Background of the Invention

[0001] The present invention relates to a nerve stimulation system and in one particular example, to a nerve stimulation system for stimulating the occipital and/or cervical nerves for use in treating pain, such as head and/or neck pains.

Description of the Prior Art

[0002] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that the prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

[0003] Millions of patients are affected by pain and have been prescribed systemic opioids (typically oral) as part of their treatment plan by healthcare providers. In the pain continuum, chronic pain can start with acute pain. Both pain types prompt an urgency of addressing patient’s needs, often with systemic opioids. This is despite the limited evidence on the benefits of long-term systemic opioid therapy and evidence that long-term systemic opioid therapy is associated with increased risk for opioid misuse, addiction, and death. The opioid epidemic cannot be solved, until we address the global pain crisis.

[0004] The COVID- 19 pandemic is further masking the current opioid epidemic, which has had a devastating impact across the world. For example, in 2018 opioids were involved in 46,802 overdose deaths and represented 69% of all fatal drug overdoses (67,367) in the US alone. The opioid epidemic is also highly prevalent in Australia, where more than 3 million people are getting at least one opioid prescription per year and the opioid death rate has more than doubled in the past decade.

[0005] Neurostimulation is a credible and well-respected alternative to opioid prescription, in the treatment of chronic pain. The occipital and cervical nerves are sensory nerves extending from the upper part of the neck to the back of the head, and along the spine, respectively. These nerves have a role in head and neck pain. For example, occipital neuralgia is a form of headache that causes pain, such as throbbing, aching, burning, or sharp, stabbing pain, along the upper neck and back of the head. It is known to employ nerve stimulation techniques in order to mitigate head and neck pain.

[0006] US-7,848,803 describes methods of facilitating stimulation of a stimulation site within a patient include implanting a distal portion of a first stimulating member such that the distal portion of the first stimulating member is in communication with a first stimulation site located within a patient, securing the distal portion of the first stimulating member at a first securing site with a first securing device positioned proximal to the first stimulation site, forming a first loop of at least 360 degrees with a portion of the first stimulating member proximal to the first securing device, securing the first loop with a second securing device at a second securing site having a position that is greater than or equal to substantially 180 degrees but less than or equal to substantially 315 degrees along the first loop from the first securing site, and positioning the second securing device and a stimulator to be coupled to a proximal end of the first stimulating member to maintain a curve in the first stimulating member of at least 45 degrees between the second securing device and the stimulator.

[0007] US-8,774,924 describes an apparatus for treating pain by electrical stimulation. A lead is placed subcutaneously in the region of pain. The subcutaneous tissue is electrically stimulated to cause paraesthesia. The method encompasses subcutaneous placement of an electrical lead near the region of pain and subsequent electrical stimulation of the tissue to cause paraesthesia. In particular, an apparatus for treating intractable occipital neuralgia using percutaneous electrostimulation techniques is disclosed.

[0008] However, these approaches are complex to implement from a surgical perspective and only target limited nerves, meaning some symptoms of head and neck pain remain unresolved.

[0009] US 2019/0091480 describes a method for subcutaneously treating pain in a patient includes first providing a neurostimulator with an IPG body and at least a primary, a secondary, and a tertiary integral lead with electrodes disposed thereon. A primary incision is opened to expose the subcutaneous region below the dermis in a selected portion of the body. A pocket is then opened for the IPG through the primary incision and the integral leads are inserted through the primary incision and routed subcutaneously to desired nerve regions along desired paths. The IPG is disposed in the pocket through the primary incision. The primary incision is then closed and the IPG and the electrodes activated to provide localized stimulation to the desired nerve regions and at least three of the nerves associated therewith to achieve a desired pain reduction response from the patient.

[0010] However, this approach only targets head pain, and in practice many individuals suffer from both head and neck pain. Additionally, this approach places the whole implant in the head in an attempt to mitigate lead migration issues, but this in turn results in a more complex surgical approach and is only effective where stimulation only targets nerve groups within the subcutaneous portion of the head.

[0011] US-7,613,519 describes a system and/or method for treating auditory dysfunction by somatosensory system stimulation. The system and/or method comprises a probe and a device to stimulate the probe. The probe has a stimulation portion implanted in communication with a predetermined peripheral nerve site. The stimulation portion of the probe may be implanted in contact with a peripheral nerve dorsal root ganglia, cranial nerve or dermatome area, for example C2 dermatome area or a trigeminal dermatome area. The stimulation portion may be a laminotomy, paddle, surgical, or multiple electrode lead. The device to stimulate the probe may be implanted subcutaneously or transcutaneously.

[0012] However, this approach does nothing to address head or neck pain.

[0013] US 2006/0293737 discusses, among other things, a lead assembly including a lead body, a first conductor extending through the lead body and coupled to a first electrode, a second conductor extending through the lead body and coupled to a second electrode, and a multi-filar coil extending through the lead body. The multi-filar coil includes electrically independent first and second filars respectively coupled to first and second sensing or pacing electrodes. In an example, the second filar of the multi-filar coil is substantially coaxial with the first filar. An example method includes extending first and second conductors and a multi- filar coil through lumens in a lead body and coupling electrodes to the conductors and coils.

[0014] However, again this approach does nothing to address head or neck pain. [0015] Mironer E 'Combined use of cervical spinal cord stimulator (SCS) and occipital nerve stimulator (ONS)' Pain Medicine. June 2000. Vol 1 No 2 pg 193 describes placing a cervical neurostimulation lead directly onto the spinal cord to treat neck pain. Additionally separate occipital nerve stimulation was attempted but this initially failed due to lead migration.

Summary of the Present Invention

[0016] In one broad form, an aspect of the present invention seeks to provide a nerve stimulation system for stimulating occipital and/or cervical nerves in a biological subject, the system including: a lead including: a lead body having: a first portion positioned proximate a distal end of the lead body; a second portion spaced from the first portion; and, a connecting portion interconnecting the first and second portions; at least one first electrode carried by the first portion, the at least one first electrode being configured to be provided proximate an occipital nerve; at least one second electrode carried by the second portion, the at least one second electrode being configured to be provided proximate a cervical nerve; at least one connection extending from the electrodes; a signal generator electrically connected to the at least one connection to generate electrical signals including: first signals that are applied to the at least one first electrode to thereby modulate the occipital nerve; and, second signals that are applied to the at least one second electrode to thereby modulate the cervical nerve.

[0017] In one embodiment the connecting portion is at least one of: electrically non- conductive; at least partially elastic; and, flexible.

[0018] In one embodiment the system includes at least one of: an anchoring arrangement; an anchor member configured to engage tissue in the subject and the lead to thereby at least partially anchor the lead body; at least one tine configured to at least partially anchor the lead body by at least one of: engaging the tissue in the subject; and, engaging an anchor member; and, at least one wing configured to at least partially anchor the lead body by at least one of: engaging the tissue in the subject; and, engaging an anchor member.

[0019] In one embodiment the lead body includes at least one of: at least one anchoring arrangement provided on the first portion; and, at least one anchoring arrangement proximate a proximal end of the first portion. [0020] In one embodiment the lead body includes at least one of: at least one anchoring arrangement provided on the second portion; and, at least one anchoring arrangement proximate a proximal end of the second portion.

[0021] In one embodiment the lead body includes at least one of: at least two spaced apart first electrodes carried by the first portion; four spaced apart first electrodes carried by the first portion; a first connection for all of the first electrodes; and, a respective first connection for each first electrode.

[0022] In one embodiment the lead body includes at least one of: at least two spaced apart second electrodes carried by the second portion; four spaced apart second electrodes carried by the second portion; eight spaced apart second electrodes carried by the second portion; more than four spaced apart second electrodes carried by the second portion; a second connection for all of the second electrodes; and, a second cervical connection for each second electrode.

[0023] In one embodiment first electrodes and second electrodes have at least one of: different lengths; different spacings; similar lengths; and, similar spacings.

[0024] In one embodiment the connecting portion has a length that is at least one of: greater than 1cm; greater than 2cm; less than 10cm; and, between 2cm and 6cm.

[0025] In one embodiment 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; 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.

[0026] In one embodiment electrodes are spaced by at least one of: less than 12mm; less than 10mm; less than 8mm; less than 6mm; less than 4mm; greater than 1mm; greater than 1.5mm; greater than 2.0mm; greater than 2.5mm; about 3-4mm; about 3mm; about 4mm; about 3.3mm; about 3.4mm; and, about 3.5mm.

[0027] In one embodiment a section between electrodes has a length of at least one of: less than 11mm; less than 12mm; less than 13mm; less than 14mm; less than 15mm; less than 16mm; less than 17mm; greater than 5mm; greater than 6mm; greater than 7mm; greater than 8mm; greater than 9mm; greater than 10mm; and, about 10.5mm.

[0028] In one embodiment therapy signals are signals having a frequency that is at least one of: less than 100kHz; less than 50kHz; less than 20kHz; less than 10kHz; less than 1kHz; less than 500Hz; less than 200Hz; less than 100Hz; less than 75Hz; less than 1Hz; an ultralow frequency; greater than 1Hz; greater than 2Hz; greater than 5Hz; greater than 10Hz; greater than 20Hz; about 50Hz.

[0029] In one embodiment therapy signals are signals having a pulse width of at least one of: less than 5,000ps; less than 2,500ps; less than l,000ps; less than 500ps; less than 200ps; less than lOOps; less than 75ps; greater than Ips; greater than 2ps; greater than 5ps; greater than lOps; greater than 20ps; and, about 50ps.

[0030] In one embodiment therapy signals are signals having a voltage that is at least one of: 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.

[0031] In one embodiment therapy 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.

[0032] In one embodiment the lead body includes at least one of: at least one conducting filar; at least one insulating layer; an inner insulating layer; a braided shield; and, an outer insulating layer.

[0033] In one embodiment each connection is defined by a respective conducting filar.

[0034] In one embodiment the conducting filars are braided with at least one standard wire.

[0035] In one embodiment the standard wire is made at least one of: titanium alloys; and, titanium alloy MP35N.

[0036] In one embodiment the braided shield is made from tantalum. [0037] In one embodiment an insulating layer is made from at least one of: biomedical elastomers; thermoplastic polyether polyurethane; and, 55D polyurethane.

[0038] In one embodiment the lead body is configured to be MRI compatible.

[0039] In one embodiment the signals are configured to at least one of: stimulate activity of at least one of the occipital and cervical nerves; and, inhibit activity of at least one of the occipital and cervical nerves.

[0040] In one embodiment the lead body is configured to extend to the signal generator.

[0041] In one embodiment the signal generator is an implantable signal generator.

[0042] In one embodiment the signal generator is implanted subcutaneously in an upper posterior of a torso of the subject.

[0043] In one embodiment the system includes a battery and wherein the battery is at least one of: provided externally to the subject; and, inductively coupled to the signal generator.

[0044] In one embodiment the signal generator is configured to apply a shielding signal to shielding electrodes, the shielding signal being configured to shield surrounding tissue or nerves from the therapy signal.

[0045] In one embodiment the therapy and shielding signals have opposing polarities.

[0046] In one embodiment the system includes a tunnelling tool including a straw configured to position the lead.

[0047] In one embodiment the first portion is configured to be positioned at least one of: with tines proximate to a midline inferior to inion and superior to a line extending between mastoid processes of the subject; with the first portion extending generally superiorly and laterally from proximate to a midline inferior to inion and superior to a line extending between mastoid processes of the subject; with the first portion extending generally horizontally; and, with the first portion positioned superficial to a skull, semispinalis muscle, and deep to skin of the subject, in an anatomical plane occupied by the occipital nerves at the level implanted. [0048] In one embodiment the first electrodes are configured to apply first signals to at least one of: one or more nerves in an occipital region; greater occipital nerves; lesser occipital nerves; and, a third occipital nerve.

[0049] In one embodiment the second portion is configured to be positioned at least one of: over deep paravertebral muscles of a neck of the subject; approximately 1.5cm to 3cm lateral to a midline of the subject; with the lead projecting over a lateral boarder of the lateral masses; with electrodes projecting over a C2/3 facet and extend inferiorly to C5/6; and, with the lead body extending inferiorly to approximately Tl/2.

[0050] In one embodiment the second electrodes are configured to apply second signals to at least one of: one or more nerves in a cervical region; and, branches of the dorsal rami of the cervical nerve roots.

[0051] In one embodiment the system is configured to treat at least one of: headache with associated neck pain; cervicogenic headache; migraine with cervicogenic trigger; tension type headache with neck pain; occipital neuralgia induced by tension in cervical paravertebral muscles; axial cervical pain with referred pain to occipital region; mechanical pain contributed to by structures innervated by the cervical medial branches and third occipital nerve; and, post- surgical neck pain.

[0052] In one embodiment the lead further includes: a third portion at a distal end of the lead body; and, at least one third electrode carried by the third portion, the at least one third electrode being configured to be provided proximate a frontal nerve, wherein the signal generator is configured to generate third signals that are applied to the at least one third electrode to thereby modulate the frontal nerve.

[0053] In one embodiment the lead body includes at least one of: at least two spaced apart third electrodes carried by the third portion; four spaced apart third electrodes carried by the third portion; a third connection for all of the third electrodes; and, a respective third connection for each third electrode.

[0054] In one embodiment the third portion is connected to the first portion via a second connecting portion. [0055] In one embodiment the second connecting portion has a length that is at least one of: greater than a length of the connecting portion; greater than 1cm; greater than 2cm; less than 15cm; and, between 4cm and 10cm.

[0056] In one embodiment the third electrodes are configured to apply first signals to at least one of: one or more nerves in a frontal region; one or more frontal nerves; one or more mandibular nerves; a supratrochlear nerve; a supraorbital nerve; and, an auriculotemporal nerve.

[0057] In one embodiment the system includes a controller configured to control the signal generator.

[0058] In one embodiment the controller is configured to control signal generator in accordance with at least one of: user input commands; biofeedback; and, signals from a sensor.

[0059] In one embodiment the system includes a sensor configured to sense electrical potentials via one or more of the electrodes, and wherein the controller is configured to control the signal generator in accordance with the sensed electrical signals.

[0060] In one broad form, an aspect of the present invention seeks to provide a method for stimulating occipital and/or cervical nerves in a biological subject, comprising: providing a lead in the subject, the lead including: a lead body having: an first portion positioned proximate a distal end of the lead body; a second portion spaced from the first portion; and, a connecting portion interconnecting the first and second portions; at least one first electrode carried by the first portion, the at least one first electrode being configured to be provided proximate an occipital nerve; at least one second electrode carried by the second portion, the at least one second electrode being configured to be provided proximate a cervical nerve; at least one connection extending from the electrodes; using a signal generator electrically connected to the at least one connection to generate electrical signals including: first signals that are applied to the at least one first electrode to thereby modulate the occipital nerve; and, second signals that are applied to the at least one second electrode to thereby modulate the cervical nerve. [0061] In one embodiment the signals are configured to at least one of: stimulate activity of at least one of the occipital and cervical nerves; and, inhibit activity of at least one of the occipital and cervical nerves.

[0062] In one embodiment the method includes: applying the first signals to at least one of: greater occipital nerves; lesser occipital nerves; and, a third occipital nerve; and, applying second signals to cervical medial branches.

[0063] In one embodiment the method includes positioning the first portion at least one of: with tines proximate to a midline inferior to inion and superior to a line extending between mastoid processes of the subject; with the first portion extending generally superiorly and laterally from proximate to a midline inferior to inion and superior to a line extending between mastoid processes of the subject; with the first portion extending generally horizontally; and, with the first portion positioned superficial to a skull, semispinalis muscle, and deep to skin of the subject, in an anatomical plane occupied by the occipital nerves at the level implanted.

[0064] In one embodiment the method includes positioning the second portion at least one of: over deep paravertebral muscles of a neck of the subject; approximately 2.5 to 3cm lateral to a midline of the subject; with the lead projecting over a lateral boarder of the lateral masses; with electrodes projecting over a C2/3 facet and extend inferiorly to C5/6; and, with the lead body extending inferiorly to T 1/2.

[0065] In one embodiment the method includes treating at least one of: headache with associated neck pain; cervicogenic headache; migraine with cervicogenic trigger; tension type headache with neck pain; occipital neuralgia induced by tension in cervical paravertebral muscles; axial cervical pain with referred pain to occipital region; mechanical pain contributed to by structures innervated by the cervical medial branches and third occipital nerve; and, post- surgical neck pain.

[0066] In one embodiment the method includes: creating a first incision in an occipital region; creating a second incision in a paravertebral thoracic region; inserting the lead so that: the second portion and at least part of the connection portion extend between the first and second incisions; and, the first portion extends substantially laterally from the first incision. [0067] In one embodiment the method includes: inserting the first portion of the lead; anchoring the first portion of the lead; and, once the first portion of the lead is anchored, inserting the second portion of the lead.

[0068] In one embodiment the method includes: using a tunnelling tool to tunnel between the first and second incisions; and, inserting the lead through the tunnel.

[0069] In one embodiment the tunnelling tool includes a straw, and wherein the method includes: removing the tunnelling tool from the straw; inserting the second portion of the lead through the straw; and, removing the straw through the second incision.

[0070] In one embodiment the method includes anchoring the lead at a proximal end of the second portion. It will be appreciated that the broad forms of the invention and their respective features can be used in conjunction and/or independently, and reference to separate broad forms is not intended to be limiting. Furthermore, it will be appreciated that features of the method can be performed using the system or apparatus and that features of the system or apparatus can be implemented using the method.

Brief Description of the Drawings

[0071] Various examples and embodiments of the present invention will now be described with reference to the accompanying drawings, in which: -

[0072] Figure 1A is a schematic diagram of an example of a nerve stimulation system for stimulating occipital and/or cervical nerves in a biological subject;

[0073] Figure IB is a schematic diagram of the nerve stimulation system of Figure 1A with a deformed connecting portion;

[0074] Figure 2A is a schematic rear view of a first example of the nerve stimulation system of Figure 1A in use;

[0075] Figure 2B is a schematic side view of the first example of the nerve stimulation system of Figure 1A in use; [0076] Figure 2C is a schematic rear view of a second example of the nerve stimulation system of Figure 1A in use;

[0077] Figure 3A is a schematic diagram of a further example of a nerve stimulation system lead for stimulating occipital and/or cervical nerves in a biological subject;

[0078] Figure 3B is a schematic diagram of a further example of a nerve stimulation system lead for stimulating occipital and/or cervical nerves in a biological subject;

[0079] Figure 3C is a schematic front view of an example of an anchor member;

[0080] Figure 3D is a schematic plan view of the anchor member of Figure 3C;

[0081] Figure 3E is a schematic plan view of the anchor member of Figure 3C anchoring two leads at the midline occiput between the occipital nerves at the top of the cervical mobile segment;

[0082] Figure 3F is a schematic perspective view of an example of an alternative anchor member;

[0083] Figure 3G is a schematic perspective view of an example of a further alternative anchor member;

[0084] Figure 4 is a schematic diagram of an example of an alternative lead electrode arrangement;

[0085] Figure 5 is a schematic diagram of an example of an alternative lead electrode arrangement;

[0086] Figure 6 is a schematic diagram of an example of an alternative lead electrode arrangement;

[0087] Figure 7 is a schematic diagram of an example of lead electrode dimensions;

[0088] Figure 8 is a schematic diagram of an example of a flexible lead;

[0089] Figure 9 is a schematic diagram of an example of a lead internal structure; [0090] Figure 10 is a schematic diagram of an example of a controller for a nerve stimulation system for stimulating occipital and/or cervical nerves in a biological subject;

[0091] Figure 11 is a schematic rear view of an example of incisions for placement of a lead of a nerve stimulation system for stimulating occipital and/or cervical nerves in a biological subject;

[0092] Figure 12 is a flow chart of an example of a process for implanting a lead for stimulating occipital and/or cervical nerves in a biological subject;

[0093] Figure 13 is a schematic diagram of an example of a nerve stimulation system lead for stimulating occipital, cervical and/or frontal nerves in a biological subject;

[0094] Figure 14 is a schematic side view of an example of the nerve stimulation system of Figure 13 in use;

[0095] Figure 15 is a schematic rear view of an example of incisions for placement of the lead of Figure 13; and,

[0096] Figures 16A and 16B are a flow chart of an example of a process for implanting the lead of Figure 13;

[0097] Figure 17 is a schematic diagram of an example of the concept of dual occipital and cervical nerve stimulation;

[0098] Figure 18 is a schematic diagram of an example of the concept of paravertebral PNfS dampening pain/neuroplasticity in the distribution of the dorsal posterior ramus;

[0099] Figure 19 is an illustration of an example of the ventral and dorsal nervous systems;

[0100] Figures 20A and 20B are schematic diagrams showing cervical regions in a subject;

[0101] Figures 21A and 2 IB are schematic anatomical diagrams showing surgical incisions and tunnelling within the subject; [0102] Figures 22A to 22D are images of needle placements used in demonstrating proof of concept;

[0103] Figures 23A to 23D are pictures illustrating cervico-thoracic angles, three incision points, and the final x-ray appearance; and,

[0104] Figures 24A and 24B are images of caudal/lateral cervical paravertebral lead migration.

Detailed Description of the Preferred Embodiments

[0105] An example of a nerve stimulation system will now be described in more detail with reference to Figures 1 and 2.

[0106] In this example, the system 100 includes a lead 110 including a lead body 110.1 having a first portion 111 positioned proximate a distal end of the lead body 110, a second portion 113 spaced from the first portion and a connecting portion 112 interconnecting the first and second portions 111, 113.

[0107] At least one first electrode 121 is carried by the first portion 111, while at least one second electrode 123 is carried by the second portion 113. In this example, four first and four second electrodes 121, 123 are shown, although as will become apparent from the remaining description, this is not essential and different configurations of one or more electrodes could be used. For example, in the arrangement described below with respect to Figures 13 and 14, eight second electrodes are provided.

[0108] At least one connection 124 is provided extending from the electrodes 121, 123. A signal generator 130 is electrically connected to the connection(s) 124 and is configured to generate electrical signals that are applied to the electrode(s) 121, 123. Whilst a single connection could be used, more typically a respective connection 124 is provided for each electrode 121, 123, allowing different electrical signals to be applied to each electrode 121, 123.

[0109] In use, the lead 110 is implanted within the neck and head of a subject, as shown in Figures 2A and 2B. [0110] Specifically, Figures 2A and 2B show a head 201, including a skull 202, having an inion 204 and mastoid processes 205, and connected to cervical vertebrae 203. Nerves are shown in dotted lines, including greater and lesser occipital nerves (and pre auricular nerves) 206, 207 originating near the second and third cervical vertebrae 203 and extending superiorly and laterally over a rear of the skull 202, with cervical nerves 208 and in particular including some or all of the branches of the dorsal rami of C3 to C7, for example the medial branches innervating the articular surfaces of the facet joints. In this regard, the cervical nerves are best thought of as a group of individual nerves arising from each level rather than a single descending nerve parallel to the vertebral body as shown by the dotted line in Figure 2A, which is provided for indicative purposes only. The cervical nerves extend inferiorly laterally offset from a midline on either side of the cervical vertebrae 203. It will be appreciated that the Figures are intended to be illustrative only and are not intended to reflect correct anatomical positioning of the nerves. Furthermore, for the purpose of ease of description the term cervical nerves will generally be understood to include some or all of the branches of the dorsal rami of C3 to C7, for example the medial branches innervating the articular surfaces of the facet joints.

[oni] In use, the lead 110 is implanted so that the first portion 111 is provided proximate the occipital nerves 206, 207, whilst the second portion 113 is proximate cervical nerves 208, and in particular the branches of the posterior rami of the cervical nerves. In the example, of Figure 2A, the first portion 111 extends substantially horizontally laterally from a point offset from midline at a level between the inion 204 and the mastoid processes 205, so that the first portion 111 passes over and across the occipital nerves, whist the second portion 113 extends substantially vertically offset from the midline, approximately over the lateral aspect of the lateral masses 208. As shown in Figure 2C, the first portion 111 can be angled upwards (or downwards) as long as it passes over the occipital nerves.

[0112] The signal generator 130 can be implanted within the subject, or provided external to the subject, as will be described in more detail below. Typically a respective lead will be provided on either side of the subject, although depending on the circumstances, only a single lead may be required. [0113] With these configurations, the first electrode(s) are provided proximate the occipital nerves 206, 207, while the second electrode(s) are provided proximate the cervical nerves 208. This allows the signal generator 130 to be used to apply therapy signals to the nerves, including first signals that can be applied to the first electrode(s) to thereby modulate the occipital nerve, such as the greater, lesser, third occipital nerve, or greater auricular nerve, whilst second signals can be applied to the second electrode(s) to thereby modulate the cervical nerve, such as the cervical medial branches.

[0114] In this regard, it will be appreciated that the first portion of the lead, and hence the first electrodes, are provided proximate and hence modulate occipital nerves. In this regard, the term occipital nerve will be understood to include nerves in an occipital region of the subject, and could include, but is not limited to a greater occipital nerve, a lesser occipital nerve, a third occipital nerve, a pre-auricular nerve, or other surrounding nerves or nerve branches. Similarly the second portion of the lead, and hence the second electrodes, are provided proximate and hence modulate cervical nerves. In this regard, the term cervical nerve will be understood to include nerves in a cervical region of the subject, and could include, but is not limited to branches of dorsal rami in the C3-C7 region, and other surrounding nerves.

[0115] Accordingly, the above described arrangement is capable of modulating, and in particular stimulating or inhibiting the occipital and/or cervical nerves, which in turn can be used to effectively treat a wide range of different indications, including, but not limited to any one or more of headache with associated neck pain, cervicogenic headache, migraine with cervicogenic trigger, tension type headache with neck pain, occipital neuralgia induced by tension in cervical paravertebral muscles, axial cervical pain with referred pain to occipital region, mechanical pain contributed to by structures innervated by the cervical medial branches and third occipital nerve, post-surgical neck pain, or the like.

[0116] The first and second signals can be the same, or can be different, allowing the occipital and/or cervical nerves 206, 207, 208 to be modulated collectively and/or independently, depending on the nature of the indication and the preferred intervention protocol. In this regard, stimulation can be performed concurrently, or could be performed sequentially in order to minimise interference between the stimulation signals. Similarly, crosstalk between first and second electrodes 121, 123 could be mitigated through the use of passive and/or active shielding, or could be accommodated through suitable configuration of the first or second electrodes.

[0117] Despite being capable of independently modulating the occipital and/or cervical nerves, the respective electrodes 121, 123 are presented on a common lead 110, allowing these to be implanted in a single surgical procedure, as will be described in more detail below.

[0118] Furthermore, appropriate configuration of the lead can assist in accommodating movement of the subject, particularly in regard to head, shoulder and/or neck movement, ensuring the lead and hence electrodes remain in position and do not move within the subject. For example, as shown in Figure IB, the connecting portion 112 can be designed to deform or flex, allowing the configuration of the connecting portion to alter to accommodate movement of the subject. In one particular example, a surface of the connecting portion is electrically non-conductive and at least partially elastic and/or flexible, thereby allowing the shape and/or length of the connecting portion to alter, so that the first and second portions 111, 113 remain static within the body whilst the subject’s head, shoulders and neck move. This ensures the first and second electrode(s) remain aligned with the occipital and cervical nerves 206, 207, 208, which in turn helps maintain the effectiveness of the neuro modulation. It will be appreciated that in practice electrical connections will need to extend through the connecting portion 112, to allow signals to be applied to the first electrodes.

[0119] Retaining a position of the lead within the subject can be further assisted by anchoring the lead using an anchoring arrangement, such as tines or wings attached to the lead body 110.1. Thus, for example, the lead body can include at least one tine or wing configured to engage tissue in the subject to thereby at least partially anchor the lead body within the subject. The use of an anchoring arrangement of this form can help prevent lead migration within the subject. This is particularly important as the lead spans a motion segment within the subject, which can in turn result in lead migration as the subject moves their head and/or neck. In one particular example, the lead is anchored in the occipital region and the cervico-thoracic junction, so that this precludes lead migration in the cervical portion of the system. In contrast to this, prior art configurations utilise different approaches, such as having the whole implant in the head and only targeting nerve groups within the subcutaneous portion of the head, as is the case of US 2019/0091480, or through the use of separate leads, as in Mironer E 'Combined use of cervical spinal cord stimulator (SCS) and occipital nerve stimulator (ONS)' Pain Medicine. June 2000. Vol 1 No 2 pg 193.

[0120] An example of this will now be described in more detail with reference to Figure 3A.

[0121] In this example, the lead includes at least one tine, and more typically a pair of tines 331, provided on the first portion 111 and more particularly proximate a proximal end of the first portion. This arrangement prevents the first portion undergoing movement in the event that a force is applied via the connection portion 112, for example during movement of the subject. In this example, the tines are shown orientated to prevent movement of the first portion towards the proximal end of the lead. However, it will also be appreciated that the tines could be orientated in an opposing direction, and that multiple tines could be used orientated in different directions to help further secure the first portion. Similarly, in this example, the lead includes at least one tine, and more typically a pair of tines 333, provided on the second portion 113, and more particularly on a proximal end of the second portion. This helps prevent movement of the second portion 113, for example as a result of tugging on the lead between the second portion 113 and the signal generator 130. However, it will also be appreciated that tines may not be required on the second portion, as the surgeon may be able to make a slightly larger incision to manually apply an anchor. Additionally, tines may also make the procedure more complicated, and hence may not be required in some instances.

[0122] An example of a particular tine configuration is shown in Figure 3B, with four tines 331 being provided on either side of a proximal end of the first portion 311 in this example.

[0123] However, it will also be appreciated that additional or alternative tines could be provided, for example, on a distal end of the first or second portion 111, 113, on the connecting portion 112, or elsewhere, depending on the requirements of the particular situation. Accordingly, it will be appreciated that the lead could include any number of forward and/or reverse facing tines, and that tines could be positioned anywhere along the lead, including one any one of the first, second or connecting portions, including between first or between second electrodes, and that the arrangement shown in Figures 3A and 3B are not intended to be limiting.

[0124] A further example anchoring arrangement will now be described with reference to Figures 3C to 3E.

[0125] In this example, an anchor member 332 is provided, which engages tissue in the subject and the lead body, to thereby anchor one or more leads within the subject. In this example, the anchor 332 includes a body 332. 1, having two lead openings 332.3, which are shaped to receive respective leads, with a narrow waist positioned between the two lead openings.

[0126] In use, the anchor member 332 can be used to secure two leads to the subject. In this regard, the anchor member 332 can be positioned in the subject at an upper incision site, with the leads being threaded through the lead openings 332.3, so that the tines 331 engage the body 332.1 and thereby secure the leads relative to the body 332.1. The anchor member can simply be positioned in the subject, so that the shape of the body 332.1 secures the anchor in position. Alternatively sutures can be attached to the anchor 332, around the narrow waist so that the suture is secured to the anchor member, to thereby further secure the anchor 332 in position.

[0127] It will be appreciated that in this example, two lead openings 332.3 are provided in the body 332.1 allowing two leads to be anchored within the subject. However, this is not essential and alternatively a single lead opening might be provided to anchor a single lead. In this example, this could be achieved using an opening extending laterally through the anchor body, although alternatively a longitudinally extending opening could be used and an example will now be described with reference to Figure 3F.

[0128] In this example, an anchor member 333 is provided, which engages tissue in the subject and the lead body, to thereby anchor a lead within the subject. In this example, the anchor 333 includes a body 333.1, having two laterally extending wings 333.2. A single lead opening 333.3 extends longitudinally through the body 332.1, with a suture opening 332.4 also being provided in each wing 332.2. It will be appreciated that this allows a lead to be secured within the anchor, with the wings extending laterally from the lead. In one example, an anchor of this form could be placed at lower T1-T2 incisions, although this is not essential and the arrangement could be used at the upper incision.

[0129] In the above examples, tines on the lead engage the anchor members 332, 333 to secure the lead in place. However, this is not essential and alternatively and/or additionally, a fastening arrangement could be used, an example of this will now be described with reference to Figure 3G.

[0130] In this example, an anchor member 334 is provided, which engages tissue in the subject and the lead body, to thereby anchor a lead within the subject. In this example, the anchor member 334 includes a body 334. 1, having two laterally extending wings 334.2. A single lead opening 334.3 extends longitudinally through the body 334. 1, with a suture opening 334.4 also being provided in each wing 334.2. In this example the wings 334.2 are offset along the length of the body 334.1, which can facilitate access for suturing. Additionally, in this example, a fastener, such as a blunt screw or similar, can be provided in the body 334. 1, so that tightening of the screw using a tool 334.8 results in the fastener 334.5 engaging the lead body and securing the lead in position. It will appreciated that this allows a lead to be secured within the anchor and that a similar arrangement could be used with dual lead anchor of Figure 3C.

[0131] As previously mentioned, a range of different electrode arrangements can be used, and examples of these are shown in Figures 4 to 6.

[0132] For example, as shown in Figure 4, the first portion 411 of a lead body could include a single first electrode 421, whilst Figure 5 shows an alternative configuration in which the first portion 511 of the lead body includes two spaced apart first electrodes 521. Typically corresponding connections would be provided for each electrode allowing different therapy signals to be applied to each of the electrodes.

[0133] It will be appreciated that greater numbers of electrodes could also be used. For example, in one example, the first portion could include at least two spaced apart outer electrodes and at least two spaced apart inner electrodes, with a respective connection being provided for each electrode. In another example, the first portion could include 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 first portion 611 of the lead body, with these including four inner electrodes 621. 1 and two outer electrodes 621.2. Other arrangements including greater numbers of electrodes could be used, for example, including eight, ten, twelve, fourteen or sixteen electrodes.

[0134] In one example, where multiple electrodes are provided, these could have different functions. For example, inner therapy electrodes 621. 1 could be used to apply therapy signals to the subject, whilst outer shielding electrodes 621.2, could be used to apply a shielding signal to shield surrounding tissue from the therapy signals, and/or to reduce cross talk between the first and second electrodes. In this regard, 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. In one example, individual or inner electrodes 621.1 are typically therapy electrodes, whilst outer electrodes 621.2 are shielding electrodes, although this is not essential and other arrangements could be used.

[0135] Accordingly, the lead body could include at least two spaced apart first electrodes carried by the first portion, or four or more spaced apart first electrodes carried by the first portion. Similarly, the lead body could include a first connection for all of the first electrodes or more typically a respective first connection for each first electrode.

[0136] Whilst the above variations have been described with respect to the first portion, it will be appreciated that similar variations could be used for the second electrodes. Thus, the lead body could include one or spaced apart second electrodes carried by the second portion, or could include three, four or more spaced apart second electrodes carried by the second portion. Again, a single second connection could be provided for all of the second electrodes, although more typically a respective second connection can be provided for each second electrode, allowing for independent operation.

[0137] Additionally, in the current examples, the electrodes are shown as cylindrical electrodes extending circumferentially around the lead body. However, this is not essential and other arrangements could be used. For example, the electrodes could be configured to extend only part way around the lead body. In this example, by aligning electrodes on one side of the lead, this allows signals to be applied via that side of the lead only, such that the electrodes act as a directional array, which can in turn be used to allow more effective targeting of stimulation to selected nerves.

[0138] The first and/or second therapy signals applied to the first or second electrodes can be alternating or pulsed signals, and can be generated with a variety of different waveforms, including, but not limited to sine waves, square waves, triangular waves, sawtooth waves, or the like.

[0139] The therapy signals can have a frequency that is less than 100kHz, less than 50kHz, less than 20kHz, less than 10kHz, less than 1kHz, less than 500Hz, less than 200Hz, less than 100Hz, less than 75Hz, less than 1Hz; an ultralow frequency; greater than 1Hz, greater than 2Hz, greater than 5Hz, greater than 10Hz, greater than 20Hz, and more typically about 50Hz. The therapy signals typically have a pulse width of less than 5,000ps, less than 2,500ps, less than l,000ps, less than 500ps, less than 200ps, less than lOOps, less than 75 ps, greater than Ips, greater than 2ps, greater than 5ps, greater than lOps, greater than 20ps more typically about 50ps. The therapy signals can have a voltage that is 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 or greater than IV, and 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 or greater than 1A. For example, ultralow frequency neuromodulation is described in “Neuromodulation using ultra low frequency current waveform reversibly blocks axonal conduction and chronic pain” by Martyn G. Jones, Evan R. Rogers, James P. Harris, Andrew Sullivand, Michael Ackermann, Marc Russo, Scott F. Lempka And Stephen B. Mcmahon, Science Translational Medicine Vol. 13, No. 608.

[0140] The electrodes can have a variety of dimensions, and examples of this will now be described with reference to Figure 7.

[0141] In this example, four electrodes are shown, having respective lengths Li, L2, L3, L4, and separated by respective spacings Si, S2, S3. In this example, the lead body and hence electrodes are generally cylindrical, with a diameter Dy. [0142] In one example, 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. Inner and outer electrodes might have different lengths, so that Li = L4 > L2 = L3, or Li = L4< L2 = L3.

[0143] The electrode spacings Si, S2, S3 are typically less than 12mm, less than 10mm, less than 8mm, less than 6mm, less than 4mm, greater than 1mm, greater than 1 ,5mm, greater than 2.0mm, greater than 2.5mm, about 3-4mm, about 3mm, about 4mm, about 3.3mm, about 3.4mm, and, about 3.5mm. Spacings may differ, so that the spacing between inner and outer electrodes differs to that between inner electrodes, such that Si = S3 > S2 or Si = S3 < S2.

[0144] It will also be appreciated that the first and second electrodes could have different lengths and/or spacings and/or could have similar lengths and/or spacings, and that these will typically be selected in order to optimise delivery of signals to the occipital and/or cervical nerves respectively.

[0145] In one example, a spacing S2 between electrodes is electrically non-conductive and or flexible, to allow the lead to bend between electrodes, as shown for example in Figure 8. In this example, the lead 810, includes an first portion 811, including two inner and two outer electrodes 821.1, 821.2, with an increased spacing between the inner electrodes 821.1, to allow for increased lead curvature, which can allow the first portion to undergo significant bending, which can in turn be used to facilitate positioning of the electrodes relative to the occipital nerves.

[0146] As previously mentioned, the connecting portion is also typically flexible, but more preferably is also elasticated, allowing a length of the connecting portion to vary, thereby accommodating changes in the relative position of the first and second portion of the lead as the subject moves. For example when the subject tilts and/or rotates their head, moves their arms and shoulders, or the like, this can stretch and/or compress the lead, and so making the connecting portion elasticated allows these movements to be accommodated by the connecting portion, without adversely affecting the electrode positioning. Typically the connecting portion has a length that is greater than 1cm, greater than 2cm, less than 10cm and between 2 and 6cm, although this will depend on the anatomy of the subject and the particular scenario.

[0147] An example of an internal structure of the lead is shown in Figure 9.

[0148] In this example, the lead body 911, includes an outer insulating layer 911.1, braided shield 911.2 inward of the outer insulating layer, an inner insulating layer 911.3 inside the braided shield 911.2 and one or more conducting fdars 911.4. A lumen open at a proximal end (not shown) may also be provided to allow for insertion of a stylet or guidewire, as will be described in more detail below.

[0149] In use, the conducting filars 911.4 provide the connections between the signal generator and the electrodes, whilst the inner and outer insulating layers 911.1, 911.3 provide electrical isolation from the subject, ensuring signals are transmitted to the electrodes. The braided shield 911.2 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.

[0150] The conducting filars 911.4 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 allow the patient to undergo MRI for diagnostic imaging purposes subsequent to implantation with the leads.

[0151] Once in position, the lead body is configured to extend to the signal generator. In this regard the signal generator can be provided externally to the subject, but more typically is an at least partially implantable signal generator. For example, the signal generator could be implanted in an upper torso, proximate the clavicle, or any other suitable location. Alternatively, the signal generator could be external to the subject, with the lead passing through the skin and connecting to the signal generator. Power can be supplied to the signal generator via an internal power supply. However, alternatively a separate power supply could be provided externally to the subject, and which is operatively coupled to an implanted signal generator, via inductive coupling or similar. Thus, it will be appreciated that the system could use an implantable IPG, an externalised trial or transcutaneously coupled generation of electrical signals

[0152] An example signal generator arrangement is shown in more detail in Figure 10.

[0153] In this example, 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 or long range wireless communications interface, to allow an external device, such as a computer system, smart phone or tablet, to be used to control the controller 1036.

[0154] In use, 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.

[0155] 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.

[0156] In one example, the controller 1036 includes an internal power supply, allowing the controller 1036 to be fully subcutaneously implemented. In one example, 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. In this regard, 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.

[0157] 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 subj ect, whilst still allowing the battery to be recharged as needed. It will also be appreciated that other approaches could be used, such as the use of mid-long range external power sources, depending on the application.

[0158] A further alternative is for the battery to be provided externally and used to drive an implanted controller via wired or wireless inductive connections. Thus, it will be appreciated that the control system and/or power supply can be external, implanted or a combination of the two.

[0159] In another example 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. In this regard, 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. For example, this could be used to change the timing, magnitude, waveform, frequency, or other parameters of the generated therapy and/or shielding signals.

[0160] In one example, the controller, and in particular the electronic processing device 1041, is configured to control the signal generator in accordance with one or more of user input commands, biofeedback or signals from a sensor. Thus, the therapy signals and in particular the first and second signals (and optionally third signals) can be controlled based on user inputs. For example, the user could select a particular operating mode or signal form, which is then used to control the signals that are generated. Additionally and/or alternatively this could be based on feedback, such as the efficacy of the applied signals. Thus, for example, a sensor could be used to monitor a biological effect of the stimulation, allowing the signals to be adjusted to ensure a successful outcome. [0161] In one particular example, the sensor is configured to sense electrical potentials via one or more of the electrodes. For example, the controller could incorporate a voltage sensor, which is electrically connected to one or more of the electrodes, allowing action potentials in the nerves to be sensed. Feedback regarding the action potentials can then be used to control the signals, for example adjusting the signals depending on whether action potentials are sensed or not, thereby creating the possibility of a closed loop lead system. It will also be appreciated that feedback could be obtained from other forms of sensor, such as heart rate sensors, EEG, ECG, or the like.

[0162] Additionally, the system can be configured to record the sensed action potentials, allowing operation of the system to be monitored. For example, this can be used in order to monitor effectiveness of applied therapy, in turn allowing improved therapy signals to be derived.

[0163] The lead is typically implanted into the subj ect so that the first portion I l l is configured to be positioned with tines 331 proximate to a midline inferior to inion 204 and superior to a line extending between mastoid processes 205 of the subject. The first portion 111 typically extends generally superiorly and laterally from proximate to a midline inferior to inion 204 and superior to a line extending between mastoid processes 205 of the subject, and may extend generally horizontally, although as previously described, this is not essential. In general, the first portion 111 is positioned superficially to the skull 202, and superficial to, deep to or through the semispinalis muscle (not shown), and deep to skin of the subject, in an anatomical plane occupied by the occipital nerves at the level implanted.

[0164] Similarly, the second portion 113 is configured to be implanted over deep paravertebral muscles of a neck of the subject, approximately 2.5 to 3cm lateral to a midline. The lead would typically project over a lateral boarder of the lateral masses, with electrodes projecting over a C2/3 facet and extend inferiorly to C5/6. In one example, the lead body extends inferiorly to at least Tl/2, for connection to the signal generator 130, which could be subcutaneously implanted. [0165] In general, the process of implanting the lead will involve tunnelling into the subject and inserting the lead into the tunnel. In one example, this process is performed by creating first and second incisions in the subject, as shown in Figure 11.

[0166] In this example, the first incision 1151 is created in an occipital region, at a medial aspect of occipital lead portion position, for example in a region between midline and 3cm lateral to midline and between the inion 204 and a line extending between mastoid processes 205, whilst the second incision 1152 is created in a paravertebral thoracic region, at a caudal aspect of where the cervical lead portion is intended to lay, for example offset from the midline by 2-5cm and in the T1/T2 thoracic region. Once the incisions are created, the lead can then be inserted inferiorly or superiorly depending on the preferred approach.

[0167] For example, the first portion of the lead could be inserted laterally from the first incision, and then anchored into position, before the second portion of the lead is inserted. In one example, this process is facilitated using a tunnelling tool to tunnel between the first and second incisions, with the second portion of the lead being inserted through the tunnel. In such cases, the tunnelling tool typically includes a straw that can remain in situ whilst the second portion is inserted.

[0168] A specific example, surgical procedure will now be described with reference to Figure 12.

[0169] In this example, at step 1200, the first and second incisions can be created, with a tunnelling tool being used to create a tunnel extending from the first to the second incision at step 1210. This step typically involves inserting the tunnelling tool and surrounding straw through the first incision to create the tunnel, before the tool is removed at step 1220, leaving the straw in position.

[0170] At step 1230, the first portion 111 is inserted laterally from the first incision, for example using a needle type introducer, before being anchored into position by deploying the an anchor or the wings 331.

[0171] The lead is then inserted through the straw at step 1240, before the straw is removed at step 1250 through the second incision thereby deploying the second electrodes. An inferior / caudal portion of the second portion is anchored into position and connected to the signal generator at step 1260, before the incisions are closed.

[0172] It will be appreciated however that other surgical approaches could be used, and the above described approach is for the purpose of illustration only.

[0173] A further example of a nerve stimulation system will now be described with reference to Figure 13. In this example, the nerve stimulation system of Figures 1A and IB is further modified to allow for stimulation of frontal nerves.

[0174] Specifically, in this example, the lead 110 further includes a third portion 115 provided at a distal end of the lead body. At least one third electrode 125 is carried by the third portion 115, with four third electrodes being shown in this example for the purpose of illustration.

[0175] In use the third electrode(s) are configured to be provided proximate a frontal nerve, so that the signal generator can be used to generate third signals that are applied to the third electrode(s) to thereby modulate the frontal nerve.

[0176] In this regard, it will be appreciated that the third portion of the lead, and hence the third electrodes, are provided proximate and hence modulate frontal nerves. In this regard, the term frontal nerve will be understood to include nerves in a frontal region of the subject, and could include, but are not limited to one or more frontal nerves, one or more mandibular nerves, a supratrochlear nerve, a supraorbital nerve or an auriculotemporal nerve.

[0177] A range of different third electrode arrangements could be used, and in one example, the lead body includes at least two spaced apart third electrodes or four spaced apart third electrodes. Alternatively however, the third portion could include other numbers of electrodes, such as eight spaced apart third electrodes.

[0178] The third electrodes can be electrically connected to the signal generator using a third connection for all of the third electrodes, or using a respective third connection for each third electrode, allowing different modulation signals to be applied to different frontal nerves. [0179] To allow the third portion of the lead to be correctly position, the lead typically includes a second connecting portion, which is used to connect the third portion to the first portion, and an example of this is shown in Figure 14.

[0180] In this example, the lead is shown positioned with the second connecting portion 114 extending from the first portion 111, so that the third portion 115 is positioned towards a front of the users head.

[0181] Again the second connecting potion can be designed to deform or flex, allowing the configuration of the connecting portion to alter to accommodate movement of the subject, whilst allowing the first, second and third portions 111, 113, 115 to remain static within the subject whilst the subject’s head, shoulders and neck move. This ensures the electrode(s) remain aligned with the occipital, cervical and frontal nerves 206, 207, 208, which in turn helps maintain the effectiveness of the neuro modulation. It will be appreciated that in practice electrical connections will need to extend through the connecting portions 112, 114, to allow signals to be applied to the electrodes

[0182] In one example, the second connecting portion has a length that is greater than a length of the connecting portion, and which is typically greater than 1cm, greater than 2cm, less than 15cm and between 4cm and 10cm.

[0183] It will be appreciated that third electrodes could have similar sizes and spacings to those outlined above with respect to the first and second electrodes, and that the therapy signals applied to the third electrodes could also be of a similar form to the therapy signals applied via the first and second electrodes.

[0184] The third portion could also include anchoring features, such as tines 335 or the like, positioned towards a proximal end of the third portion.

[0185] In general, the process of implanting the lead will involve creating three incisions in the subject, as shown in Figure 15.

[0186] In this example, first and second incisions 1551, 1552 are created as described above with respect to Figure 11. Additionally, a third incision 1553 is created in a region above the ear. This third (temporal) incision 1553 is created so that a needle can be inserted from the first (occipital) incision 1551 to the third incision 1553 and act as a tunneller, allowing the third lead portion 115 to be inserted. Following this, the lead can be fed back to the first incision, then fed down the straw as previously described.

[0187] A specific example surgical procedure will now be described with reference to Figures 16A and 16B.

[0188] In this example, at step 1600, the first, second and third incisions 1551, 1552, 1553 can be created, with tunnelling tools being used to create tunnels extending from the first to the second incision, and from the first to the third incision at step 1610, with the tunnelling tools being removed at step 1620 as described above. A needle is inserted from the first incision 1551 to the third incision 1552 at step 1630, acting as a tunneller to create an opening extending forwardly from the third incision.

[0189] The third portion of the lead is then inserted forwardly from the third incision 1553 at step 1640, with the second and first portions of the lead then being inserted laterally inwardly from the third incision 1553, allowing these to pass back through the tunnelling tool straw to the first incision 1551 at step 1650, with the straw being removed at step 1660 and the first portion being anchored into position at step 1670.

[0190] The second portion of the lead is then inserted through the straw of the tunnelling tool at step 1680, before the straw is removed at step 1690 through the second incision thereby deploying the second electrodes, with the second portion. An inferior / caudal portion of the second portion is anchored into position at step 1700 and connected to the signal generator, before the incisions are closed.

[0191] It will be appreciated however that other surgical approaches could be used, and the above described approach is for the purpose of illustration only.

[0192] Further details of the above described arrangements will now be described. Patho hysiology

[0193] Occipital nerves arise from the upper neck and extend to the back of the head to provide sensory innervation. The trigeminal nerve is a cranial nerve that supplies the front of the head via nerves arising in the brain. Cervical nerves give rise to the occipital nerves as well as others that supply the neck. These nerves play a significant role in head and neck pain.

[0194] Primary headaches are those that exist independently from any other medical conditions. Common examples are tension type headache, migraine headache, and cluster headache. They often involve dural vessel dysregulation.

[0195] Occipital neuralgia is a form of headache that causes pain, such as throbbing, aching, burning, or sharp, stabbing sensation, along the upper neck and back of the head. It usually results from direct irritation of the occipital nerves such as through increased posterior neck muscular tension, or even through direct trauma.

[0196] Cervicogenic headache is pain referred to the head from a source in the cervical spine. It may result from conditions such as cervical facet arthritis, whiplash injuries, cervical spine surgery, or other medical issues.

[0197] The first three cervical spine nerves and their rami are the primary peripheral nerve structures that can refer pain to the head. The C2/3 zygapophyseal joint is responsible for 70% of cervicogenic headache. Other spinal levels (Cl/2 and C3/4) may also directly refer to the head, with the potential for lower neural pathways to contribute to the development of occipital neuralgia via dysfunctional or tense posterior neck musculature, resulting in occipital nerve irritation. It is common to have lower cervical pain co-existent with upper cervical pain, as described for example in Blake, P., Burstein, R. Emerging evidence of occipital nerve compression in unremitting head and neck pain. J Headache Pain 20, 76 (2019).

Disease Burden

[0198] A study of the global burden of disease in 2015 placed migraine as number 7 of the leading causes of years lived with disability. The one-year prevalence of migraine is 11 to 13% of the population and 14% of those with episodic migraine progress to chronic migraine. Cluster headache occurs in approximately 50 per 100,000, with 15 to 20% unresponsive to pharmacological interventions. Occipital neuralgia occurs in approximately 3 per 100,000 per year ² . Prevalence of cervicogenic headache is estimated to be approximately 4% of the general population, and as high as 17% in patients with severe headaches.

Neurostimulation

[0199] Nerve stimulation techniques have been used to mitigate chronic pain. Neurostimulation is a tried and tested intervention, in the treatment of chronic pain, where electrical pulses inhibit and mask the neural transmission of pain signals; thereby, reducing a patient’s sensation of pain. It is documented that occipital nerve stimulation (ONS) is effective in treating resistant primary headache, and occipital neuralgia. Response rates to ONS for posterior occipital pain is on average 88%, however when holocephalic it reduces to approximately 40%. If an appropriate trigeminal peripheral nerve stimulation (PNS) lead (e.g., targeting the supraorbital nerve) is added to the ONS system, then the response rate climbs back to over 90%.

[0200] Several technological issues however limit the acceptability and use of ONS; notably, most procedures are undertaken with traditional neurostimulation systems, which are designed for epidural placement. Such systems are not suitable for ONS, owing to the highly mobile cervical anatomy. Adverse events associated with the use of traditional neurostimulation systems for ONS include lead and anchoring failure, including lead migration, erosion, and lead fracture. Other adverse events include extensive tissue damage owing to the requirement for excess tunneling and multiple incision sites, which inevitably leads to long surgical times and higher risk of lead failure and infection. The excess tunneling is a direct result of the need to implant up to four percutaneous leads, the use of extension connections and the requirement to tunnel to the implantable pulse generator (IPG) site.

Detailed Mechanism of Action

[0201] Trigemino-cervical convergence is how ONS is postulated to have an effect for primary and secondary headache ^{5 6} . Both the trigeminal complex and the upper three cervical nerve roots share a common area within the central nervous system, from which they arise, hence the term Trigemino-cervical complex (TCC). This area has additional input from the vagus nerve. There are connections to the sphenopalatine ganglion and therefore, dural vascular tone via the superior salivary nucleus (SSN). The dural vascular control also has connections to the trigeminal ganglion.

[0202] Figure 17 is a schematic diagram of an example of the concept of dual ONS and cervical nerve stimulation (CNS).

[0203] In one example ONS targets the greater occipital nerve (medial branch dorsal ramus C2); lesser occipital nerve (arising from the ventral ramus of C3) and the third occipital nerve (medial branch of the dorsal ramus C3). Thus, feeding in to the TCC via the upper cervical afferents. As referenced, supraorbital nerve stimulation can further enhance ONS in the treatment of primary headache; this structure feeds into the TCC via VI of the trigeminal nerve.

[0204] It follows that cervical paravertebral peripheral nerve field stimulation (PNfS) can have modulatory effects on both neck pain and headache. It should be noted that lower cervical pain is often co-existent with upper cervical pain which contributes in the majority of cases to cervicogenic headache. The cervical paravertebral stimulation mechanism of effect is postulated to be:

• Direct stimulation of the branches of the dorsal rami of the cervical nerves from C2 to C7, thus dampening pain signals arising from structures innervated by other branches of the dorsal rami, such as the facet joints

• Pain induced muscle dysfunction will therefore tend to normalise with stimulation. Tight, stiff musculature will mostly resolve and any direct irritation this has on the occipital nerves as they pierce through the insertional zone at the base of the occiput will resolve. Therefore, contributing to the resolution of occipital neuralgia / occipital nerve irritation

• Stimulation of the (mainly lateral branches) of the dorsal rami of C2 and C3 in the neck will have a direct input to the TCC, similar to occipital nerve stimulation.

[0205] Figure 18 is a schematic diagram of an example of the concept of paravertebral PNfS dampening pain/neuroplasticity in the distribution of the dorsal posterior ramus, whilst Figure 19 is an illustration of the ventral and dorsal nervous systems. [0206] Studies have shown that ‘Neuromodulation can be beneficial for patients with intractable chronic migraine although frequent complications have been consistently reported across studies.

The Current System

[0207] The above described system allows for the stimulation of both the occipital and cervical nerves (C2-C6), within one neurostimulation lead. Radiofrequency ablation (RFA) and PNfS of the upper cervical facets and/or C2 ganglion can treat both occipital pain and headache, and accordingly, adding cervical stimulation to the more established ONS can enhance patient outcomes.

[0208] The above described lead technology is implanted subcutaneously in a minimally invasive procedure for patients presenting with primary headache (such as migraine, cluster and tension type) and secondary headache (such as cervicogenic headache and occipital neuralgia).

[0209] The lead can allow for more characteristics of an ‘ideal neurostimulation system’ to be fulfdled. For example, the primary targets are both occipital and cervical nerves, with option for further lead variants that target the supra-orbital nerves, for holocephalic headache.

[0210] The lead has longitudinal stretch thus reducing the torsion forces on the anchor and therefore reducing lead migration risk and improving comfort (i.e., patient not continually feeling a tight band in their neck and head). This effect is further enhanced by the surgical technique, whereby the lead ends up with a ‘strain relief bend’, between the occipital and cervical electrode arrays

[0211] The occipital portion of the lead can double as a cranial (distal) anchor for the cervical electrode array, thereby helping eliminate caudal and lateral migration.

[0212] Positioning of the cervical portion of the lead can double as the tunnelled extension of the occipital lead, to a practical convenient location in the upper back. [0213] The occipital lead portion can be anchored by a group of deployable tines. An optional anchor can also be sutured in place, which utilises the tines to mitigate caudal lead migration further.

[0214] The cervical electrode array can be secured at the most proximal portion of the lead body (upper thoracic paravertebral region), with a more traditional lead anchor.

[0215] The proximal lead location, ‘pulse generator terminal’, can be conveniently located for an external wearable device. The position of this external wearable device would be discrete, with the ability to drape the device over a patient’s shoulders, adding to its acceptability in a wide range of situations.

[0216] The leads can also be adapted to incorporate either an internal receiver for a transcutaneous system or to attach to an implantable pulse generator. In either case, the lead design has potential to significantly reduce procedure time and cost, owing to a need to implant fewer neurostimulation leads. For example, a patient presenting with bilateral head and neck pain would only require the implantation of two leads, as opposed to current surgical practice where four leads are required, which could save tens of thousands of dollars.

[0217] Through the adoption of the above neurostimulation lead technology, the following advancements can be achieved, including reduction in procedure time by approximately one- hour, post-op recovery time reduced, lower procedure cost, surgeons net revenue increased, superior patient outcomes owing to significantly reduced lead migration and increased patient comfort owing to the IPG/extemal neurostimulator being placed proximal to T2.

[0218] In one example, the stimulation device could target occipital nerves and one or more of cervical paravertebral field stimulation and/or supra-orbital nerves. The device can have enough electrodes with the ability to independently direct current, and enough surface area to deliver the Algotec PENS algorithm as an alternative, enabling the system to provide flexibility of waveform delivery.

[0219] The system can be easily implanted, and yet provides for multiple anatomical targets with single lead. Standard surgical approaches can be used with minimal incisions, thereby reducing surgical time and infection risk. Lead characteristics include flexible, thin and with longitudinal stretch and anchoring (incorporated into lead in occipital region) able to withstand high mobility of cervico - occipital region.

[0220] The leads can be MRI compatible for 3T imaging and can allow for transcutaneous delivery from a convenient location (e.g. upper back embedded within clothing) to minimise tunnelling, further incisions and the cosmetic consequences/cost of an implantable pulse generator.

Surgical Approach

Patient Preparation

[0221] The patient is initially placed prone and sedated, or alternatively sitting unsedated with head flexed forward. Appropriate skin preparation is performed, with the skin being marked (primarily using a landmark-based approach), including a horizontal line joining mastoid processes and vertical lines from inion (greater occipital protuberance) to first palpable spinous process. Markings are provided midline at T1/T2 and a line drawn vertical 2.5cm lateral to midline from Tl/2 to C2/3.

Incisions

[0222] Appropriate local anaesthesia is used. An incision is made in a cranio-caudal direction in the midline cranially from the horizontal line between the mastoid processes approximately 1cm in length (longer if the optional anchor is used). Incision must be deep enough to be below the dermis, and long enough to enable haemostasis, and/or anchoring with the optional anchor.

[0223] One or two incisions are made (depending upon single versus bilateral lead placement) in the cranio-caudal direction, caudal from the Tl/2 level and approximately 2 to 3 cm in length.

[0224] Incisions are dissected to deep fascia, and plane cleaned with gauze squares with some undermining along deep fascia.

Tunneling

[0225] A tunneling tool is used to run along the deep fascia, beneath the red line 2101 shown in Figure 21 A, 2.5cm lateral to midline. The tunneling tool tip is angled dorsally/superficially. The skin may be ‘pinched’ between the surgeon’s non-dominant hand fingers, to assist with running the tunneling tool along the deep fascia and the shaft of the tunneling tool may need to be lifted dorsally to allow the angled tip to run along parallel to the deep fascia. Appropriate imaging may be used to assist placement, however landmark guidance alone is possible.

[0226] Under fluoroscopy, the tunneling tool should run approximately over the lateral aspect of the lateral masses, whilst under ultrasound the tunneling tool should run along the superficial aspect of the deep fascia.

[0227] Once the tunneling tool has reached the C2/3 level, the patient’s head is rotated to the opposite side so that the midline at the occiput is moved towards the side of the tunneling tool.

[0228] The tunneling tool is advanced with the angled tip rotated towards the midline at the occiput, aiming for the midline incision

[0229] A sponge holder can be placed over the midline incision to assist with aiming the tunnelling tool in the correct direction and enabling sufficient force to push through the connective tissue

[0230] If connective tissue is a barrier to exiting the tunneling tool through the midline incision, then following removal of the flexible plastic core of the tunnelling tool (through the paravertebral incisions), the options are either to use a sharp 18G needle from the midline incision and pierce the connective tissue, aiming to insert the needle into the hollow core of the tunneling tool, or alternatively, a sharp advancing core can be inserted into the tunneling tool, advancing from the proximal hollow end and pushed through the distal end to pierce the connective tissue and advance out through the incision. This advancing core can then be used as a guidewire to manoeuvre the tunneling tool in the correct direction and externalise through the midline incision

[0231] The straw that is over the tunneling tool may be kept in place as the tunneling tool is removed. Alternatively, the core of the tunneling tool can be used to place the lead.

[0232] The head can be returned to midline, however if the straw obstructs in this position, when the lead is being placed through the straw, the head may need to be returned to the rotated position. Lead Implant and Anchoring

[0233] An introducer needle is placed within the midline incision and directed towards the mastoid processes, ensuring that it always stays deep to the dermis. This may be achieved by angling the spoon part of the introducer needle towards the skin.

[0234] The core of the introducer needle can be removed, and the occipital portion of the lead is placed into it and can be advanced as far as possible. Once the lead is in place, the introducer needle is removed and the tines can be exposed to lay just lateral to midline.

[0235] If the optional anchor is used, it can be placed onto the lead at this point and secured by the tails of an anchoring suture. A slow dissolvable suture, such as 2/0 vicryl, should be placed into the deep fascia in the midline and a knot tied on the deep fascia thus leaving the tails to tie through the anchor.

[0236] The proximal lead end can then be placed through the straw/tunneling tool (at the midline incision site) and threaded caudally to the thoracic paravertebral incision. The straw/tunneling tool can be withdrawn through the thoracic paravertebral incision, which exposes the cervical electrode array in the tunneling tool path.

[0237] The proximal lead end can then be anchored to deep fascia either directly around the lead or with an anchor, before the proximal lead tail can be be connected to the chosen pulse generator.

Product Specifications

[0238] For the tunnelling tool, example specifications include that the tunnelling tool is approximately 25cm long, includes a Tuohy tip and an angled shaft close to tip to allow steering. Typically approximately 5 to 30 degrees of angulation are used with 20 to 40mm distance to tip. A straw is provided over a top of the tunnelling tool, with the straw being thick enough to ensure relative rigidity.

[0239] The tunnelling tool can also include a removable handle and plastic core, with the handle being used to allow easy steering to midline incision. [0240] The sharp advancing core, if used, is typically a sharp straight needle attached to longitudinally rigid plastic to allow it to pass into the hollow core of the tunnelling tool, navigate the angle and pass through the end and pierce any connective tissue.

[0241] The optional anchor is typically a two holed winged anchor, with a short central shaft. Holes feed over the lead, but with these not being large enough for the tines to pass through. This is designed to hold the lead in place, until scar tissue forms around the tines.

[0242] Accordingly, the above described lead arrangements contribute to an implantable system that is effective for a wider indication, is cost effective, simple, more robust with lower complications and potentially be utilised as an office-based implant, if connected to a transcutaneous pulse generator. It would appeal to and be appropriate for a wider group of patients compared to a traditional cumbersome epidural system and have more ideal characteristics than the current competition.

Clinical Evidence

[0243] The following evidence has been obtained via analysis of integrated electrical neurostimulation with RFA treatment for patients with resistant/refractory head and neck pain.

[0244] Peripheral electrical neurostimulation can be delivered either intermittently via a temporary percutaneously placed probe (PENS) or continuously with an implantable system, different to that outlined above. The bulk placements are occipital nerve and cervical paravertebral with some supra-orbital, with these being obtained via needle placement shown in Figures 22A to 22D.

[0245] The analysis revealed the following:

• 85 patients had PENS targeting either the occipital nerves or cervical paravertebral area, of these 63 had a failed response to RFA treatment, therefore PENS was used primarily as a salvage technique.

• 201 PENS procedures were performed approximately equally distributed between occipital and cervical paravertebral. o 125 Procedures demonstrated benefit o 38 procedures lost to follow up o 35 procedures did not demonstrate benefit

[0246] A trial involving PNfS and ONS, revealed:

• 8 patients implanted

• 4 patients had previous neck surgery and had continuing cervical pain and headaches. All patients either had posterior approach cervical surgery or did not want epidural leads for fear of complications. o 3 of 4 went to permanent implant o 1 explanted 12 months later for further surgery o 2 of 3 patients reported >50% relief >2 years o The 1 unsuccessful case had a successful cervical epidural trial

• 4 patients had neck pain and headache, without prior surgery o All 4 patients had successful trials o 3 went to implant, one remained pain free for >2 years o 1 needed both cervical/occipital leads. Remains at pain score 1/10 with no analgesics, post being in hospital for 8 weeks on impairing opioid doses o 1 needed occipital leads alone, remains pain score 1/10, 2.5 years post implant o 1 chose cervical leads alone and was explanted due to inadequate pain relief and drug issues

[0247] A number of reported issues were identified with permanent implants, including:

• Surgical complexity results in a lengthy procedure time and thus, the intervention is not offered to as many patients as would potentially benefit

• Difficulty tunnelling to the midline incision for the occipital leads, due to the angle between the cervical fascia and the midline occiput.

• Difficult to place 2 traditional anchors through a midline incision for the occipital leads

• When the cervical leads are originally positioned, they often provide desirable referred stimulation to the occiput through stimulating the lateral branches of the C2 and C3. Almost invariably, this stimulation is lost over time as the top of the leads migrate caudally (may only be 3 to 4mm of migration) and laterally. [0248] Figures 23A to 23D illustrate cervico-thoracic angles, three incision points, and the final x-ray appearance, whilst Figures 24A and 24B show caudal/lateral cervical paravertebral lead migration. In this regard, significant lead migration is common with commercially available neurostimulation leads, resulting in the need for surgical revision. There are numerous downsides associated with performing repeat procedures, such as: increasing healthcare and patient costs, increasing risk of adverse events (i.e., infection) and decreasing patient emotional and physical wellbeing.

[0249] Neurostimulation lead technology to date only permits for physicians to provide therapy at one neural target, when treating their patients head and neck pain. As such, there is a requirement to implant up to four leads, when targeting bilateral head and neck pain.

[0250] Throughout this specification and claims which follow, unless the context requires otherwise, 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. As used herein and unless otherwise stated, the term "approximately" means ±20%.

[0251] Persons skilled in the art will appreciate that numerous variations and modifications will become apparent. All such variations and modifications which become apparent to persons skilled in the art, should be considered to fall within the spirit and scope that the invention broadly appearing before described.