U.S. patent application number 09/727570 was filed with the patent office on 2001-06-14 for apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator.
Invention is credited to Boveja, Birinder Bob.
Application Number | 20010003799 09/727570 |
Document ID | / |
Family ID | 26873918 |
Filed Date | 2001-06-14 |
United States Patent
Application |
20010003799 |
Kind Code |
A1 |
Boveja, Birinder Bob |
June 14, 2001 |
Apparatus and method for adjunct (add-on) therapy for depression,
migraine, neuropsychiatric disorders, partial complex epilepsy,
generalized epilepsy and involuntary movement disorders utilizing
an external stimulator
Abstract
An apparatus and method for adjunct (add-on) therapy of
depression, migraine, neuropsychiatric disorders, partial complex
epilepsy, generalized epilepsy and involuntary movement disorders
comprises an implantable lead-receiver, and an external stimulator
having controlling circuitry, a power source, and a coil to
inductively couple the stimulator to the lead-receiver. The
external stimulator emits electrical pulses to stimulate a cranial
nerve such as the left vagus nerve according to a predetermined
program. In a second mode of operation, an operator may manually
override the predetermined sequence of stimulation.
Inventors: |
Boveja, Birinder Bob;
(Highlands Ranch, CO) |
Correspondence
Address: |
SHERIDAN ROSS P.C.
Suite 1200
1560 Broadway
Denver
CO
80202-5141
US
|
Family ID: |
26873918 |
Appl. No.: |
09/727570 |
Filed: |
November 30, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09727570 |
Nov 30, 2000 |
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09178060 |
Oct 26, 1998 |
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6205359 |
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Current U.S.
Class: |
607/45 |
Current CPC
Class: |
A61N 1/36017 20130101;
A61N 1/36025 20130101; A61N 1/0536 20130101; A61N 1/36064 20130101;
A61N 1/36075 20130101; A61N 1/36082 20130101 |
Class at
Publication: |
607/45 |
International
Class: |
A61N 001/05 |
Claims
What is claimed is:
1. An apparatus for electrical stimulation therapy for treatment of
at least one of depression, migraine and neuropsychiatric disorders
comprising: a) an implantable lead-receiver comprising a secondary
coil and at least one electrode capable of stimulating a cranial
nerve; b) an external stimulator comprising a power source,
circuitry to emit electrical signals, at least two predetermined
programs to control said electrical signals, and a primary coil; c)
said primary coil of said external stimulator and said secondary
coil of said implantable lead-receiver being capable of forming an
electrical connection by inductive coupling, whereby said external
stimulator is capable of controlling the stimulation of said
cranial nerve.
2. The apparatus of claim 1 wherein said neuropsychiatric disorder
comprises obsessive compulsive disorders.
3. The apparatus of claim 1, wherein said cranial nerve is the left
vagus nerve.
4. The apparatus of claim 1, wherein said external stimulator
comprises a patient override mechanism to manually activate said
external stimulator.
5. The apparatus of claim 1, wherein said predetermined programs
are capable of being modified to modify said electrical
signals.
6. The apparatus of claim 1, further comprising a program selection
mechanism wherein said at least two predetermined programs may be
selectively operated.
7. The apparatus of claim 1, wherein said primary coil of said
external stimulator is adapted to be in contact with the skin of
the patient.
8. The apparatus of claim 1, wherein said lead-receiver comprises a
lead body with at least one lumen, a lead body insulation, a
conductor, at least one electrode and a coil.
9. The apparatus of claim 8, wherein said at least one lumen is
selected from the group consisting of single, double, triple and
coaxial lumens.
10. The apparatus of claim 8 wherein said lead body insulation is
selected from the group consisting of polyurethane, silicone and
silicone with polytetrafluoroethylene.
11. The apparatus of claim 8 wherein said lead body further
comprises a coating selected from the group consisting of
lubricious PVP, antimicrobial and anti-inflammatory coatings.
12. The apparatus of claim 8 wherein said electrode comprises
amaterial selected from the group consisting of platinum,
platinum/iridium alloy, platinum/iridium alloy coated with titanium
nitride and carbon.
13. The apparatus of claim 8 wherein said electrode is selected
from the group consisting of standard ball electrodes, hydrogel
electrodes, spiral electrodes, steroid eluting electrodes, and
fiber electrodes.
14. The apparatus of claim 1, wherein said electrical signals
comprise at least one variable component selected from the group
consisting of the current amplitude, pulse width, frequency and
on-off timing sequence, and said at least two predetermined
programs controls said variable component of said electrical
signals.
15. A method to provide therapy for at least one of depression,
migraine and neuropsychiatric disorders, comprising; a) providing
an implantable lead-receiver comprising a secondary coil and at
least one electrode to stimulate a cranial nerve; b) providing an
external stimulator comprising circuitry to emit electrical
signals, at least two programs to control said electrical signals,
an external coil and a power supply; c) activating one of said at
least two programs of said external stimulator to emit said
electrical signals to said external coil; d) inductively
transferring said electrical signals from said external coil of
said external stimulator to said secondary coil of said
lead-receiver; whereby said electrical signals stimulate said
cranial nerve according to at least one of said at least two
predetermined programs.
16. The method of claim 15, wherein said cranial nerve is the left
vagus nerve.
17. The method of claim 15, wherein said cranial nerve is
stimulated by bipolar stimulation.
18. The method of claim 15, wherein said cranial nerve is
stimulated by unipolar stimulation.
19. The method of claim 15, wherein the step of activating one of
said at least two predetermined programs is manually performed.
20. The method of claim 15, further comprising manually controlling
said electrical signals to stimulate said cranial nerve.
21. The method of claim 15, wherein a) said electrical signals
comprise at least one variable component selected from the group
consisting of the current amplitude, pulse width, frequency, and
on-off timing sequence; and b) said at least two predetermined
programs controls said variable component of said electrical
signals.
22. The method of claim 15, further comprising manually disengaging
said at least two predetermined programs.
23. A method for treating symptoms of depression, migraine or
neuropsychiatric disorders comprising: a) selecting a predetermined
program to control the output of an external stimulator; b)
activating said external stimulator to emit electrical signals in
accordance with said predetermined program; and c) inductively
coupling said external stimulator with an implantable lead-receiver
to stimulate a cranial nerve.
24. The method of claim 21, further comprising implanting beneath
the skin of a patient said lead-receiver in direct electrical
contact with said cranial nerve.
Description
FIELD OF INVENTION
[0001] This is a Continuation-in-Part application claiming priority
from pending prior application Ser. No. 09/178,060 filed Oct. 26,
1998, the prior application being incorporated herein by
reference.
[0002] This invention relates generally to electrical stimulation
therapy for neurologic and neuropsychiatric disorders, more
specifically to neuromodulation therapy for depression, migraine,
and neuropsychiatric disorders, as well as adjunct treatment for
partial complex, generalized epilepsy and involuntary movement
disorders utilizing an implanted lead-receiver and an external
stimulator.
BACKGROUND
[0003] It has been observed clinically that electrical stimulation
therapy for seizures produced mood improvement independent of the
anti-seizure effects. This discovery led to medical research into
the therapeutic effects of electrical stimulation for depression.
Medical research has shown beneficial medical effects of vagus
nerve stimulation (VNS) for severely depressed patients.
[0004] Vagus nerve stimulation, and the profound effects of
electrical stimulation of the vagus nerve on central nervous system
(CNS) activity, extends back to the 1930's. Medical studies in
clinical neurobiology have advanced our understanding of anatomic
and physiologic basis of the anti-depressive effects of vagus nerve
stimulation.
[0005] Some of the somatic interventions for the treatment of
depression include electroconvulsive therapy (ECT), transcranical
magnetic stimulation, vagus nerve stimulation, and deep brain
stimulation. The vagus nerve is the 10th cranial nerve, and is a
direct extension of the brain. FIG. 1A, shows a diagram of the
brain and spinal cord 24, with its relationship to the vagus nerve
54 and the nucleus tractus solitarius 14. FIG. 1B shows the
relationship of the vagus nerve 54 with the other cranial
nerves.
[0006] Vagus nerve stimulation is a means of directly affecting
central function and is less invasive than deep brain stimulation
(DBS). As shown in FIG. 1C, cranial nerves have both afferent
pathway 19 (inward conducting nerve fibers which convey impulses
toward the brain) and efferent pathway 21 (outward conducting nerve
fibers which convey impulses to an effector). The vagus nerve is
composed of 80% afferent sensory fibers carrying information to the
brain from the head, neck, thorax, and abdomen. The sensory
afferent cell bodies of the vagus reside in the nodose ganglion and
relay information to the nucleus tractus solitarius (NTS) 14.
[0007] As shown schematically in FIGS. 1A and 1D, the nucleus of
the solitary tract relays this incoming sensory information to the
rest of the brain through three main pathways; (1) an autonomic
feedback loop, (2) direct projection to the reticular formation in
the medulla, and (3) ascending projections to the forebrain largely
through the parabrachial nucleus (PBN) 20 and the locus ceruleus
(LC) 22. The PBN 20 sits adjacent to the neucleus LC 22 (FIG. 1A).
The PBN/LC 20/22 sends direct connections to every level of the
forebrain, including the hypothalamus 26, and several thalamic 25
regions that control the insula and orbitofrontal 28 and prefontal
cortices. Perhaps important for mood regulation, the PBN/LC 20/22
has direct connections to the amygdala 29 and the bed nucleus of
the stria terminalis--structures that are implicated in emotion
recognition and mood regulation.
[0008] In sum, incoming sensory (afferent) connections ofthe vagus
nerve 54 provide direct projections to many of the brain regions
implicated in nueropsychiatric disorders. These connections reveal
how vagus nerve stimulation is a portal to the brainstem and
connected regions. These circuits likely account for the
neuropsychiatric effects of vagus nerve stimulation.
[0009] Increased activity of the vagus nerve is also associated
with the release of more serotonin in the brain. Much of the
pharmacologic therapy for treatment of migraines is aimed at
increasing the levels of serotonin in the brain. Therefore,
non-pharmacologic therapy of electrically stimulating the vagus
nerve would have benefits for adjunct treatment of migraines and
other ailments, such as obsessive compulsive disorders, that would
benefit from increasing the level of serotonin in the brain.
[0010] The vagus nerve provides an easily accessible, peripheral
route to modulate central nervous system (CNS) function. Other
cranial nerves can be used for the same purpose, but the vagus
nerve is preferred because of its easy accessibility. In the human
body there are two vagal nerves (VN), the right VN and the left VN.
Each vagus nerve is encased in the carotid sheath along with the
carotid artery and jugular vein. The innervation of the right and
left vagal nerves is different. The innervation of the right vagus
nerve is such that stimulating it results in profound bradycardia
(slowing of the heart rate). The left vagal nerve has some
innervation to the heart, but mostly innervates the visceral organs
such as the gastrointestinal tract. It is known that stimulation of
the left vagal nerve does not cause any significant deleterious
side effects.
[0011] Complex partial seizure is a common form of epilepsy, and
some 30-40% of patients afflicted with this disorder are not well
controlled by medications. Some patients have epileptogenic foci
that may be identified and resected; however, many patients remain
who have medically resistant seizures not amenable to resective
surgery. Stimulation of the vagus nerve has been shown to reduce or
abort seizures in experimental models. Early clinical trials have
suggested that vagus nerve stimulation has beneficial effects for
complex partial seizures and generalized epilepsy in humans. In
addition, intermittent vagal stimulation has been relatively safe
and well tolerated during the follow-up period available in these
groups of patients. The minimal side effects of tingling sensations
and brief voice abnormalities have not been distressing.
[0012] Most nerves in the human body are composed of thousands of
fibers, of different sizes designated by groups A, B and C, which
carry signals to and from the brain. The vagus nerve, for example,
may have approximately 100,000 fibers ofthe three different types,
each carrying signals. Each axon (fiber) of that nerve conducts
only in one direction, in normal circumstances. The A and B fibers
are myelinated (i.e., have a myelin sheath, constituting a
substance largely composed of fat), whereas the C fibers are
unmyelinated.
[0013] A commonly used nomenclature for peripheral nerve fibers,
using Roman and Greek letters, is given in the table below,
1 External Diameter Conduction Velocity Group (.mu.m) (m/sec)
Myelinated Fibers A.alpha. or IA 12-20 70-120 A.beta.: IB 10-15
60-80 II 5-15 30-80 A.gamma. 3-8 15-40 A.delta. or III 3-8 10-30 B
1-3 5-15 Unmyelinted fibers C or IV 0.2-1.5 0.5-2.5
[0014] The diameters of group A and group B fibers include the
thicknesses of the myelin sheaths. Group A is further subdivided
into alpha, beta, gamma, and delta fibers in decreasing order of
size. There is some overlapping of the diameters of the A, B, and C
groups because physiological properties, especially the form ofthe
action potential, are taken into consideration when defining the
groups. The smallest fibers (group C) are unmyelinated and have the
slowest conduction rate, whereas the myelinted fibers of group B
and group A exhibit rates of conduction that progressively increase
with diameter. Group B fibers are not present in the nerves of the
limbs; they occur in white rami and some cranial nerves.
[0015] Compared to unmyelinated fibers, myelinated fibers are
typically larger, conduct faster, have very low stimulation
thresholds, and exhibit a particular strength-duration curve or
respond to a specific pulse width versus amplitude for stimulation.
The A and B fibers can be stimulated with relatively narrow pulse
widths, from 50 to 200 microseconds (.mu.s), for example. The A
fiber conducts slightly faster than the B fiber and has a slightly
lower threshold. The C fibers are very small, conduct electrical
signals very slowly, and have high stimulation thresholds typically
requiring a wider pulse width (300-1,000 .mu.s) and a higher
amplitude for activation. Selective stimulation of only A and B
fibers is readily accomplished. The requirement of a larger and
wider pulse to stimulate the C fibers, however, makes selective
stimulation of only C fibers, to the exclusion of the A and B
fibers, virtually unachievable inasmuch as the large signal will
tend to activate the A and B fibers to some extent as well.
[0016] The vagus nerve is composed of somatic and visceral
afferents (i.e., inward conducting nerve fibers which convey
impulses toward the brain) and efferents (i.e., outward conducting
nerve fibers which convey impulses to an effector). Usually, nerve
stimulation activates signals in both directions
(bi-directionally). It is possible, however, through the use of
special electrodes and waveforms, to selectively stimulate a nerve
in one direction only (unidirectionally). The vast majority of
vagal nerve fibers are C fibers, and a majority are visceral
afferents having cell bodies lying in masses or ganglia in the
skull. The central projections terminate largely in the nucleus of
the solitary tract which sends fibers to various regions of the
brain (e.g., the hypothalamus, thalamus, and amygdala).
[0017] The basic premise of vagal nerve stimulation for control of
seizures is that vagal visceral afferents have a diffuse central
nervous system (CNS) projection, and activation of these pathways
has a widespread effect on neuronal excitability.
[0018] The cervical component of the vagus nerve (10th cranial
nerve) transmits primarily sensory information that is important in
the regulation of autonomic activity by the parasympathetic system.
General visceral afferents constitute approximately 80% of the
fibers of the nerve, and thus it is not surprising that vagal nerve
stimulation (VNS) can profoundly affect CNS activity. With cell
bodies in the nodose ganglion, these afferents originate from
receptors in the heart, aorta, lungs, and gastrointestinal system
and project primarily to the nucleus of the solitary tract which
extends throughout the length of the medulla oblongata. A small
number of fibers pass directly to the spinal trigeminal nucleus and
the reticular formation.
[0019] As might be predicted from the electrophysiologic studies,
the nucleus ofthe solitary tract has widespread projection to
cerebral cortex, basal forebrain, thalamus, hypothalamus, amygdala,
hippocampus, dorsal raphe, and cerebellum as shown in FIG. 1D (from
Epilepsia, vol. 3, suppl.2:1990, page S2).
[0020] Even though observations on the profound effect of
electrical stimulation of the vagus nerve on central nervous system
(CNS) activity, extends back to the 1930's, in the mid-1980s it was
suggested that electrical stimulation of the vagus nerve might be
effective in preventing seizures. Early studies on the effects of
vagal nerve stimulation (VNS) on brain function focused on acute
changes in the cortical electroencephalogram (EEG) of anesthetized
animals. Investigators found that VNS could temporarily synchronize
or desynchronize the electroencephalogram, depending on the level
of anesthesia and the frequency or intensity of the vagal stimulus.
These observations had suggested that VNS exerted its
anticonvulsant effect by desynchronizing cortical electrical
activity. However, subsequent clinical investigations have not
shown VNS-induced changes in the background EEGs of humans. A
study, which used awake and freely moving animals, also showed no
VNS-induced changes in background EEG activity. Taken together, the
findings from animal study and recent human studies indicate that
acute desynchronization of EEG activity is not a prominent feature
of VNS when it is administered during physiologic wakefulness and
sleep, and does not explain the anticonvulsant effect of VNS.
[0021] The mechanism by which vagal nerve stimulation (VNS) exerts
its influence on seizures is not entirely understood. An early
hypotheses had suggested that VNS utilizes the relatively specific
projection from the nucleus of the solitary track to limbic
structures to inhibit partial seizures, particularly those
involving cortex, which regulates autonomic activity or visceral
sensations such as in temporal lobe epilepsy. Afferent VNS at the
onset of a partial seizure could abort the seizure in the same way
somatosensory stimuli can abort a seizure from the rolandic cortex;
however, chronic intermittent stimulation may also produce an
alteration in limbic circuitry that outlasts the stimulus and
decreases epileptogenesis or limits seizure spread. Support for
this hypothesis comes from studies of fos immunoreactivity in the
brain of rats in response to VNS. Fos is a nuclear protein
resulting from expression of early immediate genes in highly active
neurons. VNS causes a specific fos immunolabeling in amygdala and
limbic neocortex, suggesting that the antiepileptic effect may be
mediated in these areas. Such activation of genetic mechanisms
could account for the apparent sustained antiepileptic effect of
intermittent stimulation.
[0022] Another possible mechanism that is being explored to explain
an antiseizure effect of VNS is activation of the brainstem
noradrenergic nuclei, lucus ceruleus and A5, which also show fos
immunolabeling. Noradrenergic mechanisms are well known to
influence seizure activity in genetic epilepsy-prone rats, and the
anticonvulsant effects of VNS against maximal electroshock seizures
can be blocked inactivation of the loc. ceruleus. Woodbury and
Woodbury (1990) suggested that VS acts through increasing release
of glycine or GABA since seizures induced by both PTZ and
strychnine can be blocked by VNS. Other neruotransmitter systems
may also be implicated since VNS increases cerebrospinal fluid
homovanilic acid and 5-hydroxyindoleacetate, suggesting modulation
of dopaminergic and serotonergic systems. Finally, a nonspecific
alteration of activity in the brainstem reticular system with
subsequent arousal must be considered.
[0023] VNS appears to have similar efficacy in both partial and
generalized seizures in experimental models and in human epilepsy
consistent with a nonspecific effect. Furthermore, the same
inhibition of interictal corticalspike activity as seen with VNS
occurs in animals during electrical stimulation of the midbrain
reticular formation or with thermal stimulation of somatosensory
nerves in the rat tail. Reduction of experimental generalized spike
wave by arousal has also been documented. Similarly, nonspecific
afferent stimulation has been well demonstrated in humans to
suppress focal spikes, generalized spike waves, and seizures.
[0024] VNS may inhibit seizures directly at the level of cerebral
cortical neuronal irritability, or at the level of diffuse
ascending subcortical projection systems, or both. Thus, VNS is
also well suited for the treatment of medication-resistant
symptomatic generalized epilepsy (SGE), in which,
characteristically both focal and generalized features are found on
interictal EEGs and also in clinical seizure types.
[0025] One type of prior non-pharmacological therapy for
depression, migraines, neuropsychiatric disorders, and epilepsy is
generally directed to the use of an implantable lead and an
implantable pulse generator technology or "cardiac pacemaker-like"
technology. In these applications, the pulse generator is
programmed via a personnel computer (PC) based programmer that is
modified and adapted with a programmer wand which is placed on top
of the skin over the pulse generator implant site. Each parameter
is programmed independent of the other parameters. Therefore,
millions of different combinations of programs are possible. In the
instant patent, preferably approximately nine programs are
pre-selected.
[0026] U.S. Pat. No. 3,796,221 (Hagfors) is directed to controlling
the amplitude, duration and frequency of electrical stimulation
applied from an externally located transmitter to an implanted
receiver by inductively coupling. Electrical circuitry is
schematically illustrated for compensating for the variability in
the amplitude of the electrical signal available to the receiver
because of the shifting of the relative positions of the
transmitter-receiver pair. By highlighting the difficulty of
delivering consistent pulses, this patent points away from
applications such as the current application, where consistent
therapy needs to be continuously sustained over a prolonged period
of time (24 hours a day for years). The methodology disclosed is
focused on circuitry within the receiver, which would not be
sufficient when the transmitting coil and receiving coil assume
significantly different orientation, which is likely in the current
application. The present invention discloses a novel approach for
this problem.
[0027] U.S. Pat. No. 5,304,206 (Baker, Jr. et al) is directed to
activation techniques for implanted medical stimulators. The system
uses either a magnet to activate the reed switch in the device, or
tapping which acts through the piezoelectric sensor mounted on the
case of the implanted device, or a combination of magnet and
tapping sequence.
[0028] U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 (Zabara)
generally disclose animal research and experimentation related to
epilepsy and the like and are directed to stimulating the vagus
nerve by using pacemaker technology, such as an implantable pulse
generator. These patents are based on several key hypotheses, some
of which have since been shown to be incorrect. The pacemaker
technology concept consists of a stimulating lead connected to a
pulse generator (containing the circuitry and DC power source)
implanted subcutaneously or submuscularly, somewhere in the
pectoral or axillary region, with an external personal computer
(PC) based programmer. Once the pulse generator is programmed for
the patient, the fully functional circuitry and power source are
fully implanted within the patient's body. In such a system, when
the battery is depleted, a surgical procedure is required to
disconnect and replace the entire pulse generator (circuitry and
power source). These patents neither anticipate practical problems
of an inductively coupled system for adjunct therapy of epilepsy,
nor suggest solutions to the same for an inductively coupled system
for adjunct therapy of partial complex or generalized epilepsy.
FIG. 4 in all three above Zabara patents show the stimulation
electrode around the right vagus nerve. It is well known that
stimulation of right vagus can lead to profound bradycardia
(slowing of the heart rate), an unwanted complication.
[0029] U.S. Pat. No. 5,299,569 (Wernicke et al.) is directed to the
use of implantable pulse generator technology for treating and
controlling neuropsychiatric disorders including schizophrenia,
depression, and borderline personality disorder.
[0030] U.S. Pat. No. 5,752,979 (Benabid) is directed to a method of
controlling epilepsy with stimulation directly into the brain,
utilizing an implantable generator. More specifically, Benabid
discloses electrically stimulating the external segment of the
globus palliaus nucleus of the brain causing increased excitation,
thereby increasing inhibition of neural activity in the subthalamic
nucleus and reducing excitatory input to the substantia nigra
leading to a reduction in the occurrence of seizures.
[0031] U.S. Pat. No. 5,540,734 (Zabara) is directed to stimulation
of one or both of a patient's trigeminal and glossopharyngeal nerve
utilizing an implanted pulse generator.
[0032] U.S. Pat. No. 5,031,618 (Mullett) discloses a position
sensor for chronically implanted neuro stimulator for stimulating
the spinal cord. The position sensor, located in a chronically
implanted programmable spinal cord stimulator, modulates the
stimulation signals depending on whether the patient is erect or
supine.
[0033] U.S. Pat. No. 4,573,481 (Bullara) is directed to an
implantable helical electrode assembly configured to fit around a
nerve. The individual flexible ribbon electrodes are each partially
embedded in a portion of the peripheral surface of a helically
formed dielectric support matrix.
[0034] U.S. Pat. No. 3,760,812 (Timm et al.) discloses nerve
stimulation electrodes that include a pair of parallel spaced apart
helically wound conductors maintained in this configuration.
[0035] U.S. Pat. No. 4,979,511 (Terry) discloses a flexible,
helical electrode structure with an improved connector for
attaching the lead wires to the nerve bundle to minimize
damage.
[0036] An implantable pulse generator and lead with a PC based
external programmer is advantageous for cardiac pacing applications
for several reasons, including:
[0037] 1) A cardiac pacemaker must sense the intrinsic activity of
the heart, because cardiac pacemakers deliver electrical output
primarily during the brief periods when patients either have pauses
in their intrinsic cardiac activity or during those periods of time
when the heart rate drops (bradycardia) below a certain
pre-programmed level. Therefore, for most of the time, in majority
of patients, the cardiac pacemaker "sits" quietly monitoring the
patient's intrinsic cardiac activity.
[0038] 2) The stimulation frequency for cardiac pacing is typically
close to 1 Hz, as opposed to approximately 20 Hz or higher,
typically used in nerve stimulation applications.
[0039] 3) Patients who require cardiac pacemaker support are
typically in their 60's, 70's or 80's years of age.
[0040] The combined effect of these three factors is that the
battery in a pacemaker can have a life of 10-15 years. Most
patients in whom a pacemaker is indicated are implanted only once,
with perhaps one surgical pulse generator replacement.
[0041] In contrast, patients with partial complex epilepsy or
generalized epilepsy in whom electrical stimulation is beneficial
are much younger as a group, typically ranging from 12 to 45 years
in age. Also, stimulation frequency is typically 20 Hz or higher,
and the total stimulation time per day is much longer than for
cardiac pacemakers. As a result, battery drain is typically much
higher for nerve stimulation applications than for cardiac
pacemakers.
[0042] The net result of these factors is that the battery will not
last nearly as long as in cardiac pacemakers. Because the indicated
patient population is also much younger, the expense and impact of
surgical generator replacement will become significant, and detract
from the appeal of this therapy. In fact, it has been reported in
the medical literature that the battery life can be as short as one
and half years for implantable nerve stimulator. (R. S. McLachlan,
p. 233).
[0043] There are several other advantages of the present
inductively coupled system.
[0044] 5) The hardware components implanted in the body are much
less. This is advantageous for the patient in terms of patient
comfort, and it decreases the chances of the hardware getting
infected in the body. Typically, when an implantable system gets
infected in the body, it cannot be easily treated with antibiotics
and eventually the whole implanted system has to be explanted.
[0045] 2) Because the power source is external, the physician can
use stimulation sequences that are more effective and more
demanding on the power supply, such as longer "on" time.
[0046] 3) With the controlling circuitry being external, the
physician and the patient may easily select from a number of
predetermined programs, override a program, manually operate the
device or even modify the predetermined programs.
[0047] 4) The external inductively-coupled nerve stimulation (EINS)
system is quicker and easier to implant.
[0048] 5) The external pulse generator does not need to be
monitored for "End-of-Life" (EOL) like the implantable system, thus
resulting in cost saving and convenience.
[0049] 6) The EINS system can be manufactured at a significantly
lower cost of an implantable pulse generator and programmer system,
providing the patient and medical establishment with cost effective
therapies.
[0050] 7) The EINS system makes it more convenient for the patient
or caretaker to turn the device on during an "Aura" that sometimes
precedes the seizures. Also, because programming the device is much
simpler, the patient or caretaker may reprogram the device at night
time by simply pressing one or two buttons to improve patient
comfort.
[0051] 8) Occasionally, an individual responds adversely to an
implanted medical device and the implanted hardware must be
removed. In such a case, a patient having the EINS systems has less
implanted hardware to be removed and the cost ofthe pulse generator
does not become a factor.
[0052] In the conventional manner of implanting, a cervical
incision is made above the clavicle, and another infraclavicular
incision is made in the deltapectoral region for the implantable
stimulus generator pocket. To tunnel the lead to the cervical
incision, a shunt-passing tool is passed from the cervical incision
to the generator pocket, where the electrode is attached to the
shunt-passing tool and the electrode is then "pulled" back to the
cervical incision for attachment to the nerve. This standard
technique has the disadvantage that it is time consuming and it
tends to create an open space in the subcutaneous tissue. Post
surgically the body will fill up this space with serous fluid,
which can be undesirable.
[0053] To make the subcutaneous tunneling simpler and to avoid
possible complication, one form of the implantable lead body is
designed with a hollow lumen to aid in implanting. In this
embodiment, a special tunneling tool slides into a hollow lumen.
After the cervical and infraclavicular incisions are made, the
tunneling tool and lead are simply "pushed" to the cervical
incision and the tunneling tool is pulled out. Since the tunneling
tool is inside the lead, no extra subcutaneous space is created
around the lead, as the lead is pushed. This promotes better
healing post-surgically.
[0054] The apparatus and methods disclosed herein also may be
appropriate for the treatment of other conditions, as disclosed in
co-pending applications filed on Oct. 26, 1998, entitled APPARATUS
AND METHOD FOR ADJUNCT (ADD-ON) THERAPY OF DEMENTIA AND ALZHEIMER'S
DISEASE UTILIZING AN IMPLANTABLE LEAD AND AN EXTERNAL STIMULATOR
and APPARATUS AND METHOD FOR ADJUNCT (ADD-ON) THERAPY FOR PAIN
SYNDROMES UTILIZING AN IMPLANTABLE LEAD AND AN EXTERNAL STIMULATOR,
the disclosures of which are incorporated herein by reference.
SUMMARY OF THE INVENTION
[0055] The apparatus and methodology of this invention generally
relates to the adjunct (add-on) treatment of depression, migraine,
neuropsychiatric disorders, partial complex epilepsy, generalized
epilepsy, and involuntary movement disorders such as in Parkinson's
disease. More particularly, the apparatus and methodology in
accordance with the invention provides a more adaptable and less
intrusive treatment for such conditions. In one embodiment of the
invention, the apparatus consists of an easy to implant
lead-receiver, an external stimulator containing controlling
circuitry and power supply, and an electrode containing a coil for
inductively coupling the external pulse generator to the implanted
lead-receiver. A separately provided tunneling tool may be used as
an aid for implanting the lead-receiver.
[0056] In another embodiment of the invention, the external
stimulator has two modes of operation: one with several
pre-determined programs that may be selectively locked-out by the
manufacturer or physician and another with a manual override.
[0057] In another embodiment of the invention, the implantable
lead-receiver is inductively coupled to the external stimulator via
a patch electrode containing coil. One feature of this invention is
to consistently deliver energy from an external coil to an internal
coil in an ambulatory patient. A design of the external patch
contains means for compensating for relative movement of the axis
of the external and internal coils by deflecting the energy via
targets located in the external patch.
[0058] Another feature of this invention is to provide an apparatus
to aid in implanting the lead-receiver, including a hollow lumen in
the lead body to receive a tunneling tool.
BRIEF DESCRIPTION OF THE DRAWINGS
[0059] For the purpose of illustrating the invention, there are
shown in accompanying drawing forms which are presently preferred,
it being understood that the invention is not intended to be
limited to the precise arrangement and instrumentalities shown.
[0060] FIG. 1A is a diagram of the lateral view of brain and spinal
cord, with its relationship to the vagus nerve.
[0061] FIG. 1B is a diagram of the base of brain showing the
relationship of vagus nerve to the other cranial nerves.
[0062] FIG. 1C is a diagram of brain showing afferent and efferent
pathways.
[0063] FIG. 1D is diagram of vagal nerve afferents through the
nucleus of the solitary tract.
[0064] FIG. 2A is a diagram showing a patient wearing an external
inductively-coupled nerve stimulator (EINS) system.
[0065] FIG. 2B is a diagram showing two coils along their axis, in
a configuration such that the mutual inductance would be
maximum.
[0066] FIG. 3A is a diagram showing the effects of two coils with
axes at right angles.
[0067] FIG. 3B is a diagram showing the effects of two coils with
axes at right angles, with a ferrite target included.
[0068] FIG. 4A is a side view of an external patch showing the
transmitting coil and targets.
[0069] FIG. 4B is top view of an external patch showing the
transmitting coil and targets.
[0070] FIG. 5 is a diagram showing the implanted lead-receiver and
the transmitting coil.
[0071] FIG. 6 is a diagram showing the implanted lead-receiver
underneath the skin, also showing the relative position of the
external coil
[0072] FIG. 7 is a diagram showing the proximal end of the
lead-receiver.
[0073] FIG. 8 is a diagram of circuitry within the proximal portion
of the implanted lead-receiver.
[0074] FIG. 9 is a diagram of the body of the lead-receiver.
[0075] FIG. 10 is a diagram of a tunneling tool for aiding in the
implantation of the lead-receiver.
[0076] FIG. 11 is diagram of another tunneling tool for aiding in
the implantation of the lead-receiver.
[0077] FIG. 12 is a diagram of an external patch and external pulse
generator.
[0078] FIG. 13 is a prospective view of an external pulse
generator.
[0079] FIG. 14 is a flow diagram of the external pulse
generator.
[0080] FIG. 15 is a diagram of a hydrogel electrode.
[0081] FIG. 16 is a diagram of a lead-receiver utilizing a fiber
electrode at the distal end.
[0082] FIG. 17 is a diagram of a fiber electrode wrapped around
Dacron polyester.
[0083] FIG. 18 is a diagram of a lead-receiver with a spiral
electrode.
[0084] FIG. 19 is a diagram of an electrode embedded in tissue.
[0085] FIG. 20 is a diagram of an electrode containing steroid drug
inside.
[0086] FIG. 21 is a diagram of an electrode containing steroid drug
in a silicone collar at the base of electrode.
[0087] FIG. 22 is a diagram of an electrode with steroid drug
coated on the surface of the electrode.
[0088] FIG. 23 is a diagram of cross sections of implantable
lead-receiver body showing different lumens.
[0089] The following are reference numbers in the drawings:
[0090] 1. olfactory nerve
[0091] 2. optic nerve
[0092] 3. oculomotor nerve
[0093] 4. trochlear nerve
[0094] 5. trigeminal nerve
[0095] 6. abducens nerve
[0096] 7. facial nerve
[0097] 8. acoustic nerve
[0098] 9. glossopharyngeal nerve
[0099] 11. accessory nerve
[0100] 12. hypoglosal nerve
[0101] 14. nucleus tractus solitaris
[0102] 15. parabrachial nucleus (PB)
[0103] 17. nucleus locus coeruleus
[0104] 18. pons
[0105] 19. afferent pathway
[0106] 20. parabrachial nucleus (PB)
[0107] 21. efferent pathway
[0108] 22. nucleus locus coeruleus (LC)
[0109] 24. spinal cord
[0110] 25. thalamus
[0111] 26. hypothalamus
[0112] 27. cerebellum
[0113] 28. orbito-frontal cortex
[0114] 29. amygdala
[0115] 31. cingulate gyrus
[0116] 32. patient
[0117] 34. implantable lead-receiver
[0118] 35. muscle
[0119] 36. coil-end of the external patch
[0120] 37. skin receptors
[0121] 38. wire of external patch
[0122] 39. primary somatic sensory cortex
[0123] 40. terminal end of the external patch
[0124] 41. primary motor cortex
[0125] 42. external stimulator
[0126] 43. external patch electrode
[0127] 44. belt of external stimulator
[0128] 45. ferrite target
[0129] 46. outer (transmitting primary) coil
[0130] 48. inner (receiving secondary) coil
[0131] 49. proximal end of lead-receiver
[0132] 50. adhesive portion of external patch electrode
[0133] 51. driving voltage of transmitter coil
[0134] 52. distal ball electrode
[0135] 53. zero voltage of receiver coil
[0136] 54. vagus nerve
[0137] 55. signal voltage across receiver coil
[0138] 56. carotid artery
[0139] 57. ferrite targets in external patch
[0140] 58. jugular vein
[0141] 59. body of lead-receiver
[0142] 60. working lumen of lead-receiver body
[0143] 62. hollow lumen of lead-receiver body
[0144] 64. schematic of lead-receiver circuitry
[0145] 65. cable connecting cathode and anode
[0146] 68. tuning capacitor in electrical schematic and in
hybrid
[0147] 69. selector
[0148] 70. zenor diode
[0149] 71. pre-determined programs in block diagram
[0150] 72. capacitor used in filtering
[0151] 73. patient override in block diagram
[0152] 74. resister used in filtering
[0153] 75. programmable control logic in block diagram
[0154] 76. capacitor to block DC component to distal electrode
[0155] 77. programming station in block diagram
[0156] 78. case of lead-receiver
[0157] 79. pulse frequency oscillator in block diagram
[0158] 80. distal electrode in schematic of lead-receiver
[0159] 81. battery (DC) in block diagram
[0160] 82. working lumen in a cross section
[0161] 83. amplifier in block diagram
[0162] 84. hollow lumen in a cross-section
[0163] 85. indicator in block diagram
[0164] 86. small handle of alternate tunneling tool
[0165] 87. low pass filter in block diagram
[0166] 88. big handle of the tunneling tool
[0167] 89. antenna in block diagram
[0168] 90. skin
[0169] 91. metal rod portion of the tunneling tool with big
handle
[0170] 92. punched holes in body of the lead receiver to promote
fibrosis
[0171] 93. metal rod portion of the alternative tunneling tool with
small handle
[0172] 94. alternative tunneling tool
[0173] 95. tunneling tool with big handle
[0174] 96. silicone covering proximal end
[0175] 98. hybrid assembly
[0176] 100. hydrogel
[0177] 102. platinum electrodes around hydrogel
[0178] 104. fiber electrode
[0179] 105. spiral electrode
[0180] 106. Dacron polyester or Polyimide
[0181] 108. platinum fiber
[0182] 110. exposed electrode portion of spiral electrode
[0183] 112. polyurethane or silicone insulation in spiral
electrode
[0184] 114. "virtual" electrode
[0185] 118. excitable tissue
[0186] 120. non-excitable tissue
[0187] 121. steroid plug inside an electrode
[0188] 122. body of electrode
[0189] 124. electrode tip
[0190] 126. silicone collar containing steroid
[0191] 128. steroid membrane coating
[0192] 130. anchoring sleeve
[0193] 132. A-F lumens
[0194] 134. A-C larger hollow lumen for lead introduction
DESCRIPTION OF THE INVENTION
[0195] FIG. 2A shows a schematic diagram of a patient 32 with an
implantable lead-receiver 34 and an external stimulator 42, clipped
on to a belt 44 in this case. The external stimulator 42, may
alternatively be placed in a pocket or other carrying device. An
external patch electrode 36 provides the coupling between the
external stimulator 42 and the implantable lead-receiver 34.
[0196] The external stimulator 42 is inductively coupled to the
lead-receiver 34. As shown in FIG. 2B, when two coils are arranged
with their axes on the same line, current sent through coil 46
creates a magnetic field that cuts coil 48 which is placed
subcutaneously. Consequently, a voltage will be induced in coil 48
whenever the field strength of coil 46 is changing. This induced
voltage is similar to the voltage of self-induction but since it
appears in the second coil because of current flowing in the first,
it is a mutual effect and results from the mutual inductance
between the two coils. Since these two coils are coupled, the
degree of coupling depends upon the physical spacing between the
coils and how they are placed with respect to each other. Maximum
coupling exists when they have a common axis and are as close
together as possible. The coupling is least when the coils are far
apart or are placed so their axes are at right angles. As shown in
FIG. 5, the coil 48 inside the lead-receiver 34 is approximately
along the same axis as the coil 46 in the external skin patch
36.
[0197] As shown in FIG. 3A, when the axis of transmitting coil 46
is at right angles to the axis of the receiving coil 48, a given
driving voltage 51 results in zero voltage 53 across the receiving
coil 48. But, as shown in FIG. 3B by adding ferrite target 45, a
given driving voltage 51 through the transmitting coil 46 results
in a signal voltage 55 across the receiver coil 48. The efficiency
is improved by having multiple ferrite targets. An alternate
external patch shown in FIGS. 4A and 4B contains multiple targets
57. FIG. 4A shows a side view of the patch, and FIG. 4B shows a top
view of the patch. Having multiple targets 57 in the external patch
43 compensates for non-alignment of the axis between the
transmitting coil 46 and receiving coil 48. Since relative
rotations between the axis of external transmitting coil 46 and
internal receiving coil 48 which may occur during breathing, muscle
contractions, or other artifacts are compensated for, results in
continuous prolonged stimulation.
[0198] Referring to FIG. 6, the implantable lead-receiver 34 looks
somewhat like a golf "tee" and is the only implantable portion of
the system. The "head" or proximal end 49 contains the coil 48 and
electronic circuitry (hybrid) 98 which is hermetically sealed, and
covered with silicone. It also has four anchoring sleeves 130 for
tying it to subcutaneous tissue. FIG. 7 is a close-up view of the
proximal portion 49 of the lead-receiver 34 containing the
circuitry (hybrid) 98. This circuitry is shown schematically in
FIG. 8. A coil 48 (preferably approximately 15 turns) is directly
connected to the case 78. The external stimulator 42 and external
patch 36 transmit the pulsed alternating magnetic field to receiver
64 whereat the stimulus pulses are detected by coil 48 and
transmitted to the stimulus site (vagus nerve 54). When exposed to
the magnetic field of transmitter 36, coil 48 converts the changing
magnetic field into corresponding voltages with alternating
polarity between the coil ends. A capacitor 68 is used to tune coil
48 to the high-frequency of the transmitter 36. The capacitor 68
increases the sensitivity and the selectivity of the receiver 64,
which is made sensitive to frequencies near the resonant frequency
of the tuned circuit and less sensitive to frequencies away from
the resonant frequency. A zenor diode 70 in the current path is
used for regulation and to allow the current that is produced by
the alternating voltage of the coil to pass in one direction only.
A capacitor 72 and resistor 74 filter-out the high-frequency
component of the receiver signal and thereby leave a current of the
same duration as the burst ofthe high-frequency signal. Capacitor
76 blocks any net direct current to the stimulating electrode tip
80, which is made of platinum/iridium (90%-10%). Alternatively, the
stimulating electrode can be made of platinum or platinum/iridium
in ratio's such as 80% Platinum and 20% Iridium.
[0199] The circuit components are soldered in a conventional manner
to an upper conductive layer on a printed circuit board. The case
78 is connected to the coil 48 and is made of titanium. The case 78
also serves as the return electrode (anode). The surface area of
the anode exposed to the tissue is much greater than the surface
area of the stimulating electrode 80 (cathode). Therefore, the
current density at the anode is too low to unduly stimulate tissue
that is in contact with the anode. Alternatively, a bipolar mode of
stimulation can also be used. In the bipolar mode of stimulation
the cathode and anode are in close proximity to each other.
[0200] The body of the lead-receiver 34 is made of medical grade
silicone (available from NuSil Technology, Applied silicone or Dow
Chemical). Alternatively, the lead body 59 may be made of medical
grade polyurethane (PU) of 55 D or higher durometer, such as
available from Dow Chemical. Polyurethane is a stiffer material
than silicone. Even though silicone is a softer material, which is
favorable, it is also a weaker material than PU. Therefore,
silicone coated with Teflon (PTFE) is preferred for this
application. PTFE coating is available from Alpa Flex,
Indianapolis, Ind.
[0201] FIG. 9 shows a close-up of the lead body 59 showing two
lumens 82, 84. Lumen 82 is the "working" lumen, containing the
cable conductor 65 which connects to the stimulating electrode 52.
The other lumen 84 is preferably slightly larger and is for
introducing and placing the lead in the body. Alternatively, lumen
84 may have small holes 92 punched along the length of the lead.
These small holes 92 will promote fibrotic tissue in-growth to
stabilize the lead position and inhibit the lead from
migrating.
[0202] Silicone in general is not a very slippery material, having
a high coefficient of friction. Therefore, a lubricious coating is
added to the body of the lead. Such lubricous coating is available
from Coating Technologies Inc. (Scotch Plains, N.J.). Since
infection still remains a problem in a small percentage of
patients, the lead may be coated with antimicrobial coating such as
Silver Sulfer Dizene available from STS Biopolymers, Henrietta,
N.Y. The lead may also be coated with anti-inflammatory
coating.
[0203] The distal ball electrode 52, shown in FIG. 6 is made of
platinum/iridium (90% platinum and 10% iridium). Platinum/iridium
electrodes have a long history in cardiac pacing applications.
During the distal assembly procedure, the silicone lead body 59 is
first cleaned with alcohol. The conductor cable 65 (available from
Lake Region, Minn.) is passed through the "working" lumen 82. The
cable is inserted into the distal electrode 52, and part of the
body of electrode is crimped to the cable 65 with a crimper.
Alternatively, the cable conductor 65 may be arc welded or laser
welded to the distal electrode 52. The distal end of the insulation
is then slided over the crimp such that only the tissue stimulating
portion of the distal electrode 52 is exposed. Following this, a
small needle is attached to a syringe filled with medical glue. The
needle is inserted into the distal end of insulation, and small
amounts of medical glue are injected between the distal end of the
insulation and distal electrode 52. The assembly is then cured in
an oven.
[0204] As shown in FIGS. 9 and 10, a tunneling tool 95 is inserted
into the empty lumen 84 to push the distal end (containing the
cathode electrode 52) towards the vagus nerve 54. The tunneling
tool 95, is comprised of a metal rod 91 and a handle 88. As shown
in FIG. 11, another tunneling tool 94 with a smaller handle 86 may
also be used. Both are available from Popper and Sons, New Hyde
Park, N.Y. or Needle Technology. Alternatively, the tunneling tool
may be made of strong plastic or other suitable material.
[0205] An external patch electrode 43 for inductive coupling is
shown in FIG. 12. One end of the patch electrode contains the coil
46, and the other end has an adapter 40 to fit into the external
stimulator 42. The external patch electrode 43, is a modification
of the patch electrode available from TruMed Technologies,
Burnsville, Minn.
[0206] FIG. 13 shows a front view of an external stimulator 42,
which preferably is slightly larger than a conventional pager. The
external stimulator 42 contains the circuitry and rechargeable or
replaceable power source. The external stimulator 42 has two modes
of operation. In the first mode of operation there are several
pre-determined programs, preferably up to nine, which differ in
stimulus intensity, pulse width, frequency of stimulation, and
on-off timing sequence, e.g. "on" for 10 seconds and "off" for 50
seconds in repeating cycles. For patient safety, any number of
these programs may be locked-out by the manufacturer or physician.
In the second mode, the patient, or caretaker may activate the
stimulation on at any time. This mode is useful for epileptic
patients that have the characteristic "aura", which are sensory
signs immediately preceding the convulsion that many epileptics
have. When the device is turned on, a green light emitting diode
(LED) indicates that the device is emitting electrical
stimulation.
[0207] Pre-determined programs are arranged in such a way that the
aggressiveness of the therapy increases from program #1 to Program
#9. Thus the first three programs provide the least aggressive
therapy, and the last three programs provide the most aggressive
therapy. The following are examples of least aggressive
therapy.
[0208] Program #1:
[0209] 1.0 mA current output, 0.2 msec pulse width, 15 Hz
frequency, 15 sec ON time--1.0 min OFF time, in repeating
cycles.
[0210] Program #2:
[0211] 1.5 mA current output, 0.3 msec pulse width, 20 Hz
frequency, 20 sec ON time--2.0 min OFF time, in repeating
cycles.
[0212] The following are examples of intermediate level of
therapy.
[0213] Program #5:
[0214] 2.0 mA current output, 0.2 msec pulse width, 25 Hz
frequency, 20 sec ON time--1.0 min OFF time, in repeating
cycles.
[0215] Program #6:
[0216] 2.0 mA current output, 0.25 msec pulse width, 25 Hz
frequency, 30 sec ON time--1.0 min OFF time, in repeating
cycles.
[0217] The following are examples of most aggressive therapy.
[0218] Program #8:
[0219] 2.5 mA current output, 0.3 msec pulse width, 30 Hz
frequency, 40 sec ON time-- 1.5 min OFF time, in repeating
cycles.
[0220] Program #9:
[0221] 3.0 mA current output, 0.4 msec pulse width, 30 Hz
frequency, 30 sec ON time--1.0 min OFF time, in repeating
cycles.
[0222] The majority of patients will fall into the category that
require an intermediate level of therapy, such as program #5. The
above are examples of the pre-determined programs that are
delivered to the vagus nerve. The actual parameter settings for any
given patient may deviate somewhat from the above.
[0223] FIG. 14 shows a top level block diagram of the external
stimulator 42. As previously mentioned, there are two modes of
stimulation with the external stimulator 42. The first mode is a
series of pre-determined standard programs 71, differing in the
aggressiveness of the therapy. The second mode is patient override
73, where upon pressing a button, the device immediately goes into
the active mode. The selector 69 which comprises of pre-determined
programs 71 and patient override 73 feeds into programmable control
logic 75. The programmable control logic 75 controls the pulse
frequency oscillator 79. The output of the pulse frequency
oscillator 79 is amplified 83, filtered 87 and provided to the
external coil (antenina) 89, which is then transmitted to the
implanted receiver 34 for stimulation of the nerve. The
programmable control logic 75 is connected to an indicator 85
showing on-off status, as well as the battery status. The external
stimulator 42 is powered by a DC battery 81. A programming station
77 provides the capability to download and change programs if the
need arises.
[0224] Conventional integrated circuits are used for the logic,
control and timing circuits. Conventional bipolar transistors are
used in radio-frequency oscillator, pulse amplitude ramp control
and power amplifier. A standard voltage regulator is used in
low-voltage detector. The hardware and software to deliver these
predetermined programs is well known to those skilled in the
art.
[0225] The fabrication of the lead-receiver 34 is designed to be
modular. Thus, several different components can be mixed and
matched without altering the functionality of the device
significantly. As shown in FIG. 6, the lead-receiver 34 components
are the proximal end 49 (containing coil 48, electrical circuitry
98, and case 78), the lead body 59 containing the conductor 65, and
the distal electrode (cathode) 52. In the modular design concept,
several design variables are possible, as shown in the table
below.
2 Table of lead-receiver design variables Proximal Distal End End
Circuitry Conductor and Lead Lead body- (connecting Return body-
Insulation proximal and Electrode - Electrode - electrode Lumens
materials Lead-Coating distal ends) Material Type Bipolar Single
Polyurethane Lubricious Alloy of Pure Standard ball (PVP)
Nickal-Cobalt Platinum electrode Unipolar Double Silicone
Antimicrobial Platinum- Hydrogel Iridium electrode (Pt/Ir) alloy
Triple Silicone with Anti- Pt/Ir Spiral Polytetrafluor inflammatory
coated with electrode oethylene Titanium (PTFE) Nitride Coaxial
Carbon Steroid eluting Fiber electrode
[0226] Either silicone or polyurethane is suitable material for
this implantable lead body 59. Both materials have proven to have
desirable qualities which are not available in the other.
Permanently implantable pacemaker leads made of polyurethane are
susceptible to some forms of degradation over time. The identified
mechanisms are Environmental Stress Cracking (ESC) and Metal Ion
Oxidation (MIO). For this reason silicone material is slightly
preferred over polyurethane.
[0227] Nerve-electrode interaction is an integral part of the
stimulation system. As a practical benefit of modular design, any
type of electrode described below can be used as the distal
(cathode) stimulating electrode, without changing fabrication
methodology or procedure significantly. When a standard ball
electrode made of platinum or platinum/iridium is placed next to
the nerve, and secured in place, it promotes an inflammatory
response that leads to a thin fibrotic sheath around the electrode
over a period of 1 to 6 weeks. This in turn leads to a stable
position of electrode relative to the nerve, and a stable
electrode-tissue interface, resulting in reliable stimulation of
the nerve chronically without damaging the nerve.
[0228] Alternatively, other electrode forms that are non-traumatic
to the nerve such as hydrogel, platinum fiber, or steroid elution
electrodes may be used with this system. The concept of hydrogel
electrode for nerve stimulation is shown schematically in FIG. 15.
The hydrogel material 100 is wrapped around the nerve 54, with tiny
platinum electrodes 102 being pulled back from nerve. Over a period
of time in the body, the hydrogel material 100 will undergo
degradation and there will be fibrotic tissue buildup. Because of
the softness of the hydrogel material 100, these electrodes are
non-traumatic to the nerve.
[0229] The concept of platinum fiber electrodes is shown
schematically in FIG. 16. The distal fiber electrode 104 attached
to the lead-receiver 34 may be platinum fiber or cable, or the
electrode may be thin platinum fiber wrapped around Dacron
polyester or Polyimide 106. As shown in FIG. 17, the platinum
fibers 108 may be woven around Dacron polyester fiber 106 or
platinum fibers 108 may be braided. At implant, the fiber electrode
104 is loosely wrapped around the surgically isolated nerve, then
tied loosely so as not to constrict the nerve or put pressure on
the nerve. As a further extension, the fiber electrode may be
incorporated into a spiral electrode 105 as is shown schematically
in FIG. 18. The fiber electrode 110 is on the inner side of
polyurethane or silicone insulation 112 which is heat treated to
retain its spiral shape.
[0230] Alternatively, steroid elution electrodes may be used. After
implantation of a lead in the body, during the first few weeks
there is buildup of fibrotic tissue in-growth over the electrode
and to some extent around the lead body. This fibrosis is the end
result of body's inflammatory response process which begins soon
after the device is implanted. The fibrotic tissue sheath has the
net effect of increasing the distance between the stimulation
electrode (cathode) and the excitable tissue, which is the vagal
nerve in this case. This is shown schematically in FIG. 19, where
electrode 52 when covered with fibrotic tissue becomes the
"virtual" electrode 114. Non-excitable tissue is depicted as 120
and excitable tissue as 118. A small amount of corticosteroid,
dexamethasone sodium phosphate commonly referred to as "steroid" or
"dexamethasone" placed inside or around the electrode, has
significant beneficial effect on the current or energy threshold,
i.e. the amount of energy required to stimulate the excitable
tissue. This is well known to those familiar in the art, as there
is a long history of steroid elution leads in cardiac pacing
application. It takes only about 1 mg of dexamethasone to produce
the desirable effects. Three separate ways of delivering the
steroid drug to the electrode nerve-tissue interface are being
disclosed here. Dexamethasone can be placed inside an electrode
with microholes, it can be placed adjacent to the electrode in a
silicone collar, or it can be coated on the electrode itself.
[0231] Dexamethasone inside the stimulating electrode is shown
schematically in FIG. 20. A silicone core that is impregnated with
a small quantity of dexamethasone 121, is incorporated inside the
electrode. The electrode tip is depicted as 124 and electrode body
as 122. Once the lead is implanted in the body, the steroid 121
elutes out through the small holes in the electrode. The steroid
drug then has anti-inflammatory action at the electrode tissue
interface, which leads to a much thinner fibrotic tissue
capsule.
[0232] Another way of having a steroid eluting nerve stimulating
electrode, is to have the steroid agent placed outside the distal
electrode 52 in a silicone collar 126. This is shown schematically
in FIG. 21. Approximately 1 mg of dexamethasone is contained in a
silicone collar 126, at the base of the distal electrode 52. With
such a method, the steroid drug elutes around the electrode 52 in a
similar fashion and with similar pharmacokinetic properties, as
with the steroid drug being inside the electrode.
[0233] Another method of steroid elution for nerve stimulation
electrodes is by coating of steroid on the outside (exposed)
surface area of the electrode. This is shown schematically in FIG.
22. Nafion is used as the coating matrix. Steroid membrane coating
on the outside of the electrode is depicted as 128. The advantages
of this method are that it can easily be applied to any electrode,
fast and easy manufacturing, and it is cost effective. With this
method, the rate of steroid delivery can be controlled by the level
of sulfonation.
[0234] A schematic representation of the cross section of different
possible lumens is shown in FIG. 23. The lead body 59 can have one,
two, or three lumens for conducting cable, with or without a hollow
lumen. In the cross sections, 132A-F represents lumens(s) for
conducting cable, and 134A-C represents hollow lumen for aid in
implanting the lead.
[0235] Additionally, different classes of coating may be applied to
the implantable lead-receiver 34 after fabrication. These coatings
fall into three categories, lubricious coating, antimicrobial
coating, and anti-inflammatory coating.
[0236] The advantage of modular fabrication is that with one
technology platform, several derivative products or models can be
manufactured. As a specific practical example, using a silicone
lead body platform, three separate derivative or lead models can be
manufactured by using three different electrodes such as standard
electrode, steroid electrode or spiral electrode. This is made
possible by designing the fabrication steps such that the distal
electrodes are assembled at the end, and as long as the electrodes
are mated to the insulation and conducting cable, the shape or type
of electrode does not matter. Similarly, different models can be
produced by taking a finished lead and then coating it with
lubricious coating or antimicrobial coating. In fact, considering
the design variables disclosed in table 1, a large number of
combinations are possible. Of these large number of possible
combinations, about 6 or 7 models are planned for manufacturing.
These include lead body composed of silicone and PTFE with standard
ball electrodes made of platinum/iridium alloy, and silicone lead
body with spiral electrode.
[0237] In addition to the neuromodulation of a cranial nerve such
as the vagus nerve described above, neuromodulation of other nerves
in the body can be performed. For example, neuromodulation of
sacral nerve, which has beneficial effects for urinary
incontinance, can be performed using an implantable lead-receiver
and an external stimulator containing predetermined program, where
the two are inductively coupled. In such a case, the secondary coil
wold be implanted in the lower abdominal region.
[0238] While various embodiments of the present invention have been
described in detail, it is apparent that modifications and
adaptations of those embodiments will occur to those skilled in the
art. However, it is to be expressly understood that such
modifications and adaptations are within the spirit and scope of
the present invention.
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