Download High-frequency spinal cord stimulation and dorsal root ganglion

Health Policy Advisory Committee on
Technology
Technology Brief
High-frequency spinal cord stimulation and dorsal root
ganglion stimulation for chronic pain
July 2015
© State of Queensland (Queensland Department of Health) 2015
This work is licensed under a Creative Commons Attribution Non-Commercial No Derivatives 3.0
Australia licence. In essence, you are free to copy and communicate the work in its current form for
non-commercial purposes, as long as you attribute the authors and abide by the licence terms. You
may not alter or adapt the work in any way.
To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/3.0/au/deed.en.
For further information, contact the HealthPACT Secretariat at:
HealthPACT Secretariat
c/o Healthcare Improvement Unit, Clinical Excellence Division
Department of Health, Queensland
Level 2, 15 Butterfield St
HERSTON QLD 4029
Postal Address: GPO Box 48, Brisbane QLD 4001
Email: [email protected]
Telephone: +61 7 3328 9180
For permissions beyond the scope of this licence contact: Intellectual Property Officer, Department
of Health, GPO Box 48, Brisbane QLD 4001, email [email protected], phone (07) 3328
9824.
Electronic copies can be obtained from: http://www.health.qld.gov.au/healthpact
DISCLAIMER: This Brief is published with the intention of providing information of interest. It is
based on information available at the time of research and cannot be expected to cover any
developments arising from subsequent improvements to health technologies. This Brief is based on
a limited literature search and is not a definitive statement on the safety, effectiveness or costeffectiveness of the health technology covered.
The State of Queensland acting through Queensland Health (“Queensland Health”) does not
guarantee the accuracy, currency or completeness of the information in this Brief. Information may
contain or summarise the views of others, and not necessarily reflect the views of Queensland
Health.
This Brief is not intended to be used as medical advice and it is not intended to be used to diagnose,
treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute
for a health professional's advice. It must not be relied upon without verification from authoritative
sources. Queensland Health does not accept any liability, including for any injury, loss or damage,
incurred by use of or reliance on the information.
This Brief was commissioned by Queensland Health, in its role as the Secretariat of the Health Policy
Advisory Committee on Technology (HealthPACT). The production of this Brief was overseen by
HealthPACT. HealthPACT comprises representatives from health departments in all States and
Territories, the Australian and New Zealand governments and MSAC. It is a sub-committee of the
Australian Health Ministers’ Advisory Council (AHMAC), reporting to AHMAC’s Hospitals Principal
Committee (HPC). AHMAC supports HealthPACT through funding.
This Brief was prepared by Benjamin Ellery, Jacqueline Parsons and A/Prof Tracy Merlin from
Adelaide Health Technology Assessment (AHTA), School of Population Health, University of Adelaide.
Summary of findings
Both high-frequency spinal cord stimulation (HF SCS) and dorsal root ganglion stimulation
(DRGS) are examples of neuromodulatory technologies which are yet to be widely studied in
comparative trials with large numbers of patients. The available evidence includes one
randomised controlled trial (RCT) comparing HF10 therapy and traditional SCS, one crossover study comparing HF SCS (5 kHz) and sham treatment, and six case series. Based on this
evidence, HF SCS and DRGS have shown mostly consistent benefits in terms of pain
reduction, (this applies particularly to HF10 therapy; less favourable results were observed
for modalities delivering 5 kHz stimulation). Outcomes from the RCT provide evidence that
HF10 therapy is superior to traditional SCS with some caveats; in particular given the
requirement for paraesthesia mapping with traditional SCS, neither patients nor study
investigators were blinded to the treatment allocation. This introduces some risk of bias,
and the results should be interpreted accordingly. The remaining evidence on HF10 therapy
included smaller, non-comparative studies and is therefore less reliable. However, it is also
true that SCS in various forms is often a last-line therapy for many patients by the time they
receive it, and selecting an appropriate comparator to test the effectiveness of emerging
SCS technologies is not straightforward; while use of traditional SCS as the comparator is
clinically sensible, choice of this comparator may compromise methodological rigour in
study design. On the other hand, comparison with sham treatment, as in the study
conducted by Perruchoud and colleagues seems a likely alternative, but at this stage has
only been performed in patients with prior favourable results using conventional SCS. 16 It is
difficult to conclude whether or not patients who were treated firstly with HF SCS (5 kHz)
and then went on to receive sham stimulation experienced a benefit from sham that was
independent of prior HF SCS. Future studies of HF SCS (across different frequency
parameters) and DRGS with traditional SCS and sham treatment as the comparators are
needed in patients naïve to any form of SCS to better establish the effectiveness of modified
forms of SCS relative to traditional SCS and properly investigate any placebo effect.
The included studies are not without other limitations:
HF SCS parameters at 5 kHz cannot be directly generalised to HF10 technology
currently available in Australia which operates at 10 kHz;
the potential for a Hawthorne effect cannot be ruled out (particularly applicable to
the smaller studies with only short-term follow-up);
short follow-up times are a major limitation to conclusions about the long-term
efficacy of neuromodulatory devices targeting pain.
Both clinicians and industry have emphasised the importance of careful patient selection,
including proper psychological assessment in the application of both traditional and newly
emerging SCS techniques. Application of the technology needs to be carefully considered
Spinal cord stimulation: July 2015
i
within the broad context of the pain care in Australia, which typically occurs in a fragmented
fashion across different medical disciplines, with communication and collaboration lacking
between different medical specialties, craft groups and other professional bodies. Open
communication and inter-disciplinary cooperation across the broad area of pain
management should be considered as key supports to achieve the best possible outcomes
for patients from SCS technology in the future.
HealthPACT Advice
The evidence presented in this brief has demonstrated mostly consistent benefits for
patients with neuropathic pain treated with high-frequency spinal cord stimulation or dorsal
root ganglion stimulation. However, it is unclear from the current evidence base the
possible role the placebo effect may play in terms of pain reduction. Appropriately designed
studies including a sham treatment arm would clarify any placebo effect. In addition, HF SCS
devices are considerably more expensive than conventional spinal cord stimulation devices.
Therefore HealthPACT does not support investment in this technology in clinical practice at
this time, however, HealthPACT recommends that the evidence be reviewed again in 24
months.
Spinal cord stimulation: July 2015
ii
Technology, Company and Licensing
Register ID
WP221
Technology name
High-frequency spinal cord stimulation/ dorsal root
ganglion stimulation for chronic pain
Patient indication
Chronic pain including, but not limited to, intractable pain
Description of the technology
Spinal cord stimulation (SCS) has been used for the treatment of a variety of pain conditions
for more than 40 years1, 2, especially neuropathic pain conditions such as complex regional
pain syndrome (CRPS)3 and failed back surgery syndrome (FBSS)4. In more recent years,
high-frequency (HF) SCS5, using stimulation in a frequency range beyond human perception
(1-10 kHz)6, and dorsal root ganglion stimulation (DRGS)7 have emerged as modified
techniques that avoid some of the undesirable effects associated with traditional SCS. These
techniques may also be considered for neuropathic pain conditions when patients/
physicians find the results of traditional SCS to be unsatisfactory.8, 9 Both traditional SCS and
newer variations on the technology have many features in common but also include some
important differences. These are explained in detail below.
Spinal cord stimulation
Spinal cord stimulation (SCS) is a neuromodulatory technique that refers to the treatment of
pain by epidural electrical stimulation of the dorsal columns of the spinal cord (see
Appendix A, page 34, for background on spinal cord anatomy). Historically referred to as
dorsal column stimulation, the technique involves the surgical placement of electrodes over
the dorsal column to modulate pain generation or processing. The goal of traditional SCS
(typical frequency range 50-100 Hz6) is to replace the sensation of pain with paraesthesia,
sensations often described as tingling and buzzing. These sensations are generally
considered to be acceptable to those patients for whom the treatment produces significant
relief from chronic pain.
Traditionally, SCS has been used for neuropathic or mixed neuropathic/ nociceptive pain. It
has also been used to successfully treat ischaemic pain (see Appendix B, page 37, for
descriptions of pain types).10, 11 There are some types of pain that are suited to treatment
with neuromodulatory devices and some which are not.10 It is beyond the scope of this Brief
to consider the application of pharmacological neuromodulatory agents; only information
pertinent to recent developments in devices which use electrical stimulation of the SC (i.e.
HF SCS) and neural structures within the spinal column (i.e. DRGS) are considered.
The proposed mechanisms for the observed effects of SCS and other neuromodulatory
techniques such as DRGS and HF SCS are complex and not yet fully understood. The basic
premise for the concept of SCS was the ‘gate control theory’ published by Melzack and Wall
Spinal cord stimulation: July 2015
1
in 1965.12 They proposed that pain occurs when the stimulation of small peripheral fibres
(pain nerves) opens the gate in the dorsal column of the spinal cord, thereby transmitting
pain sensation to the brain. This theory assumes that electrical stimulation of the spinal cord
preferentially recruits large fibres and leads to closure of the gate on smaller fibres, blocking
pain transmission to the brain. However, the gate control theory does not explain why
neuropathic pain is selectively targeted while nociceptive pain is mostly spared. Neither
does the theory inform why some patients report that pain does not return immediately
after stimulation is discontinued. Zhang and colleagues provide a comprehensive discussion
of ‘gate control theory’ and other theoretical models which aim to explain the mechanisms
underpinning SCS. 13
Generically, SCS devices consist of electrode leads, an extension cable, a pulse generator
and a programmer. The leads are either percutaneous, ‘paddle’ or hybrid percutaneouspaddle leads. Percutaneous and paddle leads typically have four to 16 electrodes.
Percutaneous leads are introduced into the epidural space via a Tuohy needle, while
placement of paddle leads requires open surgery to cut or remove part of the vertebra
(laminotomy/ laminectomy) in order to access the epidural space.
Table 1
Suggested lead placement for traditional SCS targeting selected body sites 6
Site of pain, condition
Lead placement, relative to spinal midline and levels of vertebrae
Lower extremity
One lead midline and one lateral to the midline
Axial back pain
One lead midline and one either side of the midline
Posterior occipital region
C2
Upper extremity
Between C2 and C5
Hand
C5, C6
Chest wall, angina
T1 to T4 (one lead midline, one more laterally)
Thigh and knee
T9 to T10
Lower leg and ankle
T10 to T12
Foot
Between T11 and L1
Sole of foot
L5 or S1 nerve root (though difficult in practice)
Note: Letters C, T, L, S refer to the sections of the vertebral column. Numbers, e.g. C1 refer to the first cervical vertebra, etc.
C, cervical; T, thoracic; L, lumbar, S, sacral
Spinal cord stimulation: July 2015
2
Traditional SCS targets specific areas of the body based on the placement of the electrode
leads. General guidelines for placement are shown in Table 1. The final positions are
adjusted from the suggested starting points based on the patient’s feedback. This is referred
to as paraesthesia mapping. For effective pain relief, traditional SCS requires that
paraesthesia is induced in the area corresponding to the area where the patient is
experiencing pain. Sedation, rather than general anaesthesia is a requirement of the
procedure, as the patient is required to give feedback to the surgeon to ensure best possible
placement of the leads.6 Prior to SCS therapy, the patient with chronic pain will undergo a
screening trial (usually 3 to 8 days in duration) with placement of temporary electrodes and
an external pulse generator. The trial provides an indication of technical success (adequate
paraesthesia coverage), clinical success (sufficient pain relief) and the patients’ tolerance of
the treatment.11
Paraesthesia coverage depends on which afferent nerves are stimulated. In clinical practice,
the SCS electrodes are placed with several millimetres of cerebral spinal fluid and dura
separating them from the pial surface (the innermost meningeal layer). This enables easy
recruitment of lateral structures including the entering dorsal roots, but results in limited,
focal paraesthesia coverage. Traditional SCS may also include unwanted motor recruitment
and discomfort due to changing intensity of paraesthesia, particularly when patients assume
certain positions (e.g. supine vs upright).11, 14
High-frequency spinal cord stimulation
A main advantage claimed for HF SCS is the provision of analgesia without the hallmark
paraesthesia observed in traditional SCS.5, 6, 15, 16 Typically, HF SCS is delivered at a frequency
range (1-10 kHz) at least 10-fold higher than traditional SCS (50-100 Hz).6 The SENZA system
(Nevro Corp, Menlo Park, CA), which is now available in Australia and Europe, provides
‘HF10™’ therapy at 10 kHz (see Figure 1).6 Another claimed advantage of HF SCS is that it
may target axial back pain more effectively than traditional SCS.5
The implantation of the leads/ electrodes and pulse generator for HF SCS are identical to the
protocols used for traditional SCS with one exception; leads are placed using only
anatomical landmarks rather than adjustments made based on patient’s feedback, as
paraesthesia mapping is not undertaken. Without the requirement for patient feedback,
placement of HF SCS components can be done under general anaesthesia, rather than under
partial sedation as is used in the implantation of traditional systems.a The two electrode
leads are placed in a staggered fashion to maximise coverage. For patients experiencing
back and/ or leg pain, the source of pain corresponds to the dorsal column range between
T9 and T11; to target pain within this range the tip of the first electrode is placed at T8 and
the second electrode tip is placed at T9.6
a
Personal communication with pain specialist, 17 March 2015.
Spinal cord stimulation: July 2015
3
Charger
Leads
IPG
Patient
remote
Figure 1
The SENZA® system for HF10™ therapy showing implantable pulse generator (IPG) with percutaneous
electrode leads attached, charger and patient remote.b
Dorsal root ganglion stimulation
Dorsal root ganglion stimulation (DRGS) may be targeted to primary low back pain and
isolated foot pain which may be difficult to treat using traditional SCS due to limited
stimulation of the deeper tracts of the spinal cord that cover the sacral dermatomes,
including those of the feet.6 The available literature also indicates that CRPS, radiculopathy,
and post-surgical pain in selected areas are common targets of DRGS.6, 17 Electrode
placement for DRGS differs substantially from the placement of electrodes for SCS. In DRGS
the electrodes are initially introduced the same way as in SCS but then steered laterally into
the neural foramen to stimulate the DRG.6 The proposed advantage of DRGS is the
avoidance of unpleasant sensations during positional changes and a reduction in unwanted
changes in paraesthesia coverage.
Despite contact with Spinal Modulation, the provider of the Axium stimulator for DRGS, we
did not secure express permission to include an image of the device in this Brief.c
Company or developer
Two distinct commercially available devices used for HF SCS and DRGS were identified. The
SENZA system for HF10 therapy is manufactured by Nevro Corporation (Menlo Park, CA),
and distributed in Australia by Emergo Asia Pacific Pty Ltd. Spinal Modulation Incorporated,
recently acquired by St Jude Medical (Minnesota, USA), offers the Axium system for DRGS.
Reason for assessment
Traditional SCS is already established in Australia. New iterations of the technology such as
HF SCS and DRGS are claimed to overcome a number of unwanted side effects typically
associated with the traditional. Based on the burden of morbidity due to chronic pain/ back
pain the cost impact of these new SCS technologies has the potential to be high.
b
SENZA, HF10, Nevro, and the Nevro logo are trademarks of Nevro Corp. Images of the Nevro system are
reproduced with the permission of Nevro Corp.
c
The request was by email on 28 April 2015 and a subsequent email to follow up was sent on May 7 2015,
without success.
Spinal cord stimulation: July 2015
4
Stage of development in Australia
Yet to emerge
Established
Experimental
Established but changed indication
or modification of technique
Should be taken out of use
Investigational
Nearly established
Australian Therapeutic Goods Administration approval
Yes
ARTG number(s):
186043 (SENZA implantable pulse generator)
202323 (Axium implantable pulse generator)
No
Not applicable
Licensing, reimbursement and other approval
The SENZA system is listed on the Australian Register of Therapeutic Goods (ARTG) and is CE
marked for compliance in the European Union (EU). It has recently received approval from
the US Federal Drug Administration (FDA).18 The EU and Australia have cleared the SENZA
system for compatibility with magnetic resonance imaging (MRI) at 3.0 Tesla.19 For patients
implanted with traditional SCS systems, MRI has usually been considered a contraindication
as it poses a significant risk of damage to the inner circuitry of neurostimulator devices.
Some SCS devices (e.g. those manufactured by Medtronic Inc) are considered compatible
with 1.5T MRI under certain conditions.20, 21 There are several ARTG listings related to the
Axium system, which comprises an implantable pulse generator (IPG), electrode leads and
several external components; the various configurations of leads and the other components
have separate ARTG numbers.
Technology type
Device
Technology use
Therapeutic
Patient Indication and Setting
Disease description and associated mortality and morbidity
Pain caused by back problems is very common. Back problems can be caused by injury,
medical conditions such as arthritis, or general degeneration associated with ageing.
Additionally, some risk factors contribute to the likelihood of experiencing back problems,
such as smoking and being overweight.22 The Australian Institute of Health and Welfare
(AIHW) reports that around three million Australians have back problems, based on selfreported data.23 Although anybody can experience back problems, they are more common
in older people, evenly distributed between males and females and more common in lower
Spinal cord stimulation: July 2015
5
socioeconomic status groups.24 Back pain is associated with considerable impact on quality
of life, including inability to work or carry out daily activities. Globally, low back pain
accounted for 3.2 per cent of disability adjusted life-years (DALYs) and 10.5 per cent of years
of life lost due to disability in the Global Burden of Disease Study conducted in 2010. 25 It
was ranked sixth globally for burden in this study, and first in Australasia, including Australia
and New Zealand.25 In New Zealand, the Health Survey in 2013/14 found that one in five
people experienced chronic pain.26 Back disorders accounted for 2.8 per cent of DALYs in
2006 and were ranked seventh in conditions contributing to DALYs.27
Chronic pain is such a serious issue in Australia that a National Pain Strategy has been
developed and endorsed by professional and consumer groups. The strategy highlights that
chronic pain is common, undertreated, and can lead to debilitating and negative effects on
mental health, social and emotional wellbeing and socioeconomic circumstances. The
Strategy aims to have pain recognised as a public health priority, to help individuals
understand and manage their pain, to encourage evidence–based practice amongst better
skilled care providers and to provide better access to interdisciplinary care, alongside health
service quality improvement and research.28
Costs associated with chronic pain were found to be in excess of $34 billion in 2007,
including direct and indirect costs such as lost productivity, health system and informal care
costs and welfare costs.29 AIHW reports that $1.2 billion was spent on inpatient and out of
hospital costs and prescription pharmaceuticals for back pain in the 2008-09 financial year;
the gap between these two figures indicates that costs associated with back pain are
primarily borne by other parts of the health system or community, through direct and
indirect costs.30
Treatment for back pain can take many forms, including physical rehabilitation, patient
education, medicinal pain management and surgery. Much of the care for back pain is
undertaken in general practice and back problems are among the most commonly managed
conditions in primary care, with the AIHW reporting that there were 3.7 million general
practitioner consultations about back pain in 2012-13.31 In the same year, there were
104,350 hospitalisations with back pain as the principal diagnosis in Australia.32
The Australian National Pain Strategy states that less than 10 per cent of people with noncancer chronic pain receive effective care, and estimates that over 80 per cent of people
with chronic pain could be helped by existing treatments.33 It also cautions that:
“current reimbursement and insurance arrangements are such that
outmoded treatments with limited evidence of efficacy, including
some invasive procedures, are often favoured over less invasive
treatments with evidence of efficacy. Some treatments provided are
not based on evidence, but funding. This risks overtreatment by
Spinal cord stimulation: July 2015
6
inappropriate methods
suboptimal outcomes.”
and
therefore
additional
costs
for
In terms of current use of implantable SCS devices, according to the Medicare Benefits
Schedule (MBS) in 2013-14, there were a total of 3,045 private claims related to the
implantation of neurostimulators and placement of leads, 3,656 claims related to
adjustment of neurostimulators and leads, and 1,333 claims related to the removal of
neurostimulators and leads.34 Current MBS items for neurostimulation are shown in Table 2.
The listed fees relate to the surgical placement and not the cost of the neurostimulation
system; these may be reimbursed by some health insurers, or covered by workers’
compensation or existing arrangements through the Department of Veteran’s Affairs (DVA).
If the patient is ineligible for coverage under any of these arrangements, the device cost is
an out-of-pocket cost borne by the patient.d
Speciality
Anaesthetics, pain relief; neurology and neurosurgery;
orthopaedics; rehabilitation and disability
Technology setting
Specialist hospitals and pain management clinics
Impact
Alternative and/ or complementary technology
Additive and substitution: Technology can be used as a substitute in some cases, but may
be used in combination with current technologies in other instances
The newer neuromodulation techniques for pain relief, including HF SCS and DRGS, are
predominantly intended to be used in patients for whom standard medical management
has failed. They may also replace established forms of SCS, or be considered as an option
where standard SCS is not effective. In other words, they are most likely to be used for
patients for whom pain is considered refractory. These new technologies may also be used
in patients for whom traditional SCS has been clinically effective but with side effects that
are considered unacceptable (e.g. recruitment of motor fibres which prevents use of
traditional SCS devices while sleeping and driving, and unpleasant sensations of ‘electric
shock’ and ‘jolting’ which can occur during positional changes).
d
Personal communication with pain specialist, 17 March 2015.
Spinal cord stimulation: July 2015
7
Table 2
MBS items related to the implantation, removal and reprogramming of neurostimulators for chronic
intractable neuropathic pain or refractory pain due to angina pectoris; items include placement of
components used in spinal cord stimulation and peripheral nerve stimulation35
Category 3 - THERAPEUTIC PROCEDURES
39130
EPIDURAL LEAD, percutaneous placement of, including intraoperative test stimulation, for the management of chronic intractable
neuropathic pain or pain from refractory angina pectoris, to a maximum of 4 leads
Multiple Services Rule
(Anaes.)
Fee: $674.15
Benefit: 75% = $505.65
39131
ELECTRODES, epidural or peripheral nerve, management of patient and adjustment or reprogramming of neurostimulator by a medical
practitioner, for the management of chronic intractable neuropathic pain or pain from refractory angina pectoris - each day
Multiple Services Rule
(Anaes.)
Fee: $127.80
Benefit: 75% = $95.85
85% = $10.865
39134
NEUROSTIMULATOR or RECEIVER, subcutaneous placement of, including placement and connection of extension wires to epidural or
peripheral nerve electrodes, for the management of chronic intractable neuropathic pain or pain from refractory angina pectoris
Multiple Services Rule
(Anaes.)
(Assist.)
Fee: $340.60
Benefit: 75% = $255.45
39135
NEUROSTIMULATOR or RECEIVER, that was inserted for the management of chronic intractable neuropathic pain or pain from
refractory angina pectoris, removal of, performed in the operating theatre of a hospital
Multiple Services Rule
(Anaes.)
Fee: $159.40
Benefit: 75% = $199.55
85% = 135.50
39136
LEAD, epidural or peripheral nerve that was inserted for the management of chronic intractable neuropathic pain or pain from refractory
angina pectoris, removal of, performed in the operating theatre of a hospital
Multiple Services Rule
(Anaes.)
Fee: $159.40
Benefit: 75% = $199.55
39137
LEAD, epidural or peripheral nerve that was inserted for the management of chronic intractable neuropathic pain or pain from refractory
angina pectoris, surgical repositioning to correct displacement or unsatisfactory positioning, including intraoperative test stimulation,
not being a service to which item 39130, 39138 or 39139 applies
Multiple Services Rule
(Anaes.)
Fee: $605.35
Benefit: 75% = $454.05
39137
EPIDURAL LEAD, surgical placement of one or more by partial or total laminectomy, including intraoperative test stimulation, for the
management of chronic intractable pain or pain from refractory angina pectoris
Multiple Services Rule
(Anaes.)
(Assist)
Fee: $605.35
Benefit: 75% = $454.05
Current technology
The current standard of care for chronic pain relies heavily on pharmacological treatment.
This includes opioids, non-steroidal anti-inflammatory drugs (NSAIDS), antidepressants,
anticonvulsants/ anti-epileptics and other analgesic therapies, nerve blocks and epidural
Spinal cord stimulation: July 2015
8
corticosteroids. Also included in the current standard of care are physical and psychological
rehabilitative therapies. For chronic back pain where injury or degeneration of vertebral
structures has occurred, or there is a deformity, surgery may be considered appropriate and
some patients seek chiropractic treatment for back problems.4, 36, 37 In some instances,
chronic pain of the back, limbs, trunk or ischaemic pain associated with angina pectoris may
be targeted with established types of neurostimulation (either traditional SCS or PNS), and
the surgical procedures related to these treatments have been funded on the MBS since
2004 (Table 2).
International utilisation
Country
Level of Use
Trials underway or
completed
Australia

Belgium

Netherlands

Switzerland

UK

USA

Limited use
Widely diffused
Diffusion of technology in Australia
Traditional SCS is an established technology in Australia; HF SCS and DRGS are recent
evolutions of the technology which are being clinically trialled in a number of pain centres
around Australia, including the Hunter Pain Clinics (Newcastle, New South Wales) and Metro
Spinal Clinics (Melbourne, Victoria).e
Cost infrastructure and economic consequences
In Australia, the pricing of all components used for any form of SCS is governed by the
Prostheses List Advisory Committee. This includes all implantables, associated external
componentry and kits comprising equipment essential for the surgical placement of leads
and implantable pulse generators (IPGs). The pricing is largely uniform across companies,
reflecting the intended purpose of each component. The price of leads can vary due to the
number of stimulation contact points required within each system (range 1-32 contacts).
SCS systems produced by several companies are listed as “no-gap” prostheses on the
Prostheses List.38 This means that each product is listed with a single benefit, and assuming
that conditions for an insured patient are met, health insurers are legally required to pay
this benefit. This is in contrast to gap-permitted prostheses which have minimum and
e
Details of these clinical trials are available from the Australian and New Zealand Clinical Trials Registry.
Spinal cord stimulation: July 2015
9
maximum benefits listed. For these prostheses, private health insurers are required to pay
at least the minimum benefit.f Table 3 shows a breakdown of costs for the SENZA system,
including two leads each with eight contact points. The full Prostheses List (Part A)38 should
be referred to for details of costings based on systems comprising leads with fewer or more
contacts. Systems with more lead contacts attract a higher minimum rebate. As shown in
Table 3 the supplier of the technology may discretionally supply leads for an initial trial
stimulation at reduced cost, but the insurer is still required to pay the minimum benefit
determined by the billing code. Where this occurs, the ‘surplus’ portion of the rebate is
presumably absorbed by the treating private hospital/ pain clinic. Currently MBS items do
not distinguish between trial lead placement procedures and permanent lead placement
procedures, in terms of the service fee. Trial leads are not reusable and so when they are
removed they are replaced with permanent leads if the doctor and/ or patient considers
that an acceptable level of pain reduction has been achieved.g
f
In cases where the treating doctor considers that a gap-permitted prosthesis is the most clinically suited option
for a patient, the doctor should disclose appropriate clinical and financial information, allowing the patient to
give fully informed consent prior to any procedure. Guidelines are available at
www.health.gov.au/internet/main/publishing.nsf/Content/69F6A026037D6093CA257BF0001B5EDA/$File/ifc_
guidelines.pdf
g
Personal communication with Spinal Modulation area director, in person meeting 28 April 2015.
Spinal cord stimulation: July 2015
10
Table 3
Cost break-down and total cost for implantables and accessory componentry used in trial and permanent
implantation of the SENZA system for HF10 therapy (courtesy of Nevro Corp).h
Description
Billing Code as per Prostheses
List
Price
LEAD1058-70B
Blue Lead Kit, 70cm with 5mm
spacing
ER006
$995
LEAD1058-70B
Blue Lead Kit, 70cm with 5mm
spacing
ER006
$995
Part
Trial leads (x2)
Total
$1,990
Permanent leads (x2)
LEAD1058-70B
Blue Lead Kit, 70cm with 5mm
spacing
ER006
$4,230
LEAD1058-70B
Blue Lead Kit, 70cm with 5mm
spacing
ER006
$4,230
Total
$8,460
All components for permanent procedure
NIPG1500
IPG Kit
ER005
$22,000
LEAD1058-70B
Blue Lead Kit, 70cm with 5mm
spacing
ER006
$4,230
LEAD1058-70B
Blue Lead Kit, 70cm with 5mm
spacing
ER006
$4,230
ACCK1015
Insertion Needle Kit, 6” (15cm)
ER037
$168
ACCK5000
Spare Lead Anchor Kit
ER040
$168
PTRC1000
Patient Remote Kit
ER009
$1,400
CHGR1000
Charger Kit
ER008
$1,346
Total
$33,542
IPG, implantable pulse generator
All costings have been verified by the evaluator as consistent with Part A of the Prostheses List with the exception of lead prices displayed for trial
implantation. This represents a discounted price relative to the rebate determined by the Prostheses List Billing Code.
Costings do not include fees for professional services rendered by the treating doctor(s), anaesthetist or hospital fees.
Prices shown are in Australian dollars.
h
Personal communication with Nevro representative (health economics & reimbursement), email 29 April 2015.
Spinal cord stimulation: July 2015
11
The training requirements for HF SCS and DRGS are in part addressed directly by the
providers of these technologies. Some of the safety issues common across the studies
included in this Brief may in part be related to surgeon experience with SCS. Spinal
Modulation also work with surgeons and other medical professionals in cadaver workshops,
thereby enabling the development of practical skills required to implant leads for DRGS.i A
representative of Nevro reported that implantation procedures for HF10 therapy are
virtually identical to traditional SCS, and as such, surgeons familiar with the older technology
would have no significant learning curve in adapting to working with HF technology.j Like
Spinal Modulation, Nevro provide instructional material for health care professionals on the
safe implantation and removal of their neurostimulation technology. In addition to manuals
and printed instructional materials, Nevro have indicatedk that they provide the following
physician training resources:
in-servicing, i.e. Nevro representatives are available in person to instruct healthcare
professionals on labelling, clinical data, product kits and their contents;
preceptorships in which physicians are given opportunities to observe the use of
HF10 therapy at experienced centres;
seminars providing ongoing professional development to discuss the latest clinical
data and other educational topics on HF10 therapy;
Nevro-sponsored plenary sessions at congresses on pain and neuromodulation;
cadaver workshops for physicians who are new to SCS in general and wish to develop
skills for implant procedures related to SCS (these are undertaken by Nevro directly
or in conjunction with medical societies).
Ethical, cultural, access or religious considerations
Under current arrangements, SCS is primarily accessed through the private health system.
The immediate outlay cost of an SCS system, including HF SCS and DRGS, would be
significant for patients without private health insurance and who do not qualify for
reimbursement under workers’ compensation or DVA arrangements.
Spinal cord stimulation technologies are typically accessed through specialist pain clinics.
This may present an issue for Australians living in rural and remote areas, as they may have
to travel long distances in order to obtain treatment. This may be particularly relevant if
adjustment of the stimulation parameters or revision of lead placement or removal is
required subsequent to the implantation procedure. Some patients may seek
accommodation near the pain centre during their trial period, thereby minimising the need
i
Personal communication with Spinal Modulation area director, in person meeting 28 April 2015.
Personal communication with Nevro representative (health economics & reimbursement), telephone
conversation 2 April 2015.
k
Personal communication with Nevro representative (health economics & reimbursement), email 17 April 2015.
j
Spinal cord stimulation: July 2015
12
to return for the permanent implantation procedure. However, for rural and remote
patients with chronic pain, one or two weeks away from home, without the regular supports
and services they may receive, is potentially an impediment to these patients seeking any
type of SCS.
Evidence and Policy
Safety and effectiveness
High-frequency spinal cord stimulation – HF10 therapy specific
Kapural et al reported on a randomised controlled trial (RCT) using the SENZA system that
was conducted in ten centres in the US. 39 The RCT enrolled 241 patients with, a) chronic leg
and back pain refractory to conservative therapyl for a minimum of three months; b)
average back pain intensity of ‘5’ or greater on a Visual Analogue Scale (VAS; range 0-10
where 0 is indicative of no pain and 10 indicates the worst pain); c) average leg pain of ‘5’ or
greater on VAS; d) Oswestry Disability Index (ODI)m version 2.1 score of 41 to 80 out of 100;
d) assessment by study investigators indicating fitness for surgery. Subjects were excluded if
they had an active disruptive psychological or psychiatric disorder or other known condition
significant enough to impact perception of pain, inability to comply with the intervention,
mechanical spine instability based on flexion and extension films of the lumbar spine or
prior experience with SCS. Of the 241 patients enrolled, 198 were randomised to undergo
either HF10 therapy (101 patients) or traditional SCS (97 patients). The study included a 14day trial phase for both the HF10 therapy and traditional SCS groups; during the trial a nonpermanent external pulse generator was used to stimulate the spinal cord of subjects at
10kHz and standard frequencies, respectively.
Patients who showed adequate treatment response during the trial phase (≥40% pain
reduction on VAS) were then eligible to proceed to implantation with a permanent IPG
device. Among subjects randomised to HF10 therapy and traditional SCS, 90 and 81 subjects
were implanted with permanent devices, respectively. Final analyses at 12-month follow-up
were reported based on these 171 permanently implanted patients.n These results are
summarised in Table 4. Note that for the permanent phase of the trial, response was
defined as a VAS rated pain reduction ≥50%, in contrast to the criterion for proceeding to
permanent implantation (≥40% pain reduction). Patient satisfaction was also assessed, with
55.5 and 32.3 per cent of patients indicating that they were very satisfied with HF10 therapy
and traditional SCS, respectively.
l
Including pain medications, physical therapy, spinal injections, pharmacological and behavioural treatments.
0-20 = minimal disability, 21-40 = moderate disability, 41-60 = severe disability, 61-80 = crippling back pain,
81-100 = patients are either bed-bound or have an exaggeration of their symptoms.
n Analyses by intention-to-treat, per protocol and permanent implant populations at three months all indicated
non-inferiority of HF10 therapy compared to traditional SCS; no notable differences in treatment response were
observed between these analyses according to population. As per the methods set out by the authors, the final
analyses were conducted to test for superiority based on the permanent implant population only.
m
Spinal cord stimulation: July 2015
13
Table 4
Results for RCT comparing SENZA® HF10™ therapy and traditional SCSo
Treatment arm
Intervention,
HF SCS
n=90
Comparator,
traditional SCS
n=81
Relative ratio [95%CI]
p-value
(between group
difference)
7.4±1.2
2.5±NR
7.8±1.2
4.3±NR
NA
NA
0.33
<0.001
7.1±1.5
2.1±NR
7.6±1.4
3.9±NR
NA
NA
0.34
<0.001
Back pain responders (≥50%
pain reduction), %
78.7
51.3
1.5 [1.2,1.9]
<0.001
Leg pain responders (≥50%
pain reduction), %
78.7*
51.3*
1.5 [1.2,2.0]
<0.001
Back pain remitters
(post-therapy pain score ≤2.5
on VAS), %
68.5
36.3
1.9 [1.3,2.7]
<0.001
Leg pain remitters
(post-therapy pain score ≤2.5
on VAS), %
67.4
42.5
1.6 [1.2,2.1]
<0.001
Patients with study-related
SAE, %
4.0
7.2
NA
0.37
0
1**
NA
NA
28 (27.7)
NR (11.9)
-
32 (33.0)
NR (10.3)
NR (11.3)
NA
NA
NA
NR (3.0)
NR (5.2)
NA
0.44
NR
NR
NR
0.49
Outcome
Back pain score, mean
VAS±SD
Baseline
12 months
Leg pain score, mean VAS±SD
Baseline
12 months
Deaths, n
Patients with study-related
non-serious AE, n (%)
Overall
Implant site pain
Uncomfortable paraesthesia
Lead migration requiring
surgical revision†
CI, confidence interval; HF, high-frequency; NA, not applicable; NR, not reported; SAE, serious adverse events; SCS, spinal cord stimulation; SD, standard
deviation; VAS, Visual Analogue Scale (scale 0-10 where, 0 = no pain and 10 = worst pain imaginable)
*Nevro, the trial sponsor, was contacted in order to confirm that the results for leg pain response, being identical to those for back pain response, have
been reported correctly. Nevro confirmed the accuracy of these results.
**Due to myocardial infarction and presumably not study-related; it is unclear whether the investigators considered the death as being study-related or
not.
†There appears to be some disagreement in the field regarding whether lead migration requiring surgical revision is a serious adverse event or not, as
indicated elsewhere in this Brief. The authors reported lead migration requiring revision specifically in the results section on non-serious adverse events.
o
Personal communication, Nevro Corp, email 16 April 2016.
Spinal cord stimulation: July 2015
14
Kapural and colleagues reported that due to practical considerations (i.e. unlike HF10
therapy, traditional SCS produces paraesthesias which must be appropriately targeted to
the correct area during surgery) neither the study subjects nor the investigators were
blinded to the assigned treatment group.39 As this introduces a risk of bias, the study results
should be interpreted accordingly. Furthermore, there is some potential for confounding as
the study investigators were permitted to adjust subjects’ pain medication use after device
activation, although the study protocol did instruct the investigators not to increase pain
medication above baseline levels. However, given that more patients receiving HF10
therapy reduced or eliminated opioid use compared to traditional SCS patients, it appears
unlikely that differences in opioid use contributed to the finding that HF10 therapy was
superior. The authors reported that their study protocol was based on best practice
guidelines for comparative efficacy trial design, referencing relevant publications produced
by the Group for Consolidated Standards of Reporting Trials (CONSORT) and the US Federal
Drug Administration (FDA).40, 41
In addition, three published studies reporting on the effects of HF10 therapy were identified
for inclusion in this Brief.
Al-Kaisy et al42 reported on the outcomes of HF10 therapy using the SENZA system (Nevro
Corp, Menlo Park, CA). A series of 83 patients (mean age 50.8±9.2 years) with chronic,
intractable pain of the low back and legs were recruited from two pain centres in Belgium
and the UK. Patients were only included if they had failed at least six months of
conventional treatment, i.e. pharmacological, physical and radiofrequency therapy, and/ or
epidural injections.
After a baseline evaluation, patients underwent a trial period with lead placement via the
percutaneous route for 14 to 30 days, based on each pain centre’s standard practice. An
external trial stimulator was used during this period to deliver a current at 10 kHz. Patients
then received an IPG if the trial was considered successful, defined as at least 50 per cent
reduction in pain as determined by their score on VAS. Of the 82 patients enrolled, 72 were
considered to have had a successful trial of the SENZA system and underwent permanent
implantation. Sixty-five patients (mean age 50.6±9.1 years) out of the 72 implanted patients
(90%) were included in the final analysis at 24 months of follow-up.42
Baseline and follow-up data included VAS ratings for back and leg pain, sleep disturbance
(subjective number of awakenings per night), Oswestry Disability Index (ODI) and opioid use.
Patients were asked to rate their satisfaction with HF10 therapy on a 5-point Likert scale and
whether they were satisfied with the treatment and would recommend the treatment to
others. The results are summarised in Table 5.
Spinal cord stimulation: July 2015
15
Table 5
Effectiveness of SENZA system in patients with chronic low back and leg pain after six and 24 months
treatment42
Baseline
6-month follow-up
24-month follow-up
p (difference from baseline
to 24 months)
Back pain VAS
score, mean±SD
8.4±0.1
2.7±0.3
3.3±0.3
<0.001
Leg pain VAS score,
mean±SD
5.4±0.4
1.4±0.3
2.3±0.3
<0.001
55±1
NR
40±2
<0.001
3.7±0.4
NR
1.4±0.2
<0.001
Proportion of
patients taking
opioids, %
86
NR
57
<0.001
Dose of oral
morphine
equivalents per
patient, mean
(mg/day)
84
NR
27
<0.001
Proportion of
patients satisfied
with treatment, %
NA
NR
88
NA
Outcome
ODI score,
mean±SD
No. subjective
sleep disturbances
per night,
mean±SD
NA, not applicable; NR, not reported; ODI, Oswestry Disability Index (0-20 = minimal disability, 21-40 = moderate disability, 41-60 = severe disability,
61-80: crippling back pain, 81-100 = patients are either bed-bound or have an exaggeration of their symptoms); SD, standard deviation; VAS, Visual
Analogue Scale (scale 0-10 where, 0 = no pain and 10 = worst pain imaginable)
Seventeen per cent of patients included in the analysis by Al-Kaisy et al42 had undergone
conventional SCS (failed SCS). Thus the majority of patients were naïve to SCS before the
study period, meaning that the results for the majority of patients (83%) are independent of
any previous experience with SCS. While the reductions in pain reported by Al-Kaisy et al42
are statistically and clinically significant, it is unknown if these results are superior to
placebo (no sham comparison performed).
Table 6 summarises the occurrence of serious adverse events attributed to treatment using
the SENZA system. The most common events were pocket pain and lead migration which
the authors reported to be the most common adverse events associated with traditional
SCS. At 24 months, no patients displayed any neurological deficit or dysfunction attributable
to prolonged treatment with HF10 therapy.
Spinal cord stimulation: July 2015
16
Table 6
Safety outcomes for SENZA system in patients with chronic low back and leg pain42
Device-related serious adverse
events
No. events
No. patients with event (%)
Pocket pain
7
7 (8.4)
Wound infection*
5
5 (6.0)
Lead migration
4
4 (4.8)
Loss of therapy effect
2
2 (2.4)
Suboptimal lead placement**
1
1 (1.2)
Skin erosion
1
1 (1.2)
*Four infections occurred during the trial phase and one in the permanent implant phase.
**Occurred in the trial phase.
Al-Kaisy et al43 also reported on the results from a UK case series (n=15 patients) using the
SENZA system for refractory neuropathic pain of the upper and lower limbs. All included
patients had failed conventional therapies including analgesic medications, tricyclic
antidepressants, anticonvulsants, opioids, transcutaneous electrical nerve stimulation,
topical treatments (lidocaine plasters, capsaicin cream), as well as rehabilitative and
cognitive-behavioural therapies. This study diverted from the usual practice for implanting
HF10 IPGs and leads in that paraesthesia mapping was conducted in the phase with trial
lead placement, to enable traditional SCS frequency parameters to be used in the event that
HF10 therapy failed. If at least 80 per cent paraesthesia coverage of the painful area was
obtained in the trial phase under traditional 50 Hz stimulation, patients then went on to a
trial of 10 kHz SCS (n=11 patients). For the 10 patients who experienced success (≥50% pain
relief) with the 10 kHz trial, a permanent IPG was implanted and follow-up conducted for six
months. Patients treated for lower limb pain had electrodes positioned between the T8 and
T12 vertebrae; for upper limb pain, placement was between C2 and C7. Reported outcome
measures were a numeric scale rating for pain, the Brief Pain Inventory, Pain
Catastrophizing Scale and European Quality of Life-5 Dimensions index. The results are
shown in Table 7.
Spinal cord stimulation: July 2015
17
Table 7
Effectiveness of SENZA system for refractory neuropathic pain of the upper and lower limbs after 6 months
treatment43
Baseline
1-month follow-up
3-month follow-up
6-month follow-up
p (difference from
baseline to 6 months)
NRS pain score,
mean±SD
8.2±1.7
2.5±0.9
2.9±1.8
3.3±1.7
<0.05
BPI score,
mean±SD
57.6±9.4
27.0±11.0
22.4±14.5
29.4±14.5
NR
PCS score,
mean±SD
33±11
7±7
7±5
7±6
NR
EQ-5D change, %
NA
↑ 116
↑ 124
↑ 101
NR
Proportion of
patients rating
therapy as
‘excellent’ or
‘good’, %
NA
NA
NA
90
NA
Proportion of
patients who would
recommend the
procedure to
others, %
NA
NA
NA
90
NA
Outcome
BPI, Brief Pain Inventory (measures pain intensity and impact of the pain on patient’s life on a 0-100 scale with higher score indicating more pain and/ or
larger impact); EQ-5D, European Quality of Life-5 Dimensions questionnaire (higher score indicates better quality of life); NA, not applicable; NR, not
reported; NRS, numeric rating scale (0 = no pain, 10 = worst pain imaginable); PCS, Pain Catastrophizing Scale (measures catastrophic thinking related to
pain; range 0-52 where increasing score indicates higher degree of catastrophic thinking related to pain)
In reporting safety outcomes, the authors stated that:
one patient developed an infection during the trial phase, requiring removal of the
leads with reimplantation scheduled in six months;
two patients required surgical revision following lead migration;
three patients experienced transient pain at the site of the IPG;
no neurological events occurred in relation to the SENZA system.
The small number of patients included in this series precludes drawing firm conclusions
about the treatment of refractory upper and lower limb pain using the SENZA system; the
authors acknowledged that larger observational studies and/ or randomised controlled
trials are required. Patients underwent a phase in which conventional SCS was used just
prior to HF10 therapy, and therefore it cannot be excluded that the observed treatment
effects are in part attributable to SCS at conventional frequency.
Spinal cord stimulation: July 2015
18
A series of patients with chronic axial back pain (n=25) recruited from five US centres
reported on the efficacy and safety of an investigational 10 kHz SCS device.44 The
predominant cause of the back pain was FBSS (21 patients). Tiede and colleagues followed a
study protocol similar to methods described by Al-Kaisy et al,42, 43 however, only an external
trial device was used and no permanent implantation was undertaken. Patients first
underwent a period of four to seven days treatment with a device that used conventional
frequency parameters to determine response to SCS. Following this, patients went on to the
second stage of trial treatment with an external HF10 device connected to their leads. Leads
were placed between the T8 and T11 vertebrae. Twenty-four patients were included in the
final analysis after a follow-up of four days. Overall pain and back pain as measured on VAS
(data on back pain available for 18 patients only), adverse events, and patient preference
were reported. Efficacy results are summarised in Table 8. The authors reported that five
patients experienced adverse events, none of which were considered serious. Notably, in
contrast to Al Kaisy et al,42 who considered lead migration as a serious complication, Tiede
and colleagues did not consider lead migration to be serious, but noted this occurrence in
two patients.p The other adverse events were undesirable sensations which occurred in two
patients but resolved with device reprogramming or without intervention, and muscle
cramps/ spasms in one patient which also resolved uneventfully.44
Table 8
Efficacy of investigational HF SCS in patients with axial back pain after four days follow-up44
Baseline
Follow-up* (4 days)
p (difference from baseline
to follow-up)
Overall pain VAS
score, mean±SD
8.7±0.5
2.0±0.8
<0.001
Back pain VAS score,
mean±SD
8.1±0.9
1.9±0.9
<0.001
Proportion of patients
who preferred HF to
conventional SCS, %
NA
88
NR
Outcome
SD, standard deviation; NA, not applicable; NR, not reported; VAS, Visual Analogue Scale (0 = no pain, 10 = worst pain imaginable)
*The results of HF SCS cannot be considered to be independent of a potential residual effect of the initial trial period using conventional frequency SCS
parameters.
The following study limitations were noted by the authors: short trial duration; small
number of patients; lack of control group and randomisation; inability to rule out the
p
Nevro Corp. expressed (email 11 May 2015) that lead migration does not necessarily constitute a serious
adverse event, but that lead migration would be considered serious in instances requiring revision and
rehospitalisation. Logically, lead migration could have an impact on the effectiveness of the therapy, but followup data to confirm or refute such a conclusion are lacking.
Spinal cord stimulation: July 2015
19
Hawthorne effectq; VAS scores rely on patient recollection and are subject to over/
underestimation; the preference for HF therapy is potentially related to the order in which
treatment was received.
In addition, confounding due to the utilisation of conventional frequency SCS and HF10
therapy in the same group of patients may have occurred, and a placebo effect cannot be
ruled out.
High-frequency spinal cord stimulation – stimulation at 5 kHz
A randomised placebo-controlled study conducted in Switzerland by Perruchoud and
colleagues reported on the efficacy of HF SCS (5 kHz)r compared to sham SCS.16 Forty
patients (mean age 54.2 years) who had achieved stable pains relief with traditional SCS
were recruited, of whom 33 had data available for analysis at the end of the study period (6
weeks). Data collected under traditional stimulation parameters were used as a baseline
from which to gauge response as indicated on the Patient Global Impression of Change
(PGIC) score, pain intensity and quality of life. HF SCS was achieved by reprogramming
previously implanted traditional neurostimulation devices provided by Medtronic
(Minneapolis, MN) to deliver currents up to 5 kHz.t
Patients randomised to HF SCS underwent a study treatment program administered by a
non-blinded study investigator in four steps: a) using a maximum of three active contacts,
paraesthesia covering the widest possible area of pain was elicited with traditional SCS; b)
while keeping the current amplitude below sensory threshold, the stimulation frequency
was increased to 5 kHz; c) the current amplitude was progressively increased to sensory
threshold; d) the current amplitude was decreased again below threshold until no
paraesthesia was felt regardless of the patient position. For patients randomised to sham
treatment, the process was identical with the exception that the investigator switched off
the stimulator after step ‘d’. A cross-over period ensued, enabling results of HF SCS and
sham to be reported for all patients. The main results are summarised in Table 9. There
were no statistical differences observed in terms of overall treatment effects, meaning that
the two neuromodulation techniques have a similar effect. The authors did report a
significant “period effect” as indicated by the difference in response due to the order of
treatment sequences (i.e. HF SCS or sham first). For the “HF first” group, the response rate
was 51.5 per cent compared to the “sham first” group which had a response rate of 21.2 per
cent (mean difference 30.3%, p=0.006). The reasons for this finding are unclear but could be
an artefact of confounding or of a lack of successful blinding in the first study period.
q
The Hawthorne effect is a phenomenon in which individuals improve in an aspect of behaviour/ experience in
response to the awareness of being observed.
r
In contrast to HF10 therapy provided by Nevro in which stimulation is at 10 kHz.
s
Patients with low back pain radiating to one or both legs were eligible.
t
The devices used, PrimeADVANCED and RestoreADVANCED, do not commercially support HF parameters.
Spinal cord stimulation: July 2015
20
Table 9
Results for pain patients treated with HF SCS at 5 kHz versus sham, adjusted for baseline values reflecting
conditions under treatment with traditional SCS16
Outcome
HF SCS, n=33
Sham, n=33
p
Response, n (%)
(based on PGIC)
14 (42.4)
10 (30.3)
NS
Pain score, mean
VAS
4.35
4.36
NS
Quality of life, mean
EQ-5D index
0.48
0.46
NS
EQ-5D, European Quality of Life-5 Dimensions questionnaire (1=perfect quality of life, 0=no quality of life); HF, high-frequency; NS, not significant; PGIC,
Patient Global Impression of Change score); SCS, spinal cord stimulation; VAS, Visual Analogue Scale
Reporting of safety outcomes was minimal in this RCT. One patient reported feeling malaise
which was attributed to a vasovagal attack at the programming session during one of the
treatment periods; the patient subsequently withdrew consent. One patient reported a
modest increase in daily oral morphine use but the magnitude of the increase was not
reported.16
The study authors noted several limitations of their trial:
therapy was applied at sub-threshold level by intention; the authors stated that
applying stimulation above the sensory threshold posed the risk of being unpleasant,
harmful and would have resulted in unblinding;
results are limited to stimulation at 5 kHz and cannot be generalised to other
stimulation modes or patterns;
due to the short study duration, it is possible that the effect of conventional SCS may
have played a significant role (i.e. inadequate washout period);
the trial only compared the effect of HF SCS and sham in patients with stable benefit
from traditional SCS and it is unknown whether these results could be replicated in
patients who are naïve to SCS or refractory to SCS.
Dorsal root ganglion stimulation
Three original studies which reported on the effects of DRGS were identified and are
discussed here.
A case series by Liem et al reported on the results of DRGS with the Axium system (Spinal
Modulation, Menlo Park, CA) in 51 patients with chronic, intractable pain of the trunk,
sacrum or lower limbs. Patients were recruited from several centres in Europe and Australia.
The methods used in electrode lead placement and implantation of the IPG were similar to
those used for standard SCS. All patients were given local anaesthesia and lightly sedated.
The study physician accessed the epidural space using a 14-gauge delivery needle. The leads
were then advanced anterogradely through the needle and steered into the intravertebral
Spinal cord stimulation: July 2015
21
foramen near the DRG under fluoroscopic guidance. Up to four leads were used at up to
four DRGs to provide coverage of the painful areas, depending on feedback from the patient
during paraesthesia mapping. Subjects completed baseline assessments and then
underwent a trial period with external stimulation for up to 30 days. If at least a 50 per cent
reduction in pain was demonstrated during the trial period, patients received a permanently
implanted IPG.
Thirty-two of the 51 patients received a permanent implant, and of these, seven patients
had the Axium system removed and were lost to follow up: two due to lack of efficacy, three
due to infection, and two due to non-compliance. After 12 months of follow-up, results for
25 patients were available for analysis.u Included outcomes were overall pain, pain specific
to the back, legs, and feet (measured on VAS, BPI and McGill Pain Questionnaire);
proportion of patients reporting pain improvement of at least 50 per cent (overall pain and
pain specific to the back legs and feet); quality of life (European Quality of Life-5
Dimensions-3 Level version; EQ-5D-3L); Profile of Mood States (POMS); patient satisfaction
on an 11-point Likert scale (0 = not satisfied, 10 = very satisfied); pain improvement based
on PGIC (a 7-point Likert scale); and, adverse events. Efficacy outcomes are shown in Table
10. Similar to all but one of the studies investigating HF SCS included in this Brief, the study
of DRGS by Liem et al45 is limited by small sample size and lack of a control group.
u
Not all outcomes were reported for all 25 patients, in part due to differences in pain aetiology for these patients
(i.e. not all patients had pain in all areas considered in the analysis).
Spinal cord stimulation: July 2015
22
Table 10
Efficacy of DRGS in patients with intractable chronic pain of the trunk, sacrum or lower limbs 45
Baseline
mean±SD
12-month follow-up
mean±SD
% change±SD
p
Overall pain VAS 0-100 mm scale
77.6±2.1 (n=32)
33.6±6.3 (n=25)
56.3±8.4
<0.005
Back pain VAS 0-100 mm scale
74.5±5.3 (n=10)
39.7±9.6 (n=9)
41.9±14.0
<0.05
Leg pain VAS 0-100 mm scale
74.6±3.3 (n=25)
28.7±7.2 (n=20)
62.4±10.8
<0.005
Foot pain VAS 0-100 mm scale
81.4±2.5 (n=13)
22.0±10.7 (n=10)
79.5±12.4
<0.05
BPI score for pain severity
6.9±0.2 (n=32)
3.2±0.6 (n=25)
NR
<0.01
BPI score for pain interference with
activities
6.5±0.4 (n=32)
3.3±0.5 (n=25)
NR
<0.01
NR (n=32)
NR (n=21)
NR
<0.001
Proportion of patients reporting pain
relief ≥50 per cent
Overall
Back
Leg
Foot
NA
60
37.5
68.4
87.5
NA
NA
Patients reporting pain as “a little
better”, “better” or “much better” as
per PGIC, n (%)
NA
23/25 (92)
NA
NA
EQ-5D index score
0.30±0.24 (n=22)
0.70±0.27 (n=18)
134.2
<0.001
EQ-5D VAS score
47.0±3.8 (n=32)
68.4±4.7 (n=25)
68.4
<0.005
POMS score
27.5±3.5 (n=32)
9.4±3.9 (n=25)
NR
<0.05
NA
10/25 (40)
NA
NA
Outcome
McGill Pain Questionnaire score
Patients rating overall satisfaction with
DRGS 8/10 or higher, n(%)
BPI, Brief Pain Inventory (measures pain intensity and impact of the pain on patient’s life on a 0-10 point scale with higher score indicating more pain and/
or larger impact); DRGS, dorsal root ganglion stimulation; EQ-5D, European Quality of Life-5 Dimensions; NA, not applicable; NR, not reported; PGIC,
Patient Global Impression of Change scale, 7-point Likert scale); POMS, Profile of Mood States (includes six mood domains with lower scores indicative of
people with more stable mood profiles; range 0-200); SD, standard deviation; VAS, Visual Analogue Scale (100 mm pain scale where 0 = no pain, 100 mm
= worst pain imaginable and VAS component of EQ-5D where 0 = worst health state imaginable and 100 = best health state imaginable)
Eighty-six adverse events occurred among 29 patients, of which half were considered
attributable to the device (Table 11). The most common adverse events were temporary
motor stimulation (12 events), cerebrospinal fluid leak with associated headache (7 events)
Spinal cord stimulation: July 2015
23
and infection (7 events). The authors commented that the number of device-attributable
adverse events was high, but that the most common events may be mitigated in the future
by improvements in choosing the implant site and programming this new device, with
optimisation having occurred over the course of the study period. Future studies will be
required to validate this claim.
Table 11
Safety outcomes for Axium DRGS for chronic pain of the trunk, sacrum or lower limbs 42
Treatment phase
Adverse event
Serious adverse event
All adverse events
Trial DRGS, n
21
3
24
Permanent DRGS, n
56
6
62
Total, n
77
9
86
40 (52)
3 (38)
43 (50)
Events possibly, probably
or definitely related to
device, n (%)
DRGS, dorsal root ganglion stimulation
Schu et al reported on a case series of 29 patients treated with DRGS for chronic
neuropathic groin pain in several European centres.17 The most common aetiology of the
groin pain was hernia repair; the other causes of pain were mostly related to genito-urinary
surgery, abdominal surgery and the nerve damage that sometimes results from these
procedures. Of the 29 patients who underwent a 30-day trial period, 25 (86.2%) were found
to have greater than 50 per cent pain improvement and underwent implantation with the
Axium IPG provided by Spinal Modulation (Spinal Modulation, Menlo Park, CA). Final lead
placement between T12 and L4 was determined based on patient feedback during
paraesthesia mapping. Data analysis was based on the results of 23 patients with a mean
(±SEMv) follow-up of 27.8 ± 4.3 weeks (range 0-68 weeks). The results of this analysis, and
an analysis of the 13 patients for whom a follow-up of at least six months was achieved, are
shown in Table 12. Adverse events were not reported. The authors noted that paraesthesia
coverage was largely unaffected by positional changes. The study results should be
interpreted with several caveats in mind, including but not limited to the small sample size,
lack of comparative data, and potential bias inherent in pain as a subjective outcome
measure.
v
Standard error of the mean.
Spinal cord stimulation: July 2015
24
Table 12
Efficacy of DRGS in patients with neuropathic groin pain17
Outcome
Baseline
Follow-up
% change ± SD
p (difference from baseline to
follow-up)
Main analysis (mean follow-up ±SEM = 27.8±4.3 weeks; range 0-68 weeks); n=23 patients
Overall pain VAS
score, mean±SD
74.5±1.8
20.7±3.9
71.4±5.6
NR
Patients with ≥50%
pain improvement,
n(%)
NA
19 (82.6)
NA
NA
Patients with ≥80%
pain improvement,
n(%)
NA
11 (47.8)
NA
NA
Analysis for patients ≥6 months follow-up; n=13 patients
Overall pain VAS
score, mean±SD
75.0±2.5
24.1±6.1
67.5±8.6
NR
Patients with ≥50%
pain improvement,
n(%)
NA
10 (76.9)
NA
NA
Patients with ≥80%
pain improvement,
n(%)
NA
7 (53.8)
NA
NA
NA, not applicable; NR, not reported; SD, standard deviation; VAS, Visual Analogue Scale (100 mm pain scale where 0 = no pain, 100 mm = worst pain
imaginable)
Another case series by Deer and colleagues reported on the efficacy and safety of the Axium
DRGS system in ten patients with chronic intractable pain of the trunk and/ or limbs.8 The
study was conducted across four centres for a period of four weeks. The study protocol and
lead implantation procedures were similar to those reported by Liem et al45; however, only
results of trial DRGS over a period of three to seven days were reported (i.e. the study did
not consider longer term effects with a permanently implanted device). Efficacy results are
shown in Table 13. Seventeen adverse events occurred of which 14 were considered to be
device-related; none were thought to be serious and most were technical issues related to
“device inactivation” which were resolved without clinical consequence. One case of lead
migration was reported.
Spinal cord stimulation: July 2015
25
Table 13
Efficacy of DRGS in patients with intractable chronic pain of the trunk and/ or limbs8
Outcome
Baseline
12-month follow-up
% change ± SD
p
73±10 (n=8)
59±17 (n=8)
70±32
<0.001
Back pain VAS 0-100 mm
scale, mean±SD
NR (n=6)
NR (n=5)
84±22
<0.001
Leg pain VAS 0-100 mm
scale, mean±SD
NR (n=8)
NR (n=8)
80±26
<0.001
Foot pain VAS 0-100 mm
scale, mean±SD
NR (n=3)
NR (n=3)
70±30
<0.001
Patients reporting ≥30% pain
reduction, %
NA
88
NA
NA
Patients reporting ≥50% pain
reduction, %
NA
75
NA
NA
Patients rating overall
satisfaction with DRGS 7/10
or higher, %
NA
78
NA
NA
Patients reporting reduced
intake of pain medication, %
NA
78
NA
NA
Overall pain VAS 0-100 mm
scale, mean±SD
NA, not applicable; NR, not reported; SD, standard deviation; VAS, Visual Analogue Scale (100 mm pain scale where 0 = no pain, 100 mm = worst pain
imaginable)
Clearly, the findings of this study are of only limited use for informing clinical practice given
the short-follow up, including only trial conditions rather than long term data based on
experience with permanently implanted systems. Given the small study sample,
improvements in pain specific to the back, legs and feet showed considerable variation. Bias
in regard to the measurement of pain outcomes cannot be ruled out.
Other safety information
In the past, the TGA has undertaken recall actions in relation to lead breakage associated
with the removal of Axium neurostimulator leads, stating that Spinal Modulation implant
instructions and warnings must be followed to help prevent lead breakage.46 In compliance
with the TGA, Spinal Modulation have undertaken actionw to clarify and provide additional
information required to ensure the safe removal of leads subsequent to permanent
implantation, and releases of the “Physician Implant Manual” after May 2014 incorporate
this information.
w
Information correct as of 23 May 2015.
Spinal cord stimulation: July 2015
26
Economic evaluation
None identified.
Ongoing research
A search of the Australian and New Zealand Clinical Trials Registry identified several clinical
trials that are either ongoing, actively recruiting, or will commence recruitment soon (Table
14).
Table 14
Clinical trials relevant to new types of SCS registered on anzctr.org.au
Study ID
Country
Intervention
Comparator
Status
ACTRN12614001274662
Australia
Short pulse width SCS (supplied
by Boston Scientific Corporation)
-
Recruiting
ACTRN12614000989640
Australia
SENZA HF10 therapy
-
Recruiting
ACTRN12614000665639
Australia
SENZA HF10 therapy
-
Recruiting
ACTRN12614000584639
Australia
Axium DRGS
-
Not yet recruiting
ACTRN12614000236695
Australia
HF SCS (device not specified)
Sham treatment
Not yet recruiting
ACTRN12614000153617
Australia
SENZA HF10 therapy
-
Recruiting
ACTRN12612000350820
Australia
SENZA HF10 therapy
-
Not yet recruiting
HF, high-frequency; DRGS, dorsal root ganglion stimulation; SCS, spinal cord stimulation
Internationally, ClinicalTrials.gov reports nine potentially relevant clinical trials of new types
of SCS, including HF SCS and DRGS (Table 15).
Table 15
Clinical trials relevant to new types of SCS registered on ClinicalTrials.gov
Study ID
Country
Intervention
Comparator
Status
NCT02112474
Netherlands
HF SCS (device not specified)
Low frequency SCS
Not yet recruiting
NCT02093793
USA
PRECISION high-rate SCS
(Boston Scientific Corporation)
Commercial rate
SCS
Recruiting
NCT01923285
USA
Axium DRGS
Conventional SCS
Active; not recruiting
NCT01624740
USA
PRECISION Plus high-rate subperception SCS
Low rate
subperception SCS
Recruiting
NCT01609972
USA
SENZA HF10 therapy
Commercially
available SCS
Active, not recruiting
NCT01750229
UK
4 different frequency settings on
RestoreSensor SCS (Medtronic)
-
Recruiting
NCT02250469
Netherlands
Axium DRGS
Medtronic SCS
Recruiting
NCT02385201
USA
SENZA HF10 therapy
-
Not yet recruiting
NCT02265848
USA
PRECISION HF SCS (1000 Hz)
Low frequency SCS
Active, not recruiting
DRGS, dorsal root ganglion stimulation; SCS, spinal cord stimulation
Spinal cord stimulation: July 2015
27
Other issues
Contributing authors to all the studies included on the safety and effectiveness of HF SCS (all
stimulation parameters) and DRGS reported conflicts of interest relating to corporate
affiliation or financial reimbursement from Nevro, Medtronic, Spinal Modulation and several
other companies. Details are shown in Table 16.
Table 16
Conflicts of interest acknowledged by authors of studies included on safety and effectiveness
Study
Conflict of interest details
Al-Kaisy et al 201442
Authors received travel sponsorship and speaker fees from Nevro and Medtronic
Al-Kaisy et al 201543
Authors received travel sponsorship and speaker fees from Nevro, Medtronic and Spinal
Modulation
Deer et al 20138
The study was funded by Spinal Modulation, Bioness, St Jude Medical, Vertos and Medtronic;
several authors declared their consultancy to these companies and membership with the affiliated
advisory boards; one author reported being a Spinal Modulation shareholder
Liem et al 201445
One author is an employee of Spinal Modulation; several others declared consultancy to Spinal
Modulation
Perruchoud et al 201316
Several authors declared their role as consultants and advisory board members for Medtronic; the
authors have also received honoraria, consulting, speaking and travel fees from Medtronic
Schu et al17
A number of Spinal Modulation employees were involved in the writing of the manuscript and data
analysis; several study authors are consultants to Spinal Modulation
Tiede et al 201344
Authors are consultants and speakers for Nevro and have received consultant fee and/ or stock
options; the study was sponsored by Nevro
One pain physician located in the Netherlands expressed concerns regarding patients who
require revision for the placement of leads used in DRGS.x It was his opinion that the
anatomical location of the leads for DRGS increases the likelihood of the leads becoming
stuck in comparison to traditional SCS. However, he also countered this statement with his
personal finding that a few patients who fail traditional SCS can have acceptable results with
DRGS. Based on his statement, it appears patient selection is particularly important. A
comment by another pain physician based in Switzerland was provided in an addendum of
the paper on the case series by Deer et al 2013.8 This physician expressed that the
applicability of DRGS in certain patient groups, such as those with foraminal stenosis, still
requires investigation. The issue of careful patient selection is also recognised by industry:
one representative from Spinal Modulation explained that in addition to clinical
considerations, patient selection needs to take into account prospective patient’s
psychological fitness. This representative commented that in the Australian private system
where the vast majority of SCS procedures occur, infrastructure and working connections
x
Personal communication, email 19 March 2015.
Spinal cord stimulation: July 2015
28
across medical and allied health disciplines are lacking, and that adequate psychological
assessment of patients being considered for SCS and appropriate follow up rarely occur.y
Following a neurostimulation workshop in 2014, Cambridge Consultants released a working
paper, “Neurostimulation 2024” that addresses the development potential of
neurostimulation for the next ten years. In an interview with a representative of Cambridge
Consultants, MedGadget identified the following themes:
a move in neuromodulation manufacturing from a focus on implant technology
(waveforms, control systems, power storage etc) to a focus on the wider
“therapeutic ecosystem”, with a vision toward infrastructure building, including
digital services linking patients to clinical stakeholders, caregivers and health system
data;
growing need for small start-up providers of medical devices to collaborate across
the “fractured clinical landscape” of neuromodulation, otherwise dominated by
select larger companies;
finding solutions based on the successful open source models used in other
industries.47
Number of studies included
All evidence included for assessment in this Technology Brief has been assessed according
to the revised NHMRC levels of evidence. A document summarising these levels may be
accessed via the HealthPACT web site.
Total number of studies: 8
Total number of Level II studies: 2
Total number of Level IV studies: 6
Search criteria to be used (MeSH terms)
MeSH terms
Spinal cord stimulation; ganglion, spinal
Text terms
Neuromodulation; “dorsal root”; “dorsal root ganglion stimulation”; “spinal cord
stimulation”; “high frequency”; “high-frequency”; “HF”
y
Personal communication with Spinal Modulation area director, in person meeting 28 April 2015.
Spinal cord stimulation: July 2015
29
References
1.
Shealy, C. N., Mortimer, J. T.& Reswick, J. B. (1967). 'Electrical inhibition of pain by
stimulation of the dorsal columns: preliminary clinical report'. Anesthesia and
analgesia, 46 (4), 489-91.
2.
Shealy, C. N., Taslitz, N. et al (1967). 'Electrical inhibition of pain: experimental
evaluation'. Anesthesia and analgesia, 46 (3), 299-305.
3.
Kemler, M. A., Barendse, G. A. et al (2000). 'Spinal cord stimulation in patients with
chronic reflex sympathetic dystrophy'. The New England journal of medicine, 343 (9),
618-24.
4.
Kumar, K., Taylor, R. S. et al (2007). 'Spinal cord stimulation versus conventional
medical management for neuropathic pain: a multicentre randomised controlled
trial in patients with failed back surgery syndrome'. Pain, 132 (1-2), 179-88.
5.
Vallejo, R. (2012). 'High-frequency spinal cord stimulation: An emerging treatment
option for patients with chronic pain'. Techniques in Regional Anesthesia and Pain
Management, 16 (2), 106-12.
6.
Song, J. J., Popescu, A.& Bell, R. L. (2014). 'Present and potential use of spinal cord
stimulation to control chronic pain'. Pain Physician, 17 (3), 235-46.
7.
Krames, E. S. (2015). 'The dorsal root ganglion in chronic pain and as a target for
neuromodulation: A review'. Neuromodulation, 18 (1), 24-32.
8.
Deer, T. R., Grigsby, E. et al (2013). 'A prospective study of dorsal root ganglion
stimulation for the relief of chronic pain'. Neuromodulation, 16 (1), 67-72.
9.
Van Buyten, J. P., Al-Kaisy, A. et al (2013). 'High-frequency spinal cord stimulation for
the treatment of chronic back pain patients: Results of a prospective multicenter
European clinical study'. Neuromodulation, 16 (1), 59-65.
10.
Deer, T. R., Mekhail, N. et al (2014). 'The appropriate use of neurostimulation of the
spinal cord and peripheral nervous system for the treatment of chronic pain and
ischemic diseases: The neuromodulation appropriateness consensus committee'.
Neuromodulation, 17 (6), 515-50.
11.
North, R. B. (2008). 'Neural interface devices: Spinal cord stimulation technology'. P
Ieee, 96 (7), 1108-19.
12.
Melzack, R.& Wall, P. D. (1996). 'Pain mechanisms: A new theory (Reprinted from
Science, vol 150, pg 971-979, 1965)'. Pain Forum, 5 (1), 3-11.
13.
Zhang, T. C., Janik, J. J.& Grill, W. M. (2014). 'Mechanisms and models of spinal cord
stimulation for the treatment of neuropathic pain'. Brain Res, 1569, 19-31.
14.
Kramer, J., Liem, L. et al (2015). 'Lack of body positional effects on paresthesias when
stimulating the dorsal root ganglion (DRG) in the treatment of chronic pain'.
Neuromodulation, 18 (1), 50-7.
15.
Deer, T., Pope, J. et al (2012). 'Neurostimulation for the treatment of axial back pain:
A review of mechanisms, techniques, outcomes, and future advances'.
Neuromodulation, 17 (S2), 52-68.
16.
Perruchoud, C., Eldabe, S. et al (2013). 'Analgesic efficacy of high-frequency spinal
cord stimulation: A randomized double-blind placebo-controlled study'.
Neuromodulation, 16 (4), 363-9.
Spinal cord stimulation: July 2015
30
17.
Schu, S., Gulve, A. et al (2014). 'Spinal cord stimulation of the dorsal root ganglion for
groin pain-A retrospective review'. Pain Practice.
18.
FDA (2015). FDA approves spinal cord stimulation system that treats pain without
tingling sensation. [Internet]. US Food and Drug Administration. Available from:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm446354.ht
m [Accessed 11 May 2015].
19.
MedGadget (2015). Nevro Senza Spinal Cord Stimulator Cleared in EU, Australia for
3T MRI Use. [Internet]. MedGadget LLC. Available from:
http://www.medgadget.com/2015/02/nevro-senza-spinal-cord-stimulator-clearedin-eu-australia-for-3t-mriuse.html?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+
Medgadget+%28Medgadget%29 [Accessed March 2015].
20.
Kumar, K.& Rizvi, S. (2014). 'Historical and present state of neuromodulation in
chronic pain'. Current Pain and Headache Reports, 18 (1).
21.
Medtronic (2015). Determining MRI Eligibility. [Internet]. Medtronic Inc. Available
from: https://professional.medtronic.com/mri/surescan-mriradiologists/scs/determining-mri-eligibility/index.htm#.VRNUAGNcKuQ [Accessed
March 2015].
22.
Australian Institute of Health and Welfare (2015). What are back problems?
Available from: http://www.aihw.gov.au/back-problems/what-are-back-problems/
[Accessed 17 Mar 2015].
23.
Australian Institute of Health and Welfare (2015). Back pain and problems. Available
from: http://www.aihw.gov.au/back-problems/ [Accessed 17 Mar 2015].
24.
Australian Institute of Health and Welfare (2015). Who gets back problems?
Available from: http://www.aihw.gov.au/back-problems/prevalence/#source-table2
[Accessed 17 Mar 2015].
25.
Australian Institute of Health and Welfare (2015). What is the health burden of back
problems? Available from: http://www.aihw.gov.au/back-problems/health-burden/
[Accessed 18 Mar 2015].
26.
Ministry of Health (2014). Annual update of key results 2013/14: New Zealand Health
Survey, Ministry of Health, Wellington. NZ
27.
Ministry of Health (2013). Health Loss in New Zealand: A report from the New
Zealand burden of diseases, injuries and risk factors study. 2006-2016, Ministry of
Health, Wellington, NZ
28.
National Pain Summit Initiative (2011). National Pain Strategy,
http://www.painaustralia.org.au/images/pain_australia/NPS/National%20Pain%20St
rategy%202011.pdf.
29.
Access Economics (2007). The high price of pain: the economic impact of persistant
pain in Australia, Access Economics, Australia
30.
Australian Institute of Health and Welfare (2015). How much is spent on back
problems? Available from: http://www.aihw.gov.au/back-problems/expenditure/
[Accessed 18 Mar 2015].
Spinal cord stimulation: July 2015
31
31.
Australian Institute of Health and Welfare (2015). What role do GPs play in treating
back problems? Available from: http://www.aihw.gov.au/back-problems/treatmentby-gps/ [Accessed 18 Mar 2015].
32.
Australian Institute of Health and Welfare (2015). What role do hospitals play in
treating back problems? Available from: http://www.aihw.gov.au/backproblems/treatment-by-hospitals/ [Accessed 18 Mar 2015].
33.
National Pain Summit Initiative (2011). National Pain Stategy. [Internet]. Pain
Australia. Available from:
http://www.painaustralia.org.au/images/pain_australia/NPS/National%20Pain%20St
rategy%202011.pdf [Accessed March 2015].
34.
Medicare Item Reports [database on the Internet]2015. Available from:
http://medicarestatistics.humanservices.gov.au/statistics/mbs_item.jsp.
35.
DoH (2015). MBS Online. [Internet]. Department of Health. Available from:
http://www.mbsonline.gov.au/internet/mbsonline/publishing.nsf/Content/Home
[Accessed March 2015].
36.
Dworkin, R. H., O'Connor, A. B. et al (2010). 'Recommendations for the
pharmacological management of neuropathic pain: an overview and literature
update'. Mayo Clinic proceedings, 85 (3 Suppl), S3-14.
37.
Dworkin, R. H., O'Connor, A. B. et al (2013). 'Interventional management of
neuropathic pain: NeuPSIG recommendations'. Pain, 154 (11), 2249-61.
38.
DoH (2015). Prostheses List. Available from:
http://www.health.gov.au/internet/main/publishing.nsf/Content/prostheses-listpdf.htm [Accessed April 2015].
39.
Kapural, L., Yu, C. et al (2015). 'Novel 10-kHz High-frequency Therapy (HF10 Therapy)
Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment
of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial'.
Anesthesiology.
40.
FDA (2015). Guidance for Industry: Non-Inferiority Clinical Trials. [Internet]. US
Federal Drug Administration. Available from:
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/g
uidances/ucm202140.pdf. [Accessed August 2015].
41.
Piaggio, G., Elbourne, D. R. et al (2012). 'Reporting of noninferiority and equivalence
randomized trials: extension of the CONSORT 2010 statement'. JAMA, 308 (24),
2594-604.
42.
Al-Kaisy, A., Van Buyten, J. P. et al (2014). 'Sustained Effectiveness of 10kHz HighFrequency Spinal Cord Stimulation for Patients with Chronic, Low Back Pain: 24Month Results of a Prospective Multicenter Study'. Pain Medicine (United States), 15
(3), 347-54.
43.
Al-Kaisy, A., Palmisani, S. et al (2015). 'The use of 10-kilohertz spinal cord stimulation
in a cohort of patients with chronic neuropathic limb pain refractory to medical
management'. Neuromodulation, 18 (1), 18-23.
44.
Tiede, J., Brown, L. et al (2013). 'Novel spinal cord stimulation parameters in patients
with predominant back pain'. Neuromodulation, 16 (4), 370-5.
Spinal cord stimulation: July 2015
32
45.
Liem, L., Russo, M. et al (2014). 'One-Year Outcomes of Spinal Cord Stimulation of
the Dorsal Root Ganglion in the Treatment of Chronic Neuropathic Pain'.
Neuromodulation.
46.
TGA (2015). Recall for Product Correction - Axium Neurostimulator Leads. [Internet].
Therapeutic Goods Administration. Available from:
http://www.tga.gov.au/SARA/arn-detail.aspx?k=RC-2014-RN-00531-1 [Accessed
April 2015].
47.
MedGadget (2014). The Next Decade of Neurostimulation: Interview with Simon
Karger from Cambridge Consultants. [Internet]. MedGadget. Available from:
http://www.medgadget.com/2014/09/the-next-decade-of-neurostimulationinterview-with-simon-karger-cambridge-consultants.html [Accessed April 2015].
48.
UTH (2015). Neuroscience Online: An Electronic Textbook for the Neurosciences.
[Internet]. Department of Neurobiology and Anatomy, The University of Texas
Medical School at Houston (UTHealth). © 1997-Present, All rights reserved. Available
from: http://nba.uth.tmc.edu/neuroscience [Accessed March 2015].
49.
Geber, C., Baumgartner, U. et al (2009). 'Revised definition of neuropathic pain and
its grading system: an open case series illustrating its use in clinical practice'. The
American journal of medicine, 122 (10 Suppl), S3-12.
50.
Woolf, C. J.& Mannion, R. J. (1999). 'Neuropathic pain: aetiology, symptoms,
mechanisms, and management'. Lancet, 353 (9168), 1959-64.
51.
Marchand, S., Bushnell, M. C. et al (1991). 'The effects of dorsal column stimulation
on measures of clinical and experimental pain in man'. Pain, 45 (3), 249-57.
52.
Julien, N., Goffaux, P. et al (2005). 'Widespread pain in fibromyalgia is related to a
deficit of endogenous pain inhibition'. Pain, 114 (1-2), 295-302.
53.
Staud, R.& Rodriguez, M. E. (2006). 'Mechanisms of disease: pain in fibromyalgia
syndrome'. Nature clinical practice Rheumatology, 2 (2), 90-8.
Spinal cord stimulation: July 2015
33
Appendix A.
Spinal cord anatomy
The spinal cord (SC) is a cylindrical structure which conveys information from the brain to
the body and from the body to the brain. The entire structure is a uniform organisation of
nervous tissue, comprising white and grey matter, and is classified in four distinct segments:
cervical (C), thoracic (T), lumbar (L) and sacral (S)(Figure 1). Two consecutive rows of nerve
roots emerge on each side of the SC. These nerve roots join distally to form 31 pairs of
spinal nerves. The spinal nerves contains two types of fibres which convey information to
and from all parts of the body: (a) motor fibres, which are involved in movement, and (b)
sensory nerve fibres involved in a variety of processes related to external and internal
sensory input. Each functional segment of the SC (C, T, L, S) innervates a dermatome (Error!
Reference source not found.).48
Figure 2
Schematic dorsal and lateral view of the spinal cord and four cross sections from cervical, thoracic, lumbar
and sacral levels, respectively: Used with permission, Department of Neurobiology and Anatomy, The
University of Texas Medical School at Houston (UTHealth). © 1997-Present, All rights reserved.48
A dermatome is an area of skin supplied by peripheral nerve fibres originating from a single
dorsal root ganglion. If a nerve is cut, sensation is lost from the corresponding dermatome.
Given that each segment of the spinal cord innervates a different region of the body,
dermatomes can be precisely mapped on the body surface, and loss of sensation in a
dermatome can indicate the exact level of spinal cord damage in clinical assessment of
injury, though it is important to realise that a degree of overlap exists between
neighbouring dermatomes. Sensory information (including pain) from the body is relayed to
Spinal cord stimulation: July 2015
34
the central nervous system (CNS) via the dorsal roots, just proximal to the dorsal root
ganglia (DRG)(Figure 3).
Figure 3
Innervation arising from single dorsal root ganglion supplied specific skin area (dermatome): Used with
permission, Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston
(UTHealth). © 1997-Present, All rights reserved.48
Note: Numbers refer to the spinal segments by which each nerve is named. C, cervical; T, thoracic; L, lumbar;
S, sacral spinal cord segments.
The dorsal root fibres are the axonsz originating from the primary sensory DRG cells. Prior to
reaching the SC, each ascending dorsal root axon divides into ascending and descending
branches and enters the SC several segments below and above its own segment. The
ascending dorsal root fibres and the descending ventral root fibres extending to and from
discrete areas of the body form the 31 pairs of spinal nerves (Figure 4). The dorsal root
fibres segregate into lateral and medial divisions. The lateral division contains most of the
axons carrying pain and temperature information. The medial division of dorsal root fibres
consists mainly of axons conducting sensory fibres from the skin, muscles and joints.
z
The long, slender projections by which neurons communicate via the conduction of electrical impulses.
Spinal cord stimulation: July 2015
35
Figure 4
Spinal cord section with its ventral and dorsal root fibres and ganglia: Used with permission, Department of
Neurobiology and Anatomy, The University of Texas Medical School at Houston (UTHealth). © 1997-Present,
All rights reserved.48
Spinal cord stimulation: July 2015
36
Appendix B.
Taxonomy of pain
Neuropathic pain
Neuropathic pain refers to pain originating from nerve damage or altered nerve function.
Mediated by a variety of neurotransmitters and receptors, it is frequently associated with
sensations of burning, shooting, tingling or electric shock. This type of pain is not normal,
unlike the type of pain which is felt in response to an external stimulus, such as in injury or
exposure to extreme temperature. Neuropathic pain is often resistant to opioid drugs or
requires analgesics in large doses to achieve relief, but may respond to anti-epileptics and
antidepressants by acting on shared mechanisms of action.36, 49
Neuropathic pain is predominant in a variety of disease states and syndromes. Notable
examples include spinal nerve root injury, peripheral nerve injury, CRPS type I and type II,
post-herpetic neuralgia, idiopathic and diabetic peripheral neuropathy, central neuropathic
pain from stroke or multiple sclerosis, spinal cord injury and ischaemic nerve
degeneration.10
Nociceptive pain
Nociceptive pain occurs as a result of normal mechanism of pain processing. It has a
biological purpose by signalling to the body that a noxious input has occurred so that an
appropriate behavioural or reflex response may occur to avoid harm. In other words, the
capacity to experience nociceptive pain has a protective role, warning of imminent or
sustained tissue damage and in turn eliciting conscious or reflex responses to avoid or
minimise such damage.50 Nociceptive pain is activated by mechanical, thermal or chemical
irritation and may take the form of sharp, dull, aching or throbbing pain sensations. This
type of pain is observed in disease states and conditions such as soft tissue trauma, various
inflammatory conditions (e.g. arthritis, pancreatitis) and metastatic cancer. Experimental
evidence has shown that animals can respond to SCS targeting nociceptive pain, but this
response has been difficult to establish in humans.10, 51
Mixed pain
Many pain states cannot be exclusively regarded as either neuropathic or nociceptive. These
are referred to as mixed pain. Examples of this type of pain include chronic pelvic pain, pain
associated with FBSS and neural compression secondary to tumour invasion of the bony
spine.10
Dysfunctional pain
For a variety of pain conditions, the underlying diagnosis/ cause is unclear; it is possible for
pain to be present without any identifiable harmful stimulus, inflammation or damage to
the nervous system. Examples of such conditions include fibromyalgia, interstitial cystitis
Spinal cord stimulation: July 2015
37
and irritable bowel syndrome. The understanding of dysfunctional pain syndromes is
growing. For example, fibromyalgia is now believed to result from a deficit in endogenous
pain inhibitory mechanisms, and some researchers believe this condition may be a target for
SCS, although evidence for this application is yet to emerge.10, 52, 53
Spinal cord stimulation: July 2015
38