U.S. patent application number 11/634523 was filed with the patent office on 2007-05-17 for systems and methods for enhancing or optimizing neural stimulation therapy for treating symptoms of parkinson's disease and/or other movement disorders.
This patent application is currently assigned to Northstar Neuroscience, Inc.. Invention is credited to Bradford Evan Gliner.
Application Number | 20070112393 11/634523 |
Document ID | / |
Family ID | 32468920 |
Filed Date | 2007-05-17 |
United States Patent
Application |
20070112393 |
Kind Code |
A1 |
Gliner; Bradford Evan |
May 17, 2007 |
Systems and methods for enhancing or optimizing neural stimulation
therapy for treating symptoms of parkinson's disease and/or other
movement disorders
Abstract
Systems and methods for treating a neurological disorder
comprising determining a first set of neural stimulation parameters
capable of treating a first subset of symptoms, determining a
second set of neural stimulation parameters capable of treating a
second subset of symptoms, and applying a neural stimulation
therapy based upon the first set of neural stimulation parameters
and the second set of neural stimulation parameters to the patient.
The first set of neural stimulation parameters can include
electrical stimulation at a first frequency, and the second set of
neural stimulation parameters can include electrical stimulation at
a second frequency. In other embodiments, a treatment method
comprises applying a first neural stimulation therapy to the
patient in a continuous or generally continuous manner during a
first time interval, and applying a second neural stimulation
therapy to the patient in a noncontinuous or interrupted manner
following the first time interval.
Inventors: |
Gliner; Bradford Evan;
(Sammamish, WA) |
Correspondence
Address: |
PERKINS COIE LLP;PATENT-SEA
P.O. BOX 1247
SEATTLE
WA
98111-1247
US
|
Assignee: |
Northstar Neuroscience,
Inc.
Seattle
WA
|
Family ID: |
32468920 |
Appl. No.: |
11/634523 |
Filed: |
December 4, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10317002 |
Dec 10, 2002 |
|
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11634523 |
Dec 4, 2006 |
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Current U.S.
Class: |
607/45 ;
607/48 |
Current CPC
Class: |
A61N 1/36167 20130101;
A61N 1/36082 20130101; A61N 1/36178 20130101; A61N 1/36067
20130101; A61N 1/0534 20130101 |
Class at
Publication: |
607/045 ;
607/048 |
International
Class: |
A61N 1/32 20060101
A61N001/32 |
Claims
1. A method for treating a set of symptoms corresponding to a
neurological disorder exhibited by a patient, comprising:
determining a first set of neural stimulation parameters capable of
treating a first subset of symptoms; determining a second set of
neural stimulation parameters capable of treating a second subset
of symptoms; and applying a neural stimulation therapy based upon
the first set of neural stimulation parameters and the second set
of neural stimulation parameters to the patient.
2. The method of claim 1, wherein the first set of neural
stimulation parameters defines a first frequency and the second set
of neural stimulation parameters defines a second frequency.
3. The method of claim 2, wherein the neural stimulation therapy
defines a frequency function that includes the first and the second
frequencies.
4. The method of claim 3, wherein the neural stimulation therapy
defines a frequency function that sweeps between the first and the
second frequencies.
5. The method of claim 1, wherein the first subset of symptoms
responds to neural stimulation more rapidly than the second subset
of symptoms.
6. The method of claim 1, further comprising positioning a set of
electrodes with respect to a target neural population within the
patient.
7. The method of claim 6, wherein at least one electrode within the
set of electrodes is configured to deliver neural stimulation
therapy to a cortical region within the patient.
8. The method of claim 7, wherein the cortical region corresponds
to a neural population that facilitates control of at least one
type of patient movement.
9. A method for treating a set of symptoms corresponding to a
neurological disorder exhibited by a patient, comprising: applying
a first neural stimulation signal having a first frequency to the
patient to treat a first subset of symptoms; and applying a second
neural stimulation signal having a second frequency to the patient
to treat a second subset of symptoms.
10. The method of claim 9, wherein the first neural stimulation
signal is applied during a first time interval and the second
neural stimulation signal is applied during a second time
interval.
11. The method of claim 10, wherein the first and second time
intervals depend upon a severity of the first subset of symptoms
relative to the second subset of symptoms.
12. A method for treating a set of symptoms corresponding to a
neurological disorder exhibited by a patient, comprising: applying
a first neural stimulation therapy to the patient in a continuous
or generally continuous manner during a first time interval; and
applying a second neural stimulation therapy to the patient in a
noncontinuous or interrupted manner following the first time
interval, wherein the second neural stimulation therapy provides an
extent of relief from a subset of patient symptoms that is
acceptable relative to an extent of relief from the subset of
patient symptoms provided by the first neural stimulation
therapy.
13. The method of claim 12, wherein the first time interval is
greater than approximately one week.
14. The method of claim 12, wherein the first time interval is
approximately one month.
15. The method of claim 12, wherein the second neural stimulation
therapy comprises continuous or generally continuous neural
stimulation during the patient's waking hours.
16. A method for treating a set of symptoms corresponding to a
neurological disorder exhibited by a patient, comprising: applying
a first neural stimulation therapy to the patient in a continuous
or generally continuous manner during a first time interval; and
applying a second neural stimulation therapy to the patient in a
noncontinuous or interrupted manner following the first time
interval, wherein the second neural stimulation therapy provides an
extent of relief from a subset of patient symptoms that is
generally identical to an extent of relief from the subset of
patient symptoms provided by the first neural stimulation therapy.
Description
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application is a continuation of U.S. patent
application Ser. No. 10/317,002, entitled "SYSTEMS AND METHODS FOR
ENHANCING OR OPTIMIZING NEURAL STIMULATION THERAPY FOR TREATING
SYMPTOMS OF PARKINSON'S DISEASE AND/OR OTHER MOVEMENT DISORDERS"
which was filed on Dec. 10, 2002, and identified by attorney docket
number 337348048US, the disclosure of which is incorporated by
reference herein in its entirety. The application also incorporates
by reference U.S. application Ser. No. 09/978,134 entitled "SYSTEMS
AND METHODS FOR AUTOMATICALLY OPTIMIZING STIMULUS PARAMETERS AND
ELECTRODE CONFIGURATIONS FOR NEURO-STIMULATORS," filed on Oct. 15,
2002 (Perkins Coie Docket No. 337348021US); and U.S. Provisional
Application No. 60/432,073 entitled "SYSTEM AND METHOD FOR TREATING
PARKINSON'S DISEASE AND OTHER MOVEMENT DISORDERS," filed on Dec. 9,
2002 (Perkins Coie Docket No. 337348040US, Express Mail No.
EV139295255US).
TECHNICAL FIEILD
[0002] The present disclosure relates generally to systems and
methods for treating symptoms of Parkinson's Disease and/or other
movement disorders. More particularly, the present disclosure
describes a system and method for enhancing or optimizing the
effectiveness of neural stimulation in treating the symptoms of
movement disorders such as Parkinson's Disease.
BACKGROUND
[0003] A wide variety of mental and physical processes are
controlled or influenced by neural activity in particular regions
of the brain. For example, various physical or cognitive functions
are directed or affected by neural activity within the sensory or
motor cortices. Across most individuals, particular areas of the
brain appear to have distinct functions. In the majority of people,
for example, the areas of the occipital lobes relate to vision; the
regions of the left interior frontal lobes relate to language;
portions of the cerebral cortex appear to be consistently involved
with conscious awareness, memory, and intellect; and particular
regions of the cerebral cortex as well as the basal ganglia, the
thalamus, and the motor cortex cooperatively interact to facilitate
motor function control.
[0004] Many problems or abnormalities with body functions can be
caused by damage, disease, and/or disorders in the brain. For
example, Parkinson's Disease (PD) is related to the degeneration or
death of dopamine producing neurons in the substantia nigra region
of the basal ganglia in the brain. Dopamine is neurotransmitter
that transmits signals between areas of the brain. As the neurons
in the substantia nigra deteriorate, the reduction in dopamine
causes abnormal neural activity that results in a chronic,
progressive deterioration of motor function control. Conservative
estimates indicate that PD may affect more than one million
individuals in the United States alone.
[0005] PD patients typically exhibit one or more of four primary
symptoms. One primary symptom is a tremor in an extremity (e.g., a
hand) that occurs while the extremity is at rest. Other primary
symptoms include a generalized slowness of movement (bradykinesia);
increased muscle rigidity or stiffness (rigidity); and gait or
balance problems (postural dysfunction). In addition to or in lieu
of these primary symptoms, PD patients may exhibit secondary
symptoms including: difficulty initiating or resuming movements;
loss of fine motor skills; lack of arm swing on the affected side
of the body while walking; foot drag on the affected side of the
body; decreased facial expression; voice and/or speech changes;
cognitive disorders; feelings of depression or anxiety; and/or
other symptoms.
[0006] Effectively treating PD or other movement disorders related
to neurological conditions can be very difficult. Current
treatments for PD symptoms include drugs, ablative surgical
intervention, and/or neural stimulation. Drug treatments or
therapies may involve, for example, the administration of a
dopamine precursor that is converted to dopamine within the central
nervous system (i.e., Levodopa (L-dopa)). Other types of drug
therapies are also available. Unfortunately, drug therapies
frequently become less effective or ineffective over time for an
undesirably large patient population. A PD patient may require
multiple drugs in combination to extend the time period of efficacy
of drug therapies. Drug treatments additionally have a significant
likelihood of inducing undesirable physical side effects; motor
function complications such as uncontrollable involuntary movements
(dyskinesias) are a particularly common side effect. Furthermore,
drug treatments may induce undesirable cognitive side effects such
as confusion and/or hallucinations.
[0007] Ablative surgical intervention for PD typically involves the
destruction of one or more neural structures within the basal
ganglia or thalamus that have become overactive because of the lack
of dopamine. Unfortunately, such neural structures reside deep
within the brain, and hence ablative surgical intervention is a
very time consuming and highly invasive procedure. Potential
complications associated with the procedure include risk of
hemorrhage, stroke, and/or paralysis. Moreover, because PD is a
progressive disease, multiple deep brain surgeries may be required
as symptoms progressively worsen over time. Although ablative
surgical intervention may improve a PD patient's motor function, it
is not likely to completely restore normal motor function.
Furthermore, since ablative surgical intervention permanently
destroys neural tissue, the effects of such intervention cannot be
readily adjusted or "fine tuned" over time.
[0008] Neural stimulation treatments have shown promising results
for reducing some of the symptoms associated with PD. Neural
activity is governed by electrical impulses or "action potentials"
generated in and propagated by neurons. While in a quiescent state,
a neuron is negatively polarized and exhibits a resting membrane
potential that is typically between -70 and -60 mV. Through
chemical connections known as synapses, any given neuron receives
excitatory and inhibitory input signals or stimuli from other
neurons. A neuron integrates the excitatory and inhibitory input
signals it receives, and generates or fires a series of action
potentials in the event that the integration exceeds a threshold
potential. A neural firing threshold, for example, may be
approximately -55 mV. Action potentials propagate to the neuron's
synapses and are then conveyed to other synaptically connected
neurons.
[0009] Neural activity in the brain can be influenced by neural
stimulation, which involves the application of electrical and/or
magnetic stimuli to one or more target neural populations within a
patient using a waveform generator or other type of device. Various
neural functions can thus be promoted or disrupted by applying an
electrical current to one or more regions of the brain. As a
result, researchers have attempted to treat certain neurological
conditions, including PD, using electrical or magnetic stimulation
signals to control or affect brain functions.
[0010] Deep Brain Stimulation (DBS) is a stimulation therapy that
has been used as an alternative to drug treatments and ablative
surgical therapies. In DBS, one or more electrodes are surgically
implanted into the brain proximate to deep brain or subcortical
neural structures. For treating PD or other movement disorders, the
electrodes are positioned in or proximate to the ventrointermediate
nucleus of the thalamus; basal ganglia structures such as the
globus pallidus internalis (GPi); or the Subthalamic Nucleus (STN).
The location of the stimulation site for the electrodes depends
upon the symptoms that a patient exhibits and the severity of the
symptoms.
[0011] In a typical DBS system, a pulse generator delivers a
continuous or essentially continuous electrical stimulation signal
having a pulse repetition frequency of approximately 100 Hz to each
of two deep brain electrodes. The electrodes are bilaterally
positioned on the left and right sides of the brain relative to
particular neural structures such as those indicated above. U.S.
Pat. No. 5,883,709 discloses one conventional DBS system for
treating movement disorders.
[0012] Although DBS therapies may significantly reduce one or more
PD symptoms, particularly when combined with drug treatments, they
are highly invasive procedures. In general, configuring a DBS
system to properly function within a patient requires two time
consuming, highly invasive surgical procedures for implanting the
DBS electrodes. Each such surgical procedure has essentially the
same risks as those described above for ablative surgical
intervention. Moreover, DBS may not provide relief from some
movement disorders.
[0013] Motor Cortex Stimulation (MCS) is another type of brain
stimulation treatment that has been proposed for treating movement
disorders. MCS involves the application of stimulation signals to
the motor cortex of a patient. One MCS system includes a pulse
generator connected to a strip electrode that is surgically
implanted over a portion of only the motor cortex (precentral
gyrus). The use of MCS to treat PD symptoms is described in
Canavero, Sergro, Extradural Motor Cortex Stimulation for Advanced
Parkinson's Disease: Case Report, Movement Disorders (Vol. 15, No.
1, 2000).
[0014] Because MCS involves the application of stimulation signals
to surface regions of the brain rather than deep neural structures,
electrode implantation procedures for MCS are significantly less
invasive and time consuming than those for DBS. As a result, MCS
may be a safer and simpler alternative to DBS for treating PD
symptoms. Present MCS techniques, however, fail to address or
adequately consider a variety of factors that may enhance or
optimize the extent to which a patient experiences short term
and/or long term relief from PD symptoms.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a schematic illustration of a neural stimulation
system for treating symptoms of Parkinson's Disease and/or other
neurological disorders according to an embodiment of the
invention.
[0016] FIG. 2 is a graph illustrating several stimulation
parameters that may define, describe, or characterize stimulation
signals.
[0017] FIG. 3 is a flowchart illustrating various methods for
refining, enhancing, or optimizing neural stimulation therapy for
treating symptoms of Parkinson's Disease and/or other movement
disorders according to an embodiment of the invention.
[0018] FIG. 4 is a flowchart illustrating various methods for
establishing, adjusting, or adapting a test protocol according to
an embodiment of the invention.
[0019] FIG. 5 is a flowchart illustrating various methods for
determining neural stimulation parameters according to an
embodiment of the invention.
[0020] FIG. 6 is a flowchart illustrating various methods for
modifying, adjusting, or adapting neural stimulation therapy in
view of a likelihood or possibility of a lasting or long term
neuroplastic change occurring within a patient over time.
DETAILED DESCRIPTION
[0021] The following disclosure describes neural stimulation
systems and methods for enhancing or optimizing the extent to which
a patient may experience relief from symptoms associated with
Parkinson's Disease (PD), other movement or motor disorders, and/or
various neurological disorders that may have multiple types of
symptoms. Such symptoms may include, for example, tremor, rigidity,
bradykinesia, postural dysfunction, spasticity, speech deficits,
visual disturbances, olfactory deficits, cognitive deficits, memory
deficits, emotional or psychiatric disturbances, paresis, pain
and/or other symptoms.
[0022] Different symptoms may respond to neural stimulation in
different manners, and/or across different time scales. For
example, neural stimulation optimized to beneficially affect tremor
and/or rigidity to a significant degree may provide less
significant or minimal benefit relative to other symptoms such as
postural dysfunction. Additionally, neural stimulation that has a
nearly immediate or reasonably rapid effect upon tremor and/or
rigidity may have a significantly or greatly delayed effect upon
other symptoms such as bradykinesia. Systems and/or methods
described herein may facilitate enhancement or optimization of
neural stimulation therapy for treating multiple patient symptoms
that may exhibit different treatment response characteristics
and/or different response timeframes.
[0023] Neural stimulation may facilitate or effectuate neuroplastic
changes within a patient's brain, for example, in a manner
described in U.S. application Ser. No. 09/802,808, which is
incorporated herein by reference. Neuroplastic changes can include
adaptive structural changes or reorganizations in particular brain
regions, which may result in enhancement or restoration of one or
more functional abilities (i.e., physical, sensory, and/or
cognitive functions) associated with such brain regions, possibly
on a long term or lasting basis. Application of neural stimulation
to a patient in accordance with the principles described herein may
increase the likelihood that neuroplastic changes can occur to
facilitate at least partial recovery of diminished or lost
functionality associated with or giving rise to one or more patient
symptoms. Such functional recovery may itself reduce the extent to
which the patient requires neural stimulation and/or other therapy
on an ongoing basis.
[0024] FIG. 1 is a schematic illustration of a neural stimulation
system 100 for treating symptoms of PD and/or other disorders
according to an embodiment of the invention. In one embodiment, the
neural stimulation system 100 comprises a pulse generator 110a
configured to deliver stimulation signals to a patient 190 using a
set of electrodes 140. The pulse generator 110a may be coupled to
the set of electrodes 140 by one or more leads 112. The pulse
generator 110a may further be configured for wireless and/or
wire-based communication with a programming unit 160. Depending
upon embodiment details, the system 100 may further include one or
more patient monitoring units 180 configured to detect, monitor,
indicate, measure, and/or assess the severity of particular types
of patient symptoms.
[0025] The set of electrodes 140 may include one or more cortical
electrodes 142 configured to provide, deliver, and/or apply
stimulation signals to particular cortical regions of the patient's
brain 192 and/or neural populations synaptically connected and/or
proximate thereto. A cortical electrode 142 may include one or more
electrically conductive contacts 144 carried by a substrate 146 in
a manner understood by those skilled in the art. The set of
electrodes 140 may alternatively or additionally include one or
more penetrating, depth, and/or deep brain electrodes. The set of
electrodes 140 may further include or provide one or more
stimulation signal return electrodes (i.e., electrodes that provide
a current return path) that may be positioned relative to a variety
of locations within and/or upon the patient's body.
[0026] The characteristics and/or placement of the set of
electrodes 140 may depend upon the nature of patient's underlying
disorder(s) and/or the type and/or severity of symptoms that the
patient 190 experiences or exhibits. In one embodiment, one or more
portions of the set of electrodes 140 may be surgically implanted
to deliver stimulation signals to target neural populations within
the patient's brain in a manner described in U.S. Provisional
Application No. 60/432,073, entitled "System and Method for
Treating Parkinson's Disease and Other Movement Disorders," filed
on Dec. 9, 2002 (Perkins Coie Docket No. 33734.8040US00).
[0027] The pulse generator 110a may comprise hardware and/or
software for generating and outputting stimulation signals to the
set of electrodes 140 in accordance with internal instruction
sequences and/or in response to control signals, commands,
instructions, and/or other information received from the
programming unit 160. The pulse generator 110a may include a power
supply, a pulse unit, a control unit, a programmable computer
medium, and a communication unit. The power supply may comprise a
battery or other type of power storage device. The pulse unit may
comprise circuitry for generating pulse sequences that may be
defined or characterized in accordance with various stimulation
signal parameters, which are further described below with reference
to FIG. 2. The control unit may comprise hardware and/or software
configured to direct or manage the local operation of the pulse
generator 110a. The communication unit may comprise a user
interface that facilitates communication with devices external to
the pulse generator 110a, for example, through telemetric signal
transfer. The programmable computer medium may comprise hardware
and/or memory resident software. The programmable computer medium
may store operational mode information and/or program instruction
sequences that may be selected and/or specified in accordance with
information received from the programming unit 160. The pulse
generator 110a may be configured to deliver stimulation signals to
particular electrodes 142 and/or specific electrical contacts 144
within the set of electrodes 140 on a selective basis at any given
time, in a manner identical, essentially identical, or analogous to
that described in U.S. application Ser. No. 09/978,134.
[0028] Each element of the pulse generator 110a may be incorporated
or embedded into a surgically implantable case or housing.
Depending upon embodiment details, the pulse generator 110a may be
surgically implanted into the patient 190 in a subclavicular
location. Alternatively, a pulse generator 110b may be surgically
implanted above the patient's neck, for example, in a skull
location posterior to the patient's ear and/or proximate to an
electrode implantation site. A surgically formed tunnel or path may
route the set of leads 112 that couple the pulse generator 110a,
110b to the set of electrodes 140, in a manner understood by those
skilled in the art. Additionally, one or more electrically
conductive portions of the pulse generator's case or housing may
serve as a return electrode for electrical current.
[0029] The programming unit 160 may comprise a device configured to
communicate control signals, commands, instructions, and/or other
information to the pulse generator 110a. The programming unit 160
may additionally be configured to receive information from the
pulse generator 110a. Communication between the programming unit
160 and the pulse generator 110a may facilitate or effectuate
specification, selection, and/or identification of operational
modes, instruction sequences, and/or procedures for treating
symptoms of PD and/or other neurological disorders in accordance
with the present invention, as described in detail below with
reference to FIGS. 3 through 6.
[0030] In one embodiment, the programming unit 160 includes a
processing unit 162, a programmable computer medium 164, and a
communication unit 166. The programmable computer medium 164 may
store an operating system, program instructions, and/or data, and
may comprise various types of hardware and memory resident
software, including volatile and/or nonvolatile memory as well as
one or more data storage devices. The communication unit 166 may
include a wire-based and/or wireless telemetry interface 170 that
employs magnetic, radio frequency (RF), and/or optical signaling
techniques to communicate with the pulse generator 110a. The
communication unit 166 may additionally or alternatively include
one or more wire-based and/or wireless interfaces that facilitate
communication with other devices such as a computer.
[0031] A patient monitoring unit 180 may comprise essentially any
type of device, subsystem, and/or system configured to detect,
monitor, indicate, measure, and/or assess the severity of one or
more types of patient symptoms associated with PD and/or other
neurological disorders. For example, a patient monitoring unit 180
may comprise a motion detection system configured to detect patient
movement associated with tremor. A motion detection system may
include light emitting and/or detecting devices and/or
accelerometers coupled to particular patient extremities. As
another example, a patient monitoring unit 180 may comprise an
Electromyography (EMG) system that includes a set of surface or
depth electrodes positioned relative to particular muscle groups
for detecting electrical signals corresponding to muscle fiber
innervation. As another example, a patient monitoring unit 180 may
comprise an Electroencephalograpy (EEG) system. As yet another
example, a patient monitoring unit 180 may comprise a neural
imaging system. As a final example, a patient monitoring unit 180
may comprise one or more electrodes and/or probes (e.g., cerebral
bloodflow monitors) positioned upon, proximate, and/or within given
target neural populations, and associated hardware and/or software
for detecting, presenting, and/or analyzing signals received
therefrom.
[0032] As previously indicated, the pulse generator 110a generates
and outputs stimulation signals. In the context of the present
invention, stimulation signals may comprise electromagnetic pulse
sequences. Any given pulse sequence may comprise at least one, and
possibly multiple, pulse trains, which may be separated by
quiescent intervals. FIG. 2 is a graph illustrating several
stimulation parameters that may define, describe, or characterize a
pulse train. A stimulus start time t.sub.0 defines an initial point
at which a pulse train is applied to one or more elements within
the set of electrodes 140. In one embodiment, the pulse train may
be a biphasic waveform comprising a series of biphasic pulses, and
which may be defined, characterized, or described by parameters
including a pulse width t.sub.1 for a first pulse phase; a pulse
width t.sub.2 for a second pulse phase; and a pulse width t.sub.3
for one or more biphasic pulses. The parameters can also include a
pulse repetition rate 1/t.sub.4 corresponding to a pulse repetition
frequency; a pulse duty cycle equal to t.sub.3 divided by t.sub.4;
a pulse burst time t.sub.5 that defines a number of pulses in a
pulse train; and/or a pulse train repetition rate t.sub.6. Other
parameters include a peak current intensity or amplitude I.sub.1
for a first pulse phase and a peak current intensity I.sub.2 for a
second pulse phase.
[0033] In various embodiments, the pulse width of successive pulses
and/or successive pulse phases may vary, such that the pulse
repetition frequency within a pulse train and/or a pulse sequence
is a function of time. A pulse train having a frequency that varies
in time may give rise to a "chirped" frequency profile.
Additionally or alternatively, the pulse intensity or amplitude may
decay during the first and/or second pulse phases, and the extent
of such decay may differ across successive or subsequent pulse
phases. Those skilled in the art will understand that a pulse may
be a charge-balanced waveform, and that in an alternate embodiment,
pulses can be monophasic or polyphasic. Additional stimulation
parameters may specify manners in which pulse trains are applied to
selected configurations of elements within the set of electrodes
140, such as particular electrodes 142 and/or contacts 144, at any
given time.
[0034] As defined herein, a test protocol may define or specify
neural stimulation parameters associated with one or more pulse
sequences to be applied to a patient 190 across or within a given
test period duration that may include one or more neural
stimulation delivery periods and possibly one or more quiescent
periods during which the patient 190 receives no neural
stimulation. A test protocol may further define or specify a
spatial and/or temporal distribution of elements within the set of
electrodes 140 to which neural stimulation may be applied during
one or more portions of the test period; and corresponding signal
polarities corresponding to particular elements within the set of
electrodes 140 relative to one or more portions of the test period.
Neural stimulation delivered in accordance with a test protocol
comprises a test therapy.
[0035] FIG. 3 is a flowchart illustrating various methods for
refining, enhancing, or optimizing neural stimulation therapy for
treating symptoms of PD and/or other neurological disorders
according to an embodiment of the invention. In one embodiment, a
method 200 includes an identification procedure 202 that involves
identification of one or more patient symptoms to which neural
stimulation therapy, possibly in conjunction with one or more
adjunctive therapies, may be directed. The method 200 may also
include a symptom selection procedure 204 that involves selection
or consideration of a first, a next, or an additional subset of
patient symptoms to which neural stimulation therapy may be
directed. The symptom selection procedure 204 may facilitate
initial selection of symptoms expected to rapidly respond to neural
stimulation, such as tremor and/or rigidity, followed by selection
of other symptoms such as bradykinesia that may respond more
slowly.
[0036] The method 200 may further include a test protocol
management procedure 206 that involves establishing, adjusting,
and/or adapting a test protocol that specifies or defines a test
therapy intended to be applied to the patient 190 for a given test
period. The test protocol may specify or define neural stimulation
parameters corresponding to the test therapy, and may also specify
parameters corresponding to one or more adjunctive therapies such
as drug therapies. The method 200 may additionally include a test
delivery procedure 208 that involves application or delivery of the
test therapy to the patient 190 in accordance with the test
protocol; and an observation procedure 210 that involves
observation, monitoring, and/or measuring of patient symptoms at
one or more times in association with and/or following the delivery
procedure 208. The observation procedure 210 may involve one or
more patient monitoring units 180, and/or direct human observation
of the patient 190.
[0037] The method 200 may further include an evaluation procedure
212 involving determination of an extent to which one or more
patient symptoms currently under consideration have improved or
changed as a result of the most recently applied test therapy. In a
manner analogous to that for the observation procedure 210, the
evaluation procedure 212 may involve one or more patient monitoring
units 180 and/or direct human evaluation of the patient 190. In the
event that further improvement of symptoms currently under
consideration is necessary, likely, or possible, the method 200 may
return to the test protocol management procedure 206.
Alternatively, in the event that additional patient symptoms
require consideration, the method 200 may return to the symptom
selection procedure 204.
[0038] In addition to procedures directed toward refining,
enhancing, or optimizing an extent to which one or more symptoms
can be successfully or adequately treated by neural stimulation
(possibly in conjunction with one or more adjunctive therapies),
the method 200 may include an ongoing treatment delivery procedure
218 that involves application of an arrived-at ongoing therapy to
the patient in accordance with an ongoing, essentially ongoing, or
generally ongoing treatment protocol. The ongoing treatment
protocol may correspond to or be based upon a previously considered
test protocol, and may involve one or more adjunctive therapies. In
particular, the ongoing treatment protocol may be identical or
essentially identical to a recently considered test protocol, with
the exception that an ongoing treatment duration corresponding to
the ongoing treatment protocol may be significantly longer than
that of the test period corresponding to such a test therapy.
[0039] The method 200 may also include a reevaluation procedure 220
that involves a one-time, occasional, or periodic reevaluation,
adjustment, and/or adaptation of a most recent ongoing treatment
protocol in view of potential or likely neuroplastic changes,
variations in ongoing treatment effectiveness, and/or overall
patient health or condition over time. Such reevaluation,
adjustment, or adaptation may occur after a predetermined time
interval, such as 1 month, several months, or 1 or more years
following initiation of an ongoing treatment delivery procedure
218. The reevaluation procedure 220 may be performed on a one-time
or repeated basis based upon the judgment of a medical
professional.
[0040] The reevaluation procedure 220 may itself involve one or
more steps of the method 200. Through a reevaluation procedure 220,
it may be determined that one or more patient symptoms may be
better, successfully, or adequately treated or managed in
accordance with a different pulse repetition frequency function; a
lower peak intensity or amplitude; less frequent neural
stimulation; a modified configuration of elements within the set of
electrodes 140 and/or modified signal polarities applied thereto;
lower dosage and/or less frequent drug therapy; and/or other
variations in or modifications to the ongoing treatment protocol.
As further described below with reference to FIG. 6, a reevaluation
procedure 220 that indicates that better, successful, or adequate
treatment or management of one or more patient symptoms may be
achieved with less intense and/or less frequent neural stimulation
may be indicative of compensatory, restorative, and/or
rehabilitative neuroplastic change within the patient 190.
[0041] FIG. 4 is a flowchart illustrating various methods for
establishing, adjusting, or adapting a test protocol according to
an embodiment of the invention. Such methods may be used in the
test protocol management procedure 206 of FIG. 3. In one
embodiment, a method 300 includes an adjustment procedure 302 that
involves adjustment, cessation, or interruption of patient
therapies currently in progress as required. Such therapies may
comprise neural stimulation and/or one or more adjunctive therapies
such as a drug therapy. The method 300 may also include a waiting
procedure 304 during which effects of recently adjusted,
discontinued, or interrupted therapies are allowed to subside,
stabilize, or "wash out." The waiting procedure 304 may maximize or
increase a likelihood that a previously applied therapy has a
minimal or negligible effect upon an upcoming test therapy (i.e.,
no carry-over effects). The method 300 may further include an
assessment procedure 306 that involves assessment, qualification,
and/or quantification of the severity of one or more patient,
symptoms, possibly to establish a baseline or reference patient
condition.
[0042] The method 300 may additionally include a duration
establishment procedure 308 that involves determination or
definition of a test period duration during which a test therapy
may be applied to the patient 190. A test period duration may be
short or relatively short, for example, approximately 1 or more
minutes or hours, to facilitate efficient determination of the
effectiveness of a test protocol upon acute or readily responsive
patient symptoms. Alternatively, a test period duration may be
relatively long, for example, approximately 1 or more days, weeks,
or even months, to facilitate determination of the effectiveness of
a test protocol upon patient symptoms having slower or prolonged
treatment response characteristics. The method 300 may further
include a first test protocol definition procedure 310 that
involves determination, selection, and/or specification of neural
stimulation parameters that comprise one or more portions of the
test protocol. The method 300 may additionally include a second
test protocol definition procedure 312 that involves determination
or definition of a set of parameters corresponding to one or more
adjunctive therapies that may form a portion of the test protocol.
Such parameters may include, for example, a drug dosage and
delivery schedule.
[0043] FIG. 5 is a flowchart illustrating various methods for
determining neural stimulation parameters according to an
embodiment of the invention. Such methods may be used in the first
test protocol definition procedure 310 of FIG. 4. In one
embodiment, a method 400 includes a delivery period selection
procedure 402 that involves determination or selection of a first
or next time interval within the current test period that neural
stimulation may be delivered to the patient 190. The method 400 may
further include a pulse sequence duration procedure 404 that
involves selection and/or specification of one or more pulse
sequence durations and/or quiescent intervals within and/or between
pulse sequences for the neural stimulation delivery period
currently under consideration. The method 400 may accommodate
multiple pulse sequences, variable types of pulse train sequences,
and/or quiescent intervals between pulse sequences to provide
enhanced flexibility with respect to establishing test protocols
that may be useful for efficiently treating symptoms of various
disorders.
[0044] Relative to treating PD symptoms, stimulation that reduces
the output activity of the globus pallidus internalis (GPi) can be
highly beneficial. Deep Brain Stimulation (DBS) research has shown
that stimulation delivered to the globus pallidus internalis (GPi)
may significantly reduce GPi activity over a period that can last
several seconds beyond the termination of such stimulation. For
example, a continuous or essentially continuous pulse train lasting
3 seconds may result in reduced or significantly reduced GPi output
activity that lasts approximately 1.5 seconds beyond termination of
the 3 second pulse train. Delivering or applying neural stimulation
to one or more target neural populations having synaptic
projections into the GPi or associated neural circuitry such that
pulse sequences or pulse trains are separated by one or more
appropriate quiescent intervals may therefore maintain or sustain
reduced GPi activity while eliminating the need to deliver
continuous stimulation. Delivery of neural stimulation in such a
manner advantageously reduces power consumption. Thus, a pulse
sequence comprising periodic pulse trains lasting approximately 3
seconds separated by quiescent intervals lasting approximately 1.5
seconds may provide significant therapeutic benefit in a power
efficient manner.
[0045] The method 400 may additionally include a waveform
definition procedure 406 that involves selection and/or
specification of a set of waveform parameters that define or
describe each pulse sequence currently under consideration. Such
waveform characteristics may include a pulse repetition frequency
or frequency function, a pulse amplitude decay function, and/or
other pulse sequence parameters. Depending upon embodiment details
and/or current symptoms under consideration, the pulse repetition
frequency may vary within any given pulse sequence, and/or from one
pulse sequence to another. By accommodating such variation, the
method may facilitate the definition of a test protocol or an
arrived-at ongoing treatment protocol that includes multiple pulse
repetition frequencies, where particular individual pulse
frequencies or pulse frequency subsets may be directed toward
maximizing or enhancing the effectiveness of neural stimulation in
treating particular PD and/or movement disorder symptoms. As an
illustrative example, if (a) a pulse repetition frequency of
approximately 25 Hz appears optimal or nearly optimal for treating
tremor, (b) a pulse repetition frequency of approximately 30 Hz
appears optimal for treating rigidity, and (c) a pulse repetition
frequency of approximately 15 Hz appears optimal for treating
bradykinesia, then a test protocol or an ongoing treatment protocol
may call for neural stimulation that periodically alternates
between these pulse repetition frequencies in accordance with given
neural stimulation delivery periods and possibly including one or
more quiescent periods therebetween. Alternatively, the test
protocol or the ongoing treatment protocol may call for neural
stimulation that sweeps between 15 and 30 Hz in a continuous or
nearly continuous manner.
[0046] In general, a test protocol may call for neural stimulation
having one or more pulse repetition frequencies specified in
accordance with a temporal and/or mathematical function that is
based upon individual pulse repetition frequencies determined to be
optimal or near-optimal for treating particular subsets of patient
symptoms. Such a temporal and/or mathematical function may be based
upon the nature and/or severity of such symptoms. For example, if
the patient's baseline or reference state indicates that the
patient experiences tremor in a significantly more severe manner
than bradykinesia, a test protocol may call for neural stimulation
in which an amount of time spent delivering stimulation optimized
or nearly optimized for treating tremor exceeds an amount of time
spent delivering stimulation optimized or nearly optimized for
treating bradykinesia. Additionally or alternatively, the test
protocol may call for neural stimulation having a frequency
function that is weighted or biased relative to individually
determined frequencies corresponding to particular symptom subsets.
Such a test protocol may call for neural stimulation that delivers,
for example, a combined frequency of 27 Hz for treating both tremor
and rigidity, as well as a pulse repetition frequency of 15 Hz for
treating bradykinesia. Furthermore, a test protocol may call for
neural stimulation having a pulse repetition frequency function
that depends upon one or more treatment response times associated
with particular symptoms, and/or one or more time intervals that
relief from particular symptoms persists in the absence of neural
stimulation.
[0047] The method 400 may further include an electrode element
selection procedure 408 that involves identifying or defining a
spatial and/or temporal distribution of electrodes 142 and/or
contacts 144 to which neural stimulation may be directed during the
delivery period under consideration. The electrode element
selection procedure 408 may alternatively or additionally select or
define signal polarities corresponding to particular electrodes 142
and/or contacts 144 relative to one or more portions of the test
period. In the event that a current test period includes more than
one delivery period, the method 400 may return to the delivery
period selection procedure 402.
[0048] The method 400 may also include a threshold determination
procedure 412 that involves determination of a minimum or near
minimum neural stimulation amplitude or intensity that evokes or
induces a given type of patient response, reaction, behavior,
and/or sensation. A neural stimulation threshold may be determined
by successively applying higher amplitude neural stimulation
signals to the patient 190 until an observable or detectable
response occurs. Each threshold determination attempt may apply a
limited duration neural stimulation signal to the patient 190, for
example, a pulse sequence lasting 0.5 seconds, 1 second, 3 seconds,
or some other length of time. A waiting, quiescent, or washout
period between successive threshold determination attempts, during
which the patient 190 receives no neural stimulation, may ensure
that each threshold determination attempt is independent or
essentially independent of residual effects associated with
previously applied signals. A quiescent period may span several
seconds to one or more minutes, for example, approximately one
minute. In one embodiment, the threshold determination procedure
412 involves determination of a motor, movement, or motion
threshold through motion detection techniques and/or visual
observation. In another embodiment, the threshold determination
procedure 412 may involve determination of an EMG threshold and/or
another type of neural stimulation threshold.
[0049] The method 400 may further include an amplitude
determination procedure 414 that involves determination or
selection of peak or average amplitudes or intensities
corresponding to the set of pulse sequences defined or specified
within the current test period based upon the results or outcome of
the threshold determination procedure 412. Depending upon
embodiment details, a peak pulse sequence amplitude may be defined
as a given percentage of a neural stimulation threshold, for
example, 50% of a movement threshold or 70% of an EMG threshold. In
some embodiments, different pulse sequences within a delivery
period or test period may have different peak amplitudes.
[0050] FIG. 6 is a flowchart illustrating various methods for
modifying, adjusting, or adapting neural stimulation therapy in
view of a likelihood or possibility of a lasting or long term
neuroplastic change occurring within a patient 190 over time. Such
methods may involve the reevaluation procedure 220 and/or other
procedures described above with in association with FIG. 3. The
propensity of a given neural population to undergo neuroplastic
change may depend upon the application of an initial neural
stimulation regimen to the neural population in a particular
manner, such as a continuous, generally continuous, or frequent
manner over a given or minimum amount of time. This may in turn
facilitate or effectuate initiation and reinforcement of chemical
and/or structural adaptations or changes in the neural population
and/or neural circuitry associated therewith, thereby "priming" the
neural population to accept and/or maintain long term or lasting
neuroplastic change.
[0051] As an illustrative example, depending upon symptom type and
severity, effective or generally effective treatment of PD or other
movement disorder symptoms may initially require continuous,
essentially continuous, or nearly continuous neural stimulation for
a neuroplastic priming period of approximately one month. After
such a neuroplastic priming period, however, effective treatment of
one or more symptoms may require stimulation for a limited number
of hours per day, such as during the patient's normal waking hours.
Alternatively, effective treatment may require continuous
stimulation for approximately 30 minutes, after which treatment may
be interrupted for approximately 30 minutes, and so on. In another
embodiment, the stimulation can be applied on a twenty four hour
basis for an initial period and then on a reduced basis for a
subsequent period. The stimulation, for example, can be applied all
throughout each day for an initial period of approximately one
month, and then it can be applied only during waking hours after
the initial period. This is expected to provide sufficient results
in many situations and conserve battery life.
[0052] One method 500 for modifying, adjusting, or adapting neural
stimulation therapy in view of a likelihood or possibility of a
lasting or long term neuroplastic change may include a first
stimulation optimization or refinement procedure 502 that involves
determination of a continuous neural stimulation protocol for
treating one or more patient symptoms. The method 500 may further
include a continuous stimulation procedure 504 that involves
delivery or application of neural stimulation to the patient 190 in
accordance with the continuous neural stimulation protocol for a
predetermined time period, for example, one or more weeks or one or
more months. The predetermined time period may correspond to an
expected or likely neuroplastic priming period. The method 500 may
additionally include a second stimulation optimization or
refinement procedure 506 that involves determination of a
noncontinuous and/or periodically interrupted neural stimulation
protocol for treating patient symptoms under consideration. The
method 500 may also include a noncontinuous or interrupted
stimulation procedure that involves delivery of noncontinuous
and/or interrupted neural stimulation to the patient 190 in
accordance with the noncontinuous and/or interrupted neural
stimulation protocol. The first and/or second stimulation
optimization or refinement procedures 502, 506 may include or
encompass one or more procedures described above in association
with FIG. 3. Additionally, the second stimulation optimization or
refinement procedure 506 may be repeated following application of
noncontinuous or interrupted stimulation to the patient 190 for a
given amount of time.
[0053] From the foregoing, it will be appreciated that specific
embodiments of the invention have been described herein for
purposes of illustration, but that various modifications may be
made without deviating from the spirit and scope of the invention.
Accordingly, the invention is not limited except as by the appended
claims.
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