U.S. patent application number 11/641977 was filed with the patent office on 2007-05-03 for treatment of movement disorders by brain stimulation.
Invention is credited to Kelly H. McClure, James P. McGivern, Todd K. Whitehurst.
Application Number | 20070100393 11/641977 |
Document ID | / |
Family ID | 37526626 |
Filed Date | 2007-05-03 |
United States Patent
Application |
20070100393 |
Kind Code |
A1 |
Whitehurst; Todd K. ; et
al. |
May 3, 2007 |
Treatment of movement disorders by brain stimulation
Abstract
Systems for treating a movement disorder include a system
control unit configured to be implanted at least partially within a
patient and to generate at least one stimulus in accordance with
one or more stimulation parameters adjusted to treat the movement
disorder. The systems further include a programmable memory unit in
communication with the system control unit and programmed to store
the one or more stimulation parameters to at least partially define
the stimulus such that the stimulus is configured to treat the
movement disorder. A means for applying the stimulus to one or more
stimulation sites within the patient is operably connected to the
system control unit.
Inventors: |
Whitehurst; Todd K.;
(Frazier Park, CA) ; McGivern; James P.;
(Stevenson Ranch, CA) ; McClure; Kelly H.; (Simi
Valley, CA) |
Correspondence
Address: |
Travis K. Laird;Rader, Fishman & Grauer PLLC
River Park Corporate Center One
10653 S. River Front Pkwy., Ste. 150
South Jordan
UT
84095
US
|
Family ID: |
37526626 |
Appl. No.: |
11/641977 |
Filed: |
December 19, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10428744 |
May 2, 2003 |
7151961 |
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11641977 |
Dec 19, 2006 |
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60383316 |
May 24, 2002 |
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Current U.S.
Class: |
607/45 ;
607/48 |
Current CPC
Class: |
A61N 1/37205 20130101;
A61N 1/36082 20130101; A61N 1/325 20130101; A61M 2210/0693
20130101; A61M 5/14276 20130101; A61N 1/0529 20130101; A61K 9/0085
20130101; A61N 1/0534 20130101; A61M 2205/3523 20130101; A61M
2205/3569 20130101 |
Class at
Publication: |
607/045 ;
607/048 |
International
Class: |
A61N 1/18 20060101
A61N001/18 |
Claims
1. A system for treating a movement disorder, said system
comprising: a system control unit configured to be implanted
entirely within the brain of a patient and to generate at least one
stimulus in accordance with one or more stimulation parameters
adjusted to treat said movement disorder; a programmable memory
unit in communication with said system control unit and programmed
to store said one or more stimulation parameters to at least
partially define said stimulus such that said stimulus is
configured to increase neural activity of the nucleus tractus
solitarius; and means, operably connected to said system control
unit, for applying said stimulus to the nucleus tractus
solitarius.
2. The system of claim 1, wherein said means for applying said at
least one stimulus comprises at least one electrode, and wherein
said stimulus comprises a stimulation current delivered to the
nucleus tractus solitarius via said at least one electrode.
3. The system of claim 2, wherein said stimulation current
comprises one or more stimulation pulses having: an amplitude
substantially greater than or equal to 0.05 milliamps and
substantially less than or equal to 5.0 milliamps; and a frequency
substantially less than or equal to 100 Hertz.
4. The system of claim 1, wherein said means for applying said at
least one stimulus comprises at least one infusion outlet, and
wherein said stimulus comprises one or more drugs delivered to the
nucleus tractus solitarius via said at least one infusion
outlet.
5. The system of claim 4, wherein said one or more drugs comprise
at least one or more of an excitatory neurotransmitter, an
excitatory cortical neurotransmitter agonist, an inhibitory
neurotransmitter antagonist, an agent that increases the level of
an excitatory neurotransmitter, and an agent that decreases the
level of an inhibitory neurotransmitter.
6. The system of claim 1, further comprising: a sensor
communicatively coupled to said system control unit and configured
to sense at least one condition related to said movement disorder;
wherein said system control unit uses said at least one sensed
condition to adjust one or more of said stimulation parameters.
7. A system for treating a movement disorder, said system
comprising: a system control unit configured to be implanted at
least partially within a patient and to generate at least one
stimulus in accordance with one or more stimulation parameters
adjusted to treat said movement disorder; a programmable memory
unit in communication with said system control unit and programmed
to store said one or more stimulation parameters to at least
partially define said stimulus such that said stimulus is
configured to increase neural activity of at least one stimulation
site within the brain of said patient; and means, operably
connected to said system control unit, for applying said stimulus
to said at least one stimulation site; wherein said at least one
stimulation site comprises at least one or more of the nucleus
tractus solitarius, pallido-subthalamic tracts, and putamen to GPi
fibers.
8. The system of claim 7, wherein said means for applying said at
least one stimulus comprises at least one electrode, and wherein
said stimulus comprises a stimulation current delivered to said at
least one stimulation site via said at least one electrode.
9. The system of claim 8, wherein said stimulation current
comprises one or more stimulation pulses having a frequency
substantially less than or equal to 100 Hertz.
10. The system of claim 8, further comprising: a lead coupled to
said system control unit; wherein said at least one electrode is
disposed on a surface of said lead.
11. The system of claim 8, wherein said at least one electrode is
disposed on an outer surface of said system control unit.
12. The system of claim 7, wherein said means for applying said at
least one stimulus comprises at least one infusion outlet, and
wherein said stimulus comprises one or more drugs delivered to said
at least one stimulation site via said at least one infusion
outlet.
13. The system of claim 12, wherein said means for applying said at
least one stimulus further comprises at least one catheter coupling
said infusion outlet to said system control unit.
14. The system of claim 7, further comprising: a sensor
communicatively coupled to said system control unit and configured
to sense at least one condition related to said movement disorder;
wherein said system control unit uses said at least one sensed
condition to adjust one or more of said stimulation parameters.
15. A system for treating a movement disorder, said system
comprising: a system control unit configured to be implanted at
least partially within a patient and to generate at least one
stimulus in accordance with one or more stimulation parameters
adjusted to treat said movement disorder; a programmable memory
unit in communication with said system control unit and programmed
to store said one or more stimulation parameters to at least
partially define said stimulus such that said stimulus is
configured to decrease neural activity of at least one stimulation
site within the brain of said patient; and means, operably
connected to said system control unit, for applying said stimulus
to said at least one stimulation site; wherein said at least one
stimulation site comprises at least one or more of the
pallido-thalamic axons, putamen to GPe fibers, and
subthalamo-pallidal fibers.
16. The system of claim 15, wherein said means for applying said at
least one stimulus comprises at least one electrode, and wherein
said stimulus comprises a stimulation current delivered to said at
least one stimulation site via said at least one electrode.
17. The system of claim 16, wherein said stimulation current
comprises one or more stimulation pulses having a frequency
substantially greater than or equal to 100 Hertz.
18. The system of claim 16, further comprising: a lead coupled to
said system control unit; wherein said at least one electrode is
disposed on a surface of said lead.
19. The system of claim 16, wherein said at least one electrode is
disposed on an outer surface of said system control unit.
20. The system of claim 15, wherein said means for applying said at
least one stimulus comprises at least one infusion outlet, and
wherein said stimulus comprises one or more drugs delivered to said
at least one stimulation site via said at least one infusion
outlet.
21. The system of claim 20, wherein said means for applying said at
least one stimulus further comprises at least one catheter coupling
said infusion outlet to said system control unit.
22. The system of claim 15, further comprising: a sensor
communicatively coupled to said system control unit and configured
to sense at least one condition related to said movement disorder;
wherein said system control unit uses said at least one sensed
condition to adjust one or more of said stimulation parameters.
Description
RELATED APPLICATIONS
[0001] The present application is a continuation application of
U.S. application Ser. No. 10/428,744, filed May 2, 2003, which
application claims the benefit of Provisional Application Ser. No.
60/383,316, filed May 24, 2002. Both applications are incorporated
herein by reference in their entireties.
BACKGROUND
[0002] Movement disorders are neurologic syndromes characterized by
either an excess or a paucity of movement. These disorders affect
approximately two million Americans, including over one million
suffering from benign essential tremor, and half a million
suffering from Parkinson's Disease. A substantial percentage of
those afflicted with movement disorders experience a significant
decrease in quality of life, suffering such problems as
incapacitating tremor, limited mobility, bradykinesia (difficulty
consciously initiating movement), dysarthria (difficulty with
speech), and consequent social isolation. The etiology of many
movement disorders, e.g., benign essential tremor, is poorly
understood. For other movement disorders, e.g., Parkinson's
disease, the mechanism of the disorder and brain cells affected
have been identified, but even with optimal care the disease may
not be reversed and may even continue to progress.
[0003] Parkinson's Disease is caused by a gradual loss of
dopaminergic (i.e., dopamine-secreting) neurons in the substantia
nigra. Consequently, levels of dopamine decrease in the striatum
(i.e., the putamen and the caudate nucleus). Although dopamine has
both excitatory and inhibitory effects on the striatum, the
predominant effect of the loss of dopamine is decreased inhibition
(by GABA) of the internal segment of the globus pallidus. This
leads to increased GABA output from the internal segment of the
globus pallidus, which inhibits the ventrolateral thalamus. This
leads in turn to decreased inhibition of (and ultimately decreased
control over) the motor cortex. The subthalamic nucleus appears to
increase its activity in Parkinson's Disease as well, and this is
believed to contribute to the symptoms of the disease.
[0004] Essential Tremor (ET), a.k.a., Benign Essential Tremor, is
the most common movement disorder. It is a syndrome characterized
by a slowly progressive postural and/or kinetic tremor, usually
affecting both upper extremities. The prevalence of ET in the US is
estimated at 0.3-5.6% of the general population. A 45-year study of
ET in Rochester, Minnesota reported an age- and gender-adjusted
prevalence of 305.6 per 100,000 and an incidence of incidence of
23.7 per 100,000.
[0005] ET affects both sexes equally. The prevalence of ET
increases with age. There are bimodal peaks of onset--one in late
adolescence to early adulthood and a second peak in older
adulthood. The mean age at presentation is 35-45 years. ET usually
presents by 65 years of age and virtually always by 70 years.
Tremor amplitude slowly increases over time. Tremor frequency
decreases with increasing age. An 8 12 Hz tremor is seen in young
adults and a 6 8 Hz tremor is seen in the elderly. Although ET is
progressive, no association has been found between age of onset and
severity of disability.
[0006] Disability stemming from ET is common. Significant changes
in livelihood and socializing are reported by 85% of individuals
with ET, and 15% report being seriously disabled due to ET.
Decreased quality of life results from both loss of function and
embarrassment. In a study of hereditary ET, 60% did not seek
employment, 25% changed jobs or took early retirement, 65% did not
dine out, 30% did not attend social functions, and 20% stopped
driving.
SUMMARY
[0007] Systems for treating a movement disorder include a system
control unit configured to be implanted at least partially within a
patient and to generate at least one stimulus in accordance with
one or more stimulation parameters adjusted to treat the movement
disorder. The systems further include a programmable memory unit in
communication with the system control unit and programmed to store
the one or more stimulation parameters to at least partially define
the stimulus such that the stimulus is configured to treat the
movement disorder. A means for applying the stimulus to one or more
stimulation sites within the patient is operably connected to the
system control unit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] The accompanying drawings illustrate various embodiments of
the principles described herein and are a part of the
specification. The illustrated embodiments are merely examples and
do not limit the scope of the disclosure.
[0009] FIG. 1A depicts the dorsal surface of the brain stem
according to principles described herein.
[0010] FIGS. 1B and 1C are section views through the brain stem
depicted in FIG. 1A according to principles described herein.
[0011] FIG. 2A depicts the medial surface of the brain according to
principles described herein.
[0012] FIG. 2B is a coronal section view of the brain of FIG. 2A
according to principles described herein.
[0013] FIGS. 3A, 3B, and 3C show some possible configurations of an
implantable microstimulator of the present invention according to
principles described herein.
[0014] FIG. 4 illustrates a lateral view of the skull and
components of an exemplary system control unit according to
principles described herein.
[0015] FIG. 5 illustrates internal and external components of a
stimulation system according to principles described herein.
[0016] FIG. 6 illustrates various external components of a system
control unit according to principles described herein.
[0017] FIG. 7 depicts a system of implantable devices that
communicate with each other and/or with external
control/programming devices according to principles described
herein.
[0018] Throughout the drawings, identical reference numbers
designate similar, but not necessarily identical, elements.
DETAILED DESCRIPTION
[0019] Methods and systems for treating one or more movement
disorders are described herein. An implanted stimulator is
configured to apply at least one stimulus to a stimulation site
within a patient in accordance with one or more stimulation
parameters. The stimulus is configured to treat a movement disorder
and may include electrical stimulation and/or drug stimulation. As
used herein, and in the appended claims, "treating" a movement
disorder refers to any amelioration of one or more causes and/or
one or more symptoms of the movement disorder.
[0020] In the following description, for purposes of explanation,
numerous specific details are set forth in order to provide a
thorough understanding of the present systems and methods. It will
be apparent, however, to one skilled in the art that the present
systems and methods may be practiced without these specific
details. Reference in the specification to "one embodiment" or "an
embodiment" means that a particular feature, structure, or
characteristic described in connection with the embodiment is
included in at least one embodiment. The appearance of the phrase
"in one embodiment" in various places in the specification are not
necessarily all referring to the same embodiment.
[0021] The pathophysiology of many movement disorders is unknown.
For example, the cause of essential tremor ("ET") is unknown.
However, it has been hypothesized that ET is the result of an
abnormally functioning central oscillator, which is located in
Guillain Mollaret triangle near the brainstem, and involves the
inferior olivary nucleus. It is also believed that there is
probable involvement of cerebellar-brainstem-thalamic-cortical
circuits.
[0022] When Harmaline, a Monoamine Oxidase (MAO) inhibitor, is
administered to primates with lesions of ventromedial tegmental
tract or lateral cerebellum, an ET-like tremor is produced. In
these animals, inferior olivary nucleus neurons file synchronously
at the tremor frequency. C-2-deoxyglucose PET studies demonstrate
hypermetabolism in the inferior olivary nuclei of rats and cats
with harmaline-induced tremor. Stimulation of the vagus nerve
helped resolve tremor in rats with harmaline-induced tremor.
[0023] In patients with ET, [.sup.18F]-fluorodeoxyglucose PET
studies identified increased glucose consumption in the medulla.
[.sup.15O]-H.sub.2O PET studies demonstrate an increase in
medullary regional cerebral blood flow (CBF) in subjects with ET,
only after the administration of ethanol, and showed bilateral
overactivity of cerebellar circuitry.
[0024] The nucleus tractus solitarius (NTS) sends fibers
bilaterally to the reticular formation and hypothalamus that are
important in the reflex control of cardiovascular, respiratory, and
gastrointestinal functions. The NTS also provides input to the
dorsal motor nucleus of the vagus that enables the parasympathetic
fibers of the vagus nerve to control these reflex responses. The
NTS runs the entire length of the medulla oblongata, and the NTS
receives somatic sensory input from all cranial nerves, with much
of its input coming from the vagus nerve. Since the NTS receives
much of its input from the vagus nerve, and since electrical
stimulation of the vagus nerve has been demonstrated to be
effective in the treatment of an animal model of essential tremor
(i.e., for harmaline-induced tremor), then electrical stimulation
of the NTS may be effective in the treatment of movement disorders
such as essential tremor.
[0025] Patients suffering from tremor and other symptoms may
undergo surgery to lesion a part of the brain (e.g., the ventral
intermediate (Vim) nucleus of the thalamus the internal segment of
the globus pallidus (GPi), or the subthalamic nucleus (STN)), which
may afford some relief. However, a lesion is irreversible, and may
lead to side effects such as dysarthria or cognitive disturbances.
Additionally, lesions generally yield effects on only one side of
the body (the contra-lateral side), and bilateral lesions are
significantly more likely to produce side effects. Other surgical
procedures, such as fetal tissue transplants, are costly and
unproven.
[0026] Other areas of the brain exhibit decreased neural activity
in some patients with movement disorders. For instance, some
Parkinson's disease patients demonstrate decreased neural activity
in parts of the caudate and putamen, the external segment of the
globus pallidus (GPe), substantia nigra, and/or parts of the
thalamus.
[0027] An article published online by Gill, et al. describes
delivery of glial cell line-derived neurotrophic factor (GDNF)
directly into the putamen of five Parkinson patients in a phase 1
safety trial. [See Gill, et al. "Direct brain infusion of glial
cell line-derived neurotrophic factor in Parkinson disease." Nature
Medicine epub ahead of print: Mar. 2003, 31.] Baseline positron
emission tomography (PET) scans indicated that the posterior
segment of the putamen in all patients had low [.sup.18F]dopa
uptake. After 18 months, PET scans showed a 28% increase in putamen
dopamine storage, in contrast to the predicted decline of up to 20%
over this period for Parkinson disease patients. The authors note,
however, that the exact mechanism by which GDNF works has yet to be
established.
[0028] Levy, et al., 2001, present data based on microelectrode
recordings from the GPi and the STN during administration of
apomorphine, a fast-acting non-selective D.sub.1-dopamine and
D.sub.2-dopamine receptor agonist. [See Levy, et al. "Effects of
apomorphine on subthalamic nucleus and globus pallidus internus
neurons in patients with Parkinson's disease." Journal of
Neurophvsiology 2001 July;86(1):249-60.] Apomorphine has previously
been demonstrated to ameliorate symptoms of Parkinson's disease. In
the study, the authors administered doses of apomorphine sufficient
to produce relief of Parkinson symptoms, but not sufficient to
induce common side effects such as dyskinetic movements. Following
baseline microelectrode recordings, apomorphine was administered.
The spontaneous discharge of neurons encountered before, during,
and after the effect of apomorphine had waned was also sampled.
[0029] A reduction in Parkinson symptoms (e.g., limb tremor) was
observed in patients when apomorphine reached therapeutic levels.
Apomorphine significantly decreased the overall firing rates of GPi
neurons, but there was no change in the overall firing rate of
neurons in the STN. Concurrent with a reduction in limb tremor, the
percentage of cells with tremor-related activity (i.e., tremor
cells) was found to be significantly reduced from 19% to 6% in the
STN and from 14% to 0% in the GPi following apomorphine
administration. Apomorphine also decreased the firing rate of STN
tremor cells. As the effects of apomorphine waned, the overall
firing rates of GPi neurons increased. In contrast to the findings
above, Stefani, et al., 2002, found that administration of
apomorphine did indeed reduce the firing rates of all STN cells in
patients with Parkinson's disease, concurrent with a reduction in
the clinical symptoms of Parkinson's disease. [See Sefani, et al.,
"Subdyskinetic apomorphine responses in globus pallidus and
subthalamus of parkinsonian patients: lack of clear evidence for
the `indirect pathway`." Clinical Neurophvsioloqy August
2002;113(1):91-100.] These results suggest that the discharge
frequency of the GPi and possibly of the STN is a measurable
quantity that correlates with the clinical efficacy of
medication.
[0030] While not previously observed, this GPi discharge frequency
phenomenon may occur during deep brain stimulation (DBS) as well.
The subthalamic nucleus (STN) is believed to demonstrate increased
neurotransmitter release in Parkinson's disease, and it responds to
deep brain stimulation. Thus, it may demonstrate a similar
discharge frequency phenomenon as the GPi. Since the Vim nucleus of
the thalamus also responds to deep brain stimulation, it may also
demonstrate a similar discharge frequency phenomenon.
[0031] In addition, high frequency chronic electrical stimulation
(i.e., frequencies above 100 Hz) of certain areas of the brain has
been demonstrated to be as efficacious as producing a lesion in any
one of those areas. In contrast to ablation surgery, chronic
electrical stimulation is reversible. Additionally, stimulation
parameters may be adjusted to minimize side effects while
maintaining efficacy; such "fine tuning" is unavailable when
producing a lesion.
[0032] An implantable chronic stimulation device for DBS is
available and similar systems are under development. DBS has proven
to be effective for treating some patients with movement disorders;
however, the current procedure is highly invasive, and the initial
surgery for placement of the available system requires essentially
an entire day. These systems require the power source and
stimulation electronics to be implanted far from the electrodes,
generally in the chest or elsewhere in the trunk of the body. These
bulky systems therefore require extensive invasive surgery for
implantation, and breakage of the long leads is highly likely. In
addition, current DBS systems for movement disorders use no
feedback for regulation of stimulation.
[0033] FIG. 1A depicts the dorsal surface of the brain stem, and
FIGS. 1B and 1C are section views through the brain stem depicted
in FIG. 1A, while FIG. 2A depicts the medial surface of the brain
and FIG. 2B is a coronal section view of the brain of FIG. 2A. FIG.
1B shows the location of the nucleus tractus solitarius (NTS) 100.
FIG. 1C shows the locations of the substantia nigra pars reticulata
102 (as seen in the figure, the substantia nigra pars reticulata is
included in the substantia nigra, as is the substantia nigra pars
compacta), the ventral intermediate (Vim) thalamic nucleus 104, the
pallidosubthalamic tracts 106, and the pallido-thalamic axons 107
(as seen in the figure, pallido-thalamic axons are found in the
lenticular fasciculus and the ansa lenticularis). FIG. 2B shows the
location of the putamen to GPe fibers 108. FIGS. 1C and 2B show the
locations of the internal globus pallidus (GPi) 110, the external
globus pallidus (GPe) 112, the putamen 116, and the subthalamic
nucleus (STN) 120.
[0034] It is believed that applying a stimulus to one or more of
the above-mentioned areas may be useful in treating one or more
movement disorders. As mentioned, "treating" a movement disorder
refers to any amelioration or prevention of one or more causes,
symptoms, and/or sequelae of the movement disorder. Consequently,
an SCU, also referred to herein as a stimulator, may be implanted
within a patient to deliver a stimulus to one or more stimulation
sites within the patient to treat one or more nerve compression
syndromes. In some examples, the stimulus may include an electrical
stimulation current and/or one or more drugs that are infused into
the stimulation site.
[0035] The one or more stimulation sites referred to herein, and in
the appended claims, may include, but are not limited to, the NTS,
the ventral intermediate thalamic nucleus, the GPi, the GPe, the
STN, the pallidosubthalamic tracts, the substantia nigra pars
reticulate, the pallido-thalamic axons, the putamen to GPe fibers,
the subthalamo-pallidal fibers, the putamen to GPi fibers, the
cerebellum, and/or any other suitable location within the brain. In
some examples, as will be described in more detail below, the
stimulus is configured to adjust the level of neural activity in
one or more of these areas, and thereby treat one or more movement
disorders.
[0036] For instance, for patients who demonstrate increased neural
activity of ventral intermediate thalamic nucleus, pallido-thalamic
axons, putamen to GPe fibers, GPi, STN, subthalamo-pallidal fibers,
and/or the cerebellum, inhibitory stimulation may be applied to one
or more of these areas in order to treat one or more movement
disorders. On the other hand, for patients who exhibit decreased
neural activity of NTS, substantia nigra pars reticulata,
pallido-subthalamic tracts, GPe, putamen, and/or putamen to GPi
fibers, excitatory stimulation may be applied to one or more of
these areas in order to treat one or more movement disorders. As
used herein, the terms "stimulate", "stimulation", and
"stimulating" refer to infusion of one or more drugs at the
stimulation site and/or applying one or more electrical current
pulses to the stimulation site.
[0037] As such, infusion parameters and/or electrical current
parameters are sometimes referred to herein as simply stimulation
parameters, which parameters may include amplitude, volume, pulse
width, infusion rate, and the like. Similarly, stimulation pulses
may be pulses of electrical energy and/or pulses of drugs infused
by various means and rates of infusion, such as intermittent
infusion, infusion at a constant rate, and bolus infusion.
[0038] Herein, stimulating drugs may include medications and other
pharmaceutical compounds, anesthetic agents, synthetic or natural
hormones, neurotransmitters, interleukins, cytokines, lymphokines,
chemokines, growth factors (e.g., glial cell line-derived
neurotrophic factor (GDNF), brain cell line-derived neurotrophic
factor (BDNF)), and other intracellular and intercellular chemical
signals and messengers, and the like. Certain neurotransmifters,
hormones, and other drugs are excitatory for some tissues, yet are
inhibitory to other tissues. Therefore, where, herein, a drug is
referred to as an "excitatory" drug, this means that the drug is
acting in an excitatory manner, although it may act in an
inhibitory manner in other circumstances and/or locations.
Similarly, where an "inhibitory" drug is mentioned, this drug is
acting in an inhibitory manner, although in other circumstances
and/or locations, it may be an "excitatory" drug. In addition,
stimulation of an area herein may include stimulation of cell
bodies and axons in the area.
[0039] A number of drugs have demonstrated efficacy in the
treatment of Parkinson's disease. For example, a drug referred to
as "Levodopa" is effective in some patients with Parkinson's
disease. Levodopa is typically administered with a dopa
decarboxylase inhibitor in order to prevent systemic side
effects.
[0040] Patent Cooperation Treaty publication WO 00/38669(A2), which
is incorporated herein by reference in its entirety, teaches
administration of naloxone to the substantia nigra for the
prevention of neural degeneration. (Naloxone is an opiate
antagonist.) Since degeneration of the substantia nigra is the
primary pathology of Parkinson's disease, administration of
naloxone to the substantia nigra may be therapeutic.
[0041] In some examples, the SCU includes an implantable signal
generator coupled to one or more electrodes and/or an implantable
pump connected to a catheter(s). These systems deliver electrical
stimulation and/or one or more stimulating drugs to specific areas
in the brain. One or more electrodes are surgically implanted in
the brain to provide electrical stimulation, and/or one or more
catheters are implanted in the brain to infuse the stimulating
drug(s).
[0042] In some examples, the SCU includes an implantable
microstimulator, such as a BION.RTM. microstimulator (Advanced
Bionics.RTM. Corporation, Valencia, Calif.). Exemplary
microstimulators will be described in connection with FIGS. 3A-3C.
Various details associated with the manufacture, operation, and use
of implantable microstimulators are disclosed in U.S. Pat. Nos.
5,193,539; 5,193,540; 5,312,439; 6,185,452; 6,164,284; 6,208,894;
and 6,051,017. All of these listed patents are incorporated herein
by reference in their respective entireties.
[0043] As shown in FIGS. 3A, 3B, and 3C, an exemplary
microstimulator SCU 160 may include a narrow, elongated capsule 152
containing electronic circuitry 154 connected to electrodes 172 and
172', which may pass through the walls of the capsule at either
end. Alternatively, electrodes 172 and/or 172' may be disposed on
the outer surface or case of the SCU 160 and/or arranged on a
catheter or at the end of a lead, as described below.
[0044] In some examples, electrodes 172 and 172' may include a
stimulating electrode (to be placed close to the target) and an
indifferent electrode (for completing the circuit). Other
configurations of microstimulator SCU 160 are possible.
[0045] Certain configurations of implantable microstimulator SCU
160 are sufficiently small to permit placement in or adjacent to
the structures to be stimulated. For instance, in these
configurations, capsule 152 may have a diameter substantially equal
to or less than 4-5 millimeters and a length substantially equal to
or less than 25-35 mm. The shape of the microstimulator may be
determined by the structure of the desired target, the surrounding
area, and the method of implantation. A thin, elongated cylinder
with electrodes at the ends, as shown in FIGS. 3A, 3B, and 3C, is
one possible configuration, but other shapes, such as cylinders,
disks, spheres, and helical structures, are possible, as are
additional electrodes, infusion outlets, leads, and/or
catheters.
[0046] 3 Microstimulator SCU 160, when certain configurations are
used, may be implanted with a surgical tool such as a tool
specially designed for the purpose, or with a hypodermic needle, or
the like. Alternatively, microstimulator SCU 160 may be implanted
via conventional surgical methods (e.g., via a small incision), or
may be placed using endoscopic or laparoscopic techniques.
[0047] In some examples, the microstimulator SCU 160 may be
implanted with the aid of a stereotactic frame via a minimal
surgical procedure (e.g., through a small burr hole) adjacent to or
at the sites mentioned above. As mentioned, the microstimulator SCU
160 may be sufficiently small to be able to fit through a
conventional burr hole in the skull. Alternative implantation
methods include CT scan or ultrasound image guidance.
[0048] The external surfaces of microstimulator SCU 160 may
advantageously be composed of biocompatible materials. Capsule 152
may be made of, for instance, glass, ceramic, or other material
that provides a hermetic package that will exclude water vapor but
permit passage of electromagnetic fields used to transmit data
and/or power. Electrodes 172 and 172' may be made of a noble or
refractory metal or compound, such as platinum, iridium, tantalum,
titanium, titanium nitride, niobium or alloys of any of these, in
order to avoid corrosion or electrolysis which could damage the
surrounding tissues and the device.
[0049] In some examples, the microstimulator SCU 160 may include
two leadless electrodes disposed on an outer surface or case
thereof. Alternatively, either or both electrodes 172 and 172' may
alternatively be located at the ends of short, flexible leads. The
use of such leads permits, among other things, electrical
stimulation to be directed more locally to targeted tissue(s) a
short distance from the surgical fixation of the bulk of
microstimulator SCU 160, while allowing most elements of the
microstimulator to be located in a more surgically convenient site.
This minimizes the distance traversed and the surgical planes
crossed by the device and any lead(s).
[0050] In some examples, as depicted in FIG. 4, the SCU 160 may be
implanted beneath the scalp, such as in a surgically-created
shallow depression or opening in the skull 140. The
surgically-created shallow depression or opening may be located in
the parietal bone 141, the temporal bone 142, and/or the frontal
bone 143. In some examples, the SCU 160 is configured to conform to
the profile of surrounding tissue(s) and/or bone(s). This may
minimize pressure applied to the skin or scalp, which pressure may
result in skin erosion or infection.
[0051] As shown in FIG. 4, one or more electrode leads 170 and/or
catheters 180 attached to SCU 160 run subcutaneously, for instance,
in a surgically-created shallow groove(s) in the skull, to an
opening(s) in the skull, and pass through the opening(s) into or
onto the brain parenchyma and surrounding tissue. Recessed
placement of the SCU and the lead(s) and/or catheter(s) may
decrease the likelihood of erosion of the overlying skin, and may
minimize any cosmetic impact.
[0052] As shown in FIG. 4, electrode(s) 172 are carried on lead 170
having a proximal end coupled to SCU 160. The lead contains
insulated wires electrically connecting electrodes 172 to SCU 160.
SCU 160 contains electrical components 154 that produce electrical
stimulation pulses that travel through the wires of lead 170 and
are delivered to electrodes 172, and thus to the tissue surrounding
electrodes 172. To protect the electrical components inside SCU
160, some or all of the case of the SCU may be hermetically sealed.
For additional protection against, e.g., impact, the case may be
made of metal (e.g. titanium) or ceramic, which materials are also,
advantageously, biocompatible. In addition, SCU 160 may be
configured to be Magnetic Resonance Imaging (MRI) compatible.
[0053] In some alternatives, the electrical stimulation may be
provided as described in International Patent Application Serial
Number PCT/US01/04417 (the '417 application), filed Feb. 12, 2001,
and published Aug. 23, 2001 as WO 01/60450, which application is
incorporated herein by reference in its entirety.
[0054] In the case of treatment alternatively or additionally
constituting drug infusion, SCU 160 (which herein refers to IPGs,
implantable pumps, IPG/pump combinations, microstimulators for drug
and/or electrical stimulation, and/or other alternative devices
described herein) may contain at least one pump 162 for storing and
dispensing one or more drugs through outlet(s) 182/182' and/or
catheter(s) 180/180' into a predetermined site(s) in the brain
tissue. When a catheter is used, it includes at least one infusion
outlet 182, usually positioned at least at a distal end, while a
proximal end of the catheter is connected to SCU 160.
[0055] In some examples, as depicted in FIG. 5, at least one lead
170 may be coupled to SCU 160 via a suitable connector 168.
Additional leads 170' and/or catheter(s) 180' may be attached to
SCU 160 as may serve a particular application. Hence, FIG. 5 shows
(in phantom lines) a second catheter 180', and a second lead 170',
having electrodes 172' thereon, also attached to SCU 160.
Similarly, the SCUs 160 of FIGS. 3A, 3B, and 3C have outlets 182,
182' for infusing a stimulating drug(s) and electrodes 172,172' for
applying electrical stimulation.
[0056] In some examples, the catheters 160 and/or leads 170 are
substantially cylindrical. In some alternative examples, one or
more of the leads 170 may be paddle-shaped. Electrodes 172,172' on
leads 170,170' may be arranged as an array, for instance, as two or
more collinear electrodes, or even as four or more collinear
electrodes, or they may not be collinear. A tip electrode may also
be supplied at the distal end of one or more leads.
[0057] In some examples, SCU 160 is programmable to produce either
monopolar electrical stimulation, e.g., using the SCU case as an
indifferent electrode, or bipolar electrical stimulation, e.g.,
using one of the electrodes of the electrode array as an
indifferent electrode. In some examples, the SCU 160 may have at
least four channels and drive up to sixteen or more electrodes.
[0058] As shown in FIG. 5, SCU 160 may additionally or
alternatively include electronic circuitry 154 for receiving data
and/or power from outside the body by inductive radio frequency
(RF), or other electromagnetic coupling. To this end, electronic
circuitry 154 may include an inductive coil for receiving and
transmitting RF data and/or power, an integrated circuit (IC) chip
for decoding and storing stimulation parameters and generating
stimulation pulses (either intermittent or continuous), and
additional discrete electronic components required to complete the
electronic circuit functions, e.g. capacitor(s), resistor(s),
coil(s), and the like.
[0059] In some examples, electronic circuitry 154 includes a
processor and/or other components configured to generate one or
more stimulation pulses that are applied to a patient 208 through
electrodes 172 in accordance with one or more stimulation
parameters stored in a programmable memory unit 164. Additionally
or alternatively, the processor may be configured to control
stimulation parameters associated with drug stimulation. For
example, the processor may be configured to cause the SCU 160 to
vary the rate of infusion (e.g., intermittent infusion, infusion at
a constant rate, and bolus infusion).
[0060] As mentioned, SCU 160 may also include a programmable memory
164 for storing one or more sets of data and/or stimulation
parameters. Among other things, memory 164 may allow electrical
and/or drug stimulation to be adjusted to settings that are safe
and efficacious with minimal discomfort for each individual.
Specific parameters may provide therapeutic advantages for various
types and severities of movement disorders. For instance, some
patients may respond favorably to intermittent stimulation, while
others may require continuous treatment for relief. In some
examples, electrical and drug stimulation parameters are controlled
independently, e.g., continuous electrical stimulation and no drug
stimulation. However, in some instances, they may advantageously be
coupled, e.g., electrical stimulation may be programmed to occur
only during drug infusion.
[0061] In addition, different stimulation parameters may have
different effects on neural tissue. Therefore, parameters may be
chosen to target specific neural populations and/or to exclude
others, or to increase neural activity in specific neural
populations and/or to decrease neural activity in others. For
example, relatively low levels of stimulation current (e.g.,
anywhere between about 0.05 mA to about 5.0 mA) are likely to
recruit only relatively large diameter fibers. In some examples,
the stimulation may be configured to selectively increase neural
activity of only the relatively large diameter fibers of NTS 100.
Relatively low amplitude electrical current pulses are likely to
produce such selective excitation.
[0062] As another example, relatively low frequency
neurostimulation (i.e., less than about 100-150 Hz) typically has
an excitatory effect on surrounding neural tissue, leading to
increased neural activity, whereas relatively high frequency
neurostimulation (i.e., greater than about 100-150 Hz) may have an
inhibitory effect, leading to decreased neural activity. Similarly,
excitatory neurotransmitters (e.g., glutamate, dopamine,
norepinephrine, epinephrine, acetylcholine, serotonin), agonists
thereof (e.g., glutamate receptor agonist(s), apomorphine), and
agents that act to increase levels of an excitatory
neurotransmitter(s) (e.g., edrophonium, Mestinon) generally have an
excitatory effect on neural tissue, while inhibitory
neurotransmitters (e.g., dopamine, glycine, and gamma-aminobutyric
acid, a.k.a. GABA), agonists thereof (e.g., muscimol, apomorphine),
and agents that act to increase levels of an inhibitory
neurotransmitter(s) generally have an inhibitory effect. (Dopamine
acts as an excitatory neurotransmitter in some locations and
circumstances, and as an inhibitory neurotransmitter in other
locations and circumstances.) However, antagonists of inhibitory
neurotransmitters (e.g., bicuculline) and agents that act to
decrease levels of an inhibitory neurotransmitter(s) have been
demonstrated to excite neural tissue, leading to increased neural
activity. Similarly, excitatory neurotransmitter antagonists (e.g.
prazosin, metoprolol, atropine, benztropine) and agents that
decrease levels of excitatory neurotransmitter(s) (e.g.,
acetylcholinesterase, Group II metabotropic glutamate receptor
(mGluR) agonists such as DCG-IV) may inhibit neural activity.
[0063] The SCU 160 may also include a power source 166. In some
examples, the power source 166 may include a self-contained power
source utilizing any suitable means of generation or storage of
energy (e.g., a primary battery, a replenishable or rechargeable
battery such as a lithium ion battery, an electrolytic capacitor, a
super- or ultra-capacitor, or the like), a rechargeable power
source, and/or means receiving power from an external power source.
In cases where the power source 166 includes a rechargeable power
source, the SCU 160 may be configured to receive power from an
external battery charging system (EBCS) 192, typically through an
inductive link 194.
[0064] In some examples, the SCU 160 operates independently.
Alternatively, the SCU 160 operates in a coordinated manner with
other SCU(s), other implanted device(s), and/or other device(s)
external to the patient's body. For instance, an SCU 160 may
control or operate under the control of another implanted SCU(s),
other implanted device(s), and/or other device(s) external to the
patient's body. An SCU may communicate with other implanted SCUs,
other implanted devices, and/or devices external to a patient's
body via, e.g., an RF link, an ultrasonic link, a thermal link,
and/or an optical link. Specifically, an SCU may communicate with
an external remote control (e.g., patient and/or physician
programmer) that is configured to send commands and/or data to an
SCU and that may also be capable of receiving commands and/or data
from an SCU.
[0065] For example, the SCU 160 may be activated, deactivated,
programmed, and/or tested through a hand held programmer (HHP) 200
(which may also be referred to as a patient programmer and may be,
but is not necessarily, hand held), a clinician programming system
(CPS) 202 (which may also be hand held), and/or a manufacturing and
diagnostic system (MDS) 204 (which may also be hand held). HHP 200
may be coupled to SCU 160 via an RF link 195. Similarly, MDS 204
may be coupled to SCU 160 via another RF link 196. In a like
manner, CPS 202 may be coupled to HHP 200 via an infra-red link
197; and MDS 204 may be coupled to HHP 200 via another infra-red
link 198. Other types of telecommunicative links, other than RF or
infra-red may also be used for this purpose. Through these links,
CPS 202, for example, may be coupled through HHP 200 to SCU 160 for
programming or diagnostic purposes. MDS 204 may also be coupled to
SCU 160, either directly through RF link 196, or indirectly through
IR link 198, HHP 200, and RF link 195.
[0066] External components for programming and/or providing power
to the SCU 160 are also illustrated in FIG. 6. When communication
with such an SCU 160 is desired, patient 208 is positioned on or
near external appliance 220, which appliance contains one or more
inductive coils 222 or other means of communication (e.g., RF
transmitter and receiver). External appliance 220 is connected to
or is a part of external electronic circuitry appliance 230 which
may receive power 232 from a conventional power source. External
appliance 230 contains manual input means 238, e.g., a keypad,
whereby the patient 208 or a caregiver 242 may request changes in
electrical and/or drug stimulation parameters produced during the
normal operation of SCU 160. In these examples, manual input means
238 includes various electromechanical switches and/or visual
display devices that provide the patient and/or caregiver with
information about the status and prior programming of SCU 160.
[0067] In some examples, the patient 208 switches SCU 160 on and
off by use of controller 210, which may be handheld. SCU 160 is
operated by controller 210 by any of various means, including
sensing the proximity of a permanent magnet located in controller
210, sensing RF transmissions from controller 210, or the like.
[0068] Additionally or alternatively, external electronic appliance
230 is provided with an electronic interface means 246 for
interacting with other computing means 248, such as by a serial
interface cable or infrared link to a personal computer or to a
telephone modem or the like. Such interface means 246 may permit a
clinician to monitor the status of the implant and prescribe new
stimulation parameters from a remote location.
[0069] The external appliance(s) may be embedded in a cushion,
pillow, hat, or the like. Other possibilities exist, including a
head band, patch, or other structure(s) that may be affixed to the
patient's body or clothing. External appliances may include a
package that can be, e.g., worn on the belt, may include an
extension to a transmission coil affixed, e.g., with a Velcro.RTM.
band or an adhesive, or may be combinations of these or other
structures able to perform the functions described herein.
[0070] In order to determine the strength and/or duration of
electrical stimulation and/or the amount and/or type(s) of
stimulating drug(s) required to produce the desired effect, a
patient's response to and/or need for treatment may be sensed. For
example, head acceleration, electrical activity of the brain (e.g.,
EEG or discharge frequency of a neural population), nerve activity
(e.g., ENG), muscle activity (e.g., limb EMG), or other activity
may be sensed.
[0071] For instance, one or more electrodes may be used for
recording electrical signals from the brain. Recording of the
neural activity of one or more areas being stimulated, e.g., NTS
100 or pallido-subthalamic tracts 106, may be performed in order to
determine the discharge frequency of the neural population. This
sensing may occur during stimulation or during a temporary
suspension of stimulation. In some examples, the amplitude of
stimulation is increased if the discharge frequency is above a
programmable threshold frequency, and the amplitude of stimulation
is decreased if the discharge frequency is less than another
programmable threshold frequency. The two programmable threshold
frequencies may be the same or may be different in order to achieve
hysteresis.
[0072] In another example, one or more accelerometers may be used
for sensing acceleration of the head. Rhythmic acceleration of the
head is seen in head tremor. Thus, the amplitude of rhythmic head
acceleration is an indicator of the amplitude of head tremor. The
amplitude of stimulation is increased if the amplitude of rhythmic
head acceleration is above a programmable threshold amplitude, and
the amplitude of stimulation is decreased if the amplitude of
rhythmic head acceleration is below a programmable threshold
amplitude. The two programmable threshold amplitudes may be the
same or may be different in order to achieve hysteresis. This
sensing may advantageously be used for patients with significant
head tremor as a component of their movement disorder, such as
certain patients with benign essential tremor.
[0073] Other measures of the state of the patient may additionally
or alternatively be sensed. For instance, one or more
neurotransmitter levels, their associated breakdown product levels,
hormone levels, or other substances, such as dopamine levels,
interleukins, cytokines, lymphokines, chemokines, growth factors,
electrolytes, enzymes, medication, and/or other drug levels, or
levels of any other bloodborne substance(s), and/or changes in one
or more of these may be sensed, using, e.g., one or more Chemically
Sensitive Field-Effect Transistors (CHEMFETs) such as
Enzyme-Selective Field-Effect Transistors (ENFETs) or Ion-Sensitive
Field-Effect Transistors (ISFETs, as are available from Sentron CMT
of Enschede, The Netherlands). For example, when electrodes of SCU
160 are implanted in or adjacent to pallido-subthalamic tracts 106,
a stimulating electrode of SCU 160, or other sensing means
contained in the electrode lead, catheter, IPG, microstimulator, or
any part of the system may be used to sense changes in neural
firing frequency of the pallido-subthalamic tracts 106 resulting
from the electrical and/or drug stimulation applied to the
pallido-subthalamic tracts 106. (As used herein, "adjacent" or
"near" means as close as reasonably possible to targeted tissue,
including touching or even being positioned within the tissue, but
in general, may be as far as about 150 mm from the target
tissue.)
[0074] Alternatively, an SCU dedicated to sensory processes
communicates with an SCU providing stimulation pulses. The implanrt
circuitry 154 may, if necessary, amplify and transmit these sensed
signals, which may be digital or analog. Other methods of
determining the required electrical and/or drug stimulation include
measuring impedance, acidity/alkalinity (via a pH sensor), muscle
EMG, head or limb acceleration (e.g., via accelerometer), EEG, ENG,
other methods mentioned herein, and others that will be evident to
those of skill in the field upon review of the present disclosure.
The sensed information may be used to control stimulation
parameters in a closed-loop manner.
[0075] For instance, in some examples, a first and second "SCU" are
provided. The second "SCU" periodically (e.g. once per minute)
records firing rate of neurons in GPi 110 (or the level of a
substance, e.g., dopamine or L-Dopa, or an amount of electrical
activity, etc.), which it transmits to the first SCU. The first SCU
uses the sensed information to adjust electrical and/or drug
stimulation parameters according to an algorithm programmed, e.g.,
by a physician. For example, the amplitude and/or frequency of
electrical stimulation may be increased in response to increased
firing rate of neurons in GPi 110. In some alternative examples,
one SCU performs both the sensing and stimulating functions.
[0076] While an SCU 160 may also incorporate means of sensing
symptoms or other prognostic or diagnostic indicators of movement
disorders, e.g., via sensing of tremor (e.g., via accelerometer),
sensing of dopamine or dopamine agonist levels (e.g., L-dopa),
and/or sensing of neural electrical activity (e.g., firing rate of
neurons in pallido-subthalamic tracts 106), it may alternatively or
additionally be desirable to use a separate or specialized
implantable device to record and telemeter physiological
conditions/responses in order to adjust electrical stimulation
and/or drug infusion parameters. This information may be
transmitted to an external device, such as external appliance 220,
or may be transmitted directly to implanted SCU(s) 160. However, in
some cases, it may not be necessary or desired to include a sensing
function or device, in which case stimulation parameters are
determined and refined, for instance, by patient feedback, or the
like.
[0077] Thus, one or more external appliances may be provided to
interact with SCU 160, and may be used to accomplish at least one
or more of the following functions:
[0078] Function 1: If necessary, transmit electrical power to the
SCU 160 in order to power the SCU 160 and/or recharge the SCU
160.
[0079] Function 2: Transmit data to the SCU 160 in order to change
the stimulation parameters used by the SCU 160.
[0080] Function 3: Receive data indicating the state of the SCU 160
(e.g., battery level, drug level, stimulation parameters,
etc.).
[0081] By way of example, an exemplary method of treating one or
more movement disorders (e.g., Parkinson's disease) may be carried
out according to the following sequence of procedures. The steps
listed below may be modified, reordered, and/or added to as best
serves a particular application.
[0082] 1. A first SCU 160 is implanted so that its electrodes 172
and/or infusion outlet 182 are located in or on or near
pallido-subthalamic tracts 106. Electrodes 172' and/or infusion
outlets 182' may additionally or alternatively be located in or on
or near NTS 100 or putamen to GPi fibers.
[0083] 2. Using Function 2 described above (i.e., transmitting
data) of external electronic appliance 230 and external appliance
220, first SCU 160 is commanded to produce a series of excitatory
electrical stimulation pulses, possibly with gradually increasing
amplitude, and possibly while infusing gradually increasing amounts
of an excitatory neurotransmitter, e.g., glutamate, or an
inhibitory neurotransmitter antagonist, e.g., bicuculline.
[0084] 3. After each stimulation pulse, series of pulses, or at
some other predefined interval, any change in, e.g., tremor
(sensed, e.g., via accelerometer in limb) resulting from the
electrical and/or drug stimulation is sensed, for instance, by one
or more electrodes 172, 172' or sensors of a second SCU 160,
preferably a microstimulator SCU 160, implanted in or on or near a
limb(s). These responses may be converted to data and telemetered
out to external electronic appliance 230.
[0085] 4. From the response data received at external appliance 230
from second SCU 160, or from other assessment, the stimulus
threshold for obtaining a response is determined and used by a
clinician 242 acting directly 238 or by other computing means 248
to transmit the desired electrical and/or drug stimulation
parameters to first SCU 160. Alternatively, the second SCU 160 uses
the response data to determine the stimulation parameters and
transmits the parameters to first SCU 160. In yet another
alternative, the second SCU 160 transmits the response data to
first SCU 160, which uses the response data directly to determine
the stimulation parameters. Finally, some combination of the above
may be used.
[0086] 5. When patient 208 desires to invoke electrical stimulation
and/or drug infusion, patient 208 employs controller 210 to set
first SCU 160 in a state where it delivers a prescribed stimulation
pattern from a predetermined range of allowable stimulation
patterns.
[0087] 6. To cease electrical and/or drug stimulation, patient 208
employs controller 210 to turn off first SCU 160 and possibly also
second SCU 160.
[0088] 7. Periodically, the patient or caregiver recharges the
power source/storage device 166 of first and/or second SCU 160.
[0089] In another example, a treatment for movement disorders,
e.g., essential tremor, may be carried out according to the
following sequence of procedures:
[0090] 1. An SCU 160 is implanted so that its electrodes 172 and
possibly also infusion outlet 182 are located in or on or near NTS
100.
[0091] 2. First SCU 160 is commanded to produce a series of
excitatory electrical stimulation pulses, possibly with gradually
increasing amplitude, and possibly while infusing gradually
increasing amounts of an excitatory neurotransmitter, e.g.,
glutamate, or an inhibitory neurotransmitter antagonist, e.g.,
bicuculline.
[0092] 3. After each stimulation pulse, series of pulses, or at
some other predefined interval, any change in movement disorder
signs and symptoms, e.g., change in neural firing rate in GPi 110,
resulting from the electrical and/or drug stimulation is sensed,
for instance, by one or more of the electrodes 172 of SCU 160.
These responses are converted to data and telemetered out to
external electronic appliance 230.
[0093] 4. From the response data received at external appliance 230
from SCU 160, or from other assessment, the stimulus threshold for
obtaining a response is determined and is used by a clinician 242
acting directly 238 or by other computing means 248 to transmit the
desired electrical and/or drug stimulation parameters to SCU.
160.
[0094] 5. When patient 208 desires to invoke electrical stimulation
and/or drug infusion, patient 208 employs controller 210 to set SCU
160 in a state where it delivers a prescribed stimulation pattern
from a predetermined range of allowable stimulation patterns.
[0095] 6. To cease electrical and/or drug stimulation, patient 208
employs controller 210 to turn off SCU 160.
[0096] 7. Periodically, the patient or caregiver recharges the
power source/storage device 166 of SCU 160.
[0097] For the treatment of any of the various types and severities
of movement disorders, it may be desirable to modify or adjust the
algorithmic functions performed by the implanted and/or external
components, as well as the surgical approaches, in ways that would
be obvious to skilled practitioners of these arts. For example, in
some situations, it may be desirable to employ more than one SCU
160, each of which could be separately controlled by means of a
digital address. Multiple channels and/or multiple patterns of
electrical and/or drug stimulation might thereby be programmed by
the clinician and controlled by the patient in order to, for
instance, deal with complex or multiple symptoms or conditions,
such as Parkinson's disease coupled with side effects from
medication, e.g., dyskinesia.
[0098] In some examples a group of two or more SCUs 160 is
controlled via closed-loop operation. A need for and/or response to
stimulation is sensed via SCU 160, or by an additional SCU (which
may or may not be dedicated to the sensing function), or by another
implanted or external device. If necessary, the sensed information
is transmitted to SCU 160. In some cases, the sensing and
stimulating are performed by one SCU. In some examples, the
parameters used by SCU 160 are automatically adjusted based on the
sensed information. Thus, the electrical and/or drug stimulation
parameters are adjusted in a closed-loop manner to provide
stimulation tailored to the need for and/or response to the
electrical and/or drug stimulation.
[0099] For instance, as shown in the example of FIG. 7, a first SCU
160, implanted beneath the skin of the patient 208, provides a
first medication or substance; a second SCU 160' provides a second
medication or substance; and a third SCU 160'' provides electrical
stimulation via electrodes 172 and 172'. As mentioned earlier, the
implanted devices may operate independently or may operate in a
coordinated manner with other similar implanted devices, other
implanted devices, or other devices external to the patient's body,
as shown by the control lines 262, 263 and 264 in FIG. 7. That is,
the external controller 250 controls the operation of each of the
implanted devices 160, 160' and 160''.
[0100] In some examples wherein the SCU 160 is configured to infuse
one or more drugs at a stimulation site, the SCU 160 may
incorporate communication means for communicating with one or more
external or site-specific drug delivery devices, and, further, may
have the control flexibility to synchronize and control the
duration of drug delivery. The associated drug delivery device
typically provides a feedback signal that lets the control device
know it has received and understood commands. The communication
signal between the implanted SCU 160 and the drug delivery device
may be encoded to prevent the accidental or inadvertent delivery of
drugs by other signals.
[0101] In some examples, the electrical and/or drug stimulation
decreases activity of one or more areas of the brain that exhibit
chronic increased activity, relative to control subjects, in
patients experiencing a movement disorder(s). These areas may
include one or more of the pallido-thalamic axons 107, putamen to
GPe fibers 108, and/or subthalamo-pallidal fibers. Such inhibitory
stimulation is likely to be produced by relatively high-frequency
electrical stimulation (e.g., greater than about 100-150 Hz), an
excitatory neurotransmitter antagonist(s) (e.g. prazosin,
metoprolol, atropine), an inhibitory neurotransmitter(s) (e.g.,
GABA), an agonist thereof, an agent that increases the level of an
inhibitory neurotransmitter, an agent that decreases the level of
an excitatory neurotransmitter (e.g., DCG-IV), a local anesthetic
agent (e.g., lidocaine), and/or an analgesic medication. This
stimulation may be applied to one or more of the pallido-thalamic
axons 107, putamen to GPe fibers 108, and subthalamo-pallidal
fibers to treat movement disorder(s).
[0102] In some alternative examples, the electrical and/or drug
stimulation increases activity of one or more of those areas of the
brain that exhibit chronic decreased activity, relative to control
subjects, in patients experiencing a movement disorder(s), thereby
treating or preventing such disorder(s) and/or the symptoms and/or
pathological consequences thereof. These areas may include one or
more of the NTS 100, pallido-subthalamic tracts 106, and putamen to
GPi fibers. Such excitatory stimulation is likely to be produced by
relatively low-frequency electrical stimulation (e.g., less than
about 100-150 Hz), an excitatory neurotransmitter (e.g., glutamate,
acetylcholine), an excitatory cortical neurotransmitter agonist
(e.g., glutamate receptor agonist, L-aspartic acid,
N-methyl-D-aspartic acid (NMDA), bethanechol, norepinephrine), an
inhibitory neurotransmitter antagonist(s) (e.g., bicuculline), an
agent that increases the level of an excitatory neurotransmitter
(e.g., edrophonium), and/or an agent that decreases the level of an
inhibitory neurotransmitter. This stimulation may be applied to one
or more of the NTS 100, pallidosubthalamic tracts 106, and putamen
to GPi fibers to treat movement disorder(s).
[0103] In some examples, the stimulation selectively increases
neural activity of the relatively large diameter fibers of the
nucleus tractus solitarius (NTS 100). Relatively low amplitude
(e.g., about 0.05 mA to about 5.0 mA) electrical current pulses are
likely to produce such selective excitation.
[0104] In some examples, one or more stimulating drugs, possibly in
combination with electrical stimulation, are infused into the
brain. For instance, a growth factor, such as glial cell
line-derived neurotrophic factor (GDNF) may be infused into the
putamen 116, possibly while providing electrical stimulation as
described above. Other stimulating drugs are described previously
herein and include brain cell line-derived neurotrophic factor
(BDNF), naloxone, and levodopa.
[0105] In some examples, sensing means described earlier may be
used to orchestrate first the activation of SCU(s) targeting an
area(s) of the brain, and then, when appropriate, SCU(s) targeting
another area(s) and/or by different means. Alternatively, this
orchestration may be programmed, and not based on a sensed
condition.
[0106] The preceding description has been presented only to
illustrate and describe embodiments of the invention. It is not
intended to be exhaustive or to limit the invention to any precise
form disclosed. Many modifications and variations are possible in
light of the above teaching.
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