U.S. patent application number 14/102388 was filed with the patent office on 2014-04-10 for implantable stimulator.
This patent application is currently assigned to BOSTON SCIENTIFIC NEUROMODULATION CORPORATION. The applicant listed for this patent is BOSTON SCIENTIFIC NEUROMODULATION CORPORATION. Invention is credited to Tom Xiaohai He, Alfred E. Mann.
Application Number | 20140100633 14/102388 |
Document ID | / |
Family ID | 38049329 |
Filed Date | 2014-04-10 |
United States Patent
Application |
20140100633 |
Kind Code |
A1 |
Mann; Alfred E. ; et
al. |
April 10, 2014 |
IMPLANTABLE STIMULATOR
Abstract
An implantable stimulator includes a tube assembly that is
configured to house a number of components that are configured to
apply at least one stimulus to at least one stimulation site within
a patient. The tube assembly has a shape that allows the stimulator
to be implanted within said patient in a pre-determined
orientation. Exemplary methods of stimulating a stimulation site
within a patient include applying an electrical stimulation current
to a stimulation site via one or more electrodes extending along
one or more sides of a stimulator. The stimulator has a shape
allowing the stimulator to be implanted within the patient in a
pre-determined orientation.
Inventors: |
Mann; Alfred E.; (Beverly
Hills, CA) ; He; Tom Xiaohai; (Simi Valley,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BOSTON SCIENTIFIC NEUROMODULATION CORPORATION |
Valencia |
CA |
US |
|
|
Assignee: |
BOSTON SCIENTIFIC NEUROMODULATION
CORPORATION
Valencia
CA
|
Family ID: |
38049329 |
Appl. No.: |
14/102388 |
Filed: |
December 10, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13053031 |
Mar 21, 2011 |
8630705 |
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14102388 |
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11280620 |
Nov 16, 2005 |
7920915 |
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13053031 |
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Current U.S.
Class: |
607/59 ; 607/116;
607/62 |
Current CPC
Class: |
A61N 1/3605 20130101;
A61N 1/37518 20170801; A61N 1/3756 20130101; A61N 1/0551 20130101;
A61N 1/37205 20130101 |
Class at
Publication: |
607/59 ; 607/116;
607/62 |
International
Class: |
A61N 1/375 20060101
A61N001/375 |
Claims
1-26. (canceled)
27. An implantable stimulator comprising: an elongate casing
defining an interior cavity and including an outer surface having a
generally rectangular cross-section with four rounded corners that
are effective to hinder rotation of the implantable stimulator
within a patient; a plurality of discrete electrodes disposed on
the outer surface of the casing; stimulation circuitry housed in
the interior cavity defined by the casing; and at least one
electrical conductor coupling the discrete electrodes to the
stimulation circuitry housed in the interior cavity.
28. The implantable stimulator of claim 27, wherein the at least
one electrical conductor comprises a plurality of electrical
conductors respectively coupling the discrete electrodes to the
stimulation circuitry housed in the interior cavity.
29. The implantable stimulator of claim 28, further comprising an
electrical insulator on which at least portions of the plurality of
electrical conductors are disposed.
30. The implantable stimulator of claim 29, wherein the electrical
insulator comprises an insulator film.
31. The implantable stimulator of claim 31, wherein the outer
surface of the elongate casing has asymmetric lateral sections.
32. The implantable stimulator of claim 31, wherein the discrete
electrodes are each dimensioned to occupy a portion of a long side
of the generally rounded rectangular lateral sections.
33. The implantable stimulator of claim 27, wherein the stimulation
circuitry is adjustable to deliver electrical stimulus to a site
within a patient via one or more of the discrete electrodes.
34. The implantable stimulator of claim 27, further comprising a
feed through assembly coupled to the casing, the feed through
assembly comprising a number of conductive feed throughs that
electrically couple the stimulation circuitry housed within the
casing to the electrodes.
35. The implantable stimulator of claim 34, further comprising: a
first connecting band hermetically coupled to an end of the casing;
a second connecting band hermetically coupled to an end of the feed
through assembly, wherein the first connecting band and the second
connecting band are hermetically coupled to each other.
36. The implantable stimulator of claim 27, further comprising a
battery coupled to the elongate casing, the battery configured to
provide power for the stimulation circuitry housed within the
casing.
37. The implantable stimulator of claim 36, further comprising: a
first connecting band coupled to an end of the casing; and a second
connecting band coupled to an end of the battery, wherein the first
connecting band and the second connecting band are hermetically
coupled to each other.
38. The implantable stimulator of claim 27, further comprising an
indifferent electrode for completing one or more stimulation
circuits.
39. The implantable stimulator of claim 27, wherein the casing
comprises a material configured to allow passage of a magnetic
field.
40. The implantable stimulator of claim 27, wherein the casing is
composed of a ceramic material.
41. The implantable stimulator of claim 27, wherein the stimulation
circuitry housed within the casing comprises: a programmable memory
unit storing one or more stimulation parameters; and electrical
circuitry configured to generate an electrical stimulus.
42. The implantable stimulator of claim 41, further comprising a
sensor device for sensing at least one parameter related to a
medical condition of a patient, wherein the stimulation circuitry
is configured to adjust the electrical stimulus based on the one or
more stimulation parameters.
43. The implantable stimulator of claim 27, wherein a height of the
implantable stimulator is equal to or less than 4.25 millimeters, a
width of the implantable stimulator is equal to or less than 7.25
millimeters, and a length of the implantable stimulator is equal to
or less than 28 millimeters.
Description
BACKGROUND
[0001] A wide variety of medical conditions and disorders have been
successfully treated using an implanted stimulator. Such a
stimulator will typically stimulate internal tissue, such as a
nerve, by emitting an electrical stimulation current according to
programmed stimulation parameters.
[0002] One class of such implantable stimulators, also known as
BION.RTM. devices (where BION.RTM. is a registered trademark of
Advanced Bionics Corporation, of Valencia, Calif.), are typically
characterized by a small, cylindrical housing that contains
electronic circuitry that produces the desired electric stimulation
current between spaced electrodes. These stimulators, also referred
to as microstimulators, are implanted proximate to the target
tissue so that the stimulation current produced by the electrodes
stimulates the target tissue to reduce symptoms or otherwise
provide therapy for a wide variety of conditions and disorders.
[0003] For example, urinary urge incontinence may be treated by
stimulating the nerve fibers proximal to the pudendal nerves of the
pelvic floor. Erectile or other sexual dysfunctions may be treated
by providing stimulation of the cavernous nerve(s). Other
disorders, e.g., neurological disorders caused by injury or stroke,
may be treated by providing stimulation to other appropriate
nerve(s).
[0004] In U.S. Pat. No. 5,312,439, entitled Implantable Device
Having an Electrolytic Storage Electrode, an implantable device for
tissue stimulation is described. U.S. Pat. No. 5,312,439 is
incorporated herein by reference in its entirety.
[0005] Another microstimulator known in the art is described in
U.S. Pat. No. 5,193,539, "Implantable Microstimulator," which
patent is also incorporated herein by reference in its entirety.
The '539 patent describes a microstimulator in which power and
information for operating the microstimulator are received through
a modulated, alternating magnetic field. A coil in the
microstimulator is adapted to function as the secondary winding of
a transformer. This induction coil receives energy from outside the
patient's body and a capacitor is used to store electrical energy
which is released to the microstimulator's exposed electrodes under
the control of electronic control circuitry.
[0006] In U.S. Pat. Nos. 5,193,540 and 5,405,367, which patents are
incorporated herein by reference in their respective entireties, a
structure and method of manufacture of an implantable
microstimulator are disclosed. The microstimulator has a structure
which is manufactured to be substantially encapsulated within a
hermetically-sealed housing that is inert to body fluids, and of a
size and shape capable of implantation in a living body with
appropriate surgical tools. Within the microstimulator, an
induction coil receives energy or data from outside the patient's
body.
[0007] In yet another example, U.S. Pat. No. 6,185,452, which
patent is likewise incorporated herein by reference in its
entirety, there is disclosed a device configured for implantation
beneath a patient's skin for the purpose of nerve or muscle
stimulation and/or parameter monitoring and/or data communication.
Such a device contains a power source for powering the internal
electronic circuitry. This power supply is a battery that may be
externally charged periodically, e.g., once each day. Similar
battery specifications are found in U.S. Pat. No. 6,315,721, which
patent is additionally incorporated herein by reference in its
entirety.
[0008] Other microstimulator systems prevent and/or treat various
disorders associated with prolonged inactivity, confinement or
immobilization of one or more muscles. Such microstimulators are
taught, e.g., in U.S. Pat. No. 6,061,596 "Method for Conditioning
Pelvis Musculature Using an Implanted Microstimulator;" U.S. Pat.
No. 6,051,017 "Implantable Microstimulator and Systems Employing
the Same;" U.S. Pat. No. 6,175,764 "Implantable Microstimulator
System for Producing Repeatable Patterns of Electrical Stimulation;
U.S. Pat. No. 6,181,965 "Implantable Microstimulator System for
Prevention of Disorders;" U.S. Pat. No. 6,185,455 "Methods of
Reducing the Incidence of Medical Complications Using Implantable
Microstimulators;" and U.S. Pat. No. 6,214,032 "System for
Implanting a Microstimulator." The applications described in these
additional patents, including the power charging techniques, may
also be used with the present invention. The '596, '017, '764,
'965, '455, and '032 patents are incorporated herein by reference
in their respective entireties.
[0009] As will be readily appreciated, a key part of patient
treatment using an implanted stimulator is the proper placement of
the stimulator such that the stimulation electrodes are proximate
to the target tissue to be stimulated. If the stimulation
electrodes are optimally placed near the target tissue, stimulation
can be affected over a wide range of parameters with optimally
minimal power consumption.
SUMMARY
[0010] An exemplary implantable stimulator includes a tube assembly
that is configured to house a number of components that are
configured to apply at least one stimulus to at least one
stimulation site within a patient. The tube assembly has a shape
that allows the stimulator to be implanted within said patient in a
pre-determined orientation.
[0011] Exemplary methods of stimulating a stimulation site within a
patient include applying an electrical stimulation current to a
stimulation site via one or more electrodes extending along one or
more sides of a stimulator. The stimulator has a shape allowing the
stimulator to be implanted within the patient in a pre-determined
orientation.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The accompanying drawings illustrate various embodiments of
the present invention and are a part of the specification. The
illustrated embodiments are merely examples of the present
invention and do not limit the scope of the invention.
[0013] FIG. 1 is a block diagram illustrating a number of
components of an exemplary implantable stimulator according to
principles described herein.
[0014] FIG. 2 illustrates an exemplary structure of the implantable
stimulator according to principles described herein.
[0015] FIG. 3 illustrates an exemplary ceramic tube assembly
according to principles described herein.
[0016] FIG. 4 illustrates an exemplary stimulator battery according
to principles described herein.
[0017] FIG. 5 illustrates an exemplary feed through assembly
according to principles described herein.
[0018] FIG. 6 shows the feed through assembly, ceramic tube
assembly, and battery laser-welded together to form a sealed
hermetic enclosure for the stimulator according to principles
described herein.
[0019] FIG. 7 illustrates an exemplary film electrode assembly
according to principles described herein.
[0020] FIG. 8 illustrates an exemplary stimulator wherein the
electrodes are coupled directly to the surface of the stimulator
according to principles described herein.
[0021] FIG. 9 illustrates an exemplary stimulator according to
principles described herein which is adapted to be easily and
readily positioned at an optimal location in a patient according to
principles described herein.
[0022] FIGS. 10-12 illustrated various steps in an exemplary method
of implanting a stimulator proximal to a stimulation site according
to principles described herein.
[0023] FIG. 13 is a flowchart further illustrating the exemplary
method illustrated in FIGS. 10-12 and according to principles
described herein.
[0024] FIG. 14 illustrates various systems and external devices
that may be used to support the implanted stimulator according to
principles described herein.
[0025] FIG. 15 depicts a number of stimulators configured to
communicate with each other and/or with one or more external
devices according to principles described herein.
[0026] FIG. 16 depicts the upper cervical spine area of a patient
and shows a number of nerves originating in the upper cervical
spine area that can be stimulated with an implanted stimulator
according to principles described herein.
[0027] FIG. 17 shows various nerves in the back of the head and
neck that can be stimulated with an implanted stimulator according
to principles described herein.
[0028] Throughout the drawings, identical reference numbers
designate similar, but not necessarily identical, elements.
DETAILED DESCRIPTION
[0029] The present application is related to U.S. patent
application Ser. No. 11/142,154, filed Jun. 1, 2005, entitled
"Implantable Microstimulator with External Electrodes Disposed on a
Film Substrate and Methods of Manufacture and Use," and to a U.S.
patent application entitled "Methods and Systems for Placing an
Implanted Stimulator for Stimulating Tissue" to He et al., client
docket number AB-565U, which application was filed on Sep. 21,
2005.
[0030] An implantable stimulator having a shape that allows the
stimulator to be implanted within a patient in a pre-determined
orientation and methods of using such a stimulator are described
herein. The stimulator includes a tube assembly, a battery, and a
film electrode assembly. The tube assembly is configured to house a
number of components that generate at least one stimulus that is
applied to at least one stimulation site within a patient. The
battery is coupled to the tube assembly and is configured to
provide power for the components housed within the tube assembly.
The film electrode assembly includes a number of electrodes and is
coupled to the stimulator such that the electrodes extend along one
or more sides of the stimulator.
[0031] In the following description, for purposes of explanation,
numerous specific details are set forth in order to provide a
thorough understanding of the present systems and methods. It will
be apparent, however, to one skilled in the art that the present
systems and methods may be practiced without these specific
details. Reference in the specification to "one embodiment" or "an
embodiment" means that a particular feature, structure, or
characteristic described in connection with the embodiment is
included in at least one embodiment. The appearance of the phrase
"in one embodiment" in various places in the specification are not
necessarily all referring to the same embodiment.
[0032] As used herein and in the appended claims, the term
"stimulator" will be used broadly to refer to any type of device
that is implanted to deliver a stimulus to a stimulation site
within a patient. As used herein and in the appended claims, unless
otherwise specifically denoted, the term "stimulation site" will be
used to refer to any nerve, muscle, organ, or other tissue within a
patient that is stimulated by an implantable stimulator. For
example, in the case of urinary incontinence, the stimulation site
may be, but is not limited to, any nerve or muscle in the pelvic
floor. Nerves in the pelvic floor region that may be targeted for
stimulation include, but are not limited to, the pudendal nerve,
pelvic nerve, and the clitoral branches of the pudendal nerve.
[0033] The stimulus applied to the stimulation site may include
electrical stimulation, also known as neuromodulation. Electrical
stimulation will be described in more detail below. The stimulator
may additionally or alternatively be configured to infuse
therapeutic dosages of one or more drugs into the stimulation site
or function in a coordinated manner with a drug delivery system
configured to infuse the therapeutic dosages of one or more drugs
into the stimulation site. Consequently, as used herein and in the
appended claims, the term "stimulus" or "stimulation," unless
otherwise indicated, will broadly refer to an electrical
stimulation, drug stimulation, or both.
[0034] The one or more drugs that may be applied to a stimulation
site may have an excitatory effect on the stimulation site.
Additionally or alternatively, the one or more drugs may have an
inhibitory effect on the stimulation site. Exemplary excitatory
drugs that may be applied to a stimulation site include, but are
not limited to, at least one or more of the following: an
excitatory neurotransmitter (e.g., glutamate, dopamine,
norepinephrine, epinephrine, acetylcholine, serotonin); an
excitatory neurotransmitter agonist (e.g., glutamate receptor
agonist, L-aspartic acid, N-methyl-D-aspartic acid (NMDA),
bethanechol, norepinephrine); an inhibitory neurotransmitter
antagonist(s) (e.g., bicuculline); an agent that increases the
level of an excitatory neurotransmitter (e.g., edrophonium,
Mestinon); and/or an agent that decreases the level of an
inhibitory neurotransmitter (e.g., bicuculline).
[0035] Exemplary inhibitory drugs that may be applied to a
stimulation site include, but are not limited to, at least one or
more of the following: an inhibitory neurotransmitter(s) (e.g.,
gamma-aminobutyric acid, a.k.a. GABA, dopamine, glycine); an
agonist of an inhibitory neurotransmitter (e.g., a GABA receptor
agonist such as midazolam or clonidine, muscimol); an excitatory
neurotransmitter antagonist(s) (e.g. prazosin, metoprolol,
atropine, benztropine); an agent that increases the level of an
inhibitory neurotransmitter; an agent that decreases the level of
an excitatory neurotransmitter (e.g., acetylcholinesterase, Group
II metabotropic glutamate receptor (mGluR) agonists such as
DCG-IV); a local anesthetic agent (e.g., lidocaine); and/or an
analgesic medication. It will be understood that some of these
drugs, such as dopamine, may act as excitatory neurotransmitters in
some stimulation sites and circumstances, and as inhibitory
neurotransmitters in other stimulation sites and circumstances.
[0036] Additional or alternative drugs that may be applied to a
stimulation site include at least one or more of the following
substances: non-steroidal anti-inflammatory medications (NSAIDS)
(e.g., ibuprofen, naproxen, VIOXX); estrogens (e.g., estrone,
estradiol, estriol, esters of estradiol, synthetic estrogens such
as diethylstilbestrol, quinestrol, chlorotrianisene); progestins
(e.g., naturally occurring progesterone, medroxyprogesterone
acetate, norethindrone acetate, hydroxyprogesterone acetate,
norgestrel, norethindrone); antiestrogens (e.g., clomiphene,
tamoxifen); gonadotropin releasing hormone agonist analogues (e.g.,
leuprolide acetate, nafarelin); androgens (e.g., testosterone,
testosterone cypionate, fluoxymesterone, fluoxymesterone, danazol,
testolactone); antiandrogens (e.g., cyproterone acetate,
flutamide); opiods (e.g., morphine); ziconitide; and/or
antidepressants (e.g., serotonin specific reuptake inhibitors and
tricyclic antidepressants).
[0037] Any of the above listed drugs, alone or in combination, or
other drugs developed or shown effective to treat a medical
condition or its symptoms may be applied to the stimulation site.
In some embodiments, the one or more drugs are infused chronically
into the stimulation site. Additionally or alternatively, the one
or more drugs may be infused acutely into the stimulation site in
response to a biological signal or a sensed need for the one or
more drugs.
[0038] Turning to the appended drawings, FIG. 1 is a block diagram
illustrating a number of components of an exemplary implantable
stimulator (100). The components of the stimulator (100) of FIG. 1
may be similar to the components included within a BION.RTM.
microstimulator (Advanced Bionics.RTM. Corporation, Valencia,
Calif.), for example. Various details associated with the
manufacture, operation, and use of BION implantable
microstimulators are disclosed in U.S. Pat. Nos. 5,193,539;
5,193,540; 5,312,439; 6,185,452; 6,164,284; 6,208,894; and
6,051,017 and in U.S. application Ser. No. 10/609,457. All of these
listed patents and application are incorporated herein by reference
in their respective entireties.
[0039] As shown in FIG. 1, the stimulator (100) may include a
battery (145), a programmable memory (146), electrical circuitry
(144), and a coil (147). The battery (145) is configured to output
a voltage used to supply the various components within the
stimulator (100) with power. The battery (145) also provides power
for any stimulation current applied by the stimulator (100) to the
stimulation site. The battery (145) may be a primary battery, a
rechargeable battery, a capacitor, or any other suitable power
source. Systems and methods for recharging the battery (145), where
the battery (145) is rechargeable, will be described below.
[0040] The coil (147) is configured to receive and/or emit a
magnetic field (also referred to as a radio frequency (RF) field)
that is used to communicate with or receive power from one or more
external devices that support the implanted stimulator (100),
examples of which will be described below. Such communication
and/or power transfer may include, but is not limited to,
transcutaneously receiving data from the external device,
transmitting data to the external device, and/or receiving power
used to recharge the battery (145).
[0041] The programmable memory unit (146) is used for storing one
or more sets of data, for example, stimulation parameters. The
stimulation parameters may include, but are not limited to,
electrical stimulation parameters and drug stimulation parameters.
The programmable memory (146) allows a patient, clinician, or other
user of the stimulator (100) to adjust the stimulation parameters
such that the electrical stimulation and/or drug stimulation are at
levels that are safe and efficacious for a particular medical
condition and/or for a particular patient. Electrical stimulation
and drug stimulation parameters may be controlled independently.
However, in some instances, the electrical stimulation and drug
stimulation parameters are coupled, e.g., electrical stimulation
may be programmed to occur only during drug stimulation. The
programmable memory (146) may be any type of memory unit such as,
but not limited to, random access memory (RAM), static RAM (SRAM),
a hard drive, or the like.
[0042] The electrical stimulation parameters may control various
parameters of the stimulation current applied to the stimulation
site including, but not limited to, the frequency, pulse width,
amplitude, burst pattern (e.g., burst on time and burst off time),
duty cycle or burst repeat interval, ramp on time and ramp off time
of the stimulation current that is applied to the stimulation site.
The drug stimulation parameters may control various parameters
including, but not limited to, the amount of drugs infused into the
stimulation site, the rate of drug infusion, and the frequency of
drug infusion.
[0043] Specific electrical stimulation and drug stimulation
parameters may have different effects on different types of medical
conditions. Thus, in some embodiments, the electrical stimulation
and/or drug stimulation parameters may be adjusted by the patient,
a clinician, or other user of the stimulator (100) as best serves a
particular medical condition. The electrical stimulation and/or
drug stimulation parameters may also be automatically adjusted by
the stimulator (100), as will be described below. For example, the
amplitude of the stimulation current applied to a target nerve may
be adjusted to have a relatively low value so as to target
relatively large diameter fibers of the target nerve. The
stimulator (100) may also increase excitement of a target nerve by
applying a stimulation current having a relatively low frequency to
the target nerve (e.g., less than 100 Hz). The stimulator (100) may
also decrease excitement of a target nerve by applying a relatively
high frequency to the target nerve (e.g., greater than 100 Hz). The
stimulator (100) may also be programmed to apply the stimulation
current to a target nerve intermittently or continuously.
[0044] The stimulator (100) is coupled to a number of electrodes
E.sub.1-E.sub.n (142) configured to apply the electrical
stimulation current to the stimulation site. As shown in FIG. 1,
there may be any number of electrodes (142) as best serves a
particular application. In some examples, one or more of the
electrodes (142) may be designated as stimulating electrodes and
one of the electrodes (142) may be designated as an indifferent
electrode used to complete one or more stimulation circuits. The
electrodes (142) will be described in more detail below.
[0045] The electrical circuitry (144) is configured to produce
electrical stimulation pulses that are delivered to the stimulation
site via the electrodes (142). In some embodiments, the stimulator
(100) may be configured to produce monopolar stimulation. The
stimulator (100) may alternatively or additionally be configured to
produce multipolar, e.g., bipolar or tripolar, stimulation.
Monopolar electrical stimulation is achieved, for example, using
the housing or a portion of the housing of the stimulator (100) as
an indifferent electrode. Bipolar or tripolar electrical
stimulation is achieved, for example, using one or more of the
electrodes (142) as an indifferent electrode.
[0046] The electrical circuitry (144) may include one or more
processors configured to decode stimulation parameters and generate
the corresponding stimulation pulses. In some embodiments, the
stimulator (100) has at least four channels and drives up to
sixteen electrodes or more. The electrical circuitry (144) may
include additional circuitry such as capacitors, integrated
circuits, resistors, coils, and the like configured to perform a
variety of functions as best serves a particular application.
[0047] The drug delivery system described herein may include any of
a variety of different mechanisms configured to infuse one or more
drugs into the stimulation site. Drug delivery systems based upon a
mechanical or electromechanical infusion pump may be used. In other
examples, the drug delivery system can include a diffusion-based
delivery system, e.g., erosion-based delivery systems (e.g.,
polymer-impregnated with drug placed within a drug-impermeable
reservoir in communication with the drug delivery conduit of a
catheter), electrodiffusion systems, and the like. Another example
is a convective drug delivery system, e.g., systems based upon
electroosmosis, vapor pressure pumps, electrolytic pumps,
effervescent pumps, piezoelectric pumps and osmotic pumps.
[0048] Exemplary pumps or controlled drug release devices suitable
for use as described herein include, but are not necessarily
limited to, those disclosed in U.S. Pat. Nos. 3,760,984; 3,845,770;
3,916,899; 3,923,426; 3,987,790; 3,995,631; 3,916,899; 4,016,880;
4,036,228; 4,111,202; 4,111,203; 4,203,440; 4,203,442; 4,210,139;
4,327,725; 4,360,019; 4,487,603; 4,627,850; 4,692,147; 4,725,852;
4,865,845; 5,057,318; 5,059,423; 5,112,614; 5,137,727; 5,234,692;
5,234,693; 5,728,396; 6,368,315 and the like. All of these listed
patents are incorporated herein by reference in their respective
entireties.
[0049] In some examples, the stimulator (100) is cylindrically
shaped. However, because a cylindrical stimulator (100) can easily
rotate during and after implantation, the stimulator (100) cannot
be implanted with a pre-determined orientation about its central
axis. Hence, a single stimulation electrode is often arranged in a
ring-like formation about the cylindrical stimulator (100) so that
the stimulator (100) can be implanted in any arbitrary orientation.
This ring-like arrangement of the electrode causes the electrical
field emitted by the stimulator (100) to spread in all 360 degrees
of space. In cases where the target tissue or nerve is only located
on one side of the stimulator (100), a 360 degree spread of energy
is inefficient and reduces the battery life of the stimulator (100)
and/or increases the battery recharging frequency of the stimulator
(100). Furthermore, additional power may be consumed in attempts to
provide effective stimulation, and at some point, the stimulating
current may become uncomfortable to the patient if the stimulation
current is increased to compensate for the inefficient energy
spread.
[0050] FIG. 2 illustrates an exemplary structure of the implantable
stimulator (100). In some embodiments, as shown in FIG. 2, the
stimulator (100) has a rectangular cross-section with corner
rounding. The rectangular cross-section shape of the stimulator
(100) allows the stimulator (100) to be implanted within a patient
in a pre-determined orientation. In addition, the slightly
significant aspect ratio (cross-section) of the stimulator (100)
minimizes the profile, or height (107), of the stimulator (100),
which reduces implantation discomfort in many patients. It will be
recognized, however, that the rectangular shape of the stimulator
(100) shown in FIG. 2 is merely exemplary of the many different
dimensional configurations of the stimulator (100). For example,
the stimulator (100) may have a long oval shape or any other shape
that allows the stimulator (100) to be implanted within the patient
in a pre-determined orientation. In general, the stimulator (100)
may have any non-cylindrical shape such that the stimulator (100)
may be implanted within the patient in a pre-determined
orientation.
[0051] As shown in FIG. 2, the stimulator (100) has a height (107),
width (108), and length (109). An exemplary height (107) is
substantially equal to 4.25 millimeters (mm), an exemplary width
(108) is substantially equal to 7.25 mm, and an exemplary length
(109) is substantially equal to 28 mm. It will be recognized that
these dimensions are merely illustrative and that the dimensions of
the stimulator (100) may be greater or less than the exemplary
dimensions given as best serves a particular application.
[0052] In some embodiments, the length (109) of the stimulator
(100) is longer than conventional stimulators so that the battery
(145) may be relatively larger than batteries in conventional
stimulators. A relatively large (145) battery, as will be described
in more detail below, increases the battery life of the stimulator
(100) and reduces the recharging frequency of the stimulator
(100).
[0053] The stimulator (100) of FIG. 2 includes a number of
components. A ceramic tube assembly (101) is coupled on one end to
the battery (145) and on the other end to a feed through assembly
(103). The tube assembly (101) houses the electrical circuitry
(144; FIG. 1), the programmable memory (146; FIG. 1), the coil
(147; FIG. 1), and any other components of the stimulator (100) as
best serves a particular application. The feed through assembly
(103) includes a number of feed throughs (111) coupled to the
electrical circuitry (144; FIG. 1). The feed throughs (111) are
also coupled to a film electrode assembly (105) that includes a
number of electrodes (142). The stimulator (100) may also include
an indifferent electrode (102) coupled to the battery (145). Many
of these components will be described in more detail below in
connection with FIGS. 3-7.
[0054] FIG. 3 illustrates an exemplary tube assembly (101) that can
be used in constructing the stimulator (100) of FIG. 2. As shown in
FIG. 3, the tube assembly (101) includes a tube (230) with
connecting rings (231) at either end. The tube (230) houses the
electrical circuitry (144; FIG. 1), the programmable memory (146;
FIG. 1), the coil (147; FIG. 1), and any other components of the
stimulator (100) as best serves a particular application. The tube
(230) may be made out of any suitable material that allows the coil
(147; FIG. 1) to emit and receive a magnetic field used to
communicate with an external device or with another implanted
device. For example, the tube (230) may be made out of a ceramic
material, glass, a metal (e.g., Titanium) configured to allow the
passage of a magnetic field, or any other suitable material. It
will be assumed that the tube (230) is a ceramic tube in the
examples given herein for illustrative purposes.
[0055] As shown in FIG. 3, the tube (230) has a substantially
rectangular cross-section with rounded corners. However, the shape
of the tube (230) may vary as best serves a particular
application.
[0056] A connecting ring (231) is hermetically brazed to both ends
of the ceramic tube (231). The connecting rings (231) are used to
hermetically seal or couple the ceramic tube assembly (101) to the
battery (145; FIG. 2) and to the feed through assembly (103; FIG.
2). The connecting rings (231) may be made out of titanium or any
other suitable material (e.g., platinum, iridium, tantalum,
titanium nitride, niobium, alloys of any of these, a titanium
alloy, etc.) for hermetically sealing the ceramic tube assembly
(101) to the battery (145; FIG. 2) and to the feed through assembly
(103; FIG. 2). The connecting rings (231) are hermetically brazed
to the ceramic tube (231) using any suitable metal brazing process.
The connecting rings (231) may additionally or alternatively be
made out of metallic materials, glass, ceramic materials, or other
biocompatible materials that are connected to the tube (231) using
an appropriate process (e.g., brazing, welding, molding, and/or
bonding with adhesive).
[0057] FIG. 4 illustrates an exemplary battery (145). The battery
(145) has a cross section substantially equal to the cross section
of the ceramic tube assembly (101; FIG. 3). As previously
mentioned, the battery (145) is configured to present an output
voltage used to supply power to the various components housed
within the ceramic tube assembly (101; FIG. 3). The battery (145)
also provides power for any stimulation current applied by the
stimulator (100) to a stimulation site. Hence, the battery (145)
includes one or more terminals (240) that may be electrically
coupled to the electrical components housed within the ceramic tube
assembly (101; FIG. 3).
[0058] The outer surface of the battery (145) may be made out of
any insulative material such as ceramic or glass. The outer surface
of the battery (145) may additionally or alternatively be insulated
with a non-conductive coating, such as, but not limited to,
Parylene.TM. or Teflon.TM.. A connecting ring (241) is hermetically
brazed or otherwise attached to a proximal end of the battery
(145). The connecting ring (241) may be made out of titanium or any
other material suitable for hermetically attaching the battery
(145) to the ceramic tube assembly (101; FIG. 3).
[0059] In some alternative embodiments, the outer surface of the
battery (145) is made out of a conductive metal (e.g., Titanium). A
metal housing allows the casing of the battery to be relatively
thin, thereby maximizing the space within the battery casing for
battery contents. The metal surface of the battery (145) may be
used as an indifferent electrode.
[0060] The amount of power or energy that the battery (145) may
provide to the various components of the stimulator (100) is
substantially proportional to the physical size of the battery
(145). Hence, the larger the battery (145), the more power the
battery (145) can provide to the components of the stimulator (100;
FIG. 2). Some conventional microstimulators have relatively small
batteries and therefore for some applications have to be recharged
multiple times every day. In some embodiments, the battery (145) of
the present stimulator (100; FIG. 2) is relatively larger than
batteries found in conventional microstimulators. Therefore, the
life of the battery (145) may be up to fifteen times greater or
more than the battery life of conventional stimulator batteries. In
some examples, the battery (145) of the present stimulator (100;
FIG. 2) may for some applications operate up to two weeks or more
without having to be recharged.
[0061] FIG. 5 illustrates an exemplary feed through assembly (103).
The feed through assembly (103) has a cross section substantially
equal to the cross section of the ceramic tube assembly (101; FIG.
3). The feed through assembly (103) includes an outer surface or
wall (251) made of an insulative material such as ceramic or glass.
A connecting ring (252) is hermetically brazed or otherwise
attached to the feed through assembly (103). The connecting ring
(252) may be made out of titanium or any other suitable material
for hermetically attaching the feed through assembly (103) to the
ceramic tube assembly (101; FIG. 3).
[0062] A number of feed throughs (111), each corresponding to an
electrode (142; FIG. 2), are electrically coupled to the outputs of
the electrical circuitry (144; FIG. 1) housed within the ceramic
tube assembly (101; FIG. 3). In some embodiments, the feed throughs
(111) include metal contact pads located on the outer wall (251)
that are coupled to metal vias extending through the feed through
assembly (103) to an inside wall (not shown) of the feed through
assembly (103). These metal vias may be hermetically buried or
brazed inside the feed through assembly (103) and electrically
coupled to the outputs of the electrical circuitry (144; FIG. 1)
housed within the ceramic tube assembly (101; FIG. 3). In this
manner, the feed throughs (111) essentially extend the outputs of
the electrical circuitry (144; FIG. 1) to the outer surface (251)
of the feed through assembly (103). As will be explained in more
detail below, the feed throughs (111) are coupled to a number of
film electrodes (142; FIG. 2) that may be selectively controlled by
the electrical circuitry (144; FIG. 1) housed within the ceramic
tube assembly (101; FIG. 3).
[0063] FIG. 6 shows the feed through assembly (103), ceramic tube
assembly (101), and battery (145) laser welded together to form a
sealed hermetic enclosure for the stimulator (100). The connecting
ring (241) of the battery (145) is laser welded to the connecting
ring (231-1) of the ceramic tube assembly (101) and the connecting
ring (252) of the feed through assembly (103) is laser welded to
the connecting ring (231-2) of the ceramic tube assembly (101). It
will be recognized that the laser welding may include or be
replaced by any suitable technique for hermetically coupling the
connecting rings (241, 252, 231), including forming a mechanical
and electrical bond with a conductive adhesive, such as an
epoxy.
[0064] FIG. 7 illustrates an exemplary film electrode assembly
(105). The film electrode assembly (105) is made out of a polymer
film or any other suitable material and includes a number of film
electrodes (142). The polymer film may be any thickness as best
serves a particular application. Eight film electrodes (142) are
shown in FIG. 7 for illustrative purposes only. There may be more
or less than eight film electrodes (142) as best serves a
particular application.
[0065] Each film electrode (142) is coupled to one of the feed
throughs (111; FIG. 2) via a metal trace (270). Each metal trace
(270) is deposited on the film electrode assembly (105) using any
suitable technique, such as sputtering. The metal traces (270) are
covered or insulated by a thin film of polymer that is deposited
after the metal traces (270) are deposited on the film electrode
assembly (105).
[0066] The feed through assembly (105) may also include a number of
metal contacts (271). The metal contacts (271) are positioned to
make contact with the feed throughs (111; FIG. 2) to form a
conductive path from the feed throughs (111; FIG. 2) to the
electrodes (142). Chemical etching or lithographic techniques may
be used to open areas on the traces (270) to expose the metal to
form the electrodes (142) and the metal contacts (271). It will be
recognized that the electrodes (142) and metal contacts (271) may
be made using any suitable method or technique. The physical
dimensions of the electrodes (142) and the metal contacts (271) may
vary as best serves a particular application.
[0067] It will be noted that the film electrode assembly (105) is
merely exemplary of the many possible electrode configurations that
may be used with the exemplary stimulator (100) described herein.
For example, one or more leads having a number of electrodes may
alternatively or additionally be coupled to the stimulator
(100).
[0068] Alternatively, the electrodes (142) may be coupled directly
to the surface of the stimulator (100). For example, FIG. 8
illustrates an exemplary stimulator (100) wherein the electrodes
(142) are coupled directly to the surface of the stimulator (100).
The electrodes (145) may be disposed on any portion of the
stimulator (100) and, in some examples, may be selectively
configured to act as cathodes or anodes.
[0069] As shown in FIG. 7 and in FIG. 2, the film electrode
assembly (105) is configured to wrap around one or more sides of
the body of the stimulator (100; FIG. 2) such that the electrodes
(142) are aligned along one or more sides of the body of the
stimulator (100; FIG. 2). In some embodiments, the film electrode
assembly (105) includes a top extending member (272) and a bottom
extending member (273) each including a number of electrodes (142).
For example, the top extending member (272) of the film electrode
assembly (105) shown in FIG. 7 includes four electrodes (142-1
through 142-4). Likewise, the bottom extending member (273) of the
film electrode assembly (105) includes four electrodes (142-5
through 142-8). However, the film electrode assembly (105) may
alternatively only include one extending member (e.g., the top
extending member (272)).
[0070] In yet another alternative embodiment, the film electrode
assembly (105) includes more than two extending members. These
multiple extending members may be aligned along any side of the
body of the stimulator (100; FIG. 2). For example, the film
electrode assembly (105) may include four extending members that
extend along all four sides of the stimulator (100; FIG. 2). Each
of the four extending members may include one or more electrodes
(142).
[0071] The film electrode assembly (105) may be coupled to the body
of the stimulator (100) using a medical adhesive or any other
suitable attachment material or device. The film electrode assembly
(105) is aligned such that the metal contacts (271) make contact
with the feed throughs (111; FIG. 2). Mechanical pressure may be
applied, if needed, to ensure that the metal contacts (271) make
sufficient contact with the feed throughs (111; FIG. 2).
[0072] In some embodiments, each of the electrodes (142) may be
selectively controlled. In other words, the electrical stimulation
parameters may be adjusted or programmed to control the stimulation
current output via each of the electrodes (142). For example, if
the electrode (142-4) shown in FIG. 2 is nearest the desired
stimulation site, the electrical stimulation parameters may be
adjusted such that stimulation current is only delivered via
electrode (142-4). By selectively applying stimulation current via
any one of the electrodes (142), a number of different stimulation
therapies may be applied to a patient.
[0073] In addition, the electrical field emitted by the electrodes
(142) may be more efficiently directed towards a desired
stimulation site by using the stimulator configuration described in
connection with FIGS. 2-8 as opposed to using a cylindrically
shaped stimulator with ring-like electrodes. For example, the
stimulation parameters may be programmed such that only the
electrodes (142-1 through 142-4) included in the top extending
member (272; FIG. 7) emit an electrical current. In this manner,
the electrical stimulation current is only emitted from one side of
the stimulator (100), as opposed to being emitted in all 360
degrees of space.
[0074] The stimulator configuration described in connection with
FIGS. 2-8 also facilitates the proper implantation and placement of
the stimulator (100). Because the stimulator (100) is configured to
be able to selectively apply electrical stimulation current to any
of a number of locations via the multiple electrodes (142), the
stimulator (100) may be implanted in a location that is only
approximately near the desired stimulation site. The patient or
clinician may then activate the electrode(s) closest to the desired
stimulation site.
[0075] The stimulator (100) of FIG. 2 may be implanted within a
patient using any suitable surgical procedure such as, but not
limited to, injection, small incision, open placement, laparoscopy,
or endoscopy. The stimulator (100) may be implanted within a
patient with a surgical tool such as a hypodermic needle, bore
needle, or any other tool specially designed for the purpose. In
general, the stimulator (100) is implanted with a tool that is used
to push the stimulator (100) through a needle, cannula or incision
to a position proximate to the target tissue to be stimulated.
[0076] For example, a tool used to implant a stimulator (100) may
be an elongated, tubular, rigid or semi-rigid tool with a handle at
one end and some mechanism at the tip for engaging the stimulator.
The engagement mechanism at the tip holds the stimulator in place
on the tool until released. With the stimulator engaged by the
tool, the tool is used to push the stimulator into place.
[0077] In some instances, it may be difficult, however, to
accurately position the stimulator (100) with this push insertion
method. The clinician placing the stimulator (100) often pushes the
stimulator (100) through resistive tissue using the handle of the
insertion tool. Any slight movement of the hand during this
procedure can produce a significant direction shift at the tool
tip, possibly resulting in a placement of the stimulator (100)
relatively distant from a desired implant location and target
tissue.
[0078] Additionally, when the stimulator (100) is finally
positioned, the mechanism engaging the stimulator (100) is
released. The act of releasing the stimulator (100) may also affect
the position of the stimulator (100). If the position of the
stimulator (100) shifts after the tool has been disengaged, it may
be difficult to reposition the stimulator (100).
[0079] There are some locations in the human body where a
stimulator (100) would be implanted, such as in a limb or in the
neck, where a needle can be inserted, passed proximal to the target
tissue to be stimulated and then exit through the skin. A line
(e.g., fine wire or thread) can be attached to this pass-through
needle so as to then pass through the patient proximal to the
target tissue for stimulation. A stimulator (100) is then attached
to this line which is used to pull the stimulator (100) into place
proximal to the target tissue to be stimulated within the patient.
This process will be illustrated and described in detail below.
[0080] Turning to FIG. 9, at either end of the stimulator (100) an
eyelet (182) is formed. A line (185) is then attached to the eyelet
(182) at either or both ends of the stimulator (100). This line may
be any line that can be pulled through a portion of a patient's
body and then used to position the stimulator (100) as described
herein. For example, the line (185) may be, but is not limited to,
a string, a suture line, a silk line, a wire, a filament and the
like. In some examples, the line is dissolvable, meaning that the
line will naturally dissolve if left in the patient's tissue.
[0081] Alternative to the eyelets (182), any other means of
attaching or anchoring the line (185) to the stimulator (100) may
be used. For example, the line may be tied to the eyelet (182),
integrated into the stimulator (100) itself, tacked or adhered to
the stimulator (100), etc.
[0082] Each attachment point of the line (185) to the stimulator
(100) may be encapsulated. For example, a polymer cap (183) of, for
example, silicone may be placed over the attachment points where
the line (185) is secured to the stimulator (100).
[0083] An exemplary method of implanting the stimulator (100) of
FIG. 9 will now be described with reference to FIGS. 10-12. In FIG.
10, the body (150) represents a portion of the human body where
tissue targeted for stimulation (i.e., a stimulation site) is
located between a needle insertion point and a needle exit point as
will be described herein. Consequently, the body (150) may
represent, for example, a patient's neck or limb or some other
location relatively near the surface under a patient's skin.
[0084] As shown in FIG. 10, a needle (111), to which the line (185)
is attached, has a sharp tip (112) that is threaded through the
patient's body between an insertion point (113) and an exit point
(114). The needle (111) is inserted through an insertion point
(113) in the patient's body (150). The needle (111) is then passed
proximal to the stimulation site (also referred to as target
tissue) (116) that is targeted for stimulation. The tip (112) of
the needle (111) then exits the patient's body (150) through an
exit point (114).
[0085] As the needle (111) is threaded between the insertion point
(113) and exit point (114), it may be useful to confirm that the
needle (111) has been inserted proximal to the stimulation site
(116) as intended. Consequently, an electrical pulse generator
(110) may be electrically connected to the needle (111) as shown in
FIG. 10. The pulse generator (110) is also connected to an
indifferent electrode (115) that may be placed on the patient's
skin near to the stimulation site (116).
[0086] The pulse generator (110) is then used to provide an
electrical stimulation pulse through the needle (111) to the
stimulation site (116). The needle (111) is made of metal or some
other electrically conductive material so as to conduct the
electrical stimulation pulse from the pulse generator (110). In
some examples, most of the length of the needle is covered with an
insulating material and only the tip (112) delivers the electrical
stimulation pulse to the surrounding tissue. If the needle (111) is
properly placed, the stimulation pulse from the pulse generator
(110) will cause a predictable effect that should result from
stimulation of the stimulation site (116), for example, a
paresthesia. The patient can be questioned or otherwise monitored
as to the effect created by the pulse generator (110) so as to
confirm the proper placement of the needle (111). In this way, it
can be ascertained that the needle (111) has been inserted proximal
to the tissue (116) to be stimulated.
[0087] The needle (111) is then pulled through the exit point (114)
leaving the line (185) threaded through the body (150) and running
next to the target tissue (116). As shown in FIG. 11, the
stimulator (100) is attached to the line (185) outside the
insertion point (113). The portion of the line (185) extending from
the exit point (114) is then pulled to pull the stimulator (100)
though the insertion point (113) and through the patient's body
(150) to a position proximal to the tissue (116) targeted for
stimulation.
[0088] FIG. 12 illustrates the stimulator (100) positioned inside
the body (150) proximal to the tissue (116) targeted for
stimulation. As shown in FIG. 12, a second line (186) is attached
to the other end of the stimulator (100) and extends from the
insertion point (113) even after the stimulator (100) has been
pulled into the patient's body (150). Consequently, if the
stimulator (100) is pulled too far into the patient's body (150)
using the line (185) extending from the exit point (114), past the
tissue (116) targeted for stimulation, the clinician placing the
stimulator (100) can pull the stimulator (100) back into the
optimal placement by pulling on the second line (186). In fact, the
clinician can pull on either line (186, 185) as needed, with a
flossing action, to determine and obtain the optimal placement for
the stimulator (100). During this process, the stimulator (100) may
be active and providing an electrical stimulation about which the
patient can be questioned or monitored to determine the most
efficacious placement for the stimulator (100).
[0089] FIG. 13 is a flowchart illustrating an example of the method
described above with respect to FIGS. 10-12. As shown in FIG. 13, a
pull-through needle is first inserted at the stimulation site (step
300). The needle is inserted so as to be pass proximal to the
tissue to be stimulated and through a location where the stimulator
is optimally placed. To determine if the needle has been inserted
as intended, a series of pulses or stimulation current may be
applied to the needle (step 301). This may be done with the pulse
generator and indifferent electrode described above.
[0090] By gauging the effect of the electric stimulation delivered
via the needle, it can be determined if the needle was positioned
within the patient as intended (determination 302). If not, the
needle is repositioned (step 303), and the test stimulation is
repeated.
[0091] Once the needle is confirmed as having passed proximal to
the tissue to be stimulated and through the desired site for the
stimulator, the needle is pulled through an exit point in the
patient's skin (step 304). A line is attached to the needle and
follows the needle through the patient's body between the insertion
point and exit point.
[0092] The stimulator being implanted is attached to this line and
pulled into place using the line extending from the needle exit
point, as illustrated above (step 304). A second line is attached
to the stimulator and continues to extend out through the needle
insertion point.
[0093] The effect of the stimulator can then be gauged to determine
whether the stimulator is, in fact, optimally placed within the
patient (determination 305). If the stimulator is not optimally
placed, the lines extending from the needle insertion and exit
points can be selectively pulled to "floss" the stimulator into the
optimal location.
[0094] Once the stimulator is optimally positioned (determination
305), the stimulator is secured at that location. This may be
accomplished, for example, by suturing or otherwise securing or
adhering the lines attached to the stimulator at both the needle
insertion point and the needle exit point. In this way, the
stimulator will be held at the desired location. Over time, tissue
will grow around the stimulator securing it at the desired
location. Additionally, as described above, the lines attached to
the stimulator may be dissolvable so as to naturally disintegrate
with time in the patient's body. As a result, the stimulator is
easily placed at a desired target location with great precision and
using a minimally invasive procedure.
[0095] It will be recognized that the exemplary method of
implanting the stimulator (100) described in connection with FIGS.
10-13 is merely illustrative of the many different methods that may
be used to implant the stimulator (100). Other methods may include
injection, small incision, open placement, laparoscopy, endoscopy,
or any other suitable implantation method.
[0096] FIG. 14 illustrates an exemplary implanted stimulator (100)
and examples of the various systems and external devices that may
be used to support the implanted stimulator (100). For example, an
external battery charging system (EBCS) (151) may provide power
used to recharge the battery (145, FIG. 1) via an RF link (152).
External devices including, but not limited to, a hand held
programmer (HHP) (155), clinician programming system (CPS) (157),
and/or a manufacturing and diagnostic system (MDS) (153) may be
configured to activate, deactivate, program, and test the
stimulator (100) via one or more RF links (154, 156). One or more
of these external devices (153, 155, 157) may also be used to
control the stimulator (100). For example, the external devices
(153, 155, 157) may be used to provide or update the stimulation
parameters and other data stored in the programmable memory (146,
FIG. 1) of the stimulator (100).
[0097] In some cases, two or more of the various illustrated
external devices (153, 155, 157) may be used in the treatment of a
particular implant patient (150). If multiple external devices are
used in the treatment of a patient, there may be some communication
among those external devices, as well as with the implanted
stimulator (100). For example, the CPS (157) may communicate with
the HHP (155) via an infrared (IR) link (158) or via any other
suitable communication link. Likewise, the MDS (153) may
communicate with the HHP (155) via an IR link (159) or via any
other suitable communication link.
[0098] The HHP (155), MDS (153), CPS (157), and EBCS (151) are
merely illustrative of the many different external devices that may
be used in connection with the stimulator (100). Furthermore, it
will be recognized that the functions performed by the HHP (155),
MDS (153), CPS (157), and EBCS (151) may be performed by a single
external device. One or more of the external devices (153, 155,
157) may be embedded in a seat cushion, mattress cover, pillow,
garment, belt, strap, pouch, or the like, so as to be conveniently
placed near the implanted stimulator (100) when in use.
[0099] The stimulator (100) of FIG. 14 may be configured to operate
independently. Alternatively, as will be described in more detail
below, the stimulator (100) may be configured to operate in a
coordinated manner with one or more additional stimulators, other
implanted devices, or other devices external to the patient's
body.
[0100] In order to determine the amount and/or type(s) of
stimulating drug(s) and/or the strength and/or duration of
electrical stimulation required to most effectively treat a
particular medical condition, various indicators of the medical
condition and/or a patient's response to treatment may be sensed or
measured. These indicators include, but are not limited to, muscle
or limb activity (e.g., electromyography (EMG)), electrical
activity of the brain (e.g., EEG), neurotransmitter levels, hormone
levels, and/or medication levels. In some embodiments, the
stimulator (100) may be configured to change the stimulation
parameters in a closed loop manner in response to these
measurements. The stimulator (100) may be configured to perform the
measurements. Alternatively, other sensing devices may be
configured to perform the measurements and transmit the measured
values to the stimulator (100).
[0101] Thus, it is seen that one or more external appliances may be
provided to interact with the stimulator (100), and may be used to
accomplish at least one or more of the following functions:
[0102] Function 1: If necessary, transmit electrical power to the
stimulator (100) in order to power the stimulator (100) and/or
recharge the battery (145, FIG. 1).
[0103] Function 2: Transmit data to the stimulator (100) in order
to change the stimulation parameters used by the stimulator
(100).
[0104] Function 3: Receive data indicating the state of the
stimulator (100) (e.g., battery level, stimulation parameters,
etc.).
[0105] Additional functions may include adjusting the stimulation
parameters based on information sensed by the stimulator (100) or
by other sensing devices.
[0106] By way of example, an exemplary method of treating a
particular medical condition within a patient may be carried out
according to the following sequence of procedures. The steps listed
below may be modified, reordered, and/or added to as best serves a
particular application.
[0107] 1. A stimulator (100) is implanted so that its electrodes
(142, FIG. 1) and/or infusion outlet (201, FIG. 1) are coupled to
or located near a stimulation site. If the stimulator (100) is a
microstimulator, such as the BION microstimulator, the
microstimulator itself may be coupled to the stimulation site.
[0108] 2. The stimulator (100) is programmed to apply electrical
stimulation to the stimulation site. The stimulator (100) may also
be configured to control the operation of a drug delivery system
configured to apply drug stimulation to the stimulation site.
[0109] 3. When the patient desires to invoke electrical, the
patient sends a command to the stimulator (100) (e.g., via a remote
control) such that the stimulator (100) delivers the prescribed
electrical stimulation. The stimulator (100) may be alternatively
or additionally configured to automatically apply the electrical
stimulation in response to sensed indicators of the particular
medical condition.
[0110] 4. To cease electrical stimulation, the patient may turn off
the stimulator (100) (e.g., via a remote control).
[0111] 5. Periodically, the battery (145, FIG. 1) of the stimulator
(100) is recharged, if necessary, in accordance with Function 1
described above.
[0112] For the treatment of any of the various types of medical
conditions, it may be desirable to modify or adjust the algorithmic
functions performed by the implanted and/or external components, as
well as the surgical approaches. For example, in some situations,
it may be desirable to employ more than one stimulator (100), each
of which could be separately controlled by means of a digital
address. Multiple channels and/or multiple patterns of electrical
stimulation may thereby be used to deal with multiple medical
conditions.
[0113] For instance, as shown in the example of FIG. 15, a first
stimulator (100) implanted beneath the skin (208) of the patient
provides a stimulus to a first location; a second stimulator (100')
provides a stimulus to a second location; and a third stimulator
(100'') provides a stimulus to a third location. As mentioned
earlier, the implanted devices may operate independently or may
operate in a coordinated manner with other implanted devices or
other devices external to the patient's body. That is, an external
controller (250) may be configured to control the operation of each
of the implanted devices (100, 100', and 100''). In some
embodiments, an implanted device, e.g. stimulator (100), may
control or operate under the control of another implanted
device(s), e.g. stimulator (100') and/or stimulator (100'').
Control lines (262-267) have been drawn in FIG. 15 to illustrate
that the external controller (250) may communicate or provide power
to any of the implanted devices (100, 100', and 100'') and that
each of the various implanted devices (100, 100', and 100'') may
communicate with and, in some instances, control any of the other
implanted devices.
[0114] As a further example of multiple stimulators (100) operating
in a coordinated manner, the first and second stimulators (100,
100') of FIG. 15 may be configured to sense various indicators of a
particular medical condition and transmit the measured information
to the third stimulator (100''). The third stimulator (100'') may
then use the measured information to adjust its stimulation
parameters and apply electrical stimulation to a stimulation site
accordingly.
[0115] Alternatively, the external device (250) or other external
devices communicating with the external device may be configured to
sense various indicators of a patient's condition. The sensed
indicators can then be transmitted to the external device (250) or
to one or more of the implanted stimulators which may adjust
stimulation parameters accordingly. In other examples, the external
controller (250) may determine whether any change to stimulation
parameters is needed based on the sensed indicators. The external
device (250) may then signal a command to one or more of the
stimulators to adjust stimulation parameters accordingly.
[0116] The stimulator (100; FIG. 2) described herein can be applied
in the treatment of a wide variety of different medical,
psychiatric, and neurological conditions and/or disorders. A number
of these conditions and disorders will now be described below.
However, it will be understood that this description is merely
exemplary and is not limiting in any way. The stimulator (100; FIG.
2) described herein may be used to treat any condition or disorder
where stimulation from an implanted stimulator is helpful to treat
the symptoms or cause of the condition or disorder.
[0117] For example, the stimulator (100; FIG. 2) described herein
may be implanted within a patient's head or neck for the treatment
of various conditions and/or disorders such as headaches, facial
pain, and/or epilepsy. However, it will be recognized that
headaches, facial pain, and epilepsy are merely illustrative of the
many different types of medical, psychiatric, and neurological
conditions and disorders that exist and may be treated according to
the principles described herein.
Epilepsy
[0118] Epilepsy is characterized by a tendency to recurrent
seizures that can lead to loss of awareness, loss of consciousness,
and/or disturbances of movement, autonomic function, sensation
(including vision, hearing and taste), mood, and/or mental
function. Epilepsy afflicts one to two percent of the population in
the developed world. The mean prevalence of active epilepsy (i.e.,
continuing seizures or the need for treatment) in developed and
undeveloped countries combined is estimated to be 7 per 1,000 of
the general population, or approximately 40 million people
worldwide. Studies in developed countries suggest an annual
incidence of epilepsy of approximately 50 per 100,000 of the
general population. However, studies in developing countries
suggest this figure is nearly double at 100 per 100,000.
[0119] Epilepsy is often but not always the result of an underlying
brain disease. Any type of brain disease can cause epilepsy, but
not all patients with the same brain pathology will develop
epilepsy. The cause of epilepsy cannot be determined in a number of
patients; however, the most commonly accepted theory posits that it
is the result of an imbalance of certain chemicals in the brain,
e.g., neurotransmitters. Children and adolescents are more likely
to have epilepsy of unknown or genetic origin. The older the
patient, the more likely it is that the cause is an underlying
brain disease such as a brain tumor or cerebrovascular disease.
[0120] Trauma and brain infection can cause epilepsy at any age,
and in particular, account for the higher incidence rate in
developing countries. For example, in Latin America,
neurocysticercosis (cysts on the brain caused by tapeworm
infection) is a common cause of epilepsy. In Africa, AIDS and its
related infections, malaria and meningitis, are common causes. In
India, AIDS, neurocysticercosis and tuberculosis, are common
causes. Febrile illness of any kind, whether or not it involves the
brain, can trigger seizures in vulnerable young children, which
seizures are called febrile convulsions. About 5% of such children
go on to develop epilepsy later in life. Furthermore, for any brain
disease, only a proportion of sufferers will experience seizures as
a symptom of that disease. It is therefore suspected that those who
do experience such symptomatic seizures are more vulnerable for
similar biochemical/neurotransmitter reasons.
[0121] Recent studies in both developed and developing countries
have shown that up to 70 percent of newly diagnosed children and
adults with epilepsy can be successfully treated (i.e., complete
control of seizures for several years) with anti-epileptic drugs.
After two to five years of successful treatment, drugs can be
withdrawn in about 70 percent of children and 60 percent of adults
without the patient experiencing relapses. However, up to 30
percent of patients are refractory to medication. There is evidence
that the longer the history of epilepsy, the harder it is to
control. The presence of an underlying brain disease typically
results in a worse prognosis in terms of seizure control.
Additionally, partial seizures, especially if associated with brain
disease, are more difficult to control than generalized
seizures.
[0122] Patients suffering from epilepsy may undergo surgery to
remove a part of the brain in which the seizures are believed to
arise, i.e., the seizure focus. However, in many patients a seizure
focus cannot be identified, and in others the focus is in an area
that cannot be removed without significant detrimental impact on
the patient. For example, in temporal lobe epilepsy, patients may
have a seizure focus in the hippocampi bilaterally. However, both
hippocampi cannot be removed without adversely affecting a
patient's long-term memory. Other patients may have a seizure focus
that lies adjacent to a critical area such as the speech
center.
[0123] Vagus nerve stimulation (VNS) has been applied with partial
success in patients with refractory epilepsy. In this procedure, a
stimulus may be applied to the left vagus nerve in the neck. Based
on a number of studies, approximately five percent of patients
undergoing VNS are seizure-free, and an additional 30-40 percent of
patients have a greater than 50 percent reduction in seizure
frequency.
[0124] In addition to this relatively low efficacy, VNS may lead to
significant side effects. The vagus nerve provides parasympathetic
innervation to the cardiac tissue, and thus VNS may lead to
bradycardia, arrhythmia, or even graver cardiac side effects. In
fact, VNS systems may only be used on the left vagus nerve, as the
right vagus nerve contributes significantly more to cardiac
innervation. Additionally, VNS may interfere with proper opening of
the vocal cords, which has led to hoarseness and shortness of
breath in a significant number of VNS patients.
[0125] The exact mechanism of seizure suppression using VNS is
unknown. The nucleus of tractus solitarius (NTS; a.k.a., nucleus of
the solitary tract) is a primary site at which vagal afferents
terminate. Because afferent vagal nerve stimulation has been
demonstrated to have anticonvulsant effects, it is likely that
changes in synaptic transmission in the NTS can regulate seizure
susceptibility. To demonstrate this, Walker, et al. ("Regulation of
limbic motor seizures by GABA and glutamate transmission in nucleus
tractus solitarius," Epilepsia, August 1999) applied muscimol, an
agonist of the inhibitory neurotransmitter GABA, to the NTS in a
murine model of epilepsy. Muscimol applied to the NTS attenuated
seizures in all seizure models tested, whereas muscimol applied to
adjacent regions of NTS had no effect. Additionally, bicuculline
methiodide, a GABA antagonist, injected into the NTS did not alter
seizure responses. Finally, anticonvulsant effects were also
obtained with application of lidocaine, a local anesthetic, into
the NTS. Unilateral injections were sufficient to afford seizure
protection. Walker, et al. conclude that inhibition of the NTS
outputs enhances seizure resistance in the forebrain and provides a
potential mechanism for the seizure protection obtained with vagal
stimulation.
[0126] The NTS sends fibers bilaterally to the reticular formation
and hypothalamus, which are important in the reflex control of
cardiovascular, respiratory, and gastrointestinal functions. The
NTS also provides input to the dorsal motor nucleus of the vagus,
which enables the parasympathetic fibers of the vagus nerve to
control these reflex responses. The NTS runs the entire length of
the medulla oblongata, and the NTS (as well as the trigeminal
nuclei) receives somatic sensory input from all cranial nerves,
with much of its input coming from the vagus nerve.
[0127] Convincing evidence has been given that a significant number
of neurons in the trigeminal nerve project to the NTS. By applying
horseradish peroxidase to peripheral branches of the trigeminal
nerve in a cat, it was found that branches of the trigeminal nerve
(the lingual and pterygopalatine nerves) were found to contain
fibers which ended ipsilaterally in the rostral portions of the
NTS, massively in the medial and ventrolateral NTS, moderately in
the intermediate and interstitial NTS, and sparsely in the ventral
NTS. (The rostral-most part of the NTS was free from labeled
terminals.) After injecting the enzyme into the NTS portions
rostral to the area postrema, small neurons were scattered in the
maxillary and mandibular divisions of the trigeminal ganglion. It
was concluded that trigeminal primary afferent neurons project
directly to the NTS. By staining for substance P immunoreactivity,
it was found that Substance P containing trigeminal sensory neurons
project to the NTS.
[0128] Convincing evidence has also been reported that a
significant number of neurons in the trigeminal nuclei project to
the NTS. Menetrey, et al used the retrograde transport of a
protein-gold complex to examine the distribution of spinal cord and
trigeminal nucleus caudalis neurons that project to the NTS in the
rat. [See Menetrey, et al. "Spinal and trigeminal projections to
the nucleus of the solitary tract: a possible substrate for
somatovisceral and viscerovisceral reflex activation." J Comp
Neurol 1987 Jan. 15; 255(3):439-50.] The authors found that
retrogradely labeled cells were numerous in the superficial laminae
of the trigeminal nucleus caudalis, through its rostrocaudal
extent. Since the NTS is an important relay for visceral afferents
from both the glossopharyngeal and vagus nerves, the authors
suggest that the spinal and trigeminal neurons that project to the
NTS may be part of a larger system that integrates somatic and
visceral afferent inputs from wide areas of the body. The
projections may underlie somatovisceral and/or viscerovisceral
reflexes, perhaps with a significant afferent nociceptive
component.
[0129] Another study utilized microinfusion and retrograde
transport of D [3H] aspartate to identify excitatory afferents to
the NTS. The authors found that the heaviest labeling was localized
bilaterally in the trigeminal nucleus with cells extending through
its subdivisions and the entire rostrocaudal axis.
[0130] In addition, a study by Fanselow, et al. ("Reduction of
pentylenetetrazole-induced seizure activity in awake rats by
seizure-triggered trigeminal nerve stimulation," Journal of
Neuroscience, November 2000) demonstrated that unilateral
stimulation via a chronically implanted nerve cuff electrode
applied to the infraorbital branch of the trigeminal nerve led to a
reduction in electrographic seizure activity of up to 78 percent.
The authors reported that bilateral trigeminal stimulation was even
more effective.
[0131] The thalamus is believed to play a major role in some types
of epilepsy by acting as a center for seizure onset or as a relay
station in allowing a focal seizure to propagate. In a Single
Positron Emission Computed Tomography (SPECT) study of patients
with left-sided VNS systems, a consistent decrease of activity was
found in the left thalamus caused by VNS. The authors concluded
that left-sided VNS reduces seizure onset or propagation through
inhibition of the thalamic relay center.
[0132] Thalamic relay neurons are essential in generating 3 Hz
absence seizures and are believed to be involved in other types of
epilepsy. Thalamic nuclei of some patients suffering from epilepsy
display neuronal activities described as "low-threshold calcium
spike bursts," which have been shown to be related to a state of
membrane hyperpolarization of thalamic relay neurons. This thalamic
rhythmicity is transmitted to the related cortex, thanks to
thalamocortical resonant properties. In the cortex, an asymmetrical
corticocortical inhibition (edge effect) at the junction between
low and high frequency zones is proposed to be at the origin of a
cortical activation of high frequency areas bordering low frequency
ones.
Migraine Headache
[0133] The mechanism of a migraine is not well understood.
Prevalent theories suggest that a migraine is a central nervous
system neurovascular disorder and that the trigeminal or occipital
nerves may play a prominent role. The trigeminal nerve carries
virtually all of the sensation from the face, and thus it likely
plays a role in any pain felt at the front or the top of the
head.
[0134] In "Pathophysiology of migraine--new insights" (Canadian
Journal of Neurological Sciences, November 1999), Hargreaves, et
al. state that "the exact nature of the central dysfunction that is
produced in migraines is still not clear and may involve spreading
depression-like phenomena and activation of brainstem monoaminergic
nuclei that are part of the central autonomic, vascular, and pain
control centers. It is generally thought that local vasodilation of
intracranial extracerebral blood vessels and a consequent
stimulation of surrounding trigeminal sensory nervous pain pathways
is a key mechanism underlying the generation of headache pain
associated with migraine. This activation of the trigeminovascular
system is thought to cause the release of vasoactive sensory
neuropeptides, especially CGRP, that increase the pain response.
The activated trigeminal nerves convey nociceptive information to
central neurons in the brain stem trigeminal sensory nuclei that in
turn relay the pain signals to higher centers where headache pain
is perceived. It has been hypothesized that these central neurons
may become sensitized as a migraine attack progresses." The
disorder of migraine may ultimately evoke changes in blood vessels
within pain-producing intracranial meningeal structures that give
rise to headache pain.
[0135] Hargreaves, et al. further state that "the `triptan`
anti-migraine agents (e.g., sumatriptan, rizatriptan, zolmitriptan,
and naratriptan) are serotonergic agonists that have been shown to
act selectively by causing vasoconstriction through 5 HT1B
receptors that are expressed in human intracranial arteries and by
inhibiting nociceptive transmission through an action at 5-HT1D
receptors on peripheral trigeminal sensory nerve terminals in the
meninges and central terminals in brainstem sensory nuclei. These
three complementary sites of action underlie the clinical
effectiveness of the 5 HT1B/1D agonists against migraine headache
pain and its associated symptoms."
[0136] In "Current concepts of migraine pathophysiology" (Canadian
Journal of Neurological Sciences, Autumn 1999), Hamel cites
evidence that indicates migraine originates in the brain and, in
its process and evolution, affects the meningeal blood vessels and
leads to the development of head pain. Hamel states that "this
manifestation is related to the activation of the trigeminovascular
sensory nerves, which release neuropeptides that mediate
vasodilation, and the proinflammatory reaction thought to be
involved in pain generation and transmission. Such a concept
underscores the fact that the relationship between the nerves and
the blood vessels is of paramount importance in the manifestation
of the disease's symptoms."
[0137] It has also been suggested that primary headache syndromes,
such as cluster headache and migraine, share an anatomical and
physiologic substrate, namely the neural innervation of the cranial
circulation. In "The Trigeminovascular System in Humans:
Pathophysiologic Implications for Primary Headache Syndromes of the
Neural Influences on the Cerebral Circulation" (Journal of Cerebral
Blood Flow Metabolism, February 1999), May, et al. report that
observations of vasodilation were made in an experimental
trigeminal pain study. They conclude that the observed dilation of
these vessels in trigeminal pain is not inherent to a specific
headache syndrome, but rather is a feature of the trigeminal neural
innervation of the cranial circulation. They also state that
clinical and animal data suggest that the observed vasodilation is,
in part, an effect of a trigeminoparasympathetic reflex. They
suggest that the trigeminal innervation of the cranial circulation
and the observed vasodilation of the associated vasculature during
headache syndromes may be an underlying pathophysiological
mechanism of headache.
[0138] In "Intraoral Chilling versus Oral Sumatriptan for Acute
Migraine" (Heart Disease, November-December 2001), Friedman, et al.
state that "recent evidence suggests that the primary inflammation
occurs in the maxillary nerve segment [of the trigeminal nerve],
accessible intraorally. Local tenderness, related to symptom
laterality, has been palpated in asymptomatic migraine
patients."
[0139] In "Cluster Headache" (Current Treatment Options in
Neurology, November 1999), Salvesen suggests a possible link
between the trigeminal nerve and cluster headache: "for a very
limited group of patients with chronic cluster headache, surgery
may be a last resort. The best surgical options are probably
radio-frequency rhizotomy or microvascular decompression of the
trigeminal nerve." In a recent study involving eighteen patients,
fifteen patients obtained immediate pain relief from chronic
intractable cluster headaches after one or two injections of
percutaneous retrogasserian glycerol rhizolysis. However, cluster
headache recurred in seven patients over the course of the study,
suggesting that permanent trigeminal destruction may not be an
effective treatment.
[0140] For many years, Transcutaneous Electrical Nerve Stimulation
(TENS) has been applied with some success to the control of
headache and facial pain symptoms. TENS is used to modulate the
stimulus transmissions by which pain is felt by applying
low-voltage electrical stimulation to large peripheral nerve fibers
via electrodes placed on the skin. A study of 282 migraineurs had
patients undergo Punctual (i.e., episodic) Transcutaneous
Electrical Nerve Stimulation (PuTENS) via pocket
electrostimulators. After more than 6 months PuTENS was
prophylactically effective in eighty percent of the patients in the
study, i.e., their frequency of attacks and use of drugs were
reduced by at least fifty percent. However, TENS devices can
produce significant discomfort and can only be used
intermittently.
[0141] The International Headache Society (IHS) published
"Classification and Diagnostic Criteria for Headache Disorders,
Cranial Neuralgias and Facial Pain" in 1988. IHS identified 13
different general groupings of headache, given below in Table
1.
TABLE-US-00001 TABLE 1 Groupings of Headache Disorders and Facial
Pain 1) Migraine 2) Tension-type headache 3) Cluster headache and
chronic paroxysmal hemicrania 4) Miscellaneous headaches
unassociated with structural lesions 5) Headache associated with
head trauma 6) Headache associated with vascular disorders 7)
Headache associated with non-vascular intracranial disorder 8)
Headache associated with substances or their withdrawal 9) Headache
associated with non-cephalic infections 10) Headaches associated
with metabolic disorders 11) Headache or facial pain associated
with disorder of cranium, neck, eyes, ears, nose, sinuses, teeth,
mouth or other facial or cranial structures 12) Cranial neuralgias,
nerve trunk pain and deafferentation pain 13) Non-classifiable
headache
[0142] The IHS classification of the most common types of headache
is summarized in Table 2 below.
TABLE-US-00002 TABLE 2 IHS Classification of Primary Headaches 1.
Migraine 1.1 Migraine without aura 1.2 Migraine with aura 1.2.1
Migraine with typical aura 1.2.2 Migraine with prolonged aura 1.2.3
Familial hemiplegic migraine headache 1.2.4 Basilar migraine 1.2.5
Migraine aura without headache 1.2.6 Migraine with acute onset aura
1.3 Ophthalmoplegic migraine 1.4 Retinal migraine 1.5 Childhood
periodic syndromes that may be precursors to or associated with
migraine 1.5.1 Benign paroxysmal vertigo of childhood 1.5.2
Alternating hemiplegia of childhood 1.6 Complications of migraine
1.6.1 Status migrainosus 1.6.2 Migrainous infarction 1.7 Migrainous
disorder not fulfilling above criteria 2. Tension-type headache 2.1
Episodic tension-type headache 2.1.1 Episodic tension-type headache
associated with disorder of pericranial muscles 2.1.2 Episodic
tension-type headache not associated with disorder of pericranial
muscles 2.2 Chronic tension-type headache 2.2.1 Chronic
tension-type headache associated with disorder of pericranial
muscles 2.2.2 Chronic tension-type headache not associated with
disorder of pericranial muscles 2.3 Headache of the tension-type
not fulfilling above criteria 3. Cluster headache and chronic
paroxysmal hemicrania 3.1 Cluster Headache 3.1.1 Cluster headache,
periodicity undetermined 3.1.2 Episodic cluster headache 3.1.3.
Chronic Cluster Headache 3.1.3.1 Unremitting from onset 3.1.3.2
Evolved from episodic 3.2 Chronic paroxysmal hemicrania 3.3 Cluster
headache-like disorder not fulfilling above Criteria
[0143] The IHS classification provides diagnostic criteria for
migraine without and with aura, summarized in Tables 3 and 4
below.
TABLE-US-00003 TABLE 3 IHS Diagnostic Criteria for Migraine Without
Aura A. At least five attacks fulfilling B-D below: B. Headache
attacks lasting 4-72 hours (untreated or unsuccessfully treated) C.
Headache has at least two of the following characteristics: 1.
Unilateral location 2. Pulsating quality 3. Moderate or severe
intensity (inhibits or prohibits daily activities) 4. Aggravation
by walking stairs or similar routine physical activity D. During
headache at least one of the following: 1. Nausea and/or vomiting
2. Photophobia and phonophobia E. At least one of the following: 1.
History and physical do not suggest headaches secondary to organic
or systemic metabolic disease 2. History and/or physical and/or
neurologic examinations do suggest such disorder, but is ruled out
by appropriate investigations 3. Such disorder is present, but
migraine attacks do not occur for the first time in close temporal
relation to the disorder
TABLE-US-00004 TABLE 4 IHS Diagnostic Criteria for Migraine With
Aura A. At least two attacks fulfilling B below: B. At least three
of the following four characteristics: 1. One or more fully
reversible aura symptoms indicating focal cerebral cortical and/or
brain stem dysfunction 2. At least one aura symptom develops
gradually over more than four minutes or two or more symptoms occur
in succession 3. No aura symptom lasts more than 60 minutes. If
more than one aura symptom is present, accepted duration is
proportionally increased 4. Headache follows aura with a free
interval of less than 60 minutes. It may also begin before or
simultaneously with the aura. C. At least one of the following: 1.
History and physical and neurologic examinations do not suggest
headaches secondary to organic or systemic metabolic disease 2.
History and/or physical and/or neurologic examinations do suggest
such disorder, but it is ruled out by appropriate investigations 3.
Such disorder is present, but migraine attacks do not occur for the
first time in close temporal relation to the disorder
[0144] The IHS classification includes several different types of
migraine variants. Basilar migraine is defined as a migraine with
an aura involving the brainstem. Symptoms include ataxia,
dysarthria, vertigo, tinnitus and/or changes in consciousness and
cognition. Ophthalmoplegic migraine is associated with acute
attacks of third nerve palsy with accompanying dilation of the
pupil. In this setting, the differential diagnosis includes an
intracranial aneurysm or chronic sinusitis complicated by a
mucocele. The ophthalmoplegia can last from hours to months.
Hemiplegic migraine is distinguished by the accompanying
hemiplegia, which can be part of the aura, or the headache may
precede the onset of hemiplegia. Hemiplegic migraine can be
familial and may last for days or weeks, clinically simulating a
stroke. An additional differential diagnosis includes focal
seizures.
[0145] Status migrainosus describes a migraine lasting longer than
72 hours with intractable debilitating pain, and typically occurs
in a setting of inappropriate and prolonged use of abortive
anti-migraine drugs. These patients may require hospitalization,
both for pain control, detoxification from the abused drugs, and
treatment of dehydration resulting from prolonged nausea and
vomiting.
[0146] A migraine prevalence survey of American households was
conducted in 1992, and included 20,468 respondents 12-80 years of
age. Using a self-administered questionnaire based on modified IHS
criteria, 17.6% of females and 5.7% of males were found to have one
or more migraine headaches per year. A projection to the total US
population suggests that 8.7 million females and 2.6 million males
suffer from migraine headache with moderate to severe disability.
Of these, 3.4 million females and 1.1 million males experience one
or more attacks per month. Prevalence is highest between the ages
of 25 and 55, during the peak productive years.
[0147] Based on published data, the Baltimore County Migraine
Study, MEDSTAT's MarketScan medical claims data set, and statistics
from the Census Bureau and the Bureau of Labor Statistics, it has
been estimated that migraineurs require 3.8 bed rest days for men
and 5.6 days for women each year, resulting in a total of 112
million bedridden days. Migraine costs American employers about $13
billion a year because of missed workdays and impaired work
function--close to $8 billion is directly due to missed workdays.
Patients of both sexes aged 30 to 49 years incurred higher indirect
costs compared with younger or older employed patients. Annual
direct medical costs for migraine care are about $1 billion, with
about $100 spent per diagnosed patient. Physician office visits
account for about 60% of all costs; in contrast, emergency
department visits contribute less than 1% of the direct costs.
Tension-Type Headache
[0148] The diagnostic criteria for tension-type headaches are
summarized in Table 5 below. However, migraine symptoms may overlap
considerably with those of tension-type headaches. Tension-type
headaches are believed by some experts to be a mild variant of
migraine headache. Patients with tension-type headaches who also
have migraines may experience nausea and vomiting with a tension
headache, though when they do, it typically is mild and for a
shorter duration compared to that with a migraine. Tension-type
headache may be a disorder unto itself in individuals who do not
have migraines, and may manifest as attacks of mild migraine in
individuals with migraines.
TABLE-US-00005 TABLE 5 IHS Criteria for Various Forms of
Tension-Type Headache Tension-type headache At least two of the
following pain characteristics: 1. Pressing/tightening
(non-pulsating) quality 2. Mild or moderate intensity (may inhibit,
but does not prohibit activities) 3. Bilateral location 4. No
aggravation by walking stairs or similar routine physical activity
Both of the following: 1. No nausea or vomiting (anorexia may
occur) 2. Photophobia and phonophobia absent, or only one is
present At least one of the following: 1. History and physical do
not suggest headaches secondary to organic or systemic metabolic
disease 2. History and/or physical and/or neurologic examinations
do suggest such disorder, but is ruled out by appropriate
investigations 3. Such disorder is present, but tension-type
headache does not occur for the first time in close temporal
relation to the disorder Episodic tension-type headache (ETTH)
Diagnostic criteria: A. At least 10 previous episodes, <180
days/year (<15/mo) with headache B. Headache lasting from 30
minutes to 7 days Chronic tension-type headache (CTTH) Diagnostic
criteria: A. Average frequency .gtoreq.1 day/month (.gtoreq.189
days/year) for .gtoreq.6 months Tension-type headache associated
with disorder of pericranial muscles At least one of the following:
1. Increased tenderness of pericranial muscles demonstrated by
manual palpation or pressure algometer. 2. Increased
electromyographic level of pericranial muscles at rest or during
physiologic tests. Tension-type headache not associated with
pericranial muscle disorder No increased tenderness of pericranial
muscles. If studied, electromyography of pericranial muscles shows
normal levels of activity.
[0149] Based on a telephone survey of 13,345 people, the 1-year
period prevalence of episodic tension-type headache (ETTH) is
estimated to be 38.3%, according to IHS criteria. Women had a
higher 1-year ETTH prevalence than men in all age, race, and
education groups, with an overall prevalence ratio of 1.16.
Prevalence peaked in the 30- to 39-year-old age group in both men
(42.3%) and women (46.9%). Prevalence increased with increasing
educational levels in both sexes, reaching a peak in subjects with
graduate school educations of 48.5% for men and 48.9% for women. Of
subjects with ETTH, 8.3% reported lost workdays because of their
headaches, while 43.6% reported decreased effectiveness at work,
home, or school.
Chronic Daily Headache
[0150] Chronic tension-type headache (CTTH) is a subtype of tension
headaches, with patients experiencing headaches daily or almost
every day. In practice, the term "chronic daily headache" is
commonly used to describe headaches lasting for greater than 4
hours per day and for at least 15 days per month. The
classification of chronic daily headaches is summarized below in
Table 6.
TABLE-US-00006 TABLE 6 Classification of Chronic Daily Headache
Transformed migraine 1. With medication overuse 2. Without
medication overuse Chronic tension-type headache (CTTH) 1. With
medication overuse 2. Without medication overuse New daily
persistent headache 1. With medication overuse 2. Without
medication overuse Hemicrania continua 1. With medication overuse
2. Without medication overuse
[0151] In the study of 13,345 people cited above, the 1-year period
prevalence of chronic tension-type headache (CTTH) was estimated to
be 2.2%. This prevalence was higher in women and declined with
increasing education. Subjects with CTTH reported more lost
workdays (mean of 27.4 days vs. 8.9 days for those reporting lost
workdays) and reduced-effectiveness days (mean of 20.4 vs. 5.0 days
for those reporting reduced effectiveness) compared with subjects
with ETTH.
[0152] Chronic daily headaches are best conceptualized as an
umbrella category term referring to a group of headache disorders
characterized by headaches which occur greater than 15 days per
month, with an average untreated duration of greater than 4 hours
per day. There are many secondary causes of chronic daily headache,
including post-traumatic headache, arthritis, intracranial mass
lesions, etc. There are also short-lived primary headache disorders
that occur greater than 15 days per month, such as chronic cluster
headache or the paroxysmal hemicranias. The most common primary,
chronic daily headache disorders include transformed migraine,
chronic tension-type headaches, new daily persistent headache, or
hemicrania continua. Each of these diagnoses can be complicated by
medication overuse (e.g., barbiturates, acetaminophen, aspirin,
caffeine, ergotamine tartrate and opioids). When used daily, all of
these medications can lead to a vicious cycle of rebound
headaches.
Cluster Headache
[0153] The 1988 IHS classification system recognized the uniqueness
of cluster headache as a clinical and epidemiological entity.
Formerly classified as a vascular migraine variant, cluster
headache (a.k.a. suicide headache) is thought to be one of the most
severe headache syndromes. It is characterized by attacks of severe
pain, generally unilateral and orbital and lasting 15 minutes to 3
hours, with one or more symptoms such as unilateral rhinorrhea,
nasal congestion, lacrimation, and conjunctival injection. In most
patients, headaches occur in episodes, generally with a regular
time pattern. These "cluster periods" last for weeks to months,
separated by periods of remission lasting months to years. These
headaches primarily affect men and in many cases patients having
distinguishing facial, body, and psychological features. Several
factors may precipitate cluster headaches, including histamine,
nitroglycerin, alcohol, transition from rapid eye movement (REM) to
non-REM sleep, circadian periodicity, environmental alterations,
and change in the level of physical, emotional, or mental activity.
The IHS classification system gives specific diagnostic criteria
for cluster headache, as given in Table 7 below.
TABLE-US-00007 TABLE 7 IHS Diagnostic Criteria for Cluster Headache
3.1 Cluster Headache A. At least 5 attacks fulfilling B-D below: B.
Severe unilateral, orbital, supraorbital and/or temporal pain
lasting 15-180 minutes untreated C. At least one of the following
signs present on the pain side: 1. Conjunctival injection 2.
Lacrimation 3. Nasal congestion 4. Rhinorrhea 5. Forehead and
facial sweating 6. Miosis 7. Ptosis 8. Eyelid edema D. Frequency of
attacks: from 1 every other day to 8 per day E. At least one of the
following: 1. History, physical and neurological examinations do
not suggest one of the disorders listed in groups 5-11 of Table 1
2. History and/or physical and/or neurological examinations do
suggest such disorder, but it is ruled out by appropriate
investigations 3. Such disorder is present, but cluster headache
does not occur for the first time in close temporal relation to the
disorder 3.1.1 Cluster headache periodicity undefined A. Criteria
for 3.1 fulfilled B. Too early to classify as 3.1.2 or 3.1.3 3.1.2
Episodic cluster headache Description: Attacks lasting between 1
week and 3 months occur in periods lasting 1 week to one year
separated by pain free periods lasting 14 days or more. A. All the
letter headings of 3.1 B. At least 2 periods of headaches (cluster
periods) lasting (untreated) from 7 days to one year, separated by
remissions of at least 14 days. 3.1.3 Chronic cluster headache
Description: Attacks lasting between 2 weeks and 3 months occur for
more than one year without remission or with remissions lasting
less than 14 days. A. All the letter headings of 3.1 B. Absence of
remission phases for one year or more or with remissions lasting
less than 14 days. 3.1.3.1 Chronic cluster headache unremitting
from onset A. All the letter headings of 3.1.3 B. Absence of
remission periods lasting 14 days or more from onset. 3.1.3.2
Chronic cluster headache evolved from episodic A. All the letter
headings of 3.1.3 B. At least one interim remission period lasting
14 days or more within one year after onset, followed by
unremitting course for at least one year.
[0154] The estimated prevalence of cluster headache is 69 cases per
100,000 people. Men are affected more commonly than women in a
proportion of 6:1. Although most patients begin experiencing
headache between the ages of 20 and 50 years (mean of 30 years),
the syndrome may begin as early as the first decade and as late as
the eighth decade.
Cervicogenic Headache
[0155] Cervicogenic headache (CEH) is a headache with its origin in
the neck area. The source of pain is in structures around the neck
that have been damaged. These structures can include joints,
ligaments, muscles, and cervical discs, all of which have complex
nerve endings. When these structures are damaged, the nerve endings
send pain signals up the pathway from the upper nerves of the neck
to the brainstem. These nerve fibers may synapse in the same
brainstem nuclei as the nerve fibers of the trigeminal nerve. Since
the trigeminal nerve is responsible for the perception of head
pain, the patient experiences the symptoms of headache and/or
facial pain.
[0156] While many patients who are diagnosed with CEH have the
traditional symptoms of tension-type headache, some of the patients
who have the traditional symptoms of migraine and cluster headache
also respond to CEH diagnosis and treatment.
Facial Pain
[0157] Facial pain may be due to a number of underlying disorders.
Among the most common is Trigeminal Neuralgia (also known as tic
douloureux). More than 50,000 people in the United States suffer
from trigeminal neuralgia. This disorder may cause episodes of
intense, stabbing, electric shock-like pain in the areas of the
face where the branches of the nerve are distributed (e.g., the
lips, eyes, nose, scalp, forehead, upper jaw, and lower jaw). A
less common form of the disorder, Atypical Trigeminal Neuralgia,
may cause less intense, constant, dull burning or aching pain,
sometimes with occasional electric shock-like stabs. Both forms of
the disorder most often affect one side of the face, but some
patients experience pain at different times on both sides. Onset of
symptoms occurs most often after age 50, and it affects women more
often than men. For patients with this disorder, an ordinary touch
of the face, such as when brushing teeth or applying makeup, can
trigger an attack. Trigeminal neuralgia is believed to be due to
hyper-excitability of fibers of the trigeminal nerve or its
ganglion. Microelectrode recordings from the trigeminal ganglion
have demonstrated sustained high-frequency bursts during pain
episodes of trigeminal neuralgia.
[0158] Trigeminal neuralgia may be treated medically with drugs
that decrease neural excitability, e.g., carbamazepine or
phenytoin. However, such medications prove ineffective for many
patients over the course of the disease. Thus, a number of surgical
interventions (e.g., microvascular decompression of the trigeminal
ganglion or it nerve fibers, radio-frequency rhizotomy) have been
developed.
[0159] Another cause of facial pain is Temporomandibular Joint
(TMJ) Dysfunction Syndrome. Most TMJ discomfort is temporary and
can be treated with inexpensive remedies. However, some TMJ
dysfunction patients are afflicted with persistent and sometimes
unbearable pain. The symptoms of this chronic dysfunction include
persistent pain in the facial muscles on one or both sides, a
clicking or popping sensation when opening the mouth or working the
jaw, recurring headaches, and difficulty chewing. Analgesics and
anti-inflammatory medication may relieve the pain in some patients.
Others turn to TMJ surgery in desperation.
[0160] Yet another cause of facial pain is Postherpetic Neuralgia,
which is a possible complication of herpes zoster reactivation
("shingles"). The herpes zoster virus may cause chicken pox upon
initial infection. When reactivated, the virus causes shingles--a
painful disease characterized by eruptions along a nerve path often
accompanied by severe neuralgia and a skin rash. It can affect the
torso or limbs (spinal ganglia shingles) or the face (trigeminal
ganglia shingles). Approximately one in five adults develops
shingles, usually after age 50. For most people, shingles is an
acute condition with pain typically lasting one month. However, in
older patients or patients with a compromised immune system,
singles can lead to postherpetic neuralgia, a very painful chronic
condition in which the pain associated with the shingles persists
beyond one month, even after the rash is gone. The incidence of
postherpetic neuralgia is almost negligible before age 50, but at
least 50% of patients older than 60 years and almost 75% beyond age
70 become affected following a shingles attack. Postherpetic
neuralgia tends to improve over time without treatment. Some
estimates suggest that only two to three percent of patients have
pain lasting more than one year. However, since more than 60,000
new cases develop annually in the US, the collective morbidity is
still substantial. Treatment of postherpetic neuralgia consists of
symptomatic relief of severe pain with tricyclic antidepressants
and opioids.
Other Medical, Psychiatric, and Neurological Conditions and
Disorders
[0161] Other medical, psychiatric, and neurological conditions
and/or disorders that may be treated with the stimulator (100; FIG.
2) described herein include, but are not limited to, the
following:
[0162] 1) Pain resulting from one or more medical conditions
including, but not limited to: migraine headaches, including but
not limited to migraine headaches with aura, migraine headaches
without aura, menstrual migraines, migraine variants, atypical
migraines, complicated migraines, hemiplegic migraines, transformed
migraines, and chronic daily migraines; episodic tension headaches;
chronic tension headaches; analgesic rebound headaches; episodic
cluster headaches; chronic cluster headaches; cluster variants;
chronic paroxysmal hemicrania; hemicrania continua; post-traumatic
headache; post-traumatic neck pain; post-herpetic neuralgia
involving the head or face; pain from spine fracture secondary to
osteoporosis; arthritis pain in the spine, headache related to
cerebrovascular disease and stroke; headache due to vascular
disorder; musculoskeletal neck pain; reflex sympathetic dystrophy,
cervicalgia; glossodynia, carotidynia; cricoidynia; otalgia due to
middle ear lesion; gastric pain; sciatica; maxillary neuralgia;
laryngeal pain, myalgia of neck muscles; trigeminal neuralgia;
post-lumbar puncture headache; low cerebro-spinal fluid pressure
headache; temporomandibular joint disorder; atypical facial pain;
ciliary neuralgia; paratrigeminal neuralgia; petrosal neuralgia;
Eagle's syndrome; idiopathic intracranial hypertension; orofacial
pain; myofascial pain syndrome involving the head, neck, and
shoulder; chronic migraneous neuralgia, cervical headache;
paratrigeminal paralysis; sphenopalatine ganglion neuralgia;
carotidynia; Vidian neuralgia; and causalgia.
[0163] 2) Epilepsy, including, but not limited to, generalized and
partial seizure disorders.
[0164] 3) Cerebrovascular diseases resulting from one or more
medical conditions including, but not limited to, atherosclerosis,
aneurysms, strokes, and cerebral hemorrhage.
[0165] 4) Autoimmune diseases resulting from one or more medical
conditions including, but not limited to, multiple sclerosis.
[0166] 5) Sleep disorders resulting from one or more medical
conditions including, but not limited to, sleep apnea and
parasomnias.
[0167] 6) Autonomic disorders resulting from one or more medical
conditions including, but not limited to: gastrointestinal
disorders, including, but not limited to, gastrointestinal motility
disorders, nausea, vomiting, diarrhea, chronic hiccups,
gastroesphageal reflux disease, and hypersecretion of gastric acid;
autonomic insufficiency; excessive epiphoresis; excessive
rhinorrhea; and cardiovascular disorders including, but not limited
to, cardiac dysrythmias and arrythmias, hypertension, and carotid
sinus disease.
[0168] 7) Urinary bladder disorders resulting from one or more
medical conditions including, but not limited to, spastic and
flaccid bladder.
[0169] 8) Abnormal metabolic states resulting from one or more
medical conditions including, but not limited to, hyperthyroidism
and hypothyroidism.
[0170] 9) Disorders of the muscular system resulting from one or
more medical conditions including, but not limited to, muscular
dystrophy and spasms of the upper respiratory tract and face.
[0171] 10) Neuropsychiatric disorders resulting from one or more
medical conditions including, but not limited to, depression,
schizophrenia, bipolar disorder, autism, personality disorders, and
obsessive-compulsive disorder.
[0172] 11) Urinary and fecal incontinence.
[0173] 12) Erectile or other sexual dysfunctions.
[0174] For ease of explanation, the term "medical condition" will
be used herein and in the appended claims, unless otherwise
specifically denoted, to refer to any medical, psychiatric, and/or
neurological condition and/or disorder described herein, listed
above, or related or similar to any condition or disorder described
or listed herein.
[0175] FIGS. 16 and 17 depict the upper cervical spine (C1-C4) area
of a patient. As shown in FIGS. 16 and 17, a number of nerves arise
from the upper cervical spine (C1-C4). Examples of such nerves
include, but are not limited to, the greater occipital nerve(s)
(130), the lesser occipital nerve(s) (132), the third occipital
nerve(s) (134), greater auricular nerve(s) (136), transverse
cervical nerve(s) (138), the supraclavicular nerve(s) (139), and/or
branches of any of these nerves. As shown in FIG. 17, the occipital
nerves (130, 132, 134) are relatively easily accessed, especially
in their distal portions, since they lie subcutaneously in the back
of the head and upper neck.
[0176] In some embodiments, at least one stimulus is applied with
the stimulator (100; FIG. 2) described herein to one or more target
nerves within a patient to treat and/or prevent one or more of the
medical conditions listed above. The target nerve may be, for
example, any nerve originating in the upper cervical spine area
(i.e., C1-C4) or any branch of a nerve originating in the upper
cervical spine area. For example, the target nerve may include, but
is not limited to, the greater occipital nerve(s) (130), the lesser
occipital nerve(s) (132), the third occipital nerve(s) (134),
greater auricular nerve(s) (136), transverse cervical nerve(s)
(138), the supraclavicular nerve(s) (139), and/or branches of any
of these nerves. The greater (130), lesser (132), and third
occipital nerves (134), as well as the greater auricular nerves
(136), are relatively easily accessed, especially in their distal
portions, since they lie subcutaneously in the back of the head and
upper neck. The stimulator (100; FIG. 2) may thus be easily
implanted adjacent to one or more of these nerves and then
optimally positioned using the systems and methods described
herein. A more complicated surgical procedure may be required for
sufficient access to one or more of these nerves and/or for
purposes of fixing the stimulator in place. The sites of injection
or skin incision may be selected such that the resulting scars
would likely be covered by hair on most people.
[0177] It will be recognized that the stimulus may be applied with
the stimulator (100; FIG. 2) to any nerve, tissue, organ, or other
stimulation site within the patient to treat any of the above
listed medical conditions. For example, urinary incontinence may be
treated by stimulating the nerve fibers proximal to the pudendal
nerves of the pelvic floor. Erectile or other sexual dysfunctions
may be treated by providing stimulation of the cavernous nerve(s).
Other disorders, e.g., neurological disorders caused by injury or
stroke, may be treated by providing stimulation to other
appropriate nerve(s).
[0178] The preceding description has been presented only to
illustrate and describe embodiments of the invention. It is not
intended to be exhaustive or to limit the invention to any precise
form disclosed. Many modifications and variations are possible in
light of the above teaching.
* * * * *