U.S. patent application number 13/458697 was filed with the patent office on 2012-11-01 for selective stimulation to modulate the sympathetic nervous system.
Invention is credited to Mir A. Imran, Daniel H. Kim, Jeffery M. Kramer.
Application Number | 20120277839 13/458697 |
Document ID | / |
Family ID | 47068549 |
Filed Date | 2012-11-01 |
United States Patent
Application |
20120277839 |
Kind Code |
A1 |
Kramer; Jeffery M. ; et
al. |
November 1, 2012 |
SELECTIVE STIMULATION TO MODULATE THE SYMPATHETIC NERVOUS
SYSTEM
Abstract
Systems, methods and devices are provided for the targeted
treatment of a variety of medical conditions by directly
neuromodulating a target anatomy associated with the condition
while minimizing or excluding undesired neuromodulation of other
anatomies. Typically, the target anatomy includes one or more
dorsal root ganglia, dorsal roots, dorsal root entry zones, or
portions thereof. Such target stimulation areas are utilized due in
part to their effect on the sympathetic nervous system.
Inventors: |
Kramer; Jeffery M.; (San
Francisco, CA) ; Kim; Daniel H.; (Houston, TX)
; Imran; Mir A.; (Los Altos, CA) |
Family ID: |
47068549 |
Appl. No.: |
13/458697 |
Filed: |
April 27, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12369706 |
Feb 11, 2009 |
8229565 |
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13458697 |
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11222516 |
Sep 7, 2005 |
7502651 |
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12369706 |
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61480958 |
Apr 29, 2011 |
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60608357 |
Sep 8, 2004 |
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Current U.S.
Class: |
607/118 |
Current CPC
Class: |
A61N 1/36135 20130101;
A61N 1/36071 20130101; A61N 1/36114 20130101; A61N 1/36057
20130101; A61N 1/0551 20130101 |
Class at
Publication: |
607/118 |
International
Class: |
A61N 1/05 20060101
A61N001/05 |
Claims
1. A method of modulating a neural pathway in the sympathetic
nervous system, comprising: positioning at least one electrode of a
lead in close proximity to a dorsal root ganglion upstream of at
least one ganglion of the sympathetic nerve chain; and providing
energy to the at least one electrode so as to neuromodulate the
dorsal root ganglion in a manner that influences a condition
associated with the at least one ganglion of the sympathetic nerve
chain while excluding neuromodulation of an associated ventral
root.
2. The method according to claim 1 wherein neuromodulating a dorsal
root ganglion comprises neuromodulating a dorsal root ganglion in a
manner that influences functional activation of a bodily system
associated with the at least one ganglion along the sympathetic
nerve chain.
3. The method according to claim 2 wherein neuromodulating a dorsal
root ganglion comprises neuromodulating a dorsal root ganglion in a
manner that influences functional activation of an organ associated
with the at least one ganglion along the sympathetic nerve
chain.
4. The method according to claim 1 wherein neuromodulating a dorsal
root ganglion comprises neuromodulating a dorsal root ganglion in a
manner that influences functional inhibition of a bodily system
associated with the at least one ganglion along the sympathetic
nerve chain.
5. The method according to claim 4 wherein neuromodulating a dorsal
root ganglion comprises neuromodulating a dorsal root ganglion in a
manner that influences functional inhibition of an organ associated
with the at least one ganglion along the sympathetic nerve
chain.
6. The method according to claim 1 wherein neuromodulating a dorsal
root ganglion comprises neuromodulating a dorsal root ganglion in a
manner that lessens vascular resistance of a blood vessel
associated with the at least one ganglion along the sympathetic
nerve chain.
7. The method according to claim 1 wherein neuromodulating a dorsal
root ganglion comprises neuromodulating a dorsal root ganglion in a
manner that improves vascular perfusion to an ischemic body region
or tissue.
8. The method according to claim 1 wherein the condition comprises
an ischemic disorder, diabetes, peripheral vascular disease,
stroke, erectile dysfunction, a sympathetically maintained or
mediate pain condition, Raynaud's disease, heart disease, angina
pectoris, vascular disease, a skin ulceration, a wound healing
disorder, asthma, hypertension, an immune system disorder or a
renal disorder.
9. The method according to claim 1 wherein the at least one
ganglion of the sympathetic nerve chain is a cervical ganglion.
10. The method according to claim 1 wherein the at least one
ganglion of the sympathetic nerve chain is a thoracic ganglion.
11. The method according to claim 1 wherein the at least one
ganglion of the sympathetic nerve chain is a lumbar ganglion.
12. The method according to claim 1 wherein the positioning step
comprises positioning the at least one electrode on the dorsal root
ganglion epinurium.
13. The method according to claim 1 further comprising directly
applying stimulation to the at least one ganglion along the
sympathetic nerve chain.
14. The method according to claim 13 wherein the directly applying
stimulation step for the at least one ganglion along the
sympathetic nerve chain is performed using an electrode exposed to
the at least one ganglion along the sympathetic nerve chain.
15. A method of modulating a portion of a neural pathway in the
sympathetic nervous system, comprising: positioning at least one
electrode of a lead in close proximity to a target dorsal root
ganglion associated with the portion of the neural pathway; and
energizing the at least one electrode so that the portion of the
neural pathway is altered and energy provided by the at least one
electrode dissipates within the target dorsal root ganglion while
excluding an associated ventral root.
16. A method as in claim 15, wherein the energy provided by the at
least one electrode selectively stimulates a soma and/or one of the
ascending or descending axons within the target dorsal root
ganglion which activates a premotor neuron.
17. A method as in claim 16, wherein the activation of the premotor
neuron acts upon a sympathetic motor neuron causing inhibition of
the release of norephinephrine by the sympathetic motor neuron.
18. A method as in claim 16, wherein the activation of the premotor
neuron acts upon a sympathetic motor neuron causing inhibition of
vascular resistance in a blood vessel influenced by the sympathetic
motor neuron.
19. A method as in claim 15, wherein the altering of the portion of
the neural pathway increases perfusion to a region of the body
associated with the portion of the neural pathway.
20. A method as in claim 19, wherein the region of the body
comprises a brain.
21. A method as in claim 19, wherein the region of the body
comprises an ischemic limb.
22. A method as in claim 19, wherein the altering of the portion of
the neural pathway increases perfusion to a portion of a peripheral
vascular system affected by a peripheral vascular disease.
23. A method as in claim 15, wherein the altering of the portion of
the neural pathway alleviates sympathetically mediated pain or
sympathetically maintained pain.
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. 119(e) to
U.S. Provisional Patent Application No. 61/480,958, entitled
"Selective Stimulation of Dorsal Root Ganglion to Modulate the
Sympathetic Nervous System", filed on Apr. 29, 2011, which is
incorporated by reference in its entirety. This application is also
a continuation-in-part of U.S. patent application Ser. No.
12/369,706, entitled "Methods of Stimulating a Dorsal Root
Ganglion", filed on Feb. 11, 2009, now U.S. Publication No.
US-2009-0210041-A1, which is a divisional of U.S. patent
application Ser. No. 11/222,516, entitled "Methods for Stimulating
a Dorsal Root Ganglion", filed on Sep. 7, 2005, now U.S. Pat. No.
7,502,651, which claims priority under 35 U.S.C. 119(e) to U.S.
Provisional Patent Application No. 60/608,357, entitled
"Neurostimulation Systems and Methods", filed on Sep. 8, 2004, all
of which are incorporated herein by reference in their
entirety.
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED
RESEARCH AND DEVELOPMENT
[0002] NOT APPLICABLE
REFERENCE TO A "SEQUENCE LISTING," A TABLE, OR A COMPUTER PROGRAM
LISTING APPENDIX SUBMITTED ON A COMPACT DISK
[0003] NOT APPLICABLE
BACKGROUND
[0004] A variety of diseases and medical conditions plague the
population causing pain, dysfunction, distress, social problems,
and ultimately death. These may be caused by external factors, such
as infectious disease, or caused by internal dysfunctions, such as
autoimmune diseases. Such conditions usually affect people not only
physically but also emotionally.
[0005] Consequently, a vast array of medical treatments and
therapies have been generated in an attempt to prevent, improve,
palliatively treat or cure these medical conditions. Examples of
such treatments have included the development of drugs, medical
devices, gene therapy, hormone therapy, biotherapy, virotherapy,
bacteriophage therapy, ozonotherapy, hydrotherapy, neuromodulation,
phototherapy, and radiation, to name a few.
[0006] However, many of these treatments cause adverse effects in
addition to or in place of the intended therapeutic effect. Common
adverse effects include alteration in body weight, change in enzyme
levels, loss of function, development of pain, or pathological
changes detected at the microscopic, macroscopic or physiological
level, to name a few. The severity of adverse effects can range
from nausea to death.
[0007] Therefore, there remains a need for the further development
of devices, systems and methods of treating various medical
conditions while reducing or eliminating adverse effects. Such
devices, systems and methods should be targeted with minimal
deleterious effects on unaffected body regions. At least some of
these objectives will be met by the present invention.
SUMMARY OF THE DISCLOSURE
[0008] The present invention provides targeted treatment of a
variety of medical conditions by directly neuromodulating a target
anatomy associated with the condition while minimizing or excluding
undesired neuromodulation of other anatomies. In preferred
embodiments, the target anatomy includes one or more dorsal root
ganglia, dorsal roots, dorsal root entry zones, or portions
thereof. Such target stimulation areas are utilized due in part to
their effect on the sympathetic nervous system. In particular, many
of these target anatomies house sensory fibers that are isolated
from motor fibers. Sensory fibers are involved in a variety of
reflexes and feed-forward physiologic processes that control the
sympathetic nervous system and these reflexes and processes can be
utilized in the treatment of various disorders. In addition, in
some embodiments, such targeted neuromodulation reduces or
eliminates undesired side effects, such as painful tingling or
unwanted movements caused by direct stimulation of motor nerves,
such as within the ventral root. Further, such targeted therapy
minimizes or eliminates global activation or inactivation of the
sympathetic nervous system and the complications that arise from
such activation or inactivation.
[0009] In a first aspect of the present invention, a method is
provided of modulating a neural pathway in the sympathetic nervous
system. In some embodiments, the method comprises positioning at
least one electrode of a lead in close proximity to a dorsal root
ganglion upstream of at least one ganglion of the sympathetic nerve
chain, and providing energy to the at least one electrode so as to
neuromodulate the dorsal root ganglion in a manner that influences
a condition associated with the at least one ganglion of the
sympathetic nerve chain while excluding neuromodulation of an
associated ventral root.
[0010] In some embodiments, neuromodulating a dorsal root ganglion
comprises neuromodulating a dorsal root ganglion in a manner that
influences functional activation of a bodily system associated with
the at least one ganglion along the sympathetic nerve chain. In
other embodiments, the neuromodulating a dorsal root ganglion
comprises neuromodulating a dorsal root ganglion in a manner that
influences functional activation of an organ associated with the at
least one ganglion along the sympathetic nerve chain.
[0011] In some embodiments, neuromodulating a dorsal root ganglion
comprises neuromodulating a dorsal root ganglion in a manner that
influences functional inhibition of a bodily system associated with
the at least one ganglion along the sympathetic nerve chain.
Further, in some embodiments, neuromodulating a dorsal root
ganglion comprises neuromodulating a dorsal root ganglion in a
manner that influences functional inhibition of an organ associated
with the at least one ganglion along the sympathetic nerve
chain.
[0012] In some embodiments, neuromodulating a dorsal root ganglion
comprises neuromodulating a dorsal root ganglion in a manner that
lessens vascular resistance of a blood vessel associated with the
at least one ganglion along the sympathetic nerve chain. In other
embodiments, neuromodulating a dorsal root ganglion comprises
neuromodulating a dorsal root ganglion in a manner that improves
vascular perfusion to an ischemic body region or tissue.
[0013] It may be appreciated that in some embodiments the condition
comprises an ischemic disorder, diabetes, peripheral vascular
disease, stroke, erectile dysfunction, a sympathetically maintained
or mediate pain condition, Raynaud's disease, heart disease, angina
pectoris, vascular disease, a skin ulceration, a wound healing
disorder, asthma, hypertension, an immune system disorder or a
renal disorder, but is not so limited. It may also be appreciated
that in some embodiments the at least one ganglion of the
sympathetic nerve chain is a cervical ganglion, a thoracic ganglion
or a lumbar ganglion.
[0014] In some embodiments, the positioning step comprises
positioning the at least one electrode on the dorsal root ganglion
epinurium.
[0015] In other embodiments, the method further comprises directly
applying stimulation to the at least one ganglion along the
sympathetic nerve chain. In some instances, the directly applying
stimulation step for the at least one ganglion along the
sympathetic nerve chain is performed using an electrode exposed to
the at least one ganglion along the sympathetic nerve chain.
[0016] In a second aspect of the present invention, another method
is provided of modulating a portion of a neural pathway in the
sympathetic nervous system. In some embodiments, the method
includes positioning at least one electrode of a lead in close
proximity to a target dorsal root ganglion associated with the
portion of the neural pathway, and energizing the at least one
electrode so that the portion of the neural pathway is altered and
energy provided by the at least one electrode dissipates within the
target dorsal root ganglion while excluding an associated ventral
root.
[0017] In some embodiments, the energy provided by the at least one
electrode selectively stimulates a soma and/or one of the ascending
or descending axons within the target dorsal root ganglion which
activates a premotor neuron. In some instances, the activation of
the premotor neuron acts upon a sympathetic motor neuron causing
inhibition of the release of norephinephrine by the sympathetic
motor neuron. In some instances, the activation of the premotor
neuron acts upon a sympathetic motor neuron causing inhibition of
vascular resistance in a blood vessel influenced by the sympathetic
motor neuron.
[0018] In some embodiments, altering of the portion of the neural
pathway increases perfusion to a region of the body associated with
the portion of the neural pathway. In some instances, the region of
the body comprises a brain. In other instances, the region of the
body comprises an ischemic limb. In some embodiments, altering of
the portion of the neural pathway increases perfusion to a portion
of a peripheral vascular system affected by a peripheral vascular
disease. And in some embodiments, altering of the portion of the
neural pathway alleviates sympathetically mediated pain or
sympathetically maintained pain.
[0019] Other objects and advantages of the present invention will
become apparent from the detailed description to follow, together
with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] FIG. 1 illustrates an embodiment of an implantable
stimulation system.
[0021] FIG. 2 illustrates example placement of the leads of the
embodiment of FIG. 1 within a patient anatomy.
[0022] FIG. 3 illustrates an example cross-sectional view of an
individual spinal level showing a lead positioned on, near or about
a target dorsal root ganglion.
[0023] FIG. 4 illustrates a lead positioned near a dorsal root
ganglion so as to influence the sympathetic nervous system in the
treatment of a condition or disorder.
[0024] FIG. 5 is a schematic illustration of a portion the
sympathetic nervous system.
[0025] FIG. 6 is an illustration of a portion of sympathetic
nervous system neuromodulated by an embodiment of the present
invention.
[0026] FIG. 7 is an illustration of embodiments of the present
invention implanted for the direct stimulation of a single
sympathetic nerve ganglion and a single dorsal root ganglion on the
same spinal level.
DETAILED DESCRIPTION
[0027] The sympathetic system is responsible for mobilizing the
body's responses under stressful situations, also known as the
`flight or fight` response. The sympathetic system acts on many
different organs of the body including the eyes (contraction and
dilation of the pupils), heart (increase in heart rate, blood flow,
blood pressure), lungs (dilation of bronchioles), digestive system
(inhibiting movement of food), kidney (increase secretion of
rennin), and penis (promote ejaculation). The sympathetic system is
also active at a basal level on these and many organs so as to
maintain a state of homeostasis in the body.
[0028] Given the unique role of the sympathetic system in the body
and the ability of the sympathetic system to affect a wide array of
internal organs, the sympathetic system may be utilized to treat a
variety of conditions throughout the body. Such conditions include,
but are not limited to, ischemic disorders, diabetes, peripheral
vascular disease, stroke, erectile dysfunction, sympathetically
maintained or mediate pain conditions, Raynaud's disease, heart
disease, angina pectoris, vascular disease, skin ulcerations, wound
healing disorders, asthma, hypertension, immune system disorders,
and renal disorders, to name a few.
[0029] Many of these conditions involve ischemia or impaired blood
flow to a particular region of the body. Although such impairment
of blood flow is caused by a myriad of factors depending on the
condition suffered by the patient, increase in blood flow to these
areas can assist in treating these conditions and can be achieved
by affecting the sympathetic nervous system.
[0030] Blood flow and pressure is continuously regulated by nerves.
At specific locations in the walls of blood vessels, including the
aortic arch and carotid sinus, blood pressure is sensed based on
the amount of stretch in the walls. When blood pressure increases
for any reason, nerve signals are sent to the blood pressure
regulating centers located in the brainstem and suprabulbar
regions. In response to the nerve signals, the blood pressure
regulating centers send out nerve signals that slow the heart and
dilate the blood vessels resulting in lowering of the blood
pressure back toward its normal basal level. The basal level can be
considered vascular tone. In general, vascular tone refers to the
degree of constriction experienced by a blood vessel relative to
its maximally dilated state. All arterial and venous vessels under
basal conditions exhibit some degree of smooth muscle contraction
that determines the diameter, and hence tone, of the vessel. Basal
vascular tone differs among organs. Those organs having a large
vasodilatory capacity (e.g., myocardium, skeletal muscle, skin,
splanchnic circulation) have high vascular tone, whereas organs
having relatively low vasodilatory capacity (e.g., cerebral and
renal circulations) have low vascular tone.
[0031] Vascular tone is determined by many different competing
vasoconstrictor and vasodilator influences acting on the blood
vessel. These influences can be separated into extrinsic factors
that originate from outside of the organ or tissue in which the
blood vessel is located, and intrinsic factors that originate from
the vessel itself or the surrounding tissue. The primary function
of extrinsic factors is to regulate arterial blood pressure by
altering systemic vascular resistance, whereas intrinsic mechanisms
are important for local blood flow regulation within an organ.
Vascular tone at any given time is determined by the balance of
competing vasoconstrictor and vasodilator influences.
[0032] In general, activation of extrinsic factors and control
mechanisms can either increase or decrease vascular tone (i.e.,
cause vasoconstriction). In one such example, increasing
sympathetic nerve activity can increase vascular tone, thus causing
an increase in vasoconstriction. Therefore, inhibition of the
sympathetic nervous system causes arterial vasodilation and
improved blood flow to areas that suffer from restricted blood
flow. Thus, treatment of a condition involving ischemia or impaired
blood flow to a particular region of the body may be treated by
inhibition of portions of the sympathetic nervous system. However,
it may be appreciated that in some instances, treatment of a
condition (including conditions involving ischemia or impaired
blood flow) may be treated by activation of portions of the
sympathetic nervous system. The present invention provides for such
types of treatment, in addition to other utilizations of the
sympathetic nervous system to treat a variety of conditions.
[0033] The present invention provides for targeted treatment of
such conditions with minimal deleterious side effects, such as
undesired motor responses, undesired stimulation of unaffected body
regions, global activation or inactivation of the sympathetic
nervous system and the complications that arise from such
activation or inactivation. This is achieved by directly
neuromodulating a target anatomy associated with the condition
while minimizing or excluding undesired neuromodulation of other
anatomies. In most embodiments, neuromodulation comprises
stimulation, however it may be appreciated that neuromodulation may
include a variety of forms of altering or modulating nerve activity
by delivering electrical or pharmaceutical agents directly to a
target area. For illustrative purposes, descriptions herein will be
provided in terms of stimulation and stimulation parameters,
however, it may be appreciated that such descriptions are not so
limited and may include any form of neuromodulation and
neuromodulation parameters.
[0034] Typically, the systems and devices are used to neuromodulate
portions of neural tissue of the central nervous system, wherein
the central nervous system includes the spinal cord and the pairs
of nerves along the spinal cord which are known as spinal nerves.
The spinal nerves include both dorsal and ventral roots which fuse
to create a mixed nerve which is part of the peripheral nervous
system. At least one dorsal root ganglion (DRG) is disposed along
each dorsal root prior to the point of mixing. Thus, the neural
tissue of the central nervous system is considered to include the
dorsal root ganglions and exclude the portion of the nervous system
beyond the dorsal root ganglions, such as the mixed nerves of the
peripheral nervous system. Typically, the systems and devices of
the present invention are used to selectively stimulate one or more
dorsal root ganglia, while minimizing or excluding undesired
stimulation of other tissues, such as surrounding or nearby
tissues, ventral root and portions of the anatomy associated with
body regions which are not targeted for treatment. In other
embodiments, dorsal roots, dorsal root entry zones, or portions are
targeted for stimulation. It may be appreciated that stimulation of
other tissues are contemplated.
[0035] The target stimulation areas of the present invention,
particularly the dorsal root ganglia, are utilized due in part to
their effect on the sympathetic nervous system. It is in these
areas that sensory fibers are isolated from motor fibers. Sensory
fibers are involved in a variety of reflexes and feed-forward
physiologic processes that control the sympathetic nervous system
and these reflexes and processes can be utilized in the treatment
of various disorders. Thus, by stimulating sensory fibers in these
areas, fundamental reflexes and processes can be affected to lessen
the symptoms of a variety of disorders. In addition, such targeted
stimulation reduces undesired side effects, such as painful
tingling or unwanted movements caused by direct stimulation of
motor nerves, such as within the ventral root.
[0036] The present invention utilizes such reflex arcs and
feed-forward processes to treat patients presenting with one or
more disorders. FIG. 1 illustrates an embodiment of an implantable
stimulation system 100 for treatment of such patients. The system
100 includes an implantable pulse generator (IPG) 102 and at least
one lead 104 connectable thereto. In preferred embodiments, the
system 100 includes four leads 104, as shown, however any number of
leads 104 may be used including one, two, three, four, five, six,
seven, eight, up to 58 or more. Each lead 104 includes at least one
electrode 106. In preferred embodiments, each lead 104 includes
four electrodes 106, as shown, however any number of electrodes 106
may be used including one, two, three, four five, six, seven,
eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen,
sixteen or more. Each electrode can be configured as off, anode or
cathode. In some embodiments, even though each lead and electrode
are independently configurable, at any given time the software
ensures only one lead is stimulating at any time. In other
embodiments, more than one lead is stimulating at any time, or
stimulation by the leads is staggered or overlapping.
[0037] Referring again to FIG. 1, the IPG 102 includes electronic
circuitry 107 as well as a power supply 110, e.g., a battery, such
as a rechargeable or non-rechargeable battery, so that once
programmed and turned on, the IPG 102 can operate independently of
external hardware. In some embodiments, the electronic circuitry
107 includes a processor 109 and programmable stimulation
information in memory 108.
[0038] The implantable stimulation system 100 can be used to
stimulate a variety of anatomical locations within a patient's
body. In preferred embodiments, the system 100 is used to stimulate
one or more dorsal roots, particularly one or more dorsal root
ganglions. FIG. 2 illustrates example placement of the leads 104 of
the embodiment of FIG. 1 within the patient anatomy. In this
example, each lead 104 is individually advanced within the spinal
column S in an antegrade direction. Each lead 104 has a distal end
which is guidable toward a target DRG and positionable so that its
electrodes 106 are in proximity to the target DRG. Specifically,
each lead 104 is positionable so that its electrodes 106 are able
to selectively stimulate the DRG, either due to position, electrode
configuration, electrode shape, electric field shape, stimulation
signal parameters or a combination of these. FIG. 2 illustrates the
stimulation of four DRGs, each DRG stimulated by one lead 104.
These four DRGs are located on three levels, wherein two DRGs are
stimulated on the same level. It may be appreciated that any number
of DRGs and any combination of DRGs may be stimulated with the
stimulation system 100 of the present invention. It may also be
appreciated that more than one lead 104 may be positioned so as to
stimulate an individual DRG and one lead 104 may be positioned so
as to stimulate more than one DRG.
[0039] It may be appreciated that selective stimulation or
neuromodulation concepts described herein may be applied in a
number of different configurations. Unilateral (on or in root
ganglion(s) on one level on one side of the spinal cord),
bi-lateral (on or in two root ganglions on the same level on
opposite sides of the spinal cord), unilevel (one or more root
ganglion on the same level) or multi-level (at least one root
ganglion is stimulated on each of two or more levels) or
combinations of the above including stimulation of a portion of the
sympathetic nervous system and one or more dorsal root ganglia
associated with the neural activity or transmission of that portion
of the sympathetic nervous system. As such, embodiments of the
present invention may be used to create a wide variety of
stimulation control schemes, individually or overlapping, to create
and provide zones of treatment.
[0040] FIG. 3 illustrates an example cross-sectional view of an
individual spinal level showing a lead 104 of the stimulation
system 100 positioned on a target DRG. In this example, the lead
104 is advanced within the epidural space along the spinal cord S
to the appropriate spinal level wherein the lead 104 is advanced
laterally toward the target DRG. In some instances, the lead 104 is
advanced through or partially through a foramen. At least one, some
or all of the electrodes 106 are positioned on, near, about or in
proximity to the DRG. In preferred embodiments, the lead 104 is
positioned so that the electrodes 106 are disposed along a surface
of the DRG opposite to the ventral root VR, as illustrated in FIG.
3. It may be appreciated that the surface of the DRG opposite the
ventral root VR may be diametrically opposed to portions of the
ventral root VR but is not so limited. Such a surface may reside
along a variety of areas of the DRG which are separated from the
ventral root VR by a distance.
[0041] In some instances, such electrodes 106 may provide a
stimulation region indicated by dashed line 110, wherein the DRG
receives stimulation energy within the stimulation region and the
ventral root VR does not as it is outside of the stimulation
region. Thus, such placement of the lead 104 may assist in reducing
any possible stimulation of the ventral root VR due to distance.
However, it may be appreciated that the electrodes 106 may be
positioned in a variety of locations in relation to the DRG and may
selectively stimulate the DRG due to factors other than or in
addition to distance, such as due to stimulation profile shape and
stimulation signal parameters, to name a few. It may also be
appreciated that the target DRG may be approached by other methods,
such as a retrograde epidural approach. Likewise, the DRG may be
approached from outside of the spinal column wherein the lead 104
is advanced extraforaminally, from a outside a foramen toward the
spinal column, optionally passing through or partially through a
foramen and is implanted so that at least some of the electrodes
106 are positioned on, about or in proximity to the DRG.
[0042] In order to position the lead 104 in such close proximity to
the DRG, the lead 104 is appropriately sized and configured to
maneuver through the anatomy. In some embodiments, such maneuvering
includes atraumatic epidural advancement along the spinal cord S,
through a sharp curve toward a DRG, and optionally through a
foramen wherein the distal end of the lead 104 is configured to
then reside in close proximity to a small target such as the DRG.
Consequently, the lead 104 is significantly smaller and more easily
maneuverable than conventional spinal cord stimulator leads.
Example leads and delivery systems for delivering the leads to a
target such as the DRG are provided in U.S. patent application Ser.
No. 12/687,737, entitled "Stimulation Leads, Delivery Systems and
Methods of Use", incorporated herein by reference for all
purposes.
[0043] FIG. 4 illustrates the lead 104 positioned near a DRG so as
to influence the sympathetic nervous system in the treatment of a
condition or disorder. In this schematic illustration, a sensory
neuron SN is shown having a soma SA disposed within the DRG and an
axon AX which extends through the dorsal root DR to the dorsal horn
of the spinal cord S. The sensory neuron SN connects with an
interconnector neuron IN within the spinal cord S which connects
with sympathetic premotor neuron SPMN. The sympathetic premotor
neuron SPMN includes a soma SA1 disposed within the ventral horn of
the spinal cord S and an axon AX1 which extends through the ventral
root VR and enervates a sympathetic ganglion SG. Here, the
sympathetic premotor neuron SPMN synapses with a sympathetic motor
neuron SMN that ultimately affects a blood vessel BV and alters
vascular resistance. The sympathetic motor neuron SMN releases
norepinephrine, a neurotransmitter. Norepinephrine increases
vascular resistance or blood pressure by increasing vascular tone
through .alpha.-adrenergic receptor activation. It may be
appreciated that in other embodiments, the sympathetic motor neuron
may release or co-release other transmitters.
[0044] As mentioned previously, treatment of a condition involving
ischemia or impaired blood flow to a particular region of the body
may be treated by inhibition of the sympathetic nervous system.
Referring again to FIG. 4, at least one, some or all of the
electrodes 106 are positioned on, about or in proximity to the
target DRG. In some embodiments, the involved sensory neuron SN,
particularly its soma SA within the target DRG, is selectively
stimulated by energy provided by at least one of the electrodes
106. Such stimulation is transmitted through the interneuron IN to
the sympathetic premotor neuron SPMN which acts upon a sympathetic
motor neuron SMN via the associated sympathetic ganglion SG. This
inhibits release of norepinephrine by the sympathetic motor neuron
SMN which in turn lessens vascular resistance and improves blood
flow to the areas that had suffered from restricted blood flow.
[0045] In some embodiments, selective stimulation of the involved
sensory neuron SN is achieved with the choice of the size of the
electrode(s), the shape of the electrode(s), the position of the
electrode(s), the stimulation signal, pattern or algorithm, or any
combination of these. Such selective stimulation stimulates the
targeted neural tissue while excluding untargeted tissue, such as
surrounding or nearby tissue. In some embodiments, the stimulation
energy is delivered to the targeted neural tissue so that the
energy dissipates or attenuates beyond the targeted tissue or
region to a level insufficient to stimulate modulate or influence
such untargeted tissue. In particular, selective stimulation of
tissues, such as the dorsal root, DRG, or portions thereof, exclude
stimulation of the ventral root wherein the stimulation signal has
an energy below an energy threshold for stimulating a ventral root
associated with the target dorsal root while the lead is so
positioned. Examples of methods and devices to achieve such
selective stimulation of the dorsal root and/or DRG are provided in
U.S. patent application Ser. No. 12/607,009, entitled "Selective
Stimulation Systems and Signal Parameters for Medical Conditions",
incorporated herein by reference for all purposes. It may be
appreciated that indiscriminant stimulation of the ventral root,
such as from an electrode which emits stimulation energy which
directly stimulates the ventral root, typically causes unpleasant
sensations for the patient, such as tingling, buzzing or undesired
motions or movements. Therefore, it is desired to stimulate
sympathetic premotor neurons via synapses in the spinal cord rather
than directly via the ventral root.
[0046] As mentioned previously, given the unique role of the
sympathetic system in the body and the ability of the sympathetic
system to affect a wide array of internal organs, the sympathetic
system may be utilized to treat a variety of conditions throughout
the body. In particular, a condition involving ischemia or impaired
blood flow to a particular region of the body may be treated by
inhibition or activation of the sympathetic nervous system. Some of
these conditions will be described in more detail below. However,
it may be appreciated that other disorders and conditions may also
be treated with the devices, systems and methods of the present
invention.
Diabetes
[0047] Diabetes is a metabolism disorder in which the quantity of
glucose in the blood is too elevated (hyperglycemia). This is
because the body either does not produce enough insulin, produces
no insulin, or has cells that do not respond properly to the
insulin the pancreas produces. Since insulin makes it possible for
cells to take in glucose, this metabolic disorder results in too
much glucose building up in the blood.
[0048] Elevated blood sugar levels cause a variety of health
problems and complications for diabetic patients. A very common
complication is foot problems, including nerve damage or peripheral
neuropathy that results in loss of feeling or pain and burning
sensations in the feet and legs. Once nerve damage progresses, it
triggers loss of motor control and abnormal gait and can result in
ulcers and amputations. The major cause of such nerve damage is
loss of circulation. High blood sugars damage both large and small
blood vessels that carry oxygen and nutrients to the nerves. If
there is not enough blood being sent to the nerves, the nerves are
damaged wherein electrical signals can no longer pass or pass at a
slower speed. Good messaging in nerves also depends on an outer
protective coating called myelin. This electrical insulator is also
vulnerable to damage from high blood sugars. Preventing such foot
problems in diabetes begins by preventing the loss of circulation
that will result in serious nerve damage.
[0049] Diabetic patients are also twice as likely to have a heart
attack or stroke. This is because diabetes worsens atherosclerosis,
a condition in which arteries narrow. High blood sugar levels have
two effects on cells lining blood vessels. First, it increases the
production of free radicals, highly reactive molecules that damage
sensitive cell components like DNA, causing premature cell death
(apoptosis). Second, it reduces the availability of nitric oxide
(NO), which would otherwise enable blood vessels to relax and blood
flow to increase. In patients without diabetes, fast blood flow
triggers a cascade which leads to dilation of blood vessels and
reduced inflammation. The diabetic patient does not have the
benefit of such triggering due to the reduction in blood flow,
which in turn worsens the condition.
[0050] Therefore the diabetic patient may be beneficially treated
by increasing blood flow to areas of the body by stimulating
associated dorsal root ganglions as described above. In particular,
such increase in blood flow may reduce the incidence of nerve
damage, heart attack and stroke in those suffering from
diabetes.
Peripheral Vascular Disease
[0051] Peripheral vascular disease (PVD), refers to the obstruction
of large arteries in the periphery of the vascular system. PVD
causes either acute or chronic ischemia (lack of blood supply). PVD
also includes a subset of diseases classified as microvascular
diseases resulting from episodal narrowing of the arteries
(Raynaud's phenomenon), or widening thereof (erythromelalgia). For
the patient, PVD can manifest as claudication (pain, weakness,
numbness, or cramping in muscles due to decreased blood flow),
sores, wounds, or ulcers that heal slowly or not at all, noticeable
changes in skin color (blueness or paleness) or temperature
(coolness) when compared to the other limbs, or diminished hair and
nail growth on affected limb and digits, to name a few. Individuals
with PVD may require amputation and can have an elevated risk for
cardiovascular events and eventual death of a cardiac or
cerebrovascular etiology. Thus, patients suffering from peripheral
vascular disease may be beneficially treated by increasing blood
flow to portions of the peripheral vascular system by stimulating
associated dorsal root ganglions as described above.
Limb Ischemia
[0052] Limb ischemia is an obstruction of the arteries that
seriously decreases blood flow to the extremities (hands, feet and
legs) and has progressed to the point of severe pain and even skin
ulcers or sores. Limb ischemia is often present in people suffering
from severe cases of peripheral vascular disease. However, there
are a variety of risk factors for developing the disease, including
age, smoking, diabetes, obesity, sedentary lifestyle, high
cholesterol, high blood pressure, and family history of
atherosclerosis or claudication. Thus, patients suffering from limb
ischemia for any reason may be beneficially treated by increasing
blood flow to the limb by stimulating associated dorsal root
ganglions as described above.
Myocardial Ischemia
[0053] Myocardial Ischemia develops when coronary blood flow
becomes inadequate to meet myocardial oxygen demand. In some
instances, myocardial ischemia results from abnormal constriction
or deficient relaxation of coronary microcirculation (ie,
resistance vessels). Coronary spasm can also reduce coronary flow
reserve significantly by causing dynamic stenosis of coronary
arteries. Myocardial ischemia causes myocardial cells to switch
from aerobic to anaerobic metabolism, with a progressive impairment
of metabolic, mechanical, and electrical functions. Angina
pectoris, often described as severe chest pain, is a common
clinical manifestation of myocardial ischemia. It is caused by
chemical and mechanical stimulation of sensory afferent nerve
endings in the coronary vessels and myocardium. These nerve fibers
extend from the first to fourth thoracic spinal nerves, ascending
via the spinal cord to the thalamus, and from there to the cerebral
cortex.
[0054] The heart and coronary arteries are innervated by
sympathetic afferent fibers that have their cell bodies
concentrated in the dorsal root ganglia of the T2 to T6 spinal
segments but can extend as far as the C8 to T9 segments. Dorsal
root ganglion cells have axons that enter the tract of Lissauer and
terminate in the same segment, or the axons can ascend and descend
a few segments before terminating in the spinal gray matter.
Patients suffering from myocardial ischemia may be beneficially
treated by increasing blood flow in the coronary vascular system by
stimulating associated dorsal root ganglions as described above.
Likewise, patients presenting with angina pectoris may be
beneficially treated for pain symptoms by stimulating associated
dorsal root ganglions as described above.
Stroke
[0055] Initial treatment for a stroke varies depending on whether
it is an ischemic stroke (caused by a blood clot) or a hemorrhagic
stroke (caused by bleeding in the brain). For an ischemic stroke,
initial treatment focuses on restoring blood flow. Permanent damage
from a stroke often occurs within the first few hours so swift
restoration of blood flow will lessen damage that will occur.
Current treatments include a clot-dissolving medicine called tissue
plasminogen activator (t-PA), which can increase chances of
survival and recovery. In addition, the patient may receive aspirin
or aspirin combined with another antiplatelet medicine. However,
aspirin is not recommended within 24 hours of treatment with t-PA.
Other medicines may be given to control blood sugar levels, fever,
and seizures. Patients suffering from an ischemic stroke may be
beneficially treated by quickly restoring blood flow to the brain
by stimulating associated dorsal root ganglions as described
above.
Erectile Dysfunction
[0056] Erectile dysfunction is a sexual dysfunction characterized
by the inability to develop or maintain an erection of the penis. A
penile erection is the hydraulic effect of blood entering and being
retained in sponge-like bodies within the penis. Thus, there are a
variety of circulatory causes of erectile dysfunction. The most
common circulatory causes are cardiovascular disease and diabetes.
By treating these circulatory maladies with the devices, systems
and methods described herein, erectile dysfunction may be prevented
or treated.
Sympathetically Mediated Pain
[0057] Sympathetically mediated pain and sympathetically maintained
pain refers to pain signals that are transmitted to the brain from
the sympathetic nervous system, the part of the nervous system
controlling `involuntary` functions of the body such as heart rate,
sweating, constriction of blood vessels, and digestion. In certain
abnormal situations the pain signals from the sympathetic nervous
system become constant and severe, even though there is no obvious
cause of pain. The mechanism by which this happens is complex and
not fully understood.
[0058] Sympathetic pain usually has a severe, burning
characteristic and often begins in the hand or foot. The affected
area is very hypersensitive to even the lightest touch. Pink or
bluish discoloration of the involved area may occur because of
abnormal circulation, and abnormal sweating may also be noticed.
There are a number of diagnostic phrases used by physicians when
discussing sympathetic pain syndromes. In the past the most
commonly used phrase was Reflex Sympathetic Dystrophy, or RSD.
Other terms used to describe the condition include causalgia and
sympathetically mediated pain. Recently, "Chronic Regional Pain
Syndrome" or CRPS has become commonly used. Such sympathetic pain
can also be treated by selective stimulation of one or more dorsal
root ganglions since sympathetic afferents can travel through the
DRG. In some embodiments, a negative feedback loop on efferent
sympathetic activity is created. And, in other embodiments, a
stellate ganglion blockade is used in treating certain pain
conditions.
[0059] Thus, blood vessels are just one of many targets that can be
influenced by affecting the sympathetic nervous system via
selective stimulation of one or more dorsal root ganglions. A
variety of other end organs may also be influenced by selective
stimulation of one or more dorsal root ganglions to treat medical
conditions associated with these end organs. For example, the lungs
may be influenced in the treatment patients suffering from
constriction of air passages. There are a variety of circumstances
and conditions that cause the bronchi of the lungs to become
narrow, or constrict, making it difficult to breathe.
Bronchoconstriction, or the narrowing of the airways, is typically
caused by the muscles surrounding the lungs becoming tight. A
build-up of excess mucous as well as inflammation can also cause
constriction. The constriction results in coughing, wheezing and
shortness of breath. There are several conditions that cause this;
such conditions include but are not limited to: Chronic lung
disease (CLD), Emphysema, Exercise-Induced bronchoconstriction,
Allergen-induced bronchoconstriction, and Asthma. In some
embodiments, bronchodilation, the process by which the bronchi
(tubes in the lungs made of connective tissue and muscle) are
dilated, or opened, is achieved by selective stimulation of one or
more dorsal root ganglions.
[0060] It is known that bronchodilation can occur as part of the
body's natural response. When the sympathetic nervous system is
activated in what is commonly known as the "fight or flight"
response, the hormones and neurotransmitters of adrenaline (also
called epinephrine) and noradrenaline (also called norepinephrine)
are released. This response can be naturally triggered by physical
or mental stress. And, aspects of this natural response can be
harnessed to treat patients suffering from bronchoconstriction. In
particular, one or more dorsal root ganglia associated with
portions of the sympathetic nervous system involved in
bronchodilation are selectively stimulated using the devices,
systems and method described and referenced herein. Such selective
stimulation leads to desired bronchodilation in treatment of the
medical condition suffered by the patient.
[0061] As mentioned, a variety of end organs may also be influenced
by selective stimulation of one or more dorsal root ganglions to
treat medical conditions associated with these end organs. FIG. 5
is a schematic illustration of a portion of the sympathetic nervous
system and associated target organs and tissues that can be
influenced. As shown, each sympathetic ganglion SG along the
sympathetic chain is associated with a spinal level, in particular,
a dorsal root ganglion on a spinal level. And, one or more
sympathetic ganglions SG are associated with a particular organ,
system or tissue, such as the heart, liver or stomach, to name a
few. It may be appreciated that stimulation of one or more dorsal
root ganglions may alternatively or additionally influence other
ganglions, such as mesenteric ganglions, celiac ganglions, stellate
ganglions and cervical ganglions, to name a few. These ganglions in
turn affect particular organs, systems or tissues.
[0062] FIG. 6 illustrates how embodiments of the present invention
may be advantageously utilized for neurostimulation of the
sympathetic chain using direct stimulation of an associated DRG.
This aspect of the present invention takes advantage of the
anatomical placement of the DRG relative to the sympathetic chain
in conjunction with gate control theory to direct DRG stimulation
for control of the sympathetic system. Thus, selective
neurostimulation techniques of the present invention may be
advantageously employed to, for example, provide and/or augment
therapeutic tools in regards to weight control, hormonal
regulation, vascular perfusion, etc. Additional alternative
embodiments include the use of specific stimulation to provide
organ system autonomic modulation. Through implantation of
stimulation electrodes and systems of the present invention to
stimulate the appropriate DRG upstream of the associated portion(s)
of the sympathetic chain, the associated system may be controlled,
modulated or influenced utilizing the electrical and/or
pharmacological agent stimulation techniques described herein.
Thus, there is provided a method of modulating a neural pathway in
the sympathetic nervous system by stimulating a spinal dorsal root
ganglion upstream of at least one ganglion of the sympathetic nerve
chain to influence a condition associated with the at least one
ganglion of the sympathetic nerve chain.
[0063] In one specific example, by stimulating the DRG 40
associated with spinal level 13.3, as shown in FIG. 6, the portion
of the sympathetic chain associated with hormonal regulation may be
altered, modified, influenced or controlled. Similarly, by
stimulating the DRG 40' associated with spinal level 13.2 and/or
the DRG 40'' associated with level 13.1, the portion of the
sympathetic chain associated with the gastrointestinal tract, or
urinary incontinence (i.e., urinary bladder, urethra, prostate,
etc.) may be altered, modified, influenced or controlled.
[0064] Optionally or additionally, the direct stimulation
techniques described herein may be used to directly stimulate
individual nerve ganglion of the sympathetic nervous system, such
as, for example, the celiac ganglion, superior mesenteric ganglion,
inferior mesenteric ganglion and others listed in FIGS. 5, 6 or
known to those of ordinary skill. It is to be appreciated that the
stimulation systems, pulse generators, leads, electrodes, and/or
microelectrodes and other components are modified and sized as
needed to allow for direct stimulation of the ganglion including
implanting into the ganglion or within adjacent nerve sheaths
leading to the ganglion. FIG. 7 illustrates an embodiment of a
combined direct stimulation of a DRG 38 with microelectrode 115 as
well as a suitably sized microelectrode 115 implanted in a
sympathetic nerve root ganglion 63. The electrodes in FIG. 7 may
stimulate independently or in a coordinated fashion to achieve the
desired clinical outcome or other desired result. Similar to the
discussion above for electrode placement in, on or about the DRG,
electrode placement for the sympathetic chain may also be
unilateral, bilateral, on adjacent portions of the chain or
separate portions of the chain as needed.
[0065] One aspect of the present invention is a method of
modulating a neural pathway in the sympathetic nervous system
including stimulating a spinal dorsal root ganglion upstream of at
least one ganglion of the sympathetic nerve chain to influence a
condition associated with the at least one ganglion of the
sympathetic nerve chain. In one specific embodiment, stimulating a
spinal dorsal root ganglion comprises stimulating a spinal dorsal
root ganglion upstream of at least one ganglion of the sympathetic
nerve chain to influence functional activation of a bodily system
associated with the at least one ganglion along the sympathetic
nerve chain, to influence functional activation of an organ
associated with the at least one ganglion along the sympathetic
nerve chain, or to influence functional inhibition of a bodily
system associated with the at least one ganglion along the
sympathetic nerve chain. In specific embodiments, the ganglion of
the sympathetic nerve chain is a cervical ganglion, a thoracic
ganglion, a lumbar ganglion or a sacral ganglion.
[0066] It may be appreciated that embodiments of the present
invention may be used in conjunction with other neurostimulation
techniques by combining an upstream stimulation using specific DRG
stimulation of the present invention with another stimulation
acting downstream of the DRG stimulation. As used herein,
downstream and upstream refer to pathways closer to the brain
(i.e., upstream) or further from the brain (i.e., downstream). For
example, several stimulation techniques are described by Rezai in
US Patent Publication 2002/0116030 and U.S. Pat. No. 6,438,423 and
by Dobak in publication 2003/0181958, all of which are incorporated
herein by reference. In specific aspects, embodiments of the
present invention may be used to provide electrical and
combinational (i.e., with a pharmacological agent) stimulation of
the sympathetic nerve chain as described by Rezai alone (i.e.,
using the appropriate DRG stimulation or implanting directly into a
nerve root ganglion.). Alternatively or additionally, embodiments
of the present invention provide specific, direct stimulation of
one or more DRG and are used in combination with the stimulation
techniques described by Rezai (i.e., conventional stimulation of
the sympathetic chain using one or more of Rezai's techniques).
[0067] Referring back to FIG. 1, in some embodiments, the
implantable pulse generator (IPG) 102 comprises circuitry which
initiates or modifies the electrical stimulation in response to one
or more sensors. Example sensors include, among others, blood
glucose sensors, blood pressure sensors, blood flow sensors
(including Doppler and other techniques), heart rate sensors, blood
oxygen sensors, temperature sensors, accelerometers, strain gauges,
electrocardiograms, brain wave detectors (electroencephalograms,
other interiorly and exteriorly measured composite neuronal
activity), electrical devices which measure electrical activity in
muscles and/or nerves, or other devices capable of measuring
physiological parameters indicative of symptoms of the disorder
under treatment.
[0068] In some embodiments, the one or more sensors sense the
status of one or more symptoms of the disorder. Such status
information is utilized to modify the electrical stimulation to a
level which is appropriate to improve status of the disorder in
real time. This modification of electrical stimulation may be
particularly beneficial in the treatment of conditions which have a
time dependency, such as stroke.
[0069] In some embodiments, the sensor detects one or more of the
following functions or aspect of the body: carbon dioxide pressure
in a target tissue, action potential conduction (such as in a
target nerve), body movement, balance, motor activity including
muscle tone, heart rate, blood pressure, capillary pressure, venous
pressure, arterial pressure, blood flow, circulation (including
blood and lymphatic), perfusion, electrocardiogram, oxygenation
(including blood oxygenation levels, oxygen saturation levels,
oxygen consumption, oxygen pressure), concentration of certain
biological molecules/substances in the body (such as, for example,
glucose, liver enzymes, electrolytes, hormones, creatinine,
medications, concentration of various cells, platelets, or
bacteria), pH levels, chemical production, neurotransmitter levels,
electrolyte levels in the circulation/tissue, nitrogen pressure,
respiratory function, chest wall expansion, diaphragmatic movement,
cognitive activity, electroencephalogram, flushing, galvanic skin
responses, perspiration, body temperature regulation, response to
external stimulation, pain, speech, temperature, visual activity,
intra-bladder pressure, and water pressure.
[0070] In some embodiments, the sensor is positioned so as to
measure sympathetic nerve outflow. In such embodiments, the sensor
may be positioned on or near the sympathetic chain.
[0071] In some embodiments, the implantable pulse generator (IPG)
102 comprises circuitry which initiates or modifies the electrical
stimulation in response to a timer or clock. Thus, stimulation may
be reduced or eliminated during times in which it is determined
that the patient desires reduced or no treatment. Such periods of
reduced usage may extend the life of the power supply 110.
[0072] Although the foregoing invention has been described in some
detail by way of illustration and example, for purposes of clarity
of understanding, it will be obvious that various alternatives,
modifications, and equivalents may be used and the above
description should not be taken as limiting in scope of the
invention which is defined by the appended claims.
INCORPORATION BY REFERENCE
[0073] All publications and patent applications mentioned in this
specification are herein incorporated by reference to the same
extent as if each individual publication or patent application was
specifically and individually indicated to be incorporated by
reference.
* * * * *