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EP-4291290-B1 - ELECTRO-STIMULATION SYSTEMS AND METHODS FOR REHABILITATION AND TREATMENT OF SEXUAL DISORDERS

EP4291290B1EP 4291290 B1EP4291290 B1EP 4291290B1EP-4291290-B1

Inventors

  • FRAGA DA SILVA, RODRIGO ARAUJO
  • STERGIOPULOS, NIKOLAOS
  • STURNY, MIKAEL NILS
  • JOSEPH, Fiona

Dates

Publication Date
20260506
Application Date
20220208

Claims (15)

  1. An implantable system for treating erectile dysfunction, the system comprising: a flexible paddle (202) having an array of electrodes (204), the array of electrodes (204) comprising a first region (222a) and a second region (222b); and a programmable controller (300) comprising a stimulation circuit (312), a microprocessor (404) and a memory, the stimulation circuit (312) operatively coupled to the array, the microprocessor (404) configured to execute programmed instructions stored in the memory to: cause the stimulation circuit (312) to selectively activate a first pair of electrodes of the array to create a first current flow therebetween in a first direction, the first current flow configured to stimulate a cavernous nerve to elicit a first erectile response; cause the stimulation circuit (312) to selectively activate a second pair of electrodes of the array to create a second current flow therebetween in a second direction, the second direction different than the first direction, the second current flow configured to stimulate the cavernous nerve to elicit a second erectile response; identify either the first erectile response or the second erectile response as a first preferred erectile response; store an identity of either the first direction or the second direction as a preferred current direction for subsequent stimulation of the cavernous nerve; cause the stimulation circuit to selectively activate electrodes in the first region with the preferred current direction to generate a third erectile response; cause the stimulation circuit to selectively activate electrodes in the second region with the preferred current direction to generate a fourth erectile response; identify either the third erectile response or the fourth erectile response as a second preferred erectile response; and store an identity of either the first region or the second region as a preferred region.
  2. The implantable system of claim 1, wherein the microprocessor (404) further is configured to execute programmed instructions stored in the memory to: cause the stimulation circuit (312) to sequentially activate subsets of electrodes within the preferred region with the preferred current direction to elicit a series of erectile responses; identify a favorable erectile response from amongst the series of erectile responses; and store an identity of at least one subset of electrodes within the preferred region as a preferred set of excitation electrodes for subsequent stimulation of the cavernous nerve.
  3. The implantable system of claim 2, wherein the microprocessor (404) further is configured to execute programmed instructions stored in the memory to: cause the stimulation circuit (312) to selectively activate the preferred set of excitation electrodes in the preferred current direction with a series of stimulation parameters to elicit a further series of erectile responses; identify an optimal response from amongst the series of further erectile responses; and store as preferred stimulation parameters the stimulation parameters that elicit the optimal response.
  4. The implantable system of any of the preceding claims, wherein the programmed instructions identify either the first erectile response or the second erectile response as the first preferred erectile response, either the third erectile response or the fourth erectile response as a second preferred erectile response, the favorable erectile response from amongst the series of erectile responses, and/or the optimal response from amongst the series of further erectile responses responsive to input generated by a sensor system (308) associated with the programmable controller (300), or responsive to input provided by an external patient controller (400) or an external physician controller (500).
  5. The implantable system of claims 3 or 4, wherein the programmed instructions that store the preferred stimulation parameters store stimulation parameters that elicit a rapid erectile response, and optionally wherein the programmable controller (300) is configured to activate the stimulation circuit to apply the stimulation parameters that elicit the rapid erectile response responsive to a command received from an external patient controller (400).
  6. The implantable system of any of claims 3 to 5, wherein the programmed instructions that store the preferred stimulation parameters store stimulation parameters that rehabilitate neural transmission via the cavernous nerve, and optionally wherein the programmable controller (300) is configured to automatically activate the stimulation circuit to apply the stimulation parameters that rehabilitate neural transmission at least once per day.
  7. The implantable system of any of claims 3 to 6, wherein the programmed instructions that determine the preferred current direction, the preferred region, the preferred set of excitation electrodes and the preferred stimulation parameters are configured to be periodically executed after the implantable system is implanted responsive to a command from an external patient controller (400) or an external physician controller (500).
  8. The implantable system of any of claims 3 to 7, wherein the programmable controller (300) is configured to adjust the preferred stimulation parameters using at least one of machine learning or artificial intelligence.
  9. The implantable system of any of the preceding claims, wherein the flexible paddle (202) is configured to be implanted at the pelvic plexus via a laparoscopic surgery.
  10. The implantable system of any of the preceding claims, wherein the flexible paddle (202) has a hemispherical shape and the array of electrodes (204) comprises at least two rows of electrodes and at least two columns of electrodes.
  11. The implantable system of any of the preceding claims, wherein the second direction of the second current flow is oblique to the first direction of the first current flow.
  12. The implantable system of any of the preceding claims, wherein the microprocessor (404) is further configured to execute programmed instructions stored in the memory to cause the stimulation circuit (312) to selectively activate a set of excitation electrodes within the array of electrodes (204) to stimulate one or more nerves of the patient's pelvic plexus to induce at least partial penile tumescence, wherein the programmed instructions cause activation of the stimulation circuit (312) at least once daily during a recuperation period following prostatectomy to reduce a risk of penile fibrosis, and optionally wherein the programmed instructions further cause the stimulation circuit (312) to excite the set of excitation electrodes with a series of stimulation parameters to identify an optimal set of stimulation parameters for inducing penile tumescence, and optionally wherein the programmed instructions store the optimal set of stimulation parameters.
  13. The implantable system of claim 12, wherein the programmable controller (300) is coupled to a sensor that monitors a degree of penile tumescence, and the programmed instructions further store as the optimal set of stimulation parameters the set of stimulation parameters that generates a highest degree of penile tumescence.
  14. The implantable system of any of the preceding claims, wherein the stimulation circuit (312) applies a current amplitude in a range of 0.5 to 25mA at a frequency between 10 to 48 Hz with a pulse width between 0.1 to 1.0 milliseconds.
  15. The implantable system of any of the preceding claims, wherein the microprocessor (404) is further configured to execute programmed instructions stored in the memory to: cause the stimulation circuit (312) to activate a subset of electrodes within the array in accordance with a first set of stimulation parameters to elicit an erection responsive to an "on-demand" input from an external patient controller (400) or an external physician controller (500); and activate, at least daily, the subset of electrodes within the array with a second set of stimulation parameters to elicit an erectile response that promotes penile rehabilitation responsive to a schedule input from the external patient controller (400) or the external physician controller (500), and optionally wherein the programmed instructions further cause the stimulation circuit (312) to activate, at least daily, the subset of electrodes within the array with a third set of stimulation parameters to elicit an erectile response that promotes rehabilitation of a cavernous nerve responsive to a schedule input from the external patient controller (400) or the external physician controller (500), and optionally wherein the third set of stimulation parameters applies a current amplitude in a range of 0.1 to 2mA at a frequency between 10 to 48 Hz with a pulse width between 0.01 to 1.0 milliseconds.

Description

FIELD OF THE INVENTION The present disclosure relates to improved implantable electrical stimulation systems for treating and preventing sexual disorders such as erectile dysfunction, erectile dysfunction following prostatectomy surgery, and erectile dysfunction associated with spinal cord injury. The inventive system also may be used to rehabilitate the cavernous nerves, to reduce penile fibrosis, or to treat urinary incontinence. BACKGROUND OF THE INVENTION A sexual disorder (e.g., sexual dysfunction, sexual malfunction) is a complication experienced by an individual, male or female, or a couple during any stage of normal sexual activity, including erection, physical pleasure, desire, preference, arousal, or orgasm. Sexual dysfunctions generally have a profound impact on an individual's quality of life. The most prevalent sexual disorders are erectile dysfunction (ED) and female sexual arousal disorders (FSAD). 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 the flaccid state, the penile smooth muscles are tonically contracted, allowing only a small amount of blood flow for nutritional purposes. Penile erection occurs when sexual stimulation triggers release of neurotransmitters, mainly nitric oxide, from the cavernous nerve terminals. The neurotransmitters cause relaxation of the smooth muscle cells in cavernosal arterioles and sinuses, resulting in increased blood flow into the penis. This causes the cavernous sinuses to fill with blood and expand against the tunica albuginea, partially occluding the venous outflow, thus resulting in an erection. ED is a multi-causal disease with diversified etiologies, and may be psychogenic, vasculogenic, hormonal, or neurogenic. However, studies show that the neurogenic and vasculogenic causes are the most prevalent. In general, the major mechanisms responsible for ED are a failure in the neuronal response (e.g., prostatectomy, cystectomy, abdominoperineal resection, spinal cord injury, or diabetes) or an increase in the tone and/or contractility of the smooth muscle within the corpus cavernosum and penile arteries (e.g., hypertension, atherosclerosis and diabetes). See, Sadeghi-Nejad H., Penile prosthesis surgery: a review of prosthetic devices and associated complications, Sex Med. 2007 Mar; 4(2):296-309. Prostatectomy is known to cause severe ED. This essential surgical procedure, generally for treatment of prostate cancer, often leads to ED due to the inevitable disruption of the neural pathway for erectile function. These intimal nerves are located around the prostate, and may be damaged during the surgery. Currently, surgeons attempt to perform a nerve-sparing surgery; however, in the actual scenario, an astounding 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. Pharmacological treatments are currently available for ED. These drugs (e.g., sildenafil, Viagra®; tadalafil, Cialis® or vardenafil, Levitra®) are efficient for the majority of ED patients; however, they show low effectiveness for ED resulting from prostatectomy or others causes associated with failure in the neuronal response. Such drugs act by potentiating the actions 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 responsible for breaking down the intracellular second messenger cGMP generated by NO stimulus. cGMP is involved in the regulation of some protein-dependent kinases, which relax smooth muscle cells and facilitate erection. Thus, patients with disruption of the erectile neural response do not respond well to such medications. One alternative for these patients is intrapenial injections of vasodilators, which produce direct erection, independent of the neural pathway. See, Leungwattanakij S, Flynn V Jr, Hellstrom WJ, Intracavernosal injection and intraurethral therapy for erectile dysfunction, Urol Clin North Am. 2001 May; 28(2):343-54 and Harding LM, Adeniyi A, Everson R, Barker S, Ralph DJ, Baranowski AP, Comparison of a needle-free high-pressure injection system with needle- tipped injection of intracavernosal alprostadil for erectile dysfunction, Int J Impot Res. 2002 Dec; 14(6):498-501. Alprostadil (Prostaglandin E1, PGE1) is the most common vasodilator used for ED. See, Harding and Eardley I, Donatucci C, Corbin J, El-Meliegy A, Hatzimouratidis K, McVary K, Munarriz R, Lee SW, Pharmacotherapy for erectile dysfunction, J Sex Med. 2010 J