Patent Application
20220409922
Electrical stimulation can be applied to nervous or other tissues to alleviate pain or to provide other medical benefits. Such electrical stimulation can be provided by fully implantable stimulator systems, which can include a pulse generator unit and one or more flexible leads attached thereto. Such lead(s) can include array(s) of electrical contacts (electrodes) that can be used to deliver pulses of electrical stimulus to neurological or other tissue. To provide stimulation to tissue of the spinal cord, such stimulator leads can be installed percutaneously, via a needle inserted into the epidural space and then ‘steered’ into position within the epidural space using a stylet. Additionally or alternatively, a ‘paddle’ style stimulator lead can be implanted surgically by way of an open laminotomy. To stimulate peripheral nervous tissue, a stimulator lead may be positioned adjacent to the peripheral nerve or other peripheral neurological tissue percutaneously or via open surgical techniques. Once implanted, a pulse generator, which can be positioned subcutaneously in a location position distant from the end of a stimulator lead, can apply electrical energy via the electrodes of the stimulator lead. This delivered electrical energy (e.g., time-varying electrical fields, injected electrical currents, etc.) in turn can modify the function of the nervous system in order to alleviate chronic pain, reduce tremor, facilitate locomotor rehabilitation following injury, etc.
In a first aspect, an implantable stimulator is provided that is configured to be secured proximate to a target tissue, the stimulator comprising: (i) an elongate cylindrical lead body, wherein the lead body comprises a first plurality of cylindrical segments that alternate with a second plurality of cylindrical segments along a long axis of the lead body; (ii) a plurality of electrodes, wherein each electrode of the plurality of electrodes forms at least part of an external surface of a respective one of the first plurality of cylindrical segments of the lead body; and (iii) a plurality of light emitters, wherein each light emitter of the plurality of light emitters is disposed within a respective one of the second plurality of cylindrical segments of the lead body, and wherein each light emitter of the plurality of light emitters is configured to emit light at at least one specified wavelength.
In some examples of the first aspect, at least part of an outer surface of a given one of the second plurality of cylindrical segments is formed from a transparent flexible material that at least partially encloses a light emitter of the plurality of light emitters that is disposed within the given one of the second plurality of cylindrical segments. For example, the transparent flexible material can include poly(methyl methacrylate). Additionally or alternatively, the transparent flexible material can have a cylindrical shape and all of the outer surface of the given one of the second plurality of cylindrical segments can be formed from the transparent flexible material.
In some examples of the first aspect, the implantable stimulator additionally includes a transverse element, wherein the transverse element is disposed within one of the first plurality of cylindrical segments, and wherein the transverse element has a central aperture shaped to permit passage of a stylus. For example, the transverse element can also have a plurality of peripheral apertures disposed around the central aperture, and the implantable system can additionally include a wire that is connected to one of the light emitters and that passes through one of the peripheral apertures.
In some examples of the first aspect, the elongate cylindrical lead body has an outer circumference between 1 millimeter and 2.5 millimeters and a total length between 25 centimeters and 90 centimeters, wherein at least one of the first plurality of cylindrical segments has a length between 2 millimeters and 5 millimeters, and wherein at least one of the second plurality of cylindrical segments has a length between 3 millimeters and 6 millimeters.
In some examples of the first aspect, a first light emitter and a second light emitter of the plurality of light emitters are located proximate to each other within the elongate cylindrical lead body such that light emitted from the first light emitter constructively and destructively interferes with light emitted from the second light emitter, thereby enhancing the optical excitation of a focal volume within a portion of the target tissue while reducing the optical excitation of one or more other volumes within the portion of target tissue when the stimulator is proximate to the target tissue.
In some examples of the first aspect, the implantable stimulator additionally includes a controller, wherein the controller includes one or more processors configured to perform controller operations comprising: (a) operating a first light emitter of the plurality of light emitter to emit light at the at least one specified wavelength to provide optical excitation to a portion of the target tissue; and (b) operating the first electrode to provide electrical excitation to the portion of the target tissue at the same time that the first light emitter is emitting light.
In some examples of the first aspect, the implantable stimulator additionally includes a controller, wherein the controller includes one or more processors configured to perform controller operations comprising: (a) operating the first electrode to provide electrical excitation to a portion of the target tissue; and (b) subsequent to operating the first electrode to provide electrical excitation, operating the first light emitter to emit light at the at least one specified wavelength to provide optical excitation to the portion of the target tissue.
In some examples of the first aspect, at least one light emitter of the plurality of light emitters is configured to emit non-coherent light at the at least one specified wavelength. For example, the at least one light emitter can include a superluminescent diode.
In some examples of the first aspect, the at least one specified wavelength includes a wavelength that is between 600 nanometers and 700 nanometers or between 770 nanometers and 1200 nanometers.
In a second aspect, an implantable stimulator is provided that is configured to be secured proximate to a target tissue, the stimulator comprising: (i) an elongate cylindrical lead body, wherein the lead body comprises a first plurality of cylindrical segments that alternate with a second plurality of cylindrical segments along a long axis of the lead body; (ii) a plurality of light emitters, wherein each light emitter of the plurality of light emitters is disposed within a respective one of the second plurality of cylindrical segments of the lead body, and wherein each light emitter of the plurality of light emitters is configured to emit light at at least one specified wavelength, and wherein at least part of an outer surface of a given one of the second plurality of cylindrical segments is formed from a transparent flexible material that at least partially encloses a light emitter of the plurality of light emitters that is disposed within the given one of the second plurality of cylindrical segments; and (iii) a transverse element, wherein the transverse element is disposed within one of the first plurality of cylindrical segments, and wherein the transverse element has a central aperture shaped to permit passage of a stylus.
In some examples of the second aspect, the transparent material includes poly(methyl methacrylate).
In some examples of the second aspect, the transparent flexible material has a cylindrical shape and all of the outer surface of the given one of the second plurality of cylindrical segments is formed from the transparent flexible material.
In some examples of the second aspect, the transverse element also has a plurality of peripheral apertures disposed around the central aperture, and the implantable system additionally includes a wire that is connected to one of the light emitters and that passes through one of the peripheral apertures.
In some examples of the second aspect, a first light emitter and a second light emitter of the plurality of light emitters are located proximate to each other within the elongate cylindrical lead body such that light emitted from the first light emitter constructively and destructively interferes with light emitted from the second light emitter, thereby enhancing the optical excitation of a focal volume within a portion of the target tissue while reducing the optical excitation of one or more other volumes within the portion of target tissue when the stimulator is proximate to the target tissue.
In a third aspect, an implantable stimulator is provided that is configured to be secured proximate to a target tissue, the stimulator comprising: (i) a paddle-shaped lead body having a first side and a second side; (ii) a plurality of electrodes, wherein each electrode of the plurality of electrodes is disposed at a respective location on the first side of the lead body; and (iii) a plurality of light emitters, wherein each light emitter of the plurality of light emitters is configured to emit light at at least one specified wavelength from the first side of the lead body, and wherein the plurality of light emitters are disposed within the lead body relative to the plurality of electrodes such that a portion of the target tissue can receive optical excitation from at least one of the light emitters and electrical excitation from at least one of the electrodes.
In some examples of the third aspect, the electrodes are arranged in pairs of electrodes along a long axis of the lead body, and the pairs of electrodes alternate with the light emitters along the long axis of the lead body.
In some examples of the third aspect, each pair of electrodes includes first and second electrodes that have mirrored locations and shapes about the long axis of the lead body
The foregoing summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the figures and the following detailed description and the accompanying drawings.
The following detailed description describes various features and functions of the disclosed systems and methods with reference to the accompanying figures. The illustrative system and method embodiments described herein are not meant to be limiting. It may be readily understood that certain aspects of the disclosed systems and methods can be arranged and combined in a wide variety of different configurations, all of which are contemplated herein.
I. Overview
Monochromatic light can be provided to a variety of tissues to provide a variety of benefits, including improved wound healing and pain management or other neuromodulatory effects. However, it can be difficult to provide light of sufficient intensity at the necessary wavelength(s) to target tissues, especially where those tissues are deep, within bone, etc. (e.g., to tissues of the spinal cord or dorsal root ganglia). These difficulties are compounded by the need to provide such stimulation from a device that can be easily and reliably surgically implanted and interfaced with an implanted pulse generator unit and/or other implanted systems.
It is also beneficial to provide electrical stimulation and optical stimulation to tissue simultaneously, alternatingly, or according to some other protocol. However, the difficulties above in providing high-power, monochromatic optical stimulation to a target tissue are further compounded by the added requirement that a device also provide electrical stimulation, especially where it is desired that the device be capable of providing electrical and optical stimulation to the same tissue.
Embodiments described herein provide a variety of devices for providing such high-power monochromatic optical stimulation and/or collocated electrical stimulation to deep nervous or other tissues in a manner that is compatible with existing implanted systems and surgical implantation methods and tools. These embodiments include incorporating superluminescent LEDs (SLEDs) or other small, high-power, high-efficiency monochromatic or otherwise configured light emitters into thin, narrow, or otherwise appropriately dimensioned stimulators. This allows the stimulators to be accurately implanted into clinically relevant anatomy (e.g., through natural or surgically-formed passages into the lumen of the spinal column to permit stimulation of the spinal cord).
Additionally, placing appropriate light-emitting elements within the stimulator allows the light emitted from the light emitters to be delivered directly to the target tissue. This avoids the use of optical fibers or other means for coupling light from more remote light emitters (e.g., lasers located in a pulse generator that is distant from the stimulator) to the target tissue. Thus, the present embodiments provide improved efficiency and reliability while avoiding complicated routing, assembly, and minimum bend radius constraints that can be associated with the use of optical fibers.
Electrical power can be provided to the light emitters in such a stimulator using wiring similar to that used in contemporary stimulators (e.g., multi-electrode cylindrical catheter-type stimulators) to provide electrical signals to electrodes. Thus, reliable fabrication methods used to assemble prior electrical stimulators can be applied to fabricate the optical or combined optical/electrical stimulators described herein. This can lead to reduced development and fabrication costs, eased regulatory certification, increased reliability, and other benefits.
Electrical stimulation of the spinal cord can be used to treat control chronic pain (Joosten, E. A. and Franken, G. (2020) ‘Spinal cord stimulation in chronic neuropathic pain: mechanisms of action, new locations, new paradigms’, Pain. NLM (Medline), 161(1), pp. S104-S113). It had been hypothesized that this electrical treatment modulates pain transmission by manipulating a gating mechanism within the dorsal columns of the spinal cord, this gating mechanism having been proposed by Melzack and Wall in 1965 (Melzack, R. and Wall, P. D. (1965) ‘Pain mechanisms: A new theory’, Science. Science, 150(3699), pp. 971-979). The first implantable spinal cord electrical stimulator device for chronic pain was implanted in 1971 (Shealy, C. N., Mortimer, J. T. and Hagfors, N. R. (1970) ‘Dorsal column electroanalgesia.’, Journal of neurosurgery. J Neurosurg, 32(5), pp. 560-564). However, electrical stimulation for the treatment of chronic pain rarely provides complete abolition of chronic pain, with clinical ‘success’ defined as an average improvement in pain intensity of 50%. This level of success is seen in approximately 67-100% of patients in the period of 12 months or less following implantation and in only 46-76% of patients thereafter (Baranidharan, G. et al. (2021) ‘Efficacy and safety of 10 kHz spinal cord stimulation for the treatment of chronic pain: A systematic review and narrative synthesis of real-world retrospective studies’, Biomedicines. MDPI AG, 9(2), pp. 1-21).
Photobiomodulation (PBM) is the application of monochromatic light through the skin with a low energy density to induce non thermal photochemistry effects at a cellular level (Desmet, K. D. et al. (2006) ‘Clinical and experimental applications of NIR-LED photobiomodulation’, Photomedicine and Laser Surgery. Photomed Laser Surg, pp. 121-128.). Previously termed Low Level Laser Light Therapy, PBM was discovered in 1967 by Endre Mester at the Semmelweis University in Hungary. Mester investigated the effects of low powered laser light on malignant tumours in rodents and observed a heightened rate of hair growth and accelerated wound healing (Mester, Adam and Mester, Andrew (2017) ‘The History of Photobiomodulation: Endre Mester (1903-1984)’, Photomedicine and Laser Surgery. Mary Ann Liebert Inc., pp. 393-394). PBM has developed as a clinical treatment that involves the application of various wavelengths of monochromatic light through the skin to achieve a biological effect on a target tissue beneath the skin. The light source is placed near or in contact with the skin to such that light emitted therefrom penetrates tissue and leads to molecular and cellular changes (Cheng, K. et al. (2021) ‘Mechanisms and Pathways of Pain Photobiomodulation: A Narrative Review’, The Journal of Pain. Elsevier B V. doi: 10.1016). PBM is limited in that light must penetrate the skin to achieve an effect. Gursoy and Bradley in 1996 showed that the light wavelength frequently used in PBM devices (near infra-red 830 nm) was only able to penetrate up to 5 cm beneath the skin surface (Gursoy B and Bradley P F (no date) ‘A study of soft tissue penetration by 830 nm wavelength using radiometer and CCD camera.’, Proceedings of the International Congress on Lasers in Dentistry. London p. 105). Photobiomodulation has the capacity to modulate pain (Cheng et al., 2021). Light stimulation does not induce paraesthesia or have motor effects. Light stimulation at red and near infra-red wavelengths is not carcinogenic or mutagenic.
A variety of mechanisms have been proposed to explain the physiological effects of PBM. Mitochondria contain chromophores which absorb photons from PBM. The primary chromophore to absorb red and near-infrared light is the enzyme cytochrome c oxidase (CCO), which is located at unit IV of the mitochondrial respiratory chain. This endogenous photoreceptor, when stimulated by red light, is up-regulated and activates light-altered signalling pathways. Red (600-700 nm) and near-infrared (770-1200 nm) light at low irradiance excites cytochrome c oxidase and promotes electron transport. Longer wavelengths (>900 nm) and wavelengths in the blue and green light range may influence calcium channels. Up-regulating CCO concentration enhances the capacity for cellular oxygen metabolism. Because neurons are highly dependent on oxygen metabolism, this mechanism results in metabolic and haemodynamic alterations that modify neuronal functioning (Cheng et al., 2021). PBM has been shown to disrupt fast axonal transport by causing perturbation of microtubule arrays of small diameter neurons in rat dorsal root ganglia in culture and by reducing ATP synthesis in axonal mitochondria (Chow, R. T. and Armati, P. J. (2016) Photobiomodulation: Implications for anesthesia and pain relief, Photomedicine and Laser Surgery. Mary Ann Liebert Inc., 34(12), pp. 599-609). PBM using 830 nm irradiation specifically suppresses in vivo nerve conduction in small diameter, thinly myelinated Ad and unmyelinated C fibres that have been electrically stimulated (Tsuchiya, K. et al. (1994) ‘Laser irradiation abates neuronal responses to nociceptive stimulation of rat-paw skin’, Brain Research Bulletin. Brain Res Bull, 34(4), pp. 369-374). 830 nm laser irradiation of rat DRG cultures induces the formation of static axonal varicosities in small and medium diameter, TRPV-1 positive neurons, which resolve after 24 hrs. Laser irradiation also induces a progressive and statistically significant decrease in mitochondrial membrane potential in and between the axonal varicosities where the mitochondria are seen as clusters (Holanda, V. et al. (2018) ‘The Mechanistic Basis for Photobiomodulation Therapy of Neuropathic Pain by Near Infrared Laser Light’, Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery. John Wiley and Sons Inc., 37(04), pp. 317-325). In a mouse sciatic nerve crush model, PBM reduced mechanical hypersensitivity and decreased spinal cord and sciatic nerve levels of TNFa (Cidral-Filho, F. J. et al. (2013) light-emitting diode therapy induces analgesia and decreases spinal cord and sciatic nerve tumour necrosis factor—A levels after sciatic nerve crush in mice’, European Journal of Pain (United Kingdom). Eur J Pain, 17(8), pp. 1193-1204). PBM treated animals exhibit a decrease in pro-inflammatory markers (tumor necrosis factor (TNF), interleukin 1β (IL-1β), and hypoxia-inducible factor 1-α (HIF-1 a)) at a chronic constriction injury site in the rat sciatic nerve when compared with non-treated-injured animals (Hsieh, Y. L. et al. (2012) ‘Low-level laser therapy alleviates neuropathic pain and promotes function recovery in rats with chronic constriction injury: Possible involvements in hypoxia-inducible factor 1α (HIF-1α)’, Journal of Comparative Neurology. J Comp Neurol, 520(13), pp. 2903-2916).
Holanda et al delivered 808 nm laser light to the dorsal root ganglia of patients with chronic axial low back pain through a needle positioned in the 2nd lumbar intervertebral foramen. 70% of the patients treated with laser light reported 50% pain relief at one month post treatment (Holanda, V. M. et al. (2016) Photobiomodulation of the dorsal root ganglion for the treatment of low back pain: A pilot study’, Lasers in Surgery and Medicine. John Wiley and Sons Inc., 48(7), pp. 653-659).
Delivery of a subthreshold electrical stimulus concurrently with infrared light lowered the required optical energy per pulse to achieve stimulation and delivering a subthreshold electrical stimulus to enhance the excitability of neural tissue to optical stimuli occurs in a nonlinear fashion (Duke, A. R. et al. (2009) ‘Combined optical and electrical stimulation of neural tissue in vivo’, Journal of Biomedical Optics. SPIE-Intl Soc Optical Eng, 14(6), p. 060501).
A stimulator as described herein could have a cylindrical geometry, a paddle-shaped geometry, or some other geometry appropriate to providing optical or combined electrical and optical stimulation to a target tissue and to surgically implanting the stimulator in position to provide such stimulation. As described in detail below, the target tissue could be tissue of the spinal cord, spinal nerves, dorsal root ganglia, or other nervous tissue associated with the spinal cord. However, the stimulators described herein could alternatively be used and/or adapted to provide stimulus to peripheral nerves, cranial nerves, nervous tissue of the brain, mesenteric nervous tissue, or some other nervous tissue. Additionally or alternatively, the stimulators described herein could be used and/or adapted to provide stimulus to muscle or other non-nervous tissues.
Additionally, a stimulator as described herein could be used as part of a fully-implanted stimulation system. For example, such a stimulator could include connectors to facilitate electrical connection to an implantable pulse generator and/or some other implantable system and/or to a cable that could be configured to electrically couple the stimulator to such an implantable system. In another example, such a stimulator could be provided already connected to (e.g., assembled as part of) an implantable system that include pulse generator, cabling, and/or other components. Alternatively, a stimulator as described herein could be used as part of a percutaneous stimulator system, with cabling or other means electrically connecting the wholly or partially implanted stimulator to a pulse generator or other components located outside the body. In some examples, such a stimulator could be configured to be implanted and initially operated using a non-implanted system (e.g., an extra-corporeal clinical stimulus generator connected to the stimulator via transcutaneous cabling) to determine optimal positioning and stimulus parameters. Once the clinical efficacy, optimal stimulus parameters, or other information about the stimulator is determine using the non-implanted system, the stimulator could then be disconnected from the non-implanted system and coupled to a fully-implanted system (e.g., programmed using the information generated using the non-implanted system).
The embodiments described herein are particularly adapted to providing optical or combined electrical and optical stimulation to tissue of the spinal cord, dorsal root ganglia, and peripheral nerves in order to inhibit pain or to provide other neuromodulatory effects. Conventional electrical stimulation may be supplemented by stimulation with light from single or multiple light sources contained within the same stimulator (e.g., lead or paddle array). Alternatively, such a stimulator could lack electrodes and could operate, using light emitters located within the stimulator, to provide optical stimulation alone.
Although example implementations are described below with reference to modulating the dorsal column, dorsal horn, dorsal root, dorsal root entry zone, and/or other particular regions of the spinal column to control pain, the modulation may in some instances be directed to other neurological structures and/or target neural populations of the spinal cord and/or other neurological tissues. Some implementations can have configurations, components, or procedures different than those described in this section, and other implementations may eliminate particular components or procedures.
As noted above, it is beneficial to provide active light-emitting elements (e.g., SLEDs or other elements configured to provide substantially monochromatic or otherwise spectrally specified light) within a stimulator (e.g., 140) in order to provide therapeutic light directly to target tissue. This avoids the negative aspects of providing light from outside the body and/or using optical fibers to couple light from a distant source (e.g., a laser located in the pulse generator 130) to the target tissue via the stimulator 140. It is also beneficial that these light emitters have size, power, efficiency, and other parameters that are compatible with incorporation into standard-sized cylindrical catheter-style stimulators (e.g., that also include central lumens for the use of stylets to guide insertion of the stimulators), paddle-style stimulators, or other geometries commonly used to provide electrical stimulus to target tissues. This allows existing surgical techniques and instruments to be applied to implant these improved stimulators in the sort of anatomical sites commonly used for electrical stimulation.
A variety of small, high-power, high-efficiency light emitting elements, including a variety of light-emitting diodes (LEDs), have recently become available that satisfy the above operational parameters. These LED light sources have suitably small sizes (e.g., a largest dimension less than 1 mm) to be incorporated into conventional stimulator geometries and suitably high emitted light powers at the desired wavelength (e.g., greater than 1 J/cm2) to provide clinically relevant optical stimulation to neurological tissue or other tissue of interest. Such LED sources are also superior to the laser sources traditionally employed in non-implanted PBM systems in that they have lower current requirements and higher efficiencies while still providing substantially monochromatic light, allowing these LED sources to be driven by circuitry of implantable pulse generators, which can be limited with respect to maximum drive current, instantaneous power output, and total stored energy.
Suitable LED light emitters include conventional LEDs, organic LEDs (OLEDs), perovskite LEDs (PLEDs), and superluminescent LEDs (SLEDs). An example of a suitable commercially available light emitter is the Osram Firefly SFH 4055, which exhibits a peak wavelength at 860 nm and a radiant intensity of 40 mW/sr while having dimensions of 1.0 mm×0.55 mm×0.325 mm. Indeed, these light emitters are now capable of sufficiently narrow emission spectra that a stimulator as described herein could include two (or more) different light emitters that emit light at slightly different emission wavelengths such that the light from the two (or more) light emitters constructively and destructively interfere. The locations, orientations, wavelengths, and emission profiles of these two (or more) light emitters could then be specified within a stimulator such that the pattern of constructive and destructive interference enhances the excitatory or other clinical effect of the emitted light on tissue within certain volume(s) relative to the stimulator. For example, such that light emitted from a first light emitter constructively and destructively interferes with light emitted from a second light emitter, thereby enhancing a magnitude of optical excitation of a focal volume within a portion of a target tissue that is proximate to the first and second light emitters while reducing a magnitude of optical excitation of one or more other volumes within the portion of the target tissue.
As noted above, the application of LED light stimulation (e.g., at red and near-infrared wavelengths) and electrical stimulation to the same neurological tissue (e.g., simultaneous and/or sequentially) may be synergistic, providing greater clinical benefits than either type of stimulation alone. For example, a patient can receive effective pain relief by the combination of LED light stimulation and electrical stimulation by virtue of a synergistic mechanism. The patient can receive effective pain relief by the addition of LED light stimulation to electrical stimulation by targeting additional pain relieving mechanisms at a cellular level and/or by enhancement of the effect of the mechanism of the electrical stimulus due to the optical stimulation increasing the degree of effect of the electrical stimulus on the tissue. The small size and location within the stimulator of the light emitters described herein allows those light emitters to target the same, small target tissues with both electrical and optical stimulus. As described in greater detail below, this can be done by disposing the light emitters and electrodes alternatingly along the axis of a cylindrical catheter-type stimulator or by disposing the electrodes and light emitters near each other on/within a stimulator according to some other pattern.
The implementations described herein are predominantly described in the context of treating chronic neuropathic spinal pain and radicular pain with electrical and light modulation applied to the spinal cord in the lower thoracic vertebral territory (T9-T12). However, clinically relevant modulation signals or other therapeutic stimulus can be applied to other patient locations to address other indications. For example, optical and/or electrical stimulus may be applied to the dorsal root ganglia and foramen region laterally outward from the center of the spinal cord/spinal column. Stimulus may be applied to other spinal levels including the sacrum (e.g., to treat urinary or faecal incontinence) or above the thoracic territory (e.g., to treat angina). Stimulus may be applied to the cervical region to address radicular pain, complex regional pain and/or total body pain. Stimulation may be applied to the occipital nerves, for example, in the treatment of migraine.
As noted above, the stimulators described herein could be used to provide optical and/or electrical stimulus to a variety of target tissues in order to address a variety of symptoms or other clinically relevant issues. For example, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C1-C5 region (e.g., C2-C3) in order to address one or more of a variety of headache pain syndromes, including but not limited to herpes zoster (shingles) (providing stimulus to C4-C5 and/or the trigeminal nerve), migraine, cluster headaches, swimmer's headaches, analgesic rebound headaches, and/or occipital neuralgia.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C2-C4 region (e.g., C2-C3) in order to address one or more pain syndromes, including but not limited to trigeminal neuralgia, temporomandibular joint dysfunction, atypical facial pain, myofascial pain syndrome of the face, cancer pain, hyoid syndrome, and/or reflex sympathetic dystrophy of the face.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C2-C6 region (e.g., C3-C4) in order to address one or more neck and/or brachial plexus pain syndromes, including but not limited to cervical facet syndrome, cervical radiculopathy, fibromyalgia of the cervical musculature, myofascial pain syndrome experienced in the cervical musculature, cervical strain, cervicothoracic interspinous bursitis syndrome, spinal stenosis, brachial plexopathy, Pancoast's syndrome, and/or thoracic outlet syndrome.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C2-C6 region (e.g., C3-C5) in order to address one or more shoulder pain syndromes, including but not limited to arthritic shoulder pain, acromio-clavicular joint pain, shoulder fibromyalgia, shoulder myofascial pain syndrome, subdeltoid bursitis, bicipital tendonitis, supraspinatus syndrome, rotator cuff tear, deltoid syndrome, teres major syndrome, and/or scapulocostal syndrome.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C2-C6 region (e.g., C3-C5) in order to address one or more elbow pain syndromes, including but not limited to arthritic elbow pain, tennis elbow, golfer's elbow, anconeus syndrome, supinator syndrome, brachioradialis syndrome, ulnar nerve entrapment at the elbow, lateral antebrachial cutaneous nerve syndrome, and/or olecranon bursitis.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C2-C6 region (e.g., C3-C5) in order to address one or more other upper extremity pain syndromes, including but not limited to fibromyalgia-related arm pain, myofascial pain syndrome, and/or phantom limb pain.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C2-C6 region (e.g., C3-C5) in order to address one or more wrist pain syndromes, including but not limited to arthritic wrist pain, carpal tunnel syndrome, De Quervain's tenosynovitis, and/or arthritic carpometacarpal joint pain.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C2-C6 region (e.g., C3-C5) in order to address one or more hand pain syndromes, including but not limited to arthritic finger pain, trigger thumb, trigger finger, ganglion cysts of the wrist & hand, sesamoiditis of the hand, plastic bag palsy, carpal boss syndrome, and/or Dupuytren's contracture.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T1-T12 region in order to address one or more chest wall pain syndromes, including but not limited to costosternal syndrome, manubriosternal joint pain, intercostal neuralgia, diabetic truncal neuropathy, Tietze's syndrome, precordial catch syndrome, pain related to fractured ribs, and/or post-thoracotomy pain.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T1-T12 region in order to address one or more thoracic spine pain syndromes, including but not limited to acute herpes zoster expressing in the thoracic dermatome, cancer pain, costovertebral arthritis pain, post-herpetic neuralgia, spinal stenosis, and/or pain related to thoracic vertebral compression fractures.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T6-T12 region in order to address one or more abdominal & groin pain syndromes, including but not limited to acute pancreatitis, cancer pain, chronic pancreatitis, ilioinguinal neuralgia, visceral pain (peritoneum, stomach, duodenum, intestine, colon, liver, spleen, pancreas, kidney, adrenal gland, appendix, gall bladder, etc.), post-vasectomy pain syndrome, genitofemoral neuralgia, and/or interstitial cystitis.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T8-T12 region in order to address one or more lumbar spine & sacroiliac joint pain syndromes, including but not limited to lumbar musculature fibromyalgia, myofascial pain syndrome, lumbar radiculopathy, latissimus dorsi muscle syndrome, spinal stenosis, arachnoiditis, and/or sacroiliac joint pain.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T12-L5 region in order to address one or more pelvic pain syndromes, including but not limited to osteitis pubis, cancer pain, gluteus maximus syndrome, visceral pain (pelvis, coccyx, ovaries, fallopian tubes, uterus, vulva, clitoris, perineum, urinary bladder, testicles, rectum, etc.), piriformis syndrome, ishiogluteal bursitis, levator ani syndrome, coccydynia, interstitial cystitis, and/or vulvodynia.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T7-T12 region in order to address one or more hip & lower extremity pain syndromes, including but not limited to lower extremity musculature fibromyalgia, lower extremity myofascial pain syndrome, musculature pain, arthritic hip pain, snapping hip syndrome, restless leg syndrome, iliopectinate bursitis, ischial bursitis, meralgia paresthetica, phantom limb pain (e.g., by stimulating at t7-t10), and/or trochanteric bursitis.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T8-T12 region in order to address one or more knee pain syndromes, including but not limited to arthritic knee pain, medial collateral ligament pain, jumper's knee syndrome, runner's knee syndrome, suprapatellar bursitis, prepatellar bursitis, superficial infrapatellar bursitis, deep infrapatellar bursitis, baker's cyst, and/or pes anserine bursitis.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T8-T12 region in order to address one or more ankle pain syndrome, including but not limited to arthritic ankle pain, arthritic midtarsal joints, deltoid ligament strain, anterior tarsal tunnel syndrome, posterior tarsal tunnel syndrome, and/or Achilles tendonitis.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the T8-T12 region in order to address one or more foot pain syndromes and/or foot syndromes associated with pain, including but not limited to arthritic toe pain, bunion pain, gout, Morton's neuroma, plantar fasciitis, calcaneal spur syndrome, mallet toe syndrome, and/or hammer toe syndrome.
In some examples, a stimulator as described herein could be implanted to provide stimulus to spinal cord tissue in the C2-C4 region e.g., C3-C4) in order to address one or more whole body pain syndromes, including but not limited to fibromyalgia, cancer pain, and/or multiple-limb chronic regional pain syndrome.
II. Example Stimulators
As noted above, it is beneficial to provide active light-emitting elements within a stimulator in order to provide therapeutic light directly to target tissue, thus avoiding the negative aspects of providing light from outside the body and/or using optical fibers to couple light from a distant source. It is also beneficial that these light emitters have size, power, efficiency, and other parameters that are compatible with incorporation into stimulators having geometries the same as or similar to existing implantable electrical stimulation devices. Appropriate light emitting elements include a variety of LEDs having suitably small sizes (e.g., a largest dimension less than 1 mm) to be incorporated into conventional stimulator geometries and suitably high emitted light powers at the desired wavelength (e.g., greater than 1 J/cm2) to provide clinically relevant optical stimulation to neurological tissue or other tissue of interest. Such LED sources include organic LEDs (OLEDs), perovskite LEDs (PLEDs), superluminescent LEDs (SLEDs), and two-way LEDs that incorporate quantum dots. Such light emitting elements could be configured to emit light at one or more specified therapeutic wavelengths, including but not limited to ultraviolet wavelengths (e.g., 1-380 nm), visible light wavelengths (e.g., 380-750 nm), near infrared wavelengths (e.g., 700-1300 nm), and infrared wavelengths (e.g., at or greater than 1330 nm)
Stimulators including such light emitters (e.g., linear or otherwise-configured arrays of such light emitters) could have narrow and/or thin geometries to permit them to be guided through naturally-existing or surgically-formed holes or other features of bones to access a variety of target tissues (e.g., tissue of the spinal cord, dorsal root ganglia, etc.). For example, such stimulators could have a cylindrical or other catheter-style geometry. In another example, such stimulators could have a paddle-style geometry, with light emitters and/or electrodes distributed across one side of the paddle. Such a paddle-style stimulator could be installed on the surface of the spinal cord following, e.g., laminectomy to expose the spinal cord. Electrodes could also be included as part of such stimulators, e.g., alternating with the light emitters to allow electrical stimulation and optical stimulation to be applied to the same small regions of target tissue.
As depicted in
As shown in
The stimulator 200 and/or elements thereof could have dimensions specified to facilitate implantation into a body proximate a target tissue, to increase the overall compliance of the stimulator 200, to facilitate use of standard surgical techniques and/or tools in the implantation of the stimulator 200, to control a shape and/or size of individual volumes of a target tissue that can be stimulated with optical and/or electrical stimuli emitted from the stimulator 200, or to satisfy some other consideration. For example, the cylindrical stimulator 200 could have an outer circumference between 1 and 2.5 mm (e.g., 1.2 mm), the length of the electrodes 220 (or other elements arranged between the transparent segments 235) could be between 2 mm and 5 mm (e.g., 3 mm), the length of the transparent segments 235 could be between 3 mm and 6 mm (e.g., 4 mm) and the overall length of the stimulator 200, including the lead 210, could be between 25 cm and 90 cm (e.g., 50 cm). The light emitters 230 could be very small, with a largest dimension less than 1 mm (e.g., 1 mm×0.5 mm×0.5 mm).
In order to provide current/voltage to the light emitters 230 and electrodes 220, wiring can be routed along the length of the lead 210 and stimulator 200 to the light emitters 230 and electrodes 220. Such wiring can be routed within one or more spaces or cavities within the stimulator 200. It may also be desirable to provide a central lumen running along the length of the stimulator 200 into which a stylet or other guide could be emplaced during implantation, in order to stiffen the stimulator 200 and guide it into position. Such a stylet could also allow the stimulator 200 to have a higher compliance, since the stiffness of the stylet could facilitate implantation of the stimulator 200 (e.g., penetration of intervening tissues).
The transverse element 225 includes a central aperture 227. The central aperture 227 could be sized and/or shaped (e.g., with one or more keys or other alignment features) to accept a stylet that could be inserted into the stimulator 200 in order to facilitate implantation of the stimulator 200.
The transverse element 225 also includes a number of peripheral apertures 229 disposed around the central aperture 227. Wires (e.g., 240) can pass through the peripheral apertures 229 to provide current/voltage to the electrodes 220 and/or light emitters 230 of the stimulator 200. Routing the wires through the peripheral apertures 229 facilitates assembly of the stimulator 200, provides organization to the wiring, and also protects the wiring from damage when a stylet or other elements are inserted into/removed from the central aperture 227.
As shown in
As noted above, the optical or combined optical and electrical stimulators described herein could have a variety of geometries according to an application (e.g., the cylindrical, catheter-type geometry depicted in
Note that the stimulator 400 depicted in
III. Example Systems
As shown in
Where the communication interface 502 is present, it may function to allow system 500 to communicate, using analog or digital modulation of electric, magnetic, electromagnetic, optical, or other signals, with other devices, access networks, and/or transport networks. Thus, communication interface 502 may facilitate receiving programming updates, updated stimulation profiles or other information related to treatment using the system 500, or other operational data. Additionally or alternatively, the communication interface 502 may facilitate receiving commands from a user-controlled device (e.g., a cell phone or other generic device adapted to transmit such commands and/or a purpose-built device for transmitting such commands). Such commands could include commands to stop or start stimulation or some other therapy, to adjust an amplitude or other parameter of such operation (e.g., to increase or decrease an amplitude of electrical and/or optical stimulus generated by the device), to switch between therapeutic modes, or to control some other aspect of operation of the system 500.
Where the user interface 504 is present, it may function to allow system 500 to interact with a user, for example to receive input from and/or to provide output to the user. Where the system 500 is wholly implanted, this could include operating a mechanical switch, magnetic field sensor or magnetic switch, or other elements to receive inputs from a user to modify some aspect of operation of the system 500. Where the system 500 only partially implanted (e.g. only the stimulator 514 is located within a patient's body), user interface 504 may include input components such as a keypad, keyboard, touch-sensitive or presence-sensitive panel, computer mouse, trackball, joystick, microphone, and so on. User interface 504 may also include one or more output components such as a display screen which, for example, may be combined with a presence-sensitive panel. The display screen may be based on CRT, LCD, and/or LED technologies, or other technologies now known or later developed. User interface 504 may also be configured to generate audible output(s), via a speaker, speaker jack, audio output port, audio output device, earphones, and/or other similar devices.
Processor 506 may comprise one or more general purpose processors—e.g., microprocessors—and/or one or more special purpose processors—e.g., digital signal processors (DSPs), graphics processing units (GPUs), floating point units (FPUs), network processors, tensor processing units (TPUs), or application-specific integrated circuits (ASICs). In some instances, special purpose processors may be capable of determining the timing, amplitude, shape, and other properties of pulses of electrical and/or optical stimulus provided via one or more electrodes and/or light emitters of the stimulator 514.
The stimulator 514 may be any type of optical and/or combined electrical and optical stimulator as described herein. The pulse generator 508 include timers, current sources, voltage sources, digital to analog converters, amplifiers, fuses or other current or voltage limiting elements, blocking capacitors, and/or any other circuitry or components configured to drive the electrode(s) and/or light emitter(s) of the stimulator 514 to provide optical and/or combined electrical and optical stimulation as described herein. The battery 512 provides power to the system 500 and may be sized to provide a desired level and amount of stimulus for at least a specified period of time, after which point the system 500 and/or components thereof (e.g., the battery 512, a pulse generator unit that includes the battery 512) may be replaced surgically.
IV. Conclusion
It should be understood that arrangements described herein are for purposes of example only. As such, those skilled in the art will appreciate that other arrangements and other elements (e.g. machines, interfaces, operations, orders, and groupings of operations, etc.) can be used instead, and some elements may be omitted altogether according to the desired results. Further, many of the elements that are described are functional entities that may be implemented as discrete or distributed components or in conjunction with other components, in any suitable combination and location, or other structural elements described as independent structures may be combined.
While various aspects and implementations have been disclosed herein, other aspects and implementations will be apparent to those skilled in the art. The various aspects and implementations disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope being indicated by the following claims, along with the full scope of equivalents to which such claims are entitled. It is also to be understood that the terminology used herein is for the purpose of describing particular implementations only, and is not intended to be limiting
V. Enumerated Example Implementations
Aspects of the present disclosure may thus relate to one of the enumerated example embodiments (EEIs) listed below. It will be appreciates that features indicated with respect to one EEI can be combined with other EEIs.
EEI 1 is an implantable stimulator configured to be secured proximate to a target tissue, the implantable stimulator comprising: (i) an elongate cylindrical lead body, wherein the lead body comprises a first plurality of cylindrical segments that alternate with a second plurality of cylindrical segments along a long axis of the lead body; (ii) a plurality of electrodes, wherein each electrode of the plurality of electrodes forms at least part of an external surface of a respective one of the first plurality of cylindrical segments of the lead body; and (iii) a plurality of light emitters, wherein each light emitter of the plurality of light emitters is disposed within a respective one of the second plurality of cylindrical segments of the lead body, and wherein each light emitter of the plurality of light emitters is configured to emit light at at least one specified wavelength.
EEI 2 is the implantable stimulator of EEI 1, wherein at least part of an outer surface of a given one of the second plurality of cylindrical segments is formed from a transparent flexible material that at least partially encloses a light emitter of the plurality of light emitters that is disposed within the given one of the second plurality of cylindrical segments.
EEI 3 is the implantable stimulator of EEI 2, wherein the transparent flexible material comprises poly(methyl methacrylate).
EEI 4 is the implantable stimulator of EEI 2, wherein the transparent flexible material has a cylindrical shape and wherein all of the outer surface of the given one of the second plurality of cylindrical segments is formed from the transparent flexible material.
EEI 5 is the implantable stimulator of EEI 1, further comprising a transverse element, wherein the transverse element is disposed within one of the first plurality of cylindrical segments, and wherein the transverse element has a central aperture shaped to permit passage of a stylus.
EEI 6 is the implantable stimulator of EEI 5, wherein the transverse element also has a plurality of peripheral apertures disposed around the central aperture, and wherein the implantable stimulator additionally includes a wire that is connected to one of the light emitters and that passes through one of the peripheral apertures.
EEI 7 is the implantable stimulator of EEI 1, wherein the elongate cylindrical lead body has an outer circumference between 1 millimeter and 2.5 millimeters and a total length between 25 centimeters and 90 centimeters, wherein at least one of the first plurality of cylindrical segments has a length between 2 millimeters and 5 millimeters, and wherein at least one of the second plurality of cylindrical segments has a length between 3 millimeters and 6 millimeters.
EEI 8 is the implantable stimulator of EEI 1, wherein a first light emitter and a second light emitter of the plurality of light emitters are located proximate to each other within the elongate cylindrical lead body such that light emitted from the first light emitter constructively and destructively interferes with light emitted from the second light emitter, thereby enhancing a magnitude of optical excitation of a focal volume within a portion of the target tissue while reducing a magnitude of optical excitation of one or more other volumes within the portion of the target tissue when the implantable stimulator is proximate to the target tissue.
EEI 9 is the implantable stimulator of EEI 1, further comprising a controller, wherein the controller comprises one or more processors configured to perform controller operations comprising: (i) operating a first light emitter of the plurality of light emitters to emit light at the at least one specified wavelength to provide optical excitation to a portion of the target tissue; and (ii) operating a first electrode of the plurality of electrodes to provide electrical excitation to the portion of the target tissue while the first light emitter is emitting light.
EEI 10 is the implantable stimulator of EEI 1, further comprising a controller, wherein the controller comprises one or more processors configured to perform controller operations comprising: (i) operating a first electrode of the plurality of electrodes to provide electrical excitation to a portion of the target tissue; and (ii) subsequent to operating the first electrode to provide electrical excitation, operating a first light emitter of the plurality of light emitters to emit light at the at least one specified wavelength to provide optical excitation to the portion of the target tissue.
EEI 11 is the implantable stimulator of EEI 1, wherein at least one light emitter of the plurality of light emitters is configured to emit non-coherent light at the at least one specified wavelength.
EEI 12 is the implantable stimulator of EEI 11, wherein the at least one light emitter comprises a superluminescent diode.
EEI 13 is the implantable stimulator of EEI 1, wherein the at least one specified wavelength comprises a wavelength that is between 600 nanometers and 700 nanometers or between 770 nanometers and 1200 nanometers.
EEI 14 is an implantable stimulator configured to be secured proximate to a target tissue, the implantable stimulator comprising: (i) an elongate cylindrical lead body, wherein the lead body comprises a first plurality of cylindrical segments that alternate with a second plurality of cylindrical segments along a long axis of the lead body; (ii) a plurality of light emitters, wherein each light emitter of the plurality of light emitters is disposed within a respective one of the second plurality of cylindrical segments of the lead body, and wherein each light emitter of the plurality of light emitters is configured to emit light at at least one specified wavelength, and wherein at least part of an outer surface of a given one of the second plurality of cylindrical segments is formed from a transparent flexible material that at least partially encloses a light emitter of the plurality of light emitters that is disposed within the given one of the second plurality of cylindrical segments; and (iii) a transverse element, wherein the transverse element is disposed within one of the first plurality of cylindrical segments, and wherein the transverse element has a central aperture shaped to permit passage of a stylus.
EEI 15 is the implantable stimulator of EEI 14, wherein the transparent material comprises poly(methyl methacrylate).
EEI 16 is the implantable stimulator of EEI 15, wherein the transparent flexible material has a cylindrical shape and wherein all of the outer surface of the given one of the second plurality of cylindrical segments is formed from the transparent flexible material.
EEI 17 is the implantable stimulator of EEI 14, wherein the transverse element also has a plurality of peripheral apertures disposed around the central aperture, and wherein the implantable stimulator additionally includes a wire that is connected to one of the light emitters and that passes through one of the peripheral apertures.
EEI 18 is the implantable stimulator of EEI 14, wherein a first light emitter and a second light emitter of the plurality of light emitters are located proximate to each other within the elongate cylindrical lead body such that light emitted from the first light emitter constructively and destructively interferes with light emitted from the second light emitter, thereby enhancing a magnitude of optical excitation of a focal volume within a portion of the target tissue while reducing a magnitude of optical excitation of one or more other volumes within the portion of the target tissue when the implantable stimulator is proximate to the target tissue.
EEI 19 is an implantable stimulator configured to be secured proximate to a target tissue, the implantable stimulator comprising: (i) a paddle-shaped lead body having a first side and a second side; (ii) a plurality of electrodes, wherein each electrode of the plurality of electrodes is disposed at a respective location on the first side of the lead body; and (iii) a plurality of light emitters, wherein each light emitter of the plurality of light emitters is configured to emit light at at least one specified wavelength from the first side of the lead body, and wherein the plurality of light emitters are disposed within the lead body relative to the plurality of electrodes such that a portion of the target tissue can receive optical excitation from at least one of the light emitters and electrical excitation from at least one of the electrodes.
EEI 20 is the implantable stimulator of EEI 19, wherein the electrodes are arranged in pairs of electrodes along a long axis of the lead body, and wherein the pairs of electrodes alternate with the light emitters along the long axis of the lead body.
EEI 21 is the implantable stimulator of EEI 19, wherein each pair of electrodes includes first and second electrodes that have mirrored locations and shapes about a long axis of the lead body.
