U.S. patent application number 12/871865 was filed with the patent office on 2011-01-06 for drug eluting lead systems.
This patent application is currently assigned to NEUROPACE, INC.. Invention is credited to C. Lance Boling, Daniel Chao, Martha J. Morrell, Benjamin D. Pless, Thomas K. Tcheng, Brett M. Wingeier.
Application Number | 20110004282 12/871865 |
Document ID | / |
Family ID | 39686547 |
Filed Date | 2011-01-06 |
United States Patent
Application |
20110004282 |
Kind Code |
A1 |
Boling; C. Lance ; et
al. |
January 6, 2011 |
Drug Eluting Lead Systems
Abstract
Medical electrical lead systems and related methods are
described. The lead systems may be configured to be at least
partially implanted in neural tissue of a subject, such as a brain
of a subject. Some variations of the lead systems may comprise a
lead body, an electrode connected to the lead body, and a bioactive
agent. The electrode and/or lead body may comprise a substrate, and
the bioactive agent may be supported by the substrate (e.g., by a
substantial portion of the area of the substrate). Examples of
bioactive agents that may be used in the lead system include
bioactive agents that promote neural adhesion and living cells that
have been biologically manipulated, engineered cells, and cells of
a particular phenotype and/or adapted to induce a desired neural or
glial response. Methods described herein may comprise contacting
the substrate of a lead body and/or an electrode of a medical
electrical lead system with at least one bioactive agent, where the
lead body and the electrode are connected to each other.
Inventors: |
Boling; C. Lance; (San Jose,
CA) ; Chao; Daniel; (San Francisco, CA) ;
Morrell; Martha J.; (Portola Valley, CA) ; Pless;
Benjamin D.; (Atherton, CA) ; Tcheng; Thomas K.;
(Pleasant Hill, CA) ; Wingeier; Brett M.; (San
Francisco, CA) |
Correspondence
Address: |
NEUROPACE, INC.
1375 SHOREBIRD WAY
MOUNTAIN VIEW
CA
94043
US
|
Assignee: |
NEUROPACE, INC.
Mountain View
CA
|
Family ID: |
39686547 |
Appl. No.: |
12/871865 |
Filed: |
August 30, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11704549 |
Feb 8, 2007 |
|
|
|
12871865 |
|
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Current U.S.
Class: |
607/116 |
Current CPC
Class: |
A61N 1/0539 20130101;
B22F 3/10 20130101; A61N 1/0529 20130101; A61N 1/36082 20130101;
A61N 1/0551 20130101; B22F 2998/10 20130101; B22F 2003/241
20130101; B22F 2003/242 20130101; A61N 1/0536 20130101; B22F 3/24
20130101; B22F 2998/10 20130101; B22F 3/10 20130101 |
Class at
Publication: |
607/116 |
International
Class: |
A61N 1/05 20060101
A61N001/05 |
Claims
1. A medical electrical lead system configured to be at least
partially implanted in neural tissue of a subject, comprising: a
lead body; an electrode connected to the lead body and comprising a
substrate; and at least one bioactive agent adapted to promote
neural adhesion supported by a substantial portion of the area of
the first substrate of the first electrode.
2. The lead system of claim 1 wherein the lead system is configured
to be at least partially implanted in a brain of a subject.
3. The lead system of claim 1 wherein the at least one bioactive
agent is comprised of cell adhesion molecules.
4. The lead system of claim 1 wherein the at least one bioactive
agent is selected from the group consisting of plasmids, linear DNA
fragments, linear RNA fragments, and growth factors.
5. The lead system of claim 1 wherein the at least one bioactive
agent contacts the substrate.
6. The lead system of claim 1 wherein the at least one bioactive
agent is in the form of a coating on the substrate.
7. The lead system of claim 1, further comprising a material that
is supported by the substrate and that is different from the at
least one bioactive agent.
8. The lead system of claim 7 wherein the at least one bioactive
agent is dispersed in the material.
9. The lead system of claim 7 wherein the at least one bioactive
agent is encapsulated in the material.
10. A medical electrical lead system configured to be at least
partially implanted in neural tissue of a subject, comprising: a
lead body comprising a substrate; an electrode connected to the
lead body; and at least one bioactive agent adapted to promote
neural adhesion supported by the substrate of the lead body.
11. The lead system of claim 10 wherein the lead system is
configured to be at least partially implanted in a brain of a
subject.
12. The lead system of claim 10 wherein the at least one bioactive
agent is comprised of cell adhesion molecules.
13. The lead system of claim 10 wherein the at least one bioactive
agent is selected from the group consisting of plasmids, linear DNA
fragments, linear RNA fragments, and growth factors.
14. The lead system of claim 1 wherein the at least one bioactive
agent contacts the substrate.
15. A medical electrical lead system configured to be at least
partially implanted in neural tissue of a subject, comprising: a
lead body comprising a substrate; an electrode connected to the
lead body; and at least one antiepileptic agent supported by the
substrate of the lead body.
16. A method comprising: at least partially implanting a lead
system in neural tissue of a subject, wherein the lead system
comprises a lead body, an electrode connected to the lead body and
comprising a substrate, and at least one bioactive agent adapted to
promote neural adhesion supported by a substantial portion of the
area of the substrate of the electrode.
17. The method of claim 16 wherein the method comprises at least
partially implanting the lead system in a brain of the subject.
18. The method of claim 16 wherein the at least one bioactive agent
is selected from the group consisting of plasmids, linear DNA
fragments, linear RNA fragments, and growth factors.
19. The method of claim 16 wherein the at least one bioactive agent
contacts the substrate.
20. A medical electrical lead system configured to be at least
partially implanted in neural tissue of a subject, comprising: a
lead body; an electrode connected to the lead body and comprising a
sintered metal characterized by a plurality of pores; and at least
one bioactive agent adapted to promote neural adhesion, wherein the
electrode acts as a reservoir for the at least one bioactive agent
and the pores in the sintered metal are adapted to release the at
least one bioactive agent from the reservoir into the neural
tissue.
21. A medical electrical lead system configured to be at least
partially implanted in neural tissue of a subject, comprising: a
lead body comprising a sintered metal characterized by a plurality
of pores, an electrode connected to the lead body; and at least one
bioactive agent adapted to promote neural adhesion, wherein the
lead body as a reservoir for the at least one bioactive agent and
the pores in the sintered metal are adapted to release the at least
one bioactive agent from the reservoir into the neural tissue.
22. A medical electrical lead system configured to be at least
partially implanted in neural tissue of a subject, comprising: a
lead body; an electrode connected to the lead body and comprising a
substrate; and at least one bioactive agent comprising living
cells.
23. The medical electrical lead system of claim 22 wherein the
living cells are adapted to induce a desired neural response.
24. The medical electrical lead system of claim 22 wherein the
living cells are adapted to induce a desired glial response.
25. The medical lead system of claim 22 wherein the living cells
are adapted to induce a desired immune response.
26. The medical lead system of claim 22 wherein the living cells
are selected from the group consisting of living cells that have
been biologically manipulated, engineered cells, and cells of a
particular phenotype.
27. The medical lead system of claim 22 wherein the living cells
comprise at least one layer on the substrate.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation of U.S. Ser. No. 11/704,549 filed
Feb. 8, 2007. U.S. Ser. No. 11/704,549 is hereby incorporated by
reference herein in the entirety.
TECHNICAL FIELD
[0002] The methods and devices described herein relate generally to
the field of medical electrical lead systems. More specifically,
the methods and devices described herein relate to medical
electrical lead systems for treatment of neural tissue, such as
brain tissue, where the lead systems include at least one bioactive
agent and/or are configured to provide a therapeutic effect to the
neural tissue. The methods and devices described herein may have
particular utility in the area of treatment of neurological
disorders.
BACKGROUND
[0003] Neurological disorders are prevalent in the United States
and around the rest of the world, with millions of people suffering
from various types of neurological disorders of varying severity. A
person who has a neurological disorder may be substantially
debilitated, and may experience a significant decline in quality of
life.
[0004] One example of a neurological disorder is epilepsy, which is
characterized by the occurrence of seizures. Because epilepsy is
characterized by seizures, its sufferers can be limited in the
kinds of activities in which they may participate. For example, an
epileptic may have limited or no ability to drive, work, or
participate in recreational activities. Some epilepsy sufferers
have serious seizures with such high frequency that they are
effectively incapacitated. Additionally, in some cases, epilepsy is
progressive, and can be associated with degenerative disorders and
conditions. Over time, epileptic seizures may become more frequent
and serious, and in particularly severe cases, may lead to the
deterioration of other brain functions, as well as physical
impairment.
[0005] Drug therapy and surgery are examples of current methods
that may be used to treat epilepsy. Various antiepileptic drugs are
available, and may be administered, for example, at the onset of
pre-seizure symptoms or auras, to mitigate the effects of epilepsy.
Surgical procedures include radical surgical resections, such as
hemispherectomies, corticectomies, lobectomies and partial
lobectomies, as well as less radical procedures, including
lesionectomies, transections, and stereotactic ablation. An
additional procedure that may be used to treat epilepsy is
electrical stimulation, in which seizures may be treated and/or
terminated by applying electrical stimulation to the brain.
Typically, the detection and responsive treatment of seizures via
electrical stimulation can include analysis of electroencephalogram
(EEG) waveforms and electrocorticogram (ECoG) waveforms. An EEG
waveform includes signals representing aggregate neuronal activity
potentials detectable via electrodes applied to a patient's scalp,
and/or signals obtained from deep in a patient's brain via depth
electrodes and the like. An ECoG waveform includes signals obtained
from internal electrodes near the cortex of the brain (generally on
or under the dura mater), and/or brain signals from deeper
structures.
[0006] Generally, it is preferable to detect and treat a seizure at
or near its inception, or even before it has begun. The beginning
of a seizure, or an onset, may be a clinical onset or an
electrographic onset. A clinical onset represents the beginning of
a seizure as manifested through observable clinical symptoms, such
as involuntary muscle movements or neurophysiological effects such
as lack of responsiveness. An electrographic onset, which typically
occurs before a clinical onset and which may enable intervention
before the patient suffers symptoms, refers to the beginning of
detectable electrographic activity indicative of a seizure.
[0007] Epilepsy is only one example of a neurological disorder.
Additional examples of neurological disorders include movement
disorders (e.g., Parkinson's disease), psychiatric disorders, sleep
disorders, and language disorders. As briefly discussed above,
these and other neurological disorders can severely disrupt a
person's quality of life. Thus, it would be preferable to provide
devices and methods that may be used to provide drugs and/or other
bioactive agents to a target site to treat a neurological
disorder.
BRIEF SUMMARY
[0008] Described here are medical electrical lead systems for
treatment of neurological disorders, as well as related methods.
The lead systems may be configured to be at least partially
implanted in a body of a subject. For example, the lead systems may
be configured to be at least partially implanted into neural
tissue, such as brain tissue. The lead systems may be used to
release one or more bioactive agents, such as therapeutic agents,
into the body of the subject. These bioactive agents may be
released in conjunction with the application of other treatment
methods, such as electrostimulation, or may be released
independently of any other treatment methods.
[0009] The lead systems generally comprise a lead body, an
electrode that is connected to the lead body, and at least one
bioactive agent. The electrode and/or lead body comprises a
substrate, and the bioactive agent is supported by the substrate.
In some variations, the bioactive agent may be supported by a
substantial portion of the area of the substrate.
[0010] The methods include methods of using lead systems. Some
variations of the methods comprise at least partially implanting a
lead system in neural tissue of a subject, such as a brain of a
subject. In certain variations, the lead system comprises a lead
body, an electrode connected to the lead body, and at least one
bioactive agent. The electrode and/or lead body comprises a
substrate, and the bioactive agent is supported by the substrate.
In some variations, the bioactive agent may be supported by a
substantial portion of the area of the substrate. In certain
variations in which the lead system is at least partially implanted
in neural tissue, the result may be the formation of at least one
microlesion in the neural tissue. In such variations, at least one
of the lead body and the electrode may include a bioactive agent
that is adapted to inhibit neuronal regeneration and/or neuronal
reconnection. Alternatively, a bioactive agent that is adapted to
encourage glial proliferation and/or healing of microlesions may be
used in the lead systems for certain applications.
[0011] A lead system may include just one bioactive agent or
multiple bioactive agents. In some variations, a lead system may
include a substrate and a bioactive agent that contacts the
substrate, such as a bioactive agent that is in the form of a
coating on the substrate. The bioactive agent may comprise an
antiproliferative agent, a bactericidal agent, a bacteriostatic
agent, an antiepileptic agent, an antifungal agent, or any other
appropriate bioactive agent. Examples of antiproliferative agents
that may be used as bioactive agents here include antiproliferative
agents that are capable of limiting or preventing glial
encapsulation (e.g., of a lead body and/or an electrode), as well
as other types of antiproliferative agents. Specific examples of
antiproliferative agents include bone morphogenic proteins, ciliary
neurotrophic factor, ribavirin, sirolimus, mycophenolate, mofetil,
azathioprine, paclitaxel, and cyclophosphamide. Examples of
bactericidal and/or bacteriostatic agents that may be used in the
lead systems described herein include quinolone, fluoroquinolone,
beta-lactam, aminoglycoside, penicillin, macrolide, monobactam,
lincosamide, tetracycline, cephalosporin, lipopeptide,
streptogramin, carbapenem, sulfonamide, aminoglycoside,
oxalodinone, nitrofuran, ketolide, glycylcycline families of
antibiotics, and silver ions. Examples of antiepileptic agents that
may be used in the lead systems include acetazolamide,
carbamazepine, clonazepam, clorazepate, diazepam, divalproex,
ethosuximide, ethotoin, felbamate, fosphenytoin, gabapentin,
lamotrigine, levetiracetam, mephobarbital, methsuximide,
oxcarbazepine, phenacemide, phenobarbital, phenytoin, pregabalin,
primidone, thiopental, tiagabine, topiramate, trimethadione,
valproate, zonisamide, and tetrodotoxin. Additionally, examples of
antifungal agents that may be appropriate for use in the lead
systems include amphotericin B, anidulafungin, butenafine,
butoconazole, caspofungin, ciclopirox, clioquinol, econazole,
fluconazole, flucytosine, griseofulvin, traconazole, ketoconazole,
micafungin, miconazole, naftifine, natamycin, nystatin,
oxiconazole, sulconazole, sulfanilamide, terbinafine, terconazole,
undecylenic, and voriconazole. Other types of bioactive agents may
also be used.
[0012] In certain variations, the lead systems may include a
substrate, a bioactive agent, and a material that is supported by
the substrate and that is different from the bioactive agent. The
bioactive agent may be encapsulated within the material, or the
material may be in the form of a layer over the bioactive agent. In
some variations, the bioactive agent may be in the form of a layer
over the material. The material may be, for example, silicone or a
hydrogel. In variations in which the material is silicone, the
density of the silicone can be manipulated to modulate the elution
characteristics of the silicone. As the elution characteristics of
the silicone change, the rate of bioactive agent release from the
silicone also can change.
[0013] In certain variations, the material may be bioerodible. In
other words, the material may be bioabsorbable, such that the body
absorbs the material, and/or biodegradable, such that the body
degrades and eventually excretes the material. For example, the
material may comprise a bioerodible polyanhydride or polyanhydride
compound. Examples of bioerodible polyanhydrides and polyanhydride
compounds include fatty acid-terminated polyanhydrides, poly(fatty
acid dimer), copolymers of poly(sebacic acid) and fatty acid, and
copolymers of dimer fatty acids. Specific examples of bioerodible
polyanhydrides and polyanhydride compounds include
poly[1,3-bis(carboxyphenoxy)propane-co-sebacic-acid], poly(fumaric
acid), poly(sebacic acid), poly(erucic acid dimer), copolymers of
fumaric acid and sebacic acid, poly(sebacic-co-ricinoleic acid
maleate), poly(sebacic-co-ricinoleic acid succinate), and
poly(sebacic-co-12-hydroxystearic acid succinate).
[0014] Some variations of the lead systems may include at least one
polymer, such as a bioerodible polymer, that is supported by the
substrate. Examples of polymers that may be included in the lead
systems include poly (3,4-ethylenedioxythiopene) (PEDOT) and poly
(3,4-ethylenedioxythiopene) poly(styrenesulfonate) (PEDOT:PSS). In
certain variations, the bioactive agent may be dispersed
throughout, and/or encapsulated within, the polymer. In some
variations, the polymer may be in the form of a layer over the
bioactive agent. In certain variations, the bioactive agent may be
in the form of a layer over the polymer.
[0015] A lead system may include just one electrode or a plurality
of electrodes (e.g., two, three, four, five, six, eight, or ten
electrodes) that are connected to its lead body. Some variations of
lead systems may include at least two electrodes, each of which
comprises a substrate supporting a bioactive agent. The substrates
of the electrodes may be formed of the same or different materials,
and the bioactive agents may be the same as each other or different
from each other.
[0016] Some of the methods described here are methods of making
lead systems. Certain variations of these methods comprise coating
an electrode and/or a lead body of a medical electrical lead system
with at least one bioactive agent, where the electrode and the lead
body are connected to each other. Some variations of the methods
may comprise coating a substantial portion of the area of the
electrode and/or lead body with the bioactive agent. Certain
variations of the lead systems may be configured to release at
least one bioactive agent when the lead systems are at least
partially implanted in neural tissue of a subject. In some
variations in which a lead system includes both a bioactive agent
and a bioerodible material that is different from the bioactive
agent, erosion of the bioerodible material, when the lead system is
at least partially implanted in neural tissue of a subject, may
result in the release of the bioactive agent into the neural tissue
of the subject. Coating methods that may be used in the methods
described herein include vapor deposition (e.g., physical vapor
deposition), ionic plasma deposition, spraying, and/or dipping, as
well as other methods.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is an illustration of a cranium of a subject, showing
an implantable neurostimulation device as implanted, and a medical
electrical lead system connected to the implantable
neurostimulation device and extending to the brain of the
subject.
[0018] FIG. 2 is a partial top view of the device and lead system
of FIG. 1.
[0019] FIG. 3A is a side view of a portion of a medical electrical
lead system.
[0020] FIG. 3B is a cross-sectional view of the portion of the lead
system of FIG. 3A, taken along line 3B-3B.
[0021] FIG. 3C is a cross-sectional view of the portion of the lead
system of FIG. 3B, taken along line 3C-3C.
[0022] FIG. 3D is a cross-sectional view of the portion of the lead
system of FIG. 3B, taken along line 3D-3D.
[0023] FIG. 4 is a flowchart representation of a method of using a
lead system in a body of a subject.
[0024] FIG. 5A is a top view of a portion of a medical electrical
lead system.
[0025] FIG. 5B is a side cross-sectional view of the lead system of
FIG. 5A.
DETAILED DESCRIPTION
[0026] Described here are devices and related methods for treating
neurological disorders with one or more bioactive agents. The
devices generally are medical electrical lead systems including a
lead body and at least one electrode that is connected to the lead
body. The lead systems can further include at least one bioactive
agent, and/or can be configured to provide a therapeutic effect to
neural tissue in the central and/or peripheral nervous systems. In
some variations of the lead systems, at least one of the electrode
and the lead body comprises a substrate that supports a bioactive
agent. For example, the bioactive agent may be in the form of a
coating on the substrate. In such variations, the lead systems may
be used to deliver the bioactive agent to a target site, such as
neural tissue (e.g., brain tissue). The bioactive agent may be
dispersed throughout, and/or encapsulated by, one or more other
materials on the substrate, such as a polymer coating. The lead
systems may be configured to provide a continuous supply of
bioactive agent to a target site over a period of time.
Furthermore, the lead systems may be connected to one or more
implantable medical devices, such as electrostimulation and/or
recording devices, which allow the lead systems to provide other
treatments in addition to the bioactive agent treatment.
[0027] Turning now to the figures, FIG. 1 shows an implantable
medical device 110, such as an electrostimulation device, affixed
to a cranium 114 of a subject by way of a ferrule 116. Ferrule 116
is a structural member that is adapted to fit into a cranial
opening, attach to the cranium, and retain device 110. One example
of a method that may be used to implant device 110 and affix it to
cranium 114 includes performing a craniotomy in the parietal bone
(not shown) anterior to the lamboid suture 112 to define an opening
118 slightly larger than device 110. Ferrule 116 is then inserted
into opening 118 and affixed to cranium 114. Thereafter, device 110
is inserted into, and affixed to, ferrule 116. The presence of
ferrule 116 may, for example, help to ensure that device 110 is
tightly and securely implanted.
[0028] As shown in FIG. 1, device 110 includes an outer housing
126, and a lead connector 120 configured to receive one or more
electrical lead systems. Housing 126 may provide protection to the
components of device 110, and may be formed of, for example, one or
more metals, such as titanium. Additionally, housing 126 may
enclose a battery and any electronic circuitry that may be required
or desired to provide device 110 with its functionality. In some
variations, a telemetry coil may be located in the interior of
device 110, or may be provided outside of housing 126 and
integrated with lead connector 120, to facilitate communication
between device 110 and external devices.
[0029] In FIG. 1, lead connector 120 is connected to a lead body
122 of a medical electrical lead system 200 (shown in FIG. 2). Lead
body 122 extends through a burr hole 124 or other opening in
cranium 114. Though not shown, in FIG. 2, the portion of lead body
122 that extends past burr hole 124 is coupled to four electrodes
that are implanted into a desired location in the subject's brain.
If the length of lead body 122 is substantially greater than the
distance between device 110 and burr hole 124, then any excess may
be urged into a configuration, such as an uncoiled configuration,
that consolidates the excess lead body (e.g., under the scalp). In
some variations, burr hole 124 may be sealed after implantation to
limit or prevent further movement by lead system 200. This sealing
may be provided, for example, by affixing a burr hole cover
apparatus to cranium 114 at least partially within burr hole 124.
Burr hole sealing is described, for example, in U.S. Pat. No.
6,006,124, which is hereby incorporated by reference in its
entirety.
[0030] Lead connector 120 helps to secure lead body 122 to device
110. Lead connector 120 also facilitates electrical connection
between circuitry within device 110 and one or more conductors in
lead body 122. The conductors, in turn, are coupled to the
electrodes. Lead connector 120 may accomplish the above-described
functions in a substantially fluid-tight environment and in a
biocompatible manner.
[0031] In general, device 110 may be used to treat one or more
neurological disorders. For example, device 110 may treat epilepsy
by detecting epileptiform activity or an electrographic seizure
from the brain, and applying neurostimulation to the brain. A
device such as device 110 may be able to both sense epileptiform
activity, and provide electrical stimulation to the brain in
response. However, in some variations, separate devices may be used
for monitoring brain activity and applying electrical stimulation
or neurostimulation. Brain activity may be detected, for example,
by comparing ongoing activity to typical epileptiform activity,
including identifying characteristics of epileptiform activity or
an electrographic seizure from ongoing brain activity. Once
activity is detected, stimulation may be applied to the affected
region. Additional stimulation to secondary brain regions may also
be applied.
[0032] As described above, device 110 may be an electrostimulation
device or neurostimulation device. Neurostimulation devices are
described, for example, in U.S. Pat. No. 7,353,065 issued Apr. 1,
2008 for "Responsive Therapy for Psychiatric Disorders" to Morrell
and U.S. Patent Application Publication No. 2008/0077191, published
Mar. 27, 2008 for "Treatment of Language, Behavior and Social
Disorders" to Morrell, both of which are hereby incorporated by
reference in their entirety. Other examples of implantable medical
devices include recording devices. Moreover, in some variations, an
implantable medical device may be configured to detect and/or
respond to neurological activity other than epileptiform activity.
Non-limiting examples of such neurological activity include
activity associated with movement disorders, psychiatric disorders,
sleep disorders, language disorders, migraine headaches, and/or
chronic pain. While an implantable medical device such as device
110 may have a therapeutic function, some or all of the actions
performed by a medical device used in conjunction with a lead
system may not be therapeutic. For example, the actions may involve
data recording or transmission, providing warnings to the subject,
or any of a number of alternative actions. In some variations, a
neurostimulation device may not be a single device, but may be a
system of component devices. Thus, a neurostimulation device may
also function as a diagnostic device, and may be interfaced with
external equipment.
[0033] While device 110 is shown as being affixed to cranium 114,
devices may be positioned in any of a number of different places
either within or outside of a body of a subject. For example, in
some variations, a device may be implanted under a subject's scalp,
but external to the subject's cranium. In certain variations (e.g.,
when it is not possible to implant a device intracranially), a
device may be implanted pectorally, with leads extending through
the subject's neck and between the subject's cranium and scalp, as
necessary. Any other suitable positions for a device may also be
used.
[0034] FIG. 2 shows an enlarged view of a portion of device 110, as
well as lead system 200 including the lead body 122 shown in FIG.
1. As shown in FIG. 2, in addition to including lead body 122,
which has a proximal end 211 and a distal end 212, lead system 200
also includes multiple cylindrical electrodes 204, 206, 208, and
210. Electrodes 204, 206, 208, and 210 are located at distal end
212 of lead body 122, and are connected to conductors (not shown)
embedded within the lead body. The connection between the
electrodes and the conductors allows electrical stimulation to be
transmitted from device 110 to the brain of the subject. The
electrodes of lead system 200 may be configured, for example, to
sense brain activity, to apply neurostimulation, and/or to record
brain signals.
[0035] FIGS. 3A-3D show a distal portion of another variation of a
medical electrical lead system. As shown there, a medical
electrical lead system 300 includes a lead body 302 and multiple
cylindrical electrodes 304, 306, 308, and 310 that are connected to
the lead body at its distal end 312. Four conductors 314, 316, 318,
and 320 (the positioning of which is shown in FIG. 3D) are embedded
within lead body 302 and are connected to the electrodes. The
conductors provide electrical connection between the electrodes and
circuitry within a device that is connected to the lead system
during use, such as an implantable electrostimulation device. While
electrodes 304, 306, 308, and 310 are shown as being ring-shaped,
electrodes having other shapes, such as disc-shaped electrodes, may
alternatively or additionally be used in lead systems. Lead system
300 further includes a coating 322 over the cylindrical electrodes
and portions of the lead body. Coating 322 includes one or more
bioactive agents. During use of lead system 300, the bioactive
agents in coating 322 may be released into the body of the subject
and may, for example, provide a therapeutic effect.
[0036] A coating such as coating 322 may be formed of any of a
number of different biocompatible materials. In some variations, a
coating on a lead system may be formed simply of one or more
bioactive agents. In certain variations, a coating on a lead system
may include one or more bioactive agents in combination with one or
more other materials, such as silicone. The bioactive agents may,
for example, be dispersed throughout, or encapsulated by, the other
materials. Moreover, in some variations, the other materials may
form one or more coatings over the bioactive agents, and/or the
bioactive agents may form one or more coatings over the other
materials.
[0037] Examples of other materials that may be used in a coating on
a lead system include polymers, such as electrically conductive
polymers. In variations in which a coating includes one or more
electrically conductive polymers, the electrically conductive
polymers may enhance the electrical connection between a target
site in the body of a subject, and the electrodes and conductors of
the lead system. Examples of polymers that may be included in a
coating on a lead system include poly (3,4-ethylenedioxythiopene)
and poly (3,4-ethylenedioxythiopene) poly(styrenesulfonate). Other
polymers may also be appropriate.
[0038] In certain variations, one or more bioerodible materials may
be used in a coating on a lead system. As the bioerodible materials
erode in the body, they may provide controlled release of a
bioactive agent or agents. Examples of bioerodible materials
include bioerodible polyanhydrides and polyanhydride compounds.
Examples of bioerodible polyanhydrides and polyanhydride compounds
include fatty acid-terminated polyanhydrides, poly(fatty acid
dimer), copolymers of poly(sebacic acid) and fatty acid, and
copolymers of dimer fatty acids. Specific examples of bioerodible
polyanhydrides and polyanhydride compounds include
poly[1,3-bis(carboxyphenoxy)propane-co-sebacic-acid], poly(fumaric
acid), poly(sebacic acid), poly(erucic acid dimer), copolymers of
fumaric acid and sebacic acid, poly(sebacic-co-ricinoleic acid
maleate), poly(sebacic-co-ricinoleic acid succinate), and
poly(sebacic-co-12-hydroxystearic acid succinate).
[0039] Further examples of materials that may be used in a coating
include porous materials, such as hydrogels. The materials may, for
example, have a pore volume percent of from about 10 to about 100
nanometers. Such porous materials may be used to deliver one or
more bioactive agents to a target site over a sustained period of
time. For example, a bioactive agent may elute from a hydrogel
coating over a period of about one to ten days. Other bioerodible
materials or non-bioerodible materials may alternatively or
additionally be used, as deemed appropriate.
[0040] While a lead system with one coating has been described,
lead systems may have multiple coatings, such as two, three, four,
five, or ten coatings. Some or all of the coatings may include the
same materials and/or bioactive agents, or some or all of the
coatings may include different materials and/or bioactive agents.
The bioactive agent or agents that are used in a particular coating
may be selected, for example, based on the anticipated position of
that coating once the lead system has been implanted at a target
site. Lead systems may include lead bodies and/or electrodes that
are entirely coated, or may include lead bodies and/or electrodes
having coated regions and uncoated regions. Moreover, a lead system
may include just one coating layer, or may include multiple layers
of coatings.
[0041] The bioactive agents that are delivered to a target site
from a lead system may be any of a number of different types of
bioactive agents, depending on the disorder or disorders which are
desired to be treated.
[0042] As an example, for treatment of epilepsy, one or more of the
bioactive agents typically would include an antiepileptic agent.
Examples of antiepileptic agents include acetazolamide,
carbamazepine, clonazepam, clorazepate, benzodiazepine derivatives
(e.g., diazepam), divalproex, ethosuximide, ethotoin, felbamate,
fosphenytoin, gabapentin, lamotrigine, levetiracetam,
mephobarbital, methsuximide, oxcarbazepine, phenacemide,
phenobarbital, phenytoin, pregabalin, primidone, thiopental,
tiagabine, topiramate, trimethadione, valproate, vigabatrin,
zonisamide, tetrodotoxin, allopregnanolone, and ganaxolone.
[0043] Additional examples of bioactive agents include
antiproliferative agents, bactericidal agents, bacteriostatic
agents, antifungal agents, etc.
[0044] Examples of antiproliferative agents include
antiproliferative agents that are capable of limiting or preventing
glial encapsulation of the substrates on which the
antiproliferative agents are coated. For example, the
antiproliferative agents may be used to limit or prevent glial
encapsulation of at least one of the lead body and the electrode or
electrodes of a lead system. Limitation of glial activity and/or
proliferation may, for example, enhance electrical connectivity
between electrodes and neural tissue in which the electrodes are
implanted. Other types of antiproliferative agents may also be
used. Specific examples of antiproliferative agents include bone
morphogenic proteins (BMPs), ciliary neurotrophic factor (CNF),
ribavirin, sirolimus (also known as rapamycin), mycophenolate,
mofetil, azathioprine, paclitaxel, and cyclophosphamide.
[0045] Bactericidal and/or bacteriostatic agents, as well as
antifungal agents, may be used, for example, to limit
post-operative risk of infection. Examples of bactericidal and/or
bacteriostatic agents include quinolone, fluoroquinolone,
beta-lactam, aminoglycoside, penicillin, macrolide, monobactam,
lincosamide, tetracycline, cephalosporin, lipopeptide,
streptogramin, carbapenem, sulfonamide, aminoglycoside,
oxalodinone, nitrofuran, ketolide, glycylcycline families of
antibiotics, and silver ions. Examples of antifungal agents include
amphotericin B, anidulafungin, butenafine, butoconazole,
caspofungin, ciclopirox, clioquinol, econazole, fluconazole,
flucytosine, griseofulvin, traconazole, ketoconazole, micafungin,
miconazole, naftifine, natamycin, nystatin, oxiconazole,
sulconazole, sulfanilamide, terbinafine, terconazole, undecylenic,
and voriconazole.
[0046] Other examples of bioactive agents include benzodiazapenes
and barbiturates. In some variations, cancer drugs such as
antineoplastics may be used as bioactive agents (e.g., to inhibit
cellular proliferation). In certain variations, the bioactive
agents that are used in a lead system may be adapted to promote
neural adhesion. For example, the bioactive agents may be cell
adhesion molecules. Other examples of bioactive agents include
plasmids, linear DNA or RNA fragments, other DNA- or RNA-based
molecules, and growth factors. These bioactive agents may be used,
for example, to induce a desired neural, glial, and/or immune
response. Still further examples of bioactive agents include cells,
such as living cells that have been biologically manipulated,
engineered cells, and cells of a particular phenotype. For example,
a lead system may include a layer of cells. The types of cells that
are used can be selected based on the desired effect. In some
cases, electrical stimulation may be used to cause the cells to
release desired neurotransmitters. Additional examples of bioactive
agents include neurotrophic factors and neuropeptides, proteins
exhibiting bioactive activity, glycans, and enzymes (e.g., enzymes
that help metabolize glutamate).
[0047] Moreover, while certain bioactive agents described herein
have been described as treating certain disorders, the bioactive
agents described herein may be able to treat more than one type of
disorder or condition. As an example, tetrodotoxin may be used to
treat disorders other than epilepsy. Generally, the bioactive
agents described herein may be employed when they can provide any
function that is desirable and/or useful.
[0048] Still further examples of bioactive agents that may be used
include bioactive agents that treat motor disorders (e.g.,
Parkinson's disease, dystonia, or tremors such as essential
tremor), psychiatric disorders (e.g., bipolar disorder or
depression, such as major depression disorder), language disorders,
sleep disorders, and Tourette's syndrome. These are merely examples
of different types of bioactive agents. Any other bioactive agents
suitable for treating neurological disorders or other disorders of
the body, or for providing other benefits, such as preventive care,
may be used with the lead systems described herein as appropriate.
For example, in some variations, bioactive agents having
anti-inflammatory properties, such as steroids, may be used.
Anti-inflammatory agents may advantageously limit the extent of
inflammation resulting from, for example, the process of implanting
electrodes into and/or upon neural tissue. The process of
implantation may include mechanically and chemically manipulating
the neural tissue in such a way as to cause inflammation which, in
turn, may produce edema and swelling. As a result, the time for
application of needed therapy may be delayed. Accordingly,
providing one or more anti-inflammatory agents to the neural tissue
may be desirable.
[0049] In certain variations, bioactive agents that may typically
exhibit central nervous system (CNS) or systemic side effects,
difficult deliverability, and/or unfavorable pharmacokinetics may
be used with the lead systems described herein (e.g., because the
lead systems may deliver the bioactive agents directly to a target
location relatively efficiently).
[0050] Some bioactive agents may be used to facilitate
neurostimulation. The bioactive agents may be delivered to neural
tissue in conjunction with, prior to, and/or after,
neurostimulation of the neural tissue. Examples of bioactive agents
that may be used to facilitate neurostimulation include
carbamazepine, oxcarbazepine, and phenytoin. These bioactive agents
may inhibit rapid firing, and may preferentially encourage a
depolarization-block response to high-frequency neurostimulation
(rather than a neural-firing response). Additional examples of
bioactive agents that may be used to facilitate neurostimulation
include glutamate-blocking agents such as lamotrigine and
topiramate. These glutamate-blocking agents may diminish excitatory
effects of neurostimulation. Further examples of bioactive agents
that may be used to facilitate neurostimulation include GABAergic
agents, such as topiramate, allopregnanolone, ganaxolone,
benzodiazepines, barbiturates, tiagabine, or other agents which
potentiate inhibition and which may be expected to potentiate
inhibitory effects of neurostimulation.
[0051] Certain bioactive agents may be adapted to facilitate the
recording of one or more signals from a brain of a subject, and
thus may be used to enhance a recording procedure. These bioactive
agents may also be delivered to neural tissue in conjunction with,
prior to, and/or after, recording. Examples of bioactive agents
that may facilitate recording (and that may also facilitate
neurostimulation) include agents that limit or prevent an
inflammatory response, and thereby also limit or prevent
undesirable physical changes to the electrode-tissue interface.
Examples of such bioactive agents include anti-inflammatory agents,
antiproliferative agents (e.g., bone morphogenic proteins, ciliary
neurotrophic factor, ribavirin, sirolimus, mycophenolate, mofetil,
azathioprine, paclitaxel, and cyclophosphamide), and anti-gliotic
agents. In some variations, one or more bioactive agents that
facilitate brain signal recording may be delivered to neural tissue
over a relatively long period of time, and may have a cumulative
effect on the neural tissue.
[0052] In some variations, a lead system may include one or more
bioactive agents that are adapted to inhibit neuronal regeneration
and/or neuronal reconnection. When the lead system is at least
partially implanted into neural tissue, it may form at least one
microlesion in the neural tissue. The bioactive agents may be used
to at least temporarily maintain that microlesion. It is believed
that, in some instances and/or under certain circumstances,
microlesions may result in a decreased occurrence of seizures.
Thus, it may be desirable in some cases to purposefully maintain
microlesions in neural tissue. By contrast, in certain cases, it
may be desirable to enhance the healing of microlesions, as they
may result in post-traumatic epileptiform activity. By using
bioactive agents that hasten the healing of microlesions, the
occurrence of seizures shortly after surgery may be limited.
[0053] Electrodes such as electrodes 304, 306, 308, and 310
described above may be configured, for example, to sense brain
activity, to apply neurostimulation, and/or to record brain
signals. Electrodes may be formed of any of a number of different
materials. Examples of electrode materials include titanium,
platinum, platinum alloyed with iridium, titanium nitride, iridium
oxide, no nickel stainless steels, conductive organic materials
(e.g., solid carbon), silicon, and/or any other materials and
combinations of materials that are known to be suitable for use in
electrodes. In certain variations, an electrode may be a
semiconductor electrode. Furthermore, in some variations, a lead
system may include one or more optical electrodes, or optodes, that
are configured to optically measure signals. In such variations,
the optodes may also be used to monitor bioactive agent levels at a
target site. In certain variations, an electrode may be formed of
one or more sintered metal materials, and may serve as a reservoir
for a bioactive agent. The bioactive agent may be released from the
reservoir through pores or holes in the sintered metal materials.
In some variations, the sintered electrode may be back-filled with
a material, such as a hydrogel or a rubber, that is compounded with
one or more bioactive agents. The bioactive agents may then be
released from the hydrogel or rubber and through pores or holes in
the sintered metal materials.
[0054] Referring back to FIG. 2, electrodes 204, 206, 208, and 210
are located at distal end 212 of lead body 122. However, some
variations of lead systems may alternatively or additionally
include one or more electrodes that are located proximal to the
distal end of the lead body. The locations of the electrodes of a
lead system may be selected based on, for example, the
characteristics of the target site.
[0055] A lead body such as lead body 122 may be formed of any of a
number of different materials. In certain variations, a lead body
may be substantially formed of one or more insulating materials. In
some variations, a lead body may be formed of one or more polymers,
such as polyurethanes, polytetrafluoroethylene, polyesters, and
polyamides (e.g., nylon). In certain variations, a lead body may be
formed of silicone.
[0056] While lead systems including four conductive wires have been
shown, lead systems may include any number of conductive wires,
such as one, two, three, four, five, or ten conductive wires. One
or more of the wires may extend straight through the side wall of a
lead body, and/or may wind or coil within the lead body. In some
variations, the conductive wires themselves may be coated or
sheathed within a non-conductive and/or protective material, such
as silicone, polyurethane, or polyethylene.
[0057] In certain variations, the dimensions of a lead system may
be selected to provide the lead system with a relatively low
profile. This low profile may prevent the lead system from being
easily visible from the outside when the lead system is implanted
within a subject's head (e.g., so that the lead system does not
form a protrusion on the subject's head). Such lead systems may,
for example, include one or more relatively thin coatings, the
thinness of which generally will depend on the particular type of
coating that is used. For example, if the coating is formed from
titanium nitrate (TiN), iridium oxide (IrOx), or platinum iridium
(PtIr), the thinness of the coating may be on the order of three to
twenty microns.
[0058] Various methods may be employed to deliver one or more
bioactive agents to a target site within a body of a subject, using
one of the lead systems described herein. FIG. 4 provides a
flowchart representation of one variation of such a method 400. As
shown there, method 400 includes at least partially implanting a
lead system in a brain of a subject 410. The lead system includes a
lead body, at least one electrode, and a coating including at least
one bioactive agent. The lead system also is connected to an
implantable medical device. The lead system may be entirely
implanted in the brain of the subject, or at least one of its
components may be located outside of the brain of the subject. The
implantable medical device may be partially or entirely implanted
into the head of the subject, such as intracranially in the
subject's parietal bone, in a location anterior to the lambdoid
suture (as described, for example, with reference to FIG. 1
above).
[0059] After the lead system has been at least partially implanted
in the brain of the subject, the medical device is activated 420.
The medical device may be configured, for example, to sense brain
activity, such as epileptic activity. Method 400 further includes
allowing bioactive agent to be released from the coating on the
lead system and out into the brain of the subject 430. The
bioactive agent may be released over a relatively short period of
time or over a relatively long period of time, depending on the
intended or desired effect of the agent and/or on the particular
characteristics or properties of the agent being used. For some
intended effects with some agents, a relatively short period of
time may be one day. For other intended effects with other agents,
a relatively long period of time may be ten days. Another method
that might be used to deliver one or more bioactive agents to a
target site within a body of a subject, using one of the lead
systems described herein, include the application of
electroporation to cause a desired effect or effects with the
agents.
[0060] While a lead system comprising a depth lead has been
described with reference to FIGS. 2 and 3A-3D above, other types of
lead systems, such as branched depth electrodes and two-dimensional
electrode arrays, may include one or more bioactive agents. For
example, and referring to FIGS. 5A and 5B, a lead system 500
includes a lead body 502 and an enlarged end portion 504 at the
distal end 514 of the lead system. Enlarged end portion 504
includes four disc electrodes 506, 508, 510, and 512 encapsulated
in a coating 516. Coating 516 includes one or more bioactive agents
that may be released into a target site when lead system 500 is
being used. A conductor 518 is embedded within lead body 502 and
runs along the length of the lead body, electrically connecting the
electrodes to a medical device. Lead system 500 is a cortical strip
lead, and may, for example, be positioned on a surface of brain
tissue during use.
[0061] Lead systems that are directly connected to neurostimulation
devices have been described here. However, in certain variations, a
lead system may be indirectly connected to an implantable medical
device. For example, a lead system may be wirelessly connected to
an implantable medical device.
[0062] While the methods and devices have been described in some
detail here by way of illustration and example, such illustration
and example is for purposes of clarity of understanding only. It
will be readily apparent to those of ordinary skill in the art in
light of the teachings herein that certain changes and
modifications may be made thereto without departing from the spirit
and scope of the appended claims.
* * * * *