US20180272132A1 - High frequency stimulation for treating sensory and/or motor deficits in patients with spinal cord injuries and/or peripheral polyneuropathy, and associated systems and methods - Google Patents

Abstract

High frequency stimulation for treating sensory and/or motor deficits in patients with spinal cord injuries and/or peripheral polyneuropathy, and associated systems and methods. A representative method includes addressing the patient's somatosensory dysfunction and/or motor dysfunction, resulting from neuropathy and/or spinal cord injury, by directing an electrical therapy signal to the patient's spinal cord region, the therapy signal having a frequency in a frequency range from 1.5 kHz to 100 kHz.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• The present application claims priority to the following U.S. Provisional Patent Applications: U.S.Provisional Patent Application 62/448,320, filed on Jan. 19, 2017; and U.S.Provisional Patent Application 62/588,185, filed on Nov. 17, 2017; both of which are incorporated herein by reference in their entireties.
TECHNICAL FIELD
• The present disclosure is directed generally to high frequency electrical stimulation for treating sensory and/or motor deficits in patients with spinal cord injuries and/or peripheral polyneuropathy, and associated systems and methods.
BACKGROUND
• An estimated 20 million people in the United States have some form of peripheral neuropathy, a condition that develops as a result of damage to the peripheral nervous system (“PNS”). The PNS is a vast communications network that connects the central nervous system (“CNS”) to the limbs and organs, essentially serving as a communication relay going back and forth between the brain and spinal cord with the rest of the body. Damage to the PNS interferes with this communication pathway, and symptoms can range from numbness or tingling, to pricking sensations or muscle weakness. Peripheral neuropathy has been conventionally treated with medication, injection therapy, physical therapy, surgery, and light. More recently, diabetic peripheral neuropathy has been treated by applying a surface electrical stimulation at a specified frequency to the muscles and nerves. Most treatments are designed to treat the underlying cause of the neuropathy, but in many cases, the cause of the neuropathy is unknown or, even if the cause has been identified, a specific treatment may not exist. Accordingly, there is a need for systems and methods for treating peripheral neuropathy.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a partially schematic illustration of an implantable spinal cord modulation system positioned at the spine to deliver therapeutic signals in accordance with embodiments of the present technology.
• FIGS. 2-3 are partially schematic, cross-sectional illustrations of a patient's spine, illustrating representative locations for implanted lead bodies in accordance with embodiments of the present technology.
• FIG. 4 is a table showing selected clinical data gathered from Applicant's clinical study showing treatment of sensory deficit with high frequency spinal cord stimulation, in accordance with embodiments of the present technology.
• FIGS. 5A-5C illustrate clinical results for patients treated for peripheral polyneuropathy with high frequency stimulation in accordance with embodiments of the present technology.
DETAILED DESCRIPTION1.0 Introduction
• The present technology is directed generally to systems and methods for treating peripheral neuropathy, peripheral polyneuropathy (PPN), painful diabetic neuropathy (PDN), dysesthesia, sensory deficits, motor deficits, and/or spinal cord injury using high frequency electrical stimulation. In particular, the systems and methods of the present technology may at least partially restore sensory loss in patients suffering from peripheral neuropathy and/or other indications. In one embodiment, the present technology includes improving the patient's somatosensory function by delivering an electrical signal, having a frequency of from 1.5 kHz to 100 kHz to the patient's spinal cord via at least one implantable signal delivery device, and wherein the electrical signal has a frequency of from 1.5 kHz to 100 kHz.
• Definitions of selected terms are provided under heading 1.0 (“Definitions”). General aspects of the anatomical and physiological environment in which the disclosed technology operates are described below under heading 2.0 (“Introduction”). Representative treatment systems and associated methods, are described under heading 3.0 (“Representative Treatment Systems and Associated Methods”) with reference toFIGS. 1-3. Representative clinical data generated from the use of Applicant's treatment systems and methods disclosed herein are described under heading 4.0 (“Representative Clinical Data”) with reference toFIG. 4-5C. The foregoing headings are provided for organizational purposes only. Features defined and/or described above under any of the foregoing headings may be combined with and/or applied to features described under any of the other headings, in accordance with embodiments of the present technology.
2.0 Definitions
• As used herein, the terms “high frequency” and “HF” refer to a frequency of from about1.2 kHz to about 100 kHz, or from about 1.5 kHz to about 100 kHz, or from about 2 kHz to about 50 kHz, or from about 3 kHz to about 20 kHz, or from about 3 kHz to about 15 kHz, or from about 5 kHz to about 15 kHz, or from about 3 kHz to about 10 kHz, or 1 kHz, 2 kHz, 3 kHz, 4 kHz, 5 kHz, 10 kHz, 15 kHz, 20 kHz, 50 kHz, or 100 kHz, unless otherwise stated. Unless otherwise stated, the term “about” refers to values within 10% of the stated value. As used herein, “low frequency” or “LF” refers to a frequency less than 1.2 kHz or less than 1 kHz.
• As used herein, “peripheral neuropathy” refers to damage to or disease affecting one or more peripheral nerves or groups of peripheral nerves. Peripheral neuropathy may refer to nerve damage or disease in one nerve or area of the body (mononeuropathy), multiple nerves or multiple areas of the body (polyneuropathy), and/or in the same place on both sides of the body (symmetric neuropathy). Representative systems and methods in accordance with embodiments of the present technology are configured to treat all types of peripheral neuropathy, irrespective of whether it is inherited or acquired. Inherited causes include Charcot-Marie Tooth, Kennedy's disease (X-linked bilbospinal muscular atrophy), Van Allen's Syndrome (hereditary amyloid neuropathy), Refsum's disease, Tangier disease, and others. Causes of acquired peripheral neuropathy addressed by the systems and methods of the present technology include nerve compression, entrapment or laceration (e.g., crutches, ulnar neuropathy, thoracic outlet syndrome, meralgia paresthetica, Morton's metatarsalgia); metabolic (diabetes mellitus, hypothyroidism) and autoimmune disorders (lupus, rheumatoid arthritis, Guillain-Barre Syndrome, Miller Fisher Syndrome); kidney disease, liver disease, toxin-induced (alcohol, tobacco, asbestos, arsenic, lead, mercury); cancer (e.g., malignant lymphoma, lung cancer, etc.); viral or bacterial infections (HIV, Lyme disease, leprosy, poliomyelitis); medication-induced (e.g., chemotherapy, etc.); trauma; repetition (carpal tunnel syndrome, cubital tunnel syndrome); and vitamin deficiency (especially vitamin B).
• As used herein, “treat” or “treatment” with reference to peripheral neuropathy includes preventing, ameliorating, suppressing, or alleviating one or more of the symptoms of abnormal sensory responses caused by peripheral neuropathy. In some cases, the treatment protocols of the present technology result in the reactivation of the nerve (e.g., restoring the ability of the nerve to depolarize and conduct signals).
• As used herein, (the terms “sensory deficit,” “sensory loss,” “abnormal sensory response,” “abnormal sensory function,” etc. refer to all symptoms caused by disease and/or damage to the peripheral nerves (large and/or small fiber) of the somatosensory system, such as numbness, decreased responsiveness to light touch, pain, thermal sensation, and vibratory sensation, impaired joint position sense, impaired balance, and decreased muscle strength. The terms “somatosensory” refers generally to sensations (such as pressure, pain, or warmth) that can occur anywhere in the body, as opposed to a particular organ-specific sense, such as sight or smell. The foregoing terms also include “dysesthesia”, an unpleasant and/or abnormal sense of touch, which in turn can include sensations of burning, wetness, itching, electric shock, and/or pins and needles, and which can affect any tissue, including but not limited to the mouth, skin, scalp and/or legs. When addressing or treating somatosensory dysfunction using high-frequency therapy signals in accordance with the present technology, the therapy signals may well have an effect on the patient's perception of pain—but in a different manner than that associated with existing techniques for treating chronic pain via high frequency signals. In particular, existing high frequency therapy signal regimens for addressing chronic pain are generally designed to reduce or eliminate pain (e.g., chronic, neuropathic pain). By contrast, when high frequency therapy signals are administered in accordance with the present technology to address or treat somatosensory dysfunction, they may operate to improve, restore or at least partly restore the patient's ability to detect and/or perceive pain. Now, if the patient also suffers from chronic pain, the high frequency therapy signal can be administered in a manner that also addresses (reduces) chronic pain, in addition to addressing somatosensory deficits.
3.0 Representative Treatment Systems and Associated Methods
• FIG. 1 schematically illustrates arepresentative treatment system100 for treating peripheral neuropathy and/or other sensory deficits, positioned relative to the general anatomy of a patient's spinal column S. Thetreatment system100 can include asignal delivery system101 having a signal generator102 (e.g., a pulse generator) and asignal delivery device103 comprising one or more signal delivery elements104 (referred to individually as first and secondsignal delivery elements104a,104b, respectively). Thesignal generator102 can be connected directly to the signal delivery element(s)104, or it can be coupled to the signal delivery element(s)104 via a signal link108 (e.g., an extension). In some embodiments, thesignal generator102 may be implanted subcutaneously within a patient P. As shown inFIG. 1, the signal delivery element(s)104 is configured to be positioned at or proximate to the spinal cord to apply a high frequency electrical signal to the spinal cord (e.g., to the white matter and/or glial cells of the spinal cord). Without being bound by theory, it is believed that glial cells are present in large concentrations within both white and grey matter, and that high frequency modulation at or proximate to the white and grey matter can affect electrically deficient glial cells. However, the therapies described herein may provide effective treatment via other mechanisms of action.
• In representative embodiments, thesignal delivery device103 includes the first and secondsignal delivery elements104a,104b, each of which comprises a flexible, isodiametric lead or lead body that carries features or structures, for delivering an electrical signal to the treatment site after implantation. As used herein, the terms “lead” and “lead body” include any of a number of suitable substrates and/or support members that carry structures, for providing therapy signals to the patient. For example, the lead body can include one or more electrodes or electrical contacts that direct electrical signals into the patient's tissue, such as to directly affect a cellular membrane. In some embodiments, thesignal delivery device103 and/or signal delivery elements104 can include devices other than a lead body (e.g., a paddle) that also direct electrical signals and/or other types of signals to the patient. Additionally, althoughFIG. 1 shows an embodiment utilizing two signal delivery elements104, in some embodiments thesignal delivery system101 and/orsignal delivery device103 can include more or fewer signal delivery elements (e.g., one signal delivery element,104 three signal delivery elements104, four signal delivery elements104, etc.), each configured to apply electrical signals at different locations and/or coordinate signal delivery to deliver a combined signal to the same (or generally the same) anatomical location.
• As shown inFIG. 1, the firstsignal delivery element104acan be implanted on one side of the spinal cord midline M, and the secondsignal delivery element104bcan be implanted on the other side of the spinal cord midline M. For example, the first and secondsignal delivery elements104a,104bshown inFIG. 1 may be positioned just off the spinal cord midline M (e.g., about 1 mm offset) in opposing lateral directions so that the first and secondsignal delivery elements104a,104 are spaced apart from each other by about 2 mm. In some embodiments, the first and secondsignal delivery elements104a,104bmay be implanted at a vertebral level ranging from, for example, about T8 to about T12. In some embodiments, one or more signal delivery devices can be implanted at other vertebral levels, depending, for example, on the specific indication for which the patient is being treated.
• Thesignal generator102 can transmit signals (e.g., electrical therapy signals) to the signal delivery element104 that up-regulate (e.g., stimulate or excite) and/or down-regulate (e.g., block or suppress) target nerves (e.g., local vagal nerves). As used herein, and unless otherwise noted, to “modulate,” “stimulate,” or provide “modulation” or “stimulation” to the target nerves refers generally to having either type of the foregoing effects on the target nerves. Thesignal generator102 can include a machine-readable (e.g., computer-readable) medium containing instructions for generating and transmitting suitable therapy signals. Thesignal generator102 and/or other elements of thetreatment system100 can include one ormore processors110,memories112 and/or input/output devices140. Accordingly, the process of providing electrical signals, detecting physiological parameters of the patient, adjusting the modulation signal, and/or executing other associated functions can be performed by computer-executable instructions contained by computer-readable media located at thesignal generator102 and/or other system components. Thesignal generator102 can include multiple portions, elements, and/or subsystems (e.g., for directing signals in accordance with multiple signal delivery parameters) housed in a single housing, as shown inFIG. 1, or in multiple housings.
• Thesignal delivery system101 can include one ormore sensing elements113 for detecting one or more physiological parameters of the patient before, during, and/or after the application of electrical therapy signals. In some embodiments, one or more of thesensing elements113 can be carried by thesignal generator102, the signal delivery element104, and/or other implanted components of thesystem101. In some embodiments, thesensing element113 can be an extracorporeal or implantable device separate from thesignal generator102 and/or signal delivery element104.Representative sensing elements113 include one or more of: a subcutaneous sensor, a temperature sensor, an impedance sensor, a chemical sensor, a biosensor, an electrochemical sensor, a hemodynamic sensor, an optical sensor and/or other suitable sensing devices. Physiological parameters detected by the sensing element(s)113 include neurotransmitter concentration, local impedance, current, and/or voltage levels, and/or any correlates and/or derivatives of the foregoing parameters (e.g., raw data values, including voltages and/or other directly measured values).
• Thesignal generator102 can also receive and respond to one or more input signals received from one or more sources. The input signals can direct or influence the manner in which the therapy and/or process instructions are selected, executed, updated, and/or otherwise performed. The input signals can be received from one or more sensors (input devices,140 (e.g., the sensor113) shown schematically inFIG. 1 for purposes of illustration) that are carried by thesignal generator102 and/or distributed outside the signal generator102 (e.g., at other patient locations) while still communicating with thesignal generator102. Thesensor113 and/orother input devices140 can provide inputs that depend on or reflect patient state (e.g., patient position, patient posture, and/or patient activity level), and/or inputs that are patient-independent (e.g., time). Still further details are included in U.S. Pat. No. 8,355,797, which is incorporated herein by reference.
• In some embodiments, thesignal generator102 can obtain power to generate the therapy signals from anexternal power source114. Theexternal power source114 can transmit power to the implantedsignal generator102 using electromagnetic induction (e.g., RF signals). For example, theexternal power source114 can include anexternal coil116 that communicates with a corresponding internal coil (not shown) within theimplantable signal generator102. Theexternal power source114 can be portable for ease of use.
• In some embodiments, thesignal generator102 can obtain the power to generate therapy signals from an internal power source, in addition to or in lieu of theexternal power source114. For example, the implantedsignal generator102 can include a non-rechargeable battery or a rechargeable battery to provide such power. When the internal power source includes a rechargeable battery, theexternal power source114 can be used to recharge the battery. Theexternal power source114 can in turn be recharged from a suitable power source (e.g., conventional wall power).
• During at least some procedures, an external generator120 (e.g., a trial stimulator or modulator) can be coupled to the signal delivery element104 during an initial procedure, prior to implanting thesignal generator102. For example, a practitioner (e.g., a physician and/or a company representative) can use theexternal generator120 to provide therapy signals and vary the modulation parameters provided to the signal delivery elements104 in real time, and select optimal or particularly efficacious parameters. These parameters can include the location from which the electrical signals are emitted, as well as the characteristics of the electrical signals provided to the signal delivery elements104. In some embodiments, input is collected via theexternal generator120 and can be used by the clinician to help determine what parameters to vary. In a typical process, the practitioner uses acable assembly128 to temporarily connect theexternal generator120 to the signal delivery element104. The practitioner can test the efficacy of the signal delivery elements104 in an initial position. The practitioner can then disconnect the cable assembly128 (e.g., at a connector130), reposition the signal delivery elements104, and reapply the electrical signal. This process can be performed iteratively until the practitioner obtains the desired signal parameters and/or position for the signal delivery element104. Optionally, the practitioner can move the partially implanted signal delivery element104 without disconnecting thecable assembly128. Furthermore, in some embodiments, the iterative process of repositioning the signal delivery elements104 and/or varying the therapy parameters may not be performed. Instead, the practitioner can place signal delivery element(s)104 at an approximate anatomical location, and then select which electrodes or contacts deliver the therapy signal, as a way of varying the location to which the therapy signal is directed, without repositioning the signal delivery element(s).
• After the signal delivery elements104 are implanted, the patient P can receive therapy via signals generated by theexternal generator120, generally for a limited period of time. During this time, the patient wears thecable assembly128 and the external generator outside the body. Assuming the trial therapy is effective or shows the promise of being effective, the practitioner then replaces theexternal generator120 with the implantedsignal generator102, and programs thesignal generator102 with therapy programs selected based on the experience gained during the trial period. Optionally, the practitioner can also replace the signal delivery elements104. The signal delivery parameters provided by thesignal generator102 can still be updated after thesignal generator102 is implanted, via a wireless physician's programmer124 (e.g., a physician's remote) and/or a wireless patient programmer126 (e.g., a patient remote). Generally, the patient P has control over fewer parameters than does the practitioner. For example, the capability of thepatient programmer126 may be limited to starting and/or stopping thesignal generator102, and/or adjusting the signal amplitude. Thepatient programmer126 may be configured to accept pain relief input as well as other variables, such as medication use.
• Thesignal generator102, the lead extension, theexternal programmer120 and/or theconnector130 can each include a receivingelement109. Accordingly, the receivingelements109 can be implantable elements (implantable within the patient), or the receivingelements109 can be integral with an external patient treatment element, device or component (e.g., theexternal generator120 and/or the connector130). The receivingelements109 can be configured to facilitate a simple coupling and decoupling procedure between the signal delivery elements104, the lead extension, thesignal generator102, theexternal generator120, and/or theconnector130. The receivingelements109 can be at least generally similar in structure and function to those described in U.S. Patent Application Publication No. 2011/0071593.
• FIG. 2 is a cross-sectional illustration of a spinal cord SC and an adjacent vertebra VT (based generally on information from Crossman and Neary, “Neuroanatomy,” 1995 (published by Churchill Livingstone)), along with multiple signal delivery elements104 (shown as signal delivery elements104a-104f) implanted at representative locations. For purposes of illustration, multiple signal delivery elements104 are shown inFIG. 2 implanted in a single patient. In actual use, any given patient will likely receive fewer than all the signal delivery elements104 shown inFIG. 2.
• As shown inFIG. 2, the spinal cord SC is situated within a vertebral foramen F, between a ventrally located ventral body VB and a dorsally located transverse process TP and spinous process SP. Arrows V and D identify the ventral and dorsal directions, respectively. The spinal cord SC itself is located within the dura mater DM, which also surrounds portions of the nerves exiting the spinal cord SC, including the ventral roots VR, dorsal roots DR and dorsal root ganglia DRG. The dorsal roots DR enter the spinal cord SC at the dorsal root entry zone E, and communicate with dorsal horn neurons located at the dorsal horn DH. In one embodiment, the first and secondsignal delivery elements104a,104bare positioned just off the spinal cord midline M (e.g., about1 mm offset) in opposing lateral directions so that the twosignal delivery elements104a,104bare spaced apart from each other by about 2 mm. In other embodiments, a lead or pairs of leads can be positioned at other epidural locations, e.g., toward the outer edge of the dorsal root entry zone E as shown by a thirdsignal delivery element104c, or at the dorsal root ganglia DRG, as shown by a fourthsignal delivery element104d, or approximately at the spinal cord midline M, as shown by a fifthsignal delivery element104e, or near the ventral roots, as shown by a sixthsignal delivery element104f. In some embodiments, the leads are positioned near the exit of the ventral roots may be advantageous to modify ventral motor pools located in the gray matter. For example, modification of these ventral motor pools may treat spasticity, motor disorders and/or other disorders arising from the ventral motor pools.
• In some embodiments, it may be advantageous to position one or more signal delivery elements104 within the dura mater DM to target neural tissue and one or more glial cells present in the gray and white matter of the spinal cord SC. For example, as shown in the cross-sectional view of a spinal cord SC inFIG. 3, in some embodiments a seventhsignal delivery element104gand an eighthsignal delivery element104iare positioned along the spinal cord midline M on the dorsal and ventral sides of the spinal cord SC, respectively. In some embodiments, one or more signal delivery elements104 can be positioned at other locations. For example, in some embodiments a ninthsignal delivery element104hand a tenth signal delivery element104jare positioned off the spinal cord midline M on opposing lateral sides of the spinal cord SC. High frequency signals applied to the tenth signal delivery element104jmay be especially effective at reducing sympathetic outflow. In some embodiments, high frequency signals applied to the tenth signal delivery element104jmay treat heart failure, hypertension, complex regional pain syndrome, peripheral vascular disease, and other diseases where elevated sympathetic tone is implicated. In some embodiments, one or more signal delivery elements104 may be positioned in other suitable locations within the subdural space. Additionally, in some embodiments, a physician may position one or more signal delivery elements in the epidural space and one or more signal delivery elements in the subdural space. More generally any one of the foregoing signal delivery elements may be used alone or in combination with any other signal delivery element(s)104, depending upon the patent indication(s).
4.0 Representative Clinical Data
• FIG. 4 is a table 400 of selected clinical data gathered during Applicant's clinical study in which patients were implanted with one or more signal delivery elements in accordance with the devices, systems, and methods described in under heading 3.0 above. In particular, patients received electrical therapy signals at a frequency of 10 kHz, a pulse width of 30 microseconds, and an amplitude that ranged from about 0.5 mA to about 6 mA.
• Table 400 includes the following acronyms/abbreviations:
• SCI—spinal cord injury
• ITP—Intrathecal pump
• UL—Upper Limb
• R—Right
• SC—Spinal cord
• MA program—Multi-area program
• LBP—Low back pain
• As shown in the first row of the table 400,Patient1 suffered from upper and lower back pain caused by a spinal cord injury at the eighth thoracic vertebrae.Patient1 was paraplegic and presented with dystonia, spasms (“dancing legs”), and low back and chest wall pain. Before treatment,Patient1 was able to sit comfortably for only 10-15 minutes. Based onPatient1's pain location (lower and upper back), the lead electrodes were placed at or between the eighth and the eleventh thoracic vertebrae (T8-T11). After treatment,Patient1's spasms were gone, andPatient1 was able to sit for several hours.
• As shown in the second row of table 400,Patient2 suffered from thoracic pain caused by a cervical spinal cord injury.Patient2 presented with a paralyzed leg, and spasticity. Before treatment,Patient2 required a crutch for walking. Based onPatient2's pain location (thoracic), the lead electrodes were placed at or near the vertical midpoint of the second thoracic vertebrae (T2). After treatment,Patient2 had improved movement (i.e., improved “tone”, and was able to walk smoothly), renewed functional capacity in the paralyzed leg, a reduction in thoracic pain, improvement in spasticity, and was able to transition from seated to standing positions that caused spasms or tone problems before treatment.
• As shown in the third row of table 400,Patient3 suffered from low back pain caused by a partial spinal cord injury with significant damage at the ninth and tenth thoracic vertebra (T9-T10).Patient3 was paraplegic and also presented with migraines.
• Based onPatient3's pain indications, the lead electrodes were placed at the third cervical vertebrae (C3).Patient3's migraine and low back pain were successfully treated. After treatment,Patient3's ability to sense slight itching was restored, andPatient3 was able to sense pinpricks in the legs as long as the high frequency stimulation was being delivered.Patient3 was also able to flex both ankles in dorsi- and plantar-flexion, bend his legs at both knees, stand up and bear weight with support, and had spontaneous return of erectile function.
• As shown in the fourth row of table 400,Patient4 presented with foot pain from small fiber neuropathy (peripheral neuropathy) and could not sense a pin-prick sensation in that foot.Patient4 presented with Babinski reflex, severe and constant muscle spasms in the back, constant burning sensation at the skin, and stabbing pain in the low- and mid-back. Based onPatient4's pain indication, the lead electrodes were placed to span from the superior aspect of the eighth thoracic vertebrae (T8) to the superior aspect of the twelfth thoracic vertebrae (T12). After treatment,Patient4 experienced restored pin-prick sensations in the foot, the Babinski reflex disappeared and the patient experienced reduced pain in the foot.
• As shown in the fifth row of table 400,Patient5 presented with no pin prick sensation. After a trial period,Patient5 had restored pin prick sensation in the feet. Sensation was maintained at follow-up visits. Ten additional patients (not represented in table 400) also presented with no pin prick sensation, and also had their pinprick sensation restored following treatment in accordance with the foregoing parameters (frequency of 10 kHz, a pulse width of 30 microseconds, and an amplitude that ranged from about 0.5 mA to about 6 mA). These cases, as well as others discussed herein, are representative of patients recovering pain-based sensory responses via a high frequency electrical therapy.
• An additional patient, not represented in table 400, was a paraplegic SCI patient, with a lesion at T11 and with neuropathic lower back pain. His T10-L2 vertebral bodies were fused as a result of injury. Following several failed (more conservative) therapies, he received a high frequency therapy regimen in accordance with the foregoing parameters via a single lead positioned epidurally between the T10-L1 vertebral bodies. In general, leads for high frequency therapy are placed at T8-T11 for back pain, but in this case, the lead could not be advanced (in a rostral direction) past mid-T10. The patient had a dural puncture during the procedure and the resulting headache prevented accurate reporting of pain scores for the first two days of the trial period. However, by the third day, the patient reported significant back pain relief. At the end of the seven day trial period, the patient reported 80% pain relief and was able to voluntarily move his leg for the first time in 15 years. Sensation to touch and pin prick were restored from the L1-S1 dermatomes. His neurological status improved from spastic paralysis at baseline to non-spastic weakness. In addition, for the last three days of the trial, the patient had regained micturition control and had stopped self-catheterizing.
• The electrical therapy treatment methods of the present technology may be used with other therapies (e.g., conventional therapies) for peripheral neuropathy treatment. Such therapies include, but not limited to: corticosteroids; IV immunoglobulins; plasma exchange or plasmapheresis; immunosuppressive agents; surgery; mechanical aids; avoiding toxins including alcohol; aldose reductase inhibitors; fish oil; gamma-linolenic acid; gangliosides; lipoic acid; myoinositol; nerve growth factor; protein kinase C inhibitors; pyridoxine; ruboxistaurin mesylate; thiamine; vitamin B12; pain relievers including codeine; anti-seizure medications including gabapentin, topiramate, pregabalin, carbamazepine, and phenytoin; topical anesthetics such as lidocaine; tricyclic antidepressant medications such as amitriptyline and nortriptyline; selective serotonin and norepinephrine reuptake inhibitors such as duloxetine; and mexiletine. The agents may also include, for example, dopamine uptake inhibitors, monoamine oxidase inhibitors, norepinephrine uptake inhibitors, dopamine agonists, acetocholinesterase inhibitors, catechol O-methyltransferase inhibitors, anticholinergic agents, antioxidants, as well as synaptic and axonal enhancing medications. Additionally, it has been observed that HF therapy can reduce the need for supplemental medications. For example, in a randomized controlled trial of HF therapy for low back and leg pain, concomitant morphine-equivalent medication use and dosage were significantly reduced. Thus, in the context of the present technology, those agents used as primary, supplemental, or adjuvant treatments can be reduced, bringing the benefit of both reduced side-effects and patient compliance burden, when HF therapy is successfully applied.
Further Clinical Results
• The following sections described further clinical results obtained by treating patients with therapy signals at frequencies in the range of 1.5 kHz to 100 kHz.
• (a) Peripheral Polyneuropathy
• FIGS. 5A-5C illustrate data obtained from six peripheral polyneuropathy patients, all presenting with bilateral lower extremity pain. Each of the patients was treated with a therapy signal at 10 kHz, applied to the patient at the T8-T11 vertebral level. The signal had a pulse width of 30 microseconds, and an amplitude that varied from patient to patient. As shown inFIG. 5A, three patients were diagnosed with diabetic peripheral neuropathy, two patients with idiopathic peripheral neuropathy, and one patient with chronic inflammatory demyelinating polyneuropathy. Five of the six patients experienced at least a 50% reduction in pain during an approximately one week trial period, and all were implanted with a pulse generator and signal delivery device.
• As shown inFIG. 5B, four of the five patients who received medication prior to receiving treatment via the 10 kHz therapy signal had their medication reduced or eliminated. As is also shown inFIG. 5B, several of the patients also reported an improvement in sensation level relative to baseline.
• FIG. 5C illustrates the pain scores of the patients at baseline, at the end of the temporary trial, and as of a subsequent follow-up (10.7 months, plus orminus 6 months). These data indicate that the patients received a significant reduction in pain, which was sustained over a significant period after the trial period.
• Anecdotally, an additional diabetic patient (not included in the data shown inFIGS. 5A-5C) suffered a significant amount of pain in his lower legs, which were ulcerated. He was near to receiving an amputation of his leg, prior to receiving electrical signal therapy at 10 kHz via an implanted stimulation device in accordance with the foregoing parameters. After stimulation for a period of two months, the patient's pain was reduced, the patient's wounds were healing, the color returned to the patient's legs, and the patient was walking, whereas previously the patient had been in a wheelchair.
• (b) Post-Stroke Pain
• In still a further example, patients were treated for central post-stroke pain (CPSP). CPSP refers to chronic neuropathic pain resulting from lesions of the central somatosensory nervous system, particularly the spinothalamocortical pathway. The prevalence of CPSP is 1-12% in stroke patients, and symptom onset usually occurs within six months. Most patients complain of burning, allodynia, and hyperalgesia. CPSP is typically pharmacoresistant, and therapeutic options for refractory cases are limited.
• An 85-year-old male with a prior history of hypertension, pre-diabetes, and stroke presented for management of right lower extremity (RLE) pain. One year earlier, he had presented with a new left-sided weakness. Following a stroke diagnosis, he underwent intensive rehabilitation and had near complete resolution of left hemibody weakness. However, six months later, he began to experience new RLE pain. Workup for re-stroke was negative. The patient's pain was constant and burning, with an average intensity of8 on a numerical rating scale of 0-10 for pain assessment, and associated with allodynia and hyperalgesia. He received no benefit from amitriptyline, physical therapy or a right lumbar sympathetic block.
• The patient received spinal cord stimulation at 10 kHz, with a signal delivery device spanning the T8-T11 vertebral bodies. The patient received a successful trial and then underwent permanent implantation. At an 8-week follow-up, he reported greater than 80% pain relief, with an average pain score of 2 and significant improvement in his quality of life. Based at least upon this patient's outcome, it is believed that stimulation in accordance with the foregoing parameters can prove effective for medically refractory CPSP.
• (c) Foot Drop
• In another example, two patients presented with both chronic low back pain, and bilateral foot drop following complications from prior spinal surgeries.Patient1, a 62-year-old woman, experienced persistent foot drop for 13 years, ambulating with aides. Electromyogram (EMG) tests revealed mild sensorimotor axonal polyneuropathy, with demyelinating features. The patient was affected by chronic neurogenic deficits affecting vertebral levels L4-L5 and S1 bilaterally, with active denervation affecting the L5 root on the right side. The patient had been prescribed with analgesics for control of pain at a level of 8 out of 10 on the numerical rating scale, which induced unpleasant side effects.
• Patient2 was a 45-year-old male who suffered from acute paraplegia complications following spinal surgery. His neurological deficit gradually improved, but his back pain and bilateral lower extremity weakness remained, with this right side worse, resulting in an ankle-foot orthosis. Arachnoiditis was evident at the L4-L5 level, with significant clumping of the nerve roots at this level. The patient received strong analgesics for his back pain, which was at a level of 5-8/10 on the numerical rating scale.
• After receiving stimulation at 10 kHz during a trial, both patients proceeded to a permanent implant at a vertebral level of T8-T11. By three months post-implant, both patients no longer required orthotics, and began weaning opioids. At six months,Patient1's foot drop had completely resolved, with a return of sensation and no pain. At nine months,Patient1 had weaned off opioids completely, reporting significant improvements in function without aides, and was able to drive a car.Patient2 no longer used opioids at six months post-implant, and reported almost complete resolution of his foot drop. In addition,Patient2 reported an average pain score of one on a scale of ten, improved walking, and the ability to ride a bicycle.
• It is expected that dorsally positioned electrodes can provide the foregoing motor benefits. For example, dorsal white matter tracts feed into spinal grey matter circuits to inhibit/facilitate reflex and motor coordination. In pathologic states, or in the absence of descending control, these circuits may become dysfunctional, e.g., spastic, tonic, and/or dis-coordinated. HF therapy can ‘normalize’ these circuits via grey matter and/or glial effects, to restore patient function and activities of daily living.
• (d) Dysesthesia
• In still further example, several patients suffering from dysesthesia were treated with spinal cord stimulation at a frequency of 10 kHz, a pulse width of 30 microseconds, and a current amplitude that varied from patient to patient. Prior to treatment, the patients were diagnosed with peripheral polyneuropathy and/or painful diabetic neuropathy. Some patients experienced the inability to feel the bottoms of their feet, which created balance and gait issues, and some patients experienced foot numbness and tingling. After 6-7 days of receiving therapy at 10 kHz, the foot numbness and tingling disappeared, and the patients experienced an improvement in gait.
• The foregoing gait and sensory improvements can be particularly significant for patients suffering from diabetes, because when such patients can walk, they are better able to control their blood sugar. Patients are also better able to avoid falls and fractures, which are additional issues associated with diabetic patients.
• Based on the foregoing, it is expected that stimulation in accordance with the foregoing parameters can be used to address lower limb pain, foot and ankle pain, other types of focal, neuropathic pain, and/or dysesthesia. These results are expected to be achieved with spinal cord stimulation delivered at 10 kHz or other high frequency values, to the dorsal column of the patient's spinal cord. This is contrary to conventional techniques, which may require that stimulation be applied to the dorsal root ganglion.
• In addition, based on the foregoing results, stimulation in accordance with the parameters disclosed herein can produce benefits in addition to, or in lieu of, pain reduction. Such benefits involve restoration of sensory and/or motor functions.
Further Indications
• The discussion above describes representative therapies in the context of treatment for spinal cord injury, peripheral neuropathy and other indications. In some embodiments, the therapy can be administered to patients with peripheral polyneuropathy indications. More generally, the therapy can be applied to patients with other indications, other indications that are associated with sensory loss, and/or motor deficits. As an example, in at least some cases, the observed sensory improvement is correlated (e.g., other indications directly or indirectly) with motor improvement. Accordingly, the foregoing techniques can be used to facilitate sensory and/or motor function recovery. In particular, at least one patient (Patient2 described above with reference toFIG. 4) experienced a reduction in spasticity, as well as other motor-related improvements, in addition to a reduction in pain.
• It is expected that, in at least some embodiments, the foregoing therapies can be used to address sensory deficit, and/or motor deficit, and/or spinal cord injury, in combination with treating pain. In some embodiments, the foregoing therapies can be used to address sensory deficit, and/or motor deficit, and/or spinal cord injury, independent of whether or not the therapy is also used to treat pain. In at least some embodiments, the target location of the therapy signal may be different, depending on whether the therapy is used to address pain, or one or more of a sensory deficit, motor deficit, or spinal cord injury. For example, in at least some cases, it was found that therapy delivered to treat segmental pain also produced an improvement in sensory response, but at a location rostral or caudal to the segmental pain indication.
• It is also believed that sensory deficit can be reversed when treating polyneuropathy, without moving the therapy treatment site, and that foot pain can be addressed with a more generalized treatment location (e.g., T8-T12), as opposed to a specific location (such as the DRG at L5 or S1). More generally, it is believed that the therapy can be applied to the spinal cord instead of the DRG (which is where at least some conventional low frequency treatments are applied). Advantages of applying the therapy signal to the spinal cord rather than the DRG include (a) a lower incidence of adverse events/safety concerns, and/or (b) a broader electric field spread that may have additional pain and/or other benefits, whereas DRG stimulation is typically very focal. In addition, implanting the signal delivery device at the spinal cord may be simpler and easier to “standardize” than implanting the signal delivery device at the DRG.
• Several embodiments of the present technology were described above in the context of therapy signals applied to the patient's spinal cord region. In other embodiments, the therapy signal may be applied to other locations, e.g., peripheral locations.
• Without being bound by theory, it is possible that treating motor and sensory deficits may result from different mechanisms of action. For example, it may be that hyperpolarization of the lamina I/II interneurons explains the resolution of spastic/dystonic (motor) symptoms (e.g., caused by a barrage of spontaneous firing), and the therapies described above hyperpolarize those cells resulting a reduced/normalized neuronal activity level. Because sensory deficit may be due to lack of input from neurons, the ability to address sensory deficit as well as motor symptoms via the same therapy signal may be an indication that different mechanisms of action are responsible for each result. For example, the beneficial effect on motor symptoms may result from a reversal of inhibition or hyperpolarization. Alternatively, the normalization of the sensory input may be the cause of a reduced motor dysfunction. In other words, the sensorimotor reflex may be returned to normal when the sensory neuron returns to normal.
Representative Signal Delivery Parameters
• The therapy signals described above may be delivered in accordance with several suitable signal delivery parameters. For example, the signal frequency may be from about 1.2 kHz to about 100 kHz, or from about 1.5 kHz to about 100 kHz, or from about 2 kHz to about 50 kHz, or from about 3 kHz to about 20 kHz, or from about 3 kHz to about 15 kHz, or from about 5 kHz to about 15 kHz, or from about 3 kHz to about 10 kHz, or 1 kHz, 2 kHz, 3 kHz, 4 kHz, 5 kHz, 10 kHz, 15 kHz, 20 kHz, 50 kHz, or 100 kHz. In particular embodiments, representative current amplitudes for the therapy signal are from 0.1 mA to 20 mA, or 0.5 mA to 10 mA, or 0.5 mA to 7 mA, or 0.5 mA to 5 mA. Representative pulse widths range from about 10 to about 333 microseconds, about 10 to about 166 microseconds, about 25 to about 166 microseconds, about 20 to about 100 microseconds, about 30 to about 100 microseconds, about 30 to about 40 microseconds, about 10 to about 50 microseconds, about 20 to about 40 microseconds, about 25 to about 35 microseconds, about 30 to about 35 microseconds, and about 30 microseconds. Duty cycles can range from about 10% to about 100%, and in a particular duty cycle, signals are delivered for 20 seconds and interrupted for 2 minutes (an approximate 14% duty cycle). In other embodiments, these parameters can have other suitable values. Other suitable parameters and other therapy features are disclosed in the following materials, each of which is incorporated by reference: U.S. Patent Application Publication No. US2009/0204173; U.S. Patent Application Publication No. US2014/0296936; and U.S. Patent Application Publication No. US2010/0274314.
• From the foregoing, it will be appreciated that specific embodiments of the disclosed technology have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Certain aspects of the technology described in the context of particular embodiments may be combined or eliminated in other embodiments. Further, while advantages associated with certain embodiments of the disclosed technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein. The following examples provide further representative embodiments of the presently disclosed technology.
• As used herein, the phrase “and/or,” as in “A and/or B” refers to A alone, B alone, and A and B. To the extent any materials incorporated by reference herein conflict with the present disclosure, the present disclosure controls.

Claims (37)

I/we claim:

1. A method for treating a patient, comprising:

addressing the patient's somatosensory dysfunction and/or motor dysfunction, resulting from neuropathy and/or spinal cord injury, by directing an electrical therapy signal to the patient's spinal cord region, the therapy signal having a frequency in a frequency range from 1.5 kHz to 100 kHz.

2. The method ofclaim 1 wherein addressing the patient's somatosensory dysfunction includes at least partially improving the patient's ability to detect pain.

3. The method ofclaim 2 wherein addressing the patient's somatosensory dysfunction includes restoring the patient's sensation of pin prick.

4. The method ofclaim 1 wherein the therapy signal is directed to the patient to reduce or inhibit patient pain in addition to addressing the patient's somatosensory dysfunction.

5. The method ofclaim 1 wherein the electrical signal is delivered to the patient to treat peripheral polyneuropathy in the patient.

6. The method ofclaim 1 wherein the electrical signal is delivered to the patient to treat diabetic neuropathy.

7. The method ofclaim 1 wherein the somatosensory dysfunction includes dysesthesia.

8. The method ofclaim 1 wherein the somatosensory dysfunction includes foot numbness.

9. The method ofclaim 1 wherein the somatosensory dysfunction includes an inability on the part of the patient to feel the patient's foot.

10. The method ofclaim 1 wherein addressing motor dysfunction includes reducing spasticity.

11. The method ofclaim 1 wherein the frequency is 10 kHz.

12. The method ofclaim 1 wherein the therapy signal is directed to the spinal cord from at least one epidural electrical contact.

13. The method ofclaim 1 wherein the therapy signal is directed from at least one electrical contact having a thoracic vertebral location.

14. The method ofclaim 1 wherein an amplitude of the therapy signal is in an amplitude range of 0.5 milliamps to 10 milliamps.

15. The method ofclaim 1 wherein a pulse width of the therapy signal is in a pulse width range of 10 microseconds to 333 microseconds.

16. A method for treating a patient, comprising:

receiving a diagnosis for the patient corresponding to a somatosensory dysfunction, and/or a motor dysfunction, resulting from neuropathy and/or spinal cord injury; and

in response to the diagnosis, directing an electrical therapy signal to the patient's spinal cord region to address the patient's somatosensory dysfunction and/or motor dysfunction, the therapy signal having a frequency in a frequency range from 1.5 kHz to 100 kHz.

17. The method ofclaim 16 wherein addressing the patient's somatosensory dysfunction includes at least partially improving the patient's ability to detect pain.

18. The method ofclaim 17 wherein addressing the patient's somatosensory dysfunction includes restoring the patient's sensation of pin prick.

19. The method ofclaim 16 wherein the therapy signal is directed to the patient to reduce or inhibit patient pain in addition to addressing the patient's non-pain somatosensory dysfunction.

20. The method ofclaim 16 wherein the electrical signal is delivered to the patient to treat peripheral polyneuropathy in the patient.

21. The method ofclaim 16 wherein the electrical signal is delivered to the patient to treat diabetic neuropathy.

22. The method ofclaim 16 wherein the somatosensory dysfunction includes dysesthesia.

23. The method ofclaim 16 wherein the somatosensory dysfunction includes foot numbness.

24. The method ofclaim 16 wherein the somatosensory dysfunction includes an inability on the part of the patient to feel the patient's foot.

25. The method ofclaim 16 wherein addressing motor dysfunction includes reducing spasticity.

26. The method ofclaim 16 wherein the frequency is 10 kHz.

27. The method ofclaim 16 wherein the therapy signal is directed to the spinal cord from at least one epidural electrical contact.

28. A method for treating a patient, comprising:

addressing the patient's peripheral neuropathy by directing an electrical therapy signal to the patient's spinal cord region, the therapy signal having a frequency in a frequency range from 1.5 kHz to 100 kHz.

29. The method ofclaim 28 wherein the peripheral neuropathy includes peripheral polyneuropathy.

30. The method ofclaim 28 wherein the peripheral neuropathy includes diabetic neuropathy.

31. The method ofclaim 28 wherein the peripheral neuropathy affects sensation in the patient's foot, leg, hand, and/or arm.

32. The method ofclaim 28 wherein the therapy signal is directed to the patient's spinal cord from at least one epidural electrical contact.

33. A method for treating a patient, comprising:

receiving a diagnosis for the patient corresponding to an indication of peripheral neuropathy; and

addressing the patient's peripheral neuropathy by directing an electrical therapy signal to the patient's spinal cord region, the therapy signal having a frequency in a frequency range from 1.5 kHz to 100 kHz.

34. The method ofclaim 34 wherein the electrical signal is delivered to the patient to treat peripheral polyneuropathy in the patient.

35. The method ofclaim 34 wherein the electrical signal is delivered to the patient to treat diabetic neuropathy.

36. The method ofclaim 34 wherein the electrical signal is delivered to the patient to treat neuropathy in the patient's foot, leg, hand, and/or arm.

37. The method ofclaim 34 wherein the therapy signal is directed to the patient's spinal cord from at least one epidural electrical contact.

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