U.S. patent application number 11/078114 was filed with the patent office on 2006-01-05 for electrical stimulation system and method for stimulating tissue in the brain to treat a neurological condition.
Invention is credited to Dirk De Ridder.
Application Number | 20060004422 11/078114 |
Document ID | / |
Family ID | 34975357 |
Filed Date | 2006-01-05 |
United States Patent
Application |
20060004422 |
Kind Code |
A1 |
De Ridder; Dirk |
January 5, 2006 |
Electrical stimulation system and method for stimulating tissue in
the brain to treat a neurological condition
Abstract
According to one aspect, a stimulation system is provided for
electrically stimulating a predetermined site to treat a
neurological condition. The system includes an electrical
stimulation lead adapted for implantation in communication with a
predetermined site, wherein the site is brain tissue site. The
stimulation lead includes one or more stimulation electrodes
adapted to be positioned in the predetermined site. The system also
includes a stimulation source that generates the stimulation pulses
for transmission to the one or more stimulation electrodes of the
stimulation lead to deliver the stimulation pulses to the
predetermined site to treat a neurological disorder or
condition.
Inventors: |
De Ridder; Dirk; (Zelzate,
BE) |
Correspondence
Address: |
Fulbright & Jaworski L.L.P.
Suite 5100
1301 McKinney
Houston
TX
77010-3095
US
|
Family ID: |
34975357 |
Appl. No.: |
11/078114 |
Filed: |
March 11, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60552674 |
Mar 11, 2004 |
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Current U.S.
Class: |
607/45 |
Current CPC
Class: |
A61N 1/0531 20130101;
A61N 1/361 20130101; A61N 1/36071 20130101; A61N 1/0529 20130101;
A61N 1/0551 20130101; A61N 1/36082 20130101; A61N 1/36096 20130101;
A61B 5/055 20130101; A61N 1/36067 20130101 |
Class at
Publication: |
607/045 |
International
Class: |
A61N 1/18 20060101
A61N001/18 |
Claims
1. A method of treating a neurological condition in a subject
comprising the steps of: determining a target site of in a brain of
the subject to be stimulated, wherein said determining comprises
mapping the brain to identify an area of the brain having altered
neuronal activity, said identified area is the target site; placing
an electrode in communication with the target site; and providing a
stimulation signal to the electrode to stimulate the target site to
treat the neurological condition.
2. The method of claim 1, wherein the neurological condition is
selected from the group consisting of pain, tinnitus, depression,
phantom perception, pareshesias, synesthesia, hyperalgesia,
allodynia, dysesthesias, dyskinesia, tremor, dystonia, chorea and
ballism, tic syndromes, Tourette's Syndrome, myoclonus,
drug-induced movement disorders, Wilson's Disease, Paroxysmal
Dyskinesias, Stiff Man Syndrome and Akinetic-Ridgid Syndromes and
Parkinsonism.
3. The method of claim 1, wherein the altered neuronal activity is
an increase in neuronal activity.
4. The method of claim 1, wherein the altered neuronal activity is
a decrease in neuronal activity.
5. The method of claim 1, wherein the identified area is located in
the cortex.
6. The method of claim 1, wherein the identified area is located in
the somatosensory cortex.
7. The method of claim 1, wherein the identified area is located in
a cortical or cerebellar area of reorganization.
8. The method of claim 1, wherein the neurological condition is
acute pain, subacute pain or chronic pain.
9. The method of claim 2, wherein the mapping is neurophysiological
mapping.
10. The method of claim 2, wherein the mapping is performed by the
techniques selected from the group consisting of positron emission
tomography (PET), magnetic resonance imaging (MRI), functional MRI
(fMRI), electroencephalography (EEG), magnetoencephalography (MEG),
x-ray computed tomography (CT), single photon emission computed
tomography (SPECT), brain electrical activity mapping (BEAM),
transcranial magnetic stimulation (TMS), electrical impedance
tomography (EIT), near-infrared spectroscopy (NIRS) and optical
imaging.
11. An electrical stimulation system for electrically stimulating a
target tissue in a brain of a subject to treat a neurological
condition, comprising: an electrode for electrical stimulation of
the target tissue; a pulse generating source operable to generate
electrical stimulation pulses for transmission to the electrodes to
cause the electrodes to deliver electrical stimulation pulses to
the target tissue to treat neuroplasticity effects in the subject's
brain while delivering electrical stimulation pulses for treating
the neurological condition.
12. The system of claim 12, wherein the target tissue is identified
using brain mapping to determine a site of altered neuronal
activity.
13. The system of claim 12, wherein the electrode is positioned in
communication with the target tissue.
14. The system of claim 12, wherein the pulse generating source is
operable to generate the electrical stimulation pulses according to
one or more stimulation sets each specifying a plurality of
stimulation parameters, the stimulation parameters for a
stimulation set comprising a polarity for each electrode at each of
one or more times within a stimulation pulse for the stimulation
set.
15. The system of claim 12, wherein treating neuroplasticity
effects in the person's brain comprises reducing neuroplasticity
effects in the person's brain.
16. The system of claim 12, wherein treating neuroplasticity
effects in the person's brain comprises enhancing neuroplasticity
effects in the person's brain.
17. The system of claim 12, wherein the electrode is a percutaneous
lead or laminotomy lead.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional
Application No. 60/552,674 filed Mar. 11, 2004, which is
incorporated herein by reference in its entirety.
TECHNICAL FIELD
[0002] This invention relates generally to electrical stimulation
of a person's brain and in particular to an electrical stimulation
system and method for stimulating tissue in the brain to treat a
neurological condition, for example pain.
BACKGROUND OF THE INVENTION
[0003] Many people experience adverse conditions associated with
functions of the cortex, the thalamus, and other brain structures.
Such conditions have been treated effectively by delivering
electrical energy to one or more target areas of the brain. One
method of delivering electrical energy to the brain involves
inserting an electrical stimulation lead through a burr hole formed
in the skull and then positioning the lead in a precise location
proximate a target area of the brain to be stimulated such that
stimulation of the target area causes a desired clinical effect.
For example, one desired clinical effect may be cessation of tremor
from a movement disorder such as Parkinson's Disease. A variety of
other clinical conditions may also be treated with deep brain
stimulation, such as essential tremor, tremor from multiple
sclerosis or brain injury, or dystonia or other movement disorders.
The electrical stimulation lead implanted in the brain is connected
to an electrical signal generator implanted at a separate site in
the body, such as in the upper chest.
[0004] Chronic pain afflicts approximately 86 million Americans and
it is estimated that United States business and industry loses
about $90 billion dollars annually to sick time, reduced
productivity, and direct medical and other benefit costs due to
chronic pain among employees. Because of the staggering number of
people affected by chronic pain, a number of therapies have been
developed that attempt to alleviate the symptoms of this condition.
Such therapies include narcotics, non-narcotics, analgesics,
antidepressants, anticonvulsants, physical therapy, biofeedback,
transcutaneous electrical nerve stimulation (TENS), as well as less
conventional or alternative therapies. Other treatment options
involve neuroaugmentive techniques such as spinal cord stimulation
or intrathecal pumps. For a subset of patients, however, these
therapies are inefficacious and more invasive procedures such as
blocks, neurolysis and ablative procedures become the only options
for treatment. In particular, ablative procedures, although
infrequently utilized, are the primary alternative for patients
unresponsive to other modes of treatment. Such procedures, however,
have the fundamental limitation of being inherently irreversible
and being essentially a "one-shot" procedure with little chance of
alleviating or preventing potential side effects. In addition,
there is a limited possibility to provide continuous benefits as
the pathophysiology underlying the chronic pain progresses and the
patient's symptoms evolve. Because of the inherent disadvantages of
ablative procedures, electrical stimulation of the brain has become
an attractive neurosurgical alternative to alleviate the symptoms
of chronic pain.
[0005] Electrical stimulation of the brain for chronic pain has
been used since the 1950s when temporary electrodes were implanted
in the septal region for psychosurgery in patients with
schizophrenia and metastatic carcinoma. In particular, electrodes
were placed in the septum pellucidum in a region anterior and
inferior to the foramen of Monro. In the 1960s, there were reports
of stimulation of both the caudate nucleus and the septal region in
six patients with intractable pain, but successful pain relief was
obtained in only one patient. Despite these earlier reports of
septal and caudate stimulation, current applications of electrical
stimulation for pain involve thalamic, medial lemniscus, internal
capsule stimulation, periventricular gray and pariaqueductal gray
stimulation. For example, thalamic stimulation for pain relief was
first reported for stimulation along the ventroposterolateral
nucleus and ventralis posterior to relieve chronic intractable
deafferentation pain and stimulation along the ventroposteromedial
nucleus to relieve refractory facial pain. With respect to internal
capsule stimulation, chronic stimulating electrodes have been
implanted in the posterior limb of the internal capsule in a number
of patients, including patients with lower-extremity pain and
spasticity following spinal cord injury.
[0006] Although the above-mentioned target sites are all deep brain
stimulation target sites, several studies have supported the role
of motor cortex stimulation for pain control. For example, in the
process of performing sensory cortex stimulation in an attempt to
relieve thalamic pain, it was found that stimulation of the
precentral gyrus/motor cortex was effective in relieving thalamic
pain. Interestingly, stimulation of the sensory cortex exacerbated
the pain in many patients.
[0007] Therefore, despite previous attempts to alleviate the
symptoms of chronic pain by deep brain or cortical stimulation,
there is still an unmet need for a method of treating chronic pain
that is effective in a larger subset of the patient population.
BRIEF SUMMARY OF THE INVENTION
[0008] The electrical stimulation system and method of the present
invention may reduce or eliminate certain problems and
disadvantages associated with previous techniques for treating
neurological conditions, such as pain, for example.
[0009] According to one embodiment, an electrical stimulation
system is provided for electrically stimulating target tissue in a
person's brain to treat a neurological condition. The system
includes an electrode adapted for implantation into a person's
skull for electrical stimulation of target tissue in the person's
brain. The system also includes a pulse generating source operable
to generate electrical stimulation pulses for transmission to the
electrodes to deliver the electrical stimulation pulses to the
target tissue in the brain to adjust the level of activity in the
target tissue in the brain to treat the neurological condition.
[0010] The target tissue can be a cortical tissue site, for example
the somatosensory cortex or sensory cortex. The smoatosensory
cortex includes, but is not limited to the primary somatosensory
cortex, the secondary somatosensory cortex, and the somatosensory
association complex. Yet further, the target tissue can be
identified by mapping the person's brain. Mapping a person's or
subject's brain provides information to identify areas of the brain
that exhibit altered neuronal activity, such as increased or
decreased neuronal activity. Areas of altered neuronal activity can
therefore be identified as target sites for stimulation. Still
further, a target site for stimulation can also include areas
identified in the cortex are undergoing or have undergone
reorganization.
[0011] Additional target sites also include, but are not limited to
the cerebellum, which can also be activated in sensory stimulation.
Thus, other targets can also include any region of the brain
associated or in communication with the sensory cortex, which
includes any region or structure, as well as any connections to and
from the sensory cortex. Association with the sensory cortex
includes the functional areas of the sensory cortex for example,
but not limited to the primary somatosensory cortex, the secondary
somatosensory cortex, the somatosensory association complex,
primary visual cortex, secondary and tertiary visual cortices,
visual association cortex, primary auditory cortex, auditory
association cortex, gustatory cortex, and vestibular cortex, other
brain regions that receive somatic inputs, for example, the
posterior parietal lobe, as well as any brain region that is
stimulated by sensory stimulation, such as the cerebellum. Thus,
stimulation of the sensory cortex includes the somatosensory
processing cortical regions of the brain and sub-cortical regions
or structures, as well as the any brain region in which there are
projection connections for example, the basal ganglia, the
striatum, the motor cortex, supplementary motor cortex or area, the
posterior parietal cortex, the thalamus (e.g., the ventral
posterior nucleus of the thalamus), brainstem, periaqueductal grey,
dorsal column nuclei, and the spinal cord (e.g., dorsal horn of the
spinal cord).
[0012] Accordingly, the present invention relates to modulation of
neuronal activity to affect neurological, neuropsychological or
neuropsychiatric activity. The present invention finds particular
application in the modulation of neuronal function or processing to
affect a functional outcome. The modulation of neuronal function is
particularly useful with regard to the prevention, treatment, or
amelioration of neurological, psychiatric, psychological, conscious
state, behavioral, mood, and thought activity (unless otherwise
indicated these will be collectively referred to herein as
"neurological activity" which includes "psychological activity" or
"psychiatric activity"). When referring to a pathological or
undesirable condition associated with the activity, reference may
be made to a neurological disorder which includes "psychiatric
disorder" or "psychological disorder" instead of neurological
activity or psychiatric or psychological activity. Although the
activity to be modulated usually manifests itself in the form of a
disorder such as a attention or cognitive disorders (e.g., Autistic
Spectrum Disorders); mood disorder (e.g., major depressive
disorder, bipolar disorder, and dysthymic disorder) or an anxiety
disorder (e.g., panic disorder, posttraumatic stress disorder,
obsessive-compulsive disorder and phobic disorder);
neurodegenerative diseases (e.g., multiple sclerosis, Alzheimer's
disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease,
Huntington's Disease, Guillain-Barre syndrome, myasthenia gravis,
and chronic idiopathic demyelinating disease (CID)), movement
disorders (e.g, dyskinesia, tremor, dystonia, chorea and ballism,
tic syndromes, Tourette's Syndrome, myoclonus, drug-induced
movement disorders, Wilson's Disease, Paroxysmal Dyskinesias, Stiff
Man Syndrome and Akinetic-Ridgid Syndromes and Parkinsonism),
epilepsy, tinnitus, pain, phantom pain, diabetes neuropathy, one
skilled in the art appreciates that the invention may also find
application in conjunction with enhancing or diminishing any
neurological or psychiatric function, not just an abnormality or
disorder. Neurological activity that may be modulated can include,
but not be limited to, normal functions such as alertness,
conscious state, drive, fear, anger, anxiety, repetitive behavior,
impulses, urges, obsessions, euphoria, sadness, and the fight or
flight response, as well as instability, vertigo, dizziness,
fatigue, fotofobia, fonofobia, concentration dysfunction, memory
disorders, symptoms of traumatic brain injury (whether physical,
emotional, social or chemical), autonomic functions, which includes
sympathetic and/or parasympathetic functions (e.g., control of
heart rate), somatic functions, and/or enteric functions.
[0013] Particular embodiments of the present invention may provide
one or more technical advantages. According to the present
invention, an electrical stimulation system is used to provide
therapeutic electrical stimulation to target tissue in a person's
brain to treat a neurological condition. In particular, brain
mapping or brain imaging information and/or neurophysiological
information (e.g., evoked potentials, induced potentials, EEG, MEG)
can be used to identify target tissue in a person's brain having a
notable level of activity associated with a neurological condition,
such as pain or tinnitus, for example. Such techniques to map the
brain include, but are not limited to positron emission tomography
(PET), magnetic resonance imaging (MRI), functional MRI (fMRI),
electroencephalography (EEG), magnetoencephalography (MEG), x-ray
computed tomography (CT), single photon emission computed
tomography (SPECT), brain electrical activity mapping (BEAM),
transcranial magnetic stimulation (TMS), electrical impedance
tomography (EIT), near-infrared spectroscopy (NIRS) and optical
imaging.
[0014] The brain mapping information may include imaging
information obtained by imaging at least a portion of the person's
brain using one or more imaging techniques. Instead or in addition,
the brain imaging information may include imaging information
obtained from imaging of the brains of one or more other patients
who experience the same or similar condition as the person. In
certain embodiments, an electrode or an electrical stimulation lead
having a number of electrodes is implanted inside a person's skull
such that one or more of the electrodes are located in
communication with the identified target tissue in the brain. The
electrodes deliver electrical stimulation pulses to the identified
target tissue, which partially or completely alleviates the
condition in the person's body, which may significantly increase
the person's quality of life. The electrode or electrical
stimulation lead may be precisely positioned using a
neuronavigation system that includes brain imaging information and
mapping data obtained from the imaging of the person's brain or
from the imaging of the brains of one or more other patients. In
addition, non-invasive transcranial magnetic stimulation (TMS) of
the target tissue may be performed before surgically implanting the
electrical stimulation lead in order to determine whether the
person is a candidate for receiving an implanted electrical
stimulation system.
[0015] In certain embodiments, the electrical stimulation system
may also be able to provide electrical stimulation of the same or
different target tissue in the brain to reduce, enhance, or
otherwise treat neuroplasticity effects that may be associated with
the electrical stimulation of the target tissue for treating the
neurological condition. As a result, in certain embodiments, the
efficacy period associated with a particular set of stimulation
parameters may be extended. This may help prevent the additional
time and expense associated with one or more return visits to the
treating physician for determining and entering new sets of
efficacious parameters. Especially where the treatment is to
continue over a relatively long period of time, such as a number of
months or years, avoiding this additional time and expense may
provide a significant advantage. As another example, in other
situations, the further development of neuroplasticity effects
already in existence due to injury or disease may be prevented,
delayed, or otherwise reduced, or such pre-existing neuroplasticity
effects may be reversed in whole or in part. As a result, in
certain embodiments, undesirable conditions resulting from such
pre-existing neuroplasticity effects may be prevented from
progressing further, may be reduced, or may even be eliminated. In
certain other embodiments, such as where the person has experienced
a stroke, for example, the electrical stimulation system may
provide electrical stimulation of the same or different target
tissue in the brain to enhance or promote neuroplasticity
effects.
[0016] The foregoing has outlined rather broadly the features and
technical advantages of the present invention in order that the
detailed description of the invention that follows may be better
understood. Additional features and advantages of the invention
will be described hereinafter which form the subject of the claims
of the invention. It should be appreciated by those skilled in the
art that the conception and specific embodiment disclosed may be
readily utilized as a basis for modifying or designing other
structures for carrying out the same purposes of the present
invention. It should also be realized by those skilled in the art
that such equivalent constructions do not depart from the spirit
and scope of the invention as set forth in the appended claims. The
novel features which are believed to be characteristic of the
invention, both as to its organization and method of operation,
together with further objects and advantages will be better
understood from the following description when considered in
connection with the accompanying figures. It is to be expressly
understood, however, that each of the figures is provided for the
purpose of illustration and description only and is not intended as
a definition of the limits of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawing(s) will be provided by the Office
upon request and payment of the necessary fee.
[0018] For a more complete understanding of the present invention,
reference is now made to the following descriptions taken in
conjunction with the accompanying drawing, in which:
[0019] FIGS. 1A-1B illustrate example electrical stimulation
systems for electrically stimulating target nerve tissue in the
brain identified through imaging of the brain to treat a condition
in the body and, in certain embodiments, provide reduced or
enhanced neuroplasticity effects in the brain;
[0020] FIGS. 2A-2I illustrate example electrical stimulation leads
that may be used to electrically stimulate target nerve tissue in
the brain identified through imaging of the brain to treat a
condition in the body and, in certain embodiments, provide reduced
or enhanced neuroplasticity effects in the brain;
[0021] FIG. 3 illustrates example placement of the electrical
stimulation system shown in FIGS. 1A-1B within a person's body;
[0022] FIG. 4 is a cross-section of a portion of the person's head
shown in FIG. 3, illustrating an example location of the electrical
stimulation lead;
[0023] FIG. 5 illustrates an example method for determining an
optimal location and implanting the stimulation system of FIGS.
1A-1B into a person in order to electrically stimulate target nerve
tissue in the brain identified through imaging of the brain to
treat a condition in the body;
[0024] FIG. 6 illustrates an example stimulation set;
[0025] FIG. 7 illustrates a number of example stimulation programs,
each of which includes a number of stimulation sets; and
[0026] FIG. 8 illustrates example execution of a sequence of
stimulation sets within an example stimulation program.
[0027] FIGS. 9A and FIG. 9B illustrate fMRI activity (thresholded
at T>7) overlayed on saggital, transverse and coronal slices
(FIG. 9A) as well as a surface reconstruction of the patient's
brain (FIG. 9B). Arrow indicates area of V1 pain sensation, located
within the left postcentral gyrus. Other areas of activity were
found in left primary sensorymotor cortex, supplementary motor
area, right cerebellum and are related to the motor activity of the
left hand and arm rubbing the right V1 skin area.
[0028] FIG. 10 shows that the amount of pain suppression is related
to the stimulation frequency used. The same relation is seen for
the time required for the phantom eye to disappear.
[0029] FIGS. 11A-11C show site of stimulation. FIG. 11A shows a
postoperative X-ray demonstrating the position of the lead. FIG.
11B shows postoperative CT comparison to preoperative fMRI (FIG.
11C). Comparing the anatomy of the preoperative fMRI with the
postoperative CT scan demonstrates the lead is positioned over the
somatosensory cortex. The area of the V1 pain sensation is located
more caudally (FIG. 9) and cannot be seen on these images.
DETAILED DESCRIPTION OF THE INVENTION
[0030] It is readily apparent to one skilled in the art that
various embodiments and modifications can be made to the invention
disclosed in this Application without departing from the scope and
spirit of the invention.
I. DEFINITIONS
[0031] As used herein, the use of the word "a" or "an" when used in
conjunction with the term "comprising" in the claims and/or the
specification may mean "one," but it is also consistent with the
meaning of "one or more," "at least one," and "one or more than
one." Still further, the terms "having," "including," "containing"
and "comprising" are interchangeable and one of skill in the art is
cognizant that these terms are open ended terms.
[0032] As used herein, the term "affective disorders" refers to a
group of disorders that are commonly associated with co-morbidity
of depression and anxiety symptoms.
[0033] As used herein, the term "chronic pain" can generally be
characterized as being nociceptive or non-nociceptive including
neuropathic pain. Yet further, it can also be characterized as pain
that has lasted for a period of time, for example, more than three
months. Chronic pain generally also has significant psychological
and emotional affects and can limit a person's ability to fully
function.
[0034] As used herein, the term "acute pain" refers to more a
recent onset of pain, pain associated with an injury or trauma or
immediate pain triggered by injury. Acute pain can also be referred
to as "phasic." Generally, acute pain is associated with a greater
intensity of pain and/or an impairment in functionality for the
person.
[0035] As used herein, the term "sub-acute pain" refers to slow,
insidious onset of pain, which can also be characterized as dull
and achy. At times, sub-acute pain can not be easily localized,
however, it may be possible to localize the pain depending upon the
condition. Typically, sub-acute pain creates a discomfort for the
person, but does not typically impair functionality for the
person.
[0036] As used herein, the term "dementia" refers to the loss, of
cognitive and intellectual functions without impairment of
perception or consciousness. Dementia is typically characterized by
disorientation, impaired memory, judgment, and intellect, and a
shallow labile affect.
[0037] As used herein, the term "deafferentation" refers to a loss
of the sensory input from a portion of the body.
[0038] As used herein, the term "in communication" refers to the
stimulation lead being adjacent, in the general vicinity, in close
proximity, or directly next to or directly on the predetermined
stimulation site, for example an area of the cortex, or an area
associated with the sensory cortex, or any subcortical area or
structure that is projections to or from the sensory cortex, or any
identified brain region or area determined by mapping the brain of
a subject suffering from a neurological condition. Thus, one of
skill in the art understands that the lead or electrode is "in
communication" with the target tissue or site if the stimulation
results in a modulation of neuronal activity resulting in the
desired response, such as modulation of the neurological
disorder.
[0039] The terms "mammal," "mammalian organism," "subject," or
"patient" or "person" are used interchangeably herein and include,
but are not limited to, humans, dogs, cats, horses and cows. The
preferred patients are humans.
[0040] As used herein the term "modulate" refers to the ability to
regulate positively or negatively neuronal activity. Thus, the term
modulate can be used to refer to an increase, decrease, masking,
altering, overriding or restoring of neuronal activity.
[0041] As used herein, the term "neurology" or "neurological"
refers to conditions, disorders, and/or diseases that are
associated with the nervous system. The nervous system comprises
two components, the central nervous system, which is composed of
the brain and the spinal cord, and the peripheral nervous system,
which is composed of ganglia and the peripheral nerves that lie
outside the brain and the spinal cord. One of skill in the art
realizes that the nervous system may be separated anatomically, but
functionally they are interconnected and interactive. Yet further,
the peripheral nervous system is divided into the autonomic system
(parasympathetic and sympathetic), the somatic system and the
enteric system. Thus, any condition, disorder and/or disease that
effects any component or aspect of the nervous system (either
central or peripheral) is referred to as a neurological condition,
disorder and/or disease. As used herein, the term "neurological" or
"neurology" encompasses the terms "neuropsychiatric" or
"neuropsychiatry" and "neuropsychological" or "neuropsychological".
Thus, a neurological disease, condition, or disorder includes, but
is not limited to cognitive disorders, affective disorders,
movement disorders, mental disorders, pain disorders, sleep
disorders, etc. For non-inclusive examples, neurological disorders
include pain, chronic pain, tinnitus, stroke, hypertension,
migraine headaches, depression, and epilepsy.
[0042] As used herein, the term "neuropsychiatry" or
"neuropsychiatric" refers to conditions, disorders and/or diseases
that relate to both organic and psychic disorders of the nervous
system.
[0043] As used herein, the term "neuropsychological" or
"neuropsychologic" refers to conditions, disorders and/or disease
that relate to the functioning of the brain and the cognitive
processors or behavior.
[0044] As used herein, the term "neuronal" or "nervous" refers to a
neuron which is a morphologic and functional unit of the brain,
spinal column, and peripheral nerves.
[0045] As used herein, the term "nociceptive pain" involves direct
activation of the nociceptors, such as mechanical, chemical, and
thermal receptors, found in various tissues, such as bone, muscle,
vessels, viscera, and cutaneous and connective tissue. Nociceptive
pain can also be referred to as somatic pain. The afferent
somatosensory pathways are thought to be intact in nociceptive pain
and examples of such pain include cancer pain from bone or tissue
invasion, non-cancer pain secondary to degenerative bone and joint
disease or osteoarthritis, and failed back surgery.
[0046] As used herein, the term "non-nociceptive pain" occurs in
the absence of activation of peripheral nociceptors.
Non-nociceptive pain can also be referred to as neuropathic pain,
or deafferentation pain. Non-nociceptive pain often results from
injury or dysfunction of the central or peripheral nervous system.
Such damage may occur anywhere along the neuroaxis and includes
thalamic injury or syndromes (also referred to as central pain,
supraspinal central pain, or post-stroke pain); stroke; traumatic
or iatrogenic trigeminal (trigeminal neuropathic) brain or spinal
cord injuries; phantom limb or stump pain; postherpetic neuralgia;
anesthesia dolorosa; brachial plexus avulsion; complex regional
pain syndrome I and II; postcordotomy dysesthesia; and various
peripheral neuropathies, inclusive of pain associated with or
related to vascular pathology (vasculitis, angina pectoris, etc.)
both peripheral vascular pathology, central or cerebral vascular
pathology, and/or cardiac vascular abnormalities.
[0047] The term "pain" as used herein refers to an unpleasant
sensation or altered sensory perception. For example, the subject
experiences discomfort, distress or suffering. Pain of a moderate
or high intensity is typically accompanied by anxiety. Thus, one of
skill in the art is cognizant that pain may have dual properties,
for example sensation and emotion. Examples of pain or altered
sensory perception can include, but are not limited to
paresthesias, dysesthesias, synesthesia, hyperalgesia, allodynia,
phantom perceptions, pressure feeling, as well as motor system
activities depending on sensory input (e.g., Parkinsons,
myoclonias, dystonias, tremor, stiff man syndrome, dyskinesia,
tremor, dystonia, chorea and ballism, tic syndromes, Tourette's
Syndrome, myoclonus, drug-induced movement disorders, Wilson's
Disease, Paroxysmal Dyskinesias, Stiff Man Syndrome and
Akinetic-Ridgid Syndromes and Parkinsonism, etc.). Pain can include
chronic pain, acute pain or subacute pain.
[0048] As used herein, the term "somatosensory system" refers to
the peripheral nervous system division comprising primarily
afferent somatic sensory neurons and afferent visceral sensory
neurons that receive sensory information from skin and deep tissue,
including the 12 cranial and 21 spinal nerves.
[0049] As used herein, the term "somatosensory cortex" or "sensory
cortex" includes the primary somatosensory cortex, secondary
somatosensory cortex and the somatosensory association cortex, as
well as the Brodmann areas associated therewith. Still further, the
sensory cortex includes all cortical sites having projections to or
from the sensory cortex, as well as the subcortical sites having
projections to or from the sensory cortex.
[0050] As used herein, the term "primary somatosensory cortex"
refers to the brain region located in the postcentral gyrus and in
the posterior part of the paracentral lobule. The primary
somatosensory cortex also includes Brodmann areas 3, 1 and 2.
[0051] As used herein, the term "secondary somatosensory cortex"
refers to the brain region that lies ventral to the primary
somatosensory area along the superior bank of the lateral
sulcus.
[0052] As used herein, the term "somatosensory association cortex"
refers to the brain areas of the superior parietal lobule, and
supramarginal gyrus. The somatosensory association cortex also
includes Brodmann areas 5, 7, and 40.
[0053] As used herein, the term "stimulate" or "stimulation" refers
to electrical, chemical, magnetic, heat/cold and/or ultrasonic
stimulation that modulates the predetermined sites in the
brain.
[0054] As used herein, the term "treating" and "treatment" refers
to stimulating a peripheral nervous tissue site so that the subject
has an improvement in the disease, for example, beneficial or
desired clinical results. For purposes of this invention,
beneficial or desired clinical results include, but are not limited
to, alleviation of symptoms, alleviation of pain, diminishment of
extent of disease, stabilized (i.e., not worsening) state of
disease, delay or slowing of disease progression, amelioration or
palliation of the disease state, and remission (whether partial or
total), whether detectable or undetectable. One of skill in the art
realizes that a treatment may improve the disease condition, but
may not be a complete cure for the disease.
[0055] As used herein, the term "proximate" means on, in, adjacent,
or near. Thus, one or more of the electrodes on an electrical
stimulation lead are adapted to be positioned on, in, adjacent, or
near the identified target tissue in the brain.
[0056] As used herein, the term "tissue in the brain" includes any
tissue in any associated with the brain, including gray matter and
white matter that make up the brain.
II. Electrical Stimulation System
[0057] According to the present invention, an electrical
stimulation system is used to electrically stimulate target tissue
in a person's brain to treat a neurological condition. The target
tissue can be in a cortical region of the brain, for example, the
somatosensory cortex, which includes the primary, the secondary
somatosensory cortex, and the somatosensory association complex.
Still further, the somatosensory cortex also includes Brodmann
areas 1, 2, 3, 5, and 7. The somatosensory cortex, in certain
embodiments, is stimulated either directly or indirectly to treat
pain.
[0058] Yet further, an another embodiment of the present invention
comprises, at least a portion of a person's brain is imaged using
one or more imaging techniques to identify target tissue in the
brain having a notable level of activity, such as overactivity or
underactivity, for example, associated with a condition, such as
pain or tinnitus. An electrical stimulation lead having a number of
electrodes is implanted inside a person's skull such that one or
more of the electrodes are located in communication with the
identified target tissue in the brain.
[0059] The electrodes deliver electrical stimulation pulses to the
identified target brain tissue to adjust the level of activity in
the identified target nerve tissue in the brain to treat the
neurological condition. For example, if the identified target
tissue in the brain is overactive, the one or more electrodes may
deliver appropriate electrical stimulation pulses to decrease the
activity of the identified target tissue to treat the condition.
Similarly, if the identified target tissue in the brain is
underactive, the one or more electrodes may deliver appropriate
electrical stimulation pulses to increase the activity of the
identified target tissue to treat the neurological condition.
[0060] The neurological condition may be any condition associated
with a notable level of activity, such as overactivity or
underactivity for example, in the identified target tissue in the
person's brain. Example conditions may include pain in a region of
the person's body, tinnitus, depression, and other neurological
disorders. In some instances, the notable level of activity in the
identified target tissue in the person's brain, and thus the
condition in the person's body, is caused by damaged, altered or
otherwise abnormally functioning nerve tissue in the person's body
correlating to the identified target tissue in the person's brain.
For example, with respect to pain, damaged, altered or otherwise
abnormally functioning nerve tissue in a region of a person's body
that causes pain in that region or another region of the person's
body may cause overactivity or underactivity in tissue in the
person's brain that correlates to the abnormally functioning nerve
tissue. As another example, with respect to tinnitus, damaged,
altered or otherwise abnormally functioning nerve tissue in a
person's auditory system or brain that causes tinnitus may cause
overactivity or underactivity in nerve tissue in the person's brain
that correlates to the abnormally functioning nerve tissue.
[0061] FIGS. 1A-1B illustrate example electrical stimulation
systems 10 for electrically stimulating target tissue in the brain
identified through imaging of the brain to treat a condition in the
body and, in certain embodiments, to provide reduced or enhanced
neuroplasticity effects in the brain. Stimulation system 10
generates and applies a stimulus to target tissue in a person's
brain, for example, the somatosensory cortex. In certain
embodiments, the target tissue is identified through imaging of the
person's brain as having a notable level of activity to adjust the
level of activity in the identified target tissue to treat a
neurological condition.
[0062] In general terms, stimulation system 10 includes an
implantable electrical stimulation source 12 and an implantable
electrical stimulation lead 14 for applying the stimulation signal
to the predetermined site or target tissue site. In operation, both
of these primary components are implanted in the person's body. In
certain embodiments, stimulation source 12 is coupled directly to a
connecting portion 16 of electrical stimulation lead 14. In certain
other embodiments, stimulation source 12 is not coupled directly to
stimulation lead 14 and stimulation source 12 instead communicates
with stimulation lead 14 via a wireless link. For example, such a
stimulation system 10 are described in the following patents U.S.
Pat. Nos. 6,748,276; 5,938,690, each of which is incorporated by
reference in its entirety. In certain other embodiments,
stimulation source 12 and electrodes 18 are contained in an
"all-in-one" microstimulator or other unit, such as a Bion.RTM.
microstimulator manufactured by Advanced Bionics Corporation. In
any case, stimulation source 12 controls the electrical stimulation
pulses transmitted to electrodes 18 (which may be located on a
stimulating portion 20 of an electrical stimulation lead 14),
implanted in communication with the target tissue, according to
appropriate stimulation parameters (e.g., duration, amplitude or
intensity, frequency, etc.). A doctor, the patient, or another user
of stimulation source 12 may directly or indirectly input or modify
stimulation parameters to specify or modify the nature of the
electrical stimulation provided.
[0063] In one embodiment, as shown in FIG. 1A, stimulation source
12 includes an implantable pulse generator (IPG). An example IPG
may be one manufactured by Advanced Neuromodulation Systems, Inc.,
such as the Genesis.RTM. System, part numbers 3604, 3608, 3609, and
3644. In another embodiment, as shown in FIG. 1B, stimulation
source 12 includes an implantable wireless receiver. An example
wireless receiver may be one manufactured by Advanced
Neuromodulation Systems, Inc., such as the Renew.RTM. System, part
numbers 3408 and 3416. The wireless receiver is capable of
receiving wireless signals from a wireless transmitter 22 located
external to the person's body. The wireless signals are represented
in FIG. 1B by wireless link symbol 24. A doctor, the patient, or
another user of stimulation source 12 may use a controller 26
located external to the person's body to provide control signals
for operation of stimulation source 12. Controller 26 provides the
control signals to wireless transmitter 22, wireless transmitter 22
transmits the control signals and power to the wireless receiver of
stimulation source 12, and stimulation source 12 uses the control
signals to vary the stimulation parameters of electrical
stimulation pulses transmitted through electrical stimulation lead
14 to the stimulation site. An example wireless transmitter 122 may
be one manufactured by Advanced Neuromodulation Systems, Inc., such
as the Renew.RTM. System, part numbers 3508 and 3516.
[0064] FIGS. 2A-2I illustrate example electrical stimulation leads
14 that may be used to provide electrical stimulation to a target
brain tissue site. As described above, each of the one or more
leads 14 incorporated in stimulation system 10 includes one or more
electrodes 18 adapted to be positioned near the target tissue site
and used to deliver electrical stimulation energy to the target
tissue site in response to electrical signals received from
stimulation source 12. A percutaneous lead 14, such as example
leads shown in FIGS. 4A-4D, includes one or more circumferential
electrodes 18 spaced apart from one another along the length of
lead 14. An example of an eight-electrode percutaneous lead is an
OCTRODE.RTM. lead manufactured by Advanced Neuromodulation Systems,
Inc. A stimulation system such as is described in U.S. Pat. No.
6,748,276 is also contemplated. Circumferential electrodes 18 emit
electrical stimulation energy generally radially in all
directions.
[0065] A laminotomy, paddle, or surgical stimulation lead 14, such
as example stimulation leads 14 described in FIGS. 2E-I, includes
one or more directional stimulation electrodes 18 spaced apart from
one another along one surface of stimulation lead 14. An example of
an eight-electrode, two column laminotomy lead is a LAMITRODE.RTM.
and C-series LAMITRODE.RTM. 44 leads manufactured by Advanced
Neuromodulation Systems, Inc. Directional stimulation electrodes 18
emit electrical stimulation energy in a direction generally
perpendicular to the surface of stimulation lead 14 on which they
are located.
[0066] Although various types of stimulation leads 14 are shown as
examples, the present invention contemplates stimulation system 10
including any suitable type of stimulation lead 14 in any suitable
number. In addition, stimulation leads 14 may be used alone or in
combination. In addition, the leads may be used alone or in
combination. For example, unilateral stimulation of nerve tissue in
the brain is typically accomplished using a single lead 14
implanted in one side of the brain, while bilateral stimulation of
the brain is typically accomplished using two leads 14 implanted in
opposite sides of the brain.
[0067] Whether using percutaneous leads, laminotomy leads, or some
combination of both, the leads are coupled to one or more
conventional neurostimulation devices, or signal generators. The
devices can be totally implanted systems and/or radio frequency
(RF) systems. An example of an RF system is a MNT/MNR-916CC system
manufactured by Advanced Neuromodulation Systems, Inc.
[0068] The preferred neurostimulation systems should allow each
electrode of each lead to be defined as a positive, a negative, or
a neutral polarity. For each electrode combination (i.e., the
defined polarity of at least two electrodes having at least one
cathode and at least one anode), an electrical signal can have at
least a definable amplitude (i.e., voltage), pulse width, and
frequency, where these variables may be independently adjusted to
finely select the sensory transmitting nerve tissue required to
inhibit transmission of neuronal signals. Generally, amplitudes,
pulse widths, and frequencies are determinable by the capabilities
of the neurostimulation systems.
[0069] Voltage or intensity that can be used may include a range
from about 1 millivolt to about 1 volt or more, e.g., 0.1 volt to
about 50 volts, e.g., from about 0.2 volt to about 20 volts and the
frequency may range from about 1 Hz to about 2500 Hz, e.g., about 1
Hz to about 1000 Hz, e.g., from about 2 Hz to about 100 Hz in
certain embodiments. The pulse width may range from about 1
microsecond to about 2000 microseconds or more, e.g., from about 10
microseconds to about 2000 microseconds, e.g., from about 15
microseconds to about 1000 microseconds, e.g., from about 25
microseconds to about 1000 microseconds. The electrical output may
be applied for at least about 1 millisecond or more, e.g., about 1
second, e.g., about several seconds, where in certain embodiments
the stimulation may be applied for as long as about 1 minute or
more, e.g., about several minutes or more, e.g., about 30 minutes
or more may be used in certain embodiments.
[0070] It is envisaged that the patient will require intermittent
assessment with regard to patterns of stimulation. Different
electrodes on the lead can be selected by suitable computer
programming, such as that described in U.S. Pat. No. 5,938,690,
which is incorporated by reference here in full. Utilizing such a
program allows an optimal stimulation pattern to be obtained at
minimal voltages. This ensures a longer battery life for the
implanted systems.
[0071] In certain embodiments, the electrical stimulation system of
the present invention includes a system that is capable of being
programmed with three or more stimulation settings to generate a
corresponding number of electrical stimulation pulses. These and
other objects of the system are obtained by providing a
microcomputer controlled system. To control the stimulation setting
and associated amplitude broadcast to the receiver, the transmitter
includes a programmable setting time generator which is controlled
by the microcomputer. The setting time generator generates a
treatment interval which is sent to a programmable setting counter.
The treatment interval is the interval that a particular
stimulation setting is broadcast before the transmitter switches to
the next stimulation setting. In the "simultaneous" operations
mode, the treatment modality is set such that the patient cannot
discern the switching between stimulation setting intervals, or
pulses, and feels only the cumulative effect of all settings. The
setting counter uses the treatment interval to control the select
lines of the setting and amplitude multiplexers. The counter allows
the setting counter to cycle through the desired stimulation
settings substantially sequentially and ensures that all elected
settings are broadcast. The system further includes a clock to
provide a signal at a continuous frequency. Similar systems are
further described in U.S. Pat. No. 6,609,031, U.S. Provisional
Application No. 60/561,437, entitled "Pulse Generator Circuit
Universal Custom Output Driver" filed Apr. 12, 2004, U.S.
Provisional Application No. 60/648,556, entitled "Efficient
Fractional Voltage Converter" filed Jan. 31, 2005, and U.S.
Provisional Application No. 60/568,384, entitled
"Multi-Programmable Trial Stimulator" filed May 5, 5, 2004, each of
which is incorporated herein by reference in its entirety.
III. Implantation of System
[0072] One technique that offers the ability to affect neuronal
function is the delivery of electrical stimulation for
neuromodulation directly to target tissues via an implanted system
having an electrode. The electrode can also be comprised within a
stimulation lead. The electrode is coupled to system to stimulate
the target site.
[0073] Techniques for implanting electrodes or stimulation leads
such as stimulation lead 14 are known to those skilled in the art.
In certain embodiments, for example, patients who are to have an
electrical stimulation lead or electrode implanted into the brain,
generally, first have a stereotactic head frame, such as the
Leksell, CRW, or Compass, mounted to the patient's skull by fixed
screws. However, frameless techniques may also be used. Subsequent
to the mounting of the frame, the patient typically undergoes a
series of magnetic resonance imaging sessions, during which a
series of two dimensional slice images of the patient's brain are
built up into a quasi- three dimensional map in virtual space. This
map is then correlated to the three dimensional stereotactic frame
of reference in the real surgical field. In order to align these
two coordinate frames, both the instruments and the patient must be
situated in correspondence to the virtual map. The current way to
do this is to rigidly mount the head frame to the surgical table.
Subsequently, a series of reference points are established to
relative aspects of the frame and patient's skull, so that either a
person or a computer software system can adjust and calculate the
correlation between the real world of the patient's head and the
virtual space model of the patient MRI scans. The surgeon is able
to target any region within the stereotactic space of the brain
with precision (e.g., within 1 mm). Initial anatomical target
localization is achieved either directly using the MRI images or
functional imaging (PET or SPECTscan, fMRI, MSI), or indirectly
using interactive anatomical atlas programs that map the atlas
image onto the stereotactic image of the brain. As is described in
greater detail elsewhere in this application, the anatomical
targets or predetermined site or target site may be stimulated
directly or affected through stimulation in another region of the
brain.
[0074] FIG. 3 illustrates example placement of the electrical
stimulation system 10 shown in FIGS. 1A-1B within a person's body
30. Electrical stimulation lead 14 is implanted under the person's
skull 32 proximate or in communicate with a particular region of
the person's brain. In certain embodiments, electrical stimulation
lead 14 is positioned within the extradural region adjacent the
brain such that one or more electrodes 18 are located proximate
target nerve tissue 34 within one or more regions 38 of the brain,
for example, the frontal lobe, the occipital lobe, the parietal
lobe, the temporal lobe, the cerebellum, or the brain stem. More
particularly, the target tissue 34 in the brain may be located in
one or more of the somatosensory cortex, more particularly, the
primary somatosensory cortex or the secondary somatosensory cortex
or the somatosensory association complex, or associated with the
somatosensory cortex.
[0075] Additional target sites also include, but are not limited to
the cerebellum, which can also be activated in sensory stimulation.
Thus, other targets can also include any cortical region of the
brain associated or in communication with the sensory cortex, as
well as any subcortical region of the brain in association or
communication with the sensory cortex. Regions of the brain that
are in association with the sensory cortex includes the functional
areas of the sensory cortex for example, but not limited to the
primary somatosensory cortex, the secondary somatosensory cortex,
the somatosensory association complex, primary visual cortex,
secondary and tertiary visual cortices, visual association cortex,
primary auditory cortex, auditory association cortex, gustatory
cortex, and vestibular cortex, other brain regions that receive
somatic inputs, for example, the posterior parietal lobe, as well
as any brain region that is stimulated by sensory stimulation, such
as the cerebellum. Thus, stimulation of the sensory cortex includes
the somatosensory processing cortical regions of the brain and
sub-cortical regions or structures, as well as the any brain region
in which there are projection connections for example, the basal
ganglia, the striatum, the motor cortex, the posterior parietal
cortex, the thalamus (e.g., the ventral posterior nucleus of the
thalamus), brainstem, dorsal column nuclei, and the spinal cord
(e.g., dorsal horn of the spinal cord).
[0076] In certain embodiments, the target sites may include brain
areas that are known to be involved in pain perception for example
the lateral thalamus, primary and second somatosensory regions, the
insular cortex, the posterior parietal cortex, the prefrontal
cortex, periaqueductal grey, basal ganglia, supplementary motor
cortex or area, and cerebellum. More particularly, the target sites
may include the areas or regions implicated in pain inhibition, for
example, but not limited to periaqueductal grey, basal ganglia,
supplementary motor cortex or area, and cerebellum.
[0077] Still further other target sites include, but are not
limited to the putamen, the thalamus, the insula, the anterior
cingulate cortex, the supplementary motor area, the frontal
operculum, the auditory cortex, such as the primary auditory
cortex, AI, also known as the transverse temporal gyri of Heschl
(Brodmann's areas 41 and 42), the secondary auditory cortex, All
(Brodmann's areas 22 and 52), the remote projection region, the
ventral medial geniculate, which projects almost entirely to AI,
the surrounding auditory areas, which receive projections from the
rest of the geniculate body, and the medial geniculate body, which
is the major auditory nucleus of the thalamus. Other target areas
can include those identified by the methodology discussed
below.
[0078] In certain embodiments, electrical stimulation lead 14 is
located at least partially within or below the dura mater proximate
target tissue 34. For example, electrical stimulation lead 14 may
be inserted into the cortex or deeper layers of the brain.
[0079] Stimulation source 12 is implanted within a subcutaneous
pocket within the person's torso 40 (such as in or near the chest
area or buttocks), and connecting portion 16 is tunneled, at least
in part, subcutaneously underneath the person's skin to connect
stimulation source 12 with the electrical stimulation lead 14.
However, stimulation source 12 may be located at any suitable
location within the person's body 30 according to particular
needs.
[0080] FIG. 4 is a cross-section of a portion of the person' head
shown in FIG. 3, illustrating an example location of electrical
stimulation lead 14. In certain embodiments, as discussed above,
electrical stimulation lead 14 is located in the extradural region
42 outside the dura mater 44 and proximate target nerve tissue 34
within one or more regions 38 of the brain. In other embodiments,
the electrical stimulation lead 14 is located in an intradural
region inside the dura mater and proximate target tissue within one
or more regions of the brain.
[0081] In certain embodiments of the present invention, the target
site or brain region to be stimulated is determined using
techniques that measure altered neuronal activity in the brain. For
example, the brain of an afflicted person is imaged or mapped using
standard techniques to determine altered neuronal activity includes
overactive or underactive activity. The brain imaging information
indicates whether the identified target tissue site or brain region
is overactive or underactive and the degree or intensity of such
overactivity or underactivity. Techniques used may include, for
example, positron emission tomography (PET), magnetic resonance
imaging (MRI), functional MRI (fMRI), electroencephalography (EEG),
magnetoencephalography (MEG), x-ray computed tomography (CT),
single photon emission computed tomography (SPECT), brain
electrical activity mapping (BEAM), transcranial magnetic
stimulation (TMS), electrical impedance tomography (EIT),
near-infrared spectroscopy (NIRS), and optical imaging.
[0082] FIG. 5 illustrates an example method for determining an
optimal location and implanting or placing a stimulation system
described above into a person in order to electrically stimulate a
target site.
[0083] In certain embodiments, the target brain tissue to be
stimulated is identified using standard brain mapping techniques,
such as imaging techniques, as well as other neurophysiological
techniques such as EEG, MEG, nerve condition studies. Techniques
used to map the brain may include, for example, positron emission
tomography (PET), magnetic resonance imaging (MRI), functional MRI
(fMRI), electroencephalography (EEG), magnetoencephalography (MEG),
x-ray computed tomography (CT), single photon emission computed
tomography (SPECT), brain electrical activity mapping (BEAM),
transcranial magnetic stimulation (TMS), electrical impedance
tomography (EIT), near-infrared spectroscopy (NIRS), nerve
condition studies, and optical imaging. For additional description
of identifying targets in a person's brain, see U.S. application
Ser. No. 10/993,888, which is incorporated herein by reference in
its entirety.
[0084] At step 100, at least a portion of the person's brain may be
imaged and/or mapped to obtain neuronal information that identifies
a target site in the brain having a notable level of activity, such
as overactivity or underactivity for example, which could be
associated with a neurological condition. The utilization of
techniques to map the brain enables one of skill in the art to
determine the area of the brain in which there is an altered
neuronal activity. Such altered neuronal activity can be associated
with reorganization of neuronal cells, such as cortical
reorganization. The information obtained from these maps provide
one of skill in the art with the knowledge of determining the brain
region that has an altered activity that is associated with a
neurological condition or can be correlated with the neurological
condition. In certain embodiments, it is necessary to perform these
mapping studies to identify the target site so that the appropriate
brain region is stimulated to result in treatment of the
neurological condition without such mapping it may be difficult to
determine the brain region to stimulate to achieve the optimum
benefit from the electrical stimulation.
[0085] Those in the art will understand that this technique may be
used as confirmation or investigation of the notable level of
activity of the target tissue. Additionally, those in the art will
understand that the location of the target tissue in the person's
brain may be determined using information from brain imaging
studies performed on other patients, and thus the imaging of the
person's brain at step 100 may not be performed. Such brain imaging
studies may include imaging information obtained using one or more
of the imaging techniques listed above to image the brains of
patients suffering from various types of neurological conditions.
The location of tissue in the brain correlating to various
conditions may be identified using statistical analysis of such
mapping information (imaging and/or neurophysiological studies).
Thus, at step 100, target tissue in the person's brain correlated
to the neurological condition may be identified according to the
results of such brain imaging studies.
[0086] At step 102, the brain imaging information obtained at step
100 (whether from imaging the person's brain or from imaging
studies of other patients suffering from the same or similar
condition as the person) is downloaded into a neuronavigation
system.
[0087] At step 104, TMS of the an area of the person's brain, such
as an area proximate the target brain tissue identified at step 100
for example, may be performed to determine whether the person is a
candidate for receiving an implanted electrical stimulation system
10. The TMS process, which is a non-invasive technique of
activating or deactivating focal areas of the brain, may be guided
by the navigation system that includes the brain imaging
information obtained at step 100. If the TMS process is successful
in treating the condition in the person's body, the person may be
considered for receiving an implanted electrical stimulation system
10. Those of skill in the art realize that step 104 is not
essential. In fact, in certain embodiments of the present
invention, the method skips step 104. Thus, the sequence is step
102 directly to step 106.
[0088] Electrical stimulation system 10 is implanted or placed
inside the person at steps 106 through 118. At step 106, the skull
32 is first prepared by exposing the skull 32 and creating a burr
hole in the skull 32. A burr hole cover may be seated within the
burr hole and fixed to the scalp or skull 32. Stereotactic
equipment suitable to aid in placement of an electrical stimulation
lead 14 in the brain may be positioned around the head. An
insertion cannula for electrical stimulation lead 14 may be
inserted through the burr hole into the brain at step 108, but a
cannula is not typically used where lead 14 is a laminotomy or
paddle lead 14. A cannula and electrical stimulation lead 14 may be
inserted together or lead 14 may be inserted through the cannula
after the cannula has been inserted. Guided by the navigation
system that includes the brain imaging information obtained at step
100, electrical stimulation lead 14 is precisely positioned
proximate the brain at step 110 such that one or more electrodes 18
are located proximate the target nerve tissue in the brain
identified at step 100. In certain embodiments, electrical
stimulation lead 14 is positioned extradurally, such as shown in
FIG. 4.
[0089] At step 112, stimulation source 12 is activated, which
generates and sends electrical stimulation pulses via electrical
stimulation lead 14 to the target nerve tissue proximate one or
more electrodes 18 on stimulation lead 14. The electrical
stimulation pulses delivered to the tissue by electrodes 18 may
adjust the activity of the target tissue in an appropriate manner
to treat the neurological condition. For example, if the brain
imaging information obtained at step 100 indicates that the
identified target tissue is overactive, stimulation source 12 may
generate, and the one or more electrodes 18 may deliver,
appropriate electrical stimulation pulses to decrease the activity
of the target tissue proximate the one or more electrodes 18 to
treat the neurological condition. Similarly, if the brain imaging
information obtained at step 100 indicates that the identified
target nerve tissue is underactive, stimulation source 12 may
generate, and the one or more electrodes 18 may deliver,
appropriate electrical stimulation pulses to increase the activity
of the target nerve tissue proximate the one or more electrodes 18
to treat the neurological condition.
[0090] At step 114, the person indicates whether the condition in
the person's body is adequately alleviated by electrical
stimulation system 10. If the condition is not adequately
alleviated, electrical stimulation lead 14 may be moved
incrementally at step 116 until the person indicates that the
condition is adequately alleviated. Once electrical stimulation
lead 14 has been positioned in the brain, lead 14 is uncoupled from
any stereotactic equipment if present, and the cannula and
stereotactic equipment if used are removed. Where stereotactic
equipment is used, the cannula may be removed before, during, or
after removal of the stereotactic equipment. Connecting portion 16
of electrical stimulation lead 14 is laid substantially flat along
the skull. Where appropriate, any burr hole cover seated in the
burr hole may be used to secure electrical stimulation lead 14 in
position and possibly to help prevent leakage from the burr hole
and entry of contaminants into the burr hole. Example burr hole
covers that may be appropriate in certain embodiments are
illustrated and described in co-pending U.S. Application Nos.
60/528,604 and 60/528,689, both filed Dec. 11, 2003 and entitled
"Electrical Stimulation System and Associated Apparatus for
Securing an Electrical Stimulation Lead in Position in a Person's
Brain", both of which are incorporated herein in their
entirety.
[0091] Once electrical stimulation lead 14 has been inserted and
secured, stimulation source 12 is implanted at step 120. The
implant site is typically a subcutaneous pocket formed to receive
and house stimulation source 12. The implant site is usually
positioned a distance away from the insertion site, such as near
the chest area or buttocks or another place in the torso 40.
Connecting portion 16 of lead 14 extends from the lead insertion
site to the implant site at which stimulation source 12 is
implanted. A doctor, the patient, or another user of stimulation
source 12 may directly or indirectly input stimulation parameters
for controlling the nature of the electrical stimulation provided.
Still further, the stimulation parameters can be adjusted
accordingly to maintain or achieve the optimum benefit. Such
adjustments may require providing neuroplasticity signals or
altered signals, increase the signals or enhance the signals, etc.
See the below discussion of neuroplasticity, which is incorporated
herein. Still further, adjustments can be made by increasing the
amount of signals, for example, stimulating more than one location
in the brain as described in U.S. Provisional Application No.
60/645,405 entitled "Electrical Stimulation System and Method for
Stimulating Multiple Locations of Target Nerve Tissue in the Brain
to Treat Multiple Conditions in the Body" filed Jan. 19, 2005, and
U.S. Pat. No. 6,609,031 each of which is incorporated herein by
reference in its entirety.
[0092] Although example steps are illustrated and described, the
present invention contemplates two or more steps taking place
substantially simultaneously or in a different order. In addition,
the present invention contemplates using methods with additional
steps, fewer steps, or different steps, so long as the steps remain
appropriate for imaging the brain of a person suffering from a
condition--or using brain imaging studies regarding patients
suffering from the same or similar condition as the person--to
identify target nerve tissue having a notable level of activity and
implanting an example stimulation system 10 into a person for
electrical stimulation of the person's brain to adjust the level of
activity in identified target tissue in the person's brain to treat
the person's condition.
IV. Methods to Treat Neurological Disorders
[0093] The present invention utilizes a stimulation system to alter
neuronal activity in the brain. More particularly, the stimulation
system can be used to stimulate the brain and cause/allow the brain
to act in the best interest of the host through use of the brain's
natural mechanisms.
[0094] The present disclosure describes apparatuses and systems for
applying electrical stimulation to cortical and other sites on a
patient. Stimulation systems and methods described herein may be
used to treat a variety of neurological conditions. Depending on
the nature of a particular condition, neural stimulation applied or
delivered in accordance with various embodiments of such systems
and/or methods may facilitate or effectuate reorganization of
interconnections or synapses between neurons to (a) provide at
least some degree of recovery of a lost function; and/or (b)
develop one or more compensatory mechanisms to at least partially
overcome a functional deficit. Such reorganization of neural
interconnections may be achieved, at least in part, by a change in
the strength of synaptic connections through a process that
corresponds to a mechanism commonly known as Long-Term Potentiation
(LTP). Electrical stimulation applied to one or more target neural
populations either alone or in conjunction with behavioral
activities and/or adjunctive or synergistic therapies may
facilitate or effectuate neural plasticity and the reorganization
of synaptic interconnections between neurons.
[0095] Accordingly, the present invention relates to modulation of
neuronal activity to affect neurological, neuropsychological or
neuropsychiatric activity. The present invention finds particular
application in the modulation of neuronal function or processing to
affect a functional outcome. The modulation of neuronal function is
particularly useful with regard to the prevention, treatment, or
amelioration of neurological, psychiatric, psychological, conscious
state, behavioral, mood, and thought activity (unless otherwise
indicated these will be collectively referred to herein as
"neurological activity" which includes "psychological activity" or
"psychiatric activity"). When referring to a pathological or
undesirable condition associated with the activity, reference may
be made to a neurological disorder which includes "psychiatric
disorder" or "psychological disorder" instead of neurological
activity or psychiatric or psychological activity. Although the
activity to be modulated usually manifests itself in the form of a
disorder such as a attention or cognitive disorders (e.g., Autistic
Spectrum Disorders); mood disorder (e.g., major depressive
disorder, bipolar disorder, and dysthymic disorder) or an anxiety
disorder (e.g., panic disorder, posttraumatic stress disorder,
obsessive-compulsive disorder and phobic disorder);
neurodegenerative diseases (e.g., multiple sclerosis, Alzheimer's
disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease,
Huntington's Disease, Guillain-Barre syndrome, myasthenia gravis,
and chronic idiopathic demyelinating disease (CID)), movement
disorders (e.g, dyskinesia, tremor, dystonia, chorea and ballism,
tic syndromes, Tourette's Syndrome, myoclonus, drug-induced
movement disorders, Wilson's Disease, Paroxysmal Dyskinesias, Stiff
Man Syndrome and Akinetic-Ridgid Syndromes and Parkinsonism),
epilepsy, tinnitus, pain, phantom pain, diabetes neuropathy, one
skilled in the art appreciates that the invention may also find
application in conjunction with enhancing or diminishing any
neurological or psychiatric function, not just an abnormality or
disorder. Neurological activity that may be modulated can include,
but not be limited to, normal functions such as alertness,
conscious state, drive, fear, anger, anxiety, repetitive behavior,
impulses, urges, obsessions, euphoria, sadness, and the fight or
flight response, as well as instability, vertigo, dizziness,
fatigue, fotofobia, fonofobia, concentration dysfunction, memory
disorders, symptoms of traumatic brain injury (whether physical,
emotional, social or chemical), autonomic functions, which includes
sympathetic and/or parasympathetic functions (e.g., control of
heart rate), somatic functions, and/or enteric functions.
[0096] In certain embodiments, neurological disorders or conditions
that can be treated using the present invention include, for
example, but are not limited to cardiovascular diseases, e.g.,
atherosclerosis, coronary artery disease, hypertension,
hyperlipidemia, cardiomyopathy, volume retention; neuroinflammatory
diseases, e.g., viral meningitis, viral encephalitis, fungal
meningitis, fungal encephalitis, multiple sclerosis, charcot joint;
myasthenia gravis; orthopedic diseases, e.g., osteoarthritis,
inflammatory arthritis, reflex sympathetic dystrophy, Paget's
disease, osteoporosis; lymphoproliferative diseases, e.g.,
lymphoma, lymphoproliferative disease, Hodgkin's disease;
autoimmune diseases, e.g., Graves disease, hashimoto's, takayasu's
disease, kawasaki's diseases, arthritis, scleroderma, CREST
syndrome, allergies, dermatitis, Henoch-schlonlein purpura,
goodpasture syndrome, autoimmune thyroiditis, myasthenia gravis,
Reiter's disease, lupus, rheumatoid arthritis; inflammatory and
infectious diseases, e.g., sepsis, viral and fungal infections,
wound healing, tuberculosis, infection, human immunodeficiency
virus; pulmonary diseases, e.g., tachypnea, fibrotic diseases such
as cystic fibrosis, interstitial lung disease, desquamative
interstitial pneumonitis, non-specific interstitial pneumonitis,
lymphocytic interstitial pneumonitis, usual interstitial
pneumonitis, idiopathic pulmonary fibrosis; transplant related side
effects such as rejection, transplant-related tachycardia, renal
failure, typhlitis; transplant related bowel dysmotility,
transplant-related hyperreninemia; sleep disorders, e.g., insomnia,
obstructive sleep apnea, central sleep apnea; gastrointestinal
disorders, e.g., hepatitis, xerostomia, bowel dysmotility, peptic
ulcer disease, constipation, post-operative bowel dysmotility;
inflammatory bowel disease; endocrine disorders, e.g.,
hypothyroidism, hyperglycemia, diabetes, obesity, syndrome X;
cardiac rhythm disorders, e.g., sick sinus syndrome, bradycardia,
tachycardia, QT interval prolongation arrhythmias, atrial
arrhythmias, ventricular arrhythmias; genitourinary disorders,
e.g., bladder dysfunction, renal failure, hyperreninemia,
hepatorenal syndrome, renal tubular acidosis, erectile dysfunction;
cancer; fibrosis; skin disorders, e.g., wrinkles, cutaneous
vasculitis, psoriasis; aging associated diseases and conditions,
e.g., shy dragers, multi-system atrophy, osteoporosis, age related
inflammation conditions, degenerative disorders; autonomic
dysregulation diseases; e.g., headaches, concussions,
post-concussive syndrome, coronary syndromes, coronary vasospasm;
neurocardiogenic syncope; neurologic diseases such as epilepsy,
seizures, stress, bipolar disorder, migraines and chronic
headaches; conditions related to pregnancy such as amniotic fluid
embolism, pregnancy-related arrhythmias, fetal stress, fetal
hypoxia, eclampsia, preeclampsia; conditions that cause hypoxia,
hypercarbia, hypercapnia, acidosis, acidemia, such as chronic
obstructive lung disease, emphysema, cardiogenic pulmonary edema,
non-cardiogenic pulmonary edema, neurogenic edema, pleural
effusion, adult respiratory distress syndrome, pulmonary-renal
syndromes, interstitial lung diseases, pulmonary fibrosis, and any
other chronic lung disease; sudden death syndromes, e.g., sudden
infant death syndrome, sudden adult death syndrome; vascular
disorders, e.g., acute pulmonary embolism, chronic pulmonary
embolism, deep venous thrombosis, venous thrombosis, arterial
thrombosis, coagulopathy, aortic dissection, aortic aneurysm,
arterial aneurysm, myocardial infarction, coronary vasospasm,
cerebral vasospasm, mesenteric ischemia, arterial vasospasm,
malignant hypertension; primary and secondary pulmonary
hypertension, reperfusion syndrome, ischemia, cerebral vascular
accident, cerebral vascular accident and transient ischemic
attacks; pediatric diseases such as respiratory distress syndrome;
bronchopulmonary dysplasia; Hirschprung disease; congenital
megacolon, aganglionosis; ocular diseases such as glaucoma; and the
like.
[0097] The present invention finds particular utility in its
application to human neurological disorders, for example
psychological or psychiatric activity/disorder and/or physiological
disorders and/or other neurological conditions. One skilled in the
art appreciates that the present invention is applicable to other
animals which exhibit behavior that is modulated by the neuronal
tissue. This may include, for example, primates, canines, felines,
horses, elephants, dolphins, etc. Utilizing the various embodiments
of the present invention, one skilled in the art may be able to
modulate neuronal functional outcome to achieve a desirable
result.
[0098] One technique that offers the ability to affect neuronal
function is the delivery of electrical and/or ultrasonic and/or
magnetic stimulation for neuromodulation directly to target tissues
or predetermined tissue sites via an implanted device having a
probe. The probe can be stimulation lead or electrode assembly. The
electrode assembly may be one electrode, multiple electrodes, or an
array of electrodes in or around the target area. The proximal end
of the probe is coupled to a system to operate the device to
stimulate the target site. Thus, the probe is coupled to an
electrical signal source, which, in turn, is operated to stimulate
the target tissue or predetermined site.
[0099] Treatment regimens may vary as well, and often depend on the
health and age of the patient. Obviously, certain types of disease
will require more aggressive treatment, while at the same time,
certain patients cannot tolerate more taxing regimens. The
clinician will be best suited to make such decisions based on the
known subject's history.
[0100] The therapeutic system or of the present invention is
surgically implanted in the subject's body as described herein. One
of skill in the art is cognizant that a variety of electrodes or
electrical stimulation leads may be utilized in the present
invention. It is desirable to use an electrode or lead that
contacts or conforms to the target site for optimal delivery of
electrical stimulation. One such example, is a single multi contact
electrode with eight contacts separated by 21/2 mm each contract
would have a span of approximately 2 mm. Another example is an
electrode with two 1 cm contacts with a 2 mm intervening gap. Yet
further, another example of an electrode that can be used in the
present invention is a 2 or 3 branched electrode to cover the
target site. Each one of these three pronged electrodes have four
contacts 1-2 mm contacts with a center to center separation of 2 of
2.5 mm and a span of 1.5 mm
[0101] According to one embodiment of the present invention, the
target site is stimulated using stimulation parameters such as,
pulse width of about 1 to about 500 microseconds, more preferable,
about 1 to about 90 microseconds; frequency of about 1 to about 300
Hz, more preferably, about 100 to about 185 Hz; and voltage of
about 0.1 to about 10 volts, more preferably about 1 to about 10
volts. It is known in the art that the range for the stimulation
parameters may be greater or smaller depending on the particular
patient needs and can be determined by the physician. Other
parameters that can be considered may include the type of
stimulation for example, but not limited to acute stimulation,
subacute stimulation, and/or chronic stimulation.
[0102] Using the stimulation system of the present invention, the
predetermined site or target area is stimulated in an effective
amount or effective treatment regimen to decrease, reduce, modulate
or abrogate the neurological disorder. Thus, a subject is
administered a therapeutically effective stimulation so that the
subject has an improvement in the parameters relating to the
neurological disorder or condition including subjective measures
such as, for example, neurological examinations and
neuropsychological tests (e.g. Minnesota Multiphasic Personality
Inventory, Beck Depression Inventory, Mini-Mental Status
Examination (MMSE), Hamilton Rating Scale for Depression, Wisconsin
Card Sorting Test (WCST), Tower of London, Stroop task, MADRAS,
CGI, N-BAC, or Yale-Brown Obsessive Compulsive score (Y-BOCS)),
motor examination, and cranial nerve examination, and objective
measures including use of additional psychiatric medications, such
as anti-depressants, or other alterations in cerebral blood flow or
metabolism and/or neurochemistry.
[0103] Patient outcomes may also be tested by health-related
quality of life (HRQL) measures: Patient outcome measures that
extend beyond traditional measures of mortality and morbidity, to
include such dimensions as physiology, function, social activity,
cognition, emotion, sleep and rest, energy and vitality, health
perception, and general life satisfaction. (Some of these are also
known as health status, functional status, or quality of life
measures.)
[0104] Functional imaging may also be used to measure the
effectiveness of the treatment. This includes electrical methods
such as electroencephalography (EEG), magnetoencephalography (MEG),
single photon emission computed tomography (SPECT), as well as
metabolic and blood flow studies such as functional magnetic
resonance imaging (fMRI), and positron emission tomography (PET)
which can be utilized to localize brain function and dysfunction.
Also, electrophysiological examinations, such as electromyography
(EMG) and nerve conduction studies (NCS), can also be utilized to
assess the effectiveness of the treatment.
[0105] Clinical observations may indicate that the efficacy of
treatment may be correlated to the amplitude or intensity. For
example, stimulation of the somatosensory cortex may include
stimulation parameters that are sub-threshold. In the treatment of
pain, the intensity or amplitude of the electrical stimulation of
the somatosensory cortex is sub-threshold as to be beneficial to
alleviate pain and not exacerbate the pain condition.
[0106] In certain embodiments, it may be necessary to monitor the
stimulation signals or parameters in the instance that adjustments
need to be made to obtain the optimum benefit of the stimulation
system. Such monitoring may be performed by the subject or a
clinician. Monitoring may include observing any changes in symptoms
or any other clinical observations, as well as performing
neurophysiological studies, neurological examinations,
psychological examinations, functional imaging studies, etc. Based
upon the information obtained from this type of monitoring, the
stimulation parameters or signals may be adjusted if necessary.
[0107] Thus, stimulation signals or the series of electrical or
magnetic pulses used can affect neurons within a target neural
population. Stimulation signals may be defined or described in
accordance with stimulation signal parameters that include pulse
amplitude, pulse frequency, duty cycle, stimulation signal
duration, and/or other parameters. Electrical or magnetic
stimulation signals applied to a population of neurons can
depolarize neurons within the population toward their threshold
potentials. Depending upon stimulation signal parameters, this
depolarization can cause neurons to generate or fire action
potentials.
[0108] Neural stimulation that elicits or induces action potentials
in a functionally significant proportion of the neural population
to which the stimulation is applied is referred to as
supra-threshold stimulation; neural stimulation that fails to
elicit action potentials in a functionally significant proportion
of the neural population is defined as sub-threshold stimulation.
In general, supra-threshold stimulation of a neural population
triggers or activates one or more functions associated with the
neural population, but sub-threshold stimulation by itself does not
trigger or activate such functions. Supra-threshold neural
stimulation can induce various types of measurable or monitorable
responses in a patient. For example, supra-threshold stimulation
applied to a patient's motor cortex can induce muscle fiber
contractions in an associated part of the body to produce an
intended type of therapeutic, rehabilitative, or restorative
result. Still further, sub-threshold stimulation applied to a
patient's somatosensory cortex can alleviate pain without inducing
paresthesia, which is a sensation of numbness or tingling.
[0109] For purposes of this invention, beneficial or desired
clinical results include, but are not limited to, alleviation of
symptoms, improvement of symptoms, diminishment of extent of
disease, stabilized (i.e., not worsening) state of disease, delay
or slowing of disease progression, amelioration or palliation of
the disease state, and remission (whether partial or total),
whether objective or subjective. The improvement is any observable
or measurable improvement. Thus, one of skill in the art realizes
that a treatment may improve the patient condition, but may not be
a complete cure of the condition or disease.
[0110] In certain embodiments, in connection with improvement in
one or more of the above or other neurological disorders, the
electrical stimulation may have a "brightening" effect on the
person such that the person looks better, pain-free, feels better,
moves better, thinks better, and otherwise experiences an overall
improvement in quality of life.
[0111] The present invention relates to methods of affecting pain
(e.g., chronic pain) to regulate, prevent, treat, alleviate the
symptoms of and/or reduce the effects of pain. Although not wishing
to be bound to any particular definition or characterization,
chronic pain can generally be characterized as being nociceptive or
non-nociceptive pain. Nociceptive pain, also referred to as somatic
pain, involves direct activation of the nociceptors, such as
mechanical, chemical, and thermal receptors, found in various
tissues, such as bone, muscle, vessels, viscera, and cutaneous and
connective tissue. The afferent somatosensory pathways are thought
to be intact in nociceptive pain and examples of such pain include
cancer pain from bone or tissue invasion, non-cancer pain secondary
to degenerative bone and joint disease or osteoarthritis, and
failed back surgery. The foregoing examples of nociceptive pain are
in no way limiting and the methods of the present invention
encompass methods of affecting all types of nociceptive pain.
[0112] Non-nociceptive pain, also referred to as neuropathic pain,
or deafferentation pain, occurs in the absence of activation of
peripheral nociceptors. Non-nociceptive pain often results from
injury or dysfunction of the central or peripheral nervous system.
Such damage may occur anywhere along the neuroaxis and includes
thalamic injury or syndromes (also referred to as central pain,
supraspinal central pain, or post-stroke pain); stroke; traumatic
or iatrogenic trigeminal (trigeminal neuropathic) brain or spinal
cord injuries; phantom limb or stump pain; postherpetic neuralgia;
anesthesia dolorosa; brachial plexus avulsion; complex regional
pain syndrome I and II; postcordotomy dysesthesia; and various
peripheral neuropathies. The foregoing examples of non-nociceptive
pain are in no way limiting and the methods of the present
invention encompass methods of affecting all types of
non-nociceptive pain.
[0113] In certain embodiments, stimulation of the target brain
tissue may be provided to effectively treat pain, for example
chronic pain, acute pain, or subacute pain, deafferentation pain,
phantom pain, or any other type of sensory input that is related to
pain or any type of altered sensory input or altered sensory
perception.
[0114] Chronic pain is difficult to treat. After development of the
adult somatotopic representation, any alteration of the normal
sensory input (either increase or decrease) leads to a
reorganization of the entire somatosensory tract. This occurs daily
throughout life under influence of environmental stimuli (Kandel,
1991; Yuste and Sur, 1999). Thus, any type of event in the person's
life can result in alterations in this reorganization. For example,
phantom pain and phantom sensations are associated with
somatosensory cortex reorganization (Flor, 2003; Flor et al., 1995;
Peyron et al., 2000), such that the cortical area originally
corresponding to the amputated limb is taken over by sensory input
from adjacent areas on Penfield's somatosensory homunculus (Pons et
al., 1991). Furthermore magnetoecephalographic studies have shown a
clear correlation between the amount of phantom pain and the extend
of cortical reorganization (Flor et al., 1995).
[0115] In the somatosensory system, this reorganization seems to
occur in two phases (Pons et al., 1991; Doetsch et al., 1996).
Peripherally induced and maintained reorganization is initiated
immediately after injury or training (Doetsch et al., 1996; Wiech
et al., 2000). This first phase encompasses minutes to weeks and
leads to axonal growth and synaptic sprouting. If maintained by
peripheral input in a second phase permanent cortical,
thalamothalamic or corticothalamic connections occur (Pons et al.,
1991, Wieh et al., 2000) leading to intractable phantom limb pain.
Changes in peripheral input afterwards do not affect the changes of
the second phase (Wiech et al., 2000). This explains why the
phantom pain becomes very difficult to treat once it exists for
more than 6 months (Ramachandran and Hirstein, 1998).
[0116] Thus, the stimulation system and method used in the present
alters or modulates this cortical reorganization to treat pain. The
present invention utilizes techniques similar to the ones described
in U.S. application Ser. No. 10/993,888, which is incorporated
herein by reference in its entirety, as well as the techniques
described in De Ridder et al., 2004. The technique involves mapping
the brain mapping using standard functional neuroimaging techniques
such as PET scan, fMRI or MSI to determine a target area, for
example, the area of the brain possessing reorganization. Once
target area or area of reorganization is determined, then an
electrode, for example a cortex lead, can be implanted extradurally
in communication with the target area.
[0117] Still further, in certain embodiments, stimulation of a
target brain tissue site may be provided to effectively treat
fibromyalgia or other diffuse pain in any one or more regions of
the body.
[0118] In certain embodiments, stimulation of the target brain
tissue site may effectively treat one or more neurological disorder
associated with traumatic brain injury (TBI). Physiological
conditions associated with TBI that may be treated effectively
through stimulation of a brain tissue site include, for example,
intractable localized, diffuse, or other pain in the head, neck,
shoulders, upper extremities, or low back, fibromyalgia or other
diffuse pain in one or more regions of the body, or other pain
symptoms. Instead or in addition to such physiological conditions,
psychological and other conditions associated with TBI that may be
treated effectively through stimulation of the target brain tissue
include, for example, intractable nausea (e.g., from
gastroparesis), sleep disorders, chronic fatigue, behavioral
modifications (e.g., lassitude, reduced motivation, depression,
emotional distress, irritability, aggression, anxiety, erratic mood
swings, personality changes, and loss of enjoyment), sexual
dysfunction, and other conditions. Instead or in addition to
physiological, psychological, and other conditions such as those
described above, conditions associated with TBI that may be treated
effectively through stimulation of the target brain tissue include
decreased cognitive functioning in the form of, for example,
impaired memory (e.g., short-term memory, visual memory, and
auditory memory), reduced attention and concentration, and reduced
information processing capacity (e.g., learning capacity, ability
to process complex information, ability to operate simultaneously
on different information, ability to rapidly shift attention,
ability to plan and sequence, visuomotor capability, auditory
language comprehension, and verbal fluency).
V. Programming of the Stimulation System
[0119] During the operation of stimulation system 10 according to a
particular set of stimulation parameters, the efficacy of the
stimulation associated with the particular set of stimulation
parameters may decrease over time due to neuroplasticity of the
brain. Neuroplasticity refers to the ability of the brain to
dynamically reorganize itself in response to certain stimuli to
form new neural connections. This allows the neurons in the brain
to compensate for injury or disease and adjust their activity in
response to new situations or changes in their environment. With
respect to electrical stimulation, the reduction in efficacy due to
neuroplasticity can occur after just a few weeks of treatment. In
order to regain the same efficacy, a new set of efficacious
electrical stimulation parameters must be determined, the new set
of parameters must be entered into the system, and the system is
again used to electrically stimulate the brain according to the new
set of parameters to continue to treat the condition. This may
result in the additional time and expense associated with a return
visit to the treating physician for determining and entering the
new set of parameters. Especially where treatment is to continue
over a relatively long period of time, such as months or years,
this additional time and expense poses a significant drawback.
[0120] Thus, in certain embodiments, in addition to providing
therapeutic electrical stimulation to the brain for treating the
condition in the person's body, stimulation system 10 may be
capable of applying additional electrical stimulation to the brain
to reduce neuroplasticity effects associated with the therapeutic
electrical stimulation as described in U.S. application Ser. No.
10,994,008 entitled "Electrical Stimulation System, lead and Method
Providing Reduced Neuroplasticity Effects," which is incorporated
herein by reference in its entirety.
[0121] In one embodiment, the nature of the neuroplasticity
reducing electrical stimulation may be varied more or less
continually, in a predetermined or randomized manner, to prevent,
delay, or otherwise reduce the ability of the brain to adapt to the
neuroplasticity reducing electrical stimulation and dynamically
reorganize itself accordingly. In a more particular embodiment, the
neuroplasticity reducing electrical stimulation may be randomized
or otherwise varied about the therapeutic electrical stimulation to
achieve this result. In essence, the randomized or otherwise varied
neuroplasticity reducing electrical stimulation makes it more
difficult for the brain to dynamically reorganize itself to
overcome the effects of the therapeutic electrical stimulation.
[0122] In certain other embodiments, stimulation system 10 may
similarly be capable of applying additional electrical stimulation
to the brain to enhance, rather than reduce, neuroplasticity
effects associated with the therapeutic electrical stimulation. In
one embodiment, the nature of the neuroplasticity enhancing
electrical stimulation may controlled in a predetermined
non-randomized manner to promote, accelerate, or otherwise enhance
the ability of the brain to adapt to the neuroplasticity enhancing
electrical stimulation and dynamically reorganize itself
accordingly. In essence, the predetermined non-randomized
neuroplasticity enhancing electrical stimulation facilitates the
brain dynamically reorganizing itself in response to the
therapeutic electrical stimulation. It should be understood that
techniques analogous to some or all of those discussed below for
reducing neuroplasticity effects may be employed for enhancing
neuroplasticity effects.
[0123] FIG. 6 illustrates an example stimulation set 150. One or
more stimulation sets 150 may be provided, each stimulation set 150
specifying a number of stimulation parameters for the stimulation
set 150. For example, as described more fully below with reference
to FIGS. 7-8, multiple stimulation sets 150 may be executed in an
appropriate sequence according to a pre-programmed or randomized
stimulation program. Stimulation parameters for a stimulation set
150 may include an amplitude or intensity, a frequency, phase
information, and a pulse width for each of a series of stimulation
pulses that electrodes 18 are to deliver to the target nerve tissue
during a time interval during which stimulation set 150 is
executed, along with a polarity 152 for each electrode 18 within
each stimulation pulse. In general, electric fields are generated
between adjacent electrodes 18 having different polarities 152 to
deliver electrical stimulation pulses to nerve tissue. Stimulation
parameters may also include a pulse shape, for example, biphasic
cathode first, biphasic anode first, or any other suitable pulse
shape.
[0124] For reducing neuroplasticity effects associated with
therapeutic electrical stimulation, one or more stimulation
parameters for a stimulation set 150 may be randomized or otherwise
varied in any suitable manner within the time interval in which
stimulation set 150 is executed, spanning one or more stimulation
pulses within each stimulation pulse. For example, instead of or in
addition to randomizing or otherwise varying polarities 152 for
electrodes 18 as described below, the amplitude or intensity,
frequency, phase information, and pulse width may be randomized or
otherwise varied within predetermined ranges, singly or in any
suitable combination, within each stimulation pulse. As another
example, instead of or in addition to randomizing or otherwise
varying polarities 152 for electrodes 18 over multiple stimulation
pulses as described more fully below, the amplitude or intensity,
frequency, phase information, and pulse width may be randomized or
otherwise varied within predetermined ranges, singly or in any
suitable combination, over multiple stimulation pulses, where the
combination of stimulation parameters is substantially constant
within each stimulation pulse but different for successive
stimulation pulses. Such randomization or other variation of
stimulation parameters for a stimulation set 150 reduces the
ability of the brain to adapt to the neuroplasticity reducing
electrical stimulation and dynamically reorganize itself to
overcome the effects of the neuroplasticity reducing
stimulation.
[0125] The polarity for an electrode 18 at a time 154 beginning a
corresponding stimulation pulse or sub-interval within a
stimulation pulse may be a relatively positive polarity 152, a
relatively negative polarity 152, or an intermediate polarity 152
between the relatively positive polarity 152 and relatively
negative polarity 152. For example, the relatively positive
polarity 152 may involve a positive voltage, the relatively
negative polarity 152 may involve a negative voltage, and the
relatively intermediate polarity 152 may involve a zero voltage
(i.e. "high impedance"). As another example, the relatively
positive polarity 152 may involve a first negative voltage, the
relatively negative polarity 152 may involve a second negative
voltage more negative than the first negative voltage, and the
relatively intermediate polarity 152 may involve a negative voltage
between the first and second negative voltages. The availability of
three distinct polarities 152 for an electrode 18 may be referred
to as "tri-state" electrode operation. The polarity 152 for each
electrode 18 may change for each of the sequence of times 154
corresponding to stimulation pulses or to sub-intervals within a
stimulation pulse according to the stimulation parameters specified
for the stimulation set 150. For example, as is illustrated in FIG.
6 for an example stimulation set 150 for a lead 14 with sixteen
electrodes 18, the polarities 152 of the sixteen electrodes 18 may
change for each of the sequence of times 154. In the example of
FIG. 6, a relatively positive polarity 152 is represented using a
"1," a relatively intermediate polarity 152 is represented using a
"0," and a relatively negative polarity 152 is represented using a
"-1," although any suitable values or other representations may be
used.
[0126] Where appropriate, the polarity 152 for each electrode 18
may change in a predetermined or randomized manner, randomized
changes possibly being more effective with respect to any
neuroplasticity reducing stimulation for reasons described
above.
[0127] Where stimulation system 10 provides, in addition to
therapeutic electrical stimulation, electrical stimulation to
reduce neuroplasticity effects associated with the therapeutic
electrical stimulation, each stimulation pulse or sub-interval
within a stimulation pulse may be particular to the stimulation
being provided; that is, either to therapeutic electrical
stimulation or to neuroplasticity reducing electrical stimulation.
For example, one or more stimulation pulses or sub-intervals may be
designed to provide therapeutic electrical stimulation and one or
more other stimulation pulses or sub-intervals may be designed to
reduce neuroplasticity effects. In this case, the therapeutic
stimulation pulses or sub-intervals and neuroplasticity reducing
stimulation pulses or sub-intervals may be arranged temporally in
any suitable manner. A therapeutic stimulation pulse or
sub-interval may be separated from a successive therapeutic
stimulation pulse or sub-interval by any number of neuroplasticity
reducing stimulation pulses or sub-intervals and this number may be
the same between each pair of therapeutic stimulation pulses or
sub-intervals or may vary between each pair of therapeutic
stimulation pulses or sub-intervals in a predetermined or
randomized manner. As another example, one or more stimulation
pulses or sub-intervals may be designed to concurrently provide
both-therapeutic and neuroplasticity reducing electrical
stimulation.
[0128] Similarly, where stimulation system 10 provides, in addition
to therapeutic electrical stimulation, electrical stimulation to
reduce neuroplasticity effects associated with the therapeutic
electrical stimulation, each stimulation set 150 may be particular
to either the therapeutic electrical stimulation or the
neuroplasticity reducing electrical stimulation. For example, one
or more stimulation sets 150 may be designed to provide therapeutic
electrical stimulation and one or more other stimulation sets 150
may be designed to reduce neuroplasticity effects. In this case,
the therapeutic stimulation sets 150 and neuroplasticity reducing
stimulation sets 150 may be arranged temporally in any suitable
manner. A therapeutic stimulation set 150 may be separated from a
successive therapeutic stimulation set 150 by any number of
neuroplasticity reducing stimulation sets 150 and this number may
be the same between each pair of therapeutic stimulation sets 150
or may vary between each pair of therapeutic stimulation sets 150
in a predetermined or randomized manner. As another example, one or
more stimulation sets 150 may be designed to concurrently provide
both therapeutic and neuroplasticity reducing electrical
stimulation.
[0129] In addition, the amplitude or intensity, frequency, phase
information, or pulse width for a stimulation set 150 may be
particular to the stimulation being provided. For example,
therapeutic electrical stimulation may be provided using higher
amplitude electrical energy than is used for neuroplasticity
reducing electrical stimulation. In this case, the neuroplasticity
reducing electrical stimulation may be below the therapeutic target
threshold stimulation (i.e. below the threshold where therapeutic
electrical stimulation is provided to adjust the level of activity
in the target nerve tissue in the person's brain to treat the
condition in the person's body). Alternatively, neuroplasticity
reducing electrical stimulation may be provided using the same or a
higher amplitude electrical energy than is used for therapeutic
electrical stimulation (i.e. at or above the threshold where
therapeutic electrical stimulation is provided to adjust the level
of activity in the target nerve tissue in the person's brain to
treat the condition in the person's body). In this case, the
neuroplasticity reducing electrical stimulation's primary purpose
is not to produce a therapeutic effect, but rather to reduce
neuroplasticity. In this manner, the neuroplasticity reducing
electrical stimulation could have both a therapeutic and
neuroplasticity reducing effect.
[0130] FIG. 7 illustrates a number of example stimulation programs
156, each including a number of stimulation sets 150. One or more
simulation programs 156 may be set up to reduce neuroplasticity
effects associated with therapeutic electrical stimulation of the
brain. As described above, each stimulation set 150 specifies a
number of stimulation parameters for the stimulation set 150. In
one embodiment, within each stimulation program 156, stimulation
system 10 consecutively executes the sequence of one or more
stimulation sets 150 associated with stimulation program 156. The
sequence may be executed only once, repeated a specified number of
times, or repeated an unspecified number of times within a
specified time period. For example, as is illustrated in FIG. 8 for
the third example stimulation program 156c including eight
stimulation sets 150, each of the eight stimulation sets 150 is
consecutively executed in sequence. Although the time intervals 158
(t1-t0, t2-t1, etc.) during which the stimulation sets 150 are
executed are shown as being equal, the present invention
contemplates a particular stimulation set 150 being executed over a
different time interval 158 than one or more other stimulation sets
150 according to particular needs. One or more stimulation sets 150
within at least one stimulation program 156 may be set up to
provide reduced neuroplasticity effects associated with therapeutic
electrical stimulation of the brain.
[0131] Although stimulation system 10 is illustrated by way of
example as accommodating up to twenty-four stimulation programs 156
each including up to eight stimulation sets 150, the present
invention contemplates any appropriate number of stimulation
programs 156 each including any appropriate number of stimulation
sets 150. For example, in a very simple case, a single stimulation
program 156 may include a single stimulation set 150, whereas in a
very complex case more than twenty-four stimulation programs 156
may each include more than eight stimulation sets 150.
[0132] In one embodiment, stimulation system 10 executes only a
single stimulation program 156 in response to user selection of
that stimulation program for execution. In another embodiment,
during a stimulation period, stimulation system 10 executes a
sequence of pre-programmed stimulation programs 156 for each lead
14 until the stimulation period ends. Depending on the length of
the stimulation period and the time required to execute a sequence
of stimulation programs 156, the sequence may be executed one or
more times. For example, the stimulation period may be defined in
terms of a predetermined number of cycles each involving a single
execution of the sequence of stimulation programs 156, the sequence
of stimulation programs 156 being executed until the predetermined
number of cycles has been completed. As another example, the
stimulation period may be defined in terms of time, the sequence
of. stimulation programs 156 being executed until a predetermined
time interval has elapsed or the patient or another user manually
ends the stimulation period. Although a sequence of stimulation
programs 156 is described, the present invention contemplates a
single stimulation program being executed one or more times during
a stimulation period according to particular needs. Furthermore,
the present invention contemplates each stimulation program 156
being executed substantially immediately after execution of a
previous stimulation program 156 or being executed after a suitable
time interval has elapsed since completion of the previous
stimulation program 156. Where stimulation system 10 includes
multiple leads 14, stimulation programs 156 for a particular lead
14 may be executed substantially simultaneously as stimulation
programs 156 for one or more other leads 14, may be alternated with
stimulation programs 156 for one or more other leads 14, or may be
arranged in any other suitable manner with respect to stimulation
programs 156 for one or more other leads 14.
[0133] Where stimulation system 10 provides, in addition to
therapeutic electrical stimulation, electrical stimulation to
reduce neuroplasticity effects, each stimulation program 156 may be
particular to either the therapeutic electrical stimulation or the
neuroplasticity reducing electrical stimulation. For example, one
or more stimulation programs 156 may be designed to provide
therapeutic electrical stimulation and one or more other
stimulation programs 156 may be designed to reduce neuroplasticity
effects. In this case, the therapeutic stimulation programs 156 and
the neuroplasticity reducing stimulation programs 156 may be
arranged temporally in any manner. A therapeutic stimulation
program 156 may be separated from a successive therapeutic
stimulation program 156 by any number of neuroplasticity reducing
stimulation programs 156 and this number may be the same between
each pair of therapeutic stimulation programs 156 or may vary
between each pair of therapeutic stimulation programs 156 in a
predetermined or randomized manner. As another example, one or more
stimulation programs 156 may be set up to concurrently provide both
therapeutic and neuroplasticity reducing electrical
stimulation.
[0134] In general, each stimulation program 156 may, but need not
necessarily, be set up for electrical stimulation of different
target nerve tissue in a person's brain. As an example, where
therapeutic electrical stimulation of target nerve tissue in a
particular region 38 of the brain is desired, one or more
stimulation programs 156 may be set up for therapeutic electrical
stimulation of the target nerve tissue in the particular region 38
and one or more other stimulation programs 156 may be set up for
electrical stimulation of the same target nerve tissue in the
particular region 38 to reduce neuroplasticity effects associated
with the therapeutic electrical stimulation. As another example,
one or more stimulation programs 156 may be set up for therapeutic
electrical stimulation of target nerve tissue in a particular
region 38 of the brain and one or more other stimulation programs
156 may be set up for electrical stimulation of different nerve
tissue in either the same region 38 or in a different region 38 of
the brain to reduce neuroplasticity effects associated with the
therapeutic electrical stimulation.
[0135] As described above, in one embodiment, the nature of any
neuroplasticity reducing electrical stimulation may be varied more
or less continually, whether in a predetermined or randomized
manner, to reduce, prevent, delay, enhance, promote, or otherwise
control the ability of the brain to adapt to the neuroplasticity
reducing electrical stimulation and dynamically reorganize itself
accordingly. In a more particular embodiment, where the
neuroplasticity reducing electrical stimulation is provided
concurrently with therapeutic electrical stimulation, the
neuroplasticity reducing electrical stimulation may be randomized
or otherwise varied about the therapeutic electrical stimulation to
achieve this result. In essence, the randomized or otherwise varied
neuroplasticity reducing electrical stimulation makes it more
difficult for the brain to dynamically reorganize itself to
overcome the effects of the therapeutic electrical stimulation.
[0136] The present invention contemplates any suitable circuitry
within stimulation source 12 for generating and transmitting
electrical stimulation pulses for electrically stimulating target
nerve tissue in a person's brain to treat a condition in the
person's body and, where appropriate, to reduce, enhance, or
otherwise treat neuroplasticity effects in the person's brain,
whether separate from or concurrently with the therapeutic
electrical stimulation. Example circuitry that may be used is
illustrated and described in U.S. Pat. No. 6,609,031 B1, which is
hereby incorporated by reference herein as if fully illustrated and
described herein.
VI. EXAMPLES
[0137] The following examples are included to demonstrate preferred
embodiments of the invention. It should be appreciated by those of
skill in the art that the techniques disclosed in the examples
which follow represent techniques discovered by the inventor to
function well in the practice of the invention, and thus can be
considered to constitute preferred modes for its practice. However,
those of skill in the art should, in light of the present
disclosure, appreciate that many changes can be made in the
specific embodiments which are disclosed and still obtain a like or
similar result without departing from the spirit and scope of the
invention.
Example 1
Treatment of Deafferentation Pain
[0138] In general, patients with intractable deafferentation pain
were selected for neuronavigated transcranial magnetic stimulation
(TMS) of the somatosensory cortex.
[0139] Prior to TMS a fMRI of the somatosensory cortex was
performed demonstrating the area of reorganization. A fMRI was
performed, applying tactile stimulation at the deafferented area,
inducing hyperalgesia/allodynia. The FMRI demonstrated an area of
hyperactivity on the contralateral primary/secondary somatosensory
cortex.
[0140] TMS was used to verify the potential benefit of electrical
stimulation of the somatosensory cortex. Subsequently a TMS was
performed by means of fMRI based neuronavigation (Treon, Medtronic)
at 90% motor threshold (MT). If pain suppression was obtained,
placebo stimulation at the same site was performed. Stimulation at
110% MT was also tested to exclude motor cortex involvement. The
pain suppression obtained by TMS was transient.
[0141] Five of the 8 patients had beneficial effect with TMS and
underwent an implantation of a cortical electrode on the
somatosensory cortex. Continuous pain suppression was obtained by
implantation of an epidural electrode (Lamitrode 44, ANS Inc.
Plano, Tex.) on the area of cortical reorganization as located by
fMRI based neuronavigation. In 3 of 5 patients this treatment was
highly beneficial, in 1 partly successful due to multiple
recurrences, requiring reprogrammation, in 1 pain recurs after
initial suppression.
[0142] Four out of five patients remained pain free without
paresthesias induced by the cortical stimulation. In one of these
patients multiple reprogrammations were required for continuing
pain suppression. Initially 4-7 Hz stimulation was used at low
amplitudes (0.5-2 mA). Stimulation at higher frequencies and
amplitudes induced pain in the area of deafferentation. In one
patients pain recurred after initial suppression.
[0143] Thus, stimulation of the somatosensory cortex stimulation
can be used for pain control in patients presenting with
intractable deafferentation pain.
Example 2
Treatment of Pain
Patient History
[0144] A 53 year old woman presented with a 10 year history of
persistent lancinating pain in the right supraorbital region. The
pain arose a few weeks after a surgical excision of basocellular
carcinoma on the right forehead. Initially she suffered a normal
post operative pain progressively evolving to a constant, sharp
lancinating pain. Multiple surgical procedures followed with
aggravation of the symptoms.
[0145] Except for the pain she also developed a sensation of her
right eye being located on her right maxillary arc. Despite a
normal vision as demonstrated by an extensive
neuro-ophthalmological work-up, the phantom sensation often induced
a misperception of the position of surrounding objects causing her
to run into obstacles ipsilateral to the phantom sensation.
Clinical Examination
[0146] A hyperalgesia and a loss of sensation of temperature and
vibration in the right VI dermatoma were noted. Tactile stimulation
of the medial cornea and upper eyelashes of the right eye were
sensed at the phantom eye at the right maxillary arc. Tactile
stimulation of the medial cornea and medial upper and lower
eyelashes of the phantom eye were sensed at the corresponding areas
at the ipsilateral eye. Phantom corneal reflex was not elicited.
Further clinical exams were normal.
Functional Magnetic Resonance Imaging (fMRI)
[0147] fMRI was performed on a 3T MR system using the blood oxygen
level dependend (BOLD) method and consisted of acquisition of whole
brain FFE-EPI images (resolution of 3.times.3.times.4 mm,
TE/TR=33/3000 ms) as well as high resolution T1 weighted anatomical
images. The stimulation paradigm was a blocked fMRI design
alternating 30 s epochs of sensory stimulation (the patient rubbed
the painful right V1 skin area using her left hand) with 30 s
epochs of non-stimulation (rest). Statistical comparison of brain
activity during skin stimulation to rest resulted in a significant
area of activity in the left postcentral gyrus corresponding to the
area of perception of pain located within the left primary sensory
cortex (FIG. 9). Other areas of activity were found in left primary
sensorimotor cortex, supplementary motor area, right cerebellum,
and were related to the motor activity of the left hand and arm
rubbing the right VI skin area.
Transcranial Magnetic Stimulation (TMS)
[0148] Transcranial magnetic stimulation was performed with a Super
Rapid magnetic stimulator (Magstim Inc, Wales, UK.) allowing
stimulation in a range of 1 to 50 Hz. Magnetic stimulation was
performed after neuronavigation guided localization (Stealth,
Sofamor Danek, Colo., USA) of the area of cortical reorganization
based on the predefined area on the FMRI. Several series of
stimulation were applied with different frequencies and intensities
on target and adjacent areas.
[0149] The transcranial magnetic stimulation (TMS) caused a maximum
reduction of 80% of the supraorbital pain and a complete
disappearance of the phantom sensation.
[0150] The suppression of the pain was obtained immediately after
starting the TMS and had a residual effect whereas the phantom
shifted back to its normal position after a longer period of
stimulation.
[0151] TMS on target (FIG. 9) using a rate of 1 pulse per second
(pps) during 60 seconds at an intensity of 90% motor threshold (MT)
caused an immediate pain reduction of 80% and complete
disappearance of the phantom sensation after 25 seconds of
stimulation. The same pain relief was obtained with TMS at a rate
of 5 pps and 90% MT but the phantom eye shifted back in 10 seconds.
TMS with 10 consecutive 500 ms bursts at 20 pps at 90% MT had no
beneficial effect on the pain or the phantom. Lowering the output
to 80% MT at a rate of 1 pps still induced an 80% pain reduction
but the phantom progressively disappeared after 35 seconds of
stimulation. Sham stimulation had no effect. TMS at 110% MT did not
elicit any motor activity. (FIG. 10)
[0152] Consecutively an epidural octopolar electrode (Lamitrode 44,
Advanced Neuromodulation Systems Inc, Tx, USA.) was implanted for
electrical stimulation of the somatosensory cortex. The electrode
was located at the predefined target using FMRI based frameless
stereotaxic guidance. The leads of the electrodes were tunneled
subcutaneously to the abdominal wall and connected to the internal
pulse generator (IPG) (Genesis, Advanced Neuromodulation Systems
Inc. Tx, USA) and implanted in a subcutaneous pocket. The
postoperative course was uneventful.
[0153] After recovery from the surgery the patient felt the same
pain and phantom sensation as preoperatively. On the first
postoperative day the IPG was activated and a complete suppression
of pain and a complete disappearance of the phantom eye was
obtained. Stimulation parameters were set in an alternating 30
seconds ON and 60 seconds OFF mode with 50 .mu.sec pulse width, 4
pps at 1.0 mA. Stimulating with these parameters induced
paresthesias in the right supraorbital region. Lowering the
intensity to 0.3 mA had a similar effect on the pain and phantom
but without any paresthesias. Furthermore the patient had no
problem in determining the exact position of surrounding objects
after stimulation parameters were set.
[0154] Patient was discharged 4 days after surgery completely free
of pain and phantom sensation and remained as such after 12 months
follow-up.
[0155] Postoperative images revealed a correct position of the lead
on the somatosensory cortex and not on the motor cortex (FIGS. 11A
and B). Thus, somatosensory cortex stimulation can be used for
anaesthesia dolorosa and phantom sensation.
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[0193] Although the present invention and its advantages have been
described in detail, it should be understood that various changes,
substitutions and alterations can be made herein without departing
from the spirit and scope of the invention as defined by the
appended claims. Moreover, the scope of the present application is
not intended to be limited to the particular embodiments of the
process, machine, manufacture, composition of matter, means,
methods and steps described in the specification. As one of
ordinary skill in the art will readily appreciate from the
disclosure of the present invention, processes, machines,
manufacture, compositions of matter, means, methods, or steps,
presently existing or later to be developed that perform
substantially the same function or achieve substantially the same
result as the corresponding embodiments described herein may be
utilized according to the present invention. Accordingly, the
appended claims are intended to include within their scope such
processes, machines, manufacture, compositions of matter, means,
methods, or steps.
* * * * *