Methods of for improvement of lower urinary tract function

Patent metadata

Field	Value
Publication number	US-11813446-B2
Application number	US-202016840353-A
Country	US
Kind code	B2
Filing date	Apr 4, 2020
Priority date	Apr 5, 2019
Publication date	Nov 14, 2023
Grant date	Nov 14, 2023

Abstract

The present invention relates to methods for improvement in lower urinary tract function in an individual with neurogenic urological dysfunction through epidural stimulation of the spinal cord. In certain embodiments, the methods comprise applying a pattern of epidural electrical stimulation to the spinal cord of an individual with impaired lower urinary tract under stimulation parameters sufficient to improve the storage of fluid in the bladder, sensations of fullness and/or emptying, detrusor over-activity, high detrusor pressure, voiding the bladder, transitioning from a storage state to a voiding state, and decreasing detrusor-external urethral sphincter dyssynergia. In certain embodiments, additional patterns of epidural electrical stimulation may be applied simultaneously, such as to maintain a normotensive cardiovascular state of the individual.

First claim

What is claimed is:

1. A method for improving lower urinary tract function in an individual, comprising:
applying a first pattern of epidural electrical stimulation to the spinal cord of the individual at a location, frequency, and intensity sufficient to improve bladder storage; and
applying a second pattern of epidural electrical stimulation to the spinal cord at a location, frequency, and intensity sufficient to maintain a cardiovascular state of the individual within a predetermined range;
wherein applying the second pattern of epidural electrical stimulation and applying the first pattern of epidural electrical stimulation occur simultaneously; and
wherein the method further comprises activity-based recovery training of the individual, including locomotor training.

2. The method of claim 1 , wherein the cardiovascular state is one of heart rate and blood pressure.

3. The method of claim 1 , wherein the first pattern and the second pattern are non-identical.

4. The method of claim 1 , wherein the first pattern and the second pattern are applied to the spinal cord at different locations.

5. The method of claim 1 , further comprising applying a third pattern of epidural electrical stimulation to the spinal cord of the individual at a location, frequency, and intensity sufficient to improve at least one of reflexive micturition and voluntary micturition,
wherein applying the third pattern of epidural electrical stimulation occurs subsequent to applying the first pattern of epidural electrical stimulation, and
wherein the second pattern of epidural electrical stimulation is applied during the application of the first pattern of epidural electrical stimulation and during the application of the third pattern of epidural electrical stimulation.

6. The method of claim 1 , further comprising applying a third pattern of epidural electrical stimulation to the spinal cord of the individual at a location, frequency, and intensity sufficient to improve at least one of reflexive micturition and voluntary micturition.

7. The method of claim 6 , wherein applying the third pattern of epidural electrical stimulation occurs subsequent to applying the first pattern of epidural electrical stimulation.

8. The method of claim 6 , wherein the third pattern and the first pattern are non-identical.

9. The method of claim 6 , wherein the third pattern of epidural electrical stimulation is applied at a higher frequency than the first pattern.

10. The method of claim 1 , wherein the location is one or more spinal segments.

11. The method of claim 1 , wherein improving bladder storage comprises increasing bladder storage in the individual to within the range of 300 ml to 600 ml.

12. The method of claim 1 , wherein improving bladder storage comprises decreasing detrusor leak point pressure in the individual to <40 cm H 2 O.

13. The method of claim 1 , further comprising mapping lower urinary tract responses and cardiovascular responses upon applying epidural electrical stimulation to the spinal cord of the individual using multiple stimulation parameters, and wherein the first pattern of epidural electrical stimulation is determined at least in part on said mapping.

14. The method of claim 1 , wherein the epidural electrical stimulation is applied via an implanted electrode array.

15. The method of claim 1 , wherein the individual has an injury, neurological disorder, or disease state resulting in impaired lower urinary tract function.

16. The method of claim 15 , wherein the individual has a spinal cord injury.

17. The method of claim 1 , wherein the first pattern of epidural electrical stimulation is applied with a pulse width of about 450 microseconds.

18. The method of claim 1 , wherein the activity-based recovery training step is performed before the applying steps and is performed in combination with the applying steps.

19. A method for increasing bladder capacity in an individual, comprising:
applying a first pattern of epidural electrical stimulation to the spinal cord of the individual at a location, frequency, and intensity sufficient to increase bladder capacity; and
applying a second pattern of epidural electrical stimulation to the spinal cord at a location, frequency, and intensity sufficient to maintain a cardiovascular state of the individual within a predetermined range; and
wherein the first pattern of epidural electrical stimulation and the second pattern of epidural electrical stimulation are applied simultaneously; and
wherein the method further comprises activity-based recovery training of the individual, including locomotor training.

20. A method of controlling a cardiovascular state in an individual during one of micturition and bladder filling, the method comprising:
applying a first pattern of epidural electrical stimulation to the spinal cord of the individual at a location, frequency, and intensity sufficient to improve one of micturition and bladder filling; and
applying a second pattern of epidural electrical stimulation to the spinal cord at a location, frequency, and intensity sufficient to maintain a cardiovascular state of the individual within a predetermined range; and
wherein the first pattern of epidural electrical stimulation and the second pattern of epidural electrical stimulation are applied simultaneously; and
wherein the method further comprises activity-based recovery training of the individual, including locomotor training.

21. A method for improving lower urinary tract function in an individual, comprising:
applying a first pattern of epidural electrical stimulation to the spinal cord of the individual at a frequency and intensity sufficient to reduce detrusor-external urethral sphincter dyssynergia; and
applying a second pattern of epidural electrical stimulation to the spinal cord at a location, frequency, and intensity sufficient to maintain a cardiovascular state of the individual within a predetermined range; and
wherein the first pattern of epidural electrical stimulation and the second pattern of epidural electrical stimulation are applied simultaneously; and
wherein the method further comprises activity-based recovery training of the individual, including locomotor training.

22. A method for improving lower urinary tract function in an individual, comprising:
applying a first pattern of epidural electrical stimulation to the spinal cord of the individual at a frequency and intensity sufficient to reduce detrusor over-activity; and
applying a second pattern of epidural electrical stimulation to the spinal cord at a location, frequency, and intensity sufficient to maintain a cardiovascular state of the individual within a predetermined range; and
wherein the first pattern of epidural electrical stimulation and the second pattern of epidural electrical stimulation are applied simultaneously; and
wherein the method further comprises activity-based recovery training of the individual, including locomotor training.

23. A method for improving lower urinary tract function in an individual, comprising:
applying a first pattern of epidural electrical stimulation to the spinal cord of the individual at a frequency and intensity sufficient to alleviate urinary incontinence; and
applying a second pattern of epidural electrical stimulation to the spinal cord at a location, frequency, and intensity sufficient to maintain a cardiovascular state of the individual within a predetermined range; and
wherein the first pattern

Assignees

• Univ Louisville Res Found Inc

Inventors

• Hubscher Charles S
• Harkema Susan J
• Herrity April N
• Chen Yangsheng
• Angeli Claudia

Classifications

• A61N1/36007 Primary

  of urogenital or gastrointestinal organs, e.g. for incontinence control · CPC title

• A61N1/0551

  Spinal or peripheral nerve electrodes · CPC title

• A61N1/36117

  for treating hypertension · CPC title

• A61N1/36062

  Spinal stimulation · CPC title

• A61N1/0553

  Paddle shaped electrodes, e.g. for laminotomy · CPC title