U.S. patent application number 10/661640 was filed with the patent office on 2005-11-10 for treatment of movement disorders by near-diaphragmatic nerve stimulation.
Invention is credited to Barrett, Burke T., Terry, Reese S. JR..
Application Number | 20050251222 10/661640 |
Document ID | / |
Family ID | 25439037 |
Filed Date | 2005-11-10 |
United States Patent
Application |
20050251222 |
Kind Code |
A1 |
Barrett, Burke T. ; et
al. |
November 10, 2005 |
Treatment of movement disorders by near-diaphragmatic nerve
stimulation
Abstract
A method for treating patients with movement disorders includes
unilaterally or bilaterally stimulating one or both of the left and
right branches of a patient's vagus nerve directly or indirectly
with an electrical pulse signal generated by an implantable
neurostimulator with at least one operatively coupled nerve
electrode to apply the pulse signal to the selected nerve branch at
a location in the vicinity of the patient's diaphragm, either
slightly above or slightly below the diaphragm. A device for
performing the method includes a government approved implantable
neurostimulator which is programmable to enable physician
programming of electrical and timing parameters of the pulse
signal, to generate the desired therapy regimen for alleviating the
disorder by application of the therapeutic electrical stimulation
signal to a selected nerve. Automatic detection or patient sensing
of a symptom of the disorder may be utilized for activating the
device.
Inventors: |
Barrett, Burke T.; (Houston,
TX) ; Terry, Reese S. JR.; (Houston, TX) |
Correspondence
Address: |
BLANK ROME LLP
600 NEW HAMPSHIRE AVENUE, N.W.
WASHINGTON
DC
20037
US
|
Family ID: |
25439037 |
Appl. No.: |
10/661640 |
Filed: |
September 15, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10661640 |
Sep 15, 2003 |
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09917602 |
Jul 28, 2001 |
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6622038 |
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Current U.S.
Class: |
607/48 |
Current CPC
Class: |
A61N 1/36114 20130101;
A61N 1/36082 20130101 |
Class at
Publication: |
607/048 |
International
Class: |
A61N 001/18 |
Claims
1-21. (canceled)
22. Apparatus for treating patients suffering from movement
disorder, comprising a pulse generator sanctioned by government
authority for implantation in a patient together with electrode
means to treat said disorder by stimulation of a selected cranial
nerve of the patient with a predetermined sequence of electrical
impulses from said pulse generator applied to the selected cranial
nerve at a location in a range from about two to about three inches
above or below the patient's diaphragm, for alleviating symptoms of
the movement disorder in the patient.
23. The apparatus of claim 22, wherein said pulse generator is
programmable to enable physician programming of the electrical and
timing parameters of said sequence of electrical impulses.
24. The apparatus of claim 22, wherein the selected cranial nerve
is the vagus nerve, and said electrode means comprises at least one
nerve electrode for implantation on the patient's vagus nerve for
direct stimulation thereof at said location.
25. The apparatus of claim 24, wherein said electrode means
comprises a pair of nerve electrodes for implantation of a
respective one of said pair on left and right branches of the
patient's vagus nerve for direct bilateral stimulation thereof at
said location.
26. The apparatus of claim 22, wherein said electrode means
comprises at least one electrode for implantation internally to a
portion of the patient's nervous system remote from the selected
cranial nerve to indirectly stimulate the selected cranial nerve in
the vicinity of said location.
27. The apparatus of claim 22, including a sense signal analysis
circuit associated with the pulse generator for analyzing a signal
produced by a sensor in response to movement of the patient to
assess whether the patient's movement is random, uncoordinated and
involuntary characteristic of the movement disorder being treated,
and, if it is, for activating the pulse generator to stimulate the
selected cranial nerve in the vicinity of said location.
28. The apparatus of claim 22, including means associated with the
pulse generator for enabling patient activation of the pulse
generator to stimulate the selected cranial nerve in the vicinity
of said location.
29. Apparatus for treating patients suffering from movement
disorder, comprising a pulse generator approved by a government
agency of competent authority to be implanted with at least one
interconnected nerve electrode in a patient to treat said movement
disorder by applying a programmed sequence of electrical impulses
generated by said pulse generator to a branch of the patient's
vagus nerve via said electrode implanted on said nerve at a
location in a range from about two to about three inches above or
below the patient's diaphragm, for relieving symptoms of the
movement disorder in the patient.
30. The apparatus of claim 29, wherein said pulse generator is
adapted to be programmed by a physician to provide electrical and
timing parameters of said impulses.
31. The apparatus of claim 29, wherein said electrode means has a
length sufficient to enable said nerve electrode to be implanted on
said nerve at said location.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates generally to methods and
apparatus for treating or controlling movement disorders by
application of modulating electrical signals to a selected nerve or
nerve bundle of the patient, and more particularly to techniques
for treating patients with movement disorders by application of
such signals to the vagus nerve or other suitable cranial nerve,
using an implantable neurostimulator.
[0002] It is an object of the present invention to apply the
techniques of selective modulation of vagus nerve electrical
activity to the treatment of movement disorders, using a
neurostimulator device which may be implantable, or used external
to the body with only a small portion of the circuitry implanted or
with only the nerve electrode(s) and associated lead(s) implanted
percutaneously in the body.
[0003] In U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807, J.
Zabara discloses methods and devices for treating and controlling
epileptic seizures and certain motor disorders by selective
stimulation of the vagus nerve. The disorders include involuntary
movements of the patient during an epileptic seizure, or
attributable to Parkinson's disease, palsy or spastic disorders,
for example. In the disclosure of the patents, the stimulating
electrical pulse signal is preferably applied to the nerve in the
patient's neck region. In the '734 patent, movement disorders are
also mentioned in connection with discussion of the trigeminal and
glossopharngyeal nerves.
[0004] In the '254 patent, for example, Zabara discloses methods
and devices for performing extra-physiologic electrical stimulation
of the vagus nerve for treatment of epilepsy and various forms of
involuntary movement disorders. An implantable pulse generator uses
neurocybernetic spectral discrimination, in which the external
current of the generator is tuned to the electrochemical properties
of certain inhibitory nerves that affect the reticular system of
the brain. These nerves are embedded within a bundle of other
nerves, and are selectively activated directly or indirectly by the
tuning of the generator to augment states of brain neural discharge
to control convulsions or seizures. The generator may be activated
manually by the patient upon recognizing a characteristic of the
disorder, such as the classic aura at onset of a seizure, or
automatically such as by sensory detection of instantaneous changes
in certain state parameters at onset, for treatment only for the
duration of the seizure. Alternatively, the generator may be
activated for periodic prophylactic treatment.
[0005] It is a principal aim of the present invention to provide a
new technique for treating movement disorders using stimulation of
a suitable cranial nerve, particularly the vagus nerve.
[0006] The basic stimulation strategy of the present invention may
be implemented by circadian programming to automatically activate
the stimulus generator to continuously, periodically or
intermittently generate an electrical signal appropriate for
application to the patient's vagus nerve to modulate its activity.
In another aspect, the treatment is carried out by applying the
selectively modulating electrical signals to the patient's vagus
nerve in response to the occurrence of a predetermined detectable
event.
SUMMARY OF THE INVENTION
[0007] According to the present invention, a method of treating
patients suffering from involuntary movement disorders, such as but
not limited to epileptic seizures, Parkinson's disease, palsy or
spastic disorders, comprises unilateral or bilateral stimulation of
the left and right vagi in the immediate vicinity of the patient's
diaphragm. The treatment is administered at either a
supra-diaphragmatic position (i.e., above the diaphragm) or
sub-diaphragmatic position (i.e., below the diaphragm) in the
ventral cavity. The stimulating electrical signal is preferably
applied to the vagus two to three inches above or below the
diaphragm, and may be applied either synchronously or
asynchronously to both the right and left branches, preferably in
the form of a series of pulses applied intermittently to both
branches according to a predetermined on/off duty cycle. The
intermittent application is preferably chronic, rather than acute.
However, continuous application or acute application by bilateral
stimulation of the right and left vagi or unilateral stimulation of
either branch of the nerve is also contemplated.
[0008] Automatic delivery of bilateral intermittent stimulation is
preferred, but alternatively in the case of certain movement
disorders application of the stimulating electrical signal to the
right and left vagi may be controlled by an external commencement
signal produced by the patient's placement of an external magnet or
other signal generating mechanism in proximity to the location of
the implanted device.
[0009] Preferably, the same stimulating electrical signal is
applied to both the right and left vagi, but as an alternative, a
stimulating electrical signal might be applied to the right vagus
which is different from the stimulating electrical signal applied
to the left vagus. And although two separate nerve stimulator
generators may be implanted for stimulating the left and right
vagi, respectively, as an alternative a single nerve stimulator
generator may be implanted for bilateral stimulation if the same
signal is to be applied to both the left and right branches of the
vagus nerve, whether delivered synchronously or asynchronously to
the vagi.
[0010] Preferably, the current magnitude of the stimulating signal
is programmed to be less than about 6 mA, to be below the retching
level of the patient as determined by the implanting physician at
the time the implant procedure is performed. This is desirable to
avoid patient nausea during periods of vagus nerve stimulation.
Preferably, the pulse width is set to a value not exceeding about
500 microseconds (.mu.s), the pulse repetition frequency is set at
about 20-30 Hertz (Hz), the VNS regimen follows alternating periods
of stimulation and no stimulation, with the second period about 1.8
to 6 times the length of the first period in the alternating
sequence (i.e., the on/off duty cycle is 1:1.8 to 1:6).
[0011] Alternative techniques include indirect stimulation of the
vagus, either bilaterally or unilaterally, at a location near one
or both branches of the nerve or elsewhere, which has the effect of
stimulating the vagus nerve as well. This may be accomplished
through afferents or efferents, for example. It is also
contemplated that direct or indirect unilateral or bilateral
stimulation, applied in the vicinity of the patient's diaphragm, of
one or more of the other cranial nerves of suitable sensory, motor
or mixed fiber types may be effective in treating movement
disorders, as an alternative to vagus nerve stimulation.
[0012] Some differences may be observed from stimulator to
stimulator in magnitude of current in the pulses of the stimulation
signal, and may be attributable to things such as patient
impedance, variation of the vagus nerve from right to left or
between patients, and variation in contact between the vagus and
the electrode implanted thereon from implant to implant.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] The above and still further aims, objectives, aspects,
features and attendant advantages of the present invention will be
better understood from a consideration of the following detailed
description of a presently contemplated best mode of practicing the
invention, by reference to a preferred exemplary method and
embodiment thereof, taken in conjunction with the accompanying
Figures of drawing, in which:
[0014] FIG. 1 is a simplified partial front view of a patient (in
phantom) having an implanted neurostimulator for generating the
desired signal stimuli which are applied directly and bilaterally
at a near-diaphragmatic location to the right and left branches of
the patient's vagus via an implanted lead/nerve electrode system
electrically connected to the neurostimulator;
[0015] FIG. 2 is a simplified partial front view of a patient
similar to that of FIG. 1, but in which a pair of implanted
neurostimulators is used for generating the desired signal
stimuli;
[0016] FIG. 3 is a simplified partial front view of a patient in
which an implanted neurostimulator and associated electrode is used
for unilateral stimulation of only one branch of the vagus nerve at
the near-diaphragmatic location; and
[0017] FIG. 4 is a simplified partial front view of a patient in
which the signal stimuli are applied at a portion of the nervous
system remote from the vagus nerve, for indirect stimulation of the
vagus nerve at the near-diaphragmatic location.
DESCRIPTION OF THE PRESENTLY CONTEMPLATED BEST MODE OF PRACTICING
THE INVENTION
[0018] A generally suitable form of neurostimulator for use in the
apparatus and method of the present invention is disclosed, for
example, in U.S. Pat. No. 5,154,172 (incorporated herein by
reference), assigned to the same assignee as the instant
application (the device also referred to from time to time herein
as a NeuroCybemetic Prosthesis or NCP device (NCP is a trademark of
Cyberonics, Inc. of Houston, Tex., the assignee)). Certain
parameters of the electrical stimuli generated by the
neurostimulator are programmable, preferably by means of an
external programmer (not shown) in a conventional manner for
implantable electrical medical devices.
[0019] Referring to FIG. 1, the neurostimulator (sometimes referred
to herein as stimulus generator, signal generator, pulse generator,
or simply the device), identified in the drawing by reference
number 10 is implanted in a patient 12, preferably in the abdominal
region, for example, via a left anterior thoracic or laporotomy
incision just beneath the skin or outer dermal layer. For the
preferred implementation and method of direct bilateral
stimulation, lead-electrode pair 15, 16 is also implanted during
the procedure, and the proximal end(s) of the lead(s) electrically
connected to the neurostimulator. The lead-electrode may be of a
standard bipolar lead nerve electrode type available from
Cyberonics, Inc.
[0020] It will be understood that the overall device generally is
required to be approved or sanctioned by government authority for
marketing as a medical device implantable in a patient together
with electrode means to treat the involuntary movement disorder by
stimulation of a selected cranial nerve (e.g., the vagus nerve) of
the patient. The treatment is performed using a predetermined
sequence of electrical impulses generated by the pulse generator
and applied to the selected cranial nerve at a location in a range,
preferably, from about two to about three inches above or below the
patient's diaphragm, for alleviating symptoms of the movement
disorder in the patient. In the United States, the government
agency for sanctioning such marketing and use is the U.S. Food and
Drug Administration (FDA), while in other countries, sanctioning is
typically handled by the counterpart of the FDA for the respective
country. Thus, in the United States the same device may not be
marketed or used to administer therapy to treat two different
diseases or disorders absent FDA approval of the device for
both.
[0021] According to the preferred method of the invention, the
nerve electrodes 17, 18 are implanted on the right and left
branches 19, 20, respectively, of the patient's vagus nerve at
either a supra-diaphragmatic or sub-diaphragmatic location. The
nerve electrodes are equipped with tethers for maintaining each
electrode in place without undue stress on the coupling of the
electrode onto the nerve itself. Preferably, the location of this
coupling is approximately two to three inches above or below the
patient's diaphragm 22 for each branch 19, 20.
[0022] Neurostimulator 10 generates electrical stimuli in the form
of electrical impulses according to a programmed regimen for
bilateral stimulation of the right and left branches of the vagus.
During the implant procedure, the physician checks the current
level of the pulsed signal to ascertain that the current is
adjusted to a magnitude at least slightly below the retching
threshold of the patient. Typically, if this level is programmed to
a value less than approximately 6 mA, the patient does not
experience retching attributable to the vagus nerve stimulation
(VNS) although variations may be observed from patient to patient.
In any event, the maximum amplitude of the current should be
adjusted accordingly until an absence of retching is observed, with
a suitable safety margin. The retching threshold may change
noticeably with time over a course of days after implantation, so
the level should be checked especially in the first few days after
implantation to determine whether any adjustment is necessary to
maintain an effective regimen.
[0023] The bilateral stimulation regimen of the VNS preferably
employs an intermittent pattern of a period in which a repeating
series of pulses is generated for stimulating the nerve, followed
by a period in which no pulses are generated. The on/off duty cycle
of these alternating periods of stimulation and no stimulation
preferably has a ratio in which the off time is approximately 1.8
to 6 times the length of the on time. Nominally, the width of each
pulse is set to a value not greater than about 500 .mu.s, and the
pulse repetition frequency is programmed to be in a range of about
20 to 30 Hz. The electrical and timing parameters of the
stimulating signal used for VNS as described herein for the
preferred embodiment will be understood to be merely exemplary and
not as constituting limitations on the scope of the invention.
[0024] The intermittent aspect of the bilateral stimulation resides
in applying the stimuli according to a prescribed duty cycle. The
pulse signal is programmed to have a predetermined on-time in which
a train or series of electrical pulses of preset parameters is
applied to the vagus branches, followed by a predetermined
off-time. Nevertheless, continuous application of the electrical
pulse signal may also be effective in treating movement
disorders.
[0025] Also, as shown in FIG. 2, dual implanted NCP devices 10a and
10b may be used as the pulse generators, one supplying the right
vagus and the other the left vagus to provide the bilateral
stimulation. At least slightly different stimulation for each
branch may be effective as well. Use of implanted stimulators for
performing the method of the invention is preferred, but treatment
may conceivably be administered using external stimulation
equipment on an out-patient basis, albeit only somewhat less
confining than complete hospitalization. Implantation of one or
more neurostimulators, of course, allows the patient to be
completely ambulatory, so that normal daily routine activities
including on the job performance is unaffected.
[0026] The desired stimulation of the patient's vagus nerve may
also be achieved by performing unilateral supra-diaphragmatic or
sub-diaphragmatic stimulation of either the left branch or the
right branch of the vagus nerve, as shown in FIG. 3. A single
neurostimulator 10 is implanted together with a lead 15 and
associated nerve electrode 17. The nerve electrode 17 is implanted
on either the right branch 19 or the left branch 20 of the nerve,
preferably in a location in a range of from about two to about
three inches above or below the patient's diaphragm 22. The
electrical signal stimuli are the same as described above.
[0027] In a technique illustrated in FIG. 4, the signal stimuli are
applied at a portion of the nervous system remote from the vagus
nerve, for indirect stimulation of the vagus nerve in the vicinity
of the diaphragmatic location. Here, at least one signal generator
10 is implanted together with one or more electrodes 17
subsequently operatively coupled to the generator via lead 15 for
generating and applying the electrical signal internally to a
portion of the patient's nervous system other than the vagus nerve,
to provide indirect stimulation of the vagus nerve in the vicinity
of the desired location. Alternatively, the electrical signal
stimulus may be applied non-invasively to a portion of the
patient's nervous system for indirect stimulation of the vagus
nerve at the near-diaphragmatic location.
[0028] In treating the disorder, detection strategies such as
sensing patient movement, particularly of the extremities, which
appears to be random, uncoordinated and involuntary, may be
employed to trigger the stimulation. To that end, a small
accelerometer 30 in its own case may be separately implanted such
as in a leg or arm of the patient to detect such movement. Or
instead, the accelerometer may be mounted integrally in the same
case that houses the neurostimulator. Alternatively, the vagal
stimulation may be performed without need for detection of a
symptom characteristic of the disorder or onset of the disorder. In
that case, the stimulation is continuous, or it may be periodic, or
intermittent during prescribed segments of the patient's circadian
cycle. For example, stimulation may be periodic with a random
frequency for the stimulating pulse waveform. In any event, this
regimen of vagal stimulation is programmed into the neurostimulator
device 10 (or 10a, 10b, as the case may be).
[0029] Since the patient is generally able to quickly recognize the
symptoms of the movement disorder, where it is characterized by
sudden onset or other random condition, provision may be made and
preferably is made for patient activation of the neurostimulator
for treatment of the particular movement disorder. For example,
certain techniques of manual and automatic activation of
implantable medical devices are disclosed in U.S. Pat. No.
5,304,206 to R. G. Baker, Jr. et al. (referred to herein as "the
'206 patent"), which is assigned to the same assignee as the
present application. According to the '206 patent, means for
manually activating or deactivating the stimulus generator may
include a sensor such as a piezoelectric element 31 mounted to the
inner surface of the generator case and adapted to detect light
taps by the patient on the implant site. One or more taps applied
in fast sequence to the skin above the location of the stimulus
generator in the patient's body may be programmed into the device
as the signal for activation of the generator, whereas two taps
spaced apart by a slightly longer time gap is programmed as the
signal for deactivation, for example. The therapy regimen performed
by the implanted device(s) remains that which has been
pre-programmed by means of the external programmer, according to
the prescription of the patient's physician in concert with
recommended programming techniques provided by the device
manufacturer. In this way, the patient is given limited but
convenient control over the device operation, to an extent which is
determined by the program dictated and/or entered by the attending
physician.
[0030] Where sense electrodes are to be utilized to detect onset of
the movement disorder being treated, a signal analysis circuit is
incorporated in the neurostimulator. Upon detection of the symptom
of interest of the disorder being treated, the processed digital
signal is supplied to a microprocessor in the neurostimulator
device, to trigger application of the stimulating signal to the
patient's vagus nerve.
[0031] The principles of the invention may be applicable to
selected cranial nerves other than the vagus nerve, to achieve the
desired results. Hence, although certain preferred methods and
modes of treating and controlling movement disorders through a
regimen generally of cranial nerve, and specifically vagus nerve
stimulation directly or indirectly at a near-diaphragmatic location
have been described herein, it will be appreciated by persons of
ordinary skill in the art of nerve stimulation for treatment of
diseases and disorders that variations and modifications may be
made within the scope of the present invention as defined by the
appended claims. It is therefore intended that the invention shall
be limited only as required by the appended claims and by the rules
of applicable law.
* * * * *