U.S. patent application number 12/462903 was filed with the patent office on 2009-12-10 for methods and apparatus for neuromodulation and physiologic modulation for the treatment of obesity and metabolic and neuropsychiatric disease.
Invention is credited to Daniel John DiLorenzo.
Application Number | 20090306739 12/462903 |
Document ID | / |
Family ID | 26894226 |
Filed Date | 2009-12-10 |
United States Patent
Application |
20090306739 |
Kind Code |
A1 |
DiLorenzo; Daniel John |
December 10, 2009 |
Methods and apparatus for neuromodulation and physiologic
modulation for the treatment of obesity and metabolic and
neuropsychiatric disease
Abstract
The present invention teaches a method and apparatus for
physiological modulation, including neural and gastrointestinal
modulation, for the purposes of treating several disorders,
including obesity, depression, epilepsy, and diabetes. This
includes chronically implanted neural and neuromuscular modulators,
used to modulate the afferent neurons of the sympathetic nervous
system to induce satiety as well as to modulate the efferent
neurons of the sympathetic nervous system to modulate metabolism,
including metabolic rate. Furthermore, this includes neuromuscular
stimulation of the stomach to effect baseline and intermittent
smooth muscle contraction to increase gastric intraluminal
pressure, which induces satiety, and stimulate sympathetic afferent
fibers, including those in the sympathetic trunk, splanchnic
nerves, and greater curvature of the stomach, to augment the
perception of satiety.
Inventors: |
DiLorenzo; Daniel John;
(Houston, TX) |
Correspondence
Address: |
DILORENZO BIOMEDICAL, LLC
P.O. BOX 300905
HOUSTON
TX
77230
US
|
Family ID: |
26894226 |
Appl. No.: |
12/462903 |
Filed: |
August 9, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10198871 |
Jul 19, 2002 |
7599736 |
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12462903 |
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60307124 |
Jul 23, 2001 |
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10198871 |
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12387638 |
May 5, 2009 |
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60307124 |
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Current U.S.
Class: |
607/40 |
Current CPC
Class: |
A61N 1/0551 20130101;
A61N 1/36007 20130101; A61N 1/36114 20130101; A61N 2/00 20130101;
A61N 5/00 20130101; A61N 7/00 20130101 |
Class at
Publication: |
607/40 |
International
Class: |
A61N 1/36 20060101
A61N001/36 |
Claims
1. A device for treating disease, comprising: (A) an implantable
pulse generator, comprising a processor configured to generate a
signal which modulates the spinal neurons to induce weight loss;
(B) a conducting member attached to said implantable pulse
generator; and (C) a modulator, wherein said modulator comprises a
spinal neuromodulatory interface connected to said implantable
pulse generator via said conducting member and which delivers
reversible modulation to neurons of the sympathetic nervous
system.
2. The device for treating disease as in claim 1 wherein said
modulator is in communication with intermediolateral neurons.
3. The device for treating disease as in claim 1 wherein said
modulator is in communication with the intermediolateral
nucleus.
4. The device for treating disease as in claim 1 wherein said
modulator is in communication with thoracic spinal neurons.
5. The device for treating disease as in claim 1 wherein said
modulator is in communication with the abdominal spinal
neurons.
6. The device for treating disease as in claim 1 wherein said
modulator is configured to modulate neural activity for the
treatment of obesity.
7. The device for treating disease as in claim 1 wherein said
modulator is configured to modulate neural activity for the control
of metabolism.
8. The device for treating disease as in claim 1 wherein said
modulator is configured to modulate neural activity for the control
of body weight.
9. The device for treating disease as in claim 1 wherein said
modulator delivers electrical energy.
10. The device for treating disease as in claim 1 wherein said
modulator comprises an anterior central spinal neuromodulatory
interface.
11. The device for treating disease as in claim 1 wherein said
modulator comprises at least one of an anterior right lateral
spinal neuromodulatory interface and an anterior left lateral
spinal neuromodulatory interface.
12. The device for treating disease as in claim 1 wherein said
modulator comprises a posterior central spinal neuromodulatory
interface.
13. The device for treating disease as in claim 1 wherein said
modulator comprises at least one of a posterior right lateral
spinal neuromodulatory interface and a posterior left lateral
spinal neuromodulatory interface.
14. The device for treating disease as in claim 1 wherein said
modulator comprises at least one of a right lateral spinal
neuromodulatory interface and a left lateral spinal neuromodulatory
interface.
15. The device for treating disease as in claim 1 wherein said
modulator is configured to deliver energy to afferent neurons.
16. The device for treating disease as in claim 1 wherein said
modulator is configured to deliver energy to efferent neurons.
17. The device for treating disease as in claim 1 wherein said
modulator is configured to deliver energy to somatosensory
neurons.
18. A device for treating a condition in a user, comprising: (A) a
pulse generator, comprising a processor configured to generate a
signal which modulates the spinal cord to induce weight loss; (B) a
signal transmitting member, configured to transmit said signal from
said pulse generator to a modulator; and (C) the modulator, wherein
said modulator delivers at least one modality of energy to at least
a component of the user's sympathetic nervous system.
19. The device as in claim 125, wherein said modulator delivers
electrical energy.
20. A device for treating disease, comprising: (A) an implantable
pulse generator, comprising a processor configured to generate at
least one signal which modulates spinal neurons to induce weight
loss; (B) a conducting member attached to said implantable pulse
generator; and (C) a modulator, wherein said modulator comprises at
least one spinal neuromodulatory interface connected to said
implantable pulse generator via said conducting member and which
delivers reversible multimodal modulation.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 10/198,871 (Docket GISTIM 01.01), entitled
METHOD AND APPARATUS FOR NEUROMODULATION AND PHSYIOLOGIC MODULATION
FOR THE TREATMENT OF METABOLIC AND NEUROPSYCHIATRIC DISEASE, filed
Jul. 19, 2002, and naming as inventor Daniel John DiLorenzo, which
is a continuation of U.S. Provisional Patent Application Ser. No.
60/307,124, entitled PHYSIOLOGIC MODULATION FOR THE CONTROL OF
OBESITY, DEPRESSION, EPILEPSY, AND DIABETES, filed Jul. 23, 2001,
and naming as inventor Daniel John DiLorenzo.
[0002] This application is a continuation of and incorporates by
reference U.S. Utility patent application Ser. No. 12/387,638
(Docket GISTIM 01.04), filed May 5, 2009, entitled "Methods and
Apparatus for Neuromodulation and Physiologic Modulation for the
Treatment of Obesity and Metabolic and Neuropsychiatric Disease"
and naming as inventor Daniel John DiLorenzo.
[0003] This application is a continuation of and incorporates by
reference U.S. Provisional Patent Application No. 60/500,911, filed
Sep. 5, 2003 and naming as inventor Daniel John DiLorenzo.
[0004] This application incorporates by reference U.S. Provisional
Patent Application No. 60/579,074, filed Jun. 10, 2004 and naming
as inventor Daniel John DiLorenzo.
[0005] This application incorporates by reference U.S. patent
application Ser. No. 10/008,576, entitled OPTIMAL METHOD AND
APPARATUS FOR NEURAL MODULATION FOR THE TREATMENT OF NEUROLOGICAL
DISEASE, PARTICULARLY MOVEMENT DISORDERS, filed Nov. 11, 2001, and
naming as inventor Daniel John DiLorenzo; which is a continuation
of U.S. patent application Ser. No. 09/340,326, entitled APPARATUS
AND METHOD FOR CLOSED-LOOP INTRACRANIAL STIMULATION FOR OPTIMAL
CONTROL OF NEUROLOGICAL DISEASE, filed Jun. 25, 1999, and naming as
inventor Daniel John DiLorenzo; which claims the benefit of U.S.
Provisional Patent Application Ser. No. 60/095,413 entitled OPTIMAL
METHOD AND APPARATUS FOR NEURAL MODULATION FOR THE TREATMENT OF
NEUROLOGICAL DISEASE, PARTICULARLY MOVEMENT DISORDERS, filed Aug.
5, 1998 and naming as inventor Daniel John DiLorenzo.
[0006] This application incorporates by reference U.S. Provisional
Application Ser. No. 60/427,699, entitled APPARATUS AND METHOD FOR
CLOSED-LOOP INTRACRANIAL SIMULATION FOR OPTIMAL CONTROL OF
NEUROLOGICAL DISEASE, filed Nov. 20, 2002, and naming as inventor
Daniel John DiLorenzo.
[0007] This application incorporates by reference U.S. Provisional
Application Ser. No. 60/436,792, entitled APPARATUS AND METHOD FOR
CLOSED-LOOP INTRACRANIAL STIMULATION FOR OPTIMAL CONTROL OF
NEUROLOGICAL DISEASE, filed Dec. 27, 2002, and naming as inventor
Daniel John DiLorenzo.
[0008] This application incorporates by reference U.S. Provisional
Application Ser. No. 60/438,286, entitled ADAPTIVE CLOSED-LOOP
NEUROMODULATION SYSTEM, filed Jan. 6, 2003, and naming as inventor
Daniel John DiLorenzo.
[0009] This application incorporates by reference U.S. Provisional
Application Ser. No. 60/460,140 filed Apr. 3, 2003.
INCORPORATION BY REFERENCE
[0010] All publications, patents, and patent applications mentioned
in this specification are herein incorporated by reference to the
same extent as if each individual publication, patent, or patent
application was specifically and individually indicated to be
incorporated by reference.
BACKGROUND OF INVENTION
[0011] 1. Field of the Invention
[0012] The present invention relates generally to metabolic disease
and neuropsychiatric disease and, more particularly, to stimulation
of gastric and sympathetic neural tissue for the treatment of
obesity and depression.
[0013] 2. Related Art
[0014] Physiologic studies have demonstrated the presence of a
sympathetic nervous system afferent pathway transmitting gastric
distention information to the hypothalamus. [Barone, Zarco de
Coronado et al. (1995). Gastric distension modulates hypothalamic
neurons via a sympathetic afferent path through the mesencephalic
periaqueductal gray. Brain Research Bulletin. 38: 239-51.] However,
prior techniques have generally not addressed the problems
associated with satiety, morbidity, mortality of intracranial
modulation and the risk of ulcers. Unlike prior techniques, by
specifically targeting sympathetic afferent fibers, the present
invention effects the sensation of satiety and avoids the
substantial risks of morbidity and mortality of intracranial
modulation, particularly dangerous in the vicinity of the
hypothalamus. Furthermore, this invention avoids the risk of ulcers
inherent in vagus nerve stimulation.
A. Satiety
[0015] Stimulation of intracranial structures has been proposed and
described for the treatment of obesity (U.S. Pat. No. 5,782,798).
Stimulation of the left ventromedial hypothalamic (VMH) nucleus
resulted in delayed eating by dogs who had been food deprived.
Following 24 hours of food deprivation, dogs with VMH stimulation
waited between 1 and 18 hours after food presentation before
consuming a meal. Sham control dogs ate immediately upon food
presentation. Dogs that received 1 hour of stimulation every 12
hours for 3 consecutive days maintained an average daily food
intake of 35% of normal baseline levels. [Brown, Fessler et al.
(1984). Changes in food intake with electrical stimulation of the
ventromedial hypothalamus in dogs. Journal of Neurosurgery. 60:
1253-7.]
B. Candidate Peripheral Nerve Path ways for Modulating Satiety
B1. Sympathetic Afferents
[0016] The effect of gastric distension on activity in the lateral
hypothalamus-lateral preoptic area-medial forebrain bundle
(LPA-LH-MFB) was studied to determine the pathways for this gastric
afferent input to the hypothalamus. [Barone, Zarco de Coronado et
al. (1995). Gastric distension modulates hypothalamic neurons via a
sympathetic afferent path through the mesencephalic periaqueductal
gray. Brain Research Bulletin. 38: 239-51.] The periaqueductal gray
matter (PAG) was found to be a relay station for this information.
[Barone, Zarco de Coronado et al. (1995). Gastric distension
modulates hypothalamic neurons via a sympathetic afferent path
through the mesencephalic periaqueductal gray. Brain Research
Bulletin. 38: 239-51.] This modulation of the hypothalamus was
attenuated but not permanently eliminated by bilateral transection
of the vagus nerve. This modulation was, however, significantly
reduced or eliminated by bilateral transection of the cervical
sympathetic chain or spinal transection at the first cervical
level. [Barone, Zarco de Coronado et al. (1995). Gastric distension
modulates hypothalamic neurons via a sympathetic afferent path
through the mesencephalic periaqueductal gray. Brain Research
Bulletin. 38: 239-51.] These signals containing gastric distension
and temperature stimulation are mediated to a large degree by
sympathetic afferents, and the PAG is a relay station for this
gastric afferent input to the hypothalamus. [Barone, Zarco de
Coronado et al. (1995). Gastric distension modulates hypothalamic
neurons via a sympathetic afferent path through the mesencephalic
periaqueductal gray. Brain Research Bulletin. 38: 239-51.]
[0017] For example, in the LPA-LH-MFB study, 26.1% of the 245
neurons studied were affected by gastric stimulation, with 17.6%
increasing in firing frequency and 8.6% decreasing during gastric
distension. [Barone, Zarco de Coronado et al. (1995). Gastric
distension modulates hypothalamic neurons via a sympathetic
afferent path through the mesencephalic periaqueductal gray. Brain
Research Bulletin. 38: 239-51.] The response of 8 of 8 neurons
sensitive to gastric distension were maintained, though attenuated
after bilateral vagus nerves were cut. In 2 of these 8 cells, the
effect was transiently eliminated for 2-4 minutes after left vagus
transection, and then activity recovered. In 3 LH-MFB cells, two
increased and the other decreased firing rate with gastric
distension. Following bilateral sympathetic ganglion transection,
the response of two were eliminated, and the third (which increased
firing with distension) had a significantly attenuated response.
[Barone, Zarco de Coronado et al. (1995). Gastric distension
modulates hypothalamic neurons via a sympathetic afferent path
through the mesencephalic periaqueductal gray. Brain Research
Bulletin. 38: 239-51.] Vagus stimulation resulted in opposite or
similar responses as gastric distension on the mesencephalic
cells
B2. Vagus Nerve Afferents
[0018] Gastric vagal input to neurons throughout the hypothalamus
has been characterized. [Yuan and Barber (1992). Hypothalamic
unitary responses to gastric vagal input from the proximal stomach.
American Journal of Physiology. 262: G74-80.] Nonselective
epineural vagus nerve stimulation (VNS) has been described for the
treatment of Obesity (U.S. Pat. No. 5,188,104). This suffers from
several significant limitations that are overcome by the present
invention.
[0019] The vagus nerve is well known to mediate gastric
hydrochloric acid secretion. Dissection of the vagus nerve off the
stomach is often performed as part of major gastric surgery for
ulcers. Stimulation of the vagus nerve may pose risks for ulcers in
patients, of particular concern, as obese patients often have
gastroesophageal reflux disease (GERD); further augmentation of
gastric acid secretion would only exacerbate this condition.
C. Assessment of Sympathetic and Vagus Stimulation
[0020] The present invention teaches a significantly more advanced
neuroelectric interface technology to stimulate the vagus nerve and
avoid the efferent vagus side effects, including speech and cardiac
side effects common in with existing VNS technology as well as the
potential ulcerogenic side effects. However, since sympathetic
afferent activity appears more responsive to gastric distension,
this may represent a stronger channel for modulating satiety.
Furthermore, by pacing stimulating modulators on the greater
curvature of the stomach, one may stimulate the majority of the
circular layer of gastric musculature, thereby diffusely increasing
gastric tone.
D. Neuromuscular Stimulation
[0021] The muscular layer of the stomach is comprised of 3 layers:
(1) an outer longitudinal layer, (2) a circular layer in between,
and (3) a deeper oblique layer. [Gray (1974). Gray's Anatomy. T.
Pick and R. Howden. Philadelphia, Running Press.] The circular
fibers, which lie deep to the superficial longitudinal fibers,
would appear to be the layer of choice for creating uniform and
consistent gastric contraction with elevated wall tension and
luminal pressure. Therefore, modulators should have the ability to
deliver stimulation through the longitudinal layer. If the
modulator is in the form of an electrode, then the electrodes
should have the ability to deliver current through the longitudinal
layer.
[0022] Gray's Anatomy describes innervation as including the right
and left pneumogastric nerves (not the vagus nerves), being
distributed on the back and front of the stomach, respectively. A
great number of branches from the sympathetic nervous system also
supply the stomach. [Gray (1974). Gray's Anatomy. T. Pick and R.
Howden. Philadelphia, Running Press.]
Metabolic Modulation (Efferent)
[0023] Electrical stimulation of the VMH enhances lipogenesis in
the brown adipose tissue (BAT), preferentially over the white
adipose tissue (WAT) and liver, probably through a mechanism
involving activation of the sympathetic innervation of the BAT.
[Takahashi and Shimazu (1982). Hypothalamic regulation of lipid
metabolism in the rat: effect of hypothalamic stimulation on
lipogenesis. Journal of the Autonomic Nervous System. 6:
225-35.]
[0024] The VMH is a hypothalamic component of the sympathetic
nervous system. [Ban (1975). Fiber connections in the hypothalamus
and some autonomic functions. Pharmacology Biochemistry &
Behavior. 3: 3-13.]
[0025] A thermogenic response in BAT was observed with direct
sympathetic nerve stimulation. [Flaim, Horwitz et al. (1977).
Coupling of signals to brown fat: .alpha.- and .beta.-adrenergic
responses in intact rats. Amer. J. Physiol. 232: R101-R109.] The
BAT had abundant sympathetic innervation with adrenergic fibers
that form nest-like networks around every fat cell, [Derry,
Schonabum et al. (1969). Two sympathetic nerve supplies to brown
adipose tissue of the rat. Canad. J. Physiol. Pharmacol. 47:
57-63.] whereas WAT has no adrenergic fibers in direct contact with
fat cells except those related to the blood vessels. [Daniel and
Derry (1969). Criteria for differentiation of brown and white fat
in the rat. Canad. J. Physiol. Pharmacol. 47: 941-945.]
SUMMARY OF THE INVENTION
[0026] The present invention teaches apparatus and methods for
treating a multiplicity of diseases, including obesity, depression,
epilepsy, diabetes, and other diseases. The invention taught herein
employs a variety of energy modalities to modulate central nervous
system structures, peripheral nervous system structures, and
peripheral tissues and to modulate physiology of neural structures
and other organs, including gastrointestinal, adipose, pancreatic,
and other tissues. The methods for performing this modulation,
including the sites of stimulation and the modulator configurations
are described. The apparatus for performing the stimulation are
also described. This invention teaches a combination of novel
anatomic approaches and apparatus designs for direct and indirect
modulation of the autonomic nervous system, which is comprised of
the sympathetic nervous system and the parasympathetic nervous
system.
[0027] For the purposes of this description the term GastroPace
should be interpreted to mean the devices constituting the system
of the present embodiment of this invention.
A. Obesity and Eating Disorders
[0028] The present invention teaches several mechanisms, including
neural modulation and direct contraction of the gastric
musculature, to effect the perception of satiety. This modulation
is useful in the treatment of obesity and eating disorders,
including anorexia nervosa and bulimia.
[0029] Direct stimulation of the gastric musculature increases the
intraluminal pressure within the stomach; and this simulates the
physiologic condition of having a full stomach, sensed by stretch
receptors in the muscle tissue and transmitted via neural afferent
pathways to the hypothalamus and other central nervous system
structures, where the neural activity is perceived as satiety.
[0030] This may be accomplished with the several alternative
devices and methods taught in the present invention. Stimulation of
any of the gastric fundus, greater curvature of stomach, pyloric
antrum, or lesser curvature of stomach, or other region of the
stomach or gastrointestinal tract, increases the intraluminal
pressure. Increase of intraluminal pressure physiologically
resembles fullness of the respective organ, and satiety is
perceived.
[0031] The present invention also includes the restriction of the
flow of food to effect satiety. This is accomplished by stimulation
of the pylorus. The pylorus is the sphincter-like muscle at the
distal juncture of the stomach with the duodenum, and it regulates
food outflow from the stomach into the duodenum. By stimulating
contraction of the pylorus, food outflow from the stomach is slowed
or delayed. The presence of a volume of food in the stomach
distends the gastric musculature and causes the person to
experience satiety.
B. Depression and Anxiety
[0032] An association has been made between depression and
overeating, particularly with the craving of carbohydrates; and is
believed to be an association between the sense of satiety and
relief of depression. Stimulation of the gastric tissues, in a
manner that resembles or is perceived as satiety, as described
above, provides relief from this craving and thereby relief from
some depressive symptoms.
[0033] There are several mechanisms, including those taught above
for the treatment of obesity that are applicable to the treatment
of depression, anxiety, and other neuropsychiatric conditions
C. Epilepsy
[0034] The present invention includes electrical stimulation of
peripheral nervous system and other structures and tissues to
modulate the activity in the central nervous system to control
seizure activity.
[0035] This modulation takes the form of peripheral nervous system
stimulation using a multiplicity of novel techniques and apparatus.
Direct stimulation of peripheral nerves is taught; this includes
stimulation of the vagus, trigeminal, accessory, and sympathetic
nerves. Indiscriminate stimulation of the vagus nerves has been
described for some disorders, but the limitations in this technique
are substantial, including cardiac rhythm disruptions, speech
difficulties, and gastric and duodenal ulcers. The present
invention overcomes these persistent limitations by teaching a
method and apparatus for the selective stimulation of structures,
including the vagus nerve as well as other peripheral nerves, and
other neural, neuromuscular, and other tissues.
[0036] The present invention further includes noninvasive
techniques for neural modulation. This includes the use of tactile
stimulation to activate peripheral or cranial nerves. This
noninvasive stimulation includes the use of tactile stimulation,
including light touch, pressure, vibration, and other modalities
that may be used to activate the peripheral or cranial nerves.
Temperature stimulation, including hot and cold, as well as
constant or variable temperatures, are included in the present
invention.
D. Diabetes
[0037] The response of the gastrointestinal system, including the
pancreas, to a meal includes several phases. The first phase, the
anticipatory stage, is neurally mediated. Prior to the actual
consumption of a meal, saliva production increases and the
gastrointestinal system prepares for the digestion of the food to
be ingested. Innervation of the pancreas, in an analogous manner,
controls production of insulin.
[0038] Modulation of pancreatic production of insulin may be
performed by modulation of at least one of afferent or efferent
neural structures. Afferent modulation of at least one of the vagus
nerve, the sympathetic structures innervating the gastrointestinal
tissue, the sympathetic trunk, and the gastrointestinal tissues
themselves is used as an input signal to influence central and
peripheral nervous system control of insulin secretion.
BRIEF DESCRIPTION OF THE DRAWINGS
[0039] FIG. 1 depicts GastroPace implanted along the Superior
Greater Curvature of the stomach for both Neural Afferent and
Neuromuscular Modulation
[0040] FIG. 2 depicts GastroPace implanted along the Inferior
Greater Curvature of the stomach for both Neural Afferent and
Neuromuscular Modulation
[0041] FIG. 3 depicts GastroPace implanted along the Pyloric Antrum
of the stomach for both Neural Afferent and Neuromuscular
Modulation
[0042] FIG. 4 depicts GastroPace implanted adjacent to the Gastric
Pylorus for modulation of pylorus activity and consequent control
of gastric food efflux and intraluminal pressure
[0043] FIG. 5 depicts GastroPace implanted along the Pyloric Antrum
of the stomach with modulators positioned for stimulation of Neural
and Neuromuscular structures of the Pylorus and Pyloric Antrum of
the Stomach
[0044] FIG. 6 depicts GastroPace implanted along the Pyloric Antrum
of the stomach with modulators positioned for stimulation of Neural
and Neuromuscular structures of the Pylorus, Pyloric Antrum,
Greater Curvature, and Lesser Curvature of the Stomach
[0045] FIG. 7 depicts the Nerve Cuff Electrode, comprising the
Epineural Electrode Nerve Cuff Design
[0046] FIG. 8 depicts the Nerve Cuff Electrode, comprising the
Axial Electrode Blind End Port Design
[0047] FIG. 9 depicts the Nerve Cuff Electrode, comprising the
Axial Electrode Regeneration Port Design
[0048] FIG. 10 depicts the Nerve Cuff Electrode, comprising the
Axial Regeneration Tube Design
[0049] FIG. 11 depicts GastroPace implanted along the Pyloric
Antrum of the stomach with modulators positioned for stimulation of
Afferent Neural Structures, including sympathetic and
parasympathetic fibers
[0050] FIG. 12 depicts GastroPace implanted along the Pyloric
Antrum of the stomach with modulators positioned for stimulation of
Neural and Neuromuscular structures of the Pylorus, Pyloric Antrum,
Greater Curvature, and Lesser Curvature of the Stomach and with
modulators positioned for stimulation of Afferent Neural
Structures, including sympathetic and parasympathetic fibers
[0051] FIG. 13 depicts the Normal Thoracoabdominal anatomy as seen
via a sagittal view of an open dissection
[0052] FIG. 14 depicts modulators for GastroPace positioned on the
sympathetic trunk and on the greater and lesser splanchnic nerves,
both supradiaphragmatically and infradiaphragmatically, for
afferent and efferent neural modulation.
[0053] FIG. 15 depicts GastroPace configured with multiple pulse
generators, their connecting cables, and multiple modulators
positioned on the sympathetic trunk and on the greater and lesser
splanchnic nerves, both supradiaphragmatically and
infradiaphragmatically, for afferent and efferent neural
modulation.
[0054] FIG. 16 depicts GastroPace configured with multiple pulse
generators, their connecting cables, and multiple modulators
positioned on the sympathetic trunk and on the greater and lesser
splanchnic nerves, both supradiaphragmatically and
infradiaphragmatically, for afferent and efferent neural modulation
and with modulators positioned for stimulation of Neural and
Neuromuscular structures of the Pylorus, Pyloric Antrum, Greater
Curvature, and Lesser Curvature of the Stomach
[0055] FIG. 17 depicts the Normal Spinal Cord Anatomy, shown in
Transverse Section FIG. 18 depicts GastroPace implanted with
multiple modulators positioned for modulation of Spinal Cord
structures
DETAILED DESCRIPTION
[0056] The present invention encompasses a multimodal technique,
method, and apparatus for the treatment of several diseases,
including but not limited to obesity, eating disorders, depression,
epilepsy, and diabetes.
[0057] These modalities may be used for diagnostic and therapeutic
uses, and these modalities include but are not limited to
stimulation of gastric tissue, stimulation of gastric musculature,
stimulation of gastric neural tissue, stimulation of sympathetic
nervous tissue, stimulation of parasympathetic nervous tissue,
stimulation of peripheral nervous tissue, stimulation of central
nervous tissue, stimulation of cranial nervous tissue, stimulation
of skin receptors, including Pacinian corpuscles, nociceptors,
golgi tendons, and other sensory tissues in the skin, subcutaneous
tissue, muscles, and joints.
[0058] Stimulation may be accomplished by electrical means, optical
means, electromagnetic means, radiofrequency means, electrostatic
means, magnetic means, vibrotactile means, pressure means,
pharmacologic means, chemical means, electrolytic concentration
means, thermal means, or other means for altering tissue
activity.
[0059] Already encompassed in the above description are several
specific applications of this broad technology. These specific
applications include electrical stimulation of gastric tissue,
including at least one of muscle and neural, for the control of
appetite and satiety, and for the treatment of obesity. Additional
specific uses include electrical stimulation of gastric tissue for
the treatment of depression. Further uses include electrical
stimulation of pancreatic tissue for the treatment of diabetes
A. Satiety Modulation
A1. Sympathetic Afferent Stimulation
[0060] Selected stimulation of the sympathetic nervous system is an
objective of the present invention. A variety of modulator designs
and configurations are included in the present invention and other
designs and configurations may be apparent to those skilled in the
art and these are also included in the present invention. Said
modulator may take the form of electrode or electrical source,
optical source, electromagnetic source, radiofrequency source,
electrostatic source, magnetic source, vibrotactile source,
pressure source, pharmacologic source, chemical source, electrolyte
source, thermal source, or other energy or stimulus source.
[0061] One objective of the modulator design for selective
sympathetic nervous system stimulation is the avoidance of
stimulation of the vagus nerve. Stimulation of the vagus nerve
poses the risk enhanced propensity for development of gastric or
duodenal ulcers.
[0062] Other techniques in which electrical stimulation has been
used for the treatment of obesity have included stimulation of
central nervous system structures or peripheral nervous system
structures. Other techniques have used sequential stimulation of
the gastric tissue to interrupt peristalsis; however, this broad
stimulation of gastric tissue necessarily overlaps regions heavily
innervated by the vagus nerve and consequently poses the same risks
of gastric and duodenal ulcers that stimulation of the vagus nerve
does.
[0063] One objective of the present invention is the selective
stimulation of said afferent neural fibers that innervate gastric
tissue. Avoidance of vagus nerve stimulation is an object of this
modulator configuration. Other alternative approaches to gastric
pacing involving gastric muscle stimulation secondarily cause
stimulation of the vagus nerve as well as stimulation of gastric
tissues in acid-secreting regions, consequently posing the
undesirable side effects of gastric and duodenal ulcers secondary
to activation of gastric acid stimulation.
[0064] There are a number of approaches to selective stimulation of
the sympathetic nervous system. This invention includes stimulation
of the sympathetic fibers at sites including the zones of
innervation of the stomach, the gastric innervation zones excluding
those innervated by vagus branches, the distal sympathetic branches
proximal to the stomach, the sympathetic trunk, the
intermediolateral nucleus, the locus ceruleus, the hypothalamus,
and other structures comprising or influencing sympathetic afferent
activity.
[0065] Stimulation of the sympathetic afferent fibers elicits the
perception of satiety, and achievement of chronic, safe, and
efficacious modulation of sympathetic afferents is one of the major
objectives of the present invention.
[0066] Alternating and augmenting stimulation of the sympathetic
nervous system and vagus nerve is included in the present
invention. By alternating stimulation of the vagus nerve and the
sympathetic afferent fibers, one may induce the sensation of
satiety in the implanted patient while minimizing the potential
risk for gastric and duodenal ulcers.
[0067] Since vagus and sympathetic afferent fibers carry
information that is related to gastric distention, a major
objective of the present invention is the optimization stimulation
of the biggest fibers, the afferent sympathetic nervous system
fibers, and other afferent pathways such that a maximal sensation
of satiety is perceived in the implanted individual and such that
habituation of this sensation of satiety is minimized. This
optimization is performed in any combination of matters including
temporal patterning of the individual signals to each neural
pathway, including but not limited to the vagus nerve and
sympathetic afferents, as well as temporal patterning between a
multiplicity of stimulation channels involving the same were neural
pathways
[0068] The present invention teaches a multiplicity of apparatus
and method for stimulation of afferent sympathetic fibers, as
detailed below. Other techniques and apparatus may become apparent
to those skilled in the art, without departing from the present
invention.
A1a. Sympathetic Afferents--Gastric Region
[0069] FIG. 1 through FIG. 3 demonstrate stimulation of gastric
tissue, including at least one of neural and muscular tissue.
Anatomical structures include esophagus 15, lower esophageal
sphincter 14, stomach 8, cardiac notch of stomach 16, gastric
fundus 9, greater curvature of stomach 10, pyloric antrum 11,
lesser curvature of stomach 17, pylorus 12, and duodenum 13.
[0070] Implantable pulse generator 1 is shown with modulator 2 and
modulator 3 in contact with the corresponding portion of stomach 8
in the respective figures, detailed below. Implantable pulse
generator further comprises attachment fixture 4 and attachment
fixture 5. Additional or fewer attachment fixtures may be included
without departing from the present invention. Attachment means 6
and attachment means 7 are used to secure attachment fixture 4 and
attachment fixture 5, respectively to appropriate portion of
stomach 8. Attachment means 6 and attachment means 7 may be
comprised from surgical suture material, surgical staples,
adhesives, or other means without departing from the present
invention.
[0071] FIGS. 1,2, and 3 show implantable pulse generator 1 in
several anatomical positions. In FIG. 1, implantable pulse
generator 1 is shown positioned along the superior region of the
greater curvature of stomach 10, with modulator 2 and modulator 3
in contact with the tissues comprising the greater curvature of
stomach 10. In FIG. 2, implantable pulse generator 1 is shown
positioned along the inferior region of the greater curvature of
stomach 10, with modulator 2 and modulator 3 in contact with the
tissues comprising the greater curvature of stomach 10. In FIG. 3,
implantable pulse generator 1 is shown positioned along the pyloric
antrum 11, with modulator 2 and modulator 3 in contact with the
tissues comprising the pyloric antrum 11.
[0072] Modulator 2 and modulator 3 are used to stimulate at least
one of gastric longitudinal muscle layer, gastric circular muscle
layer, gastric nervous tissue, or other tissue. Modulator 2 and
modulator 3 may be fabricated from nonpenetrating material or from
penetrating material, including needle tips, arrays of needle tips,
wires, conductive sutures, other conductive material, or other
material, without departing from the present invention.
A1b. Sympathetic Afferents--Sympathetic Trunk
[0073] The present invention teaches apparatus and method for
stimulation of sympathetic afferent fibers using stimulation in the
region of the sympathetic trunk. As shown in FIGS. 14, 15, and 16,
sympathetic trunk neuromodulatory interface 83 and 85, positioned
on right sympathetic trunk 71, and sympathetic trunk
neuromodulatory interface 85, 86 positioned on left sympathetic
trunk 72, are used to provide stimulation for afferent as well as
for efferent sympathetic nervous system modulation. Modulation of
efferent sympathetic nervous system is discussed below, and this is
used for metabolic modulation.
A1e. Sympathetic Afferents--Other
[0074] The present invention teaches apparatus and method for
stimulation of sympathetic afferent fibers using stimulation of
nerves arising from the sympathetic trunk. As shown in FIGS. 14,
15, and 16, thoracic splanchnic neuromodulatory interface 87, 89,
88, and 90, positioned on right greater splanchnic nerve 73, right
lesser splanchnic nerve 75, left greater splanchnic nerve 74, left
lesser splanchnic nerve 76, respectively, and are used to provide
stimulation for afferent as well as for efferent sympathetic
nervous system modulation. Modulation of efferent sympathetic
nervous system is discussed below, and this is used for metabolic
modulation.
A2. Gastric Musculature Stimulation
[0075] A further object of the present invention is the stimulation
of the gastric musculature. This may be performed using either or
both of closed loop and open loop control. In the present
embodiment, a combination of open and closed loop control is
employed. The open loop control provides a baseline level of
gastric stimulation. This stimulation maintains tone of the gastric
musculature. This increases the wall tension the stomach and plays
a role in the perception of satiety in the implanted patient.
Additionally, stimulation of the gastric musculature causes
contraction of the structures, thereby reducing the volume of the
stomach. This gastric muscle contraction, and the consequent
reduction of stomach volume effectively restricts the amount of
food that may be ingested. Surgical techniques have been developed
and are known to those practicing in the field of surgical
treatment of obesity. Several of these procedures are of the
restrictive type, but because of their surgical nature they are
fixed in magnitude and difficult if not impossible to reverse. The
present invention teaches a technique which employs neural
modulation and gastric muscle stimulation which by its nature is
the variable and reversible. This offers the advantages
postoperative adjustment of magnitude, fine tuning for the
individual patient, varying of magnitude to suit the patient's
changing needs and changing anatomy over time, and the potential
for reversal or termination of treatment. Furthermore, since the
gastric wall tension is generated in a physiological manner by the
muscle itself, it does not have the substantial risk of gastric
wall necrosis and rupture inherent in externally applied pressure,
as is the case with gastric banding.
[0076] FIGS. 1, 2, and 3 depict placements of the implantable pulse
generator 1 that may be used to stimulate gastric muscle tissue.
Stimulation of both longitudinal and circular muscle layers is
included in the present invention. Stimulation of gastric circular
muscle layer causes circumferential contraction of the stomach, and
stimulation of gastric longitudinal muscle layer causes
longitudinal contraction of the stomach.
[0077] This muscle stimulation and contraction accomplishes several
objectives: (1) functional reduction in stomach volume, (2)
increase in stomach wall tension, (3) reduction in rate of food
bolus flow. All of these effects are performed to induce the
sensation of satiety.
A3. Gastric Pylorus Stimulation
[0078] FIG. 4 depicts implantable pulse generator 1 positioned to
perform stimulation of the gastric pylorus 12 to induce satiety by
restricting outflow of food bolus material from the stomach 8 into
the duodenum 13. Stimulation of the pylorus 12 may be continuous,
intermittent, or triggered manually or by sensed event or
physiological condition. FIG. 4 depicts implantable pulse generator
1 positioned adjacent to the gastric pylorus 12; this position
provides secure modulator positioning while eliminating the risk of
modulator and wire breakage inherent in other designs in which
implantable pulse generator 1 is positioned remote from the gastric
pylorus 12.
[0079] FIG. 5 depicts implantable pulse generator 1 positioned to
perform stimulation of the gastric pylorus 12 to induce satiety by
restricting outflow of food bolus material from the stomach 8 into
the duodenum 13. Stimulation of the pylorus 12 may be continuous,
intermittent, or triggered manually or by sensed event or
physiological condition. FIG. 5 depicts implantable pulse generator
1 attached to stomach 8, specifically by the pyloric antrum 11;
this position facilitates the use of a larger implantable pulse
generator 1. The risk of modulator and wire breakage is minimized
by the use of appropriate strain relief and stranded wire
designs.
A4. Parasympathetic Stimulation
[0080] The parasympathetic nervous system is complementary to the
sympathetic nervous system and plays a substantial role in
controlling digestion and cardiac activity. Several routes are
described in the present invention to modulate activity of the
parasympathetic nervous system.
A4a. Parasympathetic Stimulation--Vagus Nerve
[0081] Others have advocated the use of vagus nerve stimulation for
the treatment of a number of disorders including obesity. Zabara
and others have described systems in which the vagus nerve in the
region of the neck is stimulated. This is plagued with a host of
problems, including life-threatening cardiac complications as well
as difficulties with speech and discomfort during stimulation. The
present invention is a substantial advance over that discussed by
Zabara et al, in which unrestricted fiber activation using
epineural stimulation is described. That technique results in
indiscriminate stimulation of efferent and afferent fibers. With
vagus nerve stimulation, efferent fiber activation generates many
undesirable side effects, including gastric and duodenal ulcers,
cardiac disturbances, and others.
[0082] In the present invention, as depicted in FIG. 14, vagus
neuromodulatory interface 97 and 98 are implanted adjacent to and
in communication with right vagus nerve 95 and left vagus nerve 96.
The neuromodulatory interface 97 and 98 overcomes these limitations
that have persisted for over a decade with indiscriminate vagus
nerve stimulation, by selectively stimulating afferent fibers of
the at least one of the vagus nerve, the sympathetic nerves, and
other nerves. The present invention includes the selective
stimulation of afferent fibers using a technique in which
electrical stimulation is used to block anterograde propagation of
action potentials along the efferent fibers. The present invention
includes the selective stimulation of afferent fibers using a
technique in which stimulation is performed proximal to a nerve
transection and in which the viability of the afferent fibers is
maintained. One such implementation involves use of at least one of
neuromodulatory interface 34 which is of the form shown in at least
one of Longitudinal Electrode Neuromodulatory Interface 118,
Longitudinal Electrode Regeneration Port Neuromodulatory Interface
119, Regeneration Tube Neuromodulatory Interface 120, or other
design in which a subset of the neuronal population is
modulated.
A.4.a.i. Innovative Stimulation Anatomy
[0083] FIG. 6 depicts multimodal treatment for the generation of
satiety, using sympathetic stimulation, gastric muscle stimulation,
gastric pylorus stimulation, and vagus nerve stimulation. This is
described in more detail below. Modulators 30 and 31 are positioned
in the general region of the lesser curvature of stomach 17.
Stimulation in this region results in activation of vagus nerve
afferent fibers. Stimulation of other regions may be performed
without departing from the present invention. In this manner,
selective afferent vagus nerve stimulation may be achieved, without
the detrimental effects inherent in efferent vagus nerve
stimulation, including cardiac rhythm disruption and induction of
gastric ulcers.
A.4.a.ii Innovative Stimulation Device
[0084] The present invention further includes devices designed
specifically for the stimulation of afferent fibers.
[0085] FIG. 7 depicts epineural cuff electrode neuromodulatory
interface 117, one of several designs for neuromodulatory interface
34 included in the present invention. Nerve 35 is shown inserted
through nerve cuff 36. For selective afferent stimulation, the
nerve 35 is transected distal to the epineural cuff electrode
neuromodulatory interface 117. This case is depicted here, in which
transected nerve end 37 is seen distal to epineural cuff electrode
neuromodulatory interface 117. Epineural electrode 49, 50, and 51
are mounted along the inner surface of nerve cuff 36 and in contact
or close proximity to nerve 35. Epineural electrode connecting wire
52, 53, 54 are electrically connected on one end to epineural
electrode 49, 50, and 51, respectively, and merge together on the
other end to form connecting cable 55.
[0086] FIG. 8 depicts longitudinal electrode neuromodulatory
interface 118, one of several designs for neuromodulatory interface
34 included in the present invention. Nerve 35 is shown inserted
into nerve cuff 36. For selective afferent stimulation, the nerve
35 is transected prior to surgical insertion into nerve cuff 36.
Longitudinal electrode array 38 is mounted within nerve cuff 36 and
in contact or close proximity to nerve 35. Connecting wire array 40
provides electrical connection from each element of longitudinal
electrode array 38 to connecting cable 55. Nerve cuff end plate 41
is attached to the distal end of nerve cuff 36. Nerve 35 may be
advanced sufficiently far into longitudinal electrode array 38 such
that elements of longitudinal electrode array 38 penetrate into
nerve 35. Alternatively, nerve 35 may be placed with a gap between
transected nerve end 37 and longitudinal electrode array 38 such
that neural regeneration occurs from transected nerve end 37 toward
and in close proximity to elements of longitudinal electrode array
38.
[0087] FIG. 9 depicts longitudinal electrode regeneration port
neuromodulatory interface 119, an improved design for
neuromodulatory interface 34 included in the present invention.
Nerve 35 is shown inserted into nerve cuff 36. For selective
afferent stimulation, the nerve 35 is transected prior to surgical
insertion into nerve cuff 36. Longitudinal electrode array 38 is
mounted within nerve cuff 36 and in contact or close proximity to
nerve 35. Connecting wire array 40 provides electrical connection
from each element of longitudinal electrode array 38 to connecting
cable 55. Nerve cuff end plate 41 is attached to the distal end of
nerve cuff 36. Nerve 35 may be advanced sufficiently far into
longitudinal electrode array 38 such that elements of longitudinal
electrode array 38 penetrate into nerve 35. Alternatively, nerve 35
may be placed with a gap between transected nerve end 37 and
longitudinal electrode array 38 such that neural regeneration
occurs from transected nerve end 37 toward and in close proximity
to elements of longitudinal electrode array 38. At least one of
nerve cuff 36 and nerve cuff end plate 41 are perforated with one
or a multiplicity of regeneration port 39 to facilitate and enhance
regeneration of nerve fibers from transected nerve end 37.
[0088] FIG. 10 depicts regeneration tube neuromodulatory interface
120, an advanced design for neuromodulatory interface 34 included
in the present invention. Nerve 35 is shown inserted into nerve
cuff 36. For selective afferent stimulation, the nerve 35 is
transected prior to surgical insertion into nerve cuff 36.
Regeneration electrode array 44 is mounted within regeneration tube
array 42, which is contained within nerve cuff 36. Each
regeneration tube 43 contains at least one element of regeneration
electrode array 44. Each element of regeneration electrode array 44
is electrically connected by at least one element of connecting
wire array 40 to connecting cable 55. Nerve 35 may be surgically
inserted into nerve cuff 36 sufficiently far to be adjacent to
regeneration tube array 42 or may be placed with a gap between
transected nerve end 37 and regeneration tube array 42. Neural
regeneration occurs from transected nerve end 37 toward and through
regeneration tube 43 elements regeneration tube array 42.
[0089] The present invention further includes stimulation of other
tissues that influence vagus nerve activity. These include tissues
of the esophagus, stomach, small and large intestine, pancreas,
liver, gallbladder, kidney, mesentery, appendix, bladder, uterus,
and other intraabdominal tissues. Stimulation of one or a
multiplicity of these tissues modulates activity of the vagus nerve
afferent fibers without significantly altering activity of efferent
fibers. This method and the associated apparatus facilitates the
stimulation of vagus nerve afferent fibers without activating vagus
nerve efferent fibers, thereby overcoming the ulcerogenic and
cardiac side effects of nonselective vagus nerve stimulation. This
represents a major advance in vagus nerve modulation and overcomes
the potentially life-threatening complications of nonselective
stimulation of the vagus nerve.
A4b. Parasympathetic Stimulation--Other
[0090] The present invention teaches stimulation of the cervical
nerves or their roots or branches for modulation of the
parasympathetic nervous system. Additionally, the present invention
teaches stimulation of the sacral nerves or their roots or branches
for modulation of the parasympathetic nervous system.
A5. Multichannel Satiety Modulation
[0091] FIG. 6 depicts apparatus and method for performing
multichannel modulation of satiety. Implantable pulse generator 1
is attached to stomach 8, via attachment means 6 and 7 connected
from stomach 8 to attachment fixture 4 and 5, respectively.
Implantable pulse generator 1 is electrically connected via
modulator cable 32 to modulators 24, 25, 26, 27, 28, and 29, which
are affixed to the stomach 8 preferably along the region of the
greater curvature of stomach 10. Implantable pulse generator 1 is
additionally electrically connected via modulator cable 33 to
modulators 30 and 31, which are affixed to the stomach 8 preferably
along the region of the lesser curvature of stomach 17. Implantable
pulse generator 1 is furthermore electrically connected via
modulator cable 18 and 19 to modulators 2 and 3, respectively,
which are affixed to the gastric pylorus 12. Modulator 2 is affixed
to gastric pylorus via modulator attachment fixture 22 and 23, and
modulator 3 is affixed to gastric pylorus via modulator attachment
fixture 20 and 21.
[0092] Using the apparatus depicted in FIG. 6, satiety modulation
is achieved through multiple modalities. A multiplicity of
modulators, including modulator 30 and 31 facilitate stimulation of
vagus and sympathetic afferent fibers directly, as well as through
stimulation of tissues, including gastric muscle, that in turn
influence activity of the sympathetic and vagus afferent fibers. A
multiplicity of modulators, including modulator 24, 25, 26, 27, 28,
and 29 facilitate stimulation of sympathetic afferent fibers
directly, as well as through stimulation of tissues, including
gastric muscle, that in turn influence activity of the sympathetic
fibers. Any of these modulators may be used to modulate vagus nerve
activity; however, one advancement taught in the present invention
is the selective stimulation of sympathetic nerve fiber activation,
and this is facilitated by modulators 24, 25, 26, 27, 28, and 29,
by virtue of their design for and anatomical placement in regions
of the stomach 8 that are not innervated by the vagus nerve or its
branches.
[0093] In addition to the apparatus and methods depicted in FIG. 6
for satiety modulation, the present invention further includes
satiety modulation performed with the apparatus depicted in FIG.
16, and described previously, using stimulation of right
sympathetic trunk 71, left sympathetic trunk 72, right greater
splanchnic nerve 73, left greater splanchnic nerve 74, right lesser
splanchnic nerve 75, left lesser splanchnic nerve 76 or other
branch or the sympathetic nervous system.
B. Metabolic Modulation
B.1. Sympathetic Efferent Stimulation
[0094] One objective of the modulator configuration employed in the
present invention is the selected stimulation of sympathetic
efferent nerve fibers. The present invention includes a
multiplicity of potential modulator configurations and combinations
of thereof. The present embodiment includes modulators placed at a
combination of sites to interface with the sympathetic efferent
fibers. These sites include the musculature of the stomach, the
distal sympathetic branches penetrating into the stomach,
postganglionic axons and cell bodies, preganglionic axons and cell
bodies, the sympathetic chain and portions thereof, the
intermediolateral nucleus, the locus ceruleus, the hypothalamus,
and other structures comprising or influencing activity of the
sympathetic nervous system.
[0095] Stimulation of the sympathetic efferents is performed to
elevate the metabolic rate and lipolysis in the adipose tissue,
thereby enhancing breakdown of fat and weight loss in the
patient.
B.1.a. Sympathetic Efferent Stimulation--Sympathetic Trunk
[0096] FIGS. 14, 15, and 16 depict apparatus for stimulation of the
sympathetic nervous system. FIG. 14 depicts a subset of anatomical
locations for placement of neuromodulatory interfaces for
modulation of the sympathetic nervous system. FIG. 15 depicts the
same apparatus with the further addition of a set of implantable
pulse generator 1 and connecting cables. FIG. 16 depicts the
apparatus shown in FIG. 15 with the further addition of gastric
modulation apparatus also depicted in FIG. 6.
[0097] FIG. 13 reveals the normal anatomy of the thoracic region.
Trachea 63 is seen posterior to aortic arch 57. Brachiocephalic
artery 59, left common carotid artery 60 arise from aortic arch 57,
and left subclavian artery 61 arises from the left common carotid
artery 60. Right mainstem bronchus 64 and left mainstem bronchus 65
arise from trachea 63. Thoracic descending aorta 58 extends from
aortic arch 57 and is continuous with abdominal aorta 62. Right
vagus nerve 95 and left vagus nerve 96 are shown. Intercostal nerve
69 and 70 are shown between respective pairs of ribs, of which rib
67 and rib 68 are labeled.
[0098] Right sympathetic trunk 71 and left sympathetic trunk are
lateral to mediastinum 82. Right greater splanchnic nerve 73 and
right lesser splanchnic nerve 75 arise from right sympathetic trunk
71. Left greater splanchnic nerve 74 and left lesser splanchnic
nerve 76 arise from left sympathetic trunk 72. Right
subdiaphragmatic greater splanchnic nerve 78, left subdiaphragmatic
greater splanchnic nerve 79, right subdiaphragmatic lesser
splanchnic nerve 80, and left subdiaphragmatic lesser splanchnic
nerve 81 are extensions below the diaphragm 77 of the right greater
splanchnic nerve 73, left greater splanchnic nerve 74, right lesser
splanchnic nerve 75, and left lesser splanchnic nerve 76,
respectively.
B.1.b. Sympathetic Efferent Stimulation--Splanchnics
[0099] FIG. 14 depicts multichannel sympathetic modulation
implanted with relevant anatomical structures. Sympathetic trunk
neuromodulatory interface 83 and 85 are implanted adjacent to and
in communication with right sympathetic trunk 71. Sympathetic trunk
neuromodulatory interface 84 and 86 are implanted adjacent to and
in communication with left sympathetic trunk 72. Sympathetic trunk
neuromodulatory interface 83, 84, 85, and 86 are implanted superior
to their respective sympathetic trunk levels at which the right
greater splanchnic nerve 73, left greater splanchnic nerve 74,
right lesser splanchnic nerve 75, and left lesser splanchnic nerve
76, arise, respectively.
[0100] Thoracic splanchnic nerve interface 87, 88, 89, 90 are
implanted adjacent to and in communication with the right greater
splanchnic nerve 73, left greater splanchnic nerve 74, right lesser
splanchnic nerve 75, and left lesser splanchnic nerve 76, arise,
respectively. Abdominal splanchnic nerve interface 91, 92, 93, and
94 are implanted adjacent to and in communication with the right
subdiaphragmatic greater splanchnic nerve 78, left subdiaphragmatic
greater splanchnic nerve 79, right subdiaphragmatic lesser
splanchnic nerve 80, and left subdiaphragmatic lesser splanchnic
nerve 81, respectively.
[0101] Stimulation of at least one of right sympathetic trunk 71,
left sympathetic trunk 72, right greater splanchnic nerve 73, left
greater splanchnic nerve 74, right lesser splanchnic nerve 75, and
left lesser splanchnic nerve 76, right subdiaphragmatic greater
splanchnic nerve 78, left subdiaphragmatic greater splanchnic nerve
79, right subdiaphragmatic lesser splanchnic nerve 80, and left
subdiaphragmatic lesser splanchnic nerve 81 enhances metabolism of
adipose tissue. Stimulation of these structures may be performed
using at least one of electrical energy, electrical fields, optical
energy, mechanical energy, magnetic energy, chemical compounds,
pharmacological compounds, thermal energy, vibratory energy, or
other means for modulating neural activity.
[0102] FIG. 15 depicts the implanted neuromodulatory interfaces as
in FIG. 14, with the addition of the implanted pulse generators.
Implantable pulse generator 99 is connected via connecting cable
103, 105, 107, 109, 115, to sympathetic trunk neuromodulatory
interface 83 and 85, and thoracic splanchnic neuromodulatory
interface 87 and 89, and vagus neuromodulatory interface 97,
respectively. Implantable pulse generator 100 is connected via
connecting cable 104, 106, 108, 110, 116, to sympathetic trunk
neuromodulatory interface 83 and 85, and thoracic splanchnic
neuromodulatory interface 88 and 90, and vagus neuromodulatory
interface 98, respectively. Implantable pulse generator 101 is
connected via connecting cable 111 and 113 to abdominal splanchnic
neuromodulatory interface 91 and 93, respectively. Implantable
pulse generator 102 is connected via connecting cable 112 and 114
to abdominal splanchnic neuromodulatory interface 92 and 94,
respectively.
B.1.c. Sympathetic Efferent Stimulation--Spinal Cord
[0103] FIGS. 17 and 18 depicts the normal cross sectional anatomy
of the spinal cord 151 and anatomy with implanted neuromodulatory
interfaces, respectively.
[0104] FIG. 17 depicts the normal anatomical structures of the
spinal cord 151, including several of its component structures such
as the intermediolateral nucleus 121, ventral horn of spinal gray
matter 141, dorsal horn of spinal gray matter 142, spinal cord
white matter 122, anterior median fissure 123. Other structures
adjacent to or surrounding spinal cord 151 include ventral spinal
root 124, dorsal spinal root 125, spinal ganglion 126, spinal nerve
127, spinal nerve anterior ramus 128, spinal nerve posterior ramus
129, gray ramus communicantes 130, white ramus communicantes 131,
sympathetic trunk 132, pia mater 133, subarachnoid space 134,
arachnoid 135, meningeal layer of dura mater 136, epidural space
137, periosteal layer of dura mater 138, and vertebral spinous
process 139, and vertebral facet 140.
[0105] FIG. 17 depicts the normal anatomy of the spinal cord seen
in transverse section. Spinal cord and related neural structures
include intermediolateral nucleus 121, spinal cord white matter
122, anterior median fissure 123, ventral spinal root 124, dorsal
spinal root 125, spinal ganglion 126, spinal nerve 127, spinal
nerve anterior ramus 128, spinal nerve posterior ramus 129, gray
ramus communicantes 130, white ramus communicantes 131, sympathetic
trunk 132, pia mater 133, subarachnoid space 134, arachnoid 135,
meningeal layer of dura 136, epidural space 137, periosteal layer
of dura mater 138, vertebral spinous process 139, vertebral facet
140, ventral horn of spinal gray matter 141, and dorsal horn of
spinal gray matter 142.
[0106] FIG. 18 depicts the spinal neuromodulatory interfaces
positioned in the vicinity of spinal cord 151. Neuromodulatory
interfaces positioned anterior to spinal cord 151 include anterior
central spinal neuromodulatory interface 143, anterior right
lateral spinal neuromodulatory interface 144, and anterior left
lateral spinal neuromodulatory interface 145. Neuromodulatory
interfaces positioned posterior to spinal cord 151 include
posterior central spinal neuromodulatory interface 146, posterior
right lateral spinal neuromodulatory interface 147, and posterior
left lateral spinal neuromodulatory interface 148. Neuromodulatory
interfaces positioned lateral to spinal cord 151 include right
lateral spinal neuromodulatory interface 149 and left lateral
spinal neuromodulatory interface 150. Neuromodulatory interfaces
positioned within the spinal cord 151 include intermediolateral
nucleus neuromodulatory interface 152.
[0107] Stimulation, inhibition, or other modulation of the spinal
cord 151 is used to modulate fibers of the sympathetic nervous
system, including those in the intermediolateral nucleus 121 and
efferent and efferent fibers connected to the intermediolateral
nucleus 121. Modulation of at least one of portions of the spinal
cord 151, intermediolateral nucleus 121, ventral spinal root 124,
dorsal spinal root 125, spinal ganglion 126, spinal nerve 127, gray
ramus communicantes 130, white ramus communicantes 131 and other
structures facilitates modulation of activity of the sympathetic
trunk 132. Modulation of activity of the sympathetic trunk 132, in
turn, is used to modulate at least one of metabolic activity,
satiety, and appetite. This may be achieved using intermediolateral
nucleus neuromodulatory interface 152, placed in or adjacent to the
intermediolateral nucleus 121. The less invasive design employing
neuromodulatory interfaces (144, 145, 146, 147, 148, 149, 150)
shown positioned in the in epidural space 137 is taught in the
present invention.
B.1.d. Sympathetic Efferent Stimulation--Other
[0108] The present invention further includes modulation of all
sympathetic efferent nerves, nerve fibers, and neural structures.
These sympathetic efferent neural structures include but are not
limited to distal sympathetic nerve branches, mesenteric nerves,
sympathetic efferent fibers at all spinal levels, rami
communicantes at all spinal levels, paravertebral nuclei,
prevertebral nuclei, and other sympathetic structures.
B.2. Noninvasive Stimulation
[0109] The present invention teaches a device for metabolic control
using tactile stimulation. Tactile stimulation of afferent neurons
causes alterations in activity of sympathetic neurons which
influence metabolic activity of adipose tissue. The present
invention teaches tactile stimulation of skin, dermal and epidermal
sensory structures, subcutaneous tissues and structures, and deeper
tissues to modulate activity of afferent neurons.
[0110] This device for metabolic control employs vibratory
actuators. Alternatively, electrical stimulation, mechanical
stimulation, optical stimulation, acoustic stimulation, pressure
stimulation, and other forms of energy that modulate afferent
neural activity, are used.
C. Multimodal Metabolic Modulation
[0111] To maximize efficacy while tailoring treatment to minimize
side effects, the preferred embodiment includes a multiplicity of
treatment modalities, including afferent, efferent, and
neuromuscular modulation.
[0112] Afferent signals are generated to simulate satiety. This is
accomplished through neural, neuromuscular, and hydrostatic
mechanisms. Electrical stimulation of the vagus via vagus nerve
interface 45 afferents provides one such channel to transmit
information to the central nervous system for the purpose of
eliciting satiety. Electrical stimulation of the sympathetic
afferents via sympathetic nerve interface 46 provides another such
channel to transmit information to the central nervous system for
the purpose of eliciting satiety. Electrical stimulation of gastric
circular muscle layer
[0113] In FIG. 11, multimodal stimulation is depicted, including
stimulation of gastric musculature using modulators 2 and 3, as
well as stimulation of afferent fibers of the proximal stump of
vagus nerve 47 using vagus nerve modulator 45 and stimulation of
afferent fibers of sympathetic nerve branch 48.
[0114] In FIG. 12, expanded multimodal stimulation is depicted,
including those modalities shown in FIG. 11, including stimulation
of gastric musculature using modulators 2 and 3, as well as
stimulation of afferent fibers of the proximal stump of vagus nerve
47 using vagus nerve modulator 45 and stimulation of afferent
fibers of sympathetic nerve branch 48, in addition to those
modalities shown in FIG. 6, explained in detail above, including
modulation of gastric muscular fibers, sympathetic afferent fibers
innervating gastric tissues, and vagus afferent fibers innervating
gastric tissues.
[0115] In FIG. 16, further expanded multimodal modulation is
depicted, including modalities encompassed and described above and
depicted in FIG. 15 and FIG. 12. This includes modulation of
gastric muscle fibers, fibers of the sympathetic nerve branch 48
and vagus nerve 47 that innervate gastric tissues, and a
multiplicity of structures in the sympathetic nervous system and
vagus nerve 47.
E. System/Pulse Generator Design
[0116] Neuromodulatory interfaces that use electrical energy to
modulate neural activity may deliver a broad spectrum of electrical
waveforms. One preferred set of neural stimulation parameter sets
includes pulse frequencies ranging from 0.1 Hertz to 1000 Hertz,
pulse widths from 1 microsecond to 500 milliseconds. Pulses are
charge balanced to insure no net direct current charge delivery.
The preferred waveform is bipolar pulse pair, with an interpulse
interval of 1 microsecond to 1000 milliseconds. Current regulated
stimulation is preferred and includes pulse current amplitudes
ranging from 1 microamp to 1000 milliamps. Alternatively, voltage
regulation may be used, and pulse voltage amplitudes ranging from 1
microvolt to 1000 volts. These parameters are provided as exemplary
of some of the ranges included in the present invention; variations
from these parameter sets are included in the present
invention.
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