U.S. patent application number 12/601195 was filed with the patent office on 2010-10-28 for systems and methods for the treatment of bladder dysfunctions using neuromodulation.
This patent application is currently assigned to NDI MEDICAL, INC.. Invention is credited to Maria E. Bennett, Joseph W. Boggs, II, Julie Grill, Joseph J. Mrva, Robert B. Strother, Geoffrey B. Thrope.
Application Number | 20100274310 12/601195 |
Document ID | / |
Family ID | 40130612 |
Filed Date | 2010-10-28 |
United States Patent
Application |
20100274310 |
Kind Code |
A1 |
Boggs, II; Joseph W. ; et
al. |
October 28, 2010 |
SYSTEMS AND METHODS FOR THE TREATMENT OF BLADDER DYSFUNCTIONS USING
NEUROMODULATION
Abstract
Systems and Methods treat bladder dysfunctions using
neuromodulation stimulation. Bladder emptying through stimulation
of urethral afferents, and continence through stimulation of the
dorsal genital nerve, is provided with one or more implanted pulse
generators and one or more leads. A simple surgical procedure
preserves all existing functions. A stimulating catheter is
provided to be used as a clinical screening tool. The stimulating
catheter is used to measure bladder pressures and stimulate the
urethra at the same time.
Inventors: |
Boggs, II; Joseph W.;
(Carrboro, NC) ; Bennett; Maria E.; (Beachwood,
OH) ; Grill; Julie; (Chapel Hill, NC) ; Mrva;
Joseph J.; (Girard, OH) ; Strother; Robert B.;
(Willoughby Hills, OH) ; Thrope; Geoffrey B.;
(Shaker Heights, OH) |
Correspondence
Address: |
MEDTRONIC, INC.
710 MEDTRONIC PARKWAY NE
MINNEAPOLIS
MN
55432-9924
US
|
Assignee: |
NDI MEDICAL, INC.
Cleveland
OH
|
Family ID: |
40130612 |
Appl. No.: |
12/601195 |
Filed: |
May 22, 2008 |
PCT Filed: |
May 22, 2008 |
PCT NO: |
PCT/US2008/006542 |
371 Date: |
May 27, 2010 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11891074 |
Aug 9, 2007 |
|
|
|
12601195 |
|
|
|
|
11149654 |
Jun 10, 2005 |
7565198 |
|
|
11891074 |
|
|
|
|
11150418 |
Jun 10, 2005 |
7239918 |
|
|
11891074 |
|
|
|
|
11290268 |
Nov 30, 2005 |
|
|
|
11891074 |
|
|
|
|
11729333 |
Mar 28, 2007 |
|
|
|
11290268 |
|
|
|
|
60931263 |
May 22, 2007 |
|
|
|
60578742 |
Jun 10, 2004 |
|
|
|
60578742 |
Jun 10, 2004 |
|
|
|
60599193 |
Aug 5, 2004 |
|
|
|
60680598 |
May 13, 2005 |
|
|
|
Current U.S.
Class: |
607/41 |
Current CPC
Class: |
A61N 1/36107 20130101;
A61M 2210/1067 20130101; A61N 1/0512 20130101; A61N 1/05 20130101;
A61N 1/36007 20130101; A61M 2205/054 20130101; A61N 1/0524
20130101; A61M 2210/1089 20130101 |
Class at
Publication: |
607/41 |
International
Class: |
A61N 1/36 20060101
A61N001/36 |
Goverment Interests
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
[0002] This invention was made with government support under grant
number 1RNS055393-01 awarded by the National Institutes of Health,
through the National Institute of Neurological Disorders and
Stroke. The Government may have certain rights in the invention.
Claims
1.-48. (canceled)
49. A method of providing bladder function comprising: providing a
first lead including one or more stimulation electrodes, providing
a second lead including one or more stimulation electrodes,
positioning the first lead on, in, or near a dorsal genital nerve,
positioning the second lead on in, or near urethral afferents,
applying a stimulation pulse to the first lead and to the second
lead to provide bladder function.
50. A method according to claim 49: wherein positioning the first
lead comprises: inserting the first lead midline or near midline
over the pubic symphysis aiming toward the clitoris in females or
base of penis in males, and advancing the first lead to reach the
dorsal genital nerve between the pubic symphysis and the clitoris
in females or the base of the penis in males.
51. A method according to claim 49: wherein positioning the second
lead comprises: inserting the second lead through the skin of the
perineum, advancing the second lead to a target depth necessary for
positioning along the urethra.
52. A method of improving bladder function comprising: providing a
first elongated lead comprising one or more stimulation electrodes
sized and configured to be implanted in a tissue region at or near
a target A, providing a second elongated lead comprising one or
more stimulation electrodes sized and configured to be implanted in
a tissue region at or near a target B, providing a pulse generator
to convey one or more electrical stimulation waveforms to the first
lead to stimulate the target A and to the second lead to stimulate
the target B, implanting the first lead in the tissue region at or
near the target A, implanting the second lead in the tissue region
at or near the target B, coupling the first lead and the second
lead to the pulse generator, operating the pulse generator to
convey one or more electrical stimulation waveforms to the first
lead to stimulate the target A, the stimulation waveforms conveyed
to the stimulation electrodes affecting afferent stimulation of
target A, operating the pulse generator to convey one or more
electrical stimulation waveforms to the second lead to stimulate
the target B, the stimulation waveforms conveyed to the stimulation
electrodes affecting afferent stimulation of target B, and the
afferent stimulation activating central nervous system circuitry
that coordinates and/or produces efferent activity in target A
and/or efferent activity in target B to produce and/or further
continence and/or bladder emptying.
53. A method of improving bladder function comprising: providing an
elongated lead comprising one or more stimulation electrodes sized
and configured to be implanted in a tissue region at or near a
target A and/or a target B, providing a pulse generator to convey
one or more electrical stimulation waveforms to the elongated lead
to stimulate the target A and/or the target B, implanting the
elongated lead in the tissue region at or near the target A and/or
the target B, coupling the elongated lead to the pulse generator,
operating the pulse generator to convey one or more electrical
stimulation waveforms to the elongated lead to stimulate the target
A and/or the target B, the stimulation waveforms conveyed to the
stimulation electrodes affecting afferent stimulation of target A
and/or target B, the afferent stimulation activating central
nervous system circuitry that coordinates and/or produces efferent
activity in target A and/or efferent activity in target B to
produce and/or further continence and/or bladder emptying.
54. A method according to claim 53: wherein the afferent
stimulation activating central nervous system circuitry that
coordinates and/or produces efferent activity in target A and/or
efferent activity in target B and/or the pelvic nerve (s) and/or
hypogastric nerve (s) to produce and/or further continence and/or
bladder emptying.
55. A method according to claim 53: wherein implanting the
elongated lead comprises: inserting the lead midline or near
midline over the pubic symphysis aiming toward the clitoris in
females or base of penis in males, and advancing the lead to reach
the target A and/or target B between the pubic symphysis and the
clitoris in females or the base of the penis in males.
56. A method according to claim 53: wherein implanting the
elongated lead comprises: inserting the elongated lead through the
skin of the perineum, and advancing the lead to a target depth
necessary to reach the target A and/or target B along the
urethra.
57. A method according to claim 53: wherein implanting the
elongated lead comprises: inserting the lead about 2 cm lateral and
about 2 cm caudal to the midpoint of a line defined between the
posterior superior iliac spine and the ischical tuberosity, and
advancing the lead to a target depth necessary to reach the target
A and/or the target B.
58. A method of restoring bladder function comprising: implanting a
first lead adapted for dorsal genital nerve stimulation, implanting
a second lead adapted for urethral afferent stimulation, coupling
the first lead to a pulse generator, coupling the second lead to
the pulse generator, operating the pulse generator in a continence
mode to allow the bladder to fill, and after the bladder has filled
to a level, operating the pulse generator in a micturition mode to
empty some or all of the contents of the bladder.
59. A system for restoring bladder function comprising: a first
lead adapted for dorsal genital nerve stimulation, a second lead
adapted for urethral afferent stimulation, a pulse generator
adapted to couple to the first lead and the second lead to provide
electrical stimulation to the dorsal genital nerve and the urethral
afferents, the pulse generator including a continence mode to allow
the bladder to fill, and the pulse generator including a
micturition mode to empty some or all of the contents of the
bladder after the bladder has filled to a level.
Description
RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional
Patent Application Ser. No. 60/931,263, filed May 22, 2007, and
entitled "Systems and Methods for the Treatment of Bladder
Dysfunctions Using Neuromodulation Stimulation" which is
incorporated herein by reference.
FIELD OF THE INVENTION
[0003] This invention relates to systems and methods for
stimulating nerves and/or muscles in animals, including humans, to
treat bladder dysfunctions.
BACKGROUND OF THE INVENTION
I. Neuromodulation Stimulation
[0004] Neuromodulation stimulation (the electrical excitation of
nerves to indirectly affect the stability or performance of a
physiological system) can provide functional and/or therapeutic
outcomes. While existing systems and methods can provide remarkable
benefits to individuals able to be treated with neuromodulation
stimulation, many limitations and issues still remain. For example,
existing systems can often require the user to wear an external
stimulator, which may provide a positive functional outcome, but
may also negatively affect quality of life issues.
[0005] A variety of products and treatment methods are available
for neuromodulation stimulation, including external and surgically
implanted stimulators. As an example, neuromodulation stimulation
has been used for the treatment of lower urinary tract
dysfunctions, including bladder dysfunctions, which affects both
men and women. In addition, a wide, range of other options exist
for the restoration of bladder function. Treatments include
everything from medications, devices such as catheters, and
psychological counseling.
[0006] Both external and implantable devices are available for the
purpose of neuromodulation stimulation for the restoration of
bladder function. The operation of these devices typically includes
the use of an electrode placed either on the external surface of
the skin or a surgically implanted electrode. Although these
modalities have shown the ability to provide a neuromodulation
stimulation with some positive effects, they have received limited
acceptance by patients because of their limitations of portability,
limitations of treatment regimes, and limitations of ease of use
and user control.
II. Bladder Function
[0007] In a healthy person, the lower urinary tract provides two
functions: storage of urine (continence) and urination
(micturition). During continence, the bladder is relaxed and fills
with urine while the sphincter contracts to prevent leakage of
urine. During micturition, the sphincter relaxes and the bladder
contracts to expel urine through the urethra. Flow receptors along
the urethra detect this flow of urine and send afferent (sensory)
signals to the sacral spinal cord, which augments urination by
decreasing (-) sphincter tone and increasing (+) efferent (motor)
drive to the bladder detrusor muscle (see FIG. 1). This positive
feedback continues until the urethral flow receptors no longer
detect fluid flow and stop sending afferent signals to the spinal
cord, resulting in relaxation of the bladder and the beginning of
the next continence phase.
[0008] Continence may be restored through electrical stimulation of
the dorsal genital nerve, which is a branch of the pudendal nerve.
Similarly, micturition may be restored through electrical
stimulation of urethra afferent nerves, which are also branches of
the pudendal nerve (see FIGS. 2 and 3). Electrical stimulation of
the urethral afferents can drive this positive feedback and
activate the micturition circuitry in the sacral spinal cord, just
as if the person was already in the process of urination. Just as
in micturition in a healthy person, the sacral spinal cord would
coordinate the process of urination by relaxing the sphincter and
contracting the bladder to expel urine. This method has been used
to empty the bladder in cats before and after spinal transection at
T12 and achieve bladder contraction in humans after supra sacral
spinal cord injury (SCI).
[0009] The conditions needed to evoke bladder emptying via
activation of urethral afferents are known and include bladder
volume, stimulation frequency, and neural circuitry. The bladder
must contain more than a minimum threshold volume to initiate the
micturition-like response, and the threshold volume varies markedly
from individual to individual but on average is approximately 33
percent less than the volume at which the first distention-evoked
contractions occur. Stimulation of the urethral afferents with
frequencies between 1 and 50 Hz has been shown to evoke
micturition-like responses in decerebrate and anesthetized animals.
33 Hz has been shown to be the stimulation frequency most effective
in evoking sustained bladder contractions and voiding in cats, and
stimulation frequencies of 20 to 40 Hz appear to be the most
effective in eliciting micturition-like bladder contractions in
persons with SCI. Furthermore, this frequency range has been shown
to be identical to frequencies at which urethral afferents fire
during urethral flow.
[0010] Stimulating urethral afferents at the appropriate frequency
may evoke a micturition-like reflex if the starting bladder volume
is above threshold. Electrical stimulation of urethral afferents
may evoke micturition even if some of the neural circuitry is
damaged or compromised (e.g., through disease or injury, including
spinal cord injury). However, stimulation is more likely to be
successful if the sacral spinal cord is intact because anatomical
mapping and electrophysiology studies show that the sacral cord
contains the spinal micturition circuitry. This is supported by
observations of coordinated bladder-sphincter activity in humans
with supra sacral injuries and confirmed by coordinated
micturition-like activity evoked by electrical stimulation of
urethra afferents before and after spinal transection (T10-T12) in
cats.
III. Present Treatment Methods
[0011] The inability to empty the bladder is a significant problem
that is not adequately addressed by present treatment options.
Approximately 250,000 persons in the United States are living with
a spinal cord injury (SCI), with approximately 10,000 more persons
being spinal cord injured each year, and even more persons have
damaged neural circuitry from disease or other injuries. In SCI
persons, the SCI prevents the brain stem from communicating with
the lower urinary tract, eliminating voluntary control of
continence (urine storage) and micturition (urine evacuation).
Bladder contractions become ineffective in emptying the bladder,
leaving a high residual volume. The urinary system transformed by
SCI typically results in additional complications such as ureteric
reflux and obstruction, infection of the kidneys, long-term renal
damage, episodes of autonomic dysreflexia with dangerous rises in
blood pressure, bladder trabeculation, and frequent urinary tract
infections.
[0012] For a person with SCI, the direct medical costs associated
with urinary tract dysfunction may exceed $8,000 each year, making
up a substantial component of the estimated $31,000 to $75,000
annual health care and living expenses of individuals with spinal
injury. Furthermore, the loss of control of urinary function alters
social relationships and can be personally demoralizing, and it can
lead to depression, anger, poor self-image, embarrassment,
frustration and can prevent persons from achieving their personal
goals.
[0013] As previously identified, many techniques have been
developed to treat lower urinary tract dysfunction brought about by
SCI and other conditions. Presently, self-catheterization proves to
be the best non-invasive method to care for lower urinary tract
dysfunction, but many persons with lower urinary tract dysfunction
sustain multiple infections per year, and persons with SCI often
lack the physical ability to catheterize themselves. Alternative
methods have been developed to empty the bladder by preventing the
sphincter from closing the urethra, but most of them, including
sphincterotomy, sphincter paralysis, and urethral stenting, leave
the person incontinent and lead to further complications. Other
techniques, such as balloon dilation, have a low (e.g., 15 percent)
success rate, and presently, no techniques provide effective
bladder emptying without the secondary consequences that limit
widespread acceptance among the patient population.
[0014] There is a significant market need for providing bladder
emptying with electrical stimulation. As previously stated, an
estimated 250,000 persons with SCI in the United States suffer from
urinary retention at an annual cost of $1.5 billion. VOCARE
(FineTech Medical, UK) is the only commercially available
neurostimulation system that provides bladder emptying, but it is
used by less than one percent of eligible patients. It has been
found that few people elect to receive the VOCARE system because it
requires 1) a time-consuming (e.g., more than eight hours),
invasive surgical procedure and 2) an irreversible nerve
transection, resulting in the loss of sexual function and reflex
defecation. The systems and methods of the present invention
provide an alternative approach with several significant advantages
over the VOCARE system.
[0015] The present novel invention addresses the need for a system
that is simpler to implant and more acceptable to persons with
bladder dysfunctions. Most potential VOCARE patients are unwilling
to undergo the extensive surgery and extended inpatient hospital
stay, and even fewer will consider sacrificing sexual function and
reflex defecation in exchange for bladder control.
[0016] The present novel invention provides systems and methods for
bladder control with a simple (e.g., less than two hour) outpatient
procedure that may preserve all existing functions. Implantation of
a VOCARE system requires the coordination of doctors from multiple
disciplines, but the novel approach of the present invention allows
the patient's regular Urologist to implant the system. Presently,
it is difficult to determine how effective a VOCARE system may be
prior to implantation. In comparison, the novel systems and methods
include a stimulating catheter electrode (see FIG. 20A) adapted to
be used as a quick (e.g., less than 15 minutes), minimally-invasive
way to determine how well a patient may respond to the system
before surgery. The stimulating catheter will be described further
in section "V. Stimulating Catheter." The novel systems and methods
of the present invention combine bladder emptying through
stimulation of urethral afferents and continence through
stimulation of the dorsal genital nerve to provide complete bladder
control with a simple surgical procedure that preserves all
existing functions. This innovative approach may also benefit
individuals with brainstem stroke or multiple sclerosis, who often
do not have bladder control.
[0017] There remains a need for systems and methods that can treat
lower urinary tract dysfunctions as a first line of treatment and
for those who have not responded to conventional therapies, in a
straightforward manner, without requiring drug therapy and
complicated and irreversible surgical procedures.
SUMMARY OF THE INVENTION
[0018] The novel systems and methods of the present invention
combine bladder emptying through stimulation of urethral afferents
and continence through stimulation of the dorsal genital nerve to
provide complete bladder control with a simple surgical procedure
that preserves all existing functions.
[0019] Alternatively, at least one or more leads may activate
selectively either the urethral afferent pathway to provide
micturition or the genital afferent pathway to provide continence
by changing stimulus parameters such as frequency, amplitude,
and/or pulse width.
[0020] A stimulating catheter is provided to be used as a clinical
screening tool. The stimulating catheter may be used to measure
bladder pressures and stimulate the urethra at the same time.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 is a schematic view of sensory signals and the spinal
circuitry activity that coordinates efferent and afferent nerve
activity and produces bladder functions.
[0022] FIG. 2 is a lateral section view of a male pelvic girdle
region.
[0023] FIG. 3 is a lateral section view of a female pelvic girdle
region.
[0024] FIG. 4 is an anterior anatomic view of an exemplary
embodiment of a system after implantation in a pelvic region for
restoration of bladder functions.
[0025] FIGS. 5A and 5B are front and side views of one embodiment
of the general purpose implantable pulse generator shown in FIG. 4,
which may be powered by a primary or rechargeable battery.
[0026] FIGS. 6A and 6B are front and side views of an alternative
embodiment of the general purpose implantable pulse generator as
shown in FIG. 4, which may be powered by a primary or rechargeable
battery.
[0027] FIG. 7 is a plane view of the implant system shown in FIG.
4, for restoration of bladder functions, showing implant depth and
non-inductive wireless telemetry features.
[0028] FIGS. 8 and 9 are perspective views of the lead and
electrode associated with the system shown in FIG. 4.
[0029] FIG. 10 is a side interior view of a representative
embodiment of a lead of the type shown in FIGS. 8 and 9.
[0030] FIG. 11 is an end section view of the lead taken generally
along line 11-11 in FIG. 10.
[0031] FIG. 12 is an elevation view, in section, of a lead and
electrode of the type shown in FIGS. 8 and 9 residing within an
introducer sleeve for implantation in a targeted tissue region, the
anchoring members being shown retracted within the sheath.
[0032] FIG. 13 shows an anatomical view of an anterior approach for
implanting a lead as part of the system shown in FIG. 4.
[0033] FIG. 14 shows a lateral section view of the anterior
approach for implanting a lead, as shown in FIG. 13.
[0034] FIG. 15 shows an anatomical view of a perineal approach for
implanting a lead as part of the system shown in FIG. 4.
[0035] FIG. 16 shows a lateral section view of the perineal
approach for implanting a lead, as shown in FIG. 15.
[0036] FIG. 17 shows an anatomical view of a posterior approach for
implanting a lead as part of the system shown in FIG. 4.
[0037] FIG. 18 shows a lateral section view of the posterior
approach for implanting a lead, as shown in FIG. 17.
[0038] FIG. 19 is an anatomical view showing the implant system
implanted in a pelvic region, and a clinical programmer within (or
outside) the sterile field using non-inductive wireless telemetry
to communicate with the implanted pulse generator.
[0039] FIG. 20A is a perspective view of a stimulating catheter
adapted for urethral stimulation of both males and females.
[0040] FIG. 20A is a perspective view of stimulating catheter
electrode adapted for urethral stimulation of both males and
females.
[0041] FIG. 20B is a detailed plan view of an electrode secured to
the catheter body of the stimulating catheter shown in FIG.
20A.
[0042] FIG. 20C is a perspective view of the stimulating catheter
shown in FIG. 20A, except with an alternative configuration of
electrode placement.
[0043] FIG. 21 is a cross-sectional view taken along lines 21-21 of
FIG. 20A, showing a two lumen configuration used in conjunction
with the stimulating catheter.
[0044] FIG. 22 is a cross-sectional view taken along lines 22-22 of
FIG. 20A, showing an electrode used in conjunction with the
stimulating catheter.
[0045] FIG. 23 is a lateral anatomical view showing the stimulating
catheter of FIG. 20A positioned within the urethra of a human male
to selectively stimulate urethral afferents.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0046] Although the disclosure hereof is detailed and exact to
enable those skilled in the art to practice the invention, the
physical embodiments herein disclosed merely exemplify the
invention which may be embodied in other specific structures. While
the preferred embodiment has been described, the details may be
changed without departing from the invention.
I. Restoration of Bladder Function
[0047] The present novel invention provides systems and methods of
bladder control to individuals with neurological disorders,
including spinal cord injury (SCI), who do not have volitional
control over their lower urinary tract. This lack of control
results in incontinence and inability to urinate on demand, which
frequently causes many serious adverse health effects. The only
commercially available electrical stimulation product (VOCARE,
FineTech Medical, UK) to restore full bladder control in persons
with SCI includes an electrode placed on the sacral spinal motor
nerves to empty the bladder. It also requires permanently severing
sacral spinal sensory nerves (rhizotomy) to achieve continence.
[0048] Because this rhizotomy is irreversible and because it may
result in loss of sexual function, VOCARE has not been widely
accepted among the potential patient population.
[0049] The features and benefits of the present invention provide
alternative neurostimulation systems and methods to restore bladder
control that does not require electrode placement on the spinal
nerve roots and does not require rhizotomy.
[0050] The pudendal nerve(s), their branches and/or their roots may
be stimulated to restore lower urinary tract functions, including
bladder emptying (urination) and/or storage (continence).
[0051] Electrical stimulation of the genital nerve(s) can provide
continence, and electrical stimulation of the urethral sensory
nerve(s) can provide micturition. Both of these pathways (genital
and urethral) can, be activated at multiple locations and/or
anatomical levels: at the most superficial level at and/or near the
skin and/or urethra; at and/or near the respective urethral and/or
genital nerve; at and/or near the pudendal nerve; and/or at and/or
near the sacral nerve root(s).
[0052] Both the caudal and rostral portions of the urethra are
innervated by urethral afferents in the cat, and both portions of
the urethra are thought to be innervated by urethral afferents in
the human (see FIGS. 1 to 3). One embodiment of the present
invention may include stimulation of the caudal urethra because it
contains the majority of the larger lamellated end-organs that act
as urethral flow receptors. However, if stimulation of the caudal
urethra is not effective to evoke bladder contractions, an
alternative embodiment of the present invention may stimulate the
rostral urethra because it is thought to contain a different type
of flow receptors also known to evoke micturition-like responses in
cats and humans after SCI. Or, both caudal and rostral portions of
the urethra may be stimulated.
[0053] Combinations of lead placement may be used to restore
bladder function. At least one or more lead(s) may activate the
genital sensory pathway to produce urine storage (continence). At
least one or more lead(s) may activate the urethral sensory pathway
to provide bladder emptying (micturition). These lead(s) and
functions may be combined to provide complete bladder control
(storage and emptying) or used individually to provide either
function (storage or emptying) as needed. Alternatively, at least
one or more leads may activate selectively either the urethral
afferent pathway to provide micturition or the genital afferent
pathway to provide continence by changing stimulus parameters such
as frequency, amplitude, and/or pulse width.
[0054] For example, electrical stimulation of pudendal nerve
afferents differentially activates continence-like and
micturition-like reflexes dependent on the frequency of
stimulation. Different groups of pudendal nerve afferents can
generate either inhibition or excitation of the bladder.
Stimulation of genital and/or anal sensory pathways in the pudendal
nerve inhibits the bladder by decreasing parasympathetic outflow in
the pelvic nerve to the bladder detrusor muscle and by increasing
sympathetic outflow in the hypogastric nerve. Bladder inhibition
may be evoked by low frequency stimulation (e.g., 2 to 20 Hz) of
pudendal nerve afferents; and inhibition may be lost during higher
frequency (e.g., 35 Hz) stimulation.
[0055] Excitation of the bladder can be produced by stimulation of
urethral sensory pathways over a range of stimulus frequencies.
However, higher frequency (e.g., 20 to 40 Hz) stimulation may be
more effective than 10 Hz stimulation at evoking bladder
contractions, consistent with the firing rates of urethral
afferents in response to urethral fluid flow that is capable of
evoking bladder excitation.
[0056] The compound pudendal nerve contains both genital sensory
(inhibitory) and urethral sensory (excitatory) pathways. Both
excitatory and inhibitory pathways can be accessed at the level of
the pudendal nerve and activated differentially according to
stimulus frequency. Thus, it may be possible to control selectively
both continence and micturition with a single electrode on a
peripheral nerve (i.e. the pudendal nerve and/or its branches
and/or its roots).
[0057] One embodiment of the present invention uses a lead and
electrode placed in the pelvic region near pudendal urethral
afferents to achieve urination and a lead and electrode placed in
the pelvic region near the dorsal genital nerve to achieve
continence (see FIG. 4). It is known that continence can be
achieved with dorsal genital nerve stimulation. This embodiment
includes a stimulator and two electrode leads adapted to combine
techniques for bladder emptying and continence.
II. Implant System
[0058] An implant system may be used to provide electrical
stimulation of a target nerve A and/or a target nerve B (e.g., the
pudendal nerve and/or branches and/or roots, and/or the dorsal
genital nerve, and/or urethral afferents), for the restoration of
bladder function on demand and with a simple surgical procedure
that preserves the existing anatomy. As used in this disclosure, it
is to be appreciated that at least the terms "nerve", "lead",
"electrode", and "IPG" can include both the singular or plural
meaning.
[0059] The electrical stimulation may be applied, with any type of
electrical contact such as one or more leads having one or more
electrodes placed in, on, around, or near any of the target nerves
A and/or target nerves B named above. The lead may also include the
ability to deliver medications or drugs as an adjunct to electrical
stimulation. Note that the electrode may be in contact with the
target nerve, or it may be some distance (on the order of
centimeters) away because it does not have to be in contact with
the target nerve to activate it.
[0060] Stimulation may be applied through a lead/electrode, such as
a fine wire electrode, paddle electrode, intramuscular electrode,
or adipose electrode, inserted via a needle introducer or
surgically implanted in proximity of the target nerve. When proper
placement is confirmed, as indicated by patient sensation or
visible movement of related organ(s) such as the penis, scrotum,
perineal muscle, perineal skin, and/or anal sphincter, (or clitoris
for women), the needle may be withdrawn, leaving the electrode in
place. Stimulation may also be applied through a penetrating
electrode, such as an electrode array comprised of any number
(e.g., greater than or equal to one) of needle-like electrodes that
are inserted into the target nerve. In both cases, the lead may be
placed using a needle-like introducer, allowing the lead/electrode
placement to be minimally invasive.
[0061] Alternatively, stimulation may be applied through any type
of nerve cuff (spiral, helical, cylindrical, book, flat interface
nerve electrode (FINE), slowly closing FINE, etc.) that is
surgically placed on or around a target nerve.
[0062] In all cases, the lead may exit through the skin and connect
with one or more external stimulators, or the lead(s) may be routed
subcutaneously to one or more implanted pulse generators (IPG), or
they may be connected as needed to internal and external coils. The
IPG may be located some distance (remote) from the electrode, or
the IPG may be integrated with the electrode, eliminating the need
to route the lead subcutaneously to the IPG.
[0063] Control of the stimulator and stimulation parameters may be
provided by one or more external controllers. In the case of an
external stimulator, the controller may be integrated with the
external stimulator. The IPG external controller (i.e., clinical
programmer) may be a remote unit that uses non-inductive radio
frequency (RF) wireless communication to control the IPG. The
external or implantable pulse generator may use regulated voltage
(e.g., 10 mV to 20 V), regulated current (e.g., 10 .mu.A to 50 mA),
and/or passive charge recovery to generate the stimulation
waveform.
[0064] The pulse may by monophasic, biphasic, and/or multi-phasic.
In the case of the biphasic or multi-phasic pulse, the pulse may be
symmetrical or asymmetrical. Its shape may be rectangular or
exponential or a combination of rectangular and exponential
waveforms. The pulse width of each phase may range between e.g., 10
.mu.sec and 10 to the sixth power .mu.sec.
[0065] Pulses may be applied in continuous or intermittent trains
(i.e., the stimulus frequency changes as a function of time). In
the case of intermittent pulses, the on/off duty cycle of pulses
may be symmetrical or asymmetrical, and the duty cycle may be
regular and repeatable from one intermittent burst to the next or
the duty cycle of each set of bursts may vary in a random (or
pseudo random) fashion. Varying the stimulus frequency and/or duty
cycle may improve and/or optimize the response, and assist in
preventing fatigue, warding off habituation, lessening the effects
of long term potentiation or long term de-potentiation, because of
the stimulus modulation.
[0066] The stimulating frequency may range from e.g., 1 to 300 Hz,
and the frequency of stimulation may be constant or varying. In the
case of applying stimulation with varying frequencies, the
frequencies may vary in a consistent and repeatable pattern or in a
random (or pseudo random) fashion or a combination of repeatable
and random patterns that may be cycles through.
[0067] The stimulation pulses could be applied to a left target
nerve and a right target nerve with different parameters, or the
stimulation pulses could be applied to different branches of the
same target nerve at different parameters, such as different
frequencies, to provide the best response. For example, the left
target nerve A could be stimulated at 25 Hz, and the right target
nerve A could be stimulated at 30 Hz.
[0068] By way of an additional non-limiting example, 20 Hz may be
used for all stimulation or 10 Hz may be used for target A
stimulation and 40 Hz may be used for target B stimulation, and,
target A may be stimulated at 2 mA and target B may be stimulated
at 0.050 mA or vice versa, or both target A and target B may be
stimulated at the same amplitude.
[0069] FIG. 4 shows an exemplary embodiment of an implant system 10
for the restoration of bladder function in animals, including
humans. It is to be appreciated that multiple implant system
configurations are possible. As non-limiting examples, a single IPG
18 may be coupled to a single lead 12 to unilaterally stimulate a
single target nerve (either A or B); or a single IPG may be coupled
to two leads to bilaterally stimulate a single target nerve (either
A or B); or a single IPG may be coupled to two leads to
unilaterally stimulate a target nerve A and target nerve B; or two
IPGs may be implanted, each being coupled to a single lead to
bilaterally stimulate a single target nerve (either A or B); or two
IPGs may be implanted, each being coupled to a single lead to
unilaterally stimulate a target nerve A and target nerve B; or two
IPGs may be implanted, each being coupled to two leads to
bilaterally stimulate a target nerve A and a target nerve B. It is
to be appreciated that additional system configurations exist.
[0070] Referring to FIG. 4, the system 10 includes at least one
implantable lead 12 having a proximal end and a distal end, the
distal end being coupled to an implantable pulse generator or IPG
18. The lead 12 and the implantable pulse generator 18 are shown
implanted within a pelvic region of a human or animal body,
although other implant sites are possible.
[0071] In the embodiment shown, the distal end of the lead 12
includes at least one electrically conductive surface, which will
in shorthand be called an electrode 16. The electrode 16 may be
implanted in electrical conductive contact with at least a target
nerve A and/or a target nerve B. The implantable pulse generator 18
includes a connection header 14 that desirably carries a plug-in
receptacle 15 (connector) for the distal end of the lead 12 (see
FIGS. 5A and 5B). In this way, the lead electrically connects the
electrode 16 to the implantable pulse generator 18.
[0072] The implantable pulse generator 18 may be sized and
configured to be implanted subcutaneously in tissue, desirably in a
subcutaneous pocket, which can be remote from the electrode 16, as
FIG. 4 shows. Desirably, the implantable pulse generator 18 may be
sized and configured to be implanted using a minimally invasive
surgical procedure.
[0073] The lead 12 and electrode 16 are sized and configured to be
implanted percutaneously in tissue, and to be tolerated by an
individual during extended use without pain or discomfort. The
comfort is both in terms of the individual's sensory perception of
the electrical waveforms that the electrode applies, as well as the
individual's sensory perception of the physical or mechanical
presence of the electrode and lead. In the case of the mechanical
presence, the lead 12 and electrode 16 are desirably
"imperceptible."
[0074] In particular, the lead 12 and electrode 16 are sized and
configured to reside with stability in the lower pelvic region of
the body (see FIG. 4). It has been discovered that, when properly
placed in this region, one or more lead/electrode(s) are uniquely
able to deliver electrical stimulation current to a target nerve A
and/or a target nerve B to treat bladder dysfunction.
[0075] FIGS. 5A and 5B, and 6A and 6B, show multiple embodiments of
an implantable pulse generator 18 of the present invention, and
will be described in greater detail later. The implantable pulse
generator 18 includes a circuit 20 that generates electrical
stimulation waveforms. An on-board, primary or rechargeable battery
22 desirably provides the power. The implantable pulse generator 18
also desirably includes an on-board, programmable microcontroller
24, which carries embedded code. The code expresses pre-programmed
rules or algorithms under which the desired electrical stimulation
waveforms are generated by the circuit 20. The implantable pulse
generator 18 may also include an electrically conductive case 26,
which can also serve as the return electrode for the stimulus
current introduced by the lead/electrode when operated in a
monopolar configuration.
[0076] The pulse generator 18 may be sized and configured to be
implanted subcutaneously in tissue at an implant depth of between
about five millimeters and about twenty millimeters, desirably in a
subcutaneous pocket remote from the electrode 16 (see FIG. 7) and
using a minimally invasive surgical procedure. This implant depth
may change due to the particular application, or the implant depth
may change over time based on physical conditions of the patient.
As shown in FIG. 4, the implantation site can comprise a more
medial tissue region in the lower abdomen. There, the pulse
generator 18 can reside for extended use without causing pain
and/or discomfort and/or without effecting body image.
Alternatively, the implantation site can comprise a tissue region
on the posterior hip, for example.
[0077] The implant system 10 may include an external patient
controller 80 (or controller-charger when a rechargeable battery is
used). The patient controller 80 may be sized and configured to be
held or worn by the individual to transcutaneously activate and
deactivate and/or modify the output of the pulse generator 18. The
patient controller 80 may, e.g., be a simple magnet that, when
placed near the site where the pulse generator 18 is implanted,
toggles a magnetic switch within the implantable pulse generator 18
between an on condition and an off condition, or advances through a
sequence of alternative stimulus modes pre-programmed by the
clinician into the implantable pulse generator 18.
[0078] Alternatively, and as can be seen in FIGS. 4 and 7, the
patient controller 80 may comprise more sophisticated circuitry
that would allow the individual to make these selections through RF
(Radio Frequency) wireless telemetry communications (rather that an
inductively coupled telemetry) that passes through the skin and
tissue within an arm's length distance from the implanted pulse
generator, e.g., the controller 80 may be capable of communicating
with the pulse generator 18 approximately three to six feet away
from the implanted pulse generator (and the pulse generator may be
able to communicate with the controller).
[0079] The wireless telemetry 82 provides reliable, bidirectional
communications with a patient controller-charger and a clinical
programmer, for example via an RF link in the 402 MHz to 405 MHz
Medical Implant Communications Service (MICS) band per FCC 47 CFR
Part 95, or other VHF/UHF low power, unlicensed bands.
[0080] With the use of the patient controller 80, the wireless link
82 allows a patient to control certain parameters of the
implantable pulse generator within a predefined limited range. The
parameters may include the operating modes/states,
increasing/decreasing or optimizing stimulus patterns, or providing
open or closed loop feedback from an external or internal sensor or
control source. The wireless telemetry 82 also desirably allows,
the user to interrogate the implantable pulse generator 18 as to
the status of its internal battery 22 (either primary or
rechargeable). The full ranges within these parameters may be
controlled, adjusted, and limited by a clinician, so the user may
not be allowed the full range of possible adjustments.
[0081] In one embodiment, the patient controller 80 may be sized
and configured to couple to a key chain. It is to be appreciated
that the patient controller 80 may take on any convenient shape,
such as a ring on a finger, or a watch on a wrist, or an attachment
to a belt, for example. The patient controller may also use a
magnetic switch to enable the user to turn the IPG on/off.
[0082] The clinical programmer 52 may be used by a clinician to
program the pulse generator 18 with a range of preset stimulus
parameters. The user may then turn the implant system On/Off using
the wireless patient controller 80. The patient controller 80 may
be then programmed by the pulse generator, i.e., the range of or a
subset of the preset stimulus parameters previously downloaded by
the clinical programmer 52 may be uploaded to the controller 80.
This range of preset stimulus parameters allows the user to make
adjustments to the stimulus strength within the preset range.
Stimulation may be delivered at a level that may be initially set
at or above the sensory threshold of the user, but is not
uncomfortable. The user may get accustomed to the stimulation
level, and may adjust the stimulation up or down within the preset
range.
[0083] According to its programmed rules, when switched on, the
implantable pulse generator 18 generates prescribed stimulation
waveforms through the lead 12 and to the electrode 16. These
waveforms stimulate a target nerve A and/or a target nerve B in a
manner that achieves the desired physiologic response.
[0084] Using the controller 80, the individual may turn on or turn
off the bladder function control waveforms at will or adjust the
waveforms to achieve the desired functional restoration result. As
previously discussed, bladder function is just one example of a
functional restoration result. Additional examples of desirable
therapeutic (treatment) or functional restoration indications will
be described in section "VI. Representative Indications."
[0085] The system 10 desirably includes means for selectively
varying the frequency or range of frequencies for a variable
duration at which the stimulation waveforms are applied by the one
or more electrodes 16. By modulating the frequency and/or duration
of the stimulation waveform, the same system components and
placement of electrodes can serve to achieve markedly different
physiologic responses, and in addition, reduce habituation.
[0086] The shape of the pulse waveform can vary as well. It can,
e.g., be a typical square pulse, or possess a ramped shape,
rectangle, exponential, and/or some combination. The pulse, or the
rising or falling edges of the pulse, can present various linear,
exponential, hyperbolic, or quasi-trapezoidal shapes. The
stimulation waveform can be continuous, or it can be variable and
change cyclically or in step fashion in magnitude and waveform over
time.
[0087] In a non-limiting exemplary embodiment, the stimulus
waveforms may include a variable frequency for a variable duration
(e.g., a first stimulation at 20 Hz for 2 seconds, then 30 Hz for 3
seconds, then 25 Hz for 1 second, and so on), intermittent
stimulation (apply stimulation in bursts separated by pauses in
stimulation (e.g., stimulation for 3 seconds, rest for 2 seconds,
repeat, and so on). The stimulus waveforms may also include a
continuously or intermittently applied duty cycle of pulses. This
may be considered the same as changing the frequency but it also
refers to 1) the duration of bursts of stimulation and 2) the
duration of pauses between the bursts. For example, a variable duty
cycle for intermittent pulses may include stimulation with 10
pulses, then off for 500 milliseconds, stimulation with 15 pulses,
then off for 750 milliseconds, stimulation with 5 pulses, then off
for 2 seconds, and it could keep going in this variable
pattern.
[0088] The stimulus waveforms may also include stimulation at
different amplitudes and different frequencies. Thus, amplitude
and/or frequency modulation may be used to control and/or improve
the response. Varying the amplitude may also provide another form
of anti-habituation control, allowing a bladder function (e.g.,
micturition) to be more complete than if a target nerve was
stimulated at a constant amplitude. Amplitude modulation may also
more realistically recreate the varying level of fiber activation
that occurs during urination.
[0089] The patient controller 80 and/or a clinical programmer 52,
for example, may include a manual-actuated switch or control knob
which an operator operates or tunes to acquire a desired waveform
frequency, given the desired physiologic response.
[0090] As previously described, FIG. 4 shows an exemplary
embodiment of a system 10 adapted for the functional restoration of
bladder function. The assembly includes at least one implantable
lead 12 and electrode 16 coupled to at least one implantable pulse
generator or IPG 18. The lead 12 and the implantable pulse
generator 18 are shown implanted within a pelvic region of a human
or animal body.
[0091] Desirably, the components of the implantable pulse generator
18 are sized and configured so that they can accommodate several
different indications, without major change or modification (see
FIGS. 5A to 6B). Examples of components that desirably remain
unchanged for different indications include the case 26, the
battery 22, the microcontroller 24, much of the software (firmware)
of the embedded code, the power management circuitry 40, and the
stimulus power supply, both of which are part of the circuitry 20.
Thus, a new indication may require only changes to the programming
of the microcontroller 24. Most desirably, the particular code may
be remotely embedded in the microcontroller 24 after final
assembly, packaging, and sterilization of the implantable pulse
generator 18.
[0092] Certain components of the implantable pulse generator 18 may
be expected to change as the indication changes. For example, due
to differences in leads and electrodes, the connection header 14
and associated receptacle(s) for the lead may be configured
differently for different indications. Other aspects of the circuit
20 may also be modified to accommodate a different indication; for
example, the stimulator output stage(s), sensor(s) and/or sensor
interface circuitry. In addition, the case size may change due to a
different header configuration and/or a desire to increase or
decrease the battery size or capacity (compare FIGS. 5A and 5B to
6A and 6B).
[0093] In this way, the implantable pulse generator 18 accommodates
implanting in diverse tissue regions and also accommodates coupling
to at least one lead 12 and an electrode 16 having diverse forms
and configurations, again depending upon the therapeutic or
functional effects desired. For this reason, the implantable pulse
generator can be considered to be general purpose or
"universal."
[0094] The implantable pulse generator 18 may be of the type
described in co-pending U.S. patent application Ser. No.
11/517,056, filed Sep. 7, 2006, and entitled "Implantable Pulse
Generator Systems and Methods for Providing Functional and/or
Therapeutic Stimulation of Muscles and/or Nerves and/or Central
Nervous System Tissue," which is incorporated herein by reference.
The pulse generator 18 includes a circuit that generates electrical
stimulation waveforms. An on-board battery 22 (primary or
rechargeable) provides the power. The pulse generator 18 also
includes an on-board, programmable microcontroller 24, which
carries embedded code. The code expresses pre-programmed rules or
algorithms under which the desired electrical stimulation waveforms
are generated by the circuit. The small metal case (e.g., titanium
and/or titanium 23) of the pulse generator may also serve as the
return electrode for the stimulus current introduced by the
lead/electrode when operated in a monopolar configuration.
[0095] The functional elements of the implantable pulse generator
18 (e.g., circuit 20, the microcontroller 24, the battery 22, and
the connection header 14) are integrated into a small, composite
case 26. Referring to FIGS. 5A and 5B, the case of the pulse
generator 18 defines a small cross section; e.g., desirably about
(5 mm to 10 mm thick).times.(15 mm to 40 mm wide).times.(40 mm to
60 mm long), and more desirably about (7 mm to 8 mm
thick).times.(25 mm to 35 mm wide).times.(45 mm to 55 mm long). The
pulse generator also defines a generally pear-shaped case. The
generally pear-shaped case can be described as including a bottom
portion defining a curved surface having a radius, inwardly
tapering sides, and a top portion being generally flat, as shown in
FIGS. 5A and 5B. This geometry provides a case including a larger
end (bottom portion) and a smaller end (top portion) and allows the
smaller end of the case to be placed into the skin pocket first,
with the larger end being pushed in last. The shape and dimensions
of the pulse generator 18 produce a volume of approximately seven
to nine cubic centimeters, and more desirably about eight cubic
centimeters, and a weight of approximately seventeen grams.
[0096] In an alternative embodiment seen in FIGS. 6A and 6B, the
case of the pulse generator 18 defines a small cross section; e.g.,
desirably about (7 mm to 13 mm thick).times.(45 mm to 65 mm
wide).times.(30 mm to 50 mm long), and more desirably about (9 mm
to 11 mm thick).times.(50 mm to 60 mm wide).times.(35 mm to 45 mm
long). The pulse generator also defines a generally oval-shaped
case. The generally oval-shaped case can be described as consisting
generally of two congruent semicircles and two equal and parallel
lines. The shape and dimensions of the pulse generator 18 produce a
volume of approximately fifteen to nineteen cubic centimeters, and
more desirably about seventeen cubic centimeters, and a weight of
approximately twenty-seven grams.
[0097] The pulse generator 18 can deliver a range of stimulation
parameters to the lead 12 and electrode 16, e.g., output current
ranges of about 0.1 mA to about 20 mA, pulse duration ranges of
about 0.1 microseconds to about 500 microseconds, frequency ranges
of about one pulse per second to about 130 pulses per second, and
duty cycle ranges from about zero to about 100 percent. The
delivered stimulus may be an asymmetric biphasic waveform with zero
net DC (direct current).
[0098] The implantable pulse generator 18 desirably incorporates
circuitry and/or programming to assure that the implantable pulse
generator 18 may suspend stimulation, and perhaps fall-back to only
very low rate telemetry, and eventually suspends all operations
when the battery 22 has discharged the majority of its capacity
(i.e., only a safety margin charge remains). Once in this dormant
mode, the implantable pulse generator may provide limited
communications and may be in condition for replacement if a primary
battery is used, or it must be recharged.
[0099] When a rechargeable battery is used, the battery desirably
has a capacity of as small as 30 mA-hr and up to about 120 mA-hr or
more, and recharging of the rechargeable battery may be required
less than weekly. When the rechargeable battery has only a safety
margin charge remaining, it can be recharged in a time period of
not more than six hours.
[0100] The patient controller 80 may also be belt or clothing worn
and used to charge the rechargeable batteries of the pulse
generator 18 as needed. Charging may be achieved via an inductive
RF link using a charge coil on or near the skin in close proximity
to the IPG. The patient controller 80 may also be configured to
provide the user with information on pulse generator battery status
and stimulus levels.
[0101] The implantable pulse generator 18 desirably includes a lead
connection header 14 (see FIGS. 5A to 6B), for connecting the
lead(s) 12 that may enable reliable and easy replacement of the
lead/electrode, and includes a small antenna 27 for use with the
wireless telemetry feature.
[0102] The connection header (top header) 14 may be easy to use,
reliable, and robust enough to allow multiple replacements of the
implantable pulse generator after many years (e.g., more than ten
years) of use. The surgical complexity of replacing an implantable
pulse generator is usually low compared to the surgical complexity
of correctly placing the implantable lead 12/electrode 16 in
proximity to the target nerve/tissue and routing the lead 12 to the
implantable pulse generator. Accordingly, the lead 12 and electrode
16 desirably has a service life of at least ten years with a
probable service life of fifteen years or more. Based on the
clinical application, the implantable pulse generator may not have
this long a service life. The implantable pulse generator service
life may largely be determined by the power capacity of the Lithium
Ion battery 22, and is likely to be three to ten years, based on
the usage of the device. Desirably, the implantable pulse generator
18 has a service life of at least three years.
[0103] As described above, the implantable pulse generator
preferably uses a laser welded titanium case. As with other active
implantable medical devices using this construction, the
implantable lead(s) 12 connect to the implantable pulse generator
through a molded or cast polymeric connection header 14.
Metal-ceramic or metal-glass feed-thrus maintain the hermetic seal
of the titanium capsule while providing electrical contact to the
electrical contacts of the lead 12/electrode 16.
[0104] The standard implantable connectors may be similar in design
and construction to the low-profile IS-1 connector system (per ISO
5841-3). The IS-1 connectors have been in use since the late 1980s
and have been shown to be reliable and provide easy release and
re-connection over several implantable pulse generator replacements
during the service life of a single pacing lead. Full compatibility
with the IS-1 standard, and mating with pacemaker leads, is not a
requirement for the implantable pulse generator.
[0105] The implantable pulse generator connection system may
include a modification of the IS-1 connector system, which shrinks
the axial length dimensions while keeping the format and radial
dimensions of the IS-1. For application with more than two
electrode conductors, the top header 14 may incorporate one or more
connection receptacles each of which accommodate leads with
typically four conductors. When two or more leads are accommodated
by the header, these leads may exit the connection header in
opposite directions (i.e., from opposite sides of the header), as
seen in FIGS. 6A and 6B.
[0106] These connectors can be similar to the banded axial
connectors used by other multi-polar implantable pulse generators
or may follow the guidance of the draft IS-4 implantable connector
standard. The design of the implantable pulse generator housing and
header 14 preferably includes provisions for adding the additional
feed-thrus and larger headers for such indications.
[0107] The inclusion of the antenna 27 for the wireless telemetry
inside the connection header 14 may be necessary as the shielding
offered by the titanium case may severely limit (effectively
eliminate) radio wave propagation through the case. The antenna 27
connection may be made through a feed-thru similar to that used for
the electrode connections. Alternatively, the wireless telemetry
signal 82 may be coupled inside the implantable pulse generator
onto a stimulus output channel and coupled to the antenna 27 with
passive filtering/coupling elements/methods in the connection
header 14.
III. Features of the Lead and Electrode
[0108] A. Implantation in Pelvic Region
[0109] The lead 12 and electrode 16 are sized and configured to be
inserted into and to rest in the targeted tissue region in the
lower pelvic region without causing pain or discomfort or impact
body image. Desirably, the lead 12 and electrode 16 can be inserted
using the small (e.g., smaller than 16 gauge) introducer sleeve 32
with minimal tissue trauma. The lead 12 and electrode 16 are formed
from a biocompatible and electrochemically suitable material and
possess no sharp features that can irritate tissue during extended
use. Furthermore, the lead 12 and electrode 16 possess mechanical
characteristics including mechanical compliance (flexibility) along
their axis (axially), as well as perpendicular to their axis
(radially), and unable to transmit torque, to flexibly respond to
dynamic stretching, bending, and crushing forces that can be
encountered in this body region without damage or breakage, and to
accommodate relative movement of the pulse generator coupled to the
lead 12 without imposing force or torque to the electrode 16 which
tends to dislodge the electrode.
[0110] Furthermore, one embodiment of a lead 12 and electrode 16
may also include an anchoring means 70 for providing retention
strength to resist migration within or extrusion from the targeted
tissue region in response to force conditions normally encountered
during periods of extended use (see FIGS. 8 and 9). In addition,
the anchoring means 70 is desirably sized and configured to permit
the electrode 16 position to be adjusted easily during insertion,
allowing placement at the optimal location where unilateral or
bilateral stimulation of a target nerve A and/or a target nerve B
occurs. The anchoring means 70 functions to hold the electrode at
the implanted location despite the motion of the tissue and small
forces transmitted by the lead due to relative motion of the
connected pulse generator due to changes in body posture or
external forces applied to the abdomen. However, the anchoring
means 70 should allow reliable release of the electrode 16 at
higher force levels, to permit withdrawal of the implanted
electrode 16 by purposeful pulling on the lead 12 at such higher
force levels, without breaking or leaving fragments, should removal
of the implanted electrode 16 be desired.
[0111] B. The Lead
[0112] FIGS. 8 to 11 show a representative embodiment of a lead 12
that provide the foregoing features. The implantable lead 12
comprises a molded or extruded component 72, which encapsulates one
or more stranded or solid wire elements 74, and includes the
connector 62 (shown in FIG. 12). The wire element may be bifilar,
as shown in FIG. 11, and may be constructed of coiled MP35N
nickel-cobalt wire or wires that have been coated in polyurethane.
In a representative embodiment with two electrically conductive
surfaces 16 (as described below), one wire element 74 may be
coupled to the distal electrode 16 and the pin 62A of the connector
62. A second wire element 74 may be coupled to the proximal
electrode 16 and the ring 62B on the connector 62. The molded or
extruded lead 12 can have an outside diameter ranging between about
0.05 mm to about 5.0 mm, and as small as about one (1) mm, and
desirably about 1.9 mm. The lead 12 may also include an inner lumen
13 having a diameter about 0.2 millimeters to about 0.5
millimeters, and desirably about 0.35 millimeters. The lead 12 may
be approximately 10 cm to 40 cm in length, although the lead may be
shorter or longer, depending on the target nerve to be stimulated
and the anatomy of the patient. The lead 12 provides electrical
continuity between the connector 62 and the electrode 16.
[0113] The coil's pitch can be constant or, as FIG. 10 shows, the
coil's pitch can alternate from high to low spacing to allow for
flexibility in both compression and tension. The tight pitch may
allow for movement in tension, while the open pitch may allow for
movement in compression.
[0114] A standard IS-1 or similar type connector 62 at the proximal
end provides electrical continuity and mechanical attachment to the
pulse generator 18. The lead 12 and connector 62 all may include
provisions (e.g., lumen 13) for a guidewire that passes through
these components and the length of the lead 12 to the conductive
electrode 16 at the distal end.
[0115] C. The Electrode
[0116] The electrode 16 may comprise one or more electrically
conductive surfaces. Two conductive surfaces are show in FIGS. 8
and 9. The two conductive surfaces can be, used either A) as one
two individual stimulating (cathodic) electrodes in a monopolar
configuration using the metal case of the pulse generator 18 as the
return (anodic) electrode or B) either the distal or proximal
conductive surface as a individual stimulating (cathodic) electrode
in a monopolar configuration using the metal case of the pule
generator 18 as the return (anodic) electrode or C) in bipolar
configuration with one electrode functioning as the stimulating
(cathodic) electrode and the other as the return (anodic)
electrode.
[0117] In general, bipolar stimulation is more specific than
monopolar stimulation--the area of stimulation is much
smaller--which may be good if the electrode 16 is close to the
target nerve. But if the electrode 16 is farther from the target
nerve, then a monopolar configuration could be used because with
the pulse generator 18 acting as the return electrode, activation
of the nerve may be less sensitive to exact placement than with a
bipolar configuration.
[0118] In use, a physician may first attempt to place the electrode
16 close to the target nerve so that it could be used in a bipolar
configuration, but if bipolar stimulation failed to activate the
target nerve, then the electrode 16 could be switched to a
monopolar configuration. Two separate conductive surfaces on the
electrode 16 provide an advantage because if one conductive surface
fails to activate the target nerve because it is too far from the
nerve, then stimulation with the second conductive surface could be
tried, which might be closer to the target nerve. Without the
second conductive surface, a physician would have to reposition the
electrode to try to get closer to the target nerve.
[0119] The electrode 16, or electrically conductive surface or
surfaces, can be formed from PtIr (platinum-iridium) or,
alternatively, 316L stainless steel. Each electrode 16 possess a
conductive surface of approximately 10 mm.sup.2-20 mm.sup.2 and
desirably about 16.5 mm.sup.2. This surface area provides current
densities up to 2 mA/mm.sup.2 with per pulse charge densities less
than about 0.5 .mu.C/mm.sup.2. These dimensions and materials
deliver a charge safely within the stimulation levels supplied by
the pulse generator 18.
[0120] Each conductive surface has an axial length in the range of
about three to five millimeters in length and desirably about four
millimeters. When two or more conductive surfaces are used, either
in the monopolar or bipolar configurations as described, there may
be an axial spacing between the conductive surfaces in the range of
1.5 to 2.5 millimeters, and desirably about two millimeters.
[0121] D. The Anchoring Means
[0122] In the illustrated embodiment (see FIGS. 8 and 9), the lead
may be anchored by anchoring means 70 specifically designed to
secure the electrode 16 in tissue in electrical proximity to the
target nerve, with or without the support of muscle tissue. The
anchoring means 70 takes the form of an array of shovel-like
paddles or scallops 76 proximal to the proximal-most electrode 16
(although a paddle 76 or paddles could also be proximal to the
distal most electrode 16, or could also be distal to the distal
most electrode 16). The paddles 76 as shown and described are sized
and configured so they may not cut or score the surrounding tissue.
It is to be appreciated that anchoring means are not a requirement
for the present invention.
[0123] The paddles 76 are desirably present relatively large,
generally planar surfaces, and are placed in multiple rows axially
along the distal portion of lead 12. The paddles 76 may also be
somewhat arcuate as well, or a combination of arcuate and planar
surfaces. A row of paddles 76 comprises two paddles 76 spaced 180
degrees apart. The paddles 76 may have an axial spacing between
rows of paddles in the range of six to fourteen millimeters, with
the most distal row of paddles 76 adjacent to the proximal
electrode, and each row may be spaced apart 90 degrees. The paddles
76 are normally biased toward a radially outward condition into
tissue.
[0124] In this condition, the large surface area and orientation of
the paddles 76 allow the lead 12 to resist dislodgement or
migration of the electrode 16 out of the correct location in the
surrounding tissue. In the illustrated embodiment, the paddles 76
are biased toward a proximal-pointing orientation, to better resist
proximal migration of the electrode 16 with lead tension. The
paddles 76 are desirably made from a polymer material, e.g., high
durometer silicone, polyurethane, or polypropylene, bonded to or
molded with the lead 12.
[0125] The paddles 76 are not stiff, i.e., they are generally
pliant, and can be deflected toward a distal direction in response
to exerting a pulling force on the lead 12 at a threshold axial
force level, which may be greater than expected day-to-day axial
forces. The paddles 76 are sized and configured to yield during
proximal passage through tissue in result to such forces, causing
minimal tissue trauma, and without breaking or leaving fragments,
despite the possible presence of some degree of tissue in-growth.
This feature permits the withdrawal of the implanted electrode 16,
if desired, by purposeful pulling on the lead 12 at the higher
axial force level.
[0126] Desirably, and as previously described, the anchoring means
70 may be prevented from fully engaging body tissue until after the
electrode 16 has been deployed. The electrode 16 may not be
deployed until after it has been correctly located during the
implantation (installation) process.
[0127] More particularly, and as previously described, the lead 12
and electrode 16 are intended to be percutaneously introduced
through the sleeve 32 shown in FIG. 12. As shown, the paddles 76
assume a collapsed condition against the lead 12 body when within
the sleeve 32. In this condition, the paddles 76 are shielded from
contact with tissue. Once the location is found, the sleeve 32 can
be withdrawn, holding the lead 12 and electrode 16 stationary. Free
of the sleeve 32, the paddles 76 spring open to assume their
radially deployed condition in tissue, fixing the electrode 16 in
the desired location. In the radially deployed condition, the
paddles have a diameter (fully opened) of about four millimeters to
about six millimeters, and desirably about 4.8 millimeters.
[0128] The lead has two ink markings 54, 55 to aid the physician in
its proper placement. The most distal marking 20 (about 11 cm from
the tip) aligns with the external edge of the introducer sleeve 32
when the tip of the lead is at the tip of the sleeve 32. The more
proximal marking 21 (about 13 cm from the tip) aligns with the
external edge of the sleeve 32 when the introducer has been
retracted far enough to expose the tines 76. A central lumen 13
allows for guidewire 94 insertion and removal to facilitate lead
placement. A funnel 95 may be included to aid in inserting the
guidewire 94 into the lumen 13 in the lead 12.
[0129] The anchoring means 70 may be positioned about 10
millimeters from the distal tip of the lead, and when a second
anchoring means 70 is used, the second anchoring means 70 may be
about 20 millimeters from the distal tip of the lead.
[0130] The position of the electrode 16 relative to the anchoring
means 70, and the use of the sleeve 32, allows for both advancement
and retraction of the electrode delivery sleeve 32 during
implantation while simultaneously delivering test stimulation. The
sleeve 32 can be drawn back relative to the lead 12 to deploy the
anchoring means 70, but only when the physician determines that the
desired electrode location has been reached. The withdrawal of the
sleeve 32 from the lead 12 causes the anchoring means 70 to deploy
without changing the position of electrode 16 in the desired
location (or allowing only a small and predictable, set motion of
the electrode 16). Once the sleeve 32 is removed, the flexible,
silicone-coated or polyurethane-coated lead 12 and electrode 16 are
left implanted in the tissue.
IV. Implantation Methodology
[0131] There are at least three alternative methods for placing one
or more lead/electrode(s) near one or more target nerves, and each
are described below. The patient may undergo monitored anesthesia
care (MAC), which is a planned procedure during which the patient
undergoes local anesthesia together with sedation and analgesia.
During MAC, the patient is sedated and amnestic but always remains
responsive when stimulated to do so. Local anesthesia--e.g., 1%
Lidocaine (2-5 ccs) or equivalent--may be injected prior to making
the anticipated lead 12 incision site 60. The patient preparation
may be the same for all implantation methods. Although the lateral
views show the male anatomy, similar approaches may also be used in
the female.
[0132] A. Anterior Approach
[0133] Referring the FIGS. 13 and 14, the site for the lead
insertion 60 is desirably located midline or near-midline, over the
pubic symphysis aiming toward the clitoris (or the base of the
penis in males).
[0134] Once local anesthesia is established, a needle/introducer
may be advanced percutaneously into the anesthetized site 60 to a
depth of about five centimeters to about seven centimeters
necessary to reach the target site between the pubic symphysis and
the clitoris in females, or the base of the penis in males, to
stimulate a target nerve(s) (e.g., dorsal genital nerves). The
needle/introducer may then be replaced with a lead 12 threaded
through the initially inserted sheath or needle. It is to be
appreciated that this approximate insertion depth may vary
depending on the particular anatomy of the patient. The physician
may use one hand to guide the lead 12 and the other hand to hold
surrounding tissue to stabilize the area. Once the lead 12 is
positioned, it may be coupled to a test stimulator to apply
stimulation waveforms through the lead 12 and electrode 16
concurrent with positioning of the electrode 16 to confirm the
desired location.
[0135] B. Perineal Approach
[0136] Referring to FIGS. 15 and 16, the site for the lead
insertion 60 may be perpendicular to the skin into the anesthetized
site 60 located behind the scrotum as shown or lateral to the
scrotum or near the base of the penis (e.g., lateral or posterior
to the penis base). A similar approach may also be used in the
female.
[0137] Once local anesthesia is established, a needle/introducer
may be advanced percutaneously into the anesthetized site 60 to a
target depth necessary to reach the target site along the urethra
to stimulate a target nerve(s) (e.g., urethral afferents). The
needle/introducer may then be replaced with a lead 12 threaded
through the initially inserted sheath or needle. It is to be
appreciated that insertion depths may vary depending the particular
anatomy of the patient. The physician may use one hand to guide the
lead 12 and the other hand to hold surrounding tissue to stabilize
the area. Once the lead 12 is positioned, it may be again coupled
to a test stimulator to apply stimulation waveforms through the
lead 12 and electrode 16 concurrent with positioning of the
electrode 16 to confirm the desired location.
[0138] C. Posterior Approach
[0139] The user may be placed in a lateral decubitus position with
their back, hips and legs flexed. Referring the FIGS. 17 and 18,
the site for the lead insertion 60 may be approximately 2 cm
lateral and 2 cm caudal to the midpoint of a line defined between
the posterior superior iliac spine and the ischical tuberosity.
[0140] Once local anesthesia is established, a needle/introducer
may be advanced percutaneously into the anesthetized site 60 to a
target depth necessary to reach the target site (e.g., at, along
side of, and/or near Alcock's canal) to stimulate a target nerve(s)
(e.g., pudendal nerves). The proximity of the needle tip to the
pudendal nerve may be minimized through successively finer
adjustments of the stimulus amplitude (e.g., an initial current of
3 mA, a pulse width of 0.1 sec. and a frequency of 2 Hz, for
example), and electrode tip position, until external anal sphincter
twitches can be evoked with stimuli less than 1 mA, for example.
The needle/introducer may then be replaced with a lead 12 threaded
through the initially inserted sheath or needle. It is to be
appreciated that insertion depths may vary depending on the
particular anatomy of the patient. The physician may use one hand
to guide the lead 12 and the other hand to hold surrounding tissue
to stabilize the area. Once the lead 12 is positioned, it may be
again coupled to a test stimulator to apply stimulation waveforms
through the lead 12 and electrode 16 concurrent with positioning of
the electrode 16 to confirm the desired location.
V. Stimulating Catheter
[0141] A stimulating catheter 150 may be used as a clinical
screening tool to identify appropriate candidates for the bladder
function restoration system (see FIGS. 20A through 23). If a
subject's stimulating catheter test demonstrates that urethral
stimulation may be able to empty the bladder, then a fine wire lead
known in the art (or a lead 12 as shown and described) would be
implanted near the urethra in close proximity to the urethral
afferents using one of the described approaches. Similarly, another
fine wire lead (or a lead 12 as shown and described) may be placed
near the dorsal genital nerve. After implantation of one or more
leads, the subject would be sent home for a predetermined test
period (e.g., a week) with the percutaneous leads connected to an
external pulse generator (not shown).
[0142] For this test period, an external pulse generator can be
used of the type described in U.S. Pat. No. 7,120,499, issued Oct.
10, 2006, and entitled "Portable Percutaneous Assemblies, Systems,
and Methods for Providing Highly Selective Functional or
Therapeutic Neurostimulation," which is incorporated herein by
reference. Optionally, an external pulse generator can be used of
the type described in co-pending U.S. patent application Ser. No.
11/595,556, filed Nov. 10, 2006, and entitled "Portable Assemblies,
Systems, and Methods for Providing Functional or Therapeutic
Neurostimulation," which is also incorporated herein by
reference.
[0143] If the home trial provides functional results, e.g.,
prevents the patient from leaking between voids, and achieves a
residual post-void bladder volume of a predetermined amount (e.g.,
less than 50 ml), then the patient may proceed to receive a fully
implanted system, including an implantable pulse generator (IPG) to
evaluate continence and emptying in the home environment over a
longer period (e.g., 3 to 6 months). In contrast to the
implantation of the VOCARE system on the sacral spinal roots which
requires a time consuming and invasive laminectomy, the present
systems and methods may allow urologists to place the
lead/electrode(s) near the target nerve(s) easily and reliably
because the urethra and genitals are an area in which urologists
are comfortable and familiar.
[0144] During the first period of stimulation, the subjects may be
in "continence mode" as their bladder fills, using dorsal genital
nerve stimulation via a first lead to remain dry. When they are
ready to urinate, they may press a button on their external
controller to switch into "micturition mode" to empty their bladder
with urethral afferent stimulation via a second lead. When they are
finished urinating, they may press the other button on the external
stimulator to switch back into "continence mode."
[0145] The idea of stimulating the urethra is known, but the
stimulating catheter 150 provides a unique combination of features.
The stimulating catheter 150 is adapted to be used to measure
bladder pressures and stimulate the urethra at the same time.
Previously, bladder pressure was measured with one catheter, and
another catheter-like lead, similar to a deep brain stimulation
lead, which was placed alongside it to provide the stimulation.
This arrangement is cumbersome for clinicians and provides less
accurate information about the location of stimulation because the
stimulating lead can move relative to the urethra.
[0146] As can be seen in FIG. 20A, the novel stimulating catheter
150 has a balloon 152 that may be inflated in the bladder neck that
secures the catheter and one or more stimulating electrodes 154 in
place so it does not move within the urethra. The stimulating
catheter 150 as shown has multiple electrodes 154 along its length
(e.g., 17 electrodes are shown) that can stimulate the urethra.
This means once the catheter 150 is in place, it does not have to
be moved again until it is removed. This is a crucial feature
because movement inside the urethra can activate urethral
afferents, which are the very fibers that need to be screened.
Thus, movement of the stimulating catheter 150 along the urethra
can confound the screening and also lead to unwanted elicitation of
reflexes such as a reflex bladder spasm or contraction.
[0147] Multiple stimulating electrodes 154 placed along the
catheter body 160 allow the stimulating catheter 150 to be able to
stimulate different portions of the urethra without having to move
the catheter inside the urethra once the catheter 150 is in place.
Each electrode 154 may be secured to the catheter body with an
adhesive 155 (see FIG. 20B), which also serves to provide a smooth
transition from the catheter body 160 to an edge of an electrode
154. The electrodes 154 near the proximal portion 162 of the
catheter body 160 are generally spaced about 1.0 cm to 2.0 cm
apart, and more desirably about 1.5 cm apart, and the electrodes
154 near the distal portion 164 are generally spaced about 0.1 cm
to 1.0 cm apart, and more desirably about 0.5 cm apart.
[0148] FIG. 20C shows an alternative configuration of electrodes
154. More than one configuration provides for flexibility depending
on the patients anatomy. In FIG. 20C, fifteen electrodes 154 are
shown. The electrodes 154 near the proximal portion 162 of the
catheter body 160 are generally spaced about 1.0 cm to 2.0 cm
apart, and more desirably about 1.5 cm apart, and the electrodes
154 near the distal portion 164 are generally spaced about 0.1 cm
to 1.0 cm apart, and more desirably about 0.5 cm apart. An
electrode free gap 156 may be provided between the higher
concentration of electrodes near the distal portion 164 and the
electrodes near the proximal portion 162. The gap 156 may be about
5 cm to 7 cm, and more desirably about 6 cm.
[0149] The multiple electrodes 154 are adapted to enable urethral
stimulation to elicit bilateral activation of the urethral
afferents. The multiple electrodes permit bipolar stimulation and
ensure that one electrode may be located within a short distance
(e.g. one cm or less) of the portion of the urethra most sensitive
to electrical stimulation. Animal studies have shown the caudal
urethra to be the most sensitive because electrical stimulation of
the caudal urethra evoked the largest compound nerve action
potentials in urethral afferents and sustained bladder contractions
most consistently with the lowest stimulation amplitudes compared
to other urethral locations.
[0150] The stimulating catheter 150 may also be used in both men
and women. The higher concentration of electrodes 154 near the
distal portion 164 of the catheter body 160 serves to most
effectively stimulate the shorter urethra in women (generally about
two to four cm long), and a large number of electrodes 154 along
the length of the catheter body 160 are designed to accommodate
urethras of longer lengths, and the higher concentration of
electrodes 154 may be placed to stimulate the most well innervated
portions of the urethra in either a man or a woman.
[0151] The balloon 152 may also be wedge shaped which may help
prevent leakage around the balloon and may allow iso-volumetric
measurements. This feature allows the stimulating catheter 150 to
be used to analyze bladder contractions at the same volume without
having to re-fill the bladder after each bladder contraction. This
may be beneficial for at least two reasons: 1) it takes time to
fill the bladder, and in order to make the procedure of analyzing
responses to urethral stimulation a practical out-patient
procedure, the total time needs to be kept down to about one to two
hours, and having to re-fill the bladder after each bladder
contraction would take too long (e.g., more than two hours), and 2)
it makes the screening more robust and the results simpler and
easier to analyze because the bladder reflexes are time and,
history dependent. This means that every fill has an effect on each
of the following bladder contractions, meaning that evoking bladder
contractions and filling between bladder contractions to replace
the leaked volume is not the same as evoking iso-volumetric bladder
contractions without filling between each contraction.
[0152] Additionally, the stimulating catheter has a coude (curved)
tip 158 which enables it to be inserted in men with enlarged
prostates (see FIG. 20A). Without the curved tip 158, it would be
nearly impossible to place the stimulating catheter in most men
with enlarged prostates. The stimulating catheter body 160 may be
small in diameter (e.g., twelve Fr), meaning that after the balloon
152 is deflated in the bladder neck, the rest of the catheter body
160 may not obstruct the urethra and may allow for voiding (around
the catheter body) to be monitored.
[0153] The catheter body 160 is desirably a dual lumen body having
a proximal portion 162 and a distal portion 164. The first lumen
166 extends from a fitting 168 near the proximal end 162 to the
balloon 152 near the distal end 164, and carries an insulated solid
or stranded wire element 170 for each electrode 154 (see FIGS. 21
and 22). The first lumen 166 also serves as a path for fluid flow
(i.e., saline or distilled water) to fill and drain the balloon
152. The fitting 168 may be adapted to be connected to a fluid
pump. Alternatively, a third lumen may be provided to serve as the
balloon fill lumen.
[0154] The wire elements 170 for each electrode 154 are carried in
an extension 176 which extends from the first lumen 166 to a
connector 178. The connector 178 then couples to a computer system
or external pulse generator, for example, to provide selective
stimulation to the multiple electrodes 154.
[0155] The second lumen 172 extends from a fitting 174 near the
proximal end 162 to an opening 176 near the catheter body tip 158,
and serves as a path for fluid flow to fill the bladder, and to
measure fluid pressure. The fitting 174 may be adapted to be
connected to a fluid pump and pressure transducer. The bladder is
typically filled with a saline solution, and the solution may
contain a contrast medium to allow viewing of the bladder filling
using fluoroscopy.
VI. Representative Indications
[0156] Due to its technical features, the implant system 10 can be
used to provide beneficial results in diverse therapeutic and
functional restorations indications.
[0157] For example, in the field of urology or urologic
dysfunctions, possible indications for use of the implant system
includes the treatment of (i) urinary and fecal incontinence; (ii)
micturition/retention; (iii) restoration of sexual function; (iv)
defecation/constipation; (v) pelvic floor muscle activity; and/or
(vi) pelvic pain.
[0158] The foregoing is considered as illustrative only of the
principles of the invention. Furthermore, since numerous
modifications and changes will readily occur to those skilled in
the art, it is not desired to limit the invention to the exact
construction and operation shown and described. While the preferred
embodiment has been described, the details may be changed without
departing from the invention.
* * * * *