individuals. Therefore, these barriers make the identification of cavernous nerve segments for selective stimulation extremely difficult. Systems and methods for overcoming these barriers are provided herein.

[0065] Referring to Figure 1, an overview of an exemplary electrical stimulation system constructed in accordance with the principles of this disclosure is provided. In Figure 1, the components of the system are not depicted to an exact scale, either relative or absolute. The electrical stimulation system 100 may include an implantable stimulation unit 200 having a programmable controller 300, an external patient controller 400, an external physician controller 500, and an external charger 600.

[0066] Referring again to Figures 2A and 2B, the implantable stimulation unit 200 includes at least one flexible paddle (for example, a first flexible paddle 202a and a second flexible paddle 202b: each paddle comprises an array of electrodes 204 and a suture hole 206), a cable 208, and a programmable controller 300. Each electrode 204 can be individually selected to release electrical energy to stimulate tissue. Preferably, the electrodes 204 are selected in pairs by the programmable controller of the implantable stimulation unit 200, and when activated by a user or physician (e.g., using an external patient controller 400 or a physician controller 500), they cause stimulation of erectile tissue. The electrodes 204 may be uniformly arranged and / or arranged in different spatial configurations. For example, the electrodes 204 may be spaced about 0.05 mm to about 5.0 mm apart, more preferably about 0.5 mm to about 1.5 mm apart. As an example, the electrodes 204 may be arranged in multiple rows and multiple columns, and the number of electrodes 204 may vary from about 10 to more than 50 electrodes as needed. The electrodes 204 may be subjected to bipolar stimulation such that current passes from one electrode to another, stimulating a nerve or group of nerves located between them. The array of electrodes 204 may have a tissue-friendly shape designed to reduce harmful tissue reactions that may lead to the formation of fibrous encapsulation. For example, the electrodes 204 may be sized and shaped such that convex, spherical, or flat portions are exposed on the flexible substrate, avoiding sharp surfaces that may damage or inflame the tissue. The electrodes 204 may be made from platinum, gold, or other conductive implantable materials suitable for electrical stimulation of nerves.

[0067] The flexible paddle 202 is preferably sized and shaped to be adjacent to at least a portion of the patient's pelvic plexus. As shown in Figures 2A and 2B, the first flexible substrate 202a is configured to conform to the first half of the pelvic plexus, and the second flexible paddle 202b is configured to conform to the second half of the pelvic plexus. The flexible paddle can be bent to form an arc shape that conforms to the pelvic plexus and can be embedded on the pelvic plexus (e.g., during prostatectomy surgery). Preferably, the flexible paddle 202 can conform to the anatomical shape of a portion of the pelvic plexus so that the electrode 204 is in optimal contact with the cavernous nerve, and can cover part or all of the area of ​​the pelvic plexus. The flexible paddle may have a structural matrix of silicone or other flexible, electrically nonconductive material, which allows for conformation and molding to local biostructure, optimizes placement, and minimizes tissue reaction. Flexible paddles may be designed in a suitable shape (e.g., hemisphere, rectangle, square, oval, ellipse, or trapezoid) and may have a flat structure whose dimensions are determined to better suit the biomechanism and needs of each patient.

[0068] Referring again to Figure 1, the implantable stimulation unit 200 includes a first array of electrodes 204 positioned on a first flexible paddle 202a and a second array of electrodes 204 positioned on a second flexible paddle 202b. The programmable controller 300 is preferably programmed to activate the stimulation circuit and simultaneously apply bilateral electrical stimulation to the patient's erectile function to one or more electrodes 204 positioned on the first flexible paddle 202a and one or more electrodes 204 positioned on the second flexible paddle 202b.

[0069] The implantable stimulator 200 may preferably include at least one anchor, individually attached to each flexible paddle, to maintain the flexible paddle in contact with the pelvic plexus. The anchor may consist of a suture, a biocompatible matrix, a biocompatible adhesive, or some combination thereof. In one preferred embodiment, each flexible paddle includes one or more suture holes 206 through which the suture can be fixed in place of the flexible paddle in the pelvic plexus. The implantable stimulator 200 may be encapsulated in one or more biocompatible materials (e.g., a titanium cage, a silicone cage) suitable for long-term implantation. In one embodiment, the flexible paddle 202 may include one or more cavities located between electrodes 204 or within specific areas of the paddle, allowing connective tissue growth within and / or through the paddle to enhance fixation and attachment in the pelvic cavity.

[0070] Cable 208 electrically couples the electrodes 204 of the flexible paddles 202a and 202b to the programmable controller 300. Cable 208 may be an insulated multi-conductor cable having independent wires for each electrode 204. Cable 208 may include multiple branches, as shown in the figure, to allow connection to the flexible paddles. In one embodiment, two or more cables 208 may be coupled to each of the arrays of electrodes 204 of the first flexible paddle 202a and the second flexible paddle 202b.

[0071] The programmable controller 300 is embedded in the inferior flank between the umbilical line and the iliac crest and may include a network of circuits configured to store stimulation routines and to cause the stimulation circuit to deliver electrical stimulation to a selected subset of electrodes 204 with parameters defined by a stimulation prescription plan. Parameters employed in such a stimulation prescription plan may include pulse duration, alternating current frequency, voltage, current, and duration of stimulation.

[0072] The programmable controller 300 may be controlled by an external patient controller 400 and, at will, be powered by the external patient controller 400. The external patient controller 400 preferably includes a user interface 402, which allows a user, e.g., a patient, physician, or caregiver, to adjust a limited number of operating parameters of the programmable controller 300, including initiating and stopping stimulation sessions. The programmable controller 300 communicates with the external patient controller 400 via its respective communication unit, each of which may include an induction coil and / or RF transceiver for communicating information in a bidirectional manner across the patient's skin and, at will, transmitting power to the programmable controller 300. For example, the external patient controller 400 may selectively activate the programmable controller 300 via its respective telemetry (or RF) system in the programmable controller 300 and the external patient controller 400 in response to user input received in the user interface 402.

[0073] In a preferred embodiment, a limited number of stimulation parameters may be regulated in the user interface 402 to reduce the chance of injury caused by misadjustment made by a non-physician user. In an alternative embodiment, the external patient controller 400 may also transmit to the programmable controller 300 adjustments to stimulation parameters, such as the electrodes used to apply stimulation, pulse duration, AC frequency, voltage, current, and duration of stimulation, in response to user input received in the user interface 402. In one embodiment, the external patient controller 400 may activate pre-programmed routines stored in the programmable controller 300, as described below herein, to identify an optimized set of excitation electrodes and store the identification of those electrodes in non-volatile memory.

[0074] The external patient controller 400 may be specifically designed for use with the implantable stimulation unit 200 and the programmable controller 300. Alternatively, the external patient controller 400 may be a smartphone, laptop, tablet, smartwatch, etc., 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 for communication with those devices, it may use cellular, 802.11 Wi-Fi, Zigbee®, and / or Bluetooth®. TM A chipset may be used. Specifically, an external patient controller may be programmed to selectively activate the programmable controller 300 in response to patient input.

[0075] The external physician controller 500 is programmed to communicate with the programmable controller 300 either directly or via the external patient controller 400. As shown in Figure 1, the external physician controller 500 may, for example, be a computer having a non-transient computer-readable medium programmed with instructions, which, when invoked on the computer, cause the computer to provide programming to the programmable controller 300. The external physician controller 500 may 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 may transfer programming data to the programmable controller 300 in order to reprogram the stimulation parameters programmed in the programmable controller 300. For example, the external physician controller 500 may be used to program and adjust parameters such as the electrode pair to be used for stimulation, pulse duration, AC frequency, voltage, current, and duration of stimulation. The external physician controller 500 may 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 may selectively activate a subset of desired electrodes 204, as further described below, and store the identification of those electrodes and a stimulation routine sufficient to induce sexual arousal or nerve or penile function restoration in the non-volatile memory of the programmable controller 300.

[0076] The external physician controller 500 may selectively activate the programmable controller 300 and execute a scanning protocol stored in non-volatile memory, which, when activated, determines preferred electrode pairs, current flow directions, and electrode regions that induce a rapid erectile response, enable neurological recovery, and / or reduce penile fibrosis, and stores the identification of those electrodes in the non-volatile memory of the programmable controller 300. More specifically, the scanning protocol may, in a predetermined manner as described below herein, selectively activate the electrodes 204 of the array and determine preferred current flow directions, preferred regions of the electrodes when stimulated in the preferred current flow directions, preferred electrode pairs within the preferred regions of the electrodes, and preferred stimulation parameters to be applied to those preferred electrodes, thereby causing the microprocessor of the programmable controller 300 to supply electrical stimulation via the stimulation circuit. The scanning protocol may be used to determine a stimulation pulse sequence corresponding to the erection mode of activation; optionally, a nerve function recovery stimulation pulse sequence corresponding to the function recovery mode of activation for the functional recovery of at least one cavernous nerve; and / or a penile function recovery stimulation pulse sequence corresponding to the function recovery mode of activation for inducing at least partial penile swelling and reducing penile fibrosis.

[0077] In one embodiment, the external physician controller 500 may be used to determine preferred electrode pairs and preferred stimulation parameters that produce a favorable rapid erectile response (or for nerve or penile function recovery) during the postoperative period (e.g., prostatectomy). The external physician controller 500 may be used to store in the non-volatile memory of the programmable controller 300 a first stimulation prescription plan that induces a rapid erectile response when activated on demand by the external patient controller 400, and a second stimulation prescription plan that provides a lower current intensity and restores neurotransmission through at least one cavernous nerve when activated via the external patient controller 400 or automatically by the programmable controller 300 at a predetermined time. The stimulation prescription plans are stored in the memory of the programmable controller 300, thereby allowing erections to be achieved at a later time using those parameters (e.g., in response to user input in the external patient controller 400).

[0078] The external physician controller 500 may be specifically designed for use with the implantable stimulation unit 200. Alternatively, the external physician controller 500 may be a smartphone, laptop, tablet, desktop computer, etc., programmed to communicate with the implantable stimulation unit 200. Thus, the external physician controller 500 may interface with the implantable stimulation unit 200 and / or the external patient controller 400 using software such as an application downloaded from an app store or "app," and for communication with those devices, it may use cellular, 802.11 Wi-Fi, Zigbee®, and / or Bluetooth®. TM A chipset may be used. The external physician controller 500 may communicate with the implantable stimulation unit 200 directly or via the external patient controller 400.

[0079] The external charger 600 can electrically communicate with the programmable controller 300 and charge the programmable controller 300 transcutaneously via its respective induction coils. The external charger 600 can generate an alert via an indicator LED, an audible alarm, or a vibration motor if the power level of the programmable controller 300 falls below a threshold power level.

[0080] Referring here to Figures 2A, 2B, and 3, exemplary paddle designs for an implantable stimulation unit are illustrated. The implantable stimulation unit 200 may include at least one flexible paddle 202 having an array of electrodes 204 and suture holes 206. The flexible paddle 202 may be operably coupled to a programmable controller 300 via a cable 208 having leads 210. The cable 208 may be an insulated multi-conductor cable having independent wires for each electrode 204. Figure 2A depicts one embodiment in which a single cable 208 couples the flexible paddle 202 to the programmable controller 300. Alternatively, as shown in Figure 3, two or more cables 208 may be provided to couple the flexible paddle 202 to the programmable controller 300. In the embodiment shown in Figure 3, one of the cables 208 may electrically connect a first subset of the array of electrodes 204, for example, six electrodes, to the programmable controller 300, while the other cable 208 may electrically connect a second subset of the array of electrodes 204, for example, the remaining six electrodes, to the programmable controller 300. Thus, the programmable controller 300 may include multiple ports for receiving the cables 208.

[0081] The flexible paddle 202 can bend, for example, into an arc shape, and can be embedded to contact the pelvic nerve plexus (e.g., during prostatectomy surgery). Preferably, the flexible paddle 202 can be shaped to conform to the anatomical shape of a portion of the pelvic nerve plexus. The flexible paddle 202 may comprise at least two electrode rows and at least two electrode arrays 204. In a preferred embodiment depicted in Figure 2B, the array of electrodes 204 may include 12 electrodes on each of the first flexible paddle 202a and the second flexible paddle 202b. The flexible paddle 202 may have a substantially hemispherical shape including a protruding portion 203, which extends from the corner of the flexible paddle furthest from the cable 208. The hemispherical shape is chosen to avoid damaging soft tissue, minimize injury, and reduce fibrous encapsulation that could interfere with the transmission of stimulation pulses from the electrodes to the nerves. The protruding portion 203 also allows the flexible paddle to be positioned adjacent to the cavernous nerve while accommodating the biological structures in that region, as described below with respect to Figures 8A and 8B. At least one electrode 204 may be positioned on the protruding portion 203 of the paddle.

[0082] Referring again to Figure 2B, a two-paddle embodiment is described. In this embodiment, the stimulation unit 200 (see Figure 1) includes a first flexible paddle 202a and a second flexible paddle 202b, each having an array of electrodes 204 and a suture hole 206. Each of the first flexible paddle 202a and the second flexible paddle 202b is coupled to a programmable controller 300 via a cable 208. Alternatively, a single cable 208 may include branches that connect the paddles 202a and 202b to the programmable controller 300. Since the pelvic plexus generally has two groups of nerves, each of the first flexible paddle 202a and the second flexible paddle 202b may cover part or all of the area of ​​one group of nerves such that at least one of the arrays of electrodes 204 is in contact with the cavernous nerve. For example, the first flexible paddle 202a and the second flexible paddle 202b may be implanted in the patient such that the protruding portions 203 of each hemispherical paddle face each other, as shown in Figure 2B. The protruding portions 203 may thus allow the flexible paddles to be positioned to surround the urethra, as shown in Figures 9A and 9B and 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 flexible paddle 202a and the second flexible paddle 202b may have the same or different dimensions. The distance between the two paddles, when implanted, may be about 0.5 mm to about 8 cm.

[0083] Referring here to Figures 4A and 4B, exemplary electrode shapes for use in the implantable stimulation unit 200 are described. Each of electrodes 204a, 204b, and 204c has a tissue-friendly shape configured to reduce adverse tissue reactions that could lead to fibrosis formation around the electrode. Electrode 204a has a spherical portion extending from the flexible substrate portion 212 and is independently coupled to the network of the programmable controller 300 by a wire 214a of the cable. Electrode 204b has a flat portion extending above the height of the flexible substrate portion 212 and is independently coupled to the network of the programmable controller 300 by a wire 214b of the cable. Electrode 204c is flat and coplanar with the surface of the flexible substrate portion 212 and is independently coupled to the network of the programmable controller 300 by a wire 214c of the cable. Advantageously, each of the electrode shapes does not have a sharp surface that could damage or inflame tissue. As will be understood by those skilled in the art, the array of electrodes 204 may use one, two, or three of these electrode shapes, or other preferred tissue-friendly shapes.

[0084] Referring here to Figures 4C-4E, exemplary electrode shapes are further explained, and Figures 4C-4E depict the surface charge density for each electrode shape. As shown in Figure 4C, the hemispherical shape of electrode 204a allows for a homogeneous charge distribution across the electrode surface, thereby providing efficient energy transmission from the electrode to the cavernous nerve without damage to surrounding tissue. In contrast, as depicted in Figures 4D and 4E, the charge distribution of flat disk electrodes 204b and 204c shows a large accumulation of charge on the periphery of the electrode, which can interfere with energy transmission and potentially lead to tissue damage.

[0085] With respect to Figure 5, a generalized schematic diagram of the internal functional components of the programmable controller 300 is described here. The programmable controller 300 is programmed to induce stimulation of a preferred excitation electrode according to a stimulation prescription plan stored in the memory of the programmable controller 300. The programmable controller 300 preferably includes a microprocessor 302, a non-volatile memory 304, a communication unit 306, a system sensor 308, a power supply 310, a stimulation circuit 312, and a demultiplexer 314.

[0086] The microprocessor 302 is electrically coupled to and controls the functional components of the programmable controller 300. The microprocessor 302 may comprise a commercially available microcontroller unit including 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 and system operating parameters and patient data logs. The memory of the microprocessor 302 stores program instructions that, when executed by the microprocessor 302, cause the processor and functional components of the programmable controller 300 to provide the functionality attributed to them herein. Preferably, the microprocessor 302 is programmable so that programming data (e.g., stimulation prescription plan, excitation electrode identification, stimulation parameters, etc.) is stored in the non-volatile memory 304 of the microprocessor 302 and can be adjusted using an external patient controller 400 and / or an external physician controller 500.

[0087] The microprocessor 302 may be programmable to enable electrical stimulation of any selected combination of electrodes 204 on the array, and thus provide a simple bipolar configuration. The microprocessor 302 may be further programmed with routines to selectively activate a desired subset of the array of electrodes 204, determine a subset of the array of electrodes that provides beneficial stimulation, and one or more stimulation prescription plans, and store that information in 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 that have been determined to provide a preferred erectile response for a preferred current flow direction. Furthermore, as used in this disclosure, the term “stimulation prescription plan” refers to a set of stimulation parameters that, when applied to the excitation electrodes, are judged by the patient or physician to induce a preferred rapid erectile response, or a set of stimulation parameters that are judged by the patient or physician to provide stimulation that is preferred to restore or enhance neurotransmission through at least one cavernous nerve.

[0088] For example, the microprocessor 302 may instruct the power source 310 to transmit electrical signals to a set of excitation electrodes 204 via the stimulation circuit 312, using a power-releasing demultiplexer 314. The stimulation prescription plan used by the microprocessor 302 delivers sufficient electrical stimulation to at least one cavernous nerve via the stimulation circuit 312 and the pelvic plexus to induce sexual arousal, e.g., erection, or to restore nerve or penile function. The routine may activate a subset of identified and stored electrodes automatically and / or in response to user input in the external patient controller 400 and / or external physician controller 500. In addition, as can be instructed by the external patient controller 400 or external physician controller 500, the non-volatile memory 304 stores pre-programmed routines for scanning the electrode array to enable identification of sets of excitation electrodes and stimulation parameters for preferred stimulation prescription plans both at the beginning after implantation and at subsequent times after implantation of the implantable stimulation unit 200. The set of excitation electrodes that elicits the best sexual arousal, e.g., an erectile response, is stored in memory. The identification of the set of excitation electrodes is stored for subsequent stimulation and can also be transmitted to an external patient controller 400 and / or an external physician controller 500.

[0089] Stimulation parameters are selected to provide sexual arousal, promote and / or improve nerve regeneration, and treat sexual disorders such as erectile dysfunction and sexual arousal disorder in women. For example, stimulation may induce and maintain an erection, and may promote and / or improve nerve regeneration (e.g., nerves of the pelvic plexus and / or cavernous nerves) over time. As an example, pulse duration may be programmed to be approximately 0.5 milliseconds to 10 milliseconds, approximately 0.5 milliseconds to 5 milliseconds, approximately 1 millisecond to 4 seconds, or approximately 1 millisecond to 3 milliseconds. AC frequency may be programmed to be approximately 10 Hz to 30 Hz, approximately 10 Hz to 25 Hz, approximately 10 Hz to 20 Hz, or approximately 15 Hz to 25 Hz. Voltage may be programmed to be approximately 1 V to 15 V, approximately 5 V to 10 V, approximately 1 V to 5 V, or approximately 10 V to 15 V. The current can be programmed to be approximately 1 milliampere to 100 milliamperes, approximately 1 milliampere to 50 milliamperes, approximately 1 milliampere to 20 milliamperes, approximately 20 milliamperes to 50 milliamperes, approximately 50 milliamperes to 100 milliamperes, or approximately 75 milliamperes to 100 milliamperes. The duration of stimulation can be programmed to stimulate automatically for a predetermined time, or it can be stimulated in response to user input, for example, in the user interface 402. For example, stimulation can be maintained for part or all of the desired erection period. For nerve regeneration, it may be preferable to stimulate over time at predetermined time intervals. For example, automatic stimulation may occur every hour, once a day, twice a day, three times a day, four times a day, every other day, every three days, or weekly for periods 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, stimulation for nerve regeneration is produced using oscillating current or low-frequency electrical stimulation.

[0090] The microprocessor 302 is coupled to a communication unit 306 having a network configured to communicate with an external patient controller 400 and / or an external physician controller 500. The communication unit 306 enables the transmission of stimulation commands, optionally, and power between the programmable controller 300 and the external patient controller 400, so that the programmable controller 300 can be powered, programmed, and / or controlled by the external patient controller 400. For example, the microprocessor 302 may, in response to stimulation commands received from the corresponding communication unit of the external patient controller 400 (e.g., an induction unit with a telemetry system and coils and / or an RF unit with a transceiver and antenna), start or stop a stimulation session, or perform an assessment and determine a preferred subset of the electrode array 204. The communication unit 306 further enables the transmission of programming data, optionally, and power between the programmable controller 300 and the external physician controller 500, so that the programmable controller 300 can be powered, programmed, and / or controlled by the external physician controller 500. For example, the microprocessor 302 may, in response to programming data received from the corresponding communication unit of the external physician controller 500 (e.g., a telemetry system and an induction unit having coils and / or an RF unit having a transceiver and antenna), instruct changes to a preferred stimulation prescription plan that includes not only the electrodes included in the set of excitation electrodes used for stimulation, but also the pulse duration, AC frequency, voltage, current, and / or duration of stimulation.

[0091] The communication unit 306 may include a telemetry system electrically coupled to an induction coil. Technologies for telemetry systems and coils are well known to those skilled in the art and may include magnets, short-range telemetry systems, longer-range telemetry systems (using MICS RF Telemetry, etc., available from Zarlink Semiconductor (Ottawa, Canada)), or technologies similar to pacemaker programmers. Alternatively, the coil may be used solely for power transmission, and a separate radio frequency transmitter may be provided within the programmable controller 300, external patient controller 400, and / or external physician controller 500 to establish bidirectional or unidirectional data communication.

[0092] The communication unit 306 may also include a communication circuit (with or without a telemetry system and coils) employing a transceiver coupled to an antenna (which may be inside or outside a sealed enclosure). The transceiver preferably comprises a radio frequency (RF) transceiver and is configured for bidirectional communication via the antenna with a similar transceiver circuit located in an external patient controller 400 and / or an external physician controller 500. For example, the transceiver may receive stimulation commands from the external patient controller 400 and programming data from the external physician controller 500. The microprocessor 302, 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 external physician controller 500, may instruct changes to a preferred stimulation prescription plan, including electrodes and pulse duration, AC frequency, voltage, current, and / or stimulation duration, including electrodes and pulse duration, AC frequency, voltage, current, and / or stimulation duration, to start or stop a stimulation session, and / or to perform an assessment and reassess a preferred subset of electrodes. The transceiver may also include a low-power operating mode, thereby periodically waking up, listening for incoming messages, and responding only to those messages containing a unique device identifier assigned to its programmable controller. In addition, the transceiver may employ encryption routines to ensure that messages transmitted from or received by the programmable controller 300 cannot be intercepted or forged. The communication unit 306 uses a wireless chipset, such as Wi-Fi or Bluetooth®. TM This may include cellular, Zigbee®, etc., which enable the programmable controller 300 to communicate wirelessly with an external patient controller 400 and / or an external physician controller 500.

[0093] The system sensor 308 may include one or more sensors that monitor the operation of the programmable controller 300 system, log data related to system operation and system failures, Log data may be stored in the log for later reading after using the external physician controller 500. The microprocessor 302 may be programmed to receive sensor signals from the system sensor 308 and adjust stimulation parameters based on the sensor signals. The sensor 308 may include, for example, a humidity sensor that measures humidity inside the housing of the programmable controller 300, and it may provide information related to the state of electronic components and / or temperature sensors, for example, to measure the battery temperature during charging and ensure the safe operation of the battery. Data from the system sensor may be logged by the microprocessor 302 and stored in the non-volatile memory 304 for later transmission to the external physician controller 500.

[0094] The power source 310 supplies power to the electrical components of the programmable controller 300 and may comprise a primary cell or battery, a secondary (rechargeable) cell or battery, or a combination of both. Alternatively, the power source 310 may not include a cell or battery and instead comprises 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, the power source 310 comprises a lithium-ion battery.

[0095] The stimulation circuit 312 is configured to transmit pulses to the electrode 204 using energy supplied from the power source 310 so that the selected electrode delivers electrical stimulation at the desired parameters.

[0096] The microprocessor 302 may be further coupled to a demultiplexer 314 so that any subset of electrodes 204 in the array can be selectively coupled to the stimulation circuit 312. Thus, a suitable electrode combination can be selected from a whole selection of electrodes to be implanted in the patient's body to achieve the desired therapeutic effect. The demultiplexer 314 preferably operates at high speed, thereby allowing continuous stimulation pulses to be applied to different electrode combinations.

[0097] With respect to Figure 6, a generalized schematic diagram of the internal functional components of the external patient controller 400 is described here. The external patient controller 400 may include a user interface 402, a programmable microprocessor 404, a communication unit 406, a power source 408, and an input and output network (I / O) 410. As described above, the external patient controller 400 may be specifically designed for use with the implantable stimulation unit 200, or alternatively, a multipurpose smartphone, laptop, tablet, smartwatch, etc., programmed to communicate with the implantable stimulation unit 200 and / or the external physician controller 500. In the latter case, the user interface 402, programmable microprocessor 404, communication unit 406, power source 408, and I / O 410 may be pre-installed hardware on the smartphone, laptop, tablet, smartwatch, etc.

[0098] The microprocessor 404 is configured to be electrically coupled to and control the internal functional components of the external patient controller 400. The microprocessor 404 may comprise a programmable microprocessor and a commercially available microcontroller unit that includes volatile memory, non-volatile memory such as EEPROM for storing programming, and non-volatile storage, such as flash memory, for storing firmware and system operating parameters and patient data logs. The memory of the microprocessor 404 may store program instructions that, when executed by the processor of the microprocessor 404, cause the processor and the 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 a preferred stimulation prescription plan, including electrodes included in a set of excitation electrodes used for stimulation, pulse duration, AC frequency, voltage, current, and / or duration of stimulation, in response to user input received in the user interface 402 and / or the external physician controller 500, and to transmit stimulation commands and programming data to the programmable controller 300 via the communication unit 406.

[0099] The microprocessor 404 may be coupled to a communication unit 406, which may communicate with a programmable controller 300 and an external physician controller 500. The communication unit 406 may include an induction unit and coil having a telemetry system, and / or an RF unit having a transceiver and antenna, a wireless chipset, e.g., Wi-Fi, Bluetooth®. TM With cellular, Zigbee®, etc., the external patient controller 400 can communicate wirelessly with the programmable controller 300 and / or the external physician controller 500, and optionally supply power to the programmable controller 300.

[0100] The user interface 402 receives user input and displays information to the user. The user interface 402 may 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 may display current stimulation parameters and allow the user to adjust the stimulation parameters. In a preferred embodiment, a limited number of stimulation parameters may be adjustable in the user interface 402 to reduce the chance of injury caused by adjustments made by non-physician users. For example, the user interface 402 may only allow the user to start or stop a stimulation session using excitation electrodes, such as a first stimulation pulse sequence corresponding to a first mode for inducing a rapid erectile response, a second nerve function recovery stimulation mode selected to restore function of neurotransmission in the cavernous nerve, or a third penile function recovery mode selected to reduce penile fibrosis.

[0101] The power source 408 supplies power to the electrical components of the external patient controller 400 and may comprise a primary cell or battery, a secondary (rechargeable) cell or battery, or a combination of both. Alternatively, the power source 408 may be a port, allowing the external patient controller 400 to be plugged into a conventional wall socket to supply power to its components.

[0102] The input and output network (I / O) 410 may include ports for data communication, such as wired communication with a computer, and / or ports for receiving removable memory (e.g., an SD card) on which program instructions or data related to the use of an external patient controller 400 may be stored.

[0103] Referring to Figure 7, the software implemented on the external physician controller 500 is described here. The software comprises several functional blocks graphically depicted in 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 employs an object-oriented format. In one preferred embodiment, the software is configured to run on a Microsoft Windows® (a trademark of Microsoft Corporation (Redmond, Wash.)) or Unix®-based operating system, as conventionally employed on desktop and laptop computers. As discussed above, the computer may include a transceiver, an antenna, and a wireless card, e.g., IEEE 802.11 standard, cellular, Bluetooth® TM It conforms to Zigbee® and other standards, thereby enabling the programmable controller 300 and / or external patient controller 400 to communicate wirelessly with the external physician controller 500.

[0104] The main block 502 preferably runs on the physician's computer and includes a main software routine that 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 external patient controller 400 to their office computer, and also enables 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.

[0105] The event log block 504 is a record of operational data downloaded from the programmable controller 300, and may include, for example, treatment session start and stop times, current stimulation parameters, stimulation parameters from the previous treatment session, sensor data, battery current, battery voltage, battery status, etc. The event log may also include the occurrence of events such as alarms or other abnormal conditions.

[0106] 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 has been coupled to the external physician controller 500. The data download block 506 may start downloading data stored in the event log automatically or at the instruction of a physician via the user interface block 510.

[0107] The configuration setting block 508 is a routine that configures parameters stored within the programmable controller 300 that control the operation of the programmable controller 300. Time interval timing parameters may determine, for example, how long the processor remains in sleep mode before being woken up to listen to wireless communication or to control the operation of the programmable controller 300. Time interval timing parameters may control, for example, the duration of a stimulation session. Time interval timing settings transmitted to the programmable controller 300 may also determine the time and frequency at which event data is written to memory in the microprocessor 302. In one embodiment, the external physician controller 500 is also configured to transfer data to the external patient controller 400, and the external physician controller 500 may also be used to configure timing parameters used by firmware executed by the microprocessor 404 of the external patient controller 400. Block 508 may also be used by the physician to configure parameters stored in the memory of the microprocessor 302 that relate to operational limits of the microprocessor 302. These values ​​may include the time when the programmable controller 300 may be operating and when it may not be operating.

[0108] Block 508 may also constitute parameters stored in the memory of the microprocessor 302 related to controlling the operation of the programmable controller 300. These values ​​may include stimulus parameters.

[0109] The user interface block 510 handles the display of information read from the programmable controller 300 and / or external patient controller 400 and data download block 506, presenting that information in an intuitive and easily understandable format for the physician's review. Such information may include the status of the programmable controller 300, treatment session start and stop times, current stimulation parameters, stimulation parameters from the previous treatment session, sensor data, battery status, etc. The user interface block 510 also generates a user interface screen that allows the physician to input information to configure session timing, stimulation parameters, and requests, and to determine or re-determine a subset of excitation electrodes, etc.

[0110] The alarm detection block 512 may include a routine that evaluates the data read from the programmable controller 300 and flags abnormal conditions for the physician's attention. For example, the alarm detection block 512 may flag a parameter measured by the system sensor 308 when it exceeds or falls below a predetermined threshold.

[0111] The sensor calibration block 514 may include routines for testing or measuring variations in a system sensor 308 employed within the programmable controller 300, for example, due to degradation or changes in humidity. The block 514 may then calculate an offset value to correct the measured data from the sensor and transmit the information to the programmable controller 300 for storage in the non-volatile memory of the microprocessor 302.

[0112] The firmware upgrade block 516 may include a routine for checking the version number of the controller firmware installed on the programmable controller 300 and / or external patient controller 400 and identifying whether an upgraded firmware exists. If applicable, the routine may notify the physician and allow the physician to download the revised firmware into the non-volatile memory of the programmable controller 300 and / or external patient controller 400.

[0113] The device identifier block 518 may include a unique identifier for the programmable controller 300 stored in the non-volatile memory 304 of the microprocessor 302, and a routine for reading that data when the external physician controller 500 is coupled to the programmable controller 300. The device identifier may also be used by the programmable controller 300 to verify that communications received from the external patient controller 400 and / or the external physician controller 500 are intended for that particular programmable controller. Similarly, this information is used by the external patient controller 400 and / or the external physician controller 500 to determine whether the received message was generated by the programmable controller associated with that system. Finally, the device identifier information may be used by the external physician controller 500 to verify that the external patient controller 400 and the programmable controller 300 constitute a matched pair.

[0114] The status information block 520 includes routines for querying the programmable controller 300 and reading current status data from the programmable controller 300. Such information may include, for example, battery status, stimulation parameters, the date and time on the internal clock of the treatment session, version control information regarding the firmware and hardware currently in use, and sensor data.

[0115] Figures 8A and 8B illustrate the positioning of flexible paddles 202a and 202b on the prostate and pelvic plexus, respectively. As described above with respect to Figures 2A and 2B, each of the flexible paddles 202a and 202b has an array of electrodes 204 and suture holes 206 and is connected to a programmable controller 300 via one or more cables 208. The system can be implanted laparoscopically, for example, by folding the flexible paddles and passing them through a trocar. The insets in Figures 8A and 8B depict local biostructures showing the bladder, prostate, urethra, and pelvic floor. In Figure 8A, the flexible paddle 202 is shown positioned relative to the prostate. Alternatively, the flexible paddle 202 may be positioned relative to the pelvic plexus so that the paddle 202 surrounds the urethra, as shown in Figure 8B. Implantation over the pelvic nerve plexus may be preferable for patients undergoing prostatectomy with partial or complete removal of the prostate.

[0116] Referring here to Figures 9A and 9B, the positioning of the flexible paddles 202 is described. As described above with respect to Figures 2A and 2B, each flexible paddle 202 preferably has a substantially hemispherical shape, with a protruding portion 203 extending from the corner of the flexible paddle furthest from the cable 208. The first flexible paddle 202a and the second flexible paddle 202b may be positioned such that the sides of the flexible paddles with exposed electrodes are in contact with the pelvic plexus, 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 used to fix the flexible paddles to the pelvic plexus. In Figure 9A, the first position is illustrated so that the protruding portions 203 of the paddles are close to each other. In Figure 9B, the second position is shown such that the protruding portions 203 of the paddles are further apart from each other, which may be advantageous if the patient's cavernous nerve is located further away from the urethra.

[0117] A programmable controller 300, operably coupled to the electrode array, can be programmed to selectively activate electrode 204 during paddle implantation to determine the optimal position for implanting the flexible paddle, for example, a first or second position as shown in Figures 9A and 9B. For example, the flexible paddle may be placed in a first position adjacent to the pelvic plexus and near at least one cavernous nerve (e.g., Figure 9A). The programmable controller can then instruct the stimulator circuit to activate electrode 204 at the first position, generating a first positional response. Cavernous nerve activation can be measured, for example, using a penile plethysmograph to measure penile diameter or circumferential variation and penile swelling.

[0118] The flexible paddle can then be moved to a second position different from the first position, which is adjacent to the pelvic plexus and near at least one cavernous nerve (e.g., Figure 9B). The programmable controller can again selectively activate electrode 204 at the second position to generate a second positional response. The programmable controller can also compare the first and second positional responses via feedback from sensor system 308 or in response to input from an external patient controller 400 or an external physician controller 500 to determine the position that elicits an erectile response. If two or more positions elicit an erectile response, the position that elicits the strongest or fastest erectile response without causing significant discomfort or side effects can be selected as the preferred paddle placement position.

[0119] Referring here to Figures 10A-10C, the process of assessing tissue stimulation using sequentially varying directions of current flow within the array of electrodes 204 is described. As explained above, each of the electrodes 204 on the flexible paddles 202a and 202b is individually accessible and acts as a source or sink, allowing current flow in multiple directions, as indicated by the arrows between the electrodes 204 in Figures 10A-10C. In Figure 10A, the first direction of current flow is indicated by arrow 220a diagonally toward the other flexible paddle. For example, current flows from electrode 1 to electrode 2, but not between electrode 1 and electrode 3 or 4. Figure 10B shows the second direction of current flow 220b, where current flows diagonally between the electrodes 204 in each flexible paddle, away from the other flexible paddle. As shown in Figure 10B, the second direction of current flow is preferably oblique to the first direction of current flow in order to increase the probability that the activation of the electrode pair will stimulate the nerve and thereby elicit a response. As depicted in Figure 10B, the current flows from electrode 1 to electrode 3, but not between electrode 1 and electrode 2 or 4. Figure 10C shows a third direction of current flow 220c, in which the current flows downward between electrodes 204 within each flexible paddle. For example, the current may flow from electrode 1 to electrode 4, but not from electrode 1 to electrode 2 or 3. As will be understood by those skilled in the art, depending on the number and arrangement of the array of electrodes 204, the direction of current flow may differ from those shown in Figures 10A-10C.

[0120] With respect to Figures 11A-11C, the grouping of electrodes 204 into exemplary regions is described. Figures 11A-11C correspond to the current flow directions depicted in Figures 10A-10C, respectively. Each array of electrodes 204, for example, a first array and a second array, has at least two predetermined regions of electrodes 222. For example, the first region 222a and the second region 222b of the electrodes may be arranged on a first flexible paddle, and the third region 222c and the fourth region 222d of the electrodes may be arranged on a second flexible paddle. As will be understood by those skilled in the art, each paddle may have three or more electrode regions, and the electrode regions may be varied to include different subset pairs of electrodes. The number and composition of electrodes 204 contained within each region may depend on the direction of current flow. For example, the first region 222a of the electrode in Figure 11A may include electrodes 1-5, while the first region 222a of the electrode in Figure 11B may include electrodes 1-4 and 6, and the first region 222a of the electrode in Figure 11C may include electrodes 1, 3, 4, 6, 7, 10, and 11.

[0121] Referring here to Figures 12A-12C, preferred electrode pair selections within the electrode array are shown. Each of Figures 12A-12C corresponds to the directional current flow depicted in Figures 10A-10C and each corresponds to the electrode region depicted in Figure 11A-11C. Each array of electrodes 204 has at least one electrode pair within each region 222 of the electrode, and each electrode pair contains two electrodes 204 from the electrode array. Each region 222 of the electrode may have the same or different number of electrodes 204 and electrode pairs as other regions 222 of the electrode.

[0122] Referring to Figure 13, a programmed method for identifying a subset of excitation electrodes is described, and the preferred direction of current flow, electrode region, and preferred electrode pair are determined. Following that electrode selection process, a programmed method is completed for determining parameters for a preferred stimulation formulation plan to induce a preferred erectile response. According to one aspect of the present invention, a programmable controller 300 is operably coupled to an array of electrodes and programmed to selectively activate electrode 204 and determine the excitation electrodes and preferred stimulation formulation plan.

[0123] More specifically, the programmable controller 300 is programmed to selectively activate the electrodes 204 in the electrode array in at least two directions of current flow, as shown in Figures 10A-10C. Sequential stimulation may be applied between each pair of electrodes on the electrode array, and the erectile response may be measured. To determine the erectile response, activation of the cavernous nerve may be measured, for example, using a penile plethysmograph, and penile diameter or circumferential variation and penile swelling may be measured. With respect to each electrode array, the direction of current flow that induces an erectile response may be selected as the preferred direction of current flow. If two or more directions of current flow on each electrode array induce an erectile response, the direction of current flow that induces the strongest erectile response without significant discomfort or side effects may be selected as the preferred direction of current flow. For example, Figure 13 shows that the second direction of current flow 220b is selected as the preferred direction of current flow with respect to each of the electrode arrays. As will be understood by those skilled in the art, the preferred direction of current flow on the first flexible paddle may be the same as or different from the preferred direction of current flow on the second flexible paddle.

[0124] The programmable controller 300 may be further programmed to selectively activate electrodes 204 in the electrode array region by region using a preferred current flow direction from a prior process. For example, if a second direction 220b of current flow is a preferred current flow direction, the electrode region corresponding to the preferred current flow direction may be activated as shown in Figure 11B. Sequential stimulation may be applied in each region in the preferred current flow direction between each electrode pair on each electrode array, and the erectile response is measured for each local stimulation using the same method as described above. For each electrode array, the electrode region that elicits an erectile response may be selected as the preferred electrode region. If two or more region electrodes elicit an erectile response, the electrode region that elicits the strongest erectile response without causing significant discomfort or side effects is selected as the preferred region. For example, Figure 13 illustrates that a second region 222b of the electrode on the first flexible paddle and a third region 222c of the electrode on the second flexible paddle are selected as preferred regions.

[0125] Next, the programmable controller 300 selectively activates the electrodes 204 in the electrode array in a preferred current flow direction and in a preferred region. For example, Figure 13 depicts the second direction of current flow 220b as the preferred current flow direction, and the second region 222b of the electrode on the first flexible paddle and the third region 222c of the electrode on the second flexible paddle as preferred regions. Sequential stimulation may be applied between each electrode pair on the electrode array in the preferred direction of current flow and in the preferred region, and the erectile response may be measured using the same method described above. With respect to each electrode array, one or more electrode pairs that induce an erectile response may be selected as preferred electrode pairs. If two or more electrode pairs induce an erectile response, one or more electrode pairs that induce the strongest erectile response without causing significant discomfort or side effects may be selected as preferred electrode pairs. In Figure 13, three preferred electrode pairs 224 are identified as a subset of excitation electrodes. As will be understood by those skilled in the art, the number of preferred electrode pairs on the first flexible paddle may be the same as or different from the number of preferred electrode pairs on the second flexible paddle.

[0126] After a preferred electrode pair 224 is determined, several stimulation parameters having unique combinations of frequency and intensity amplitude can be applied to the preferred electrode pair. Stimulation pulse sequences for different uses can be determined by comparing the responses produced by activating the preferred electrode pair in different modes with different stimulation parameters. For example, a stimulation pulse sequence corresponding to a mode of activation for erection can be determined. A stimulation prescription plan for inducing erection 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. Alternatively, or in addition, the device may be used to restore function to at least one cavernous nerve and to determine a nerve function recovery stimulation prescription plan corresponding to a mode of activation for nerve function recovery. A nerve function recovery stimulation prescription plan may have stimulation parameters with lower current intensity than the stimulation prescription plan for inducing erection. For example, a nerve function recovery stimulation prescription plan may 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. A neurological function recovery stimulation prescription plan can be programmed to run automatically at least once a day.

[0127] Alternatively, the device may be used to determine a penile function recovery stimulation prescription plan corresponding to a mode of activation for penile function recovery. If the cavernous nerve is damaged or completely severed after prostatectomy, a penile function recovery stimulation prescription plan may be used to induce at least partial penile swelling, increase tissue oxygenation, maintain penile function, and thereby reduce penile fibrosis. Such a stimulation prescription plan may be performed at least once a day while the cavernous nerve is spontaneously re-established or reconnected and regenerated with assistance from a nerve function recovery stimulation prescription plan. A penile function recovery stimulation prescription plan may have stimulation parameters with a higher current intensity than a nerve function recovery stimulation prescription plan and a lower current intensity than a stimulation prescription plan for producing an erection. For example, a penile function recovery stimulation prescription plan 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 function recovery stimulation prescription plan may be programmed to run automatically at least once a day, and such operation may occur at a different time than the nerve function recovery program.

[0128] The preferred direction of current flow, electrode regions, electrode pairs, and stimulation parameters can be stored in the non-volatile memory of the programmable controller 300, the external patient controller 400, and / or the external physician controller 500. Multiple stimulation prescription plans can also be stored in the memory of the programmable controller 300, the external patient controller 400, and / or the external physician controller 500, so that the programmable controller can be selectively activated in response to patient or physician input. For example, a patient may selectively activate a stimulation prescription plan to induce an erection. Alternatively, if programmed as such, the programmable controller may automatically execute a nerve function recovery stimulation prescription plan and / or penile function recovery stimulation prescription plan at least once a day following a prostatectomy, preferably for one hour with respect to each function recovery stimulation prescription plan.

[0129] With respect to Figure 14, the operation of the intraoperative scanning process is outlined. Sequential stimulation will be applied between each electrode pair within each electrode array. Stimulation of each electrode pair will be automatically applied during the pulse intervals of the other electrode pairs. The intraoperative stimulation allows for activation of the cavernous nerve, which is detected by penile plethysmography to measure penile diameter or circumferential variation and penile swelling. During the scanning procedure, a 1-2 minute interval between stimulations per configuration may be required to allow for proper measurement. A 5-minute rest period between each stimulation is allowed for stabilization and to avoid the swelling reduction refractory effect.

[0130] Figure 15 illustrates an exemplary method for determining a subset of an electrode array that, preferably after implantation, is positioned to deliver electrical stimulation to at least one cavernous nerve via the pelvic plexus to induce sexual arousal, e.g., erection. In method 700, in 702, stimulation parameters are set, which may include the pairs of electrodes 204 in the array to be used, pulse duration, alternating current frequency, voltage, current, and duration of stimulation. The stimulation parameters may be set in an external patient controller 400, but preferably in an external physician controller 500. In 704, electrical stimulation is delivered to the tissue, e.g., the pelvic plexus, between the selected electrode pairs of the array at the set stimulation parameters. The selected electrode pairs of the array at the set stimulation parameters may be selected by a physician via the external physician controller 500 and / or determined as a result of the scanning protocol described above. In 706, it is observed whether sexual arousal, e.g., erection, has been achieved. If not applicable, the stimulation parameters may be reset with respect to the selected electrode pair, or a different electrode pair may be selected for stimulation using the same parameters or with adjusted parameters. If sexual arousal is achieved, the stimulation parameters, including the electrode pair, are stored in the memory of the programmable controller 300, the external patient controller 400, and / or the physician controller 500.

[0131] Optionally, after sexual arousal has been achieved, further stimulation may be performed on the electrode pair using adjusted stimulation parameters in 710, or a different electrode pair may be selected for stimulation using the same parameters or adjusted parameters, and it may be determined in 712 whether stronger sexual arousal can be achieved. If not, stimulation may be repeated in 710 using a different configuration, or the test may be terminated, and the parameters stored in 708 may be used. If stronger sexual arousal is achieved, the stimulation parameters, including those of the electrode pair, may be stored as preferred parameters in the memory of the programmable controller 300, the external patient controller 400, and / or the physician controller 500, and previously stored parameters may be overwritten in 708. Optionally, after stronger sexual arousal has been achieved, it may be determined whether further stimulation can be performed at 710 on the electrode pair using adjusted stimulation parameters, or whether further different electrode pairs can be selected for stimulation using the same parameters or adjusted parameters, and whether even stronger sexual arousal can be achieved at 712.

[0132] Once the user is satisfied that the preferred parameters have been determined, the preferred parameters are stored in memory, since all electrode pairs in the array have been tested or preferred sexual arousal has been achieved. Thus, the stimulation routine at the preferred parameters can be initiated later, e.g., minutes, hours, days, months, or years later, by the patient external controller 400 and / or the external physician controller 500, to induce sexual arousal, e.g., erection.

[0133] Referring here to Figure 16, an exemplary method for determining the optimal positioning for a flexible paddle is described. In method 800, in step 802, an array of electrodes is placed at a first position adjacent to the pelvic plexus and near at least one cavernous nerve. At least one electrode pair is selectively activated to stimulate at least one cavernous nerve and produce a first positional response. In step 804, the same process is repeated at a second position adjacent to a different pelvic plexus and near at least one cavernous nerve than the first position. Specifically, at least one electrode pair is selectively activated to stimulate at least one cavernous nerve and produce a second positional response. In step 806, the first and second positional responses are compared to determine which response elicits a stronger positional erectile response. If two or more locations induce an erectile response, the location that induces the strongest erectile response without causing significant discomfort or side effects may be selected as the optimal location. The process may be repeated at a third location to further determine the optimal location for implanting the flexible paddle.

[0134] Referring here to Figure 17, exemplary methods for determining a preferred stimulation prescription for inducing an erection, optionally, a preferred stimulation prescription for nerve function restoration, and / or penile function restoration are described. In method 900, in step 902, an array of at least one electrode pair is selectively activated to stimulate at least one cavernous nerve. At least one electrode pair may be selectively activated in a first direction and a second direction to generate a first directional response and a second directional response, respectively. In step 904, the direction of current flow that induces a first erectile response may be determined by comparing the first directional response and the second directional response. In step 906, an array of at least one electrode pair is selectively activated in a preferred direction to stimulate at least one cavernous nerve. At least one pair of electrodes in the first region and at least one pair of electrodes in the second region can be selectively activated in a preferred direction to generate a first local response and a second local response, respectively.

[0135] In step 908, the region of electrodes that induces a second erectile response may be determined by comparing the first local response with the second local response. The process is then repeated to determine preferred electrode pairs. In step 910, an array of at least one electrode pair is selectively activated in a preferred direction within a preferred region. The first electrode pair and the second electrode pair within the preferred region are selectively activated in a preferred direction, and may generate a first pair response and a second pair response, respectively. In step 912, one or more electrode pairs that induce a third erectile response may be determined by comparing the first pair response with the second pair response.

[0136] In step 914, a preferred electrode pair may be selectively activated at different frequencies and current intensities. The preferred electrode pair may be selectively activated in a first mode having a first simulation prescription plan, and in a second mode having a second stimulation prescription plan employing different stimulation parameters from the first stimulation prescription plan, thereby generating a first response and a second response. Optionally, in step 916, the mode of activation for erection may be determined by comparing the first mode response and the second mode response. Optionally, in step 918, the comparison may be repeated to determine a mode of activation for functional recovery of at least one cavernous nerve. Optionally, in step 920, the comparison may be repeated to determine a mode of activation for penile functional recovery to reduce penile fibrosis. In step 922, the determined mode of activation may be stored in the memory of the programmable controller 300, the external patient controller 400, and / or the physician controller 500.

[0137] Referring here to Figure 18, an exemplary method for modulating a preferred mode having a stimulation prescription plan for functional restoration of neurotransmission within the cavernous nerve is described. In method 1000, steps 1002-1010 are analogous to steps 914-918 in method 900. In step 1002, the preferred electrode pair may be selectively activated in a first mode having a first stimulation prescription plan to produce a first response. In step 1004, the preferred electrode pair may be selectively activated in a second mode having a second stimulation prescription plan to produce a second response. In step 1006, the first and second responses may be compared. Optionally, in step 1008, a rapid erection mode of activation may be determined based on the comparison. Optionally, in step 1010, a mode of activation to promote functional restoration of at least one cavernous nerve may be determined based on the comparison. The neuronal function restoration mode may supply a lower current intensity stimulation than the rapid erection mode of activation. Optionally, in step 1012, the activation neuronal function recovery mode may be modulated using machine learning or other types of artificial intelligence. In addition, preferred electrodes may also be used to measure neuronal activity, and these measurements may be used in conjunction with artificial intelligence to modulate the activation neuronal function recovery mode and enable more efficient or effective neurotransmission. Alternatively, the method of Figure 18 may be used to modulate a stimulation prescription plan to induce erection or a penile function recovery stimulation prescription plan to reduce fibrosis.

[0138] In addition to stimulation prescription plans for inducing a rapid erectile response, restoring neurotransmission in the cavernous nerve, or reducing penile fibrosis, the systems and methods described herein may be used, for example, to treat urinary incontinence by electrically stimulating one or more nerves in the lower urinary tract. As described above, electrical stimulation of the pelvic floor may help promote nerve regeneration and thus improve urinary function following radical prostatectomy. In particular, low-intensity stimulation may re-establish nerve function by promoting axonal regrowth and reconnection.

[0139] Referring to FIG. 19 here, a schematic diagram of a local biological structure is shown. The nerves that control the lower urinary tract include the pelvic parasympathetic nerves, the inferior hypogastric sympathetic nerves, and the pudendal nerves. The flexible paddle is preferably configured such that the pudendal nerves that control the external sphincter are stimulated. However, depending on the implantation location of the flexible paddle and the configuration of the electrodes, additional nerves that do not come into direct contact with the electrodes, including the inferior hypogastric sympathetic nerves, can also be functionally restored.

[0140] Referring to FIGS. 20A and 20B here, cross-sectional side views of exemplary flexible paddles are shown. Flexible paddles 202 similar to those shown in FIGS. 2A and 2B can be used to treat urinary incontinence. In particular, the implantable stimulation unit can include first and second flexible paddles 202 each having an array of electrodes 204 and suture holes, a cable, and a programmable controller, as described above. The electrodes 204 can be arranged in a plurality of rows and a plurality of columns, and bipolar stimulation can be applied such that current passes from one electrode to another and stimulates the nerves or nerve groups disposed therebetween. The flexible paddle 202 is preferably sized and shaped to be adjacent to at least a portion of the patient's pelvic plexus. The first flexible substrate is configured to conform to the first half of the pelvic plexus, and the second flexible paddle is configured to conform to the second half of the pelvic plexus. The flexible paddle can bend and form an arc shape that conforms to the pelvic plexus and can be implanted, for example, over the pelvic plexus during a prostatectomy surgery. Preferably, the flexible paddle 202 conforms to the anatomical shape of a portion of the pelvic plexus such that the electrodes 204 are in optimal contact with the pudendal nerves and can cover a portion or the entire area of the pelvic plexus. The flexible paddle can comprise a structural matrix of silicone or other flexible electrically non-conductive material, which enables adaptation and molding to the local biological structure, optimizes placement, and minimizes tissue reaction. The flexible paddle is designed in a suitable shape (e.g., hemisphere, rectangle, square, oval, ellipse, or trapezoid) and can have a flat structure sized to better conform to the biological structure and needs of each patient.

[0141] As shown in FIG. 20A, the flexible paddle 202 may include a first plurality of electrodes 204a on the first surface of the paddle. As shown in FIG. 20B, the flexible paddle 202 may additionally include a second plurality of electrodes 204b on a second surface opposite the first surface of the paddle. The embodiment of FIG. 20B may be particularly beneficial for treating urinary incontinence, as damaged nerves, such as the inferior hypogastric nerves, may not be adjacent to the pelvic floor. Since low-intensity stimulation is used to restore the function of one or more nerves that control the lower urinary tract, a larger portion of the pelvic plexus can be stimulated without adverse effects.

[0142] FIGS. 20C and 20D are perspective views with insertion detail views showing the placement of the flexible paddles of FIGS. 20A and 20B, respectively, positioned on a patient's pelvic plexus. Preferably, the flexible paddle 202 is positioned relative to the pelvic plexus such that the paddle surrounds the urethra and is adjacent to the pudendal nerve. FIG. 20D shows the implantation of the flexible paddle of FIG. 20B having a first plurality of electrodes 204c and a second plurality of electrodes 204d on opposite surfaces of the paddle. The first plurality of electrodes 204c may be configured to stimulate nerves in the vicinity of the pelvic floor, and the second plurality of electrodes 204d may be configured to stimulate nerves in the vicinity of the bladder neck and internal sphincter. In particular, this configuration allows a larger area to be stimulated, which can result in the functional recovery and regeneration of the pudendal nerve, as well as the inferior hypogastric nerve or other nerves that do not come into direct contact with the electrodes.

[0143] Low-intensity stimulation can promote the regrowth of damaged axons and the reconnection of nerves and may preferably be designed not to activate the nerves. Thus, the patient should not be able to perceive the stimulation, and there should be no physiological response. In some embodiments, an optimal electrode pair need not be determined. Instead, preferably, all the electrodes on each flexible paddle are activated, which increases the area of the pelvic plexus that stimulates all the nerves within the region and promotes their regeneration. Alternatively, only one or a plurality of electrode pairs on each flexible paddle may be activated.

[0144] Preferably, the bladder nerve function recovery stimulation mode has a low current intensity similar to the current intensity for a nerve function recovery stimulation mode to restore function to at least one cavernous nerve. For example, a bladder nerve function recovery stimulation prescription plan may 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. A programmable controller may be programmed to automatically execute a bladder nerve function recovery stimulation pulse sequence at least once a day for at least one hour, at one or more predetermined times (e.g., immediately before the patient wakes up).

[0145] As described above, the programmable controller may be controlled by an external patient controller. The external patient controller preferably includes a user interface that allows a user, such as a patient, physician, or caregiver, to adjust a limited number of operating parameters of the programmable controller (including starting and stopping bladder nerve function recovery stimulation sessions). An external physician controller may be programmed to communicate with the external patient controller and the programmable controller. The external physician controller may be used to store in the non-volatile memory of the programmable controller a bladder nerve function recovery stimulation prescription plan that, when activated on demand by the external patient controller or automatically by the programmable controller at a pre-set time, restores function to neurotransmission in the nerves controlling the lower urinary tract.

[0146] Various illustrative embodiments of the present invention are described above, but it will be apparent to those skilled in the art that various changes and modifications can be made therein without departing from the present invention. The appended claims are intended to cover all such changes and modifications that fall within the true scope of the present invention.

Claims

1. An implantable system for treating erectile dysfunction, wherein the implantable system is A flexible paddle having an array of electrodes, wherein the array of electrodes comprises a first region and a second region, A programmable controller comprising a stimulation circuit, a microprocessor, and memory. Equipped with, The stimulation circuit is operably coupled to the array, The microprocessor executes programmed instructions stored in the memory, The stimulation circuit is caused to selectively activate the first electrode pair of the array, thereby generating a first current flow in a first direction between the first electrode pair, wherein the first current flow is configured to induce a first erectile response by stimulating the cavernous nerve. The stimulation circuit is instructed to selectively activate the second electrode pair of the array, thereby generating a second current flow in a second direction between the second electrode pair, wherein the second direction differs from the first direction, and the second current flow is configured to induce a second erectile response by stimulating the cavernous nerve. Identifying either the first erectile response or the second erectile response as the first preferred erectile response, The system stores the identification of either the first direction or the second direction as a preferred current direction for subsequent stimulation of the cavernous nerve. The stimulation circuit is made to generate a third erectile response by selectively activating the electrodes in the first region with the preferred current direction, The stimulation circuit is made to generate a fourth erectile response by selectively activating the electrodes in the second region with the preferred current direction, Identifying either the third erectile response or the fourth erectile response as a second preferred erectile response, A preferred area is one in which the identification of either the first area or the second area is stored. An embeddable system configured to perform the following actions.

2. The implantable system according to claim 1, wherein the programmed command identifies either the first erectile response or the second erectile response as the first preferred erectile response in response to an input generated by a sensor system associated with the programmable controller.

3. The implantable system according to claim 1, wherein the programmed command identifies either the first erectile response or the second erectile response as the first preferred erectile response in response to an input provided by an external patient controller or an external physician controller.

4. The implantable system according to claim 1, wherein the programmed command identifies either the third erectile response or the fourth erectile response as the second preferred erectile response in response to an input generated by a sensor system associated with the programmable controller.

5. The implantable system according to claim 1, wherein the programmed command identifies either the third erectile response or the fourth erectile response as the second preferred erectile response in response to an input provided by an external patient controller or an external physician controller.

6. The microprocessor executes programmed instructions stored in the memory, The stimulation circuit is made to induce a series of erectile responses by sequentially activating a subset of electrodes within the preferred region with the preferred current direction, Identifying a preferred erectile response from the aforementioned series of erectile responses, The identification of a subset of at least one electrode within the preferred region as a preferred set of excitation electrodes for subsequent stimulation of the cavernous nerve, and The embeddable system according to claim 1, further configured to perform the following:

7. The implantable system according to claim 6, wherein the programmed instruction identifies the preferred erectile response from a set of erectile responses in response to an input generated by a sensor system associated with the programmable controller.

8. The implantable system according to claim 6, wherein the programmed command identifies the preferred erectile response from the set of erectile responses in response to input provided by an external patient controller or an external physician controller.

9. The microprocessor executes programmed instructions stored in the memory, In the aforementioned preferred current direction, the stimulation circuit is instructed to selectively activate the preferred set of excitation electrodes using a series of stimulation parameters, thereby inducing a further series of erectile responses. Identifying the optimal response from the aforementioned series of further erectile responses, The preferred stimulus parameters include storing the stimulus parameters that induce the optimal response. The embeddable system according to claim 6, further configured to perform the following:

10. The implantable system according to claim 9, wherein the programmed command identifies the optimal response from a series of further erectile responses in response to an input generated by a sensor system associated with the programmable controller.

11. The implantable system according to claim 9, wherein the programmed command identifies the optimal response from a series of further erectile responses in response to input provided by an external patient controller or an external physician controller.

12. The implantable system according to claim 9, wherein the programmed command storing the preferred stimulation parameters stores stimulation parameters that induce a rapid erectile response.

13. The implantable system according to claim 9, wherein the programmed command storing the preferred stimulation parameters stores stimulation parameters that restore function of neurotransmission via the cavernous nerve.

14. The implantable system according to claim 9, wherein the programmed instructions determining the preferred current direction, the preferred region, the preferred set of excitation electrodes, and the preferred stimulation parameters are configured to be executed periodically in response to commands from an external patient controller or an external physician controller after the implantable system has been implanted.

15. The implantable system according to claim 9, wherein the programmable controller is configured to adjust the preferred stimulus parameters using at least one of machine learning or artificial intelligence.

16. The implantable system according to claim 12, wherein the programmable controller is configured to apply the stimulation parameters that induce a rapid erectile response by activating the stimulation circuit in response to a command received from an external patient controller.

17. The implantable system according to claim 13, wherein the programmable controller is configured to apply the stimulation parameters that restore neurotransmission function by automatically activating the stimulation circuit at least once a day.

18. The implantable system according to claim 1, wherein the flexible paddle is configured to be implanted in the pelvic nerve plexus via laparoscopic surgery.

19. The implantable system according to claim 1, wherein the flexible paddle has a hemispherical shape, and the electrode array comprises at least two electrode rows and at least two electrode columns.

20. The embeddable system according to claim 1, wherein the second direction of the second current flow is oblique to the first direction of the first current flow.

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