U.S. patent application number 12/359104 was filed with the patent office on 2010-07-29 for implantable medical device for providing chronic condition therapy and acute condition therapy using vagus nerve stimulation.
Invention is credited to Timothy L. Scott.
Application Number | 20100191304 12/359104 |
Document ID | / |
Family ID | 42077735 |
Filed Date | 2010-07-29 |
United States Patent
Application |
20100191304 |
Kind Code |
A1 |
Scott; Timothy L. |
July 29, 2010 |
Implantable Medical Device for Providing Chronic Condition Therapy
and Acute Condition Therapy Using Vagus Nerve Stimulation
Abstract
Disclosed herein are methods, systems, and apparatus for
treating a medical condition in a patient using an implantable
medical device (IMD). The IMD is capable of generating a first
electrical signal for treating a medical condition, for example
epilepsy. The first electrical signal relates to a long term
therapy during a first time period in which there is no indication
that the patient's brain is in an stable state, the first
electrical signal being a microburst stimulation signal. The
implantable device is also capable of generating a second
electrical signal for treating the medical condition. The second
electrical signal relates to a short term therapy during a second
time period, in response to an indication that the patient's brain
is in an unstable state. The second electrical signal in one
example, may be a conventional stimulation signal.
Inventors: |
Scott; Timothy L.; (Sugar
Land, TX) |
Correspondence
Address: |
CYBERONICS, INC.
LEGAL DEPARTMENT, 6TH FLOOR, 100 CYBERONICS BOULEVARD
HOUSTON
TX
77058
US
|
Family ID: |
42077735 |
Appl. No.: |
12/359104 |
Filed: |
January 23, 2009 |
Current U.S.
Class: |
607/45 |
Current CPC
Class: |
A61N 1/36114 20130101;
A61B 5/4047 20130101; A61B 5/369 20210101; A61N 1/361 20130101;
A61B 5/4094 20130101; A61N 1/36082 20130101 |
Class at
Publication: |
607/45 |
International
Class: |
A61N 1/36 20060101
A61N001/36 |
Claims
1. A method of treating a medical condition in a patient using an
implantable medical device, comprising: applying to a cranial nerve
a first electrical signal characterized by having at least one
microburst of a plurality of pulses during a first time period to
treat the medical condition, the first time period characterized by
a time period during which there is no indication that an acute
condition has occurred; and applying a second electrical signal to
the cranial nerve to treat the medical condition in response to an
indication of an acute event associated with the medical condition
for treating the acute event, the second electrical signal
characterized by at least one burst of a plurality of pulses during
a second time period that is greater than a microburst
duration.
2. The method of claim 1, wherein applying a second electrical
signal in response to an indication that an acute condition has
occurred comprises applying the second electrical signal in
response to at least one of an indication that an epileptic seizure
has occurred, an indication that a seizure is substantially
imminent, or than an imminent occurrence of an epileptic seizure is
highly probable, and wherein applying a first electrical signal
comprises applying a first electrical signal to provide a chronic
treatment for the epilepsy condition.
3. The method of claim 1, further comprising applying a seizure
detection algorithm to at least one sensed body parameter selected
from the group consisting of a heart rate parameter, a temperature,
an EEG signal, a breathing rate, and an eye parameter, wherein the
first time period is characterized by the seizure detection
algorithm providing no indication that the patient has entered an
unstable brain state.
4. The method of claim 1, further comprising applying a seizure
detection algorithm to at least one sensed body parameter selected
from the group consisting of a heart rate parameter, a temperature,
an EEG signal, a breathing rate, and an eye parameter, wherein
applying the second electrical signal comprises occurs in response
to the seizure detection algorithm indicating that the patient has
entered into an unstable brain state.
5. The method of claim 1, wherein applying the first electrical
signal comprises at least one of applying the microburst signal in
a predetermined timing pattern or applying the microburst signal
substantially synchronous to the patient's heartbeat.
6. The method of claim 5, wherein applying the microburst signal
substantially synchronous to the patient's heartbeat comprises the
microburst being delivered in one of a predetermined time period or
a derived time period following the R-wave of the patient's
heartbeat.
7. The method of claim 1, wherein applying the first electrical
signal comprises applying the first electrical signal characterized
by the number of pulses per microburst being from 2 pulses to about
10 pulses and the microburst duration being less than about 100
msec.
8. The method of claim 7, wherein applying the first electrical
signal comprises applying the first electrical signal characterized
by the number of pulses per microburst being from 2 to about 6 or
the microburst duration being from about 20 msec to about 80
msec.
9. The method of claim 1, further comprising providing an
electrode, coupling said electrode to the cranial nerve, providing
a programmable electrical signal generator coupled to the
electrode, and wherein applying the first and second electrical
signals to the cranial nerve comprises generating an electrical
signal with the electrical signal generator and applying the
electrical signal to the electrode.
10. The method of claim 1, wherein applying the second electrical
signal is characterized by at least about 100 pulses per burst and
a burst duration of at least about 2 sec.
11. The method of claim 1 wherein applying said electrical signal
to a cranial nerve comprises applying said electrical signal to at
least one of a left vagus nerve or the right vagus nerve of the
patient.
12. A method of treating an epilepsy condition of a patient,
comprising: coupling at least one electrode to at least one cranial
nerve of the patient; providing a programmable electrical signal
generator coupled to the electrode; generating a first electrical
signal for providing a chronic stimulation therapy for treating the
epilepsy condition; applying said first electrical signal to said
at least one cranial nerve for a first time period in which there
is no indication that the patient has entered into an unstable
brain state, said first electrical signal being a microburst
stimulation signal; generating a second electrical signal for
providing an acute stimulation therapy for treating the epilepsy
condition; and applying said second electrical signal for a second
time period in response to an indication that the patient has
entered into an unstable brain state, wherein said second
electrical signal is not a microburst signal.
13. The method of claim 12, wherein generating the first electrical
signal comprises generating a microburst stimulation signal that
comprises at least one burst, wherein each burst comprises a
plurality of pulses in the range of about 2 pulses to about 4
pulses, wherein each pulse subsequent to the first pulse is
separated from the preceding pulse by an interpulse interval in the
range of about 3 msec to about 10 msec.
14. The method of claim 12, wherein generating the first electrical
signal comprises providing a stimulation signal capable of reducing
the probability of the occurrence of a seizure.
15. The method of claim 12, wherein generating the second
electrical signal comprises generating a stimulation signal that
comprises at least one pulse burst, wherein each pulse burst is in
the range of about 7 to about 60 seconds, and wherein the pulse
bursts are further characterized by a frequency of from about 20 to
about 30 Hz.
16. The method of claim 12, further comprising applying a seizure
detection algorithm to at least one sensed body parameter selected
from the group consisting of a heart rate parameter, a temperature,
an EEG signal, a breathing rate, and an eye parameter, and wherein
said second electrical signal is applied in response to the seizure
detection algorithm indicating that the patient has entered into an
unstable brain state
17. The method of claim 12, wherein said first electrical signal is
characterized by having a number of pulses per microburst, an
interpulse interval, an interburst period, and a microburst
duration, and wherein at least one of the number of pulses per
microburst, the interpulse interval, the microburst duration, or
the interburst period is selected to enhance cranial nerve evoked
potentials.
18. A system for treating a medical condition, comprising: at least
one electrode coupled to at least one cranial nerve of a patient,
and an implantable medical device operatively coupled to the
electrode and comprising a programmable electrical signal generator
capable of generating a first electrical signal for providing a
chronic stimulation therapy for treating the medical condition,
wherein said first electrical signal is applied for a first time
period in which there is no indication of an acute event associated
with the medical condition, said first electrical signal being a
microburst stimulation signal; the implantable medical device also
being capable of generating a second electrical signal for
providing an acute stimulation therapy for treating the medical
condition, wherein said second electrical signal is applied for a
second time period in response to an indication of an acute event
associated with the medical condition, wherein said second
electrical signal is not a microburst signal.
19. The system for treating a medical condition of claim 18,
wherein: said first electrical signal is a microburst stimulation
signal that comprises at least one burst, wherein each burst
comprises a plurality of pulses in the range of 2 pulses to about 6
pulses, wherein each pulse subsequent to the first pulse is
separated from the preceding pulse by an interpulse interval in the
range of about 3 msec to about 10 msec; and said second electrical
signal is a non-microburst stimulation signal that comprises at
least one pulse burst, wherein each pulse burst comprises at least
about 100 pulses, wherein the burst is further characterized by a
pulse frequency of from about 20 to about 30 Hz.
20. A computer readable program storage device encoded with
instructions that, when executed by a computer, perform a method of
treating an epilepsy condition in a patient using an implantable
medical device, comprising: applying a first electrical signal to a
vagus nerve for a first time period in which there is no indication
that an epileptic seizure has occurred or is imminent, wherein said
first electrical signal is a microburst signal; and applying a
second electrical signal to the vagus nerve in response to an
indication that an epileptic seizure has occurred or is imminent,
wherein said second electrical signal is not a microburst
signal.
21. The computer readable program storage device encoded with
instructions that, when executed by a computer, perform the method
of claim 20, wherein applying the first electrical signal comprises
at least one of applying the microburst signal in a predetermined
timing pattern or applying the microburst signal substantially
synchronous to the patient's heartbeat.
22. The computer readable program storage device encoded with
instructions that, when executed by a computer, perform the method
of claim 20, wherein the first electrical signal is characterized
by the number of pulses per microburst being from 2 pulses to about
10 pulses and the microburst duration being less than 1 sec, and
the second electrical signal being characterized by a burst
duration of at least 2 seconds and at least about 100 pulses per
burst, wherein each burst is further characterized by a pulse
frequency of from about 20 to about 30 Hz.
Description
FIELD OF THE INVENTION
[0001] This invention relates generally to medical device systems
and, more particularly, to medical device systems for applying
electrical signals to a cranial nerve for the treatment of various
medical conditions, and for providing a chronic condition therapy
and an acute condition therapy using a microburst electrical signal
and a non-microburst electrical signal.
DESCRIPTION OF THE RELATED ART
[0002] Many advancements have been made in treating diseases such
as depression and epilepsy. Therapies using electrical signals for
treating these diseases have been found to effective. Implantable
medical devices have been effectively used to deliver therapeutic
stimulation to various portions of the human body (e.g., the vagus
nerve) for treating these diseases. As used herein, "stimulation"
or "stimulation signal" refers to the application of an electrical,
mechanical, magnetic, electromagnetic, photonic, audio and/or
chemical signal to a neural structure in the patient's body. The
signal is an exogenous signal that is distinct from the endogenous
electrical, mechanical, and chemical activity (e.g., afferent
and/or efferent electrical action potentials) generated by the
patient's body and environment. In other words, the stimulation
signal (whether electrical, mechanical, magnetic, electro-magnetic,
photonic, audio or chemical in nature) applied to the nerve in the
present invention is a signal applied from an artificial source,
e.g., a neurostimulator.
[0003] A "therapeutic signal" refers to a stimulation signal
delivered to a patient's body with the intent of treating a medical
condition by providing a modulating effect to neural tissue. The
effect of a stimulation signal on neuronal activity is termed
"modulation"; however, for simplicity, the terms "stimulating" and
"modulating", and variants thereof, are sometimes used
interchangeably herein. In general, however, the delivery of an
exogenous signal itself refers to "stimulation" of the neural
structure, while the effects of that signal, if any, on the
electrical activity of the neural structure are properly referred
to as "modulation." The modulating effect of the stimulation signal
upon the neural tissue may be excitatory or inhibitory, and may
potentiate acute and/or long-term changes in neuronal activity. For
example, the "modulating" effect of the stimulation signal to the
neural tissue may comprise one more of the following effects: (a)
initiation of an action potential (afferent and/or efferent action
potentials); (b) inhibition or blocking of the conduction of action
potentials, whether endogenous or exogenously induced, including
hyperpolarizing and/or collision blocking, (c) affecting changes in
neurotransmitter/neuromodulator release or uptake, and (d) changes
in neuro-plasticity or neurogenesis of brain tissue.
[0004] In some embodiments, electrical neurostimulation may be
provided by implanting an electrical device underneath the skin of
a patient and delivering an electrical signal to a nerve such as a
cranial nerve. As used in the present application, "open-loop"
refers to an electrical signal that is not applied in response to
an indication of a need or desire for acute treatment of the
patient's medical condition, such as an epileptic seizure detection
algorithm based upon one or more sensed body parameters. An
open-loop signal is also referred to as a chronic treatment signal.
A "closed-loop" signal, on the other hand, refers to an electrical
signal that is applied to a target structure in response to an
indication of a need or desire for acute treatment of the patient's
medical condition. A closed-loop signal is also referred to as an
acute treatment signal. The electrical signal may be applied by an
IMD that is implanted within the patient's body. In another
alternative embodiment, the signal may be generated by an external
pulse generator outside the patient's body, coupled by an RF or
wireless link to an implanted electrode.
[0005] Generally, neurostimulation signals that perform
neuromodulation are delivered by the IMD via one or more leads. The
leads generally terminate at their distal ends in one or more
electrodes, and the electrodes, in turn, are electrically coupled
to tissue in the patient's body. For example, a number of
electrodes may be attached to various points of a nerve or other
tissue inside a human body for delivery of a neurostimulation
signal.
[0006] While feedback stimulation (i.e., an electrical signal
applied in response to a sensed body parameter such as heart rate)
schemes have been proposed, conventional vagus nerve stimulation
(VNS) usually involves non-feedback stimulation characterized by a
number of parameters. Specifically, conventional vagus nerve
stimulation usually involves a series of grouped electrical pulses
defined by an "on-time" and an "off-time." Each sequence of pulses
during an on-time may be referred to as a "pulse burst." The burst
is followed by the off-time period in which no signals are applied
to the nerve. During the on-time, electrical pulses of a defined
electrical current (e.g., 0.5-2.0 milliamps) and pulse width (e.g.,
0.25-1.0 milliseconds) are delivered at a defined frequency (e.g.,
20-30 Hz) for the on-time duration, usually a specific number of
seconds, e.g., 10-60 seconds. The pulse bursts are separated from
one another by the off-time, (e.g., 30 seconds-5 minutes) in which
no electrical signal is applied to the nerve. The on-time and
off-time parameters together define a duty cycle, which is the
ratio of the on-time to the combination of the on-time and
off-time, and which describes the percentage of time that the
electrical signal is applied to the nerve.
[0007] In conventional VNS, the on-time and off-time may be
programmed to define an intermittent pattern in which a repeating
series of electrical pulse bursts are generated and applied to a
cranial nerve such as the vagus nerve. The off-time is provided to
allow the nerve to recover from the stimulation of the pulse burst,
and to conserve power. If the off-time is set at zero, the
electrical signal in conventional VNS may provide continuous
stimulation to the vagus nerve. Alternatively, the off time may be
as long as one day or more, in which case the pulse bursts are
provided only once per day or at even longer intervals. Typically,
however, the ratio of "off-time" to "on-time" may range from about
0.5 to about 10.
[0008] In addition to the on-time and off-time, the other
parameters defining the electrical signal in conventional VNS may
be programmed over a range of values. The pulse width for the
pulses in a pulse burst of conventional VNS may be set to a value
not greater than about 1 msec, such as about 250-500 .mu.sec, and
the number of pulses in a pulse burst is typically set by
programming a frequency in a range of about 20-150 Hz (i.e., 20
pulses per second to 150 pulses per second). A non-uniform
frequency may also be used. Frequency may be altered during a pulse
burst by either a frequency sweep from a low frequency to a high
frequency, or vice versa. Alternatively, the timing between
adjacent individual signals within a burst may be randomly changed
such that two adjacent signals may be generated at any frequency
within a range of frequencies.
[0009] Although neurostimulation has proven effective in the
treatment of a number of medical conditions, it would be desirable
to further enhance and optimize neurostimulation for this purpose.
For example, it may be desirable to enhance evoked potentials in
the patient's brain to aid in treating a medical condition.
Conventional VNS stimulation as described above provides little
measurable evoked potentials. It would be desirable to also
implement other types of stimulation that significantly increases
the evoked potential in the brain as compared to conventional VNS
signals.
[0010] State of the Art IMDs for cranial nerve stimulation
generally operate in an open-loop stimulation mode. Generally, IMDs
for vagus nerve stimulation (VNS) provide a conventional-type
electrical signal, which may include pulse trains that are
approximately 30-60 seconds in length at 10-30 Hz, with off-times
of from about 7-300 seconds. In this manner, the open-loop VNS
modes that provide conventional stimulation may utilize a
significant amount of battery life. Further, conventional open-loop
VNS consists of a single type of stimulation signal that is
provided based upon predetermined parameters. Typically, a
physician programs a first type of stimulation signal to be
delivered by the IMD for a period of time. After this period of
time, further evaluation of the patient's condition may prompt the
physician to alter and reprogram the IMD to provide a second
stimulation signal different, but largely similar to the first
stimulation signal. Regardless of the magnitude of the change,
however, the implementation of the second signal is done manually
by the physician, and a return to the first signal must likewise be
manually implemented by the physician. In this manner, the
conventional IMDs for VNS essentially provide just one type of
open-loop therapy at a time.
[0011] It has been proposed to provide VNS using a combined
open-loop and closed-loop stimulation technique with a conventional
stimulation signal during an open-loop phase and a slightly altered
version of the conventional stimulation signal during a closed-loop
stimulation phase. However, such VNS schemes would utilize a
greater amount of power than open-loop therapies and thereby affect
battery life. The industry generally lacks devices that provide for
an efficient stimulation signal during an open-loop cycle and a
more robust stimulation signal during a closed-loop cycle, when
more robust signals are useful in preventing or attenuating certain
epileptic side effects, such as seizures.
SUMMARY OF THE INVENTION
[0012] In one aspect of the present invention, a method of treating
a medical condition in a patient using an implantable medical
device is provided. A first electrical signal characterized by
having at least one microburst of a plurality of pulses is applied
to a cranial nerve during a first time period to treat the
patient's medical condition, which in one embodiment comprises
epilepsy. The first time period is a time period during which there
is no indication of an acute condition has occurred. In a
particular embodiment, the first time period is one in which there
is no indication that an epileptic seizure has occurred or is
imminent. In another particular embodiment, the first time period
is one in which there is no indication that the patient has entered
into an unstable brain state. A second electrical signal
characterized by at least one burst having a duration and number of
pulses greater than a microburst is applied for a second time
period in response to an indication of an acute event associated
with the medical condition for treating the acute event. In a
particular embodiment, the second time period is a treatment period
for acute treatment of an epileptic seizure following detection of
the actual or imminent occurrence of a seizure. In another
particular embodiment, the second time period is a treatment period
following detection of the patient experiencing an unstable brain
state.
[0013] In another aspect of the present invention, a method of
treating epilepsy in a patient using an implantable medical device
is provided. A programmable electrical signal generator coupled to
an electrode is provided. A first electrical signal for providing a
chronic stimulation therapy is generated for treating the epilepsy
condition. The first electrical signal is a microburst signal and
is provided during a first time period in which there is no
indication that the patient has entered an unstable brain state. In
another embodiment, the first time period is one in which there is
no indication of an acute event associated with the medical
condition. A second electrical signal for providing an acute
stimulation therapy is generated for treating the epilepsy
condition. The second electrical signal is a non-microburst signal,
and is applied for a second time period in response to an
indication that the patient has entered an unstable brain
state.
[0014] In yet another aspect of the present invention, a system for
treating a medical condition in a patient using an implantable
medical device is provided. The system includes at least one
electrode coupled to at least one cranial nerve of a patient and an
implantable medical device operatively coupled to the electrode.
The implantable medical device includes a programmable electrical
signal generator capable of generating a first electrical signal
for providing a chronic stimulation therapy for treating the
medical condition. The first electrical signal is a microburst
signal and is provided during a first time period in which there is
no indication that the patient is experiencing an unstable state.
In another embodiment, the first time period is one in which there
is no indication of an acute event associated with the medical
condition. The implantable device is also capable of generating a
second electrical signal for providing an acute stimulation therapy
for treating the medical condition. The second electrical signal is
a non-microburst signal applied to the at least one cranial nerve
for a second time period in response to an indication that the
patient has experienced an unstable brain state.
[0015] In one embodiment, the present invention provides a computer
readable program storage device encoded with instructions that,
when executed by a computer, perform a method for treating epilepsy
in a patient using an implantable medical device. The method
includes applying a first electrical signal to a vagus nerve for a
first time period. The first electrical signal is a microburst
signal, and the first time period is a time period during which
there is no indication that an epileptic seizure has occurred or is
imminent. In another embodiment, the first time period is one in
which there is no indication of an acute event associated with the
medical condition. The method also includes applying to the cranial
nerve a second electrical signal for a second time period. The
second electrical signal is not a microburst signal, and the second
time period is a treatment period for providing an acute treatment
of an epileptic seizure following detection of an actual or
imminent occurrence of a seizure. In another embodiment, the second
time period is a treatment period in response to an indication that
the patient has experienced an unstable brain state.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The invention may be understood by reference to the
following description taken in conjunction with the accompanying
drawings, in which like reference numerals identify like elements,
and in which:
[0017] FIG. 1 provides a stylized diagram of an implantable medical
device implanted into a patient's body for providing a therapeutic
electrical signal to a neural structure of the patient's body, in
accordance with one illustrative embodiment of the present
invention;
[0018] FIG. 2 is a block diagram of a medical device system that
includes an implantable medical device and an external device, in
accordance with one illustrative embodiment of the present
invention;
[0019] FIG. 3 illustrates an exemplary electrical signal of a
firing neuron as a graph of voltage at a given location at
particular times in response to application of an electrical signal
to the nerve by the neurostimulator of FIG. 2, in accordance with
one illustrative embodiment of the present invention;
[0020] FIGS. 4A, 4B, and 4C illustrate exemplary waveforms for
electrical signals for stimulating the cranial nerve for treating a
medical condition, according to one illustrative embodiment of the
present invention;
[0021] FIG. 5 shows an exemplary comparison of vagal evoked
potentials (VEPs) with different stimulus timings;
[0022] FIG. 6 illustrates a stylized depiction of the
synchronization of a vagal stimulus burst to the R-wave of a
patient's heartbeat;
[0023] FIG. 7 illustrates the localization of an early VEP in the
right thalamus and basal ganglia and a later VEP in the left
insular cortex;
[0024] FIG. 8 illustrates a stylized depiction of a chronic
stimulation block diagram and an acute stimulation block diagram,
according to one illustrative embodiment of the present
invention;
[0025] FIG. 9 illustrates a stylized depiction of an chronic
stimulation block diagram and an acute stimulation block diagram,
according to another illustrative embodiment of the present
invention; and
[0026] FIG. 10 illustrates a flowchart depiction of a method for
monitoring physiological parameters and determining whether an
acute manifestation of the medical condition has occurred, in
accordance with an illustrative embodiment of the present
invention.
[0027] While the invention is susceptible to various modifications
and alternative forms, specific embodiments thereof have been shown
by way of example in the drawings and are herein described in
detail. It should be understood, however, that the description
herein of specific embodiments is not intended to limit the
invention to the particular forms disclosed, but on the contrary,
the intention is to cover all modifications, equivalents, and
alternatives falling within the spirit and scope of the invention
as defined by the appended claims.
DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS
[0028] Illustrative embodiments of the invention are described
herein. In the interest of clarity, not all features of an actual
implementation are described in this specification. In the
development of any such actual embodiment, numerous
implementation-specific decisions must be made to achieve the
design-specific goals, which will vary from one implementation to
another. It will be appreciated that such a development effort,
while possibly complex and time-consuming, would nevertheless be a
routine undertaking for persons of ordinary skill in the art having
the benefit of this disclosure.
[0029] This document does not intend to distinguish between
components that differ in name but not function. In the following
discussion and in the claims, the terms "including" and "includes"
are used in an open-ended fashion, and thus should be interpreted
to mean "including, but not limited to." Also, the term "couple" or
"couples" is intended to mean either a direct or an indirect
electrical connection. "Direct contact," "direct attachment," or
providing a "direct coupling" indicates that a surface of a first
element contacts the surface of a second element with no
substantial attenuating medium there between. The presence of small
quantities of substances, such as bodily fluids, that do not
substantially attenuate electrical connections does not vitiate
direct contact. The word "or" is used in the inclusive sense (i.e.,
"and/or") unless a specific use to the contrary is explicitly
stated.
[0030] The term "electrode" or "electrodes" described herein may
refer to one or more stimulation electrodes (i.e., electrodes for
delivering an electrical signal generated by an IMD to a tissue),
sensing electrodes (i.e., electrodes for sensing a physiological
indication of a patient's body), and/or electrodes that are capable
of delivering a stimulation signal, as well as performing a sensing
function.
[0031] Cranial nerve stimulation has been proposed to treat a
number of medical conditions pertaining to or mediated by one or
more structures of the nervous system of the body, including
epilepsy and other movement disorders, depression, anxiety
disorders and other neuropsychiatric disorders, dementia, traumatic
brain injury, coma, migraine headache, obesity, eating disorders,
sleep disorders, cardiac disorders (such as congestive heart
failure and atrial fibrillation), hypertension, endocrine disorders
(such as diabetes and hypoglycemia), and pain (including
neuropathic pain and fibromyalgia), among others. See, e.g., U.S.
Pats. Nos. 4,867,164; 5,299,569; 5,269,303; 5,571,150; 5,215,086;
5,188,104; 5,263,480; 6,587,719; 6,609,025; 5,335,657; 6,622,041;
5,916,239; 5,707,400; 5,231,988; and 5,330,515. Despite the
numerous disorders for which cranial nerve stimulation has been
proposed or suggested as a treatment option, the fact that detailed
neural pathways for many (if not all) cranial nerves remain
relatively unknown, makes predictions of efficacy for any given
disorder difficult or impossible. Moreover, even if such pathways
were known, the precise stimulation parameters that would modulate
particular pathways relevant to a particular disorder generally
cannot be predicted.
[0032] In one embodiment, the present invention provides a method
of treating a medical condition. The medical condition can be
selected from the group consisting of epilepsy, neuropsychiatric
disorders (including but not limited to depression), eating
disorders/obesity, traumatic brain injury, coma, addiction
disorders, dementia, sleep disorders, pain, migraine, fibromyalgia,
endocrine/pancreatic disorders (including but not limited to
diabetes), motility disorders, hypertension, congestive heart
failure/cardiac capillary growth, hearing disorders (including
tinnitus), angina, syncope, vocal cord disorders, thyroid
disorders, pulmonary disorders, and reproductive endocrine
disorders (including infertility).
[0033] Improved therapeutic neurostimulation treatments for a
variety of medical conditions have recently been proposed by a new
type of electrical stimulation of the cranial nerves capable of
providing enhanced evoked potentials in the brain. See, e.g., US
Pub. No. 2007/0233193, to Arthur D. Craig ('193 publication).
"Enhanced" in the context of the '193 publication refers to
electrical potentials evoked in the forebrain by neurostimulation
that may be higher than those produced by conventional
neurostimulation alone, particularly conventional VNS with an
interpulse frequency of 20-30 Hz (resulting in a number of pulses
per burst of 140-1800, at a burst duration from 7-60 sec). The
electrical signal for the '193 publication is substantially
different from the electrical signals in conventional VNS. In
particular, the electrical signals in the '193 publication are
characterized by very short bursts of a limited number of
electrical pulses. These shorts bursts of less than 1 second are
referred to hereinafter as "microbursts," and electrical
stimulation applying microbursts to a cranial nerve is referred to
as "microburst stimulation." By applying an electrical signal
comprising a series of microbursts to, for example, a vagus nerve
of a patient, enhanced vagal evoked potentials (eVEP) are produced
in therapeutically significant areas of the brain.
[0034] The present invention involves a combination of microburst
and conventional stimulation signals, each of which is used to
treat a different aspect of the patient's medical condition. More
particularly, in one embodiment, a microburst signal may be used to
provide a chronic treatment signal and a conventional stimulation
signal may be used to provide an acute treatment signal. In some
embodiments, the conventional stimulation signal may be triggered
in response to an indication of a need or desire for acute
treatment of the patient's medical condition. In other words, in
response to an indication that an acute event associated with the
medical condition being treated has occurred (e.g., a seizure, an
imminent seizure, etc.), a stimulation that is different from the
microburst stimulation (e.g., conventional stimulation) may be
triggered.
[0035] As used herein, the term "microburst" refers to a portion of
a therapeutic electrical signal comprising a limited plurality of
pulses and a limited duration. More particularly, in one
embodiment, a microburst comprises at least two and no more than 25
electrical pulses, preferably at least 2 to and no more than 20
pulses per burst, more preferably at least 2 to and no more than 15
pulses per burst. Microbursts also have a much shorter duration
than bursts of a conventional electrical signal. Specifically, in
one embodiment, a microburst lasts for no more than 1 second,
typically no more than 100 milliseconds, and preferably from about
20 msec to about 80 msec. In one embodiment, a therapeutic
microburst electrical signal may comprise a series of microbursts
separated from one another by time intervals known as "interburst
periods" which allow a refractory interval for the nerve to recover
from the microburst and again become receptive to eVEP stimulation
by another microburst. In some embodiments, the interburst period
may be as long as or longer than the adjacent microbursts separated
by the interburst period, but must be at least 100 milliseconds.
Adjacent pulses in a microburst are separated by a time interval
known as an "interpulse interval." The interpulse interval,
together with the number of pulses and the pulse width of each
pulse, determines a "microburst duration," which is the length of a
microburst from the beginning of the first pulse to the end of the
last pulse (and thus the beginning of a new interburst period), and
which as noted cannot exceed 1 second.
[0036] Microburst electrical signals as used in the new treatment
paradigms of the present invention are thus characterized by an
interburst period, a microburst duration, a number of pulses per
microburst, and an interpulse interval. The pulses in a microburst
may be further characterized by a current amplitude and a pulse
width. Microburst electrical signals according to the present
invention may optionally include an on-time and an off-time in
which the microbursts are provided and not provided, respectively,
to a cranial nerve. At least one of the interburst period, the
burst duration, the number of pulses per microburst, the interpulse
interval, the current amplitude, the pulse width, the on-time, or
the off-time can be selected to enhance cranial nerve evoked
potentials. In addition, as used in the present invention, a
microburst electrical signal cannot include any portion of a
conventional or non-microburst electrical signal (i.e., pulse
bursts having more than 25 pulses, or which exceed 1 second in
duration).
[0037] In one embodiment, the present invention provides a method
of treating a medical condition of a patient using an implantable
medical device, comprising applying to a cranial nerve of a patient
a pulsed electrical signal comprising delivery of a microburst
electrical signal neurostimulation in one time period, as well as
conventional neurostimulation in another time period, which are
described in more details below. The microburst electrical signal
comprises a period of bursts of pulses comprising microbursts as
well as interburst periods separating adjacent microbursts. In one
embodiment, the interburst periods comprise at least 100
milliseconds each. In another embodiment, the interburst periods
comprise at least the length of one of the two microbursts
separated by the interburst period. In another embodiment, the
interburst period may be determined on a particular patient by
providing microbursts separated by increasingly smaller interburst
periods. The interburst period may be determined as any time
interval greater than that at which the eVEP significantly
diminishes or disappears.
[0038] It may be convenient to refer to a burst frequency for the
microburst electrical signal, defined as 1 divided by the sum of
the microburst duration and the interburst period, and it will be
recognized by persons of skill in the art that the interburst
period may alternatively be described in terms of a frequency of
the pulses rather than as an absolute time separating one pulse
from another.
[0039] Embodiments of the present invention provide for generating
a first or primary type of neurostimulation signal during a first
time period. The primary type of neurostimulation is an open-loop
therapy for applying a chronic therapy signal to a target structure
in the patient's body. In one embodiment, the first time period may
include a time interval in which a chronic therapy signal is
applied in response to a detected cardiac signal, such as heart
rate. In another embodiment, the first time period may be a time
interval in which a chronic therapy that is a passive electrical
signal is applied according to a timed duty cycle, independent of
any sensed body parameter. Further, the first or primary type of
neurostimulation signal may be a microburst signal, which may be
synchronized with the patient's heart rate or may be applied
according to a programmed set of parameters such as interburst
period, microburst duration, number of pulses per microburst,
interpulse interval, current amplitude, and pulse width,
independent of any sensed body parameter.
[0040] Embodiments of the present invention also include generating
a second or secondary type of neurostimulation signal during a
second time period. The secondary neurostimulation mode is a
closed-loop therapy for applying an acute therapy signal to a
target structure in response to an indication of a need or desire
for an acute treatment of the patient's medical condition (i.e.,
acute therapy). The signal indicating a need or desire for acute
treatment of the patient's medical condition may include an
indication that the patient has experienced an unstable brain state
and/or that a seizure has occurred or is imminent. However, in one
embodiment, once the secondary stimulation mode is initiated, the
termination of this mode may be independent of the continued
existence of the signal indicating the need or desire for acute
treatment, i.e., the acute treatment may terminate before or after
the termination of the signal indicating the need or desire for
acute treatment. In other words, in one embodiment, once the
secondary neurostimulation mode is initiated, this mode will run a
course that is of a pre-determined duration, independent of whether
the acute treatment signal that caused the initiation of this mode
has changed. That is, the second time period in one embodiment may
depend on whether an acute therapy signal is asserted, and in
another embodiment, may be independent of the acute therapy signal
once it has been asserted and the acute therapy signal initiated.
The predetermined duration of the secondary neurostimulation mode
may be shorter or longer than the time period when the feedback
signal that initiated the secondary neurostimulation mode is
asserted.
[0041] In another embodiment, after the second time period has
elapsed (whether by predetermined time duration or by the
discontinuation of a signal indicating need or desire for acute
treatment), the patient is again treated by the primary, chronic
therapy signal.
[0042] In one example, a microburst signal may be provided during a
primary, chronic therapy stage having a relatively long duration. A
therapy having a longer burst length, such as a conventional-type
electrical signal, may be provided during a secondary acute therapy
stage having a relatively short duration but corresponding to a
need or desire for acute treatment. The primary or chronic therapy
may refer to therapy applied during a time period in which no
seizure has recently occurred, no seizure is occurring, or no
indication of a seizure being imminent is observed. A long-term,
primary neurostimulation signal comprising a microburst signal is
applied by the IMD during this period.
[0043] In one embodiment, a seizure detection algorithm in the IMD
may be able to detect whether an epileptic seizure has occurred, is
occurring, or is in reasonable probability, imminent. The seizure
detection algorithm may involve, e.g., determination of the
existence of an unstable brain state associated with an occurring
seizure, a seizure that is imminent, or a high probability that a
seizure is imminent. Based upon an indication from the seizure
detection algorithm of an actual or imminent seizure, or a high
probability of an imminent seizure, a closed-loop therapy for
treating an acute condition, or an acute therapy signal may be
activated by the IMD. In one embodiment, as long at least one
parameter indicates that a significant probability exists that a
seizure has occurred, is occurring, or is imminent, a second type
of neurostimulation, e.g., conventional or more robust stimulation,
as opposed to the microburst stimulation, may be provided by the
IMD. In another embodiment, the parameter triggers the secondary
stimulation mode and the duration of this mode is based upon
predetermined parameters and is independent of the duration of the
signal indicating the need or desire for acute treatment. The
secondary or acute stimulation signal (e.g., conventional vagus
nerve stimulation signal) may be defined by a current amplitude, a
pulse width, a frequency, an on-time and an off-time to define a
non-microburst signal having more than 25 pulses per burst and a
burst length exceeding 1 second. In one embodiment, the acute vagus
nerve stimulation signal typically has more than 100 pulses per
burst and a burst duration of at least about 7 seconds (seq). In
another embodiment, the acute vagus nerve stimulation signal has
about 100 pulses per burst and a burst duration of at least about 2
sec. During normal operation of the IMD, when there is no
indication of a need or desire for acute treatment, a microburst
neurostimulation signal is provided by the IMD. Microburst signals
may involve lower power consumption than conventional vagus nerve
stimulation signals. In one embodiment, the various parameters
(e.g., amplitude, frequency, pulse-width, pulse-duration, number of
pulses per burst, etc.) of the microburst signal are defined such
that treatment of epilepsy is possible.
[0044] When the signal indicating a need or desire for acute
treatment is asserted, a significant change in the stimulation
signal that more resembles conventional stimulation therapy may be
triggered to interrupt the seizure, reduce the severity of the
seizure, and/or abort the seizure from occurring. Therefore,
significant improvement in the patient's quality of life may be
realized utilizing the present embodiment. Moreover, embodiments of
the present invention may improve therapy by combining microburst
stimulation with seizure interruption or prevention capabilities of
conventional VNS stimulation. Therefore, improved long-term therapy
combined with acute intervention procedures may be provided when
the patient is experiencing, or is at immediate threat of a
seizure.
[0045] The implantable medical device system of one embodiment of
the present invention provides for software module(s) that are
capable of acquiring, storing, and processing various forms of
data, such as patient data/parameters (e.g., physiological data,
side-effects data, such as heart rate, breathing rate,
brain-activity parameters, disease progression or regression data,
quality of life data, etc.) and therapy parameter data. Therapy
parameters may include, but are not limited to, electrical signal
parameters that define the therapeutic electrical signals delivered
by the IMD, medication parameters and/or any other therapeutic
treatment parameter. In an alternative embodiment, the term
"therapy parameters" may refer to electrical signal parameters
defining the therapeutic electrical signals delivered by the IMD.
Therapy parameters for a therapeutic electrical signal may also
include, but are not limited to, a current amplitude, a pulse
width, a frequency, an on-time, an off-time, an interburst period,
a number of pulses per burst, an interpulse interval, and a burst
duration.
[0046] Although not so limited, a system capable of implementing
embodiments of the present invention is described below. FIG. 1
depicts a stylized implantable medical system (IMD) 100 for
implementing one or more embodiments of the present invention. An
electrical signal generator 110 is provided, having a main body 112
comprising a case or shell with a header 116 for connecting to an
insulated, electrically conductive lead assembly 122. The generator
110 is implanted in the patient's chest in a pocket or cavity
formed by the implanting surgeon just below the skin (indicated by
a dotted line 145), similar to the implantation procedure for a
pacemaker pulse generator.
[0047] A nerve electrode assembly 125, preferably comprising a
plurality of electrodes having at least an electrode pair, is
conductively connected to the distal end of the lead assembly 122,
which preferably comprises a plurality of lead wires (one wire for
each electrode). Each electrode in the electrode assembly 125 may
operate independently or alternatively, may operate in conjunction
with the other electrodes. In one embodiment, the electrode
assembly 125 comprises at least a cathode and an anode. In another
embodiment, the electrode assembly comprises one or more unipolar
electrodes.
[0048] Lead assembly 122 is attached at its proximal end to
connectors on the header 116 of generator 110. The electrode
assembly 125 may be surgically coupled to the vagus nerve 127 in
the patient's neck or at another location, e.g., near the patient's
diaphragm or at the esophagus/stomach junction. Other (or
additional) cranial nerves such as the trigeminal and/or
glossopharyngeal nerves may also be used to deliver the electrical
signal in particular alternative embodiments. In one embodiment,
the electrode assembly 125 comprises a bipolar stimulating
electrode pair 126, 128 (i.e., a cathode and an anode). Suitable
electrode assemblies are available from Cyberonics, Inc., Houston,
Tex., USA as the Model 302 electrode assembly. However, persons of
skill in the art will appreciate that many electrode designs could
be used in the present invention. In one embodiment, the two
electrodes are wrapped about the vagus nerve, and the electrode
assembly 125 may be secured to the vagus nerve 127 by a spiral
anchoring tether 130 such as that disclosed in U.S. Pat. No.
4,979,511 issued Dec. 25, 1990 to Reese S. Terry, Jr. and assigned
to the same assignee as the instant application. Lead assembly 122
may be secured, while retaining the ability to flex with movement
of the chest and neck, by a suture connection to nearby tissue (not
shown).
[0049] In alternative embodiments, the electrode assembly 125 may
comprise temperature sensing elements and/or heart rate sensor
elements. Other sensors for other body parameters may also be
employed to trigger active stimulation. Both passive and active
stimulation may be combined or delivered by a single IMD according
to the present invention. Either or both modes may be appropriate
to treat a specific patient under observation.
[0050] In alternative embodiments, a sensor assembly 165,
comprising a sensor lead assembly 162 and a sensor 160, may be
employed to detect a body parameter of the patient.
[0051] The electrical pulse generator 110 may be programmed with an
external device (ED) such as computer 150 using programming
software known in the art. A programming wand 155 may be coupled to
the computer 150 as part of the ED to facilitate radio frequency
(RF) communication between the computer 150 and the pulse generator
110. The programming wand 155 and computer 150 permit non-invasive
communication with the generator 110 after the latter is implanted.
In systems where the computer 150 uses one or more channels in the
Medical Implant Communications Service (MICS) bandwidths, the
programming wand 155 may be omitted to permit more convenient
communication directly between the computer 150 and the pulse
generator 110.
[0052] The therapeutic electrical signal described herein may be
used to treat a medical condition by enhancing cranial nerve evoked
potentials separately, or in combination with another type of
treatment. For example, electrical signals according to the present
invention may be applied in combination with a chemical agent, such
as various drugs, to treat various medical conditions. Further, the
electrical stimulation may be performed in combination with
treatment(s) relating to a biological or chemical agent. The
electrical stimulation treatment may also be performed in
combination with other types of treatment, such as magnetic
stimulation treatment.
[0053] Turning now to FIG. 2, a block diagram depiction of the IMD
200 is provided, in accordance with one illustrative embodiment of
the present invention. The IMD 200 (such as generator 110 from FIG.
1) may comprise a controller 210 capable of controlling various
aspects of the operation of the IMD 200. The controller 210 is
capable of receiving internal data or external data and causing a
stimulation unit 220 to generate and deliver an electrical signal
to target tissues of the patient's body for treating a medical
condition. For example, the controller 210 may receive manual
instructions from an operator externally, or may cause the
electrical signal to be generated and delivered based on internal
calculations and programming. The controller 210 is capable of
affecting substantially all functions of the IMD 200.
[0054] The controller 210 may comprise various components, such as
a processor 215, a memory 217, etc. The processor 215 may comprise
one or more microcontrollers, microprocessors, etc., capable of
performing various executions of software components. The memory
217 may comprise various memory portions where a number of types of
data (e.g., internal data, external data instructions, software
codes, status data, diagnostic data, etc.) may be stored. The
memory 217 may comprise one or more of random access memory (RAM),
dynamic random access memory (DRAM), electrically erasable
programmable read-only memory (EEPROM), flash memory, etc.
[0055] The IMD 200 may also comprise a stimulation unit 220 capable
of generating and delivering electrical signals to one or more
electrodes via leads. A lead assembly such as lead assembly 122
(FIG. 1) may be coupled to the IMD 200. Therapy may be delivered to
the leads comprising the lead assembly 122 by the stimulation unit
220 based upon instructions from the controller 210. The
stimulation unit 220 may comprise various circuitry, such as
electrical signal generators, impedance control circuitry to
control the impedance "seen" by the leads, and other circuitry that
receives instructions relating to the delivery of the electrical
signal to tissue. The stimulation unit 220 is capable of delivering
electrical signals over the leads comprising the lead assembly 122.
The stimulation unit 220 is capable of delivering microburst
stimulation signals, as well as conventional stimulation signals,
and/or variations thereof.
[0056] The IMD 200 may also comprise a power supply 230. The power
supply 230 may comprise a battery, voltage regulators, capacitors,
etc., to provide power for the operation of the IMD 200, including
delivering the therapeutic electrical signal. The power supply 230
comprises a power source that in some embodiments may be
rechargeable. In other embodiments, a non-rechargeable power source
may be used. The power supply 230 provides power for the operation
of the IMD 200, including electronic operations and the electrical
signal generation and delivery functions. The power supply 230 may
comprise a lithium/thionyl chloride cell or a lithium/carbon
monofluoride (LiCFx) cell. Other battery types known in the art of
implantable medical devices may also be used.
[0057] The IMD 200 may also comprise a communication unit 260
capable of facilitating communications between the IMD 200 and
various devices. In particular, the communication unit 260 is
capable of providing transmission and reception of electronic
signals to and from an external unit 270, such as computer 150 and
a wand 155 that can communicate with the IMD 200 remotely (FIG. 1).
The communication unit 260 may include hardware, software,
firmware, or any combination thereof.
[0058] In one embodiment, the IMD 200 may also comprise a
physiological detection unit 295 that is capable of detecting
various patient parameters. For example, the physiological
detection unit 295 may comprise hardware, software, or firmware
that is capable of obtaining and/or analyzing data relating to one
or more body parameters of the patient. This data may include
heartbeat data, temperature data, respiratory data, blood pressure
data, brain signal data, etc. Based upon the data obtained and/or
calculated by the physiological detection unit 295, the IMD 200 may
deliver the electrical signal to a portion of the cranial nerve to
treat epilepsy, depression or other medical conditions. In one
embodiment, the physiological detection unit 295 may also be
capable of detecting a manual input from the patient. The manual
input may include a magnetic signal input, a tap input, a wireless
data input to the IMD 200, etc. The manual input may be indicative
of an onset of a seizure.
[0059] In one embodiment, the physiological detection unit 295 may
comprise hardware, software, or firmware that is capable of
obtaining and/or analyzing data relating to one or more body
parameters of the patient's cardiac cycle. Based upon the data
obtained by the detection unit 295, the IMD 200 may deliver the
electrical signal to a portion of the cranial nerve to treat
epilepsy, depression or other medical conditions.
[0060] The IMD 200 may also comprise a seizure detection unit 265.
The seizure detection unit 265 may receive various data from the
physiological detection unit 295. As described above, the
physiological detection unit may provide various physiological data
relating to the patient. Further, physiological detection unit 295
is also capable of detecting input from an external source, such as
the patient. Based upon data from the physiological detection unit
295, the seizure detection unit 265 is capable of determining a
need or desire for acute treatment of epilepsy, in particular
whether a seizure is taking place, whether the seizure has very
recently taken place, and/or whether a seizure is imminent. For
example, the seizure detection unit 265 may detect a sudden rise in
the patient's heart rate, wherein pre-determined/pre-programmed
data within the IMD 200 may cause the seizure detection unit 265 to
provide an indication that a seizure is impending based upon the
received heart rate. In one embodiment, the seizure detection unit
265 is capable of determining that the patient has experienced an
unstable brain state associated with the onset, imminent onset, or
high probability of the occurrence of a seizure. Based upon this
determination, a closed-loop stimulation mode to treat an acute
condition or an acute therapy mode may be entered into by the IMD
200. In this closed loop therapy mode or the acute therapy mode,
the stimulation unit 220 is capable of delivering a stimulation
signal that is a non-microburst stimulation signal, e.g., the
conventional style VNS stimulation signals described herein.
[0061] When the seizure detection unit 265 provides no indication
that there is an impending seizure, actual, or probable seizure,
the stimulation unit 220 may then deliver a microburst stimulation
signal. In another embodiment, regardless of this indication, once
triggered by this indication, the acute therapy mode will run a
course that is predetermined, and then revert back to the primary
or chronic therapy mode. This process may continue in a primary or
chronic therapy mode until the seizure detection unit 265 indicates
that a seizure is imminent, actual or highly probable. The seizure
detection unit 265 may be preprogrammed using upon various factors,
such as physiological characteristics of a particular patient, the
anticipated heart-rate deviancy that precedes a seizure, etc. Based
upon the indication provided by the seizure detection unit 265, the
controller 210 may prompt the stimulation unit 220 to perform an
acute therapy stimulation for treating an acute condition utilizing
an electrical signal that is not a microburst electrical
signal.
[0062] The external unit 270 may be a device that is capable of
programming electrical signal parameters of the IMD 200. In one
embodiment, the external unit 270 is a computer system capable of
executing a data-acquisition program. The external unit 270 may be
controlled by a healthcare provider, such as a physician, at a base
station in, for example, a doctor's office. In alternative
embodiments, the external unit 270 may be controlled by a patient
in a system providing less control over the operation of the IMD
200 than another external unit 270 controlled by a healthcare
provider. Whether controlled by the patient or by a healthcare
provider, the external unit 270 may be a computer, preferably a
handheld computer or PDA, but may alternatively comprise any other
device that is capable of electronic communications and
programming, e.g., hand-held computer system, a PC computer system,
a laptop computer system, a server, a personal digital assistant
(PDA), an Apple-based computer system, etc. The external unit 270
may download various parameters and program software into the IMD
200 for programming the operation of the IMD, and may also receive
and upload various status conditions and other data from the IMD
200. Communications between the external unit 270 and the
communication unit 260 in the IMD 200 may occur via a wireless or
other type of communication, represented generally by line 277 in
FIG. 2. This may occur using, e.g., wand 155 (FIG. 1) to
communicate by RF energy with a generator 110. Alternatively, the
wand may be omitted in some systems, e.g., systems in which
external unit 270 operates in the MICS bandwidths.
[0063] In one embodiment, the external unit 270 may comprise a
local database unit 255. Optionally or alternatively, the external
unit 270 may also be coupled to a database unit 250, which may be
separate from external unit 270 (e.g., a centralized database
wirelessly linked to a handheld external unit 270). The database
unit 250 and/or the local database unit 255 are capable of storing
various patient data. This data may comprise patient parameter data
acquired from a patient's body and/or therapy parameter data. The
database unit 250 and/or the local database unit 255 may comprise
data for a plurality of patients, and may be organized and stored
in a variety of manners, such as in date format, severity of
disease format, etc. The database unit 250 and/or the local
database unit 255 may be relational databases in one embodiment. A
physician may perform various patient management functions (e.g.,
programming parameters for the primary/chronic therapy and/or
secondary/acute therapy modes) using the external unit 270, which
may include obtaining and/or analyzing data from the IMD 200 and/or
data from the database unit 250 and/or the local database unit 255.
The database unit 250 and/or the local database unit 255 may store
various patient data.
[0064] One or more of the blocks illustrated in the block diagram
of the IMD 200 in FIG. 2, may comprise hardware units, software
units, firmware units, or any combination thereof. Additionally,
one or more blocks illustrated in FIG. 2 may be combined with other
blocks, which may represent circuit hardware units, software
algorithms, etc. Additionally, any number of the circuitry or
software units associated with the various blocks illustrated in
FIG. 2 may be combined into a programmable device, such as a field
programmable gate array, an ASIC device, etc.
[0065] FIG. 3 provides a stylized depiction of an exemplary
electrical signal of a firing neuron as a graph of voltage at a
given point on the nerve at particular times during the propagation
of an action potential along the nerve, in accordance with one
embodiment of the present invention. A typical neuron has a resting
membrane potential of about -70 mV, maintained by transmembrane ion
channel proteins. When a portion of the neuron reaches a firing
threshold of about -55 mV, the ion channel proteins in the locality
allow the rapid ingress of extracellular sodium ions, which
depolarizes the membrane to about +30 mV. The wave of
depolarization then propagates along the neuron. After
depolarization at a given location, potassium ion channels open to
allow intracellular potassium ions to exit the cell, lowering the
membrane potential to about -80 mV (hyperpolarization). About 1
msec is required for transmembrane proteins to return sodium and
potassium ions to their starting intra- and extracellular
concentrations and allow a subsequent action potential to
occur.
[0066] Referring again to FIG. 1, the IMD 100 may generate a pulsed
electrical signal in embodiments of the present invention for
application to a cranial nerve such as vagus nerve 127 according to
one or more programmed parameters. In one embodiment, the
parameters defining the electrical signal may be selected from the
group consisting of an interburst period, a number of pulses per
burst, an interpulse interval, a burst duration, a current
magnitude, a pulse width, an on-time, and an off-time. Suitable
ranges for these parameters may comprise a variety of values. In
particular, the interburst period in microburst signals according
to the present invention is 100 milliseconds or greater, preferably
about 1 second to about 5 seconds. In another embodiment, the
interburst period may be equal to or greater than the microburst
duration of one of the two adjacent microbursts that the interburst
period separates. The number of pulses comprising a microburst may
range from 2 to 25 pulses, and more specifically from 2 to about 10
pulses. Suitable interpulse intervals in the present invention may
range from about 1 millisecond to about 20 milliseconds, more
preferably from about 2 milliseconds to about 10 milliseconds.
Suitable microburst durations may range from about 2 msec to no
more than 1 second, preferably less than about 100 msec, more
preferably from about 5 msec to about 100 msec, and even more
preferably from about 20 msec to about 80 msec.
[0067] Ranges for current magnitude and pulse width of pulses in a
microburst signal may comprise values similar to those for
conventional VNS signals, e.g., current magnitudes of 0.10-6.0
milliamps, preferably 0.25-3.0 milliamps, and more preferably
0.5-2.0 milliamps. Pulse widths may range from about 0.05 to about
1.0 milliseconds, preferably 0.25 to about 0.5 milliseconds. In
view of the stated values of pulse width and interpulse intervals,
a 2-pulse microburst could comprise a microburst duration of as
little as 1.1 milliseconds, while a microburst of 25 pulses could
last as long as about 500 milliseconds, although microburst
durations of 100 milliseconds or less are preferred. In each case,
however, the microburst must be less than 1 second in duration.
[0068] In one embodiment, microburst signals of the present
invention may be applied to the nerve substantially continuously,
with microbursts being applied to the nerve separated only by the
interburst period (e.g., 1 to 5 seconds in a preferred embodiment)
or by second time periods when acute stimulation signals are
applied. In an alternative embodiment, the time period in which
microburst signals are delivered may at least partially overlap the
time period when a secondary (acute therapy), e.g., conventional
stimulation signal is applied. In other words, in an alternative
embodiment, chronic therapy may overlap at least partially with
acute therapy.
[0069] Exemplary pulse waveforms in accordance with one embodiment
of the present invention are shown in FIGS. 4A-4C. Pulse shapes in
electrical signals according to the present invention may include a
variety of shapes known in the art including square waves, biphasic
pulses (including active and passive charge-balanced biphasic
pulses), triphasic waveforms, etc. In one embodiment, the pulses
comprise a square, biphasic waveform in which the second phase is a
charge-balancing phase of the opposite polarity to the first
phase.
[0070] In microburst therapy mode according to the present
invention, the microbursts are markedly shorter in both the number
of pulses and the microburst duration compared to pulse bursts in
conventional neurostimulation signals. While conventional VNS
signals typically involve pulse bursts at a frequency of 20-30 Hz
for a period of from 7-60 seconds (resulting in a burst having from
140-1800 pulses or more), microbursts according to the present
invention, by contrast, can have a microburst duration from about 1
msec to no more than 1 second. Further, each microburst comprises
at least 2 and no more than 25 pulses, with each of the pulses
separated from an adjacent pulse by an interpulse interval of from
about 1 to about 20 milliseconds, more typically from about 2 to
about 10 milliseconds. While the individual pulses in a microburst
according to this aspect of the invention may resemble conventional
VNS signal pulses in pulse width and pulse current, the number of
pulses in a microburst is markedly smaller than in a pulse burst in
conventional VNS therapy. Consequently, microbursts are also much
shorter in duration (less than 1 second and typically less than 100
msec, such as from about 20 msec to about 80 msec) than pulse
bursts in conventional neurostimulation therapy (at least 2 seconds
and typically 20-60 seconds). More significantly, the physiological
effects of the much shorter bursts are very different from
conventional bursts in terms of evoked response in the brain. In
addition to the much smaller number of pulses and overall duration
of microbursts compared to conventional bursts, in most cases, the
interpulse interval separating the pulses is shorter than in
conventional neurostimulation (typically 2-10 msec for microbursts
compared to 30-50 msec for conventional VNS). Pulse bursts of the
present invention are termed "microbursts" because they are
significantly shorter in both the number of pulses and the total
microburst duration than conventional neurostimulation signals.
[0071] As noted, it has been discovered that microbursts according
to this aspect of the invention are capable of providing an
enhanced vagal evoked potential (eVEP) in the patient's brain that
is significantly greater than VEPs produced by conventional vagus
nerve stimulation signals. This eVEP is attenuated, however, as the
number of pulses increases beyond an optimal number of pulses.
Thus, for example, in a monkey model discussed below, where a
microburst exceeds 2-5 pulses, the eVEP begins to diminish, and
eventually disappears. To maintain the eVEP effect, microburst
signals require a small number of pulses in a microburst as well as
an interburst period separating each microburst from the adjacent
microburst in order to allow the nerve a refractory space to
recover from the microburst. Providing an appropriate interburst
period ensures that the succeeding microburst in the electrical
signal is capable of generating an eVEP. In one embodiment the
interburst period is as long as or longer than the duration of the
adjacent microbursts separated by the interburst period. In another
embodiment, the interburst period is at least 100 milliseconds,
such as from about 1 sec to about 5 sec. Each microburst comprises
a series of pulses that, in some embodiments, are intended to mimic
the endogenous afferent activity on the vagus nerve. In one
embodiment the microbursts may simulate afferent vagal action
potentials associated with each cardiac and respiratory cycle.
[0072] Although evoked potentials have been discussed above in the
context of the vagus nerve, enhanced evoked potentials can be
generated by microburst stimulation of any cranial nerve, e.g. the
trigeminal nerve or glossopharyngeal nerve, and remain within the
spirit and scope of the present invention. Thus, while the present
invention is presented, in certain embodiments, as providing
microburst stimulation to a vagus nerve of a patient, microburst
stimulation may also be applied to other cranial nerves,
particularly the trigeminal nerve and the glossopharyngeal
nerve.
[0073] The central vagal afferent pathways involve two or more
synapses before producing activity in the forebrain. Each synaptic
transfer is a potential site of facilitation and a nonlinear
temporal filter, for which the sequence of interpulse intervals in
a microburst can be optimized. Without being bound by theory, it is
believed that the use of microbursts enhances VNS efficacy by
augmenting synaptic facilitation and "tuning" the input stimulus
train to maximize the forebrain evoked potential.
[0074] For example, as shown in FIG. 5, the vagal evoked potential
(VEP) measured in the monkey thalamus is scarcely visible if
elicited by a single stimulus pulse on the vagus nerve (FIG. 5A),
and virtually disappears if the single stimuli are presented in a
train at 30 Hz, as in conventional neurostimulation (FIG. 5B).
However, as shown in the series of traces in the middle and lower
panels of the figure, the VEP is enhanced (resulting in eVEP) by
using a microburst of pulses (2-6 pulses per microburst, microburst
duration .ltoreq.1 second, FIG. 5C) at appropriate interpulse
intervals (in this case, 6.7 msec was optimal for the first
interpulse interval, shown in FIG. 5D) and at an interburst period
(i.e., burst frequency) that approximates the electrocardiogram R-R
cycle (the period between R-waves of consecutive heartbeats) in the
monkey (in this case 0.3 Hz, shown as FIG. 5E).
[0075] The use of pairs of pulses is a physiological tool for
producing central responses by stimulation of small-diameter
afferent fibers. However, according to one embodiment of the
present disclosure, a microburst with an appropriate sequence of
interpulse intervals may be used as an effective neurostimulation
signal. By selecting an appropriate interburst period, an
electrical signal for neurostimulation may comprise a series of
microbursts that each provides eVEP. As illustrated in FIG. 5, a
microburst of 3-4 pulses produced a maximal VEP in the monkey and a
first interpulse interval of 6-10 msec produced maximal
facilitation, and so according to the present disclosure, a
microburst of pulses with a total duration of 10-50 msec and with
an interpulse interval of 5-10 msec and subsequent microbursts of
similar duration with an interburst period of from about 300 msec
to about 3 seconds will produce an optimal VEP in the monkey model.
Though not to be bound by theory, the eVEP may result because such
a microburst simulates the pattern of action potentials that occur
naturally in the small-diameter afferent vagal fibers that elicit
the central response that the present enhanced and optimized
therapy may evoke (see below). Selection of an appropriate
interburst period to separate one microburst from the next may be
performed experimentally, although as previously noted, a
refractory period of at least 100 msec (such as from 100 msec to 10
min, such as 1 sec to 5 sec) and at least equal to the microburst
duration is most desired.
[0076] The sequence of interpulse intervals may vary with a
patient's heart rate variability (HRV) (reflecting cardiac and
respiratory timing) and also between individual patients, and thus,
in one embodiment, the number of pulses, the interpulse interval,
the interburst period, and the microburst duration may be optimized
for each patient. As a standard microburst sequence for initial
usage, a microburst of 2 or 3 pulses at interpulse intervals of
5-10 msec will approximate the short peak of endogenous
post-cardiac activity. The interburst period may also be determined
empirically by providing microbursts with a steadily decreasing
interburst period until the eVEP begins to decline. In one
embodiment, the interpulse interval between the pulses in an
individual microburst is a series of equal intervals (i.e., the
simplest train) or increasing intervals, simulating the pattern of
a decelerating post-synaptic potential, as illustrated in FIG. 6.
In other alternative embodiments, the interpulse intervals may
decrease through the microburst, or may be randomly determined
within a preselected range, e.g., 5-20 msec. This usage of
microburst neurostimulation in combination with conventional
neurostimulation during a seizure or an impending seizure, may
produce a significant enhancement of neurostimulation efficacy that
is applicable to many different medical conditions, such as
epilepsy.
[0077] In one embodiment, the optimization may be accomplished by
recording, using surface electrodes, a far-field VEP, which
originates from the thalamus and other regions of the forebrain,
and varying the stimulus parameters in order to maximize the
recorded potential. As illustrated in FIG. 1, standard EEG
recording equipment 194 and 16- or 25-lead electrode placement (of
which five electrodes 190 are shown, with leads 192 in electrical
communication with the EEG recording equipment 194), such as
typically used clinically for recording somatosensory or auditory
evoked potentials, will enable the VEP to be recorded and
identified as an EEG recording 198. Neurostimulation stimulus burst
timing can be used to synchronize averages of 8 to 12 epochs, if
desired. By testing the effects of varied numbers of pulses,
interpulse intervals, microburst durations, and interburst periods
in defining the microbursts, the peak-to-peak amplitude of the eVEP
in a microburst can be optimized in each patient.
[0078] Neurostimulation can be optimized in individual patients by
selected stimulus parameters that produce the greatest effect as
measured with EEG surface electrodes. The current amplitude and
pulse width is first optimized by measuring the size of the VEP
elicited by individual pulses (as opposed to a microburst). The
number of pulses, interpulse intervals, microburst durations, and
interburst periods for the microbursts are then optimized using the
current amplitude and pulse width previously determined, by
measuring the size of the eVEP induced by the microbursts. Further
measurements using the EEG electrodes may be used to optimize the
parameters for the conventional neurostimulation for attenuating a
seizure episode and/or reducing the possibility of the onset of a
seizure.
[0079] Referring again to FIG. 5, the large eVEP recorded in the
right thalamus and striatum of the anesthetized monkey using
appropriately defined microburst stimulation signals is shown.
Without being bound by theory, it is believed that this eVEP is
significant for the anti-epileptic effects of neurostimulation,
whereas another potential (in the left insular cortex) is most
significant for the anti-depression effects of neurostimulation. By
using regional EEG localization on the right or left frontal
electrodes (FIG. 7), the neurostimulation electrical signal
parameters for microbursts, according to this aspect of the
invention can be optimized appropriately by measuring the eVEP in
these respective regions for individual patients. Regardless of the
eVEP provided by microburst signals, conventional type VNS
electrical signals may be used during periods when, for example, a
seizure detection algorithm employing heart rate parameter (such as
a series of R-R intervals), a temperature, an EEG signal, a
breathing rate, or an eye parameter, indicates that a seizure has
been detected or is imminent. Thus conventional stimulation signals
much longer in duration and having a much greater number of pulses
per burst than microbursts may be used in response to an indication
of a need or desire for acute treatment to interrupt a seizure
and/or reduce the severity of an imminent seizure would occur.
[0080] The optimal microburst parameters for eliciting eVEPs from
these two areas (right thalamus/striatum and left insular cortex,
respectively) may differ. Both eVEPs are identifiable with EEG
recording methods in awake human patients, so that the appropriate
area may easily be used for parametric optimization in an epilepsy
or depression patient.
[0081] The regional EEG localization represented in FIG. 7 allows
the early VEP in the right thalamus and basal ganglia associated
with the antiepileptic effects of neurostimulation to be
distinguished from the later VEP in the left thalamus and insular
cortex that may be associated with the treatment of other medical
conditions.
[0082] In one embodiment, the present invention may include
coupling of at least one electrode to each of two or more cranial
nerves. (In this context, two or more cranial nerves mean two or
more nerves having different names or numerical designations, and
do not refer to the left and right versions of a particular nerve).
In one embodiment, at least one electrode may be coupled to either
or both vagus nerves or a branch of either or both vagus nerves.
The term "operatively" coupled may include directly or indirectly
coupling. Each of the nerves in this embodiment or others involving
two or more cranial nerves may be stimulated according to
particular activation modalities that may be independent between
the two nerves.
[0083] Another activation modality for stimulation is to program
the output of the IMD 200 to the maximum amplitude which the
patient may tolerate. The stimulation may be cycled on and off for
a predetermined period of time followed by a relatively long
interval without stimulation. Also, the amplitude may vary between
microburst and conventional stimulation signals. Where the cranial
nerve stimulation system is completely external to the patient's
body, higher current amplitudes may be needed to overcome the
attenuation resulting from the absence of direct contact with the
cranial nerve, such as vagus nerve 127, and the additional
impedance of the skin of the patient. Although external systems
typically require greater power consumption than implantable ones,
they may have an advantage in that their batteries may be replaced
without surgery. Moreover, employing microburst signals as the
primary, chronic therapy signal and conventional neurostimulation
as the secondary, acute therapy may enhance the battery life of the
IMD 200.
[0084] Returning to systems for providing cranial nerve
stimulation, such as that shown in FIGS. 1 and 2, stimulation may
be provided in at least two different modalities. Where cranial
nerve stimulation is provided based solely on programmed off-times
and on-times, the stimulation may be referred to as passive,
inactive, or non-feedback stimulation. In contrast, stimulation may
be triggered by one or more feedback loops according to changes in
the body or mind of the patient. This stimulation may be referred
to as active or feedback-loop stimulation. In one embodiment,
feedback-loop stimulation may be manually-triggered stimulation, in
which the patient manually causes the activation of a pulse burst
outside of the programmed on-time/off-time cycle. In this case the
IMD 200 may change from microburst neurostimulation to conventional
neurostimulation. The patient may manually activate the IMD 200 to
stimulate the cranial nerve, such as vagus nerve 127, to treat an
acute episode of a medical condition, e.g., a seizure. The patient
may also be permitted to alter the intensity of the signals applied
to the cranial nerve within limits established by the
physician.
[0085] Patient activation of an IMD 100 may involve use of an
external control magnet for operating a reed switch in an implanted
device, for example. Certain other techniques of manual and
automatic activation of implantable medical devices are disclosed
in U.S. Pat. No. 5,304,206 to Baker, Jr., et al., assigned to the
same assignee as the present application ("the '206 patent").
According to the '206 patent, means for manually activating or
deactivating the electrical signal generator 110 may include a
sensor such as piezoelectric element 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 electrical signal
generator 110 in the patient's body may be programmed into the
implanted medical device 100 as a signal for activation of the
electrical signal generator 110, e.g., a change from microburst
neurostimulation to conventional neurostimulation. Two taps spaced
apart by a slightly longer duration of time may be programmed into
the IMD 100 to indicate a desire to deactivate the electrical
signal generator 110, for example, e.g., change back to microburst
neurostimulation from conventional neurostimulation. The patient
may be given limited control over operation of the device to an
extent which may be determined by the program or entered by the
attending physician. The patient may also activate the IMD 100
using other suitable techniques or apparatus.
[0086] In some embodiments, feedback stimulation systems other than
manually-initiated stimulation may be used in the present
invention. A cranial nerve stimulation system may include a sensing
lead coupled at its proximal end to a header along with a
stimulation lead and electrode assemblies. A sensor may be coupled
to the distal end of the sensing lead. The sensor may include a
cardiac cycle sensor. The sensor may also include a nerve sensor
for sensing activity on a nerve, such as a cranial nerve, such as
the vagus nerve 127.
[0087] In one embodiment, the sensor may sense a body parameter
that may be analyzed to determine a parameter that corresponds to
an acute manifestation of the patient's medical condition. If the
sensor is to be used to detect a manifestatio of the medical
condition, a signal analysis circuit may be incorporated into the
IMD 200 for processing and analyzing signals from the sensor. Upon
detection of the manifestation of the medical condition, the
processed digital signal may be supplied to a microprocessor in the
IMD 200 to trigger application of an acute electrical signal to the
cranial nerve, such as vagus nerve 127. For example, the sensor may
sense physiological data (e.g., a sudden change in heart rate)
that, after processing by a seizure detection algorithm, may
indicate that an epileptic seizure is imminent. In another
embodiment, the detection of a manifestation of the medical
condition (e.g., a seizure) may trigger an acute electrical signal
that is different from a chronic electrical signal. This may entail
switching from a microburst to a non-microburst electrical
signal.
[0088] Turning now to FIG. 8, a stylized block diagram depiction of
the chronic and acute stimulation provided by the IMD 200, in
accordance with one illustrative embodiment of the present
invention, is provided. FIG. 8 illustrates two separate loops for
providing therapy for treating epilepsy using an IMD 200: the
chronic therapy, which is an open loop therapy, and the acute
therapy, which is a closed loop therapy. In one embodiment, in the
chronic therapy mode, the IMD 200 provides a microburst
neurostimulation. In one embodiment, the microburst
neurostimulation is provided as the primary stimulation for a
chronic therapy for treating a medical condition, e.g., epilepsy,
depression, eating disorders, etc. Further, the acute therapy is
provided to deliver a substantially different stimulation signal as
compared to the chronic stimulation as an intervention in response
to a determination that an acute manifestation of the medical
condition has or will imminently occur. During the acute
stimulation mode, a physiological parameter indicative of a
seizure, or a possible seizure may be used to control the duration
of the acute therapy. In other words, in the embodiment of FIG. 8,
as long as the physiological parameter that is indicative of a
seizure or a potential seizure is active or asserted, acute
stimulation therapy is applied by the IMD 200. In this embodiment,
once this parameter is deactivated or de-asserted, the acute
therapy mode is terminated and the chronic therapy mode, which
provides microburst neurostimulation, is re-activated. The chronic
therapy mode is then left active until the acute stimulation signal
is once again triggered, i.e., a seizure or imminent seizure is
detected.
[0089] The IMD 200 provides a microburst neurostimulation signal
for treating a chronic condition, e.g., epilepsy, depression,
eating disorders, etc (block 810). Microburst neurostimulation
relates to the microburst signals described herein. The IMD 200
also performs monitoring of physiological parameters (block 820).
In one embodiment, the physiological detection unit 295 is capable
of performing analysis and sensing of physiological parameters
relating to the patient. Further, the IMD 200 monitors for other
inputs, such as external tap inputs, magnet inputs, etc, (block
830). These inputs may also trigger the activation of the acute
therapy mode.
[0090] Based upon the analysis of the physiological parameters
(block 820) and/or external inputs (block 830), the IMD 200 makes a
determination whether an acute manifestation of the medical
condition, such as a seizure, has occurred (block 840). When the
IMD 200 determines that a seizure has not occurred, the IMD 200
also makes a determination whether seizure is imminent (block 845).
Together, blocks 840 and 845 determine whether the patient's
condition indicates a need or desire for acute treatment. When the
IMD 200 determines that an impending seizure is also not present,
the IMD 200 continues to maintain a microburst stimulation delivery
mode (block 850). In this manner, blocks 810-850 provide a chronic
therapy mode, in which microburst signals are delivered for
treating a chronic condition, e.g., epilepsy, depression, eating
disorders, etc.
[0091] FIG. 10 illustrates a stylized block diagram depiction of
one embodiment of performing the monitoring of physiological
parameters and determining whether an acute manifestation of the
medical condition has occurred. The IMD 200 monitors the vital
signs of the patient (block 1010). These vital signs may include
various physiological parameters, such as heartbeat, respiratory
rate, body temperature, blood pressure, etc. The IMD 200 may then
compare the detected vital signs/physiological parameters to stored
data (block 1020). The stored data may include data for use as
thresholds against the detected physiological parameters.
Particular thresholds may be preprogrammed into the IMD 200 such
that indications of seizures or possible impending seizures may be
made based upon comparison of detected physiological data and
stored data. In this manner, the IMD 200 performs analysis to
determine if a seizure is occurring based upon a comparison of the
vital signs/physiological parameters to stored data (block 1030).
Further, the IMD 200 may also perform analysis to detect if a
seizure is impending based upon the comparison of the vital signs
to the stored data (block 1040). For example, a sudden rise in the
heart rate may be indicative of a potential impending seizure.
Based upon the analysis to determine whether a seizure is
occurring, the IMD 200 may provide an indication that a seizure is
occurring to the controller 210 (block 1050). Further, based upon
the analysis of block 1040, the seizure detection unit 265 may
provide an indication that a seizure is impending to the controller
210 (block 1060).
[0092] In one embodiment, in the chronic therapy mode, the
microburst signal may comprise pulses that are synchronous to the
R-wave of the patient's heart beat. For example, a burst of
microburst pulses may be delivered to the vagus nerve after a delay
period (e.g., about 50 milliseconds) after each R-wave of the
patient's heartbeat. However, those skilled in the art, having
benefit of the present disclosure would readily appreciate that
other delivery of pulses synchronized to the heartbeat may be
provided, e.g., synchronizing the bursts to the P-wave, Q-wave,
etc. In one embodiment, the bursts may be delivered during varying
intervals after the detection of an R-wave, a P-wave, etc.
Variations to the delivery of the microburst signals described
above may be performed by those skilled in the art having benefit
of the present disclosure and still remain within the spirit and
scope of the present invention.
[0093] FIG. 8 also illustrates an acute stimulation process. Based
upon the indication that a seizure is occurring or has occurred
(block 840), the IMD 200 may generate a stimulation signal for
performing an interruption of the seizure (block 860). In the case
where a seizure has recently occurred, a stimulation signal for
responding to a previous seizure and/or for preventing a new
seizure is provided. This stimulation signal may relate to a more
robust signal, as compared to the microburst stimulation. For
example, the stimulation of the acute mode may more resemble a
conventional VNS signal and may include a burst with a duration of
5 to 60 seconds at 10-30 Hz. However, various types of signals that
are designed to perform an interruption of the seizure of a
particular patient, may be pre-programmed into the IMD 200.
[0094] Further, in response to a detection that a possible
impending seizure may occur (block 845), the IMD 200 may generate a
stimulation signal appropriate for preventing or reducing the
intensity of an imminent seizure (block 865). In response to a
determination that a seizure has occurred or is imminent, the IMD
200 may deliver the modified stimulation, e.g., a conventional
stimulation signal, to a portion of the patient's cranial nerve
(block 870). While delivering the acute therapy signal, the IMD 200
may continue to monitor physiological parameters and/or inputs from
external sources to determine whether to remain within the acute
stimulation mode (block 875). Based upon this monitoring, the
determination again is made as to whether the seizure is continuing
(block 880). Based upon a determination that the seizure is
continuing, the IMD 200 continues to generate and apply the acute
therapy signal stimulation for interrupting the seizure (See loop
from block 880 to block 860).
[0095] Further, if the seizure is not found to be continuing or
existing, the IMD 200 may further perform a determination whether a
seizure is imminent (block 885). If it is determined that a seizure
is imminent or highly probable, the IMD 200 may continue to
generate and apply the acute therapy signal that is directed to
prevent an impending seizure (See loop from block 885 to 865).
However, if a seizure is not found to be continuing, and there is
no seizure still imminent (block 885), the acute, closed-loop
stimulation mode is terminated and the chronic, microburst
neurostimulation is re-started (See loop from block 885 to block
850). Blocks 860-885 illustrate an acute therapy mode, wherein
further monitoring is performed to determine whether to stay in the
acute therapy mode, or whether to exit the acute mode. In this
manner, microburst stimulation is provided as a baseline treatment
for a chronic condition, e.g., epilepsy; inter-mixed with acute
invention using a different stimulation signal (e.g., conventional
stimulation) for either preventing an onset of a seizure or
treating the seizure. This way, a patient's chronic (e.g.,
epilepsy) condition is treated using microburst signals, thereby
saving power and more significantly, providing a robust stimulation
signal when detecting an acute condition, e.g., when a seizure or
an impending seizure is detected.
[0096] Turning now to FIG. 9, a stylized block diagram depiction of
the chronic and acute stimulation provided by the IMD 200, in
accordance with another illustrative embodiment of the present
invention, is provided. FIG. 9 also illustrates two separate loops
for providing therapy for treating epilepsy using an IMD 200: the
chronic therapy, which is an open loop therapy and the acute
therapy, which is a closed loop therapy. In one embodiment, in the
chronic therapy mode, the IMD 200 provides a microburst electrical
signal. In one embodiment, the microburst neurostimulation is
provided as the primary, chronic stimulation for treating a medical
condition, e.g., epilepsy, depression, eating disorders, etc.
Further, the acute therapy is provided to deliver a substantially
different stimulation signal as compared to the chronic therapy
signal, as an intervention in response to a determination that an
acute manifestation of the medical condition has or will imminently
occur. In the embodiment of FIG. 9, the duration of the acute
therapy mode is pre-determined and is independent of whether or not
an indication of the acute manifestation of the medical condition
continues to be asserted. In other words, the detection of the
acute condition triggers the acute therapy signal, but does not
control the duration of the acute therapy signal.
[0097] The IMD 200 provides a microburst neurostimulation signal as
a chronic electrical signal for treating a medical condition, e.g.,
epilepsy, depression, eating disorders, etc (block 910). Microburst
neurostimulation relates to the microburst signals described
herein. The IMD 200 also performs monitoring of physiological
parameters (block 920). In one embodiment, the physiological
detection unit 295 is capable of performing analysis and sensing of
physiological parameters relating to the patient. Further, the IMD
200 monitors for other inputs, such as external tap inputs, magnet
inputs, etc, (block 930). These inputs may also trigger the
activation of the acute therapy mode.
[0098] Based upon the analysis of the physiological parameters
(block 920) and/or external inputs (block 930), the IMD 200 makes a
determination whether an acute manifestation of the medical
condition has occurred (block 940). In one embodiment, an
indication of an acute manifestation of the condition may include
an indication that a seizure has occurred or is imminent, or that
the patient has entered into an unstable brain state as determined
by analysis of EEG, heart rate, temperature, breathing or eye
movement/dilation. When the IMD 200 determines that no acute
manifestation of the medical condition exists, the IMD 200
continues to maintain a microburst stimulation delivery mode as a
chronic therapy (block 950). In this manner, blocks 910-950 provide
a chronic therapy mode, in which microburst signals are delivered
for treating a medical condition, e.g., epilepsy, depression,
eating disorders, etc.
[0099] In one embodiment, in the chronic therapy mode, the
microburst signal may comprise pulses that are synchronous to the
R-wave of the patient's heart beat. For example, a burst of
microburst pulses may be delivered to the vagus nerve after a delay
period, for example about 50 milliseconds, after each R-wave of the
patient's heartbeat. However, those skilled in the art, having
benefit of the present disclosure would readily appreciate that
other delivery of pulses synchronized to the heartbeat may be
provided, e.g., synchronizing the bursts to the P-wave, Q-wave,
etc. In one embodiment, the bursts may be delivered during varying
intervals after the detection of an R-wave, a P-wave, etc.
Variations to the delivery of the microburst signals described
above may be performed by those skilled in the art having benefit
of the present disclosure and still remain within the spirit and
scope of the present invention.
[0100] FIG. 9 also illustrates an acute stimulation process. Based
upon the indication of an acute condition (block 950), the IMD 200
may generate a stimulation signal that is different from the
microburst signal (block 960). For example, the stimulation of the
acute mode may more resemble a conventional VNS signal and may
include a burst with a duration of 5 to 60 seconds at 10-30 Hz.
However, various types of signals that are designed to perform to
treat an acute condition may be pre-programmed into the IMD 200.
The duration of the acute mode may be also pre-programmed.
[0101] The IMD 200 delivers the acute therapy signal to a portion
of the patient's cranial nerve (block 970). The IMD 200 then makes
a determination whether the time period for completing the acute
therapy is finished (block 980). When a determination is made that
the acute therapy is not complete, the acute therapy stimulation
signal delivery is continued. When a determination is made that the
acute therapy is complete, the acute therapy mode is terminated and
microburst stimulation signal is delivered (i.e., delivery of
chronic therapy neurostimulation is resumed). In this manner, a
patient's medical (e.g., epilepsy) condition is treated using
microburst signals as a chronic therapy, thereby saving power
providing a first stimulation mode, and more providing a different,
non-microburst signal when detecting an acute condition, e.g., when
a seizure or an impending seizure is detected. This way, the
patient's brain is less likely to adapt to the conventional
neurostimulation, since it is only applied in the acute therapy
mode, and yet, the patients' medical condition, e.g., epilepsy is
treated using microburst neurostimulation. This may preserve the
ability of conventional electrical signal to stop an acute
condition, such as a seizure, avoiding an adaptation of the brain
to an otherwise therapeutically effective signal. Further, in an
alternative embodiment, during the off times described above, a
small amount of stimulation, i.e., background stimulation that
features an electrical signal below the threshold to generate
evoked potentials, may be applied.
[0102] All of the methods and apparatuses disclosed and claimed
herein may be made and executed without undue experimentation in
light of the present disclosure. While the methods and apparatus of
this invention have been described in terms of particular
embodiments, it will be apparent to those skilled in the art that
variations may be applied to the methods and apparatus and in the
steps, or in the sequence of steps, of the method described herein
without departing from the concept, spirit, and scope of the
invention, as defined by the appended claims. It should be
especially apparent that the principles of the invention may be
applied to selected cranial nerves other than, or in addition to,
the vagus nerve to achieve particular results in treating patients
having epilepsy, depression, or other medical conditions.
[0103] The particular embodiments disclosed above are illustrative
only as the invention may be modified and practiced in different
but equivalent manners apparent to those skilled in the art having
the benefit of the teachings herein. Furthermore, no limitations
are intended to the details of construction or design herein shown
other than as described in the claims below. It is, therefore,
evident that the particular embodiments disclosed above may be
altered or modified and all such variations are considered within
the scope and spirit of the invention. Accordingly, the protection
sought herein is as set forth in the claims below.
* * * * *