U.S. patent application number 17/164709 was filed with the patent office on 2021-12-02 for nasal stimulation for rhinitis, nasal congestion, and ocular allergies.
The applicant listed for this patent is Oculeve Inc.. Invention is credited to Douglas Michael Ackermann, Manfred Franke, Daniel N. Hamilton, James Donald Loudin.
Application Number | 20210370051 17/164709 |
Document ID | / |
Family ID | 1000005769910 |
Filed Date | 2021-12-02 |
United States Patent
Application |
20210370051 |
Kind Code |
A1 |
Loudin; James Donald ; et
al. |
December 2, 2021 |
NASAL STIMULATION FOR RHINITIS, NASAL CONGESTION, AND OCULAR
ALLERGIES
Abstract
Described here are devices, systems, and methods for treating
one or more conditions, such as allergic rhinitis, non-allergic
rhinitis, nasal congestion, ocular allergy, and/or symptoms
associated with these conditions, by providing stimulation to nasal
or sinus tissue. In some variations, the handheld devices may have
a stimulator body and a stimulator probe having one or more nasal
insertion prongs, and the nasal insertion prongs may be configured
to deliver an electrical stimulus to the tissue.
Inventors: |
Loudin; James Donald;
(Alhambra, CA) ; Hamilton; Daniel N.; (Napa,
CA) ; Franke; Manfred; (Valencia, CA) ;
Ackermann; Douglas Michael; (Reno, NV) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Oculeve Inc. |
San Francisco |
CA |
US |
|
|
Family ID: |
1000005769910 |
Appl. No.: |
17/164709 |
Filed: |
February 1, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16357033 |
Mar 18, 2019 |
10940310 |
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17164709 |
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15438577 |
Feb 21, 2017 |
10252048 |
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16357033 |
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62297734 |
Feb 19, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/0546 20130101;
A61N 1/36014 20130101; A61N 1/0456 20130101; A61N 1/36034
20170801 |
International
Class: |
A61N 1/05 20060101
A61N001/05; A61N 1/36 20060101 A61N001/36 |
Claims
1-75. (canceled)
76. A method for treating rhinitis, the method comprising:
contacting a stimulating portion of a handheld stimulator to
external facial tissue of a subject, the stimulating portion
positioned at a distal end of a stimulator body of the handheld
stimulator; and delivering a stimulus via the stimulating portion
to the external facial tissue to activate an infraorbital nerve,
thereby treating rhinitis in the subject.
77. The method of claim 76, wherein the electrical stimulus is
delivered in response to one or more symptoms of rhinitis.
78. The method of claim 77, wherein the symptoms of rhinitis
comprise one or more of itching, sneezing, congestion, runny nose,
post-nasal drip, mouth breathing, coughing, fatigue, headache,
anosmia, phlegm, throat irritation, periorbital puffiness, watery
eyes, ear pain, and fullness sensation.
79. The method of claim 76, wherein the electrical stimulus is
delivered more than once per day on a scheduled basis.
80. The method of claim 76, wherein the stimulus is a biphasic
pulse waveform.
81. The method of claim 80, wherein the biphasic pulse waveform is
symmetrical.
82. The method of claim 80, wherein the biphasic pulse waveform has
a varying peak to peak amplitude.
83. The method of claim 80, wherein the biphasic pulse waveform has
a varying frequency.
84. The method of claim 76, wherein the stimulus is pulsed.
85. The method of claim 76, wherein the stimulating portion is
releasably coupled to the stimulator body.
86. A method for treating congestion, the method comprising:
contacting an electrode of a handheld stimulator to external facial
skin of a subject, the electrode being coupled to a stimulator body
of the handheld stimulator; and delivering an electrical stimulus
via the electrode to the external nasal skin of the subject to
activate an infraorbital nerve, thereby improving the congestion of
the subject.
87. The method of claim 86, wherein the electrical stimulus is
delivered in response to one or more symptoms of congestion.
88. The method of claim 86, wherein the electrical stimulus is
delivered more than once per day on a scheduled basis.
89. The method of claim 86, wherein the stimulus is a biphasic
pulse waveform.
90. The method of claim 89, wherein the biphasic pulse waveform is
symmetrical.
91. The method of claim 89, wherein the biphasic pulse waveform has
a varying peak to peak amplitude.
92. The method of claim 89, wherein the biphasic pulse waveform has
a varying frequency.
93. The method of claim 86, wherein the stimulus is pulsed.
94. The method of claim 86, wherein the stimulating portion is
releasably coupled to the stimulator body.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional
Application No. 62/297,734, filed Feb. 19, 2016, and titled "NASAL
STIMULATION FOR RHINITIS, NASAL CONGESTION, AND OCULAR ALLERGIES,"
which is hereby incorporated by reference in its entirety.
FIELD
[0002] Described herein are methods for treating allergic rhinitis,
non-allergic rhinitis, nasal congestion, ocular allergy, and/or
symptoms associated with these conditions by delivering an
electrical stimulus.
BACKGROUND
[0003] Patients with allergic and non-allergic rhinitis and nasal
congestion often suffer from inflammation of the nasal membranes
that can cause numerous symptoms and complications. These same
patients may frequently also suffer from other types of allergies
and immunoglobulin E (IgE)-mediated disorders, including ocular
allergies. Typical treatments may include pharmacologic therapy,
such as intranasal steroids, oral antihistamines, and anti-IgE for
allergic rhinitis. However, it would be desirable to have a
non-pharmacologic, non-invasive treatment for these conditions for
use alone or in combination with pharmacologic therapy.
[0004] Allergic rhinitis in particular is an IgE-mediated
inflammatory nasal disorder that involves hyperactive nasal mucosa,
obstruction of the nasal passages, and symptoms of rhinorrhea,
sneezing, nasal pruritus, and congestion. Allergic rhinitis is also
commonly associated with conjunctivitis, itchy palate, and
aggravation of comorbid asthma. Traditionally, allergic rhinitis
has been classified as perennial, with symptoms occurring year
round, or seasonal, with symptoms occurring at particular times of
the year. Perennial symptoms are most commonly associated with dust
mites, cockroaches, and molds, whereas seasonal symptoms may be
induced by pollens.
[0005] Allergic rhinitis currently affects 10% to 25% of the
population worldwide, and 20 to 40 million people in the United
States annually, including 10% to 30% of adults and up to 40% of
children. Furthermore, incidence of allergic rhinitis seems to be
increasing globally. The management of allergic rhinitis remains
challenging because of the side effects of existing medication
classes and because of their variable effectiveness. The latter
reflects the variable nature of allergic rhinitis in the general
population. There is therefore an unmet need for a safe and
effective non-pharmacological method for treating allergic
rhinitis.
BRIEF SUMMARY
[0006] Described herein are methods for treating rhinitis (allergic
rhinitis, non-allergic rhinitis), nasal congestion, runny nose,
ocular allergy, and/or symptoms associated with these conditions.
Some methods for treating rhinitis described herein may comprise
delivering an electrical stimulus via an electrode to treat
rhinitis in a patient in need thereof. The rhinitis may be allergic
rhinitis or non-allergic rhinitis. The electrode may be in contact
with nasal tissue of the patient during delivery of the electrical
stimulus. In some variations, the electrical stimulus is delivered
in response to one or more symptoms of rhinitis. The one or more
symptoms of rhinitis may comprise one or more of itching, sneezing,
congestion, runny nose, post-nasal drip, mouth breathing, coughing,
fatigue, headache, anosmia, phlegm, throat irritation, periorbital
puffiness, watery eyes, ear pain, and fullness sensation. In other
variations of the method, the electrical stimulus is delivered more
than once per day on a scheduled basis. In some variations of a
method for treating rhinitis, the nasal tissue to which the
electrical stimulus is delivered is nasal mucosa. The nasal mucosa
may be adjacent to the nasal septum. In some variations of the
method, the electrode may be a hydrogel electrode. The electrode
may be electrically connected to a control subsystem configured to
control the electrical stimulus delivered via the electrode. The
electrode may be positioned on a stimulator probe and the control
subsystem is positioned in a stimulator body, and the stimulator
probe may be releasably connected to the stimulator body. The
electrical stimulus may be a biphasic pulse waveform.
[0007] Also described here are methods for treating rhinitis,
comprising delivering an electrical stimulus to nasal tissue of a
subject to improve rhinitis of the subject, where the electrical
stimulus is delivered by an electrode of a stimulator comprising a
control subsystem to control the electrical stimulus. The rhinitis
may be allergic rhinitis or non-allergic rhinitis. In some
variations, the electrical stimulus may be delivered in response to
one or more symptoms of rhinitis. The one or more symptoms of
rhinitis may comprise one or more of itching, sneezing, congestion,
runny nose, post-nasal drip, mouth breathing, coughing, fatigue,
headache, anosmia, phlegm, throat irritation, periorbital
puffiness, watery eyes, ear pain, and fullness sensation. In some
variations, the electrical stimulus is pulsed. In some variations
of the method, the electrical stimulus may be delivered at least
once daily during a treatment period. The electrical stimulus may
be delivered on a scheduled basis during the treatment period. In
some variations, the electrical stimulus may be a biphasic pulse
waveform. The biphasic pulse waveform may be symmetrical, may have
varying peak to peak amplitude, and/or may have a varying
frequency. In some variations of the method, the stimulator may be
configured to be hand held. In some variations, delivering the
electrical stimulus to nasal tissue may activate the ophthalmic
branch of the trigeminal nerve. In some variations, delivering the
electrical stimulus may activate the anterior ethmoidal nerve. In
some variations, delivering the electrical stimulus may activate
the internal branches of the infraorbital nerve. In some
variations, delivering the electrical stimulus may activate the
superior branches of the greater palatine nerve. In some
variations, delivering the electrical stimulus may activate the
septal nerve. In some variations, delivering the electrical
stimulus may activate the posterior superior lateral nasal branch
of the maxillary nerve.
[0008] Also described here are methods for treating nasal
congestion, comprising delivering an electrical stimulus via an
electrode to treat nasal congestion in a patient in need thereof.
The electrode may be in contact with nasal tissue of the patient
during delivery of the electrical stimulus. In some variations, the
electrical stimulus may be delivered in response to one or more
symptoms of nasal congestion. The one or more symptoms of nasal
congestion may comprise difficulty with nasal breathing, ear
fullness, facial pain, and/or facial and intracranial pressure. In
other variations, the electrical stimulus is delivered more than
once per day on a scheduled basis. The nasal tissue may be nasal
mucosa, which in some instances may be adjacent to the nasal
septum. The electrode in contact with the tissue may be a hydrogel
electrode. The electrode may be electrically connected to a control
subsystem configured to control the electrical stimulus delivered
via the electrode. The electrode may be positioned on a stimulator
probe and the control subsystem is positioned in a stimulator body,
and the stimulator probe may be releasably connected to the
stimulator body. In some variations, the electrical stimulus may be
a biphasic pulse waveform.
[0009] Also described here are methods for treating nasal
congestion comprising delivering an electrical stimulus to nasal
tissue of a subject to improve nasal congestion of the subject,
wherein the electrical stimulus is delivered by an electrode of a
stimulator comprising a control subsystem to control the electrical
stimulus. The electrical stimulus may be delivered in response to
one or more symptoms of nasal congestion. The one or more symptoms
of nasal congestion may comprise difficulty with nasal breathing,
ear fullness, facial pain, and/or facial and intracranial pressure.
In other variations, the electrical stimulus may be delivered at
least once daily during a treatment period. In some of these
variations, the electrical stimulus may be delivered on a scheduled
basis during the treatment period. In some variations of the
method, the electrical stimulus is pulsed. The electrical stimulus
may be a biphasic pulse waveform. The biphasic pulse waveform may
be symmetrical, may have varying peak to peak amplitude, and/or may
have a varying frequency. In some variations of the method, the
stimulator may be configured to be hand held. In some variations,
delivering the electrical stimulus to nasal tissue may activate the
ophthalmic branch of the trigeminal nerve. In some variations,
delivering the electrical stimulus may activate the anterior
ethmoidal nerve. In some variations, delivering the electrical
stimulus may activate the internal branches of the infraorbital
nerve. In some variations, delivering the electrical stimulus may
activate the superior branches of the greater palatine nerve. In
some variations, delivering the electrical stimulus may activate
the septal nerve. In some variations, delivering the electrical
stimulus may activate the posterior superior lateral nasal branch
of the maxillary nerve.
[0010] Also described here are methods for treating ocular allergy
comprising delivering an electrical stimulus via an electrode to
treat ocular allergy in a patient in need thereof. The electrode
may be in contact with nasal tissue of the patient during delivery
of the electrical stimulus. In some variations of the method, the
electrical stimulus is delivered in response to one or more
symptoms of ocular allergy. The one or more symptoms of ocular
allergy may comprise one or more of swelling, puffiness, itching,
tearing, and discharge. In other variations, the electrical
stimulus is delivered more than once per day on a scheduled basis.
The nasal tissue may be nasal mucosa, which in some instances may
be adjacent to the nasal septum. The electrode in contact with the
tissue may be a hydrogel electrode. The electrode may be
electrically connected to a control subsystem configured to control
the electrical stimulus delivered via the electrode. The electrode
may be positioned on a stimulator probe and the control subsystem
is positioned in a stimulator body, and the stimulator probe may be
releasably connected to the stimulator body. In some variations,
the electrical stimulus may be a biphasic pulse waveform.
[0011] Also described here are methods for treating ocular allergy
comprising delivering an electrical stimulus to nasal tissue of a
subject to improve ocular allergy of the subject, where the
electrical stimulus is delivered by an electrode of a stimulator
comprising a control subsystem to control the electrical stimulus.
The electrical stimulus may be delivered in response to one or more
symptoms of ocular allergy. The one or more symptoms of ocular
allergy may comprise one or more of swelling, puffiness, itching,
tearing, and discharge. In other variations, the electrical
stimulus may be delivered at least once daily during a treatment
period. In some of these variations, the electrical stimulus may be
delivered on a scheduled basis during the treatment period. In some
variations of the method, the electrical stimulus is pulsed. The
electrical stimulus may be a biphasic pulse waveform. The biphasic
pulse waveform may be symmetrical, may have varying peak to peak
amplitude, and/or may have a varying frequency. In some variations
of the method, the stimulator may be configured to be hand held. In
some variations, delivering the electrical stimulus to nasal tissue
may activate the ophthalmic branch of the trigeminal nerve. In some
variations, delivering the electrical stimulus may activate the
anterior ethmoidal nerve. In some variations, delivering the
electrical stimulus may activate the internal branches of the
infraorbital nerve. In some variations, delivering the electrical
stimulus may activate the superior branches of the greater palatine
nerve. In some variations, delivering the electrical stimulus may
activate the septal nerve. In some variations, delivering the
electrical stimulus may activate the posterior superior lateral
nasal branch of the maxillary nerve.
[0012] Also described here are methods of treatment comprising
delivering an electrical stimulus via an electrode to treat
allergic rhinitis in a patient in need thereof. The electrode may
be in contact with nasal tissue of the patient during delivery of
the electrical stimulus. In some variations, the electrical
stimulus delivery may treat allergic rhinitis as determined by a
reduction in a symptom of allergic rhinitis. Such symptoms may
include nasal itching, nasal congestion, rhinorrhea, or sneezing.
In other variations, the electrical stimulus may treat allergic
rhinitis as determined by a reduction in nasal inflammation; as
determined by an increase in peak nasal inspiratory flow; as
determined by an initial transient increase in nasal secretions,
followed by a reduction in nasal secretions; as determined by
normalization in temperature of a nasal area; or as determined by a
decrease in fractional exhaled nitric oxide. In some variations,
the method may further comprise expelling accumulated material in
the nasal passageways.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIGS. 1A, 1B, 1C, 1D, 1E show perspective, front, back,
cut-away back, and cut-away side views, respectively, of an
illustrative variation of a handheld stimulator.
[0014] FIG. 2 shows a block diagram schematically representing a
variation of a stimulator.
[0015] FIG. 3A and FIGS. 3B-3C show perspective and exploded views,
respectively, of a stimulator body suitable for the handheld
stimulators described here. FIG. 3D shows a perspective view of a
portion of the stimulator body of FIGS. 3A-3C.
[0016] FIGS. 4A-4C illustrate relevant anatomical locations.
[0017] FIGS. 5A, 5B, 5C, 5D, and FIGS. 5E-5F depict back, side,
cut-away back, cut-away top, and perspective views, respectively,
of a stimulator probe suitable for the handheld stimulators
described here. FIG. 5G depicts a perspective view of a rigid
support of the stimulator probe of FIGS. 5A-5F.
[0018] FIG. 6 shows a cross-sectional view of a stimulator probe
positioned in the nose of a user.
[0019] FIG. 7 depicts a perspective view of the stimulator of FIGS.
1A-1E with the stimulator probe disconnected from the stimulator
body.
[0020] FIG. 8 illustrates a schematic diagram of stimulator
circuitry.
[0021] FIGS. 9A and 9B show perspective and front views,
respectively, of the handheld stimulator of FIGS. 1A-1E with an
attached cap. FIG. 9C shows a perspective view of a cap.
[0022] FIGS. 10A-10D depict portions of a stimulator system
comprising a stimulator and a base station. FIG. 10A shows a front
view of the stimulator body docked in the base station, while FIGS.
10B, 10C, and 10D depict side, back, and top views, respectively,
of the base station.
[0023] FIGS. 11A-11B illustrate placement of an interventional
stimulator and a control stimulator.
DETAILED DESCRIPTION OF THE INVENTION
[0024] Described here are devices, systems, and methods for
treating one or more conditions, including rhinitis, nasal
congestion, ocular allergy, and/or symptoms associated with these
conditions. Generally, the devices and systems may be configured to
stimulate nasal or sinus tissue.
Devices
[0025] The stimulation described herein may in some variations be
delivered by a handheld stimulator configured to deliver an
electrical stimulus to nasal tissue. In some variations, the
devices may comprise a stimulator body and a stimulator probe,
where the stimulator probe comprises one or more nasal insertion
prongs. FIGS. 1A, 1B, 1C, 1D, 1E show perspective, front, back,
cut-away back, and cut-away side views, respectively, of an
illustrative variation of a handheld stimulator 100, respectively.
FIG. 2 shows a block diagram schematically representing the
stimulator 100. As shown in FIGS. 1A-1E, the stimulator 100 may
comprise a stimulator body 102 and a stimulator probe 104.
Generally, the stimulator body 102 may be configured to generate a
stimulus that may be delivered to the subject. The stimulator body
102 may comprise a front housing 138, back housing 140, and
proximal housing 142, which may fit together to define a body
cavity 154. The body cavity 154 may contain a control subsystem 136
and a power source 152, which together may generate and control the
stimulus.
[0026] The stimulus may be delivered to a subject via the
stimulator probe 104. In some variations the stimulator body 102
and stimulator probe 104 may be reversibly attachable, as described
in more detail herein. In other variations, the stimulator probe
may be permanently connected to the stimulator body. Some or all of
the stimulator 100 may be disposable. In variations where the
stimulator body is permanently attached to the stimulator probe,
the entire stimulator may be disposable. In other variations, one
or more portions of the stimulator 100 may be reusable. For
example, in variations where the stimulator probe 104 is releasably
connected to the stimulator body 102, the stimulator body 102 may
be reusable, and the stimulator probe 104 may be disposable and
periodically replaced, as described in more detail herein.
[0027] The stimulator probe 104 may comprise at least one nasal
insertion prong, which may be configured to be at least partially
inserted into the nasal cavity of a subject or patient. In the
handheld stimulator variation shown in FIGS. 1A-1E, the stimulator
probe 104 may comprise two nasal insertion prongs 106 and 108. The
stimulator probe 104 may further comprise ridges 120, which may
allow the patient to more easily grip the probe 104.
[0028] In some variations, the stimulus may be electrical. In these
instances, each nasal insertion prong may comprise at least one
electrode. As shown, the probe 104 may comprise a first electrode
110 on nasal insertion prong 106 and a second electrode 112 on
nasal insertion prong 108. As shown in the cut-away view of the
stimulator 100 in FIG. 1D, the electrodes 110 and 112 may be
connected to leads 130 and 132 located within prongs 106 and 108,
respectively. The leads 130 and 132 may in turn be connected to
connectors 122 and 124, respectively. Connectors 122 and 124 may
extend through lumens 208 and 210 in the proximal housing 142, and
may connect directly or indirectly to the control subsystem 136 and
power source 152. As such, the electrical stimulus may travel from
the control subsystem 136 through the connectors 122 and 124,
through the leads 130 and 132, and through the electrodes 110 and
112.
[0029] The stimulator body 102 may comprise a user interface 230
comprising one or more operating mechanisms to adjust one or more
parameters of the stimulus, as described in more detail herein. The
operating mechanisms may provide information to the control
subsystem 136, which may comprise a processor 232, memory 234,
and/or stimulation subsystem 236. In some variations, the operating
mechanisms may comprise first and second buttons 114 and 116. In
some variations, pressing the first button 114 may turn on the
stimulator and/or change one or more parameters of the stimulus
(e.g., increase the intensity of the stimulus, change the stimulus
pattern, or the like), while pressing the second button 116 may
turn off the stimulator and/or change one or more parameters of the
stimulus (e.g., decrease the intensity of the stimulus, change the
stimulation pattern, or the like). Additionally or alternatively,
the user interface may comprise one or more feedback elements
(e.g., based on light, sound, vibration, or the like). As shown,
the user feedback elements may comprise light-based indicators 118,
which may provide information to the user, as described in more
detail herein.
Stimulator Body
[0030] Turning to the stimulator body, FIG. 3A and FIGS. 3B-3C show
a perspective view and exploded views, respectively, of the
stimulator body 102. The stimulator body 102 may have any suitable
shape. In some variations, it may be desirable for the stimulator
body 102 to be shaped such that it can be easily gripped by a user,
such that it can be held with one hand, such that it can be placed
upright on a surface, and/or such that it can be easily and/or
discretely carried in a pocket or purse. As shown in FIG. 3A, the
stimulator body 102 may have a truncated ovoid shape. However, it
should be appreciated that the stimulator body may have other
shapes. The proximal end of the stimulator body 102 (formed by
proximal housing 142) may have a shape that is complementary to the
bottom of the stimulator probe 104, as described in more detail
herein.
[0031] As mentioned above, the stimulator body may comprise a
housing formed by a front housing 138, a back housing 140, and a
proximal housing 142. These may fit together to form the exterior
of the stimulator body. The front housing 138 and back housing 140
may fit together with any suitable attachment mechanism. For
example, the front 138 and back 140 housings may fit together with
a tongue-and-groove joint. The proximal housing 142 may comprise a
proximal portion 204, which may fit over the proximal ends of the
front and back housings 138 and 140, and a distal portion 206,
which may fit within a portion of the stimulator probe 104, as
described in more detail herein. The housing formed by the front
138, back 140, and proximal 142 housings may comprise any number of
suitable openings for elements of the stimulator body. For example,
the proximal housing 142 may comprise two lumens 208 and 210 that
may be configured to receive connectors 122 and 124, as described
in more detail herein. The front housing 138 may comprise an
opening configured LU receive a portion of the user interface 230,
as described in more detail herein. It should be appreciated that
while the housing is described here as comprising front, back, and
proximal housings, the housing may be constructed from any number
of separate housing components (e.g., two, three, four, five, or
more).
[0032] In some instances, it may be desirable for the stimulator
body to be sealed, such that it may be waterproof or the like. In
some of these instances, when the housing comprises a front housing
138, back housing 140, and proximal housing 142, the three housing
portions may attach so as to be watertight. For example, the
tongue-and-groove joint described above may be watertight. In some
variations, the stimulator body 102 may further comprise one or
more seals located at the interface between the front housing 138
and the back housing 140, and/or between the front 138 and back 140
housings and the proximal housing 142. In variations in which the
housing comprises openings for other elements of the stimulator
body (e.g., connectors 122 and 124, a release mechanism, or the
like), the interface between those elements and the stimulator
housing may be watertight, and/or may comprise seals.
[0033] In some variations, it may be desirable for each of the
front housing 138, back housing 140, and proximal housing 142 to be
formed from the same material in order to improve the ability of
the front housing 138, back housing 140, and proximal housing 142
to maintain a tight seal and to exhibit similar
expansion/contraction properties with changes in temperature. In
some variations, the front housing 138, back housing 140, and top
housing 142 may each comprise a rigid material, such as a rigid
plastic. For example, the front 138, back 140, and top 142 housings
may comprise a thermoplastic such as acrylonitrile butadiene
styrene (ABS), polycarbonate, polyetherimide (e.g., ULTEM.TM.
polyetherimide). However, the housing may comprise any suitable
material or materials. Furthermore, it should be appreciated that
in some variations the front housing 138, back housing 140, and/or
proximal housing 142 may comprise different materials.
[0034] In some variations the housing may comprise an alignment
mechanism. The alignment mechanism may assist in aligning the
stimulator body with the stimulator probe in variations in which
the stimulator body and stimulator probe are detachable, and/or it
may assist in keeping the stimulator body and stimulator probe
connected. Additionally or alternatively, in which the stimulator
system comprises a base station (as described in more detail
herein), it may assist in aligning the stimulator body with the
base station in variations and/or it may assist in keeping the
stimulator body and the base station connected. In variations in
which the stimulator is configured to be attached to a charging
cable, the alignment mechanism may assist in aligning the
stimulator or a portion of the stimulator with a charging cable
and/or keeping the stimulator and charging cable attached. In some
variations, the alignment mechanism may comprise a magnet. FIG. 3D
shows a perspective view of a portion of the stimulator body 102. A
magnet 134 may be connected to the interior surface of the proximal
housing 142 as shown. In other variations, a magnet may be
connected to the interior of another portion of the housing, or to
the exterior of any portion of the housing. In variations in which
the magnet 134 may assist in aligning the stimulator body 102 with
the stimulator probe 104, the stimulator probe 104 may comprise a
magnet or ferromagnetic material in a corresponding location. In
variations in which the magnet 134 may assist in aligning the
stimulator body 102 to a base station, the base station may
comprise a magnet or ferromagnetic material in a corresponding
location.
[0035] In some variations the housing may comprise a weight. It may
in some instances be desirable for the stimulator to have a
sufficient weight such that it has a substantial feel when held by
a user. In some variations, the alignment mechanism (e.g., a
magnet) may further serve as a weight. Additionally or
alternatively, the weight may comprise a dense material or
materials (e.g., iron or steel). The weight may be located in any
suitable location within the housing. In some instances, the weight
may be attached to the interior of the housing, to a printed
circuit board comprising the control subsystem (described in more
detail below), or threaded within pins holding a printed circuit
board in place (e.g., pins 144 in stimulator body 102).
[0036] In some variations, the stimulator bodies described here may
comprise features to assist the user in holding the device. For
example, one or more portions of the stimulator may comprise ridges
on both sides of the stimulator body. These ridges may act as grips
for the user to hold onto. It should be appreciated that any of the
stimulator bodies described here may comprise any suitable features
to assist the user in holding the device, such as any texturized
surface, a high-friction material (e.g., rubber), indentations, or
the like.
[0037] In instances where the stimulators described here comprise a
user interface, the user interface may comprise one or more
operating mechanisms, which may allow the user to control one or
more functions of the stimulator. For example, the operating
mechanisms may allow the user to power the device on or off, start
or stop the stimulus, change the intensity of the stimulus, change
the duration of the stimulus, change the stimulus pattern, or the
like. In some variations, the operating mechanisms may be able to
activate or deactivate different functions, and/or may be able to
change different parameters, based on their manner of operation
(e.g., pressing a button briefly, pressing a button for a prolonged
period, pressing a button with a particular pattern of pressing
actions, rotating a dial by different angles or different speeds).
Each of the one or more operating mechanisms may be any suitable
structure, such as but not limited to a button, slider, lever,
touch pad, knob, or deformable/squeezable portion of the housing,
and a stimulator may comprise any combination of different
operating mechanisms.
[0038] In one variation, the one or more operating mechanisms may
comprise one or more buttons. The stimulator body 102, for example,
may comprise two buttons 114 and 116. In the variation shown, the
two buttons 114 and 116 may be located on a single a flexible
membrane 212. The flexible membrane 212 may comprise any suitable
material or materials, such as but not limited to a flexible
polymer, such as a thermoplastic elastomer (e.g., a thermoplastic
elastomer alloy (e.g., VERSAFLEXT.TM. thermoplastic elastomer),
thermoplastic polyurethane, or the like), silicone, or the like. In
some variations in which the flexible membrane is located within
the front housing 138, the flexible membrane 212 may be attached to
the front housing 138 such that they are chemically bound. In some
variations, they may be connected via overmolding, transfer
molding, or two-shot molding. However, it should be appreciated
that the flexible membrane 212 may be attached to the housing in
any other suitable manner, such as via bonding.
[0039] The flexible membrane 212 may be separated into two buttons
114 and 116 by a divider 150. As shown in FIGS. 1E and 3C, the
divider 150 may extend interiorly into the body cavity 154 from the
interior surface of the flexible membrane 212. The end of the
divider 150 may press against a fixed surface within the body
cavity 154 of the stimulator body 154. For example, the end of the
divider 150 may press against a portion of the printed circuit
board (PCB) (128) that forms the control subsystem 136. The divider
150 may thus serve as an inflection point on the flexible membrane
212, such that each of the two buttons 114 and 116 may be pressed
separately by the user. The divider 150 may also serve to resist
separation between the flexible membrane 212 and the housing (e.g.,
by breaking the adhesion between the housing and the flexible
membrane) by limiting the movement of the flexible membrane 212
into the body cavity 154.
[0040] If the user presses one of buttons 114 or 116, the movement
of the button may be transferred to the control subsystem 136. As
shown in FIG. 3C, the interior surface of the flexible membrane 212
may comprise two raised surfaces 214 and 216 on the interior
surface of buttons 114 and 116, respectively. When button 114 or
116 is depressed, the corresponding raised surface 214 or 216 may
press against PCB button 146 or 148 (shown in FIG. 3B),
respectively, located in the printed circuit board 128, in order to
transmit information to the control subsystem 136. While the
stimulator body 102 is shown as having two buttons formed on a
single flexible membrane, it should be appreciated that in other
variations, two or more buttons may be separately formed.
[0041] In stimulator body 102, pressing the top button 114 may
power on the stimulator 100 when the stimulator 100 is off. In some
variations in which the stimulator is capable of differing stimulus
intensities, the stimulator may be powered on to the last stimulus
intensity from before the stimulator was powered off. When the
stimulator 100 is on, pressing the top button 114 may increase the
intensity of the stimulus (for example, when the stimulus is
electrical, pressing the top button 114 may increase the amplitude
of the stimulus waveform). Conversely, pressing the bottom button
116 may decrease the intensity of the stimulus (for example, when
the stimulus is electrical, pressing the bottom button 116 may
decrease the amplitude of the stimulus waveform). Pressing the
bottom button 116 also may in some instances power off the
stimulator 100. For example, pressing and holding the bottom button
116 may power off the stimulator 100; or additionally or
alternatively, pressing the bottom button 116 when the stimulus
intensity is at its lowest level may power off the stimulator 100.
However, it should be appreciated that additionally or
alternatively, the stimulator 100 may power off without user input
(e.g., after a period of idle time). In some variations, the
stimulator 100 may provide feedback to the user to indicate that
the buttons are being pressed (or that other operating mechanisms
are being operated). For example, pressing the buttons or operating
any of a stimulator's operating mechanisms may be accompanied by a
sound, vibration, tactile click, light, or the like, but need not
be. It should be appreciated that the operating mechanisms of the
stimulators described here may have any number of other suitable
configurations.
[0042] Furthermore, the stimulators may be configured to provide
feedback or otherwise convey information to a user. For example, in
stimulator 100, the user interface 230 may comprise one or more
light-based status indicators 118. The light-based status
indicators 118 may comprise one or more light sources (e.g., LEDs)
located on the printed circuit board 128, which may be connected to
or located near light-transmitting elements 158 on the front
housing 138. The light-transmitting elements 158 may transmit light
from a light source on the printed circuit board 128 to the
exterior of the housing, where it may be perceived by a user. In
some variations, the light-transmitting elements 158 may comprise
fiber optics (e.g., light pipes). In other variations, the
light-transmitting elements 158 may comprise translucent or
transparent epoxy) in the front housing 138.
[0043] Generally, the control subsystem of the stimulators
described herein may be configured to control a stimulus to be
delivered to a subject via the stimulator probe. The control
subsystem may be contained within the housing the stimulator. The
control subsystem may be connected to the operating mechanisms of
the stimulator (e.g., the buttons), which may allow the control
subsystem to receive input from a user. The control subsystem may
also be connected to mechanisms configured to provide feedback or
otherwise convey information to a user. In some variations, such as
stimulator 100, the control subsystem 136 may be located on a
printed circuit board 128. When the control subsystem 136 is
located on a printed circuit board 128, the printed circuit board
128 may be fixed within the body cavity 154 of the stimulator body
102 in any suitable manner. In some variations, the printed circuit
board 128 may be held in place relative to the housing by pins 144.
As shown in FIG. 3B, the interior surface of back housing 140 may
comprise four pins 144. The pins 144 may be configured to fit
through corresponding openings 156 in the printed circuit board
128, and may be further configured to fit into receiving recesses
238 in the front housing 138. It should be appreciated that in
other variations in which the printed circuit board is secured by
pins, the housing may comprise any number of pins 144, which may be
located on any portion of the housing.
[0044] The control subsystem 136 may include any circuitry or other
components configured to operate the stimulators as described here.
In some variations the control subsystem may comprise a processor
232, memory 234, and/or a stimulation subsystem 236. Generally, the
processor may be configured to control operation of the various
subsystems of the control subsystem. For example, the processor 232
may be configured to control the stimulation subsystem 236 to
control parameters of the stimulation provided by the stimulation
subsystem 236. The memory 234 may be configured to store
programming instructions for the stimulator, and the processor 232
may use these programming instructions in controlling operation of
the stimulator. The stimulation subsystem 236 may be configured to
generate a stimulation signal and deliver the stimulation signal to
a patient via the stimulator probe. In other variations, the
control subsystem 136 may comprise a finite state machine.
[0045] In some variations, the control subsystem 136 may comprise a
detection/recording subsystem. In these variations, the
detection/recording subsystem may be configured to monitor one or
more parameters of a subject (e.g., subject impedance), the
stimulation delivered to the subject (e.g., date and time of
stimulation, duration of the stimulation, amplitude of the
stimulation signal, pulse width, frequency), and/or the stimulator
itself (e.g., diagnostic data). The detection/recording subsystem
may record some or all of this data to the memory. Additionally or
alternatively, the control subsystem 136 may be configured to
accept and record user input regarding subject symptomology,
subject activity, or the like. Additionally or alternatively, the
control subsystem may comprise a communications subsystem. The
communication subsystem may be configured to facilitate
communication of data and/or energy between the stimulator and an
external source.
[0046] The control subsystem may in some variations comprise safety
mechanisms, such as limits on the voltage, current, frequency, and
duration of the stimulus when the stimulus is electrical. In some
variations, some of these safety mechanisms may be part of the
stimulation subsystem. For example, the stimulation subsystem 236
of the control subsystem 136 of stimulator 100 may limit the
voltage and current that may be delivered to the patient. In some
variations, the voltage may be limited by a voltage regulator. In
some of these variations, the voltage limit may be between about 1
V and about 100 V. In some of these variations, the voltage limit
may be between about 5 V and 50 V, between about 10 V and 25 V, or
between about 15 V and 20 V. In some variations, the voltage may be
regulated via a boost regulator connected to the power source 152,
but it should be appreciated that any suitable voltage regulator
may be used. In some variations, the current may be limited by a
resistor in series with the load or a current-limiting transistor,
or any other suitable combinations of elements. In some variations,
the current limit may be about between about 1 mA to about 30 mA,
between about 5 mA to about 20 mA, or about 10 mA. In some
variations, the stimulation subsystem 236 may be capacitively
coupled by one or more series capacitors on the output. This
capacitive coupling may prevent DC currents from being applied to
the patient, and may limit the total charge injection and pulse
duration.
[0047] Additionally or alternatively, some or all of the safety
mechanisms of the control subsystem 136 may be part of the
processor 232. For example, the processor 232 may comprise software
that limits the frequency to within an allowed range. In some
variations, the frequency may be limited to between about between
about 0.1 Hz and about 200 Hz, between about 10 Hz and about 60 Hz,
between about 25 Hz and about 35 Hz, between about 50 Hz and about
90 Hz, between about 65 Hz and about 75 Hz, between about 130 Hz
and about 170 Hz, between about 145 Hz and about 155 Hz, or between
about 145 Hz and about 155 Hz. Additionally or alternatively, the
processor 232 may comprise software that limits the stimulus
intensity (e.g., the current or voltage). In some of these
variations, the voltage limit may be between about 5 V and 50 V,
between about 10 V and 25 V, or between about 15 V and 20 V. In
some variations, the current limit may be about between about 1 mA
to about 30 mA, between about 5 mA to about 20 mA, or about 10 mA.
The processor 232 may additionally or alternatively comprise
software that limits the stimulus duration. In some variations, the
duration may be limited to about 1 minute, about 2 minutes, about 3
minutes, about 5 minutes, about 10 minutes, or the like. In some
variations in which the stimulator probe 104 is removably connected
to the stimulator body 102, the control subsystem 136 may prevent
the delivery of current by the stimulation subsystem 236 when the
stimulator probe 104 is disconnected from the stimulator body 102.
Additionally or alternatively, the control subsystem 136 may
prevent delivery of current by the stimulation subsystem 236 when
the stimulator probe 104 is not in contact with a patient's
tissue.
[0048] The stimulator may comprise a power source. The power source
may be any suitable power supply capable of powering one or more
functions of the stimulator, such as one or more batteries,
capacitors, or the like. As shown in FIGS. 3C-3D, in some
variations the power source may comprise a lithium coin cell
battery 152. The battery 152 may be secured in place via any
suitable method, such as a clip 160 attached to the printed circuit
board 128 comprising the control subsystem 136. In some variations,
the power source may be rechargeable.
[0049] While the stimulator body 102 comprises a power source, in
other variations the stimulator body need not comprise a power
source. In some variations, the stimulator body may comprise a
port, cord, or other mechanism for connecting the stimulator to an
external power source (such as a wall outlet or separate battery
pack), which in turn may be used to power one or more portions of
the stimulator. In some other variations, such a port, cord, or
other mechanism may be used to recharge a rechargeable power
source. The stimulator body 102 may comprise such a port (e.g., a
USB port) at any suitable location, such as between the connectors
122 and 124 on the proximal housing 142, on the back housing 140,
on the front housing 138, or at the proximal end of the stimulator
body 102 between the front 138 and back housings 140.
[0050] Other variations and features of stimulator bodies and
components thereof are described in U.S. application Ser. No.
14/256,915, filed Apr. 18, 2014, and titled "NASAL STIMULATION
DEVICES AND METHODS," which is hereby incorporated by reference in
its entirety.
Stimulator Probe
[0051] The stimulator probe of the stimulator may comprise one or
more nasal insertion prongs, which may be configured to extend at
least partially into a nasal cavity of a subject. FIGS. 5A, 5B, 5C,
5D, and FIGS. 5E-5F depict back, side, cut-away back, cut-away top,
and perspective views, respectively, of the stimulator probe 104 of
stimulator 100. As shown there, the stimulator probe 104 may
comprise a first nasal insertion prong 106 and a second nasal
insertion prong 108. The first and second prongs 106 and 108 may be
connected via a base member 126. The base member 126 may be
configured to hold at least a portion of the first and second
prongs in fixed relation to each other.
[0052] The nasal insertion prongs 106 and 108 may generally be
configured to be inserted a subject's nostrils. As shown in FIGS.
5A-5F, each nasal insertion prong 106 and 108 may comprise an
elongate portion 162 and 164, respectively. Each elongate portion
162 and 164 may have at its distal end a distal portion 176 and
178. In some variations, the distal portions 176 and 178 may have a
diameter (or greatest cross-sectional dimension) that is larger
than the diameter (or greatest cross-sectional dimension) of the
elongate portion 162 and 164 of the prongs proximal to the distal
portions. This may allow a portion of the distal portions 176
and/or 178 (e.g., the electrodes, described below) to be brought
into contact with a subject's tissue, while the elongate portions
162 and 164 are not in contact with the subject's tissue. For
example, the diameter of the nasal insertion prongs 106 and 108 at
the distal portions 176 and 178 may in some instances be between
about 3 mm and about 7 mm, while the diameter of the elongate
portions 162 and 164 may be between about 1 mm and about 6 mm
proximal to the distal portions. More specifically, in some
variations the diameter of the nasal insertion prongs at the distal
portions 176 and 178 may be about 5 mm, and the diameter of the
elongate portions 162 and 164 may be about 3 mm. The proximal
portion of the elongate portions 162 and 164 may flare outward
(i.e., have an increasing diameter or greatest cross-sectional
dimension) toward the base member, which may in some variations act
as a stop to limit the distance that the nasal insertion prongs 106
and 108 may be advanced into the nose of a user.
[0053] The first and second nasal insertion prongs 106 and 108 may
be connected to each other via a base member 126. In the variation
shown in FIGS. 5A-5F, the prongs 106 and 108 may be integrally
formed with the base member 126 by a rigid support 218 and a
flexible overlay 220, as shown in FIG. 5C. The rigid support 218
may provide support to the base of the nasal insertion prongs 106
and 108 and may interface with the top of the stimulator body 102,
as described in more detail below. The rigid support 218 may
comprise any suitable material or materials, such as a rigid
plastic. For example, in some variations, the rigid support 218 may
comprise a thermoplastic such as acrylonitrile butadiene styrene
(ABS), polycarbonate, polyetherimide (e.g., ULTEM.TM.
polyetherimide). It may in some instances be desirable for the
rigid support 218 to comprise the same material as a portion of the
stimulator body 102 (e.g., the proximal housing 142 (described
above)), in order to improve the ability to attach the stimulator
probe 104 to the stimulator body 102, as described in more detail
below. In some variations, the rigid support 218 may comprise a
bottom portion 240 configured to interface with the stimulator body
102, and a top portion comprising one or more supports 242 (e.g.,
as shown in FIG. 5G, three supports 242). The top portion may
further comprise two lumens 208 and 210, configured to receive
leads as described below. In some variations, the supports 242 may
be saddle-shaped.
[0054] The flexible overlay 220 may form the nasal insertion prongs
106 and 108 and may wrap around the rigid support 218 to form the
base member 126. The flexible overlay 220 may comprise any suitable
material or materials. The flexible overlay 220 may comprise a more
flexible material than the rigid support 218. For example, in some
variations the flexible overlay 220 may comprise a flexible
polymer, such as a thermoplastic elastomer (e.g., thermoplastic
elastomer alloys (e.g., VERSAFLEX.TM. thermoplastic elastomer),
thermoplastic polyurethanes, or the like), silicone, or the like.
Although the nasal insertion prongs 106 and 108 may be integrally
formed with the base member 126 in stimulator probe 104, in other
variations, the nasal insertion prongs may separately formed from
the base member.
[0055] The base member 126 may allow the nasal insertion prongs 106
and 108 to be manipulated as a single unit (and disposed as a
single unit, in instances where the stimulator probe is
disposable). In some variations, the base member 126 may act as a
stop to limit the distance that the nasal insertion prongs 106 and
108 may be advanced into the nose of a user. Additionally or
alternatively, one or more of the nasal insertion prongs may
include a flange or other mechanical stop to limit the distance
that the prongs may be inserted into a user's nose. The base member
126 may further help to control the relative orientation of the
prongs. For example, as shown in FIGS. 5A-5F, the two nasal
insertion prongs 106 and 108 may be connected to the base member
126 such that the two prongs are oriented substantially parallel to
each other. In some variations, having the nasal insertion prongs
oriented substantially parallel to each other may provide
advantages in manufacturing and may aid in nasal insertion.
However, in other variations, the nasal insertion prongs may not be
oriented parallel to each other. For example, in some variations,
the nasal insertion prongs may be angled toward each other.
[0056] The two nasal insertion prongs may be positioned with any
suitable distance between them (e.g., between about 3 mm and about
15 mm). In some variations, it may be desirable for the distance
between the two nasal insertion prongs to be such that they fit
simultaneously into each of the user's nostrils on either side of
the septum. Additionally or alternatively, it may be desirable for
the distance to be such that the nasal insertion prongs are
configured to self-align to the desired stimulation location
(described in more detail below) when inserted into the user's
nasal cavities. In some of these variations, the distance between
the central longitudinal axes of the two nasal insertion prongs 106
and 108 (labeled as distance "A" in FIG. 5A) may be between about
12 mm and about 16 mm. The diameter of the nasal insertion prongs
at the distal portions 176 and 178 may in some instances be about 3
mm to about 7 mm as described above, and thus the distance between
the distal portions (labeled as distance "B" in FIG. 5A) may be
about 5 mm to about 11 mm. More specifically, in some variations
the distance between the central axes of the two nasal insertion
prongs 106 and 108 may be about 14 mm, and the diameter of the
nasal insertion prongs at the distal portions 176 and 178 may be
about 5 mm, and thus the distance between the distal portions may
be about 11 mm.
[0057] The one or more nasal insertion prongs may have any suitable
length. In some variations, the length of the one or more nasal
insertion prongs may be such that when inserted into the nasal
cavity, at least a portion (e.g., distal portions 176 and 178) is
capable of reaching the area of the nasal cavity that is desired to
be stimulated. For example, the length of the one or more nasal
insertion prongs may be such that when inserted into the nasal
cavity, at least a portion is capable of reaching the nasal mucosa
or other area desired to be stimulated, as described in more detail
below. In some variations, the length of the one or more nasal
insertion prongs extending from the base member (i.e., the farthest
the nasal insertion prongs could be inserted into the nasal cavity)
may be between about 25 mm and about 45 mm. In other variations,
the length of the one or more nasal insertion prongs extending from
the base member may be between about 30 mm and about 40 mm. For
example, in some variations, such as variations in which the
stimulation target includes the anterior ethmoidal nerve, the nasal
insertion prongs 106 and 108 may have a length extending from the
base member 126 of about 37.5 mm (labeled as distance "C" in FIG.
5A). As another example, when the stimulation target includes an
internal branch of the infraorbital nerve, the length of the one or
more nasal insertion prongs extending from the base member may be
between about 8 mm and about 20 mm. As yet another example, when
the stimulation target includes a superior branch of the greater
palatine nerve, the length of the one or more nasal insertion
prongs extending from the base member may be between about 20 mm
and about 40 mm. As yet another example, when the stimulation
target includes a posterior superior lateral nasal branch of the
maxillary nerve (when the tissue to be stimulation includes the
middle and/or superior turbinates), the length of the one or more
nasal insertion prongs extending from the base member may be
between about 20 mm and 60 mm (e.g., between about 25 mm and about
35 mm, between about 30 mm and about 40 mm, between about 25 mm and
about 40 mm). In other variations the nasal insertion prongs may be
different lengths and/or adjustable lengths, and additionally or
alternative may comprise one or more bends or curves.
[0058] The nasal insertion prong dimensions and configuration
described with respect to stimulator probe 104 may allow the nasal
insertion prongs 106 and 108 to self-align to the desired
stimulation location when inserted into a user's nasal cavities.
The length of the nasal insertion prongs is desirably long enough
such that the prongs can reach the desired stimulation location
(e.g., the nasal mucosa superior to the columella, such as near the
interface between the nasal bone and the upper lateral cartilage;
tissue innervated by a nerve target, such as but not limited to the
anterior ethmoidal nerve, internal branches of the infraorbital
nerve, superior branches of the greater palatine nerve, septal
nerve, or posterior superior lateral nasal branch of the maxillary
nerve) in a range of patients. However, it should be appreciated
that in some instances it may be desirable to stimulate the
columella. For those patients having a larger distance between the
columella and the desired stimulation location, a longer portion of
the nasal insertion prongs may be inserted into the nasal cavities.
For those patients having a shorter distance between the columella
and the desired stimulation location, a shorter portion of the
nasal insertion prongs may be inserted into the nasal cavities.
Because the patient's nasal cavities may narrow from inferior to
superior, as the nasal stimulation prongs are advanced superiorly
into the nasal cavities toward the desired stimulation location,
the nasal tissue may generate a force pressing the nasal insertion
prongs medially. When the nasal insertion prongs comprise a
flexible material (e.g., a flexible polymer, such as a
thermoplastic elastomer (e.g., a thermoplastic elastomer alloy
(e.g., VERSAFLEX.TM. thermoplastic elastomer), thermoplastic
polyurethane, or the like), silicone, or the like) as described
herein, the nasal insertion prongs may flex medially, bringing them
into contact with the desired stimulation location.
[0059] In some variations, it may be desirable to have a particular
flexibility or range of flexibilities in order to allow the nasal
insertion prongs to self-align to the desired stimulation location
when inserted into a user's nasal cavities. In these variations,
properties of the nasal insertion prongs (e.g., the Young's
modulus, thickness of the flexible material or materials, the
properties of the leads located within the prongs (described in
more detail herein)) may be chosen to allow self-alignment.
Generally, it may be desirable for the prongs to be stiff enough
such that they can be pushed into the nasal cavities without
buckling, while being flexible enough to self-align and/or to be
atraumatic to the nasal tissue during regular use and insertion,
and/or during a sudden movement (e.g., a sneeze). This may also
improve comfort for the user. In some variations, the desired
hardness of the material may be between about 40 D and about 90 D,
between about 50 D and about 80 D, between about 60 D and about 70
D, or about 65 D. In addition to having material properties that
may be atraumatic to nasal tissue, it may be desirable for the
distal tips of the nasal insertion prongs to have rounded edges to
help minimize the risk of tissue damage during advancement of the
prongs into the nose.
[0060] When the stimulators described here are configured to
deliver an electrical stimulus, at least one of the nasal insertion
prongs may comprise one or more electrodes configured to deliver a
stimulus to tissue. In variations where a stimulator comprises two
nasal insertion prongs, each of the two nasal insertion prongs may
comprise at least one electrode. Having multiple electrode-bearing
prongs may allow the stimulator to provide bipolar stimulation
(and/or bilateral stimulation of two nostrils), as discussed in
more detail herein.
[0061] When a nasal insertion prong or prongs of the stimulators
describe here comprise one or more electrodes, the electrodes may
have any suitable design. In variations in which the electrodes
comprise an arc of a cylindrical surface, such as in the variation
shown in FIGS. 5A-5F, the electrodes 110 and 112 may comprise about
a 100 degree arc of a cylindrical surface. That is, openings 180
and 182 in the distal portions 176 and 178 of the nasal insertion
prongs may comprise about a 100 degree arc of a cylinder, and the
electrodes 110 and 112 may be located within the openings 180 and
182. In other variations, the electrodes may be any suitable arc
length of a cylinder and further may have any suitable shape. For
example, in some variations the electrodes may comprise a complete
cylinder (e.g., may extend 360 degrees around the distal portions
of the nasal insertions prongs), or in other variations, the
electrodes may have a domed shape that includes the distal tips of
the nasal insertion prongs. Such a complete cylinder or domed shape
may be desirable, for example, when the targeted tissue area
comprises two or more areas of tissue (e.g., stimulation is
configured to stimulate two or more target nerves simultaneously).
For example, such electrodes may be desirable when the targeted
tissue areas comprise the area innervated by the superior branches
of the greater palatine nerve and the area innervated by the
nasopalatine nerve. As another example, such electrodes may be
desirable when the targeted tissue areas comprise the area
innervated by the posterior superior lateral nasal branches of the
maxillary nerve and the area innervated by the nasopalatine
nerve.
[0062] When the nasal insertion prongs comprise one or more
electrodes, the center of the electrodes may be angled relative to
the axis intersecting the first and second prongs. In some
variations, the electrodes may be angled such that when the first
nasal insertion prong is positioned in a first nostril and the
second nasal insertion prong is positioned in the second nostril,
the electrodes may be directed toward the front of the nose. When
an electrical stimulus is delivered through the electrodes of the
first and second nasal insertion prongs, the stimulation energy may
be directed toward the front of the nose. This may allow for
selective activation of nerves in the front of the septum and nasal
mucosa, while minimizing activation of nerves toward the rear of
the nasal septum. This may reduce negative side effects that may
occur from stimulation of nerves that innervate the teeth.
Specifically, in the variation of the stimulator probe 104, as
shown in FIG. 5D, the center of the electrode 110 of the first
nasal insertion prong 106 (shown by line 226) may be rotated at an
angle .theta..sub.1 relative to the axis 166 intersecting the first
106 and second 108 nasal insertion prongs, while the center of the
electrode 112 of the second nasal insertion prong 108 (shown by
line 228) may be rotated at an angle .theta..sub.2 relative to the
axis 166.
[0063] The angles .theta..sub.1 and .theta..sub.2 of the stimulator
probe 104 may be the same or different, and may be any suitable
value (e.g., about 45 degrees, about 90 degrees, about 180 degrees,
between about 0 degrees and about 90 degrees, between about 15 and
about 75 degrees, or the like). In some variations, it may be
desirable for angles .theta..sub.1 and .theta..sub.2 to be greater
than about 10 degrees. In other variations, the center of the
electrodes may face each other (e.g., angles .theta..sub.1 and
.theta..sub.2 may be zero). This may cause the electrodes to face
toward septal tissue when each nasal insertion prong is positioned
in a nostril. In some variations, this may enhance activation of
rhinorrhea and/or may enhance constriction of the lamina propia. In
other variations, the centers of the electrodes may face in the
same direction or nearly in the same direction (e.g., angles
.theta..sub.1 and .theta..sub.2 may be between about 70 degrees and
about 90 degrees, which may cause the electrodes to face toward the
front of the nose when each nasal insertion prong is positioned in
a nostril). In other variations, the centers of the electrodes may
be oriented such that angles .theta..sub.1 and .theta..sub.2 may be
between about 10 degrees and about 50 degrees. In yet other
variations, the centers of the electrodes may be oriented such that
the electrodes face away from each other. In some instances, this
may allow for stimulation of tissue in the nasal turbinates and/or
tissue innervated by the superior branches of the greater palatine
nerve. In the variation shown in FIG. 5D, the angles .theta..sub.1
and .theta..sub.2 may each be 45 degrees. As such, when the
stimulator probe 104 or 1200 is positioned such that the first
nasal insertion prong is positioned in a first nostril and the
second nasal insertion prong is positioned in the second nostril,
the electrodes may be directed partially toward the front of the
nose. For example, FIG. 6 shows electrodes 608 positioned in
nostrils 620 against septum 622 and directed partially toward the
front of the nose.
[0064] The electrodes may be positioned on any suitable
longitudinal portion or portions of the nasal insertion prongs. The
position of the electrode along the prong may at least partially
determine the placement of the electrode relative to tissue when
the stimulator probe is advanced into the nose. In some variations,
an electrode may be located at an intermediate position along a
prong of stimulator. For example, in the variation of the
stimulator probes depicted in FIGS. 5A-5F, the electrodes 110 and
112 may be located at an intermediate position along the nasal
insertion prongs, within the distal portions 176 and 178 the prongs
but not at the distal tip of the prongs. The electrodes 110 and 112
may be located any suitable distance from the distal tip of the
prongs, such as between about 0.1 mm and about 4 mm, about 4 mm and
about 8 mm, or more than 8 mm from the distal dip of the prongs
(e.g., 1 cm from the distal tip). In some variations, the
electrodes 110 and 112 may be located about 2.5 mm from the distal
tip of the prongs. In some variations, the electrodes may be locate
such that when inserted into the nasal cavity, the electrodes are
capable of reaching the nasal mucosa or other area desired to be
stimulated. In some variations, distance from the base member of
the stimulator probe to the longitudinal center of the electrode
(i.e., the farthest the center of the electrode could be inserted
into the nasal cavity) may be between about 25 mm and about 45 mm.
In other variations, the distance from the base member of the
stimulator probe to the longitudinal center of the electrode may be
between about 30 mm and about 40 mm. For example, in some
variations the distance from the base member of the stimulator
probe to the longitudinal center of the electrode may be about 32.5
mm (labeled as distance "D" in FIG. 5A). In other variations, the
distance from the base member of the stimulator probe to the
longitudinal center of the electrode may be between about 20 mm and
about 60 mm (e.g., between about 25 mm and about 35 mm, between
about 30 mm and about 40 mm, between about 25 mm and about 45 mm,
between about 20 mm and about 40 mm). In other variations, the
distance from the base member of the stimulator probe to the
longitudinal center of the electrode may be between about 8 mm and
about 20 mm. The electrode may have any suitable length, such as
between about 1 mm and about 10 mm, between about 3 mm and about 7
mm, about 5 mm, or more than about 10 mm.
[0065] The electrode(s) described here may be made from one or more
conductive materials. In some variations, the electrodes may
comprise metals (e.g., stainless steel, titanium, tantalum,
platinum or platinum-iridium, other alloys thereof, or the like),
conductive ceramics (e.g., titanium nitride), liquids, gels, or the
like. In some variations, the electrode may comprise one or more
materials configured to promote electrical contact between
electrodes of the stimulator probe and tissue (i.e., all of an
electrodes or a portion of the electrode, such as a covering). In
some instances, the impedance provided by tissue may be at least
partially dependent on the presence or absence of fluid-like
materials (e.g., mucous) in the nasal cavity. The material(s) may
help to minimize the impact of subject tissue impedance by
providing a wet interface between the electrode and tissue, which
may act to normalize the impedance experienced by the electrodes.
This may in turn normalize the output and sensation experienced by
the user.
[0066] In the variation shown in FIGS. 5A-5F, the electrode may
comprise a hydrogel. The hydrogel may be any suitable hydrogel,
including the hydrogels described in U.S. patent application Ser.
No. 14/630,471, filed on Feb. 24, 2015, and titled "POLYMER
FORMULATIONS FOR NASOLACRIMAL STIMULATION," which is hereby
incorporated by reference in its entirety. The hydrogel may be
located within the openings 180 and 182 of the distal portions 176
and 178 of the nasal insertion prongs 106 and 108. The hydrogel
electrode may form about a 100 degree arc of a cylinder, although
it should be appreciated that the hydrogel electrode may in other
variations have other shapes (e.g., a smaller or larger arc, as
described in detail herein). The hydrogel may fill the openings 180
and 182 and the adjacent portions of the central lumens 222 and 224
of the nasal insertion prongs. As such, the hydrogel may surround
the axial portion of the leads located adjacent to the openings 180
and 182. In some variations, the distal portions 176 and 178 of the
nasal insertion prongs may further be covered by a thin hydrogel
skin. The hydrogel skin may help to retain the hydrogel electrodes
within the distal portions 176 and 178 of the nasal insertion
prongs 106 and 108. Additionally or alternatively, in variations
having a hydrogel skin, the hydrogel skin may improve
manufacturability (e.g., by allowing the electrodes to be formed by
dip coating). In some variations, the distal portions 176 and 178
of the nasal insertion prongs 106 and 108 may comprise retention
columns located between the surface of the electrode and the
central lumens 222 and 224. The retention columns may help to
retain the leads within the central lumens, and when the electrodes
comprise a hydrogel, may help to retain the hydrogel within the
opening 180 and 182.
[0067] When a nasal insertion prong or prongs of the stimulators
described here comprise one or more electrodes, the electrodes may
comprise leads. When the stimulator probe is connected to a
stimulator body, the leads may contact the circuitry of the
stimulator body to electrically connect the electrodes to the
stimulator body circuitry, as described in more detail herein. As
such, the leads may extend at least partially through each of the
nasal insertion prongs. The leads may be formed from one or more
conductive materials (e.g., stainless steel, titanium, platinum or
platinum-iridium, other alloys thereof, or the like), conductive
ceramics (e.g., titanium nitride), and may be positioned such that
at least a portion of each lead contacts a respective electrode to
provide a conduction pathway between the lead and the
electrode.
[0068] The leads of stimulator probe 104 can be seen in the
cut-away view in FIG. 5C. As shown there, the leads 130 and 132 may
each comprise a spring. The springs comprising leads 130 and 132
may comprise any suitable biocompatible conductive material or
materials. For example, in some variations, the springs may
comprise stainless steel. In other variations, the springs may
comprise gold or platinum. In some variations, the springs may
comprise two or more materials (e.g., stainless steel with gold
plating). The leads 130 and 132 may extend through the central
lumens 222 and 224 of the nasal insertion prongs 106 and 108,
respectively. A portion of the leads (e.g., the distal ends) may
contact the electrodes. For example, distal ends of the leads 130
and 132 may extend through the hydrogel forming electrodes 110 and
112, as described in more detail herein. In variations in which the
leads comprise springs, the wound coil of the springs may allow for
a greater conductive surface between the leads and the hydrogel
electrode as compared to a single straight wire. Additionally or
alternatively, the wound coil of the springs 130 and 132 may grip
the hydrogel electrode, thus better retaining it within the distal
portions 176 and 178 of the nasal insertion prongs 106 and 108. The
proximal ends of the leads 130 and 132 may extend through the
lumens 208 and 210 through the rigid support 218, such that the
proximal ends of the leads are able to contact the circuitry of the
stimulator body, as described in more detail herein. In variations
in which the leads comprise springs, the proximal ends 184 and 186
of the springs may have a tighter pitch than the rest of the
springs. This may create a more even surface to contact the
circuitry of the stimulator body. The spring force may also promote
contact between the leads and the circuitry of the stimulator body,
as described in more detail herein. Additionally or alternatively,
the proximal ends 184 and 186 may have a different (e.g., greater)
coil diameter than the rest of the springs, which may also improve
the contact between the leads and a portion of the stimulator body.
It should be appreciated the leads need not comprise springs. In
other variations, for example, stimulator probes may comprise leads
comprising a conductive loop.
[0069] Generally, when the stimulator probes described here are
configured to deliver an electrical stimulus, the external surfaces
of any of the stimulator probes described herein may be insulated,
with the exception of the electrodes. This may help to prevent
inadvertent stimulation of other tissue (e.g., by direct tissue
contact with a lead instead of with an electrode). Accordingly, in
some variations, the prongs may be formed from or otherwise coated
with one or more insulating materials (e.g., PTFE, silicone,
combinations thereof, or the like). For example, in the variation
of the stimulator probe shown in FIGS. 5A-5F, the first and second
prongs may be formed from an insulating material such as a flexible
polymer (e.g., a thermoplastic elastomer (e.g., thermoplastic
elastomer alloys (e.g., VERSAFLEX.TM. thermoplastic elastomer),
thermoplastic polyurethanes, or the like), silicone, or the like),
and the leads may be positioned inside the prongs such that they
are electrically insulated from the exterior surfaces of the first
and second prongs during use of the stimulator probe, as described
herein. Accordingly, in these instances, electrical stimulation
energy provided to the leads may be delivered via the
electrodes.
[0070] Other variations and features of stimulator probes and
components thereof are described in U.S. application Ser. No.
14/256,915, filed Apr. 18, 2014, and titled "NASAL STIMULATION
DEVICES AND METHODS," which was previously incorporated by
reference in its entirety. For example, while the stimulator probes
in the figures described herein are shown as having two nasal
stimulation prongs, it should be appreciated that in other
variations the stimulator probe may have any suitable number of
prongs (e.g., one, two, or three or more prongs). Similarly, the
stimulators may comprise any suitable number of electrodes (e.g.,
one, two, three, or four or more electrodes), and the electrodes
may be positioned on any suitable portion of the stimulator (e.g.,
the stimulator body and/or a stimulator probe).
Connection Between Stimulator Body ct Probe
[0071] The stimulator probes described here (and any prongs
thereof) may be connected to a stimulator body in any suitable
manner. In some variations, a stimulator probe may be configured to
directly connect to a stimulator body. In these variations, at
least a portion of the stimulator probe may have a fixed location
and orientation with respect to the stimulator body when the two
are connected. In some of these variations, the stimulator probe
may be permanently connected to the stimulator body. For example,
the stimulator probe and stimulator body may be formed together
such that they are permanently connected. In other variations, the
stimulator probe may clip, latch, snap onto, or otherwise
mechanically connect to the stimulator body. In some of these
variations, the stimulator probe may be releasably connected to the
stimulator body, such that the stimulator probe may be disconnected
from the stimulator body after being connected.
[0072] For example, stimulator body 102 and stimulator probe 104 of
stimulator 100 may be removably connected such that a portion of
the stimulator probe 104 directly contacts and connects to the
stimulator body 104. FIG. 7 depicts a perspective view of the
stimulator 100 showing the connection mechanism. As shown there,
the distal portion 206 of the top housing 142 of the stimulator
body 102 and the proximal portion of the stimulator probe 104 may
comprise corresponding and complementary shapes, which may allow
the stimulator body 102 and stimulator probe 104 to be attached.
For example, the distal portion 206 of the top housing 142 of the
stimulator body and the proximal surface of the rigid support 218
of the stimulator probe 104 may comprise features that allow them
to be reversibly attached. For example, in the variation shown the
distal portion 206 of the top housing 142 of the stimulator body
102 may comprise two notches 192 on a first side and two notches
194 on a second side. The proximal surface of the rigid support 218
of stimulator probe 104 may comprise four corresponding tabs: two
tabs 196 on a first side and two tabs 198 on a second side (shown
in FIG. 5E). The stimulator body 102 and stimulator probe 104 may
be snapped together by first placing tabs 198 of the stimulator
probe 104 into the notches 194 of stimulator body 102, and then
manipulating the probe 104 and body 102 such that the first side of
the simulator body 102 is rotated toward the first side of the
stimulator probe 104. In doing so, the tabs 196 of the stimulator
probe 104 may be rotatably inserted into the notches 192 of the
stimulator body 102. The tabs 196 and 198 and notches 192 and 194
may have increased height and depth, respectively, at their
proximal ends, such that the probe 104 and body 102 are held
together by the tabs and notches when connected.
[0073] Conversely, the stimulator probe 104 may be removed from the
stimulator body 102 by rotating the first side of the probe 104 and
first side of the body 102 away from each other. It may be
desirable for the stimulator to be configured such that when a user
inserts the stimulator probe 104 into his/her nasal cavities, if
the user presses a portion of the stimulator prongs (e.g., the
electrodes) against tissue (e.g., tissue near the front of the
nose), the force on the stimulator probe reinforces the connection
between the stimulator probe 104 and the stimulator body 102. That
is, the force from the user's tissue may desirably tend to push the
first side of the stimulator body 102 toward the first side of the
stimulator probe 104. If, instead, the force tended to push the
first side of the probe 104 and the first side of the body 102 away
from each other, there could be an increased risk of the probe
being inadvertently disconnected from the stimulator body during
stimulation, In some variations, as described in more detail below,
the stimulator probe 104 may further comprise tab 200 configured to
fit into notch 202 of stimulator body 102, which may help the
control subsystem 136 to register the connection of the stimulator
probe 104 to the stimulator body 102.
[0074] It should be appreciated that in other variations, the
stimulator body and stimulator probe may have any suitable features
for being attached, such as other snapping mechanisms (e.g., having
different shapes or different numbers of features), magnets,
friction fits, a latching mechanism, or the like. For example, in
some variations the stimulator body may comprise a magnet (e.g.,
magnet 134 of stimulator body 102) connected to the interior
surface of the proximal housing the stimulator body. The stimulator
probe may comprise a magnet or ferromagnetic material in a
corresponding location (e.g., in the base member of the stimulator
probe), which may retain the stimulator probe on the stimulator
body.
[0075] Generally, when the stimulators described here are
configured to deliver an electrical stimulus, the electrodes of the
stimulator may be electrically connected to the stimulator
circuitry, such that the stimulator may generate a stimulus and
deliver it to tissue via one or more of the electrodes.
Accordingly, the stimulators described here may comprise one or
more electrical connections configured to electrically connect the
electrode via a lead to a portion of the stimulator body (e.g., a
stimulation subsystem housed in the stimulator body). In variations
in which the stimulator probe and stimulator body are indirectly
connected, the indirect connection (e.g., a cable, cord, or the
like) may serve as the electrical connection between the stimulator
circuitry and the electrodes. In variations in which the stimulator
probe and the stimulator body are directly connected, the
stimulator body and stimulator probe may comprise conductive
elements configured to electrically connect the electrodes of the
stimulator probe to the stimulator circuitry when the body and
probe are connected.
[0076] For example, as shown in FIG. 1D, the electrodes 110 and 112
of stimulator probe 104 may be connected to leads 130 and 132
located within nasal insertion prongs 106 and 108, respectively.
The corresponding stimulator body 102 may comprise connectors 122
and 124 directly or indirectly connected to the control subsystem
136 and power source 152. The distal ends of the connectors 122 and
124 may be configured to connect with the proximal ends of the
leads 130 and 132 of the stimulator probe 104. As shown in FIG. 3A,
in some variations the distal ends of the connectors may comprise a
rounded surface. In variations in which the leads comprise springs,
the proximal ends of the springs may have a tighter pitch than the
rest of the springs. This may create a more even surface to contact
proximal ends of the connectors, and thus may allow for a better
electrical connection between the leads of the stimulator probe 104
and the connectors of the stimulator body 102.
[0077] When the proximal ends of the springs of stimulator probe
104 are in contact with the connectors 122 and 124 of the
stimulator body 102, the springs may be compressed. This
compression may cause the springs to generating a restoring force.
The restoring force may promote contact between the springs and the
connectors 122 and 124. However, in variations in which the
stimulator probe 104 is removably connectable to the stimulator
body 102, the restoring force may also act against the force of the
connection mechanism holding together the stimulator probe and the
stimulator body (e.g., notches 192 and 194 and tabs 196 and 198).
Thus, it may be desirable for the spring stiffness to be low enough
that the restoring force of the springs does not cause the
stimulator probe to disconnect from the stimulator body.
[0078] The connectors 122 and 124 may extend through lumens 208 and
210 in the proximal housing 142, and the proximal ends may be
directly or indirectly attached to the control subsystem. As shown
in FIG. 3D, the proximal ends of the connectors 122 and 124 may
comprise slots configured to receive the distal ends of contact
strips 244. The proximal ends of contact strips 244 may be attached
to the control subsystem 136 (i.e., may be attached to the printed
circuit board 128). The connectors and contact strips may comprise
any suitable conductive material or materials, such as but not
limited to stainless steel, titanium, copper, nickel, brass, zinc,
or the like, which may in some instances be gold-plated.
[0079] It should be appreciated that the stimulator body and
stimulator probe may additionally or alternatively be inductively
coupled, such that power may be transferred from the stimulator
body to the stimulator probe via induction. In these variations,
the stimulator body and stimulator probe may each comprise a coil.
In some variations, each of the coils may be wrapped around a
ferromagnetic (e.g., iron) core, but need not be. In some
variations, the coil of the stimulator body and/or stimulator probe
may be a printed coil.
[0080] Other variations and mechanisms for physical and electrical
connection between the stimulator body and stimulator probe are
described in U.S. application Ser. No. 14/256,915, filed Apr. 18,
2014, and titled "NASAL STIMULATION DEVICES AND METHODS," which was
previously incorporated by reference in its entirety.
[0081] In some variations, some or all of the stimulator may be
disposable. In variations where the stimulator body is permanently
attached to the stimulator probe, the entire stimulator may be
disposable. In other variations, one or more portions of the
stimulator may be reusable. For example, in variations where the
stimulator probe is releasably connected to the stimulator body,
the stimulator body may be reusable, and the stimulator probe may
be disposable. As such, the stimulator probe may be periodically
replaced. In yet other variations, a portion of the stimulator
probe may be disposable (e.g., the stimulator probe may comprise
disposable sleeves or disposable prongs) and may be periodically
replaced. In some variations, the stimulators described here may
comprise features that encourage or require a user to replace a
stimulator or stimulator components after a certain period or on a
regular basis in order to main proper hygiene.
[0082] In variations in which the entire stimulator is disposable
(e.g., when the stimulator probe is integrally formed with or
permanently attached to the stimulator body), the stimulator may be
configured to become non-operational after a certain period of time
and/or use. In some of these variations, the stimulator may be
configured to limit the duration of stimulation that may be
provided by the stimulator; after the duration limit, the
stimulator may be configured to become non-operational. For
example, the stimulator may have a power source that is only
sufficient to power stimulus delivery for a predetermined duration
(e.g., one hour of stimulation). Once the power source has been
depleted, a user may need to replace the spent stimulator with a
new stimulator. In some of these variations, the stimulator may be
configured such that the power source cannot be accessed without
rendering the device inoperable, which may help prevent users from
replacing the power source.
[0083] As another example, the stimulator additionally or
alternatively may be programmed to limit the duration or amount of
stimulus delivery with a given stimulator. In some of these
variations, the stimulator may be configured to measure and store
the duration of stimulation provided by the stimulator over time
(which may be cumulatively added over a plurality of different
treatment sessions). When the duration reaches a threshold limit
(e.g., about 10 minutes, about 30 minutes, about one hour, about 2
hours, or longer than 2 hours), the stimulator may be programmed to
switch to an inoperable state, whereby the stimulator may not be
activated to provide additional stimulation. As another example,
the stimulator additionally or alternatively may be configured to
limit the number of treatment sessions provided by the stimulator.
In some of these variations, the stimulator may be configured to
measure and store the number of treatment sessions provided by the
stimulator. When the number of treatment sessions reaches a
threshold limit (e.g., five uses, ten uses, fifteen uses, or more
than fifteen uses), the stimulator may be programmed to switch to
an inoperable state, whereby the stimulator may not be activated to
provide additional stimulation.
[0084] In these or other variations in which the entire stimulator
is disposable, the stimulator may additionally or alternatively be
configured to become non-operational after a certain period of time
after its first use. The stimulator may be configured to limit the
duration since the first use of the stimulator; after the duration
limit, the stimulator may be configured to become non-operational.
In some of these variations, the stimulator may be configured to
store date and time information regarding the first use of the
stimulator. The stimulator may be further configured to switch to
an inoperable state when a predetermined amount of time (e.g., one
day, two days, five days, one week, two weeks, or longer than two
weeks) has passed from the first use of the stimulator.
[0085] In any of these variations, the stimulator may be configured
to limit the duration of stimulus delivery, the number of treatment
sessions, or the duration since first use via a control subsystem,
which may in some instances comprise intelligence such as a
microcontroller, programmable logic (e.g., a field-programmable
gate array), or an application-specific integrated circuit (ASIC)
configured to measure, store, and limit the duration and/or number
of treatment sessions and/or the time since first use of the
stimulator. In any of these variations, when the device moves to an
inoperable state, the user may need to replace the inoperable
stimulator with a new stimulator.
[0086] In variations in which the stimulator body is reusable and
all or a portion of the stimulator probe is disposable, the
stimulator may be configured to encourage and/or require the user
to replace all or a portion of the stimulator probe. In some of
these variations, the disposable portion probe or portion of the
probe may comprise a recyclable material. In some of these
variations, the stimulator may be configured such that the
stimulator probe or a portion thereof becomes inoperable after
being attached to the stimulator body for a predetermined amount of
time (e.g., between about 1 hour and about 24 hours, between about
1 day and about 7 days, between about 1 week and about 4 weeks,
between about 1 month and about 3 months, or longer than about 3
months), after a predetermined number of treatment sessions, and/or
after a predetermined duration of stimulation (e.g., between about
2 minutes and about 30 minutes, between about 30 minutes and about
1 hour, between about 1 hour and about 3 hours, between about 3
hours and 12 hours, or longer than about 12 hours).
[0087] For example, in some variations of stimulators comprising
one or more electrodes, the electrodes of the stimulator probe may
become inoperable after being attached to the stimulator body for a
predetermined amount of time, after a predetermined number of
treatment sessions, and/or after a predetermined duration of
stimulation. For example, in some variations it may be desirable to
promote oxidation of one or more of the electrodes during
stimulation. In these variations, the electrode may be configured
to form a non-conductive (or reduced conductivity) layer on the
surface of the electrode. In some variations, this may interfere
with the ability of the electrode to stimulate tissue, and
eventually the oxide layer may substantially prevent any electrical
energy from being supplied to the user. In some instances, to form
such a layer, the stimulator may be configured to deliver biphasic
pulses using the electrodes, wherein the biphasic pulses are not
charge-balanced. By not charge-balancing the stimulation pulses,
charge may accumulate on one or more of the electrodes and/or
leads, which may facilitate oxidation of the metal of the electrode
and/or lead. The rate of the oxidation may be controlled at least
partially by the materials of the electrode and/or lead and the
parameters of the pulses delivered by stimulator, and the rate of
oxidation may be tailored to achieve a predetermined treatment
duration or number of treatment sessions before formation of an
oxide layer may render the stimulator inoperable. As another
example, in some variations, an electrode of a stimulator probe
additionally or alternatively may be configured to change color
over time (e.g., as a result of delivering stimulation, as a result
of carbon dioxide exposure, as a result of oxidation), such that a
user may be prompted to change the stimulator probe when the
electrode reaches a certain color. In these variations, the
stimulator probe or a portion of the stimulator probe (e.g., nasal
insertion prongs or sleeves comprising the electrodes) may be
replaced when the electrodes of the stimulator probe are unable to
provide stimulation or when the stimulator encourages replacement
via the color change.
[0088] As yet another example, in some variations the stimulator
may be programmed to render the stimulator probe inoperable and/or
to encourage replacement of the stimulator probe or a portion
thereof (e.g., disposable prongs or sleeves) after being attached
to the stimulator body for a predetermined amount of time, after a
predetermined number of treatment sessions, and/or after a
predetermined duration of stimulation. In some of these variations,
the stimulator may be programmed to measure the duration of
stimulation provided using a specific stimulator probe or portion
thereof, the number of treatment sessions provided using a specific
stimulator probe or portion thereof, and/or the duration of
attachment of a specific stimulator probe or portion thereof to the
stimulator, via mechanisms described in more detail herein. In
variations where the stimulator is programmed to measure multiple
of the above-listed parameters, if the measurement reaches a
threshold value, the stimulator may be configured to alert the user
and/or to enter an inoperable state until the current stimulator
probe or portion thereof is replaced. In variations where the
stimulator is programmed to measure multiple of the above-listed
parameters, the stimulator may be configured to alert the user
and/or enter the inoperable state when any of the measured
parameters reaches its threshold value, or the stimulator may
require multiple of the measured parameters to reach their
corresponding threshold values in order to alert the user and/or
enter an inoperable state. The stimulator may alert the user in any
suitable manner, including visual feedback (e.g., generating a
prompt on a display, activating a LED, notifying the user on
another device, such as a computer or mobile device, or the like),
audio feedback (e.g., generating one or more beeps or audio
prompts), and/or tactile feedback (e.g., vibrating the stimulator).
Similarly, in variations in which the stimulator has entered its
inoperable state, the stimulator may additionally or alternatively
be configured to instruct the user to replace the stimulator probe.
This may also be done in any suitable manner, including visual,
audio, or tactile feedback.
[0089] Additionally or alternatively, in some variations the
stimulator may be configured to alert the user and/or enter an
inoperable state when a used stimulator probe is attached to the
stimulator body. The stimulator may alert the user in any suitable
manner, and may additionally or alternatively be configured to
instruct the user to replace the stimulator probe, as described
herein. In these variations, the stimulators may comprise a
mechanism for determining whether the attached stimulator probe is
new (i.e., whether the stimulator probe has been previously
attached to a stimulator body or not). In some variations, the
mechanism for determining whether the stimulator probe is new may
comprise a fuse. In some variations, the fuse may temporarily short
circuit the stimulator circuitry while the probe is being connected
to the stimulator body.
[0090] One or more mechanisms for determining when a stimulator
probe is attached may also be used in some variations to render the
stimulator probe inoperable and/or to encourage replacement of the
stimulator probe or a portion thereof (e.g., disposable prongs or
sleeves) after a predetermined number of treatment sessions, and/or
after a predetermined duration of stimulation. In some of these
variations, attachment of the stimulator probe may be registered
using one or more of these mechanisms, and the stimulator may be
programmed to measure the duration of stimulation or number of
treatment sessions provided using that stimulator probe. The
stimulator may be configured to do so via intelligence in a control
subsystem, such as a microcontroller, programmable logic (e.g., a
field-programmable gate array), or an application-specific
integrated circuit (ASIC).
[0091] In some variations, the stimulators described here may be
configured such that it may be necessary to replace a disposable
stimulator probe in order to recharge the stimulator or to replace
a power supply of the stimulator. For example, in some variations
where the stimulator comprises one or more electrical contacts or
ports configured to connect to an external power source, the
stimulator probe may be configured to cover or otherwise block
access to the electrical contacts/ports when the stimulator probe
is connected to the stimulator body. In these variations, it may be
necessary to remove the stimulator probe to provide access to the
electrical contacts/ports (which may in some variations disable the
stimulator probe, as described in more detail below). Similarly, in
variations where the stimulator body includes a replaceable power
source (e.g., one or more batteries), the stimulator probe may
block access to the replaceable power source such that the
stimulator probe may need to be disconnected from the stimulator
body prior to replacing the power source.
[0092] In variations where a stimulation system comprises a base
station (as described in more detail herein), a stimulator may be
configured such that the stimulator cannot be connected to the base
station while a stimulator probe is attached to the stimulator
body. For example, in the variations of the stimulation systems
shown in FIGS. 10A-10D described in more detail herein, the base
station may comprise a recess sized and configured to receive the
stimulator body to operationally connect the stimulator body to the
base station. Specifically, the recess may be sized such that the
stimulator body can fit within the recess when the stimulator probe
is disconnected from the stimulator body (as illustrated in FIG.
10A), but is prevented from fitting in the recess when the
stimulator probe is attached to the stimulator body. In these
variations, it may be necessary to first disengage the stimulator
probe. Accordingly, to utilize one or more functions of the base
station, a user may need to first decouple a stimulation probe from
the stimulator body before connecting the stimulator body to the
base station. In some variations, the stimulator probe may comprise
a lockout mechanism that prevents the stimulator probe from being
reconnected to the stimulator body after being disconnected from
the stimulator body. For example, the stimulator may be configured
such that the stimulator probe is disabled when disengaged from the
stimulator body (e.g., when the probe is disengaged from the
stimulator body in order to connect the stimulator body to the base
station). This may prevent the stimulator probe from being
reused.
[0093] It should be appreciated that any suitable method may be
used to determine whether and for how long a stimulator probe is
attached, to alert the user and/or enter an inoperable state when a
used stimulator probe is attached to the stimulator body, and/or to
render the stimulator probe inoperable and/or to encourage
replacement of the stimulator probe or a portion thereof, including
the methods and mechanisms described in U.S. application Ser. No.
14/256,915, filed Apr. 18, 2014, and titled "NASAL STIMULATION
DEVICES AND METHODS," which was previously incorporated by
reference in its entirety.
Cap & Case
[0094] In some variations, the stimulators described here may
comprise a cap to protect the stimulator probe. For example, FIGS.
9A and 9B show perspective and front views, respectively, of
stimulator 100 with an attached cap 900. As shown there, the cap
900 may fit over the stimulator probe 104, which may protect the
probe from contamination. More particularly, it may be desirable
for the cap to protect the nasal insertion prongs, and especially
the electrodes, from contamination. The cap 900 may have any
suitable shape. In some variations, the cap 900 may cover the
operating mechanisms when attached to the stimulator. This may
prevent the operating mechanisms from being inadvertently or
accidentally manipulated. As shown in FIGS. 9A-9B, the cap 900 may
cover the buttons 114 and 116 of the stimulator body 102, while
leaving the sides of stimulator body 102 exposed. This may allow a
user to more easily grip the stimulator body 102 in order to remove
the cap 900. In some variations the cap may comprise a texturized
surface or other gripping features to assist with removal, such as
ridges 904 shown on cap 900. The cap or other enclosure may
comprise any suitable material or materials, such as a plastic or
synthetic resin. In some variations the cap or other enclosure may
be translucent or transparent, while in other variations it may be
opaque.
[0095] The cap or other enclosure may in some variations comprise
one or more features to control the exposure of the stimulator
probes to the air. When the probes comprise a hydrogel or other
liquid or wet material, the amount of exposure of air may affect
the rate at which the hydrogel or other liquid or wet material
dries out. For example, in some variations the caps may comprise
one or more openings to allow for air flow underneath the cap or
other enclosure. Cap 900, for example, may comprise an opening 902
at the distal end of the cap. In some variations the cap may be
generally conformed to the shape of the stimulator probe (e.g., by
comprising recesses having shapes corresponding to the stimulator
prongs' shape and configured to receive the prongs), such that the
air within the cap is minimal; in other variations, the cap may not
be conformed to the shape of the stimulator probe, such that there
is more air circulating within the cap around the stimulator
probe.
[0096] In some variations, the cap may comprise one or more
features to promote attachment of the cap to the stimulator body.
For example, in some variations the cap may comprise tabs or
bosses, which may be configured to mate with indentations or
cavities on the stimulator. Additionally or alternatively, the
stimulator may comprise tabs or bosses, which may be configured to
mate with indentations or cavities on the cap. In some of these
variations, the flexibility of the cap material may allow cap to be
placed on the stimulator. Additionally or alternatively, the cap
may comprise one or more living hinges or cutaways 906 and 908,
such as shown in FIG. 9C. The living hinges or cutaways may allow
the cap to flex in order to slide past a raised feature on the
stimulator (e.g., a tab or boss); for example, squeezing the top
cutaway 906 may cause the bottom portion 908 to rotate away from
the stimulator, allowing the bottom portion 908 to slide past a
raised feature when attaching or removing the cap 900. Additionally
or alternatively, the cap material and/or shape may promote
attachment of the cap to the stimulator body. For example, the cap
may be flexible in order to flex to slide over a thicker portion of
the stimulator while being attached, and then the cap may relax
into a conformal position upon reaching a thinner portion of the
stimulation.
[0097] Other variations and features of caps or enclosures, as well
as cases configured to hold stimulators, are described in U.S.
application Ser. No. 14/256,915, filed Apr. 18, 2014, and titled
"NASAL STIMULATION DEVICES AND METHODS," which was previously
incorporated by reference in its entirety.
Base Station
[0098] In some variations, the stimulation systems described here
may comprise a base station configured to connect to a portion of
the stimulator, the stimulator having a stimulator body and a
stimulator probe. The base station may be configured to releasably
connect to one or more portions of the stimulator, and may be
configured to perform one or more functions when connected to the
stimulator. FIGS. 10A-10D depict a portion of a stimulator system
comprising a base station 1000 as described here. FIG. 10A shows a
front view the stimulator body 1002 docked in the base station
1000, while FIGS. 10B, 10C, and 10D depict side, back, and top
views of the base station 1000, respectively. The stimulator body
1002 and stimulator probe (not shown) may include any of the
elements of the stimulators described herein. In variations where
the stimulator body 1002 comprises a rechargeable power source
(such as a rechargeable battery, capacitor, or the like), the base
station 1000 may be configured to recharge the rechargeable power
source. For example, the base station 1000 may comprise one or more
electrical contacts 1004, which may be configured to electrically
connect to corresponding electrical contacts on the stimulator body
1002. In some variations, these electrical contacts may be the same
electrical contacts that connect the stimulator probe and the
stimulator body (e.g., electrical contacts similar to connectors
122 and 124 of stimulator 100). This electrical connection may
allow the base station 1000 to charge the power source of the
stimulator body 1002.
[0099] In some variations, the base station may comprise a safety
mechanism that prevents power delivery to the electrical contacts
unless the stimulator is connected. For example, the base station
may comprise a sensor configured to detect the stimulator. After
the stimulator is detected, power may be delivered to the contacts.
In one variation, the sensor may comprise a magnetic field sensor
(e.g., a Hall effect sensor), and the stimulator may comprise a
magnet. When the stimulator is placed in the base station, the
magnetic field sensor may detect the presence of the magnet in the
stimulator and may in turn cause power to be delivered to the
contacts.
[0100] It should be appreciated that in other variations, the base
station may additionally or alternatively be configured to
inductively charge the stimulator. For example, the base station
may comprise a primary coil, which may or may not be wrapped around
a ferromagnetic (e.g., iron) core, and the stimulator body may
comprise a secondary coil, which may or may not be wrapped around a
ferromagnetic core. When the stimulator body is placed in the base
station, the coils and iron cores may form a complete transformer,
allowing power to be inductively transferred from the base station
to the stimulator body. Additionally or alternatively, it should be
recognized that inductive power transfer may also be used to
transfer power from the stimulator body to the stimulator
probe.
[0101] The base station may be powered in any suitable manner. In
some variations, the base station may be connectable to an external
power source (e.g., a wall outlet or separate battery back), which
may provide power to the stimulator and/or the base station. In
some variations, the base station may comprise a power cable, which
may be permanently attached via a strain relief. In other
variations, such as the variation of the base station 1000 shown in
FIGS. 10A-10D, the base station may comprise a port 1006 (e.g., a
USB port or micro-USB port), which may connect the base station
1000 to an external power source. It should be appreciated that the
base station 1000 may include any suitable port or connector for
connecting the base station to an external power source.
Additionally or alternatively, the base station may comprise a
power source (e.g., one or more batteries) operable to power the
base station 1000 (and to recharge the stimulator in variations
where the stimulator is rechargeable). The power source may or may
not be rechargeable.
[0102] The base station 1000 may be configured to rest on a surface
(e.g., a counter or table), and may comprise a weight and/or a
bottom surface with increased friction (e.g., a rubber pad 1008) to
help keep the base station 1000 in place. In variations in which
the stimulator comprises a magnet or material attracted to a
magnetic field (e.g., iron, nickel, cobalt, alloys thereof and the
like), the base station may comprise a magnet in a corresponding
location in order to hold the stimulator in place within the base
station. For example, the base station may comprise a magnet
located between the electrical contacts, which may be configured to
attract a magnet in the stimulator body (e.g., in a base station
configured to receive stimulator body 102, the base station may
comprise a magnet configured to attract the magnet 134 attached to
the interior of proximal housing 142.).
[0103] In instances where the stimulator is configured to record or
otherwise store data (e.g., the frequency or duration of
stimulation), the base station may be configured to retrieve data
from the stimulator. For example, in variations where the
stimulator and base station are configured to be electrically
connected, data may be transmitted via this electrical connection
(e.g., the connection between connectors 122 and 124 of stimulator
body 102 and electrical contacts 1004 of base station 1000). FIG. 8
illustrates a schematic diagram of stimulator circuitry allowing
for the same pins 802 to be used to transfer data from the
stimulator body to the base station, to transmit a stimulus from
the stimulator body to the stimulator probe, and to charge a
rechargeable power source in the stimulator body using the base
station. As shown, the pin drivers 804 may take input signals
either from a data communication subsystem 806 or a stimulation
subsystem 808. The input to the drivers 804 may be determined by a
switch 810. In some variations, the switch 810 may comprise a gate,
state machine, or a micro-controller. The pins 802 may also be used
to charge the stimulator. A rectification circuit 812 may be
configured to rectify a charging input signal without interfering
with any output stimulation or data waveform. In some variations,
the rectification circuit may comprise a full wave rectifier
comprising rectification diodes, but it should be appreciated that
any suitable circuit may be used. Time blocks for each function may
be synchronized in order for the system to perform each
function.
[0104] Other variations and features of base stations are described
in U.S. application Ser. No. 14/256,915, filed Apr. 18, 2014, and
titled "NASAL STIMULATION DEVICES AND METHODS," which was
previously incorporated by reference in its entirety.
[0105] In some variations the stimulators described here may be
configured to connect to an external device, such as a mobile
device (e.g., a cellular telephone, a tablet, a wearable computer
(e.g., optical head-mounted displays such as Google GLASS.TM.
wearable computing device), or the like), a computer, or the like.
The stimulators may be configured to connect to an external device
through any suitable connection method. In some variations the
connection method may be wireless (e.g., via Wi-Fi, BLUETOOTH.TM.
wireless technology, or the like), and the stimulator may comprise
an antenna or the like. Additionally or alternatively, the
connection method may be via a wired transmission line. In these
variations, the stimulator may comprise one or more ports (e.g., a
USB port), connectors and/or cables configured to physically
connect the stimulator to an external device. In some variations,
the stimulators may use a wireless or wired connection to connect
to the internet, via which they may be connected to an external
device. In these variations, the device may be at a distant
location (e.g., at the manufacturer, at a physician's office, or
the like).
[0106] In instances in which the stimulators are configured to
connect to an external device, the device may be configured to
perform one or more operations associated with the stimulator. For
example, in variations where the stimulator is configured to
collect data (e.g., one or more subject parameters, stimulation
timing or parameters, stimulator diagnostic information, such as
described in more detail herein) and store that data in a memory
unit of the stimulator, connection of the stimulator to the device
may allow for transfer of data stored in the stimulator's memory
unit to the device. Specifically, the device and stimulator may be
programmed such that upon connection of the device and the
stimulator, the device may download the recorded data stored in the
stimulator's memory. In some variations, once data has been
transferred from the stimulator to the device, the stimulator may
be configured to delete this data from the stimulator memory.
Because the amount of memory available in the device may be greater
than that in the stimulator, this transfer may increase the data
that may be accumulated for a subject.
[0107] In addition to or instead of transferring data stored in the
stimulator memory, a device may be configured to collect and store
real-time data from the stimulator when the two are connected. In
some of these variations, the stimulator may also be configured to
store this data in the stimulator memory. In some instances, the
device may be configured to transmit data (e.g., via internet
connection, cellular data network, or the like) from the device to
an external location (e.g., to a database where the data may be
analyzed, to a physician's office to allow the physician to monitor
the data and, in some instances, provide feedback).
[0108] In some variations, the device may be configured to solicit
input from a user. For example, if the stimulator is used to
provide stimulation while attached to a device, the device may be
configured to solicit the user to input data regarding the
subject's experience (e.g., a subject's level of
comfort/discomfort, status of subject's symptoms). In some
variations, the device may be configured to present data (and/or
analysis of the data) to a user. For example, the device may be
configured to display information regarding the frequency of
stimulation, the average duration of stimulation, a graph of
subject comfort levels over time, or the like. In some variations,
the device may be configured to share the data or analysis of the
data with the manufacturer, clinicians, friends, or others.
[0109] It should be appreciated that while certain handheld
stimulators have been described herein, handheld stimulators for
use in the methods described herein may have any suitable
configuration. In addition to those described herein and in U.S.
application Ser. No. 14/256,915, filed Apr. 18, 2014, and titled
"NASAL STIMULATION DEVICES AND METHODS," which was previously
incorporated by reference in its entirety, additional handheld
stimulators suitable for use in the methods described herein are
described in U.S. patent application Ser. No. 14/920,860, filed
Oct. 22, 2015, and titled "STIMULATION DEVICES AND METHODS FOR
TREATING DRY EYE," which is hereby incorporated by reference in its
entirety. Furthermore, while handheld stimulators have been
described above, it should be appreciated that in other variations
of the stimulation systems described here, the stimulation system
may comprise a stimulator configured to be implanted, either
permanently or temporarily, in a subject. It should be appreciated
that the implantable stimulators need not be surgically implanted.
In some of these instances, the implantable stimulator may be
configured such that the stimulator may be inserted and/or removed
by a user. In others of these instances, the implantable stimulator
may be configured to be inserted and/or removed by a medical
professional. In other instances, the stimulator may be configured
to be implanted in or otherwise attached to tissue within a nasal
or sinus cavity. Variations and features of implantable stimulators
are described in U.S. application Ser. No. 14/256,915, filed Apr.
18, 2014, and titled "NASAL STIMULATION DEVICES AND METHODS," which
was previously incorporated by reference in its entirety, and in
U.S. patent application Ser. No. 14/920,852, filed Oct. 22, 2015,
and titled "IMPLANTABLE NASAL STIMULATOR SYSTEMS AND METHODS,"
which is hereby incorporated by reference in its entirety.
Stimulation Methods
[0110] Generally, the stimulators and stimulation systems described
herein may be configured to stimulate nasal or sinus tissue. In
some variations, the stimulation may be used to treat allergic
rhinitis, non-allergic rhinitis, nasal congestion, ocular allergy,
and/or symptoms associated with these conditions. Generally, a
stimulator (such as described above) may be configured to stimulate
trigeminal afferent nerve fibers to activate the nasolacrimal
reflex, which may in turn reduce the symptoms associated with these
conditions. In some of these instances, the methods described
herein may comprise stimulating the anterior ethmoidal nerve. In
other instances, the methods may comprise stimulating the internal
branches of the infraorbital nerve, the superior branches of the
greater palatine nerve, the septal nerve, and/or the posterior
superior lateral nasal branches of the maxillary nerve.
Location
[0111] When an implantable stimulator is used to provide
stimulation, the implantable stimulator may be positioned in a
nasal or sinus cavity (or multiple nasal or sinus cavities). When a
handheld stimulator is used to provide stimulation, one or more
prongs of the stimulator may be inserted at least partially into
the nose of a user, and a stimulation signal (such as described
herein) may be delivered to the mucosal tissue. A portion of the
nasal insertion prong(s) may be positioned and/or manipulated to be
placed in contact with any suitable tissue. In variations in which
the stimulators are configured to deliver an electrical stimulus,
the stimulators may be positioned and/or manipulated to position
electrodes into contact with any suitable tissue. FIGS. 4A-4C
illustrate certain anatomical locations. For example, the nasal
insertion prong(s) may be placed in contact with the upper lip 402,
external nasal skin 404, nasal ala 406, mucosa of a nasal turbinate
(e.g., one or more of the inferior 408, medial 410, or superior
turbinates 412), or the like. When the stimulators are used to
treat nasal congestion, allergic rhinitis, non-allergic rhinitis,
ocular allergy, and/or symptoms associated with these conditions,
it may in some instances be desirable to position a portion of the
nasal insertion prongs (e.g., an electrode) in contact with the
nasal mucosa of a nasal turbinate (e.g., a middle and/or superior
nasal turbinate). In some instances, the targeted are may comprise
tissue innervated by the anterior ethmoidal branch of the
nasociliary nerve, as shown by shaded area 420 in FIG. 11C. In
other instances when the stimulators are used to treat nasal
congestion, allergic rhinitis, non-allergic rhinitis, ocular
allergy, and/or symptom associated with these conditions, the
targeted area may comprise tissue innervated by the internal
branches of the infraorbital nerve; tissue innervated by superior
branches of the greater palatine nerve; tissue innervated by the
septal nerve; tissue innervated by the posterior superior lateral
branches of the maxillary nerve; and/or two or more of these areas.
In some instances, the targeted area of the nasal mucosa may be
superior to the columella 414. In some of these instances, the
targeted area may be near the inferior end of the nasal bone 416
(i.e., near the interface between the nasal bone 416 and the upper
lateral cartilage 418). In other variations, the targeted area may
be the columella. In some variations, it may be desirable to place
a portion of the nasal insertion prong(s) (e.g., an electrode)
between about 20 mm and about 60 mm into the nasal cavity of the
subject. In some of these variations, it may be desirable to place
an electrode between about 20 mm and about 35 mm into the nasal
cavity of the subject. In some of these variations, it may be
desirable to place an electrode between about 25 mm and about 35 mm
into the nasal cavity of the subject. In some variations, it may be
desirable to place an electrode between about 30 mm and 40 mm into
the nasal cavity of the subject. In some variations, it may be
desirable to place an electrode between about 25 mm and about 40 mm
into the nasal cavity of the subject. In some variations, it may be
desirable to place an electrode between about 20 mm and about 40 mm
into the nasal cavity of the subject. In some variations, it may be
desirable to place and electrode between about 8 mm and about 20 mm
into the nasal cavity of the subject. In some variations, it may be
desirable to place an electrode less than about 30 mm into the
nasal cavity of the subject, less than about 35 mm into the nasal
cavity of the subject, or less than about 40 mm into the nasal
cavity of the subject.
[0112] As described herein, it may in some instances be desirable
to direct the nasal insertion prongs such that a portion (e.g., the
electrodes) is directed toward the front of the nose. This may
allow for selective activation of nerves in the front of the septum
(e.g., the ophthalmic branch of the trigeminal nerve) while
minimizing activation of nerves toward the rear of the nasal
septum, which may reduce negative side effects that may occur from
stimulation of nerves that innervate the teeth. It may also in some
instances be desirable to direct the nasal insertion prongs so as
to reduce negative side effects that may occur from stimulation of
the olfactory area. In other variations when the stimulators are
used to treat nasal congestion, allergic rhinitis, non-allergic
rhinitis, ocular allergy, and/or symptoms associated with these
conditions, it may be desirable to direct the nasal insertion
prongs such that a portion (e.g., the electrodes) is directed
toward the septum. In yet other variations when the stimulators are
used to treat nasal congestion, allergic rhinitis, non-allergic
rhinitis, ocular allergy, and/or symptoms associated with these
conditions, it may be desirable to direct the nasal insertion
prongs such that a portion (e.g., the electrodes) is directed
outward and away from the septum.
Electrical Stimulus
[0113] In some variations, the stimulation may be delivered
unilaterally (e.g., in a single nostril). For example, in
variations where a stimulator comprises a single prong, the prong
may be placed in a first nostril, and stimulation may be delivered
to the first nostril via the prong. It should be appreciated that
in some of these variations in which the stimulus is electrical, a
pad electrode or other return electrode may be temporarily affixed
to or otherwise be placed in contact with an external portion of
the nose to act as a return electrode. In some variations where a
stimulator comprises two or more prongs, each of the prongs may be
placed in a first nostril, and some or all of the prongs may be
used to deliver stimulation to mucosal tissue. In other variations
where a stimulator comprises two or more prongs, at least one prong
may be positioned in a first nostril, and at least one prong may be
positioned in a second nostril. In variations in which the stimulus
is electrical, some or all of the prongs in the first nostril may
be used to deliver unilateral electrical stimulation to the first
nostril (e.g., the prongs in the second nostril may remain
inactive), or some or all of the prongs in the second nostril may
be used to deliver unilateral electrical stimulation to the second
nostril.
[0114] In some variations, the stimulator may be used to provide
bilateral stimulation of the mucosal tissue. In these variations,
at least one prong of the stimulator may be positioned in a first
nostril and at least one prong of the stimulator may be positioned
in a second nostril. In these variations, when the stimulus is
electrical, electrical stimulation may be delivered between the
prongs in the first nostril and the prongs of the second nostril,
which may cause current to flow through the septum.
[0115] When the stimulus is electrical, the electrical stimulus
delivered by the stimulators described here may include a waveform
or waveforms, which may be tailored for specific treatment regimens
and/or specific subjects. The waveforms may be pulse-based or
continuous. It should be appreciated that the waveforms described
here may be delivered via a bipolar configuration or a monopolar
configuration. When the stimulator is configured to deliver a
continuous waveform, the waveform may be a sinusoidal,
quasi-sinusoidal, square-wave, sawtooth/ramped, or triangular
waveform, truncated-versions thereof (e.g., where the waveform
plateaus when a certain amplitude is reached), or the like.
Generally, the frequency and peak-to-peak amplitude of the
waveforms may be constant, but in some variations the stimulator
may be configured to vary the frequency and/or amplitude of the
waveform. This variation may occur according to a pre-determined
plan, or may be configured to occur randomly within given
parameters. For example, in some variations the continuous waveform
may be configured such that the peak-to-peak amplitude of the
waveform varies over time (e.g., according to a sinusoidal function
having a beat frequency). In some instances varying the amplitude
and/or frequency of a stimulation waveform over time, or pulsing
the stimulus on and off (e.g., 1 second on/1 second off, 5 seconds
on/5 seconds off), may help reduce subject habituation (in which
the subject response to the stimulation decreases during
stimulation). Additionally or alternatively, ramping the amplitude
of the stimulation waveform at the beginning of stimulation may
increase comfort.
[0116] When the stimulator is configured to create a pulse-based
electrical waveform, the pulses may be any suitable pulses (e.g., a
square pulse, a haversine pulse, or the like). The pulses delivered
by these waveforms may by biphasic, alternating monophasic, or
monophasic, or the like. When a pulse is biphasic, the pulse may
include a pair of single phase portions having opposite polarities
(e.g., a first phase and a charge-balancing phase having an
opposite polarity of the first phase). In some variations, it may
be desirable to configure the biphasic pulse to be charge-balanced,
so that the net charge delivered by the biphasic pulse is
approximately zero. In some variations, a biphasic pulse may be
symmetric, such that the first phase and the charge-balancing phase
have the same pulse width and amplitude. Having a symmetric
biphasic pulse may allow the same type of stimulus to be delivered
to each nasal cavity. The pulses of a first phase may stimulate a
first side of the nose (while providing a charge-balancing phase to
a second side of the nose), while the pulses of the opposite phase
may stimulate the second side of the nose (while providing a
charge-balancing phase to the first side of the nose). In other
variations, a biphasic pulse may be asymmetric, where the amplitude
and/or pulse width of the first pulse may differ from that of the
charge-balancing phase. Additionally, each phase of the biphasic
pulse may be either voltage-controlled or current-controlled. In
some variations, both the first phase and the charge-balancing
phase of the biphasic pulse may be current-controlled. In other
variations, both the first phase and the charge-balancing phase of
the biphasic pulse may be voltage-controlled. In still other
variations, the first phase of the biphasic pulse may be
current-controlled, and the second phase of the biphasic pulse may
be voltage-controlled, or vice-versa.
[0117] In variations where the waveform comprises a biphasic pulse,
the biphasic pulse may have any suitable frequency, pulse widths,
and amplitudes. For example, in instances where the stimulators
described here are used to treat allergic rhinitis, non-allergic
rhinitis, nasal congestion, ocular allergy, and/or symptoms
associated with these conditions by stimulating nasal or sinus
tissue, the stimulator may be configured to generate a biphasic
pulse waveform at a frequency between about 0.1 Hz and about 200
Hz. In some of these variations, the frequency is preferably
between about 10 Hz and about 60 Hz. In some of these variations,
the frequency is preferably between about 25 Hz and about 35 Hz. In
others of these variations, the frequency is preferably between
about 50 Hz and about 90 Hz. In some of these variations, the
frequency is preferably between about 65 Hz and about 75 Hz. In
other variations, the frequency is preferably between about 130 Hz
and about 170 Hz. In some of these variations, the frequency is
preferably between about 145 Hz and about 155 Hz. In some
variations, high frequencies, such as those between about 145 Hz
and about 155 Hz may be too high for each pulse to
stimulate/activate the target nerves. As a result, the stimulation
may be interpreted by the patient to have an element of randomness,
which in turn may help to reduce subject habituation.
[0118] Similarly, for the treatment of nasal congestion, allergic
rhinitis, non-allergic rhinitis, ocular allergy, and/or symptoms
associated with these conditions when the stimulus is electrical
and the first phase of the biphasic pulse is current-controlled,
the first phase may preferably have an amplitude between about 10
.mu.A and 100 mA. In some of these variations, the amplitude may be
preferably between about 0.1 mA and about 10 mA. When the first
phase of the biphasic pulse is voltage-controlled, the first phase
may preferably have an amplitude between about 10 mV and about 100
V. Additionally, the first phase may preferably have a pulse width
between about 1 .mu.s and about 10 ms. In some of these variations,
the pulse width may preferably be between about 10 .mu.s and about
100 .mu.s. In other variations, the pulse width may preferably be
between about 100 .mu.s and about 1 ms.
[0119] When an electrical pulse waveform is an alternating
monophasic pulsed waveform, each pulse delivered by the stimulator
may have a single phase, and successive pulses may have alternating
polarities. Generally, the alternating monophasic pulses are
delivered in pairs at a given frequency (such as one or more of the
frequencies listed above, such as between 30 Hz and 50 Hz), and may
have an inter-pulse interval between the first and second pulse of
the pair (e.g., about 100 .mu.s, between 50 .mu.s and 150 .mu.s or
the like). Each pulse may be current-controlled or
voltage-controlled, and consecutive pulses need not be both
current-controlled or both voltage-controlled. In some variations
where the pulse waveform is charged-balanced, the waveform may
comprise a passive charge-balancing phase after delivery of a pair
of monophasic pulses, which may allow the waveform to compensate
for charge differences between the pulses.
[0120] When a stimulator configured to deliver an electrical
stimulus is positioned to place an electrode on either side of the
nasal septum, alternating monophasic pulses may promote bilateral
stimulation of nasal tissue. The pulses of a first phase may
stimulate a first side of the nose (while providing a
charge-balancing phase to a second side of the nose), while the
pulses of the opposite phase may stimulate the second side of the
nose (while providing a charge-balancing phase to the first side of
the nose), since nerves may respond differently to anodic and
cathodic pulses. The inter-pulse interval may give time for the
stimulation provided by a first phase pulse to activate/polarize
the target nerves prior to be reversed by an opposite phase
pulse.
[0121] When a stimulator is configured to deliver a pulse-based
waveform, the stimulation amplitude, pulse width, and frequency may
be the same from pulse to pulse, or may vary over time. For
example, in some variations, the amplitude of the pulses may vary
over time. In some variations, the amplitude of pulses may vary
according to a sinousidal profile. In some variations, the
stimulation waveform may be a modulated high frequency signal
(e.g., sinusoidal), which may be modulated at a beat frequency of
the ranges described above. In such variations, the carrier
frequency may be between about 100 Hz and about 100 kHz. In other
variations, the amplitude of pulses may increase (linearly,
exponentially, etc.) from a minimum value to a maximum value, drop
to the minimum value, and repeat as necessary. In some variations,
the user may be able to control the stimulus during its delivery.
After the user has placed a portion of the nasal insertion prong(s)
(e.g., the electrode or electrodes) in contact with the nasal
tissue, the user may increase the intensity of the stimulus. It may
be desirable for the patient to increase the intensity of the
stimulus until the stimulus causes paresthesia (e.g., tingling,
tickling, prickling). As such, the patient may be able to
self-determine the proper stimulation intensity and self-adjust the
stimulus to a level effective to achieve the desired result. The
desired result or treatment effect may depend on the condition to
be treated. For example, the desired result may be relief of
symptoms of allergic rhinitis, non-allergic rhinitis, nasal
congestion, and/or ocular allergy. In some variations of a method
for treatment of allergic rhinitis, for example, the treatment
effect may comprise tear and/or mucous production. In some
variations of a method for treatment of non-allergic rhinitis, for
example, the treatment effect may comprise reduction in thickness
and/or volume of lamina propia tissue. It may be desirable for the
user to increase the intensity of the stimulus slowly in order to
minimize discomfort.
[0122] In some instances, it may be desirable to configure the
stimulation waveform to minimize side effects. In some instances,
it may be desirable to promote stimulation of larger-diameter
nerves (e.g., afferent fibers of the trigeminal nerve), which may
promote a therapeutic effect, while reducing the stimulation of
smaller nerves (e.g., a-delta fibers, c fibers, sympathetic and
parasympathetic fibers), which may result in discomfort or mucus
production. Generally, for smaller pulse-widths, the activation
threshold for larger-diameter nerves may be lower than the
activation threshold for the smaller nerve fibers. Conversely, for
larger pulse-widths, the activation threshold for larger-diameter
nerves may be higher than the activation threshold for the smaller
nerve fibers. Accordingly, in some instances, it may be desirable
to select a pulse width that preferably actuations the
larger-diameter nerves. In some variations, the pulse width may be
between 30 .mu.s and about 70 .mu.s, or may be between about 30
.mu.s and about 150 .mu.s. However, it should be appreciated that
in some variations, it may be desirable to promote stimulation of
nerves of other diameters. In some variations it may be desirable
to select a pulse width less than 30 .mu.s, and in other variations
it may be desirable to select a pulse width greater than 150
.mu.s.
[0123] While certain stimuli have been described herein, it should
be appreciated that when used for treating nasal congestion,
allergic rhinitis, non-allergic rhinitis, ocular allergy, and/or
symptoms associated with these conditions, the stimulation devices
described herein may deliver any suitable stimulus, including
suitable stimuli described in U.S. application Ser. No. 14/256,915,
filed Apr. 18, 2014, and titled "NASAL STIMULATION DEVICES AND
METHODS," which was previously incorporated by reference in its
entirety, in U.S. application Ser. No. 14/809,109, filed Jul. 24,
2015, and titled "STIMULATION PATTERNS FOR TREATING DRY EYE," which
is hereby incorporated by reference in its entirety, and in U.S.
application Ser. No. 14/920,860, filed Oct. 22, 2015, and titled
"STIMULATION DEVICES AND METHODS FOR TREATING DRY EYE," which was
previously incorporated by reference in its entirety. Additionally,
although the stimulation systems, devices, and methods described
are herein are intended for use with human users, it should be
appreciated that they may be modified for veterinary use.
Treatment Regimens
[0124] The stimulation methods described herein may be delivered
according to one or more treatment regimens to treat a
condition.
[0125] For example, to treat rhinitis (allergic rhinitis or
non-allergic rhinitis), stimulation may in some variations be
delivered to a subject as needed and/or according to a
pre-determined regimen. In some instances, a user may use one of
the stimulation devices described herein to provide a round of
stimulation when the user experiences symptoms of allergic rhinitis
and/or non-allergic rhinitis, such as but not limited to itching,
sneezing, congestion, subject sensation of "fullness," runny nose,
post-nasal drip, mouth breathing, coughing, fatigue, headache,
anosmia, phlegm, throat irritation, periorbital puffiness, watery
eyes, ear pain, or the like. In some variations, a round of
stimulation may have a suitable duration, such as but not limited
to between about 5 seconds and about 180 seconds, or between about
10 seconds and about 60 seconds. In other variations, a user may
deliver a round of stimulation until the user notices an acute
reduction in symptoms. When stimulation is delivered on an
as-needed basis, a user may delivery any suitable number of rounds
of stimulation per day. In some variations, the total number of
rounds of stimulation may be limited to 10 per day. In other
variations of methods to treat allergic rhinitis or non-allergic
rhinitis, the devices described herein may be used to provide
stimulation on a scheduled basis. For example, in some variations
in which the stimulation devices described herein are used to treat
allergic rhinitis or non-allergic rhinitis, a round of stimulation
may be delivered between 2 and 10 times per day, for a plurality of
days, on a regular pattern. Such a pattern may be, for example,
every 12 hours, every 8 hours, every 6 waking hours, every 4 waking
hours, every 3 waking hours, every 2 waking hours, every 1.5 waking
hours, or the like. In yet other variations of methods to treat
allergic rhinitis, stimulation may be delivered both on a scheduled
basis and in response to symptoms of allergic rhinitis or
non-allergic rhinitis. In some variations of methods to treat
allergic rhinitis, the methods may comprise delivery of stimulation
in combination with nose blowing. For example, a user may blow his
or her nose after a round of stimulation, or a user may pause
stimulus delivery one or more times to blow his or her nose during
a round of stimulation. Nose blowing may expel any material
accumulated in the nasal passageways during stimulation, such as a
buildup of tear secretions and/or mucus. In the case of allergic
rhinitis, expelling this accumulated material may contribute to
flushing of allergens out of the nose.
[0126] As another example, to treat nasal congestion, stimulation
may in some variations be delivered to a subject as needed and/or
according to a pre-determined regimen. In some instances, a user
may use one of the stimulation devices described herein to provide
a round of stimulation when the user experiences symptoms of nasal
congestion, such as but not limited to difficulty with nasal
breathing, ear fullness, facial pain, facial and/or intracranial
pressure, decreased sense of smell and/or taste, dizziness,
post-nasal discharge, and/or thick nasal discharge. In some
variations, a round of stimulation may have a suitable duration,
such as but not limited to between about 5 seconds and about 180
seconds, or between about 10 seconds and about 60 seconds. In other
variations, a user may deliver a round of stimulation until the
user notices an acute reduction in symptoms. When stimulation is
delivered on an as-needed basis, a user may deliver any suitable
number of rounds of stimulation per day. In some variations, the
total number of rounds of stimulation may be limited to 10 per day.
In other variations of methods to treat nasal congestion, the
devices described herein may be used to provide stimulation on a
scheduled basis. For example, in some variations in which the
stimulation devices described herein are used to treat nasal
congestion, a round of stimulation may be delivered between 2 and
10 times per day, for a plurality of days, on a regular pattern.
Such a pattern may be, for example, every 12 hours, every 8 hours,
every 6 waking hours, every 4 waking hours, every 3 waking hours,
every 2 waking hours, every 1.5 waking hours, or the like. In yet
other variations of methods to treat nasal congestion, stimulation
may be delivered both on a scheduled basis and in response to
symptoms of nasal congestion.
[0127] As another example, to treat ocular allergy, stimulation may
in some variations be delivered to a subject as needed and/or
according to a pre-determined regimen. In some instances, a user
may use one of the stimulation devices described herein to provide
a round of stimulation when the user experiences symptoms of ocular
allergy, such as but not limited to swelling or puffiness, itching,
tearing, and/or discharge. In some variations, a round of
stimulation may have a suitable duration, such as but not limited
to between about 5 seconds and about 180 seconds, or between about
10 seconds and about 60 seconds. In other variations, a user may
deliver a round of stimulation until a desired effect occurs (e.g.,
increased tearing). When stimulation is delivered on an as-needed
basis, a user may deliver any suitable number of rounds of
stimulation per day. In some variations, the total number of rounds
of stimulation may be limited to 10 per day. In other variations of
methods to treat ocular allergy, the devices described herein may
be used to provide stimulation on a scheduled basis. For example,
in some variations in which the stimulation devices described
herein are used to treat ocular allergy, a round of stimulation may
be delivered between 2 and 10 times per day, for a plurality of
days, on a regular pattern. Such a pattern may be, for example,
every 12 hours, every 8 hours, every 6 waking hours, every 4 waking
hours, every 3 waking hours, every 2 waking hours, every 1.5 waking
hours, or the like. In yet other variations of methods to treat
ocular allergy, stimulation may be delivered both on a scheduled
basis and in response to symptoms of ocular allergy.
[0128] It should be appreciated that the methods described herein
may comprise delivering a stimulus as described herein according to
other suitable treatment regimens for treating allergic rhinitis,
non-allergic rhinitis, nasal congestion, ocular allergy, and/or
symptoms associated with these conditions. For example, stimuli may
be delivered at least once daily, at least once weekly, or the
like. In some variations, the stimulation devices may be used to
deliver multiple rounds of stimulation each day (e.g., at least two
treatments daily, at least three treatments daily, at least four
treatments daily, at least five treatments daily, at least six
treatments daily, at least seven treatments daily, at least eight
treatments daily, between two and ten times daily, between four and
eight times daily, or the like). In some variations, the
stimulation may be delivered at certain times of day. In other
variations, the stimulation may be delivered at any time during the
day as desired or determined by the user. When the device is used
to provide stimulation on a scheduled basis, in some variations
each round of stimulation may be the same length (e.g., about 30
seconds, about 1 minute, about 2 minutes, about 3 minutes, about 4
minutes, about 5 minutes, about 10 minutes, or longer than 10
minutes). In other variations, some rounds of stimulation may have
different predetermined lengths. In yet other variations, the user
may choose the length of the round of stimulation. In some of these
variations, the user may be given a minimum stimulation time (e.g.,
about 5 seconds, about 10 seconds, about 30 seconds, about 1
minute, about 2 minutes, about 3 minutes, about 5 minutes, or the
like) and/or a maximum stimulation time (e.g., about 1 minute,
about 2 minutes, about 3 minutes, about 5 minutes, about 10
minutes, about 20 minutes, or the like). In some instances, the
delivery schedule or stimulation parameters may be changed based on
the time of day (e.g., daytime use vs. nighttime use). In some of
these variations, the stimulator may comprise (e.g., as part of a
control subsystem) one or more counters and intelligence (e.g., a
microcontroller, programmable logic (e.g., a field-programmable
gate array), or application-specific integrated circuit (ASIC)).
Other treatment regimens that may be used for the methods described
herein may include suitable treatment regimens described in U.S.
application Ser. No. 14/256,915, filed Apr. 18, 2014, and titled
"NASAL STIMULATION DEVICES AND METHODS," which was previously
incorporated by reference in its entirety.
[0129] In some variations, methods may comprise delivering a
stimulus as described herein in combination with other forms of
therapy for allergic rhinitis, non-allergic rhinitis, nasal
congestion, ocular allergy, and/or symptoms associated with these
conditions. For example, in some variations the methods may
comprise delivering a stimulus in combination with pharmacologic
therapy, such as but not limited to intranasal steroids, oral
antihistamines, or anti-IgE. This combined approach may be
beneficial as compared to pharmacologic therapy alone due to
reduced durations and/or reduced dosages of pharmacologic therapy,
which may in turn result in improved safety profiles (i.e., reduced
unwanted side effects from such pharmacologic therapy).
Treatment Effects
[0130] In some variations, the treatment regimens described herein
may be used to treat rhinitis, including allergic rhinitis (acute
and/or chronic) and/or non-allergic rhinitis (acute and/or
chronic), nasal congestion, ocular allergy, and/or symptoms
associated with these conditions. In contrast to current treatment
options, the treatment regimens using the stimulators described
herein may provide rapid and marked improvement in objective
measures of health and symptomatic relief, and may have fewer
unwanted side effects. In some variations, the treatment regimens
of providing the stimuli described herein may cause periodic or
regular activation of the nasolacrimal reflex, which may in turn
treat allergic rhinitis, non-allergic rhinitis, nasal congestion,
ocular allergy, and/or the symptoms associated with these
conditions.
[0131] In some variations, the treatment methods described herein
for treating allergic rhinitis may result in improvements in
measurements of one or more of the thickness and/or volume of
lamina propia tissue (e.g., as measured by direct visual
examination of the sinus cavity (e.g., by endoscopic examination or
speculum examination), use of imaging modalities such as CT or MRI,
or the like); redness of nasal mucosa; thickness and/or volume of
clear airway passages (e.g., as measured by direct visual
examination of the sinus cavity (e.g., by endoscopic examination or
speculum examination), use of imaging modalities such as CT or MRI,
or the like); microbiological assessment of sinus aspirate; degree
of inflammation of nasal mucosa; nasal fractional exhaled nitric
oxide; peak nasal inspiratory flow; acute and/or chronic change in
nasal discharge volume; viscosity of nasal discharge; nasal airway
resistance/impedance; rhinorrhea (runny nose); post-nasal drip;
sneezing; nasal congestion; mouth breathing; coughing; headache;
anosmia; phlegm volume; itchiness; and/or pain.
[0132] In some variations, the treatment methods described herein
for treating non-allergic rhinitis may result in improvements in
measures of one or more of the thickness and/or volume of lamina
propia tissue (e.g., as measured by direct visual examination of
the sinus cavity (e.g., by endoscopic examination or speculum
examination), use of imaging modalities such as CT or MRI, or the
like); redness of nasal mucosa; thickness and/or volume of clear
airway passages (e.g., as measured by direct visual examination of
the sinus cavity (e.g., by endoscopic examination or speculum
examination), use of imaging modalities such as CT or MRI, or the
like); microbiological assessment of sinus aspirate; degree of
inflammation of nasal mucosa; degree of inflammation of nasal
mucosa; nasal fractional exhaled nitric oxide; peak nasal
inspiratory flow; acute and/or chronic change in nasal discharge
volume; viscosity of nasal discharge; nasal airway
resistance/impedance; rhinorrhea (runny nose); post-nasal drip;
sneezing; nasal congestion; mouth breathing; coughing; headache;
anosmia; phlegm volume; itchiness; and/or pain.
[0133] In some variations, the treatment methods described herein
for treating nasal congestion may result in improvements in
measures of one or more of the thickness and/or volume of lamina
propia tissue (e.g., as measured by direct visual examination of
the sinus cavity (e.g., by endoscopic examination or speculum
examination), use of imaging modalities such as CT or MRI, or the
like); redness of nasal mucosa; thickness and/or volume of clear
airway passages (e.g., as measured by direct visual examination of
the sinus cavity (e.g., by endoscopic examination or speculum
examination), use of imaging modalities such as CT or MRI, or the
like); stuffy nose; and/or breathing through the mouth.
[0134] In some variations, the treatment methods described herein
for treating ocular allergy may result in improvements in measures
of one or more of itching; chemosis; eyelid swelling; excessive
tearing; foreign body sensation; and/or ocular discomfort.
EXAMPLE
[0135] A study will be carried out to explore the effectiveness of
electrical stimulation as described herein for the treatment of
symptoms of allergic rhinitis.
[0136] Participants will be randomized between 1 of 2 treatment
sequences. In a first sequence, participants will use an
interventional device to apply intranasal electrical stimulation
during a first visit, and will use a control device during a second
visit. In a second sequence, participants will use a control device
during a first visit, and will use an interventional device to
apply intranasal electrical stimulation during a second visit. The
interventional and control devices will be visually identical, but
only the interventional device will generate electrical
stimulation. The control device will apply only mechanical
stimulation. The interventional device will be applied in the upper
part of the nose in order to stimulate the nasolacrimal reflex
pathways by gently activating the anterior ethmoidal nerve, a
sub-branch of the ophthalmic branch of the trigeminal nerve that
provides neural input to the superior salivatory nucleus in the
brainstem, as shown in FIG. 11A. The control device will be applied
only in the lower part of the nose to avoid activation of the
nasolacrimal reflex, as shown in FIG. 11B. Randomization will be
stratified by type of allergy (seasonal versus perennial). During
the treatment sequences, participants will apply
electrical/mechanical stimulation with the interventional
device/control device for 3 minutes.
[0137] The interventional device will comprise a device having
features shown and described with respect to FIGS. 1A-1E. The
interventional device will comprise a reusable stimulator body
configured to generate an electrical stimulus, and a disposable
stimulator probe attachable to the stimulator body. The stimulator
probe will comprise two nasal insertion prongs configured to be
inserted into a participant's nasal cavity, with each prong
comprising a hydrogel electrode. The stimulator body will comprise
a user interface comprising two buttons, which will allow the
participant to turn on the stimulator and change the stimulus
parameters, and light-emitting diodes to indicate the stimulation
level being delivered. The interventional device will further
include a charger configured to recharge a battery within the
stimulator body and a reusable cover configured to be placed over
and protect the stimulator probe.
[0138] The stimulator body will be configured to deliver five
different levels of stimulation. Setting 1 will have a stimulation
frequency of 30 Hz; a minimum stimulation current amplitude of 0.7
mA, a maximum stimulation current amplitude of 0.7 mA, and thus no
variation in maximum stimulation current amplitude; a minimum pulse
width of 0 .mu.s; a maximum pulse width of 300 .mu.s; a pulse width
modulation frequency of 1 Hz (rising and falling according to an
exponential function); a minimum charge injection per phase (at 0
.mu.s pulse width) of 0 .mu.C; a maximum charge injection per phase
(at 0.7 mA and 300 .mu.s) of 0.21 .mu.C; and a pulse shape that is
cycled between four periods. The first period will comprise a
two-phase current-controlled waveform with symmetrical phases. The
second period will comprise a current-controlled first phase,
followed by a voltage-controlled second phase. The first phase will
have a current sourced by a first electrode and sunk by a second
electrode, while the second phase will have a current sourced by
the second electrode and sunk by the first electrode. The third
period will comprise a two-phase current-controlled waveform with
symmetrical phases (i.e., the third period may be the same as the
first period). The fourth period will comprise a current-controlled
first phase, followed by a voltage-controlled second phase. The
first phase will have a current sourced by the second electrode and
sunk by the first electrode, while the second phase will have a
current sourced by the first electrode and sunk by the second
electrode. In each period, the pulses will be charged-balanced.
Setting 2 will have a stimulation frequency of 37.5 Hz; a minimum
stimulation current amplitude of 1.33 mA, a maximum stimulation
current amplitude of 1.5 mA, a variation in maximum stimulation
current amplitude of 0.17 mA, and an amplitude modulation frequency
of 2.1 Hz; a minimum pulse width of 0 .mu.s; a maximum pulse width
of 300 .mu.s; a pulse width modulation frequency of 1 Hz (rising
and falling according to an exponential function); a minimum charge
injection per phase (at 0 .mu.s pulse width) of 0 .mu.C.; a maximum
charge injection per phase (at 1.5 mA and 300 .mu.s) of 0.45 .mu.C;
and a pulse shape that is modulated as described above with respect
to Setting 1. Setting 3 will have a stimulation frequency of 45 Hz;
a minimum stimulation current amplitude of 2.17 mA, a maximum
stimulation current amplitude of 2.5 mA, a variation in maximum
stimulation current amplitude of 0.33 mA, and an amplitude
modulation frequency of 2.6 Hz; a minimum pulse width of 0 .mu.s; a
maximum pulse width of 300 .mu.s; a pulse width modulation
frequency of 1 Hz (rising and falling according to an exponential
function); a minimum charge injection per phase (at 0 .mu.s pulse
width) of 0 .mu.C; a maximum charge injection per phase (at 2.5 mA
and 300 .mu.s) of 0.75 .mu.C; and a pulse shape that is modulated
as described above with respect to Setting 1. Setting 4 will have a
stimulation frequency of 52.5 Hz; a minimum stimulation current
amplitude of 3.2 mA, a maximum stimulation current amplitude of 3.7
mA, a variation in maximum stimulation current amplitude of 0.5 mA,
and an amplitude modulation frequency of 2.8 Hz; a minimum pulse
width of 0 .mu.s; a maximum pulse width of 300 .mu.s; a pulse width
modulation frequency of 1 Hz (rising and falling according to an
exponential function); a minimum charge injection per phase (at 0
.mu.s pulse width) of 0 .mu.C; a maximum charge injection per phase
(at 3.7 mA and 300 .mu.s) of 1.11 .mu.C; and a pulse shape that is
modulated as described above with respect to Setting 1. Setting 5
will have a stimulation frequency of 60 Hz; a minimum stimulation
current amplitude of 4.3 mA, a maximum stimulation current
amplitude of 5.0 mA, a variation in maximum stimulation current
amplitude of 0.67 mA, and an amplitude modulation frequency of 2.5
Hz; a minimum pulse width of 0 .mu.s; a maximum pulse width of 300
.mu.s; a pulse width modulation frequency of 1 Hz (rising and
falling according to an exponential function); a minimum charge
injection per phase (at 0 .mu.s pulse width) of 0 .mu.C; a maximum
charge injection per phase (at 5.0 mA and 300 .mu.s) of 1.5 .mu.C;
and a pulse shape that is modulated as described above with respect
to Setting 1. The control device will look identical to the
interventional device, but will not deliver electrical
stimulation.
[0139] A number of measures of effectiveness of intranasal
stimulation for treatment of the symptoms of allergic rhinitis will
be used. Measures will include participant-assessed allergic
rhinitis symptom score, nasal inflammation score, peak nasal
inspiratory flow, mass of nasal secretions, nasal thermal scan
(used as a surrogate marker of inflammatory changes of the nasal
cavity), and nasal fractional exhaled nitric oxide (an increase in
fractional exhaled nitric oxide may reflect a permanent
inflammation of the sinus mucosa).
[0140] Allergic rhinitis symptom score: Each participant will
evaluate four allergic rhinitis symptoms, including nasal itching,
nasal congestion, rhinorrhea, and sneezing on a 0 to 3 scale (0=no
sign/symptom is evident; 1=sign/symptom clearly present, but
minimal awareness--easily tolerated; 2=definite awareness of
sign/symptom that is bothersome, but tolerable; 3=sign/symptom that
is hard to tolerate; causes interference with activities). Symptoms
will be evaluated at 5.+-.1 minutes before nasal stimulation, and
at 5.+-.1, 10.+-.1, 15.+-.1, 20.+-.1, 30.+-.1, 45.+-.1, 60.+-.5,
75.+-.5, 90.+-.5, 105.+-.5, 120.+-.5, 135.+-.5, 150.+-.5, 165.+-.5,
and 180.+-.5 minutes after nasal stimulation. It is hypothesized
that a composite score (sum) of the four symptoms (nasal itching,
nasal congestion, rhinorrhea, and sneezing) will be lower after
intranasal electrical stimulation than prior to stimulation. It is
hypothesized that activation of the nasolacrimal reflex, via
stimulus delivery to the anterior ethmoidal nerve, will induce
increased rhinorrhea and a local sympathetic rebound leading to
vasoconstriction in the nasal cavity. Together, increased
rhinorrhea and local vasoconstriction will lead to a relief of
symptoms usually associated with allergic rhinitis.
[0141] Nasal inflammation score: Nasal inflammation score will be
evaluated by an investigator on a 0 to 4 scale using nasal digital
videos of each nostril, where characteristics of redness, swelling,
and abnormal nasal secrections will be evaluated. Nasal
inflammation will be evaluated prior to stimulation (within 30
minutes prior to the first evaluation of symptoms at -5.+-.1
minutes before stimulation) and at 180+5 minutes after nasal
stimulation. It is hypothesized that nasal inflammation will
decrease after intranasal electrical stimulation.
[0142] Peak nasal inspiratory flow: Nasal peak inspiratory flow
readings will be made using an inspiratory flow meter with nasal
adaptor. Measurements will be made in a standing position. Subjects
will be instructed to exhale residual volume, place a face mask
over the mouth and nose to create a good seal around the face mask,
and then inhale forcefully to total lung capacity, through the
nose, with mouth closed. This maneuver should be a short, sharp
inspiratory action of about 1 second in duration. Peak nasal
inspiratory flow will be evaluated prior to stimulation (within 30
minutes prior to the first evaluation of symptoms at -5.+-.1
minutes before stimulation) and at 60.+-.5, 120.+-.5, and 180.+-.5
minutes after stimulation. Three measurements will be made at each
time point. It is hypothesized that peak nasal inspiratory flow
over the time points will initially transiently decrease, and then
increase.
[0143] Mass of nasal secretions: Each subject will be given a bag
of pre-weighed disposable tissues to use during the course of each
measurement period. Used tissues will be placed in a closed
disposable plastic container, as to minimize evaporation. The
container of both used and unused tissues will be weighed after the
measurement period is complete and the mass increase, if any, due
to nasal secretions will be recorded. The mass of nasal secretions
will be measured prior to stimulation (within 30 minutes prior to
the first evaluation of symptoms at -5.+-.1 minutes before
stimulation), and at 10.+-.1, 60.+-.5, 120.+-.5, and 180.+-.5
minutes after stimulation. It is hypothesized that the mass of
nasal secretions over the time points will initially transiently
increase, and then decrease.
[0144] Nasal thermal scan: For nasal thermal scanning, the
temperature of the tissue surrounding the nasal area will be
measured as a surrogate for inflammation. A thermal camera will be
used to capture thermal images of the nasal area. The temperature
of the tissue will be recorded to identify when an allergic
response causing vasodilatation is occurring, as identified by an
acute increase in temperature. Nasal thermal scans will be
conducted prior to stimulation (within 30 minutes prior to the
first evaluation of symptoms at -5.+-.1 minutes before
stimulation), and at 15.+-.1, 30.+-.1, 45.+-.1, 60.+-.5, 90.+-.5,
120.+-.5, 150.+-.5, and 180.+-.5 minutes after stimulation. When
thermal scans are conducted at the same time point as collection of
nasal secretions, the thermal image will be taken before the
collection of nasal secretions. It is hypothesized that stimulation
will result in more rapid temperature normalization.
[0145] Nasal fractional exhaled nitric oxide: A fractional exhaled
nitric oxide-sensing machine will be used to measure nitric oxide
levels from exhalation. Fractional exhaled nitric oxide will be
evaluated prior to stimulation (within 30 minutes prior to the
first evaluation of symptoms at -5.+-.1 minutes before
stimulation), and at 30.+-.1, 60.+-.5, 90.+-.5, 120.+-.5, 150.+-.5,
and 180.+-.5 minutes after stimulation. It is expected that levels
of nitric oxide will increase as the tissue undergoes an
eosinophilic response to the allergen, and that stimulation will
result in decreased nasal fractional exhaled nitric oxide.
* * * * *