WO2021142517A1 - Système et procédé de stimulation de neurones - Google Patents

Système et procédé de stimulation de neurones Download PDF

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Publication number
WO2021142517A1
WO2021142517A1 PCT/AU2021/050028 AU2021050028W WO2021142517A1 WO 2021142517 A1 WO2021142517 A1 WO 2021142517A1 AU 2021050028 W AU2021050028 W AU 2021050028W WO 2021142517 A1 WO2021142517 A1 WO 2021142517A1
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electrical signals
electrodes
frequency
lead body
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PCT/AU2021/050028
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English (en)
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Marc RUSSO
Richard Nash
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CRPS Solutions Pty Ltd
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Application filed by CRPS Solutions Pty Ltd filed Critical CRPS Solutions Pty Ltd
Publication of WO2021142517A1 publication Critical patent/WO2021142517A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551—Spinal or peripheral nerve electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36062—Spinal stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36071—Pain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A61N1/36167—Timing, e.g. stimulation onset
    • A61N1/36171—Frequency
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36189—Control systems using modulation techniques
    • A61N1/36196—Frequency modulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A61N1/3615—Intensity
    • A61N1/36164—Sub-threshold or non-excitatory signals

Definitions

  • the present invention relates to a system for stimulating neurons and in one particular example, to a system for stimulating neurons within at least one of the dorsal column and dorsal hom, such as dendrites in a spinal cord, dorsal hom, or dorsal column.
  • Spinal cord stimulation is a known technique for relieving chronic pain.
  • the stimulation is targeted at axons in the dorsal columns of the spinal cord, which is also known as paresthesia spinal cord stimulation.
  • This type of stimulation is designed to stimulate axons in the spinal cord, which works well for pain relief, however, the stimulation are of limited efficacy. In some cases, the loss of efficacy may be about 25%.
  • US-9,089,708 provides systems and methods for stimulation of neurological tissue apply a stimulation waveform that is derived by a developed genetic algorithm, which may be coupled to a computational model of extracellular stimulation of a mammalian myelinated axon.
  • the waveform is optimized for energy efficiency.
  • an aspect of the present invention seeks to provide a system for stimulating neurons, the system includes a lead including a lead body; at least one electrode carried by a distal portion of the lead body, the at least one electrode being configured to be provided proximate a dorsal hom in the spinal cord of a subject; and at least one pair of connections extending from the electrodes; and a signal generator electrically coupled to the at least one connection and configured to generate electrical signals that are applied to the at least one electrode, and wherein the electrical signals include waveforms to stimulate neurons within at least one of the spinal cord, dorsal column and dorsal hom.
  • the waveforms include at least one of square waveforms; non square waveforms; an exponentially waveform; a ramp waveform; a sine waveform; and a triangular waveform.
  • the ramp waveform is defined by a gradient that is of a positive value or negative value.
  • the lead body includes: at least two spaced apart electrodes carried by the distal portion of the lead body; and at least two connections.
  • the lead body includes at least two spaced apart double electrodes carried by the distal portion of the lead body; and a respective connection for each electrode.
  • the lead body includes at least two spaced apart outer electrodes carried by the distal portion of the lead body; at least two spaced apart inner electrodes carried by the distal portion of the lead body; and a respective connection for each electrode.
  • the lead body includes an electrode array including two spaced apart outer electrodes; and a plurality of spaced apart inner electrodes.
  • the at least one electrode has a length that is at least one of less than 8.5mm; less than 9mm; less than 9.5mm; less than 10mm; less than 10.5mm; less than 11mm; less than 11.5mm; less than 12mm; greaterthan 1mm; greaterthan 1.5mm; greater than 2mm; greater than 2.5mm; greater than 3mm; about 3-8mm; about 3mm; about 4mm; about 5mm; about 6mm; about 7mm; and about 8mm.
  • multiple electrodes are spaced by at least one of less than 12mm; less than 10mm; less than 8mm; less than 6mm; less than 4mm; greaterthan 1mm; greaterthan 1 5mm; greaterthan 2.0mm; greaterthan 2.5mm; about 3-4mm; about 3mm; about 4mm; about 3.3mm; about 3.4mm; and about 3.5mm.
  • the lead body includes a section between electrodes that is at least one of electrically non-conductive and flexible.
  • the pulse has a width of at least one of greater than SOOps: greater than 900ps; and about lOOOps.
  • the electrical signals are signals having a frequency that is at least one of greater than 50Hz; greater than 75Hz; greater than 100Hz; and about 100Hz.
  • the electrical signals are frequency modulated.
  • the electrical signals are frequency modulated about a target frequency.
  • the electrical signals are modulated at least one of: by less than ⁇ 30% of the target frequency; by less than ⁇ 25% of the target frequency; by more than ⁇ 15% of the target frequency; by more than ⁇ 10% of the target frequency; by about ⁇ 20% of the target frequency; stochastically; and, in accordance with a distribution about the target frequency.
  • the electrical signals include: a first electrical signal having a first frequency; and, a second electrical signal having a second frequency different to the first frequency, and wherein the first and second signals are superposed to generate electrical signals having: an average frequency corresponding to a target frequency; and, a beat frequency.
  • the beat frequency is between 4Hz and 8Hz.
  • the target frequency is at least one of: greater than 50Hz; greater than 75Hz; greater than 100Hz; and, about 100Hz.
  • the electrical signals are signals having a duty cycle that is at least one of about 5%; about 10%; about 15%; about 20%; and about 50%.
  • the electrical signals are signals having a voltage that is at least one of less than 50V; less than 25V; less than 10V; less than 5 V; less than 2V; less than IV; greater than 0.1V; greater than 0.2V; greater than 0.5V; and greater than IV.
  • the electrical signals are signals having a current that is at least one of less than 50A; less than 25A; less than 10A; less than 5A; less than 2A; less than 1A; greater than 0.1 A; greater than 0.2A; greater than 0.5A; and greater than 1A.
  • the waveforms have a magnitude that is at least one of 10-60% of a paresthesia threshold; 40-80% of a paresthesia threshold; 60-99% of a paresthesia threshold; about 40% of a paresthesia threshold; about 60% of a paresthesia threshold; and about 80% of a paresthesia threshold.
  • the one or more electrodes includes at least a pair of first and second electrodes placed at least one of approximate a thoracic spine of the subject; across T8 and T9 of a thoracic spine of the subject; and across T9 and T10 of a thoracic spine of the subject.
  • the electrical signals include a sequence of first and second electrical signals that are applied to the first and second electrodes, respectively, wherein the first and second signals include a plurality of pulses and wherein pulses in the first signal have opposing polarities to pulses in the second signal.
  • the first electrical signal includes a cathodic signal and the second signal includes an anodic signal.
  • the system is configured to stimulate theta waves.
  • the method is configured to stimulate dendrites in the dorsal hom or dorsal column.
  • an aspect of the present invention seeks to provide a method for stimulating neurons, the system includes providing a lead including a lead body; at least one electrode carried by a distal portion of the lead body, the at least one electrode being configured to be provided proximate a dorsal hom in the spinal cord of a subject; and at least one pair of connections extending from the electrodes; and, using a signal generator electrically coupled to the at least one connection and configured to generate electrical signals that are applied to the at least one electrode, and wherein the electrical signals include waveforms to stimulate neurons within at least one of the spinal cord, dorsal column and dorsal hom.
  • the waveforms include at least one of square waveforms; non square waveforms; an exponentially waveform; a ramp waveform; a sine waveform and a triangular waveform.
  • the ramp waveform is defined by a gradient that is of a positive value or negative value.
  • the lead body includes at least two spaced apart electrodes carried by the distal portion of the lead body; and at least two connections.
  • the lead body includes at least two spaced apart double electrodes carried by the distal portion of the lead body; and a respective connection for each electrode.
  • the lead body includes at least two spaced apart outer electrodes carried by the distal portion of the lead body; at least two spaced apart inner electrodes carried by the distal portion of the lead body; and a respective connection for each electrode.
  • the lead body includes an electrode array including two spaced apart outer electrodes; and a plurality of spaced apart inner electrodes.
  • the at least one electrode has a length that is at least one of less than 8.5mm; less than 9mm; less than 9.5mm; less than 10mm; less than 10.5mm; less than 11mm; less than 11.5mm; less than 12mm; greaterthan 1mm; greaterthan 1.5mm; greater than 2mm; greater than 2.5mm; greater than 3mm; about 3-8mm; about 3mm; about 4mm; about 5mm; about 6mm; about 7mm; and about 8mm.
  • multiple electrodes are spaced by at least one of less than 12mm; less than 10mm; less than 8mm; less than 6mm; less than 4mm; greaterthan 1mm; greaterthan 1 5mm; greaterthan 2.0mm; greaterthan 2.5mm; about 3-4mm; about 3mm; about 4mm; about 3.3mm; about 3.4mm; and about 3.5mm.
  • the lead body includes a section between electrodes that is at least one of electrically non-conductive and flexible.
  • the pulse has a width of at least one of greater than SOOps: greater than 900ps; and about lOOOps.
  • the electrical signals are signals having a frequency that is at least one of greater than 50Hz; greater than 75Hz; greater than 100Hz; and about 100Hz.
  • the electrical signals are frequency modulated.
  • the electrical signals are frequency modulated about a target frequency.
  • the electrical signals are modulated at least one of: by less than ⁇ 30% of the target frequency; by less than ⁇ 25% of the target frequency; by more than ⁇ 15% of the target frequency; by more than ⁇ 10% of the target frequency; by about ⁇ 20% of the target frequency; stochastically; and, in accordance with a distribution about the target frequency.
  • the electrical signals include: a first electrical signal having a first frequency; and, a second electrical signal having a second frequency different to the first frequency, and wherein the first and second signals are superposed to generate electrical signals having: an average frequency corresponding to a target frequency; and, a beat frequency.
  • the beat frequency is between 4Hz and 8Hz.
  • the target frequency is at least one of: greater than 50Hz; greater than 75Hz; greater than 100Hz; and, about 100Hz.
  • the electrical signals are signals having a duty cycle that is at least one of about 5%; about 10%; about 15%; about 20%; and about 50%.
  • the electrical signals are signals having a voltage that is at least one of less than 50V; less than 25V; less than 10V; less than 5 V; less than 2V; less than IV; greater than 0.1V; greater than 0.2V; greater than 0.5V; and greater than IV.
  • the electrical signals are signals having a current that is at least one of less than 50A; less than 25A; less than 10A; less than 5A; less than 2A; less than 1A; greater than 0.1 A; greater than 0.2A; greater than 0.5A; and greater than 1A.
  • the waveforms have a magnitude that is at least one of 10-60% of a paresthesia threshold; 40-80% of a paresthesia threshold; 60-99% of a paresthesia threshold; about 40% of a paresthesia threshold; about 60% of a paresthesia threshold; and about 80% of a paresthesia threshold.
  • the one or more electrodes includes at least a pair of first and second electrodes placed at least one of approximate a thoracic spine of the subject; across T8 and T9 of a thoracic spine of the subject; and across T9 and T10 of a thoracic spine of the subject.
  • the electrical signals include a sequence of first and second electrical signals that are applied to the first and second electrodes, respectively, wherein the first and second signals include a plurality of pulses and wherein pulses in the first signal have opposing polarities to pulses in the second signal.
  • the first electrical signal includes a cathodic signal and the second signal includes an anodic signal.
  • the system is configured to stimulate neurons or dendrites in the dorsal hom or dorsal column.
  • the system is configured to stimulate theta waves.
  • Figure 1 is a schematic diagram of an example of a stimulation system for stimulating a dendrites in a spinal cord of a biological subject
  • Figure 2 is a schematic diagram of an example of use of the system of Figure 1 with a biological subject
  • Figure 3 is a schematic diagram of an example of a positioning of the lead of Figure 1 relative to a dorsal column in a biological subject;
  • Figures 4A and 4B are examples of non-square waveforms generated by a system for stimulating dendrites in a biological subject
  • Figure 5 is an example of a pair of electrical signals generated by a system for stimulating dendrites in a biological subject
  • Figure 6 is a schematic diagram of an example of an alternative lead electrode arrangement
  • Figure 7 is a schematic diagram of an example of a lead electrode dimensions
  • Figure 8 is a schematic diagram of an example of a lead internal structure
  • Figure 9 is a schematic diagram of an example of use of an alternative nerve stimulation system for stimulating a dorsal column in a biological subject
  • Figure 10 is a schematic diagram of an example of a controller for a nerve stimulation system
  • Figure 11 A is a graph illustrating results of a study showing VAS (visual analogue scale) pain levels for different types of treatment
  • Figure 1 IB is a graph illustrating results of a study showing VAS pain levels for different treatment programs
  • Figure 12A is a graph illustrating results of a study showing VAS pain levels for different treatment programs
  • Figure 12B is a graph illustrating results of a study showing BPI (brief pain inventory) severity for different treatment programs
  • Figure 12C is a graph illustrating results of a study showing mean BPI interference pain for different treatment programs
  • Figure 12D is a graph illustrating results of a study showing EQ-5D (EuroQol- 5 Dimension) measures for different treatment programs;
  • Figure 12E is a graph illustrating results of a study showing EQ-5D VAS for different treatment programs
  • Figure 13A is a graph illustrating results of a study showing clinician impression of change for different treatment programs
  • Figure 13B is a graph illustrating results of a study showing patient satisfaction for different treatment programs.
  • Figure 13C is a graph illustrating results of a study showing responder analysis for different treatment programs.
  • the system 100 includes a lead 110 including a lead body 111 having at least one pair electrodes 121, 122 carried by a distal portion 112 of the lead body 111. At least one pair of connections 123, 124 are provided extending from the pair of electrodes 121, 122.
  • a pair of electrodes are shown, including a first electrode 121 and a second electrode 122, with a respective connections 123, 124 being provided for each electrode, although as will become apparent from the remaining description, this is not essential and different configurations of one or more electrodes could be used.
  • the electrodes 121, 122 are configured to be provided proximate the dorsal hom of a subject 201. In one example, this is achieved by inserting the lead via a posterior of a torso of the subject 201, so that the lead can be provided proximate a dorsal column in a thoracic region 202 of the spine 203. In this example, the lead is provided in the epidural space of the dorsal column, and it will be understood from this that the term proximate the dorsal hom, encompasses within the dorsal column or dorsal hom. However, this is not essential and alternatively, the leads can be placed midline or either side of midline.
  • the electrodes 121, 122 may be placed approximate a cervical spine of the subject, across T8 and T9 or across T9 and T 10 of a thoracic spine of the subject for low back or leg pain.
  • the lead 111 can be positioned aligned with the spinal cord 304 so that electrodes 121, 122 are proximate (or within) dorsal column 308, allowing the dorsal column 308 to be modulated.
  • the two leads 111 are positioned proximate to respective dorsal horns 309, allowing neurons, such as dendrites, within the dorsal horns and/or dorsal column to be stimulated.
  • the lead and electrodes could be positioned proximate any part of the spinal cord, including midline, or adjacent to midline, depending on the preferred implementation.
  • the waveform can still be configured to ensure stimulation of neurons within or adjacent to the dorsal hom or dorsal column.
  • a signal generator 130 is electrically connected to the connections 123, 124 and is configured to generate electrical signals that are applied to the electrodes 121, 122.
  • the electrical signals include waveforms to stimulate dendrites in the dorsal hom.
  • the system provides an arrangement for stimulating neurons within or close to the dorsal hom and/or dorsal column in a biological subject, which effectively stimulates neurons such a dendrites by providing sufficient charge to perform the stimulation while minimising power required.
  • the electrical signals may be able to swing over to the lateral aspect of the dorsal hom, and penetrate beyond Lamina I to active Lamina II-IV, so that dendrites or other neurons are stimulated with limited nerve root stimulation and limited paresthesia being produced.
  • waveforms are generated to stimulate dendrites.
  • the waveforms may be square waveforms, non-square wave waveforms, and more typically may include alternating or pulsed signals, and can be generated with a variety of different waveforms, including, but not limited to sine waves, triangular waves, sawtooth waves, exponential waves, including waves with an exponential ramp-up and/or ramp-down, Gaussian waveforms, or the like. Examples of the waveforms are shown in Figures 4A and 4B.
  • the non-square waveforms include at least one of an exponential waveform WF1-WF4; a ramp waveform WF5, WF6; a sine waveform WF7 and a triangular waveform WFx.
  • the ramp waveforms WF5, WF 6 can be defined by a gradient.
  • the gradient of waveform WF5 is of a positive value, and the gradient of waveform WF 6 is of a negative value.
  • the waveforms may have an offset a from zero, as shown in Figure 4B.
  • the pulse may have a uniform width or variable widths, and the width may be of at least one of greater than 800ps, greater than 900ps, and about lOOOps. This allows the stimulation to spread current field out laterally (rib stimulation) and effectively stimulate dendrites. Dendrites are less responsive excitable to shorter pulses or less excitable for shorter pulses.
  • the electrical signals may have a frequency that is at least one of greater than 50Hz, greater than 75Hz, greater than 100Hz, and about 100Hz.
  • a target frequency of 100Hz is typically most effective at recruiting dendrites to relieve pain.
  • some benefits might be achieved by additionally recruiting additional neuronal population pools, for example by using stimulation signals having different frequencies.
  • the electrical signals are frequency modulated, so that the frequency of the applied signals varies, to thereby allow additional pain relieving effects to be induced.
  • the electrical signals are typically modulated about a target frequency, thereby maximising stimulation of dendrites, thereby ensuring maximum effectiveness of the therapy.
  • the electrical signals are modulated by less than ⁇ 30% of the target frequency, less than ⁇ 25% of the target frequency, by more than ⁇ 15% of the target frequency, by more than ⁇ 10% of the target frequency and more preferably by about ⁇ 20% of the target frequency.
  • the signals are typically modulated between 82 and 118 Hz.
  • the modulation is performed stochastically, as random variations can further enhance the effectiveness of the modulation, as described for example in "Frequency- difference -dependent stochastic resonance in neural systems" by Daqing Guo, Matjaz Perc, Yangsong Zhang, Peng Xu, and Dezhong Yao in PHYSICAL REVIEW E 96, 022415 (2017).
  • the signals are typically modulated in accordance with a distribution, such as a Gaussian distribution, aligned with the target frequency, so the majority of stimulation occurs at the target frequency, with less stimulation occurring further away from the target frequency. This maximises the effectiveness of dendrite stimulation, whilst also allowing benefits of stimulating other neuronal pools to be achieved.
  • the system can be configured to provide two different forms of complementary stimulation.
  • the electrical signals include a first electrical signal having a first frequency and a second electrical signal having a second frequency different to the first frequency.
  • the first and second signals have slightly different frequencies, so that when the first and second signals are superposed they result in signals having an average frequency corresponding to a target frequency and a beat frequency.
  • two signals at 97Hz and 103Hz, respectively can be applied simultaneously. The net effect is a signal with a mean frequency of 100Hz with an additional weak beat frequency generated by the neural structures of (103- 97Hz) 6Hz.
  • These signals conduct orthodromically and antidromically to the brain, and in particular to the thalamus, cortex and hippocampus, which are used by the brain in memory storage and retrieval and emotional processing.
  • the signals are selected so that the beat frequencies are of 10Hz or less, which corresponds to a "slow envelope modulation frequency", and which with moderate background noise in nerve firing (not too high or low) then stochastic resonance occurs, meaning the signals are transmitted strongly and are entrained by the system.
  • the beat frequency is between 4Hz and 8Hz, which corresponds to theta wave stimulation.
  • the hippocampus uses theta activity for long term plasticity to assist in storing new memories, such as memories of pain. Typically pain interferes with theta rhythms in the brain, and a 100Hz signal in the hippocampus can reinforce existing stored memory of pain. See for example, "Impaired Spatial Memory Performance in a Rat Model of Neuropathic Pain Is Associated with Reduced Hippocampus-Prefrontal Cortex Connectivity” by Helder Cardoso-Cruz, Deolinda Lima, and Vasco Galhardo, The Journal of Neuroscience, February 6, 2013 ⁇ 33(6):2465-2480 ⁇ 2465.
  • the frequencies can be varied by cycling between 98/102 Hz and 96/104 Hz, so that the beat frequency varies between 4Hz and 8Hz. In one example, this is performed stochastically, based on a distribution, such as a Gaussian distribution to produce theta band centred at a target beat frequency, such as 5.3Hz, depending on the subject response.
  • the electrical signals may further have a duty cycle that is at least one of about 5%, about 10%, about 15%, about 20% or about 50%. This allows dendrites to be stimulated to develop action potentials with efficient power consumption. In particular, by reducing the amount of stimulation performed, this reduces power consumption, so if the signals are only applied for 20% of the total therapy time, the battery life can be extended by up to five times.
  • An additional benefit of this approach is that over time the body can develop a tolerance to the applied signals, so reducing the duty cycle so that signals are only applied periodically, can prevent he build-up of tolerance and hence ensure the treatment remains effective.
  • the electrical signals are signals can have a voltage that is less than 50V, less than 25V, less than 10V, less than 5V, less than 2V, less than IV, greater than 0.1V, greater than 0.2V, greater than 0.5V, and greater than IV.
  • the electrical signals are signals can have a current that is less than 50A, less than 25A, less than 10A, less than 5A, less than 2A, less than 1A, greater than 0.1A, greater than 0.2A, greater than 0.5A, and greater than 1A.
  • the electrical signals may have a magnitude that is at least one of 10- 60% of a paresthesia threshold, 40-80% of a paresthesia threshold, 60-99% of a paresthesia threshold, about 40% of a paresthesia threshold, about 60% of a paresthesia threshold, and about 80% of a paresthesia threshold. This allows the stimulation to effectively penetrate beyond Lamina I to active Lamina II to IV with minimal nerve root stimulation which produce paresthesia.
  • the electrodes may further include a pair of first and second electrodes.
  • the first and second electrodes may be placed approximate a thoracic spine of the subject, across T8 and T9 of a thoracic spine of the subject, or across T9 and T10 of a thoracic spine of the subject.
  • the electrical signals include a sequence of first and second electrical signals that are applied to the first and second electrodes, respectively.
  • the first and second signals include a plurality of pulses and the pulses in the first signal have opposing polarities to pulses in the second signal.
  • the first electrical signal may be a cathodic signal and the second signal may be an anodic signal in the sequence.
  • the pair of electrodes with opposite polarities promotes effective stimulation of dendrites in the dorsal hom.
  • the one or more electrodes includes any suitable combination of anodes and cathodes, either contiguous or spaced on an electrode array.
  • the stimulation signals are cycled so that they are active for 34 seconds and inactive for 136 seconds (80/20 rule).
  • the signals are applied to the T9/10 bipole, at 80% of perception threshold, and use 1000 psec Pulse Width.
  • the signals can have a 100Hz frequency, or an average 100Hz target frequency, with stochastic variation of the frequency distributed about the target frequency.
  • the frequency used includes a series of 17 alternating pulses above/below 100Hz in 0.25Hz increments, 98/102 up to 96/104 Hz (generating 4-8Hz) with time spent proportional to a Gaussian distribution to produce a theta band centred at 5.3Hz.
  • Each set of frequencies is applied for lsec (random mix) then repeated once.
  • a therapy using this approach will scale over time using 80% of perception threshold for the 1 st month, 60% of perception threshold for the 2 nd month, then 40% of perception threshold for the 3 rd month, with the patient being monitored to assess efficacy.
  • a signal generator 130 is electrically connected to the connections 123, 124 and is configured to generate a sequence of first and second electrical signals that are applied to the first and second electrodes 121, 122, respectively.
  • a sequence Si of first and second electrical signals ESi, ES2 may be applied.
  • the first and second electrical signals ESi, ES2 include a plurality of pulses P1-P16, and the pulses Pi-Ps in the first signal ESi have opposing polarities to pulses P9-P16 in the second signal ES2.
  • the sequence Si of the first and second electrical signals ESi, ES2 has a period Ti.
  • the pulses have a frequency f, a pulse width W and a magnitude of M.
  • the first electrical signal ESi is a cathodic signal and the second signal ES2 is an anodic signal. It should be appreciated that the first electrical signal may be an anodic signal and the second electrical signal may be a cathodic signal in the sequence.
  • the sequence Si is configured to stimulate dendrites in the dorsal hom.
  • the magnitude M of the pulses P1-P16 is approximately 80% of paresthesia threshold. It should be appreciated that the magnitude of the pulses may vary in the sequence.
  • the frequency f is about 100 Hertz, and the pulse width W is about lOOOps.
  • the system provides an arrangement for stimulating the dorsal hom in a biological subject, which effectively stimulate dendrites by providing sufficient charges to stimulate dendrites while minimising power required.
  • the electrical signals may be able to swing over to the lateral aspect of the dorsal hom, and penetrate beyond Lamina I to active Lamina II-IV, so that dendrites are stimulated with limited nerve root stimulation and limited paresthesia being produced.
  • the lead body includes at least two spaced apart outer electrodes and at least two spaced apart inner electrodes, with a respective connection being provided for each electrode.
  • the lead body includes an electrode array having two spaced apart outer electrodes a plurality of spaced apart inner electrodes, and an example of this is shown in Figure 6, in which six electrodes are mounted on the lead body 611, with these including four inner electrodes 621 and two outer electrodes 622.
  • Other arrangements including greater numbers of electrodes could be used, for example, including eight, ten, twelve, fourteen or sixteen electrodes.
  • therapy electrodes could be used to apply therapy signals to the subject
  • shielding electrodes could be used to apply a shielding signal to shield surrounding tissue from the therapy signals.
  • the therapy and shielding signals typically have opposing polarities so that the shielding signals destructively interfere with the therapy signals, thereby reducing electric fields in tissue remote to the therapy electrodes.
  • individual or inner electrodes 621 are typically therapy electrodes
  • outer electrodes 622 are shielding electrodes, although this is not essential and other arrangements could be used.
  • the electrodes can have a variety of dimensions, and examples of this will now be described with reference to Figure 7.
  • the lead body and hence electrodes are generally cylindrical, with a diameter Di.
  • the electrode lengths Li, L2, L3, L4, are less than 8.5mm, less than 9mm, less than 9.5mm, less than 10mm, less than 10.5mm, less than 11mm, less than 11.5mm, less than 12mm, greater than 1mm, greater than 1.5mm, greater than 2mm, greater than 2.5mm, greater than 3mm, about 3 -8mm, about 3mm, about 4mm, about 5mm, about 6mm, about 7mm, about 8mm.
  • the lead body 811 includes an outer insulating layer 811.1, braided shield 811.2 inward of the outer insulating layer, an inner insulating layer 811.3 inside the braided shield 811.2 and one or more conducting fdars 811.4.
  • a lumen open at a proximal end may also be provided to allow for insertion of a stylet, as will be described in more detail below.
  • the conducting filars 811.4 provide the connections between the signal generator and the electrodes, whilst the inner and outer insulating layers 811.1, 811.3 provide electrical isolation from the subject, ensuring signals are transmitted to the electrodes.
  • the braided shield 811.2 can be used to reduce the magnitude of stray electrical fields in the body either through grounding or the use of an active shielding signal.
  • the conducting filars 811.4 can be braided with at least one standard wire made of titanium alloys, such as MP35N, whilst the braided shield can be made from tantalum, which assist with heat dissipation, whilst maintaining flexibility and strength.
  • the insulating layer(s) are typically made biomedical elastomers, thermoplastic polyether polyurethane, such as 55D polyurethane, or the like. These arrangements allow the lead body to be MRI compatible, which in turn allows MRI to be used to assist with lead positioning.
  • the lead body can also be configured with tines and/or wings to mitigate migration within the body, once the lead is positioned.
  • the therapy signals are configured to stimulate or inhibit activity of the dorsal column, and in one example are applied to a dorsal column proximate a T9/T10 spinal region, including but not limited to T9/T10 dorsal column, as shown in Figure 3.
  • the lead body is configured to be positioned in an anterolateral region of vertebrae, and may extend at least partially along or around vertebrae.
  • the lead body is configured to extend from the dorsal column of vertebrae to the signal generator.
  • the signal generator can be provided externally to the subject, but more typically is an implantable signal generator and an example of this is shown in Figure 9.
  • the signal generator 930 is implanted in a lower posterior of a torso of the subject 901, whilst the lead 910 extends to the dorsal column of vertebrae in the thoracic region 902 of the subject’s spine 903.
  • Power can be supplied to the signal generator via an internal power supply.
  • a separate power supply could be provided externally to the subject 901, and which is operatively coupled to the signal generator 930, via inductive coupling or similar.
  • the signal generator 1030 forms part of a controller 1036, which also includes an electronic processing device 1031 and a memory 1032, interconnected with the signal generator 1030 via a bus 1033, or other suitable arrangement.
  • An external interface 1035 is provided, which is typically a wireless interface, such as Wi-Fi, Bluetooth or another short range wireless communications interface, to allow an external device, such as a computer system, smart phone or table, to be used to control the controller 1036.
  • the electronic processing device 1031 executes instructions in the form of applications software stored in the memory 1032 to allow the required processes to be performed, and in particular to allow the signal generator to be controlled to thereby generate therapy and/or shielding signals, which are then applied to therapy and/or shielding electrodes 1021, 1022.
  • the applications software may include one or more software modules, and may be executed in a suitable execution environment, such as an operating system environment, or the like.
  • the electronic processing device could be a microprocessor, microchip processor, logic gate configuration, firmware optionally associated with implementing logic such as an FPGA (Field Programmable Gate Array), or any other electronic device, system or arrangement.
  • FPGA Field Programmable Gate Array
  • the controller 1036 includes an internal power supply, allowing the controller 1036 to be fully subcutaneously implemented.
  • the controller 1036 may include a receiving coil 1034 that is provided to allow power to be inductively received from a power supply 1040, for example, allowing this to be used to recharge the internal battery.
  • the power supply includes a processing device 1041, signal generator 1042, transmitting coil 1043 and battery 1044.
  • the electronic processing device could be a microprocessor, microchip processor, logic gate configuration, firmware optionally associated with implementing logic such as an FPGA (Field Programmable Gate Array), or any other electronic device, system or arrangement.
  • the processing device 1041 controls the signal generator 1042 to apply a signal to the transmitting coil, allowing power to be inductively coupled to the controller 1035. This avoids the need for the lead or other physical connections to pass through the skin of the subject, whilst still allowing the battery to be recharged as needed.
  • a further alternative is for the battery to be provided externally and used to drive an implanted controller via wired or wireless inductive connections.
  • the control system and/or power supply can be external, implanted or a combination of the two.
  • the power supply could include an input 1045, such as a touch screen or similar, which can be used to control operation of the system.
  • control inputs provided via the input 1045 could be detected by the processing device 1041 and used to modulate the inductive charging signal, which can in turn be detected by the processing device 1031, allowing this to be used to control operation of the signal generator.
  • this could be used to change the timing, magnitude, waveform, frequency, or other parameters of the generated therapy and/or shielding signals.
  • the above approach provides a form of spinal cord stimulation that provides paresthesia free treatment that is free of problems normally associated with Dorsal Column stimulation and which allows for an extremely low energy consumption of energy. This provides improved outcomes compared to existing best practice and can avoid accommodation/tolerance, allowing this to be used on a long term basis.
  • the word “comprise”, and variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or group of integers or steps but not the exclusion of any other integer or group of integers.
  • the term “approximately” means ⁇ 20%.

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  • Health & Medical Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Electrotherapy Devices (AREA)

Abstract

La présente invention concerne un système de stimulation de neurones, le système comprenant : un fil conducteur comprenant un corps de fil conducteur; au moins une électrode supportée par une portion distale du corps de fil conducteur, la au moins une électrode étant conçue pour être disposée près d'une corne dorsale dans la moelle épinière d'un sujet; et, au moins une paire de connexions s'étendant depuis les électrodes; un générateur de signal électriquement accouplé à la au moins une connexion et conçu pour générer des signaux électriques qui sont appliqués à la au moins une électrode, et les signaux électriques comprenant des formes d'onde pour stimuler les neurones à l'intérieur d'au moins l'une de la colonne dorsale et de la corne dorsale.
PCT/AU2021/050028 2020-01-16 2021-01-18 Système et procédé de stimulation de neurones WO2021142517A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2020900118A AU2020900118A0 (en) 2020-01-16 System and method for stimulating dendrites in a spinal cord
AU2020900118 2020-01-16

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10159837B2 (en) * 2012-09-19 2018-12-25 Boston Scientific Neuromodulation Corporation Preferential therapeutic modulation without patient-perceived paresthesia
US20190262616A1 (en) * 2015-08-06 2019-08-29 Meagan Medical, Inc. Spinal Cord Stimulation with Interferential Current
US20190269920A1 (en) * 2013-03-15 2019-09-05 Cirtec Medical Corp. Spinal cord stimulator system
US20200009386A1 (en) * 2017-03-03 2020-01-09 John Mansell Spinal cord stimulator
US20200276444A1 (en) * 2015-07-02 2020-09-03 Dirk De Ridder Methods of sensing cross-frequency coupling and neuromodulation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10159837B2 (en) * 2012-09-19 2018-12-25 Boston Scientific Neuromodulation Corporation Preferential therapeutic modulation without patient-perceived paresthesia
US20190269920A1 (en) * 2013-03-15 2019-09-05 Cirtec Medical Corp. Spinal cord stimulator system
US20200276444A1 (en) * 2015-07-02 2020-09-03 Dirk De Ridder Methods of sensing cross-frequency coupling and neuromodulation
US20190262616A1 (en) * 2015-08-06 2019-08-29 Meagan Medical, Inc. Spinal Cord Stimulation with Interferential Current
US20200009386A1 (en) * 2017-03-03 2020-01-09 John Mansell Spinal cord stimulator

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