U.S. patent application number 15/893838 was filed with the patent office on 2018-08-16 for optimizing neuromodulation stimulation parameters using blood parameter sensing.
This patent application is currently assigned to Verily Life Sciences LLC. The applicant listed for this patent is Verily Life Sciences LLC. Invention is credited to Brian Pepin, Shiv Sabesan.
Application Number | 20180229041 15/893838 |
Document ID | / |
Family ID | 61283344 |
Filed Date | 2018-08-16 |
United States Patent
Application |
20180229041 |
Kind Code |
A1 |
Pepin; Brian ; et
al. |
August 16, 2018 |
OPTIMIZING NEUROMODULATION STIMULATION PARAMETERS USING BLOOD
PARAMETER SENSING
Abstract
The present disclosure relates to implantable neuromodulation
systems and methods, and in particular to systems and methods for
sensing blood-based parameter changes triggered by neural
stimulation and subsequently optimizing the stimulation parameters
based on feedback from the sensed blood-based parameter changes.
Particularly, aspects of the present invention are directed to a
method that includes delivering neural stimulation to a nerve or
artery/nerve plexus based on a first set of stimulation parameters,
monitoring a response to the neural stimulation that includes
monitoring responses of the nerve or artery/nerve plexus and
blood-based parameters of the artery, modifying the first set of
the stimulation parameters based on the blood-based parameters to
create a second set of stimulation parameters, and delivering the
neural stimulation based on the second set of the stimulation
parameters.
Inventors: |
Pepin; Brian; (San
Francisco, CA) ; Sabesan; Shiv; (San Mateo,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Verily Life Sciences LLC |
South San Francisco |
CA |
US |
|
|
Assignee: |
Verily Life Sciences LLC
South San Francisco
CA
|
Family ID: |
61283344 |
Appl. No.: |
15/893838 |
Filed: |
February 12, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62458757 |
Feb 14, 2017 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/36067 20130101;
A61N 1/36071 20130101; A61N 1/36064 20130101; A61N 1/36135
20130101; A61N 1/36175 20130101; A61N 1/36007 20130101; A61N
1/36031 20170801; A61N 1/36171 20130101; A61N 1/0534 20130101; A61N
1/36096 20130101; A61N 1/36085 20130101; A61N 1/3614 20170801; A61N
1/36062 20170801; A61N 1/36139 20130101; A61N 1/3752 20130101 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61N 1/05 20060101 A61N001/05 |
Claims
1. A medical device comprising: an electronics module comprising: a
controller configured to provide a first set of stimulation
parameters, and a pulse generator configured to generate neural
stimulation based on the first set of stimulation parameters; a
lead body including a conductor material connected to the
electronics module; one or more stimulation electrodes connected to
the conductor material and configured to deliver the neural
stimulation generated by the pulse generator to a nerve or
artery/nerve plexus; one or more recording electrodes connected to
the conductor material and configured to: monitor a response to the
neural stimulation that includes electrical impulses traveling
through the nerve or artery/nerve plexus, and send information
regarding the electrical impulses to the controller via the
conductive material; and one or more sensors connected to the
conductor material and configured to: monitor the response to the
neural stimulation that includes blood-based parameters, and send
the blood-based parameters to the controller via the conductive
material, wherein the controller is further configured to modify
the first set of the stimulation parameters based on the
blood-based parameters to create a second set of stimulation
parameters, the pulse generator is further configured to generate
modified neural stimulation based on the second set of stimulation
parameters, and the one or more stimulation electrodes are further
configured to deliver the modified neural stimulation to the nerve
or artery/nerve plexus.
2. The medical device of claim 1, wherein the stimulation
parameters include at least one of: stimulation amplitude, pulse
width, frequency, duty cycle, stimulation waveform shape, and
electrode configuration.
3. The medical device of claim 1, wherein the blood-based
parameters include at least one of blood flow, blood pressure, and
arterial distension.
4. The medical device of claim 3, wherein the one or more sensors
include at least one of: a blood flow sensor, a blood pressure
sensor, and a distension sensor.
5. The medical device of claim 4, wherein the blood flow sensor is
a Doppler sensor configured to measure blood velocity or an
impedance sensor configured to detect changes in electrical
impedance of blood.
6. The medical device of claim 4, wherein the blood pressure sensor
is an impedance sensor configured to measure the blood pressure or
a piezoresistive pressure sensor configured to measure the blood
pressure.
7. The medical device of claim 4, wherein the arterial distension
sensor is a capacitive sensor configured to measure the arterial
distension, a photonic sensor configured to measure arterial
distension based on a change in amount of photons transmitted, or a
Doppler sensor configured to measure cardiac motion and artery
diameter pulsation.
8. A medical system comprising: an implantable neurostimulator
including: a housing; a feedthrough assembly that passes through
the housing; and an electronics module within the housing and
connected to the one or more feedthroughs, wherein the electronics
module includes a pulse generator, a controller, and a memory
storing program instructions; and a lead assembly including: a lead
body including a conductor material; a lead connector that connects
the conductor material to the feedthrough assembly; and one or more
electrodes and one or more sensors connected to the conductor
material, wherein the program instructions when operated on by the
controller, cause the controller to perform operations comprising:
delivering neural stimulation using the pulse generator and the one
or more electrodes based on a first set of stimulation parameters
to a nerve or artery/nerve plexus; monitoring a response to the
neural stimulation that includes monitoring responses of the nerve
or artery/nerve plexus and blood-based parameters of the artery
using the one or more sensors; modifying the first set of the
stimulation parameters based on the blood-based parameters to
create a second set of stimulation parameters, and delivering the
neural stimulation using the pulse generator and the one or more
electrodes based on the second set of the stimulation
parameters.
9. The medical system of claim 8, wherein the stimulation
parameters include at least one of: stimulation amplitude, pulse
width, frequency, duty cycle, stimulation waveform shape, and
electrode configuration.
10. The medical system of claim 8, wherein the blood-based
parameters include at least one of blood flow, blood pressure, and
arterial distension.
11. The medical system of claim 10, wherein the one or more sensors
include at least one of: a blood flow sensor, a blood pressure
sensor, and a distension sensor.
12. The medical system of claim 11, wherein the blood flow sensor
is a Doppler sensor configured to measure blood velocity or an
impedance sensor configured to detect changes in electrical
impedance of blood.
13. The medical system of claim 11, wherein the blood pressure
sensor is an impedance sensor configured to measure the blood
pressure or a piezoresistive pressure sensor configured to measure
the blood pressure.
14. The medical system of claim 11, wherein the arterial distension
sensor is a capacitive sensor configured to measure the arterial
distension, a photonic sensor configured to measure arterial
distension based on a change in amount of photons transmitted, or a
Doppler sensor configured to measure cardiac motion and artery
diameter pulsation.
15. The medical system of claim 8, wherein the monitoring the
response to the neural stimulation includes determining whether the
neural stimulation has a physiological effect.
16. The medical system of claim 15, wherein the determining whether
the neural stimulation has the physiological effect includes
obtaining the blood-based parameters and comparing the blood-based
parameters to one or more predetermined thresholds to determine
whether the neural stimulation has an adverse physiological effect
on the blood-based parameters.
17. The medical system of claim 16, wherein when the neural
stimulation has the adverse physiological effect, modifying the
first set of the stimulation parameters based on the blood-based
parameters to create the second set of stimulation parameters.
18. The medical system of claim 8, wherein the operations further
comprise determining whether adequate adaptation is achieved.
19. The medical system of claim 18, wherein the adequate adaptation
is achieved when at least one of the following objectives is
achieved: acceptable levels for the blood-based parameters, a
target intensity level for one or more of the stimulation
parameters, and a target physiological effect, and wherein when the
adequate adaptation is not achieved, modifying the first set of the
stimulation parameters based on the titration schedule and the
blood-based parameters to create the second set of stimulation
parameters.
20. A medical system comprising: one or more processors; and memory
coupled to the one or more processors, the memory encoded with a
set of instructions configured to perform a process comprising:
delivering, using one or more stimulation electrodes, neural
stimulation to a nerve or artery/nerve plexus based on a first set
of stimulation parameters; monitoring a response to the neural
stimulation that includes monitoring, using one or more recording
electrodes, responses of the nerve or artery/nerve plexus and
monitoring, using one or more sensors, blood-based parameters of
the artery, modifying, using the one or more processors, the first
set of the stimulation parameters based on the responses of the
nerve or artery/nerve plexus and the blood-based parameters to
create a second set of stimulation parameters, and delivering,
using the one or more stimulation electrodes, the neural
stimulation to the nerve or artery/nerve plexus based on the second
set of the stimulation parameters.
Description
PRIOR RELATED APPLICATION
[0001] This application claims priority to U.S. Provisional
Application No. 62/458,757, filed Feb. 14, 2017, entitled
"OPTIMIZING NEUROMODULATION STIMULATION PARAMETERS USING BLOOD
PARAMETER SENSING", which is hereby incorporated by reference in
its entirety herein.
FIELD OF THE INVENTION
[0002] The present disclosure relates to implantable
neuromodulation systems and methods, and in particular to systems
and methods for sensing blood-based parameter changes triggered by
neural stimulation and subsequently optimizing the stimulation
parameters based on feedback from the sensed blood-based parameter
changes.
BACKGROUND
[0003] Normal neural activity is an intricate balance of electrical
and chemical signals which can be disrupted by a variety of insults
(genetic, chemical or physical trauma) to the nervous system,
causing cognitive, motor and sensory impairments. Similar to the
way a cardiac pacemaker or defibrillator corrects heartbeat
abnormalities, neuromodulation therapies help to reestablish normal
neural balance. In particular instances, neuromodulation therapies
utilize medical device technologies to enhance or suppress activity
of the nervous system for the treatment of disease. These
technologies include implantable as well as non-implantable
neuromodulation devices and systems that deliver electrical,
chemical or other agents to reversibly modify brain and nerve cell
activity. The most common neuromodulation therapy is spinal cord
stimulation to treat chronic neuropathic pain. In addition to
chronic pain relief, some examples of neuromodulation therapies
include deep brain stimulation for essential tremor, Parkinson's
disease, dystonia, epilepsy and psychiatric disorders such as
depression, obsessive compulsive disorder and Tourette syndrome;
sacral nerve stimulation for pelvic disorders and incontinence;
vagus nerve stimulation for rheumatoid arthritis; gastric and
colonic stimulation for gastrointestinal disorders such as
dysmotility or obesity; vagus nerve stimulation for epilepsy,
obesity or depression; carotid artery stimulation for hypertension,
and spinal cord stimulation for ischemic disorders such as angina
and peripheral vascular disease.
[0004] Rheumatoid arthritis is an autoimmune disorder that occurs
when the immune system mistakenly attacks body's own tissues.
Unlike the wear and tear damage (due to age and/or extreme sports)
of osteoarthritis, rheumatoid arthritis affects the lining of the
joints, causing a painful swelling that can eventually result in
bone erosion and joint deformity. The inflammation associated with
rheumatoid arthritis is what can damage other parts of the body as
well. While new types of medications have improved treatment
options dramatically, severe rheumatoid arthritis can still cause
physical disabilities. Recently, neuromodulation has been suggested
as a potential treatment option for patients suffering from
rheumatoid arthritis. Specifically, electrical stimulation of the
vagus nerve has shown promise. However, since the vagus nerve is a
heterogeneous bundle of nerve fibers, stimulation of the vagus
nerve may cause inadvertent stimulation of other end-organs
resulting in adverse side effects. From this perspective, the
direct stimulation of the end-organ may have a higher probability
of being more treatment-specific while avoiding or minimizing the
adverse physiological effects.
[0005] In rheumatoid arthritis, this implies that stimulation of
the splenic artery or the splenic artery/nerve plexus (close to the
end-organ) to innervate the spleen may control inflammation while
avoiding or minimizing the adverse side effects. A major challenge
of stimulating a nerve or artery/nerve plexus is to ensure that
optimal stimulation parameters are identified that maximally
control inflammation while avoiding or minimizing any influence on
the functioning of peripheral organs such as blood flow via the
artery. Therefore, the ability to measure stimulus evoked blood
parameter changes locally, for example, measuring blood
oxygenation, blood flow, arterial distension, and blood pressure at
the artery, is important for the success of the neuromodulation
system. Furthermore, optimizing neural stimulation parameters and
identifying the subset of parameters that may cause the inadvertent
side effects is important from a safety perspective. Accordingly,
the need exists for neuromodulation systems and methods that have
the capability to optimize neuromodulation stimulation parameters
based on feedback from stimulus evoked blood parameter changes.
BRIEF SUMMARY
[0006] In various embodiments, a medical device is provided that
comprises a controller configured to provide a first set of
stimulation parameters, and a pulse generator configured to
generate neural stimulation based on the first set of stimulation
parameters. The medical device further comprises a lead body,
including a conductor material connected to the electronics module,
one or more stimulation electrodes connected to the conductor
material and configured to deliver the neural stimulation generated
by the pulse generator to a nerve or artery/nerve plexus, one or
more recording electrodes connected to the conductor material and
configured to: monitor a response to the neural stimulation that
includes electrical impulses traveling through the nerve or
artery/nerve plexus, and send information regarding the electrical
impulses to the controller via the conductive material, and one or
more sensors connected to the conductor material and configured to:
monitor the response to the neural stimulation that includes
blood-based parameters, and send the blood-based parameters to the
controller via the conductive material. The controller is further
configured to modify the first set of the stimulation parameters
based on the blood-based parameters to create a second set of
stimulation parameters, the pulse generator is further configured
to generate modified neural stimulation based on the second set of
stimulation parameters, and the one or more stimulation electrodes
are further configured to deliver the modified neural stimulation
to the nerve or artery/nerve plexus.
[0007] In other embodiments, a medical device is provided that
comprises an implantable neurostimulator, including a housing, a
feedthrough assembly that passes through the housing, and an
electronics module within the housing and connected to the one or
more feedthroughs. The electronics module includes a pulse
generator, a controller, and a memory storing program instructions.
The medical device further comprises a lead assembly including a
lead body including a conductor material, a lead connector that
connects the conductor material to the feedthrough assembly, and
one or more electrodes and one or more sensors connected to the
conductor material. The program instructions, when operated on by
the controller, cause the controller to perform operations
comprising delivering neural stimulation using the pulse generator
and the one or more electrodes based on a first set of stimulation
parameters to a nerve or artery/nerve plexus, monitoring a response
to the neural stimulation that includes monitoring responses of the
nerve or artery/nerve plexus and blood-based parameters of the
artery using the one or more sensors, modifying the first set of
the stimulation parameters based on the blood-based parameters to
create a second set of stimulation parameters, and delivering the
neural stimulation using the pulse generator and the one or more
electrodes based on the second set of the stimulation
parameters.
[0008] In accordance with some aspects, the stimulation parameters
include at least one of: stimulation amplitude, pulse width,
frequency, duty cycle, stimulation waveform shape, and electrode
configuration. Optionally, the blood-based parameters include at
least one of blood flow, blood pressure, and arterial distension,
and the one or more sensors include at least one of: a blood flow
sensor, a blood pressure sensor, and a distension sensor.
[0009] In accordance with some aspects, the one or more sensors
include at least one of: a blood flow sensor, a blood pressure
sensor, and a distension sensor. Optionally, the blood flow sensor
is a Doppler sensor configured to measure blood velocity.
Optionally, the blood flow sensor is an impedance sensor configured
to detect changes in electrical impedance of blood. Optionally, the
blood pressure sensor is an impedance sensor configured to measure
the blood pressure. Optionally, the blood pressure sensor is a
piezoresistive pressure sensor configured to measure the blood
pressure. Optionally, the arterial distension sensor is a
capacitive sensor configured to measure the arterial distension.
Optionally, the arterial distension sensor is a photonic sensor
configured to measure arterial distension based on a change in an
amount of photons transmitted. Optionally, the arterial distension
sensor is a Doppler sensor configured to measure cardiac motion and
artery diameter pulsation.
[0010] In various embodiments, a medical system is provided for
that includes one or more processors and a memory coupled to the
one or more processors. The memory is encoded with a set of
instructions configured to perform a process comprising delivering,
using one or more stimulation electrodes, neural stimulation to a
nerve or artery/nerve plexus based on a first set of stimulation
parameters, monitoring a response to the neural stimulation that
includes monitoring, using one or more recording electrodes,
responses of the nerve or artery/nerve plexus and monitoring, using
one or more sensors, blood-based parameters of the artery,
modifying, using the one or more processors, the first set of the
stimulation parameters based on the blood-based parameters to
create a second set of stimulation parameters, and delivering,
using the one or more stimulation electrodes, the neural
stimulation to the nerve or artery/nerve plexus based on the second
set of the stimulation parameters.
[0011] In accordance with some aspects, the stimulation parameters
include at least one of: stimulation amplitude, pulse width,
frequency, duty cycle, stimulation waveform shape, and electrode
configuration. Optionally, the blood-based parameters include at
least one of blood flow, blood pressure, and arterial distension,
and the one or more sensors include at least one of: a blood flow
sensor, a blood pressure sensor, and a distension sensor.
[0012] In accordance with some aspects, the one or more sensors
include at least one of: a blood flow sensor, a blood pressure
sensor, and a distension sensor. Optionally, the blood flow sensor
is a Doppler sensor configured to measure blood velocity.
Optionally, the blood flow sensor is an impedance sensor configured
to detect changes in electrical impedance of blood. Optionally, the
blood pressure sensor is an impedance sensor configured to measure
the blood pressure. Optionally, the blood pressure sensor is a
piezoresistive pressure sensor configured to measure the blood
pressure. Optionally, the arterial distension sensor is a
capacitive sensor configured to measure the arterial distension.
Optionally, the arterial distension sensor is a photonic sensor
configured to measure arterial distension based on a change in an
amount of photons transmitted. Optionally, the arterial distension
sensor is a Doppler sensor configured to measure cardiac motion and
artery diameter pulsation.
[0013] In accordance with some aspects, the monitoring of the
response to the neural stimulation includes determining whether the
neural stimulation has a physiological effect. Optionally, in
determining whether the neural stimulation has the physiological
effect, the process includes obtaining blood-based parameters and
comparing the blood-based parameters to one or more predetermined
thresholds to determine whether the neural stimulation has an
adverse physiological effect on the blood-based parameters. In
certain embodiments, when the neural stimulation has an adverse
physiological effect, the first set of the stimulation parameters
are modified based on the blood-based parameters to create the
second set of stimulation parameters.
[0014] In accordance with some aspects, the process further
comprises modifying the first set of the stimulation parameters
based on a titration schedule and the blood-based parameters to
create the second set of stimulation parameters. Optionally, the
process further includes determining whether adequate adaptation is
achieved. In certain embodiments, the adequate adaptation is
achieved when at least one of the following objectives is achieved:
acceptable levels for the blood-based parameters, a target
intensity level for one or more of the stimulation parameters, and
a target physiological effect. When the adequate adaptation is not
achieved, the first set of the stimulation parameters are modified
based on the titration schedule and the blood-based parameters to
create the second set of stimulation parameters.
[0015] In various embodiments, a method is provided for that
provides neurostimulation. The method includes delivering, by a
computing system, neural stimulation to a nerve or artery/nerve
plexus based on a first set of stimulation parameters, monitoring,
by the computing system, a response to the neural stimulation that
includes monitoring responses of the nerve or artery/nerve plexus
and blood-based parameters of the artery, modifying, by the
computing system, the first set of the stimulation parameters based
on the blood-based parameters to create a second set of stimulation
parameters, and delivering, by the computing system, the neural
stimulation based on the second set of the stimulation
parameters.
[0016] In accordance with some aspects, the blood-based parameters
include at least one of blood flow, blood pressure, and arterial
distension. In some embodiments, the monitoring the response to the
neural stimulation includes determining whether the neural
stimulation has a physiological effect. In some embodiments, the
determining whether the neural stimulation has the physiological
effect includes obtaining the blood-based parameters and comparing
the blood-based parameters to one or more predetermined thresholds
to determine whether the neural stimulation has an adverse
physiological effect on the blood-based parameters. In certain
embodiments, when the neural stimulation has the adverse
physiological effect, the first set of the stimulation parameters
is modified based on the blood-based parameters to create the
second set of stimulation parameters.
[0017] In accordance with some aspects, the method further includes
modifying the first set of the stimulation parameters based on a
titration schedule and the blood-based parameters to create the
second set of stimulation parameters. In some embodiments, the
method further includes determining whether adequate adaptation is
achieved. In certain embodiments, the adequate adaptation is
achieved when at least one of the following objectives is achieved:
acceptable levels for the blood-based parameters, a target
intensity level for one or more of the stimulation parameters, and
a target physiological effect. When the adequate adaptation is not
achieved, the first set of the stimulation parameters is modified
based on the titration schedule and the blood-based parameters to
create the second set of stimulation parameters.
[0018] In accordance with some aspects, the monitoring of the
response to the neural stimulation includes determining whether the
neural stimulation has a physiological effect. Optionally, the
determination of whether the neural stimulation has the
physiological effect includes obtaining the blood-based parameters
and comparing the blood-based parameters to one or more
predetermined thresholds to determine whether the neural
stimulation has an adverse physiological effect on the blood-based
parameters. In various embodiments, when the neural stimulation has
the adverse physiological effect, the first set of the stimulation
parameters is modified based on the blood-based parameters to
create the second set of stimulation parameters.
[0019] In accordance with some aspects, the method further includes
modifying the first set of the stimulation parameters based on a
titration schedule and the blood-based parameters to create the
second set of stimulation parameters. Optionally, the method
further includes determining whether adequate adaptation is
achieved. The adequate adaptation may be achieved when at least one
of the following objectives is achieved: acceptable levels for the
blood-based parameters, a target intensity level for one or more of
the stimulation parameters, and a target physiological effect. In
various embodiments, when adequate adaptation is not achieved, the
first set of the stimulation parameters is modified based on the
titration schedule and the blood-based parameters to create the
second set of stimulation parameters.
[0020] In various embodiments, a non-transitory computer readable
storage medium is provide for that stores instructions that, when
executed by one or more processors of computing system, cause the
computing system to perform operations including delivering neural
stimulation to a nerve or artery/nerve plexus based on a first set
of stimulation parameters, monitoring a response to the neural
stimulation that includes monitoring responses of the nerve or
artery/nerve plexus and blood-based parameters of the artery,
modifying the first set of the stimulation parameters based on the
blood-based parameters to create a second set of stimulation
parameters, and delivering the neural stimulation based on the
second set of the stimulation parameters.
[0021] In accordance with some aspects, the monitoring of the
response to the neural stimulation includes determining whether the
neural stimulation has a physiological effect. Optionally, the
determination of whether the neural stimulation has the
physiological effect includes obtaining the blood-based parameters
and comparing the blood-based parameters to one or more
predetermined thresholds to determine whether the neural
stimulation has an adverse physiological effect on the blood-based
parameters. In various embodiments, when the neural stimulation has
the adverse physiological effect, the first set of the stimulation
parameters is modified based on the blood-based parameters to
create the second set of stimulation parameters.
[0022] In accordance with some aspects, the operations further
include modifying the first set of the stimulation parameters based
on a titration schedule and the blood-based parameters to create
the second set of stimulation parameters. Optionally, the
operations further include determining whether adequate adaptation
is achieved. Adequate adaptation is achieved when at least one of
the following objectives is achieved: acceptable levels for the
blood-based parameters, a target intensity level for one or more of
the stimulation parameters, and a target physiological effect. In
various embodiments, when adequate adaptation is not achieved, the
first set of the stimulation parameters is modified based on the
titration schedule and the blood-based parameters to create the
second set of stimulation parameters.
[0023] In various embodiments, a system is provided for that
includes a neurostimulator configured to deliver stimulation for a
nerve or artery/nerve plexus based on a first set of stimulation
parameters, one or more sensors configured to monitor a response to
the stimulation that includes monitoring responses of the nerve or
artery/nerve plexus and blood-based parameters of the artery, and a
controller configured to modify the first set of the stimulation
parameters based on the blood-based parameters to create a second
set of stimulation parameters. The neurostimulator is further
configured to deliver the stimulation based on the second set of
the stimulation parameters.
[0024] In accordance with some aspects, the neurostimulator, the
one or more sensors, and the controller are provided within a
distributed environment, and at least the neurostimulator and the
controller are in communication via a wireless communication
network.
[0025] In accordance with other aspects, the neurostimulator, the
one or more sensors, and the controller are provided within a
distributed environment, and at least the neurostimulator and the
one or more sensors are in communication via a wireless
communication network.
[0026] In various embodiments, a medical system is provided for
that includes one or more processors and a memory coupled to the
one or more processors. The memory is encoded with a set of
instructions configured to perform a process comprising delivering,
using one or more stimulation electrodes, neural stimulation to a
nerve or artery/nerve plexus based on a first set of stimulation
parameters, monitoring a response to the neural stimulation that
includes monitoring, using one or more recording electrodes,
responses of the nerve or artery/nerve plexus and modifying, using
the one or more processors, the first set of the stimulation
parameters based on the responses of the nerve or artery/nerve
plexus and the blood-based parameters to create a second set of
stimulation parameters, and delivering, using the one or more
stimulation electrodes, the neural stimulation to the nerve or
artery/nerve plexus based on the second set of the stimulation
parameters.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] The present invention will be better understood in view of
the following non-limiting figures, in which:
[0028] FIG. 1 shows an shows a neuromodulation system in accordance
with some aspects of the present invention;
[0029] FIG. 2 shows an shows an implantable neuromodulation system
in accordance with some aspects of the present invention; and
[0030] FIGS. 3-5 show exemplary flows for titrating neuromodulation
therapy and providing neuromodulation therapy in accordance with
some aspects of the present invention.
DETAILED DESCRIPTION
[0031] I. Introduction
[0032] The following disclosure describes neuromodulation systems
and methods for affecting neural stimulation efficiency and/or
efficacy. Various embodiments of systems and/or methods described
herein may be directed toward controlling, adjusting, modifying,
and/or varying one or more manners in which neural stimulation may
be applied or delivered to a patient, thereby possibly 1)
influencing, affecting, maintaining, or improving neural
stimulation efficacy; and/or 2) influencing, affecting,
maintaining, improving, minimizing, or preventing physiological
effects caused by the neural stimulation. As used herein,
neuromodulation means the alteration of nerve activity through
targeted delivery of a stimulus, such as electrical stimulation or
chemical agents, to specific neurological sites in the body. A
neurostimulator is a device or system having electronic circuit
components and/or software configured to deliver the stimulus to
the specific neurological site (e.g., a nerve or artery/nerve
plexus) via an electrode assembly. One or more portions of the
neurostimulator may be implanted in a patient's body. For example,
an implanted pulse generator may be encased in a hermetically
sealed housing and surgically implanted in a patient. The electrode
assembly may be included as a portion of the housing or provided in
a separate location and attached to the pulse generator via one or
more leads. The stimulus, stimulation, or neural stimulation may
comprise electrical, chemical, optical, ultrasonic, and/or magnetic
stimulation signals, and may be defined in accordance with spatial,
temporal, electrical, and/or magnetic signal parameters,
properties, and/or characteristics. The neural stimulation is
generally delivered or applied to the patient in accordance with a
treatment protocol. Typically, the treatment protocol specifies an
optimal or best set of parameters directed toward maximally
alleviating one or more patient symptoms through neural stimulation
applied in a continuous, generally continuous, or nearly continuous
manner.
[0033] In various embodiments, the present invention is directed to
a neuromodulation device or system including a neurostimulator to
deliver stimulation to a nerve or artery/nerve plexus, one or more
sensors to sense physiological responses to the stimulation, and a
controller to control parameters of the stimulation based on
physiological responses. A technological problem associated with
conventional neuromodulation devices and systems, however, is that
they do not have the ability to sense both the physiological
responses of the nerve or artery/nerve plexus to the stimulation
and blood-based parameter changes of the artery, nor provide
adjustment of the stimulation parameters based on the physiological
responses of the nerve or artery/nerve plexus, changes in the
blood-based parameters, or a combination thereof. These systems and
approaches are both inefficient in effectiveness and unreasonably
risky with respect to potential for neural damage and resulting
physiological effects.
[0034] To address these technological problems, the present
invention is directed to neuromodulation devices or systems that
have a neural interface comprising one or more contacts or sensors
that can be used to monitor nerve responses and measure at least
one of: blood flow, blood pressure, and arterial distension. The
monitored nerve response and measurement of blood flow, blood
pressure, and/or arterial distension can then be used by the
neuromodulation devices or systems to determine whether a patient
is experiencing a physiological effect due to the neural
stimulation (e.g., an adverse physiological effect such as
decreased blood flow along with increased arterial distension may
suggest decreases in oxygenation in the blood that may be caused
due to an occlusion in the artery as a result of the neural
stimulation). In some embodiments, the neuromodulation devices or
systems provide on-demand neuromodulation therapy using a closed
control system or closed-loop system (feedback control) where an
open loop system is used as the forward path but one or more
feedback loops or paths are included between the output signal and
the input signal. For example, the modification of stimulation
parameters and subsequent burst or periodic release of neural
stimulation from one or more electrodes can be triggered based on
an electrical recording from one or more recording electrodes
and/or a measurement of blood flow, blood pressure, and/or arterial
distension from one or more sensors. As used herein, when an action
is "triggered by" or "based on" something, this means the action is
triggered or based at least in part on at least a part of the
something.
[0035] One illustrative embodiment of the present disclosure
comprises a medical system including one or more processors and a
memory coupled to the one or more processors. The memory is encoded
with a set of instructions configured to perform a process
comprising delivering, using one or more stimulation electrodes,
neural stimulation to a nerve or artery/nerve plexus based on a
first set of stimulation parameters, monitoring a response to the
neural stimulation that includes monitoring, using one or more
recording electrodes, responses of the nerve or artery/nerve plexus
and monitoring, using one or more sensors, blood-based parameters
of the artery, modifying, using the one or more processors, the
first set of the stimulation parameters based on the blood-based
parameters to create a second set of stimulation parameters, and
delivering, using the one or more stimulation electrodes, the
neural stimulation to the nerve or artery/nerve plexus based on the
second set of the stimulation parameters. Another illustrative
embodiment of the present disclosure comprises a medical device
including an implantable neurostimulator having a housing, a
feedthrough assembly that passes through the housing, and an
electronics module within the housing and connected to the one or
more feedthroughs. The electronics module includes a pulse
generator, a controller, and a memory storing program instructions.
The medical device further includes a lead assembly having a lead
body including a conductor material, a lead connector that connects
the conductor material to the feedthrough assembly, one or more
electrodes and one or more sensors connected to the conductor
material. In certain embodiments, the program instructions when
operated on by the controller, cause the controller to perform
operations comprising: delivering neural stimulation using the
pulse generator and the one or more electrodes based on a first set
of stimulation parameters to a nerve or artery/nerve plexus,
monitoring a response to the neural stimulation that includes
monitoring responses of the nerve or artery/nerve plexus and
blood-based parameters of the artery using the one or more sensors,
modifying the first set of the stimulation parameters based on the
blood-based parameters to create a second set of stimulation
parameters, and delivering the neural stimulation using the pulse
generator and the one or more electrodes based on the second set of
the stimulation parameters.
[0036] Advantageously, these approaches provide neuromodulation
devices and systems that are capable of detecting and/or tracking
effects due to neuromodulation therapy and closing the loop on
stimulation parameters. For example, the neuromodulation devices or
systems described herein can adjust stimulation parameters to
achieve therapeutic benefit while minimizing adverse physiological
effects. Further, the neuromodulation devices or systems described
herein can make the titration of neuromodulation therapy
personalized to each individual patient.
[0037] II. Neuromodulation Devices or Systems
[0038] FIG. 1 shows a neuromodulation system 100 in accordance with
some aspects of the present invention. In some embodiments, the
neuromodulation system 100 includes a neurostimulator 105, one or
more sensors 110, and a controller 115. The neurostimulator 105
includes software and/or electronic circuit components that record
a signal from a nerve or artery/nerve plexus and generate a signal
to deliver a voltage, current, optical, or ultrasonic stimulation
to a nerve or artery/nerve plexus. In certain embodiments, the
neurostimulator 105 is implanted within a patient at a location
remote from or near to the nerve or artery/nerve plexus and is
configured to record and deliver the signal to the nerve or
artery/nerve plexus via one or more electrodes attached to the
nerve or artery/nerve plexus. As used herein, remote means further
than 6 inches, for example 8 inches from the target of stimulation
such as the nerve or artery/nerve plexus, while near means within 6
inches, for example within 4 inches of the target of stimulation
such as the nerve or artery/nerve plexus. In other embodiments, the
neurostimulator 105 is external to the patient and configured to
record and deliver the signal to the nerve or artery/nerve plexus
via one or more electrodes implanted within the patient and
attached to the nerve or artery/nerve plexus.
[0039] The one or more sensors 110 include software and/or
electronic circuit components that sense physiological responses to
the voltage, current, optical, or ultrasonic stimulation. The
physiological responses may include responses of the nerve or
artery/nerve plexus to the stimulation, blood-based parameter
changes of the artery, or a combination thereof. In certain
embodiments, the one or more sensors 110 are implanted within a
patient at a location near to or attached to the nerve or
artery/nerve plexus and are configured to receive signal(s)
indicative of the physiological responses (e.g., nerve responses
and blood-based parameter changes of the artery).
[0040] The controller 115 includes software and/or electronic
circuit components that determine, sense, or record electrical
activity and physiological responses via the electrodes and one or
more sensors 110, control stimulation parameters of the
neurostimulator 105 (e.g., control stimulation parameters based on
feedback from desired or adverse physiological effects), and/or
causes delivery of the stimulation via the neurostimulator 105 and
electrodes. In certain embodiments, the controller 115 is implanted
within a patient at a location remote from or near to the nerve or
artery/nerve plexus and is in communication with the
neurostimulator 105 and the one or more sensors 110 via a wired or
wireless connection. In other embodiments, the controller 115 is
external to the patient and is in communication with the
neurostimulator 105 and the one or more sensors 110 via a wired or
wireless connection.
[0041] While the neurostimulator 105, one or more sensors 110, and
controller 115 are described herein as an implantable
neuromodulation system with respect to several described
embodiments, it should be understood that various systems and
arrangements comprising the neurostimulator 105, one or more
sensors 110, and controller 115 are contemplated without departing
from the spirit and scope of the present disclosure. For example,
the neuromodulation system 100 may include the neurostimulator 105,
one or more sensors 110, and controller 115 within a distributed
environment such as a cloud computing environment, and the
neurostimulator 105, one or more sensors 110, and controller 115
may be in communication via one or more communication networks 120.
Examples of communication networks 120 include, without
restriction, the Internet, a wide area network (WAN), a local area
network (LAN), an Ethernet network, a public or private network, a
wired network, a wireless network, and the like, and combinations
thereof.
[0042] FIG. 2 shows a neuromodulation system 200 in accordance with
some aspects of the present invention. In various embodiments, the
neuromodulation system 200 includes an implantable neurostimulator
205 (e.g., a neurostimulator 105 as described with respect to FIG.
1) and a lead assembly 210. The implantable neurostimulator 205 may
include a housing 212, a feedthrough assembly 213, a power source
214, an antenna 215, and an electronics module 220 (e.g., a
computing system). The housing 105 may be comprised of materials
that are biocompatible such as bioceramics or bioglasses for radio
frequency transparency, or metals such as titanium. In accordance
with some aspects of the present invention, the size and shape of
the housing 212 are selected such that the neurostimulator 205 can
be implanted within a patient. The feedthrough assembly 213 is
attached to a hole in a surface of the housing 212 such that the
housing 212 is hermetically sealed. The feedthrough assembly 213
may include one or more feedthroughs (i.e., electrically conductive
elements, pins, wires, tabs, pads, etc.) mounted within and
extending through the surface of the housing 212 or a cap from an
interior to an exterior of the housing 212. The power source 214
may be within the housing 212 and connected (e.g., electrically
connected) to the electronics module 220 to power and operate the
components of the electronics module 220. The antenna 215 may be
connected (e.g., electrically connected) to the electronics module
220 for wireless communication with external devices via, for
example, radiofrequency (RF) telemetry.
[0043] In some embodiments, the electronics module 220 is connected
(e.g., electrically connected) to interior ends of the feedthrough
assembly 213 such that the electronics module 220 is able to apply
a signal or electrical current to leads of the lead assembly 210
connected to exterior ends of the feedthrough assembly 213. The
electronics module 220 includes discrete and/or integrated
electronic circuit components that implement analog and/or digital
circuits capable of producing the functions attributed to the
neuromodulation devices or systems described herein. In various
embodiments, the electronics module 215 includes software and/or
electronic circuit components such as a pulse generator 225 that
generates a signal to deliver a voltage, current, optical, or
ultrasonic stimulation to a nerve or artery/nerve plexus via
electrodes, a controller 230 (e.g., a controller 115 as described
with respect to FIG. 1) that determines, senses, or records
electrical activity and physiological responses via the electrodes
and sensors, controls stimulation parameters of the pulse generator
225 (e.g., control stimulation parameters based on feedback from
the physiological responses), and/or causes delivery of the
stimulation via the pulse generator 225 and electrodes, and a
memory 235 with program instructions operable on by the pulse
generator 225 and the controller 230 to perform one or more
processes described herein.
[0044] In certain embodiments, the electronics module 220 is a
printed circuit board with an interposer in combination with
discrete and/or integrated electronic circuit components such as
application specific integrated circuits (ASICs). The electronics
module 220 can be remotely accessed following implant through an
external programmer, such as an external computing device. For
example, the external programmer can be used by healthcare
professionals to check and program the electronics module 220 after
implantation in a patient and to adjust stimulation parameters
during a stimulation process, e.g., providing an initial set of the
stimulation parameters. The external programmer may communicate
with the electronics module 220 via wired or wireless communication
methods, such as, e.g., wireless radio frequency transmission.
[0045] The pulse generator 225 is configured to set or adjust one
or more stimulation parameters based on commands from the
controller 230. Examples of stimulation parameters include burst
duration, burst interval, stimulation amplitude (e.g., stimulation
strength), pulse width, frequency, duty cycle, stimulation waveform
shape, and electrode configuration. In some embodiments, neural
stimulation is delivered via the pulse generator 225 in a
stimulation burst, which is a train of stimulation pulses
programmed with any combination of stimulation amplitude, pulse
width, stimulation waveform shape, and signal frequency.
Stimulation bursts can be characterized by burst durations and
burst intervals. Burst duration is the length of time that a burst
lasts. Burst interval can be identified by the time between the
start of successive bursts. The pattern of bursts can include any
combination of burst durations and burst intervals. A simple burst
pattern with one burst duration and burst interval can continue
periodically for a programmed period or can follow a more
complicated schedule. The programmed pattern of bursts can be
composed of multiple burst durations and burst interval sequences.
The programmed pattern of bursts can be characterized by a duty
cycle, which refers to a repeating cycle of neural stimulation ON
for a fixed time and neural stimulation OFF for a fixed time.
[0046] In other embodiments, the pulse generator 225 is adapted to
change electrode configuration as part of the neural stimulation in
combination with or separate from changes to the other stimulation
parameters such as burst duration, burst interval, stimulation
amplitude, pulse width, frequency, stimulation waveform shape, and
duty cycle. For example, the implantable neurostimulator 205 may
include electrode configuration switches, and the switches may be
configured to deliver neural stimulation from the pulse generator
225 to selected one or more electrodes. In some embodiments, the
pulse generator 225 is configured to control the switches to
generate a signal or electrical current to deliver neural
stimulation to a nerve or artery/nerve plexus based on one or more
stimulation parameters via a desired electrode configuration. In
other embodiments, the controller 230 is configured to control the
switches and cause the pulse generator 225 to generate a signal or
electrical current to deliver neural stimulation to a nerve or
artery/nerve plexus based on one or more stimulation parameters via
a desired electrode configuration
[0047] The controller 230 is capable of being implemented using
hardware, software, firmware or combinations thereof. In various
embodiments, the controller 230 includes one or more processors to
perform instructions embedded in the memory 235 to perform
functions associated with the neural stimulation therapy, such as
performing neural stimulation based on a stimulation or titration
schedule stored in the memory 235 and/or based on feedback received
via the electrodes and sensors. The controller 230 is in
communication with the pulse generator 225 and the one or more
sensors. For example, the controller 230 may be configured to
perform functions associated with the neural stimulation therapy
including (i) delivering, using a pulse generator 225 and at least
one stimulation electrode, neural stimulation based on a first set
of the stimulation parameters, (ii) monitoring a response to the
neural stimulation that includes (a) monitoring, using one or more
sensors such as a recording electrode, electrographic activity of
the nerve or artery/nerve plexus and (b) monitoring, using one or
more sensors such as a blood pressure sensor blood-based parameter
changes of an artery, or a combination thereof, (iii) modifying,
using a processor, the first set of the stimulation parameters
based on the monitoring to create a second set of stimulation
parameters, and (iv) delivering, using the pulse generator 225 and
at least one stimulation electrode, the neural stimulation based on
the second set of the stimulation parameters.
[0048] The memory 235 may be a non-transitory machine readable
storage medium having instructions stored thereon that when
executed by a processor (e.g., a processor of the controller 230)
causes the processor to perform one or more operations such as
generation of a signal or electric current based on one or more
stimulation parameters. In some embodiments, the memory 235
includes instructions operable on by the controller 230 to cause
the on-demand stimulation therapy, receive therapy feedback and
modify the therapy based on the feedback. The modification may
include gradually increasing or decreasing the intensity of the
neural stimulation signal to a desired or target therapeutic level
while taking into consideration blood-based parameter changes of an
artery. In other embodiments, the memory 235 includes instructions
operable on by the controller 230 to control titration of the
therapy. During the titration, the neural stimulation signal may be
delivered using different combinations of stimulation parameters
and the effects of the stimulation (e.g., the desired physiological
effects and/or adverse physiological effects such as
increased/decreased blood pressure) are evaluated for the different
parameter combinations to determine an optimal set or combination
of stimulation parameters that provide the desired therapeutic
effect while minimizing or preventing adverse physiological
effects. In yet other embodiments, the memory includes instructions
operable on by the controller to adjust or select a combination of
stimulation parameters that is determined to be effective at
generating a desired physiological effect while using feedback from
blood-based parameter changes to minimize or prevent adverse
physiological effects such as restricted blood flow.
[0049] The lead assembly 210 may include a lead body 240, a lead
connector 245, one or more electrodes 250, and one or more sensors
255. In some embodiments, the lead connector 245 is bonding
material that bonds conductor material of the lead body 240 to the
electronics module 220 of the implantable neurostimulator 205 via
the feedthrough assembly 213. The bonding material may be a
conductive epoxy or a metallic solder or weld such as platinum. In
other embodiments, the lead connector 245 is conductive wire or tab
(e.g., a wire or tab formed of copper, silver, or gold) that bonds
conductor material of the lead body 240 to the electronics module
220 of the implantable neurostimulator 205. In alternative
embodiments, the implantable neurostimulator 205 and the lead body
240 may be designed to connect with one another via a lead
connector 245 such as a pin and sleeve connector, snap and lock
connector, flexible printed circuit connectors, or other means
known to those of ordinary skill in the art.
[0050] The lead body 240 may include one or more leads of
conductive material and insulator. The one or more leads carry
electrical conductors that allow electrical coupling of the
electronics module 220 to the one or more electrodes 250 via the
lead connector 245. In some examples the one or more leads are
extruded with a dielectric material such as a polymer having
suitable dielectric, flexibility and biocompatibility
characteristics. Polyurethane, polycarbonate, silicone,
polyethylene, fluoropolymer and/or other medical polymers,
copolymers and combinations or blends can be used. In some
embodiments, the conductive material for the one or more leads may
serve as a strengthening member onto which the body of the lead is
extruded. For example, a distal electrode may couple to a centrally
located wire on which the body of lead is extruded. The conductive
material may be any suitable conductor such as stainless steel,
silver, copper or other conductive materials, which may have
separate coatings or sheathing for anticorrosive, insulative and/or
protective reasons. The conductive material may take various forms
including wires, drawn filled tubes, helical coiled conductors,
microwires, and/or printed circuits, for example.
[0051] The one or more electrodes 250 may be connected to the
conductor material of the lead body 240 via the one or more leads.
In some embodiments, the one or more electrodes 250 are placed
around, within or adjacent to a nerve or artery/nerve plexus to:
(i) stimulate the nerve or artery/nerve plexus and/or (ii) sense
electrical impulses traveling through the nerve or artery/nerve
plexus. For example, a peripheral nerve cuff placed around a nerve
or artery/nerve plexus may comprise an array of recording and
stimulation electrodes 250. The one or more electrodes 250 may be
formed of a conductive material such as a copper, silver, gold,
platinum, stainless steel, nickel-cobalt base alloy,
platinum-iridium alloy, brass, bronze, aluminum, etc., and take the
form of book electrodes, cuff electrodes, spiral cuff electrodes,
epidural electrodes, helical electrodes, probe electrodes, linear
electrodes, paddle electrodes, and intraneural electrodes, for
example.
[0052] The one or more sensors 255 may be connected to the
conductor material of the lead body 240 via the one or more leads.
In some embodiments, the one or more sensors 255 are placed around,
within or adjacent to a nerve or artery/nerve plexus to sense
physiological response of the nerve or artery/nerve plexus to the
voltage, current, optical, or ultrasonic stimulation. The
physiological responses may include nerve responses (e.g., desired
or targeted physiological effects), blood-based parameter changes
(e.g., blood pressure changes), or a combination thereof. In
various embodiments the one or more sensors 255 used to sense nerve
responses such as electrical impulses traveling through the nerve
or artery/nerve plexus include one or more recording electrodes. In
various embodiments the one or more sensors 255 used to sense the
blood-based parameter changes include one or more of: (i) a blood
flow sensor such as a Doppler sensor or impedance sensor, (ii) a
blood pressure sensor such as a piezoresistive pressure sensor or
impedance sensor, and (iii) a distension sensor such as a
capacitive sensor, a Doppler sensor, or a photonic sensor.
[0053] The arterial system has two interrelated hemodynamic
functions: (i) a conduit function to deliver an adequate blood
supply from the heart to peripheral tissues, and (ii) a cushioning
or dampening function to dampen blood flow and pressure
oscillations caused by the intermittent character of the left
ventricle ejection ensuring peripheral organ perfusion at steady
flow and pressure. Neural stimulation to a nerve or artery/nerve
plexus such as the peripheral nerves at the splenic artery or the
splenic artery/nerve plexus (close to the end-organ) to innervate
the spleen may control inflammation; however, the neural
stimulation may also adversely affect the conduit and/or
cushioning/dampening function of the artery. In order to ensure
that the neural stimulation is delivered in a manner that that
achieves the desired physiological effect while minimizing or
preventing adverse physiological effects to the artery, various
embodiments discussed herein monitor one or more blood-based
parameter parameters, for example, blood flow, blood pressure, and
arterial distension, of the artery to optimize neuromodulation
stimulation parameters based on feedback from stimulus evoked blood
parameter changes.
[0054] In some embodiments, a blood flow sensor such as a Doppler
sensor is configured to measure blood velocity by detecting a
difference in frequency between an emitted burst of ultrasound and
returning echoes from moving blood. For example, in a
pulsed-Doppler system the sample volume can be adjusted in depth by
varying the time delay between transmission of a short ultrasonic
burst and sampling of the returning echoes. The resulting Doppler
signal, which is usually in the audible range, is a summation of
the Doppler-shifted echoes from many blood cells moving at
different velocities, and the spectrum of frequencies represents
the distribution of red cell velocities within the sample volume.
The red cell velocities can be correlated to a measurement of
overall velocity of blood flow within the artery.
[0055] In other embodiments, a blood flow sensor such as an
impedance sensor is configured to detect changes in the electrical
impedance of blood. For example, there is a strong correlation
between electrical impedance and viscosity of blood. If a person
has inflammation (such as with rheumatoid arthritis), then there is
an increased risk that the red blood cells will aggregate. This
aggregation increases the risk for heart attack or strokes. Another
important factor for aggregation beyond inflammation is the
viscosity of blood. In particular, plasma resistance and cell
membrane capacitance, which are both factors for electrical
impedance, are affected by blood viscosity. The changes in the one
or more parameters including plasma resistance, cell membrane
capacitance, and overall electrical impedance may be measured as
the viscosity of the blood and correlated to overall velocity of
blood flow within the artery.
[0056] In some embodiments, a pressure sensor such as an impedance
sensor is configured to measure blood pressure. For example, blood
pressure within an artery can be determined based on the
measurement of a pulse wave velocity. The pulse wave velocity is
the velocity at which pressure pulses propagate along the arterial
wall. The pulse wave velocity may be measured and correlated to
changes in the blood pressure.
[0057] In other embodiments, a pressure sensor such as
piezoresistive pressure sensor is configured to measure blood
pressure. For example, a pressure sensor may include a diaphragm
formed on a substrate (e.g., silicon), which bends with applied
pressure. A deformation occurs in the crystal lattice of the
diaphragm because of the bending. This deformation causes a change
in the band structure of piezoresistors that may be placed on the
diaphragm, leading to a change (i.e., increase or decrease
according to orientation of the piezoresistors) in the resistivity
of the material. The change in resistivity may be measured and
correlated to blood pressure.
[0058] In some embodiments, a distension sensor such as a
capacitive sensor is configured to measure arterial distension. For
example, a distension sensor may include an oscillator and a
capacitor. As the capacitor changes its capacitance in accordance
with the change in blood pressure within the artery, the frequency
of the oscillator changes as well. The change in resonant frequency
(inclusive of the associative inductance or capacitance in low
frequency, or self-resonant in high frequency) is a function of the
change in distension to pressure applied to the artery, and may be
measured and correlated to arterial distension.
[0059] In other embodiments, the distension sensor such as a
photonic sensor is configured to measure arterial distension. For
example, the distension sensor may include stretchable
optoelectronic sensors applied to the artery that are capable of
detecting distension of the arterial wall based on transmission
photoplethysmography. Photoplethysmography is performed by
detecting a change in amount of photons transmitted across a
distending artery over a cardiac cycle. The change in amount of
photons transmitted may be measured and correlated to arterial
distension.
[0060] In yet other embodiments, a distension sensor such as a
Doppler sensor is configured to measure cardiac motion and artery
diameter pulsation, which when combined with blood pressure may
provide an index of vessel compliance. For example, the Doppler
sensor may be configured to measure the phase of blood echoes that
advance (or recede) continuously to generate the Doppler shift
frequency. Echoes from slower moving solid structures such as blood
vessel walls that move back and forth generate phase signals which
advance and recede with each cardiac cycle. Under optimal
conditions, the Doppler sensor can resolve about 1.degree. of phase
or 0.1 .mu.m of tissue motion and can determine arterial distension
continuously throughout a cardiac cycle.
[0061] While the one or more sensors 255 has been described at some
length and with some particularity with respect to several
described embodiments, it is not intended that the sensors be
limited to any such particular technology or particular embodiment.
Instead, it should be understood that the described embodiments are
provided as examples of sensors, and the one or more sensors 255
are to be construed with the broadest sense to include variations
of sensors listed above, as well as other variations that are well
known to those of ordinary skill in the art.
[0062] III. Methods for Delivering Neuromodulation
[0063] FIGS. 3-5 depict simplified flowcharts depicting processing
performed for delivering neuromodulation according to embodiments
of the present invention. As noted herein, the flowcharts of FIGS.
3-5 illustrate the architecture, functionality, and operation of
possible implementations of systems, methods, and computer program
products according to various embodiments of the present invention.
In this regard, each block in the flowchart or block diagrams may
represent a module, segment, or portion of code, which comprises
one or more executable instructions for implementing the specified
logical functions. It should also be noted that, in some
alternative implementations, the functions noted in the block may
occur out of the order noted in the figures. For example, two
blocks shown in succession may, in fact, be executed substantially
concurrently, or the blocks may sometimes be executed in the
reverse order, depending upon the functionality involved. It will
also be noted that each block of the block diagrams and/or
flowchart illustration, and combination of blocks in the block
diagrams and/or flowchart illustration, can be implemented by
special purpose hardware-based systems that perform the specified
functions or acts, or combinations of special purpose hardware and
computer instructions
[0064] FIG. 3 depicts a simplified flowchart 300 illustrating a
titration process used to gradually increase stimulation intensity
(i.e., a combination of one or more of the stimulation parameters)
to a desired therapeutic level. As will be described in greater
detail below, a desired therapeutic level may be defined based on a
composite target intensity level comprising one or more of the
following: a target level for one or more of the stimulation
parameters and a target physiological effect. If the stimulation
intensity is increased too quickly or beyond a certain threshold,
which can be patient dependent, the patient may experience adverse
physiological effects, such as an increase/decrease in blood
pressure or blood flow. The titration process gradually increases
stimulation intensity within a tolerable level, and maintains that
intensity for a period of time to permit the patient to adjust to
each increase in intensity, thereby gradually increasing the
stimulation intensity towards a desired physiological effect while
monitoring for adverse physiological effects. The titration process
continues until adequate adaptation is achieved. In various
embodiments, adequate adaptation includes achieving one or more of
the following objectives: acceptable levels for the blood-based
parameter parameters, a target intensity level, and a target
physiological effect. As will be described in greater detail below,
adequate adaptation may be determined based on a composite
threshold comprising one or more of the following: an acceptable
level for one or more blood-based parameters, a target intensity
level for one or more stimulation parameters, and a target
physiological effect. In some embodiments, the titration process is
automated and is executed by the implanted device without manual
adjustment of the stimulation intensity by the patient or health
care provider.
[0065] In step 305, a neuromodulation system (e.g., neuromodulation
system 100 described with respect to FIG. 1), including an
implantable neurostimulator and a lead assembly is implanted in a
patient. In some embodiments, electrodes of the lead assembly are
connected to a nerve or artery/nerve plexus such as the peripheral
nerves near the splenic artery or the splenic artery/nerve plexus.
In step 310, a stimulation therapy process is initiated. In some
embodiments, the stimulation therapy is initiated after an optional
post-surgery recovery period (e.g., a number of days/weeks), during
which time no stimulation therapy occurs. In alternative
embodiments, the stimulation therapy is initiated shortly (e.g.,
hours) or immediately after implantation. Initiation of the
stimulation therapy may include obtaining or generating an initial
set of stimulation parameters and providing stimulation to the
patient using the initial set of stimulation parameters. The
initial set of stimulation parameters may comprise one or more of
an initial burst duration, initial burst interval, initial
stimulation amplitude, initial pulse width, initial frequency,
initial duty cycle, initial stimulation waveform shape, and initial
electrode configuration. The various initial parameter settings may
vary, but may be selected so that one or more of the parameters are
set at levels below a predefined target parameter set level, such
that the titration process is used to gradually increase the
intensity parameters to achieve adequate adaptation. In some
embodiments, the initial burst duration, the initial burst
interval, the initial frequency, and initial electrode
configuration are set at target levels or configurations, while the
initial stimulation amplitude, initial pulse width, stimulation
waveform shape, and initial duty cycle are set below their
respective target levels. In other embodiments, the initial
electrode configuration is set at a target level or configuration,
while the initial burst duration, the initial burst interval, the
initial frequency, the initial stimulation amplitude, the initial
pulse width, stimulation waveform shape, and the initial duty cycle
are set below their respective target levels.
[0066] In step 315, stimulation therapy is provided using the
initial set of stimulation parameters and titrated by setting or
adjusting the stimulation parameters using a titration schedule to
obtain or generate subsequent sets of stimulation parameters with
the goal of achieving adequate adaptation. In some embodiments, the
titration process includes delivering stimulation using a
neurostimulator based on a set of stimulation parameters,
monitoring a response to the stimulation that includes monitoring
of nerve responses, blood-based parameter changes, or a combination
thereof, modifying one or more of the stimulation parameters based
on a titration schedule, the nerve responses, and/or the
blood-based parameter changes to create a subsequent set of
stimulation parameters, and delivering the neural stimulation using
the neurostimulator based on the subsequent set of stimulation
parameters. This process may be repeated until adequate adaptation
is achieved. In some embodiments, adequate adaptation includes
achieving one or more of the following objectives: acceptable
levels for the blood-based parameters, a target intensity level for
one or more stimulation parameters, and a target physiological
effect. The achievement of one or more of these objectives
determines the stimulation intensity including a therapeutic set of
stimulation parameters to be used for subsequent treatment doses
delivered during the remainder of stimulation therapy in step 320,
as further described herein with respect to FIG. 5.
[0067] FIG. 4 depicts a simplified flowchart 400 illustrating a
detailed titration process used to gradually increase stimulation
intensity to a desired therapeutic level. In some embodiments,
titration sessions are automatically initiated by the
neuromodulation system or initiated by the patient without
requiring any intervention by the health care provider. This can
eliminate the need for the patient to schedule a subsequent visit
to the health care provider, thereby potentially reducing the total
amount of time needed for the titration process to complete. In
these embodiments, the neuromodulation system may include the one
or more sensors, e.g., a blood flow sensor, a blood pressure
sensor, and a distension sensor, that communicates with the
neuromodulation system's control system to enable the control
system to detect the patient's physiological response to the
titration and automatically make adjustments to the titration
processes described herein with reduced or no inputs from the
patient or health care provider. The monitored signals can also
enable the control system to detect when the target physiological
effect has been achieved and conclude the titration process. The
neuromodulation system could in addition or alternatively include a
patient control input to permit the patient to communicate to the
control system that an acceptable adverse physiological effect
level has been exceeded. In these automatically initiated titration
sessions, the neuromodulation system may be configured to wait a
period of time after completing one session before initiating the
next session. This period of time may be predetermined, e.g., two
or three days, or programmable.
[0068] At step 405, the neuromodulation system is configured to
obtain or generate a set of stimulation parameters. For example, in
some embodiments, when initiating an initial titration session
(e.g., step 310 as described with respect to FIG. 3), the
neuromodulation system is configured to obtain or generate an
initial set of stimulation parameters to initialize the stimulation
therapy. In other embodiments, when executing a subsequent
titration session (e.g., a maintenance titration session), the
neurostimulator is configured to obtain or generate a set of
stimulation parameters based on the previously determined
therapeutic set of stimulation parameters (e.g., step 320 as
described with respect to FIG. 3).
[0069] In step 410, the neuromodulation system delivers stimulation
to the patient using the set of stimulation parameters (e.g., a
first set of stimulation parameters). If this is the first
titration session, then the stimulation would be delivered with the
initial set of stimulation parameters described above with respect
to step 310. If this is a subsequent titration session, then the
stimulation intensity would remain at the same level at the
conclusion of the previous titration session described above with
respect to step 320 of FIG. 3. In some embodiments, the stimulation
is a stimulation signal or electrical current.
[0070] In step 415, the neuromodulation system monitors nerve
responses (e.g., electrical impulses traveling through the nerve or
artery/nerve plexus) and blood-based parameters (e.g., blood flow,
blood pressure, and arterial distension) using one or more sensors
(e.g., sensors 255 described with respect to FIG. 2) to determine
whether the stimulation provided using the set of stimulation
parameters had zero or minimal physiological effect, achieved a
target physiological effect, and/or had an adverse physiological
effect on the patient. In various embodiments, the monitoring
includes the neuromodulation system obtaining the blood-based
parameters and comparing the blood-based parameters to one or more
predetermined thresholds to determine whether the stimulation had
an adverse physiological effect. When the stimulation provided
using a set of stimulation parameters is determined to have had an
adverse physiological effect, the process proceeds to step 420.
When the stimulation provided using a set of stimulation parameters
is determined to not have had an adverse physiological effect, the
process proceeds to step 425. In determining whether the
stimulation had an adverse physiological effect, the
neuromodulation system may be configured to wait a period of time
after delivering the stimulation in step 410 before determining
whether the stimulation did not have an adverse physiological
effect and proceeding to step 425. This period of time may be
predetermined, e.g., two or three days, or programmable at which
time the neuromodulation system continues to monitor the
blood-based parameters for an adverse physiological effect.
[0071] In some embodiments, prior to neural stimulation, baseline
values for blood flow, blood pressure, and arterial distension may
be determined and recorded for a patient. Once neural stimulation
begins on the patient, the values obtained for blood flow, blood
pressure, and arterial distension may be compared respectively to
the baseline values for blood flow, blood pressure, and arterial
distension to determine the extent of change in the blood-based
parameters. The determined extent of change for each blood-based
parameter may then be compared to predetermined threshold values
set for each blood-based parameter (e.g., threshold values that may
be indicative of an adverse physiological effect) to determine
whether the stimulation provided using a set of stimulation
parameters had an adverse physiological effect on the blood flow,
the blood pressure, or the arterial distension. As will be
described in greater detail below, an adverse physiological effect
may be determined based on the change for each blood-based
parameter or based on a combination of the changes for the
blood-based parameters.
[0072] In alternative embodiments, the monitoring includes the
neuromodulation system obtaining the blood-based parameters and
comparing each of the blood-based parameters to a predetermined
threshold for each of the blood-based parameters to determine
whether the stimulation had an adverse physiological effect. For
example, once neural stimulation begins on the patient, the values
obtained for blood flow, blood pressure, and arterial distension
may be compared respectively to predetermined threshold values set
for each blood-based parameter (e.g., threshold values that may be
indicative of an adverse physiological effect) to determine whether
the stimulation provided using a set of stimulation parameters had
an adverse physiological effect on the blood flow, the blood
pressure, or the arterial distension. As will be described in
greater detail below, an adverse physiological effect may be
determined based on each blood-based parameter or based on a
combination of the blood-based parameters.
[0073] In step 420, one or more of the stimulation parameters is
modified to bring the adverse physiological effect within
acceptable levels. In various embodiments, one or more of the
stimulation parameters is modified (e.g., using the one or more
processors) based on the responses of the nerve or artery/nerve
plexus and/or the blood-based parameters to create a modified set
of stimulation parameters (e.g., a second set of stimulation
parameters). In some embodiments, one or more of the burst
duration, the burst interval, the stimulation amplitude, the pulse
width, the frequency, the duty cycle, stimulation waveform shape,
and the electrode configuration is changed to bring the adverse
physiological effect within acceptable levels. The changes in the
parameter settings may vary, but may be selected so that one or
more of the parameters are set at levels below previously set
levels, such that the adverse physiological effect is minimized or
prevented. In some embodiments, the burst duration, the burst
interval, the frequency, and electrode configuration are maintained
at target levels or configurations, while one or more of the
stimulation amplitude, the pulse width, stimulation waveform shape,
and the duty cycle are reduced below their respective previous
levels. In other embodiments, the initial electrode configuration
is set at a target level or configuration, while one or more of the
burst duration, the burst interval, the frequency, the stimulation
amplitude, the pulse width, stimulation waveform shape, and the
duty cycle are reduced below their respective previous levels. Once
the one or more of the stimulation parameters are modified, the
process proceeds to step 410, to deliver stimulation to the patient
using the modified set of stimulation parameters and monitor nerve
responses and the blood-based parameters to determine whether the
stimulation provided using the modified set of stimulation
parameters achieved a target physiological effect and/or still had
an adverse physiological effect on the patient.
[0074] In step 425, a determination is made as to whether adequate
adaptation is achieved. In some embodiments, adequate adaptation
includes achieving one or more of the following objectives:
acceptable levels for the blood-based parameters, a target
intensity level for one or more stimulation parameters, and a
target physiological effect. When the stimulation provided using a
set of stimulation parameters is determined to achieve adequate
adaptation, the process proceeds to step 430. When the stimulation
provided using a set of stimulation parameters is determined to not
achieve adequate adaptation, the process proceeds to step 435.
[0075] At step 430, the neuromodulation system delivers stimulation
to the patient using the set of stimulation parameters during the
remainder of stimulation therapy, as further described herein with
respect to FIG. 5.
[0076] At step 435, one or more of the stimulation parameters is
modified to achieve one or more of the following objectives:
acceptable levels for the blood-based parameters, a target
intensity level for one or more stimulation parameters, and a
target physiological effect. In various embodiments, one or more of
the stimulation parameters is modified based on the responses of
the nerve or artery/nerve plexus and/or the blood-based parameters
to create a modified set of stimulation parameters. In some
embodiments, one or more of the burst duration, the burst interval,
the stimulation amplitude, the pulse width, the frequency, the duty
cycle, stimulation waveform shape, and the electrode configuration
is changed to achieve one or more of the following objectives:
acceptable levels for the blood-based parameters, a target
intensity level for one or more stimulation parameters, and a
target physiological effect. The changes in the parameter settings
may vary, but may be selected so that one or more of the parameters
are set at levels above or below previously set levels, such that
acceptable levels for the blood-based parameters are obtained, a
target intensity level for one or more stimulation parameters is
obtained, and a target physiological effect is obtained. In some
embodiments, the burst duration, the burst interval, the frequency,
and electrode configuration are maintained at target levels or
configurations, while one or more of the stimulation amplitude, the
pulse width, stimulation waveform shape, and the duty cycle are
increased above their respective previous levels towards target
levels. In other embodiments, the initial electrode configuration
is set at a target level or configuration, while one or more of the
burst duration, the burst interval, the frequency, the stimulation
amplitude, the pulse width, stimulation waveform shape, and the
duty cycle are increased above their respective previous levels
towards target levels. Once the one or more of the stimulation
parameters are modified, the process proceeds to step 410, to
deliver stimulation to the patient using the modified set of
stimulation parameters and monitor nerve responses and the
blood-based parameters to determine whether the stimulation
provided using the modified set of stimulation parameters now
achieves adequate adaptation.
[0077] FIG. 5 depicts a simplified flowchart 500 illustrating a
process used to provide a therapeutic level of neural stimulation
to achieve a desired or target physiological effect during a
remainder of stimulation therapy while minimizing or preventing an
adverse physiological effect. In some embodiments, the remainder of
stimulation therapy is automatically performed by the
neuromodulation system without requiring any intervention by the
patient or health care provider. This can eliminate the need for
the patient to schedule a subsequent visit to the health care
provider, thereby potentially reducing prolong adverse
physiological effects suffered by a patient. In these embodiments,
the neuromodulation system may include the one or more sensors,
e.g., a blood flow sensor, a blood pressure sensor, and a
distension sensor, that communicates with the neuromodulation
system's control system to enable the control system to detect the
patient's physiological responses to the stimulation therapy and
automatically make adjustments to the stimulation therapy processes
described herein with reduced or no inputs from the patient or
health care provider. The monitored signals can also enable the
control system to detect when the target physiological effect has
been achieved and maintain the stimulation therapy process. The
neuromodulation system could in addition or alternatively include a
patient control input to permit the patient to communicate to the
control system that an acceptable adverse physiological effect
level has been exceeded. In automatically controlled stimulation
therapy processes, the neuromodulation system may be configured to
wait a period of time after completing one process, e.g.,
delivering stimulation, before initiating the changing one or more
of the stimulation parameters. This period of time may be
predetermined, e.g., two or three days, or programmable.
[0078] In step 505, the neuromodulation system delivers stimulation
to the patient using a set of stimulation parameters. In some
embodiments, the set of stimulation parameters are the set of
stimulation parameters determined in step 315 or step 425 of FIGS.
3 and 4, respectively, that has achieved adequate adaptation. In
step 510, the neuromodulation system monitors nerve responses
(e.g., electrical impulses traveling through the nerve or
artery/nerve plexus) and blood-based parameters (e.g., blood flow,
blood pressure, and arterial distension) using one or more sensors
(e.g., sensors 255 described with respect to FIG. 2) to determine
whether the stimulation provided using the set of stimulation
parameters had zero or minimal physiological effect, achieved a
desired physiological effect, and/or had an adverse physiological
effect on the patient (e.g., occlusion of an artery). In various
embodiments, the monitoring includes the neuromodulation system
obtaining the blood-based parameters and comparing the blood-based
parameters to one or more predetermined thresholds to determine
whether the stimulation had an adverse physiological effect on the
blood-based parameters. When the stimulation provided using a set
of stimulation parameters is determined to have had an adverse
physiological effect on the blood-based parameters, the process
proceeds to step 515. When the stimulation provided using a set of
stimulation parameters is determined to not have had an adverse
physiological effect on the blood-based parameters, the process
continues to monitor nerve responses and the blood-based parameters
through-out the remainder of the stimulation therapy.
[0079] In some embodiments, prior to neural stimulation, baseline
values for blood flow, blood pressure, and arterial distension may
be determined and recorded for a patient. In some embodiments, the
baseline values may be recorded in the memory of the
neuromodulation system (e.g., the memory 235 as described with
respect to FIG. 2). Once neural stimulation begins on the patient,
the values obtained for blood flow, blood pressure, and arterial
distension may be compared respectively to the baseline values for
blood flow, blood pressure, and arterial distension to determine
the extent of change in the blood-based parameters. The determined
extent of change for each blood-based parameter may then be
compared to predetermined threshold values set for each blood-based
parameter (e.g., threshold values that are indicative of an adverse
physiological effect) to determine whether the stimulation provided
using a set of stimulation parameters had an adverse physiological
effect on the blood flow, the blood pressure, or the arterial
distension.
[0080] An adverse physiological effect may be determined based on
the change for each blood-based parameter. For example, in some
embodiments, if one, two, three or more of the changes for each
blood-based parameter exceeds one or more of the predetermined
threshold values, then an adverse physiological effect is
determined. In other embodiments, the blood-based parameters may be
assigned weights or priority, for example blood flow may be
designated a priority status. If (i) one, two, three or more of the
weighted changes for each blood-based parameter exceed one or more
of the predetermined threshold values, or (ii) the changes for one
or more blood-based parameters that has priority status exceeds one
or more of the predetermined threshold values, then an adverse
physiological effect is determined. The predetermined threshold
values may vary, e.g., from patient to patient, but may be selected
such that the stimulation therapy process is configured to provide
a closed-loop adjustment of the stimulation parameters based on
blood parameter sensing to minimize or prevent the adverse
physiological effect from reoccurring during the remainder of
stimulation therapy.
[0081] Optionally, the adverse physiological effect may be
determined based on a combination of the changes for the
blood-based parameters. For example, in some embodiments, a
composite predetermined threshold may be set that takes into
consideration a combination of the changes in blood-based
parameters. If the combination in the changes of the blood-based
parameters exceeds the composite predetermined threshold, then an
adverse physiological effect is determined. In other embodiments,
the blood-based parameters may be assigned weights, for example
blood flow may be designated a greater weight than blood pressure.
If the combination in the weighted changes of the blood-based
parameters exceeds the composite predetermined threshold, then an
adverse physiological effect is determined. The composite
predetermined threshold may vary, e.g., from patient to patient,
but may be selected such that the stimulation therapy process is
configured to provide a closed-loop adjustment of the stimulation
parameters based on blood parameter sensing to minimize or prevent
the adverse physiological effect from reoccurring during the
remainder of stimulation therapy.
[0082] In alternative embodiments, the monitoring includes the
neuromodulation system obtaining the blood-based parameters and
comparing each of the blood-based parameters to a predetermined
threshold for each of the blood-based parameters to determine
whether the stimulation had an adverse physiological effect on the
blood-based parameters. For example, once neural stimulation begins
on the patient, the values obtained for blood flow, blood pressure,
and arterial distension may be compared respectively to
predetermined threshold values set for each blood-based parameter
(e.g., threshold values that are indicative of an adverse
physiological effect) to determine whether the stimulation provided
using a set of stimulation parameters had an adverse physiological
effect on the blood flow, the blood pressure, or the arterial
distension.
[0083] An adverse physiological effect may be determined based on
each blood-based parameter. For example, in some embodiments, if
one, two, three or more of the blood-based parameters exceed one or
more of the predetermined threshold values, then an adverse
physiological effect is determined. In other embodiments, the
blood-based parameters may be assigned weights or priority, for
example blood flow may be designated a priority status. If (i) one,
two, three or more of the weighted blood-based parameters exceed
one or more of the predetermined threshold values, or (ii) one or
more of the blood-based parameters that has priority status exceeds
one or more of the predetermined threshold values, then an adverse
physiological effect is determined. The predetermined threshold
values may vary, e.g., from patient to patient, but may be selected
such that the stimulation therapy process is configured to provide
a closed-loop adjustment of the stimulation parameters based on
blood parameter sensing to minimize or prevent the adverse
physiological effect from reoccurring during the remainder of
stimulation therapy.
[0084] Optionally, the adverse physiological effect may be
determined based on a combination of the blood-based parameters.
For example, in some embodiments, a composite predetermined
threshold may be set that takes into consideration a combination of
the blood-based parameters. If the combination of the blood-based
parameters exceeds the composite predetermined threshold, then an
adverse physiological effect is determined. In other embodiments,
the blood-based parameters may be assigned weights, for example
blood flow may be designated a greater weight than blood pressure.
If the combination in the weighted blood-based parameters exceeds
the composite predetermined threshold, then an adverse
physiological effect is determined. The composite predetermined
threshold may vary, e.g., from patient to patient, but may be
selected such that the stimulation therapy process is configured to
provide a closed-loop adjustment of the stimulation parameters
based on blood parameter sensing to minimize or prevent the adverse
physiological effect from reoccurring during the remainder of
stimulation therapy.
[0085] In step 515, one or more of the stimulation parameters is
modified to bring the adverse physiological effect within
acceptable levels. In various embodiments, one or more of the
stimulation parameters is modified (e.g., using the one or more
processors) based on the responses of the nerve or artery/nerve
plexus and/or the blood-based parameters to create a modified set
of stimulation parameters (e.g., a second set of stimulation
parameters). In some embodiments, one or more of the burst
duration, the burst interval, the stimulation amplitude, the pulse
width, the frequency, the duty cycle, stimulation waveform shape,
and the electrode configuration is changed to bring the adverse
physiological effect within acceptable levels. The changes in the
parameter settings may vary, but may be selected so that one or
more of the parameters are set at levels below previously set
levels, such that the adverse physiological effect is minimized or
prevented from reoccurring during the remainder of stimulation
therapy. In some embodiments, the burst duration, the burst
interval, the frequency, and electrode configuration are maintained
at target levels or configurations, while one or more of the
stimulation amplitude, the pulse width, stimulation waveform shape,
and the duty cycle are reduced below their respective previous
levels. In other embodiments, the initial electrode configuration
is maintained at a target level or configuration, while one or more
of the burst duration, the burst interval, the frequency, the
stimulation amplitude, the pulse width, stimulation waveform shape,
and the duty cycle are reduced below their respective previous
levels. In yet other embodiments, the burst duration, the burst
interval, the frequency, the stimulation amplitude, the pulse
width, stimulation waveform shape, and the duty cycle are
maintained at target levels, while the electrode configuration is
modified. Once the one or more of the stimulation parameters are
modified, the process proceeds to step 505, to deliver stimulation
to the patient using the modified set of stimulation parameters and
monitor nerve responses and the blood-based parameters to determine
whether the stimulation provided using the modified set of
stimulation parameters still has an adverse physiological effect on
the patient.
[0086] While the invention has been described in detail,
modifications within the spirit and scope of the invention will be
readily apparent to the skilled artisan. It should be understood
that aspects of the invention and portions of various embodiments
and various features recited above and/or in the appended claims
may be combined or interchanged either in whole or in part. In the
foregoing descriptions of the various embodiments, those
embodiments which refer to another embodiment may be appropriately
combined with other embodiments as will be appreciated by the
skilled artisan. Furthermore, the skilled artisan will appreciate
that the foregoing description is by way of example only, and is
not intended to limit the invention.
* * * * *