- Email: [email protected]
Spinal Cord Stimulation Therapy for the Treatment of Concomitant Phantom Limb Pain and Critical Limb Ischemia
Accepted Manuscript Spinal Cord Stimulation Therapy for the Treatment of Concomitant Phantom Limb Pain and Critical Limb Ischemia Giovanni De Caridi, MD PhD, Mafalda Massara, MD, Raffaele Serra, MD PhD, Claudia Risitano, MD, Massimiliano Giardina, MD, Ignazio Eduardo Acri, MD, Pietro Volpe, MD, Antonio David, MD PII:
S0890-5096(16)00032-7
DOI:
10.1016/j.avsg.2015.10.015
Reference:
AVSG 2643
To appear in:
Annals of Vascular Surgery
Received Date: 6 October 2015 Revised Date:
29 October 2015
Accepted Date: 29 October 2015
Please cite this article as: De Caridi G, Massara M, Serra R, Risitano C, Giardina M, Acri IE, Volpe P, David A, Spinal Cord Stimulation Therapy for the Treatment of Concomitant Phantom Limb Pain and Critical Limb Ischemia, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2015.10.015. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT TITLE PAGE
1 2 3
Title: SPINAL CORD STIMULATION THERAPY FOR THE TREATMENT OF
4
CONCOMITANT PHANTOM LIMB PAIN AND CRITICAL LIMB ISCHEMIA
5
Running title: PLP AND CLI TREATED BY SPINAL CORD STIMULATION
RI PT
Authors: Giovanni De Caridi MD PhD1, Mafalda Massara MD1, Raffaele Serra MD PhD2 ,Claudia Risitano MD3, Massimiliano Giardina MD3, Ignazio Eduardo Acri MD1, Pietro Volpe MD4, Antonio David MD3.
SC
Affiliation:
1 Cardiovascular and Thoracic Department,“ Policlinico G. Martino” Hospital, University of
M AN U
Messina, Messina, Italy.
2 Department of Surgical and Medical Science, University Magna Graecia of Catanzaro, Catanzaro, Italy
3 Anesthesiological Sciences Department, “Policlinico G. Martino” Hospital, University of
TE D
Messina, Messina, Italy
4 Vascular and Endovascular Department, “OO.RR” Hospital, Reggio Calabria, Italy Source of financial support: None
7
Authorship statement:Yes
8
Conflict of interest statement:None
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Corresponding author: Giovanni De Caridi MD, PhD Via Marina Arenile, 57/a
89135 Reggio Calabria, Italy Tel +39 – 328 8147887 – Fax +39-0902213061 e-mail: [email protected] 1
ACCEPTED MANUSCRIPT 9 10 11 12
ABSTRACT Phantom limb pain (PLP) is a chronic condition experienced by about 80% of patients who have undergone amputation. In most patients, both the frequency and the intensity of pain attacks
14
diminish with time, but severe pain persists in about 5-10%. Probably, factors in both the peripheral
15
and central nervous system play a role in the occurrence and persistence of pain in the amputated
16
lower limb. The classical treatment of PLP can be divided into pharmacological, surgical,
17
anesthetic, and psychological modalities. Spinal cord stimulation (SCS) does not represent a new
18
method of treatment for this condition. However, the concomitant treatment of PLP and critical
19
lower limb ischemia by using SCS therapy has not yet been described in the current literature. The
20
aim of the present paper is to highlight the possibility of apply SCS for the simultaneous treatment
21
of PLP and critical lower limb ischemia on the controlateral lower limb after failure of medical
22
therapy in a group of 3 patients, obtaining pain relief in both lower limbs, delaying an endovascular
23
or surgical revascularization.
24
After SCS implantation and test stimulation, the pain was reduced by 50% on both the right and the
25
left side in all our patients. The main indications for permanent SCS therapy after 1 week of test
26
stimulation were represented by TcPO2 increase >75%, decrease of opiods analgesics use of at least
27
50% and a pain maintained to within 20-30/100 mm on VAS.
28
KEYWORDS: phantom limb pain, lower limb critical ischemia, spinal cord stimulation.
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ACCEPTED MANUSCRIPT 41 42 43
INTRODUCTION
44
twitching or pain in a previously amputated limb and pain before amputation seems to increase the
45
risk of phantom limb, but the relation is not simple. Up to 80% of patients who have undergone
46
amputation, whether traumatic or surgical, may be affected by PLP.[1]
47
In most patients, both the frequency and the intensity of pain attacks diminish with time, but severe
48
pain persists in about 5-10%. The mechanisms underlying pain in amputees are not fully
49
understood, but factors in both the peripheral and central nervous system play a role.
50
The treatment of PLP can be divided into pharmacological, surgical, anesthetic, and psychological
51
modalities and spinal cord stimulation (SCS) has been used as a modality for the treatment of PLP
52
since 1969.
53
Here we present the successful treatment through SCS therapy of three patients affected by
54
peripheral arterial disease, with PLP in a lower limb already submitted to amputation, accompanied
55
by rest pain and difficult wound healing (1 case) on the other side.
56
MATERIAL AND METHODS
57
We present three cases of simultaneous PLP and critical lower limb ischemia on the controlateral
58
lower limb, treated in our Institution through SCS therapy, after failure of medical therapy
59
(intravenous prostanoids infusion, low weight molecular heparin, oxycodone 40 mg twice a day and
60
gabapentin started at 300 mg 3 times day, increased every 3 days in order to tritation the effect up to
61
3600 mg 3 times a day).
62
All the patients were submitted to spinal cord neurostimulation system implant in the prone
63
position, local anesthesia was performed at T10-11 intervertebral space. A 15-gauge Tuohy
64
needle was used for double paramedian approach with a C-arm fluoroscopic image. After
65
ensuring the needle was positioned in the epidural space, two octrode electrode lead (Nevro
AC C
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Phantom limb pain (PLP) is a chronic condition in which patients experience a sensation of itching,
3
ACCEPTED MANUSCRIPT Corporation, Menlo Park, CA., USA) were placed in median peridural space for the treatment
67
of monolateral critical limb ischemia and phantom limb pain. (Fig.1)
68
The electrodes were connected to the test stimulator, and the stimulation was profound in the areas
69
with pain. After the test stimulation, the pain was reduced by 50% on both the right and the left
70
side. During 1 week of test stimulation, the patient’s pain was maintained to within 20-30/100 mm
71
on VAS, the use of opiate analgesics was decreased by 50% and the increase in TcPO2 >75% on
72
the right foot was recorded. These parameters represented the main indications for permanent SCS
73
therapy.
74
RESULTS
75
The first patient was a 72 year-old man affected by hypertension, diabetes mellitus, dyslipidemia,
76
heart failure, chronic obstructive pulmonary disease, and lower limbs critical ischemia that came to
77
our Institution approximately two years ago, complaining rest pain on the right foot and rest pain
78
and cyanosis of the left foot. He was submitted to left prosthetic iliac-deep femoral artery bypass
79
and one year ago to right superficial femoral artery and anterior tibial artery percutaneous
80
transluminal angioplasty (PTA), with pain relief of both feet. Six months ago the left iliac-deep
81
femoral artery bypass occlusion occurred, with severe ischemia of the left foot, recurrence of rest
82
pain and gangrene of all toes of the foot. Subsequently, he underwent to above the knee amputation
83
and presented phantom limb pain. Also a recurrence of rest pain on the right foot occurred:
84
ultrasonography showed the restenosis of the right vessels previously submitted to PTA.
85
The patient received intravenous prostanoids infusion, low weight molecular heparin (LWMH),
86
oxycodone 40 mg twice a day and gabapentin started at 300 mg 3 times day, increased every 3 days
87
in order to tritation the effect up to 3600 mg 3 times a day.
88
Although a number of treatments were tried, the patient complained extreme pain at the level of
89
amputation greater than 90/100 mm on the visual analogue scale (VAS) and rest pain on the right
90
foot, 60/100 mm on VAS.
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4
ACCEPTED MANUSCRIPT After three weeks of intensive pharmacological therapy he did not experienced improvement of his
92
clinical status and the surgeon proposed the implantation of a SCS, as a last resort strategy for pain
93
control.
94
At the level of the right foot, in baseline conditions the preoperative TcPO2 value was 18 in supine
95
position and 26 with dependent limb. The regional perfusion index (RPI), the ratio between the foot
96
and chest transcutaneous oxygen pressure, at baseline was 0.27.
97
Three months later the RPI increased to 0.41 on the right side, the pain was maintained within
98
30/100 mm on VAS on both right and left side, and the use of opioid analgesics was decreased
99
more than 50% compared with the pre-procedure stage.
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The second patient was a 77 years-old man affected by hypertension, dyslipidemia and diabetes
101
mellitus. Six months ago he received a right superficial femoral artery and posterior tibial artery
102
successful PTA, with rest pain relief. On the left lower limb, he was submitted to above the knee
103
amputation after failure of many attempts of revascularization, with consequently PLP. Five months
104
later, the rest pain on the right foot recurred after the restenosis of the vessels previously submitted
105
to endovascular treatment. Also this patient was submitted to intensive pharmacological treatment
106
without pain resolution after three weeks of therapy, and the surgeon proposed the SCS
107
implantation.
108
In baseline conditions, on the right foot the preoperative TcPO2 value was 17 in supine position and
109
24 with dependent limb, while the RPI was 0.25.
110
After 1 week of test stimulation, the patient’s pain was maintained to within 30-40/100 mm on
111
VAS, the use of opiate analgesics was decreased by 40% and the increase in TcPO2 >75% on the
112
right foot was recorded. Three weeks later the permanent SCS was implanted in this patient.
113
Three months later, the RPI increased to 0.40 on the right side, the pain was maintained within
114
30/100 mm on VAS on both right and left side, and the use of opioid analgesics was completely
115
stopped.
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ACCEPTED MANUSCRIPT The third patient was a 75 years-old woman suffering from diabetes mellitus, hypertension, atrial
117
fibrillation, end stage renal disease on hemodialysis and chronic pulmonary obstructive disease.
118
She presented a calcaneal lesion with an area > 2 cm2 on her left foot, accompanied by rest pain
119
(Rutherford 6); four months ago she was submitted to surgical revascularization of the lower limb,
120
through a femoro-peroneal artery bypass in great saphenous vein. During the following months she
121
obtain a rest pain reduction, with a slow and difficult wound healing, even if the bypass was well
122
functioning.
123
On the right side the patient presented an extensive lesion with severe rest pain (Rutherford 6) and
124
after failure of surgical revascularization, she received an above the knee amputation with PLP. The
125
patient was treated through medical therapy but after two weeks of treatment she didn’t present an
126
improvement of her clinical status and the surgeon proposed the SCS implantation, as adjuvant
127
therapy to promote wound healing of the left foot and to obtain PLP relief.
128
The preoperative TcPO2 value was 14 in supine position and 22 with dependent limb, while the RPI
129
was 0.21 on the left foot.
130
Three months later the RPI increased to 0.40 on the left side, the pain was maintained within 30/100
131
mm on VAS on both right and left side, and the use of opioid analgesics was stopped. The trophic
132
calcaneal lesion decreased to 0.3 cm2.
133
DISCUSSION
134
Phantom limb pain is a chronic condition affecting the majority of patients submitted to lower limb
135
amputation and pain before amputation seems to increase the risk of phantom limb. The treatment
136
of PLP can be divided into pharmacological, surgical, anesthetic, and psychological modalities.
137
Pharmacotherapy plays an important role in the management of PLP. In the past decades, a range of
138
pharmacological interventions appeared in the literature, few with conclusive efficacy and safety
139
that can meet clinical needs. In fact, clinicians have been restricted by the lack of well-designed
140
clinical trials and by the absence of evidence-based consensus guidelines.[2]
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ACCEPTED MANUSCRIPT Although, the Authors recommend many different drugs as the rational options for the treatment of
142
PLP, such as tricyclic antidepressants, gabapentin, tramadol, opioids, local anaesthetics and N-
143
methyl-D-aspartate receptor antagonists.[3]
144
The best treatment, however, seems to be a multimodal approach that combines pharmacotherapy
145
and surgical methods.
146
Spinal cord stimulation does not represent a new method for the treatment of PLP and critical lower
147
limb ischemia.
148
Many reports about the application of SCS in patients affected by peripheral arterial disease are
149
reported in literature.[4-12]
150
About the treatment of PLP, SCS has been used since 1969, with the first series being published in
151
1975 by Nielson et al.[13] Of the six patients treated through SCS, four patients were felt to have
152
excellent outcomes and one patient had a good outcome.
153
In 1980, Krainick et al.[14] reported their experience in 61 patients with PLP treated with SCS: one
154
patient reported pain relief greater than 75%, 13 had pain relief greater than 50% and 12 greater
155
than 25% pain relief while 28 patients did not receive benefit from their SCS.
156
In their Italian multicentric study, Broggi et al.[15] treated 26 patients with SCS for PLP: 23
157
patients were satisfied with the SCS trial and subsequently received permanent SCS therapy.
158
Most recently, Katayama et al.[16] treated with SCS 19 patients suffering from PLP. For this group
159
of patients, satisfactory pain control was determined by greater than 80% reduction in their visual
160
analog scale. Using this criterion, six of 19 (32%) patients had satisfactory long-term pain control
161
with SCS.
162
Miles et al.[17] reported their experience about PLP treated by electrical stimulation with excellent
163
results in 7 cases and partial relief of pain in 3 cases.
164
Viswanathan et al.[18] reported 4 cases of SCS implantation for the treatment of PLP, reporting an
165
excellent pain relief (>80%).
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ACCEPTED MANUSCRIPT Our experience differs from the others reported in literature until now, because the SCS therapy was
167
proposed not only to obtain pain relief in patients affected by PLP, but also to promote pain control
168
on the controlateral lower limb, delaying a more invasive treatment of revascularization. In
169
addition, in one case the SCS was adopted as adjuvant therapy, to speed a calcaneal wound healing,
170
in presence of a functioning distal bypass.
171
CONCLUSIONS
172
SCS does not represent a new method for the treatment of PLP and critical lower limb ischemia.
173
However, for patients in whom medical management has proven inadequate, SCS is a low-risk
174
intervention which can lead to decreased pain, decreased overall symptoms, and improved
175
functional outcome. In particular, in patients already submitted to amputation with concomitant
176
lower limb critical ischemia on the other side, SCS therapy could represent a valid option to treat
177
rest pain, delaying an endovascular or surgical revascularization.
178
REFERENCES
179
[1] Flor H, Nikolajsen L, Jensen TS. Phantom limb pain: a case of CNS plasticity? Nat Rev
180
Neurosci 2006;7:873–881.
181
[2] Halbert J, Crotty M, Cameron ID. Evidence for the optimal management of acute and chronic
182
phantom pain: a systematic review Clin J Pain 2002;18:84-92.
183
[3] Fang J, Lian YH, Xie KJ, et al. Pharmacological interventions for phantom limb pain Chin Med
184
J 2013;126:542-549.
185
[4] Brümmer U, Condini V, Cappelli P, et al. Spinal cord stimulation in hemodialysis patients with
186
critical lower-limb ischemia Am J Kidney Dis 2006 May;47:842-7.
187
[5] Petrakis IE, Sciacca V. Spinal cord stimulation in critical limb ischemia of the lower
188
extremities: our experience J Neurosurg Sci 1999 Dec;43:285-93.
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ACCEPTED MANUSCRIPT [6] Ubbink DT, Spincemaille GH, Prins MH, et al. Microcirculatory investigations to determine the
190
effect of spinal cord stimulation for critical leg ischemia: the Dutch multicenter randomized
191
controlled trial J Vasc Surg 1999 Aug;30:236-44.
192
[7] De Caridi G, Massara M, David A, et al. Spinal cord stimulation to achieve wound healing in a
193
primary lower limb critical ischemia referral center Int Wound J 2014 Apr 8. doi:
194
10.1111/iwj.12272.
195
[8] Horsch S, Schulte S, Hess S. Spinal cord stimulation in the treatment of peripheral vascular
196
disease: results of a single-center study of 258 patients Angiology 2004 Mar-Apr;55:111-18.
197
[9] Spincemaille GH, de Vet HC, Ubbink DT, et al. The results of spinal cord stimulation in critical
198
limb ischemia: a review Eur J Vasc Endovasc Surg 2001 Feb;21:99-105.
199
[10] Amann W, Berg P, Gersbach P, et al. European Peripheral Vascular Disease Outcome Study
200
SCS-EPOS. Spinal cord stimulation in the treatment of nonreconstructable stable critical leg
201
ischaemia: results of the European Peripheral Vascular Outcome Study (SCS-EPOS) Eur J Vasc
202
Endovasc Surg 2003 Sep;26:280-6.
203
[11] Ubbink DT, Vermeulen H. Spinal cord stimulation for critical leg ischemia: a review of
204
effectiveness and optimal patient selection J Pain Symptom Manage 2006 Apr;31:S30-5.
205
[12] De Caridi G, Massara M, Benedetto F, et al. Adjuvant Spinal Cord Stimulation improves
206
wound healing of peripheral tissue loss due to a steal syndrome of the hand. Clinical challenge
207
treating a difficult case Int Wound J 2014 Feb 17. doi: 10.1111/iwj.12233.
208
[13] Nielson KD, Adams JE, Hosobuchi Y. Phantom limb pain: treatment with dorsal column
209
stimulation J Neurosurg 1975;42:301–307.
210
[14] Krainick JU, Thoden U, Riechert T. Pain reduction in amputees by long-term spinal cord
211
stimulation: long term follow-up study over 5 years J Neurosurg 1980;52:346–350.
212
[15] Broggi G, Servello D, Dones I, et al. Italian multicenter study on pain treatment with epidural
213
spinal cord stimulation Stereotact Funct Neurosurg 1994;62:273–278.
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9
ACCEPTED MANUSCRIPT [16] Katayama Y, Yamamoto T, Kobayashi K, et al. Motor cortex stimulation for phantom limb
215
pain: comprehensive therapy with spinal cord and thalamic stimulation Stereotact Funct Neurosurg
216
2001;77:159–162.
217
[17] Miles J, Lipton S. Phantom limb pain treated by electrical stimulation Pain 1978 Dec;5:373-82.
218
[18] Viswanathan A, Phan PC, Burton AW. Use of spinal cord stimulation in the treatment of
219
phantom limb pain: case series and review of the literature Pain Pract 2010 Sep-Oct;10:479-84.
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FIGURE LEGENDS 10
ACCEPTED MANUSCRIPT 239
FIG. 1 Double octopolar leads positioned between T9 and T12
240
FIG. 2 Trophic calcaneal lesion
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11
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ACCEPTED MANUSCRIPT
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ACCEPTED MANUSCRIPT
S0890-5096(16)00032-7
DOI:
10.1016/j.avsg.2015.10.015
Reference:
AVSG 2643
To appear in:
Annals of Vascular Surgery
Received Date: 6 October 2015 Revised Date:
29 October 2015
Accepted Date: 29 October 2015
Please cite this article as: De Caridi G, Massara M, Serra R, Risitano C, Giardina M, Acri IE, Volpe P, David A, Spinal Cord Stimulation Therapy for the Treatment of Concomitant Phantom Limb Pain and Critical Limb Ischemia, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2015.10.015. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT TITLE PAGE
1 2 3
Title: SPINAL CORD STIMULATION THERAPY FOR THE TREATMENT OF
4
CONCOMITANT PHANTOM LIMB PAIN AND CRITICAL LIMB ISCHEMIA
5
Running title: PLP AND CLI TREATED BY SPINAL CORD STIMULATION
RI PT
Authors: Giovanni De Caridi MD PhD1, Mafalda Massara MD1, Raffaele Serra MD PhD2 ,Claudia Risitano MD3, Massimiliano Giardina MD3, Ignazio Eduardo Acri MD1, Pietro Volpe MD4, Antonio David MD3.
SC
Affiliation:
1 Cardiovascular and Thoracic Department,“ Policlinico G. Martino” Hospital, University of
M AN U
Messina, Messina, Italy.
2 Department of Surgical and Medical Science, University Magna Graecia of Catanzaro, Catanzaro, Italy
3 Anesthesiological Sciences Department, “Policlinico G. Martino” Hospital, University of
TE D
Messina, Messina, Italy
4 Vascular and Endovascular Department, “OO.RR” Hospital, Reggio Calabria, Italy Source of financial support: None
7
Authorship statement:Yes
8
Conflict of interest statement:None
AC C
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Corresponding author: Giovanni De Caridi MD, PhD Via Marina Arenile, 57/a
89135 Reggio Calabria, Italy Tel +39 – 328 8147887 – Fax +39-0902213061 e-mail: [email protected] 1
ACCEPTED MANUSCRIPT 9 10 11 12
ABSTRACT Phantom limb pain (PLP) is a chronic condition experienced by about 80% of patients who have undergone amputation. In most patients, both the frequency and the intensity of pain attacks
14
diminish with time, but severe pain persists in about 5-10%. Probably, factors in both the peripheral
15
and central nervous system play a role in the occurrence and persistence of pain in the amputated
16
lower limb. The classical treatment of PLP can be divided into pharmacological, surgical,
17
anesthetic, and psychological modalities. Spinal cord stimulation (SCS) does not represent a new
18
method of treatment for this condition. However, the concomitant treatment of PLP and critical
19
lower limb ischemia by using SCS therapy has not yet been described in the current literature. The
20
aim of the present paper is to highlight the possibility of apply SCS for the simultaneous treatment
21
of PLP and critical lower limb ischemia on the controlateral lower limb after failure of medical
22
therapy in a group of 3 patients, obtaining pain relief in both lower limbs, delaying an endovascular
23
or surgical revascularization.
24
After SCS implantation and test stimulation, the pain was reduced by 50% on both the right and the
25
left side in all our patients. The main indications for permanent SCS therapy after 1 week of test
26
stimulation were represented by TcPO2 increase >75%, decrease of opiods analgesics use of at least
27
50% and a pain maintained to within 20-30/100 mm on VAS.
28
KEYWORDS: phantom limb pain, lower limb critical ischemia, spinal cord stimulation.
SC
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29 30 31 32 33 34 35 36 37 38 39 40
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2
ACCEPTED MANUSCRIPT 41 42 43
INTRODUCTION
44
twitching or pain in a previously amputated limb and pain before amputation seems to increase the
45
risk of phantom limb, but the relation is not simple. Up to 80% of patients who have undergone
46
amputation, whether traumatic or surgical, may be affected by PLP.[1]
47
In most patients, both the frequency and the intensity of pain attacks diminish with time, but severe
48
pain persists in about 5-10%. The mechanisms underlying pain in amputees are not fully
49
understood, but factors in both the peripheral and central nervous system play a role.
50
The treatment of PLP can be divided into pharmacological, surgical, anesthetic, and psychological
51
modalities and spinal cord stimulation (SCS) has been used as a modality for the treatment of PLP
52
since 1969.
53
Here we present the successful treatment through SCS therapy of three patients affected by
54
peripheral arterial disease, with PLP in a lower limb already submitted to amputation, accompanied
55
by rest pain and difficult wound healing (1 case) on the other side.
56
MATERIAL AND METHODS
57
We present three cases of simultaneous PLP and critical lower limb ischemia on the controlateral
58
lower limb, treated in our Institution through SCS therapy, after failure of medical therapy
59
(intravenous prostanoids infusion, low weight molecular heparin, oxycodone 40 mg twice a day and
60
gabapentin started at 300 mg 3 times day, increased every 3 days in order to tritation the effect up to
61
3600 mg 3 times a day).
62
All the patients were submitted to spinal cord neurostimulation system implant in the prone
63
position, local anesthesia was performed at T10-11 intervertebral space. A 15-gauge Tuohy
64
needle was used for double paramedian approach with a C-arm fluoroscopic image. After
65
ensuring the needle was positioned in the epidural space, two octrode electrode lead (Nevro
AC C
EP
TE D
M AN U
SC
RI PT
Phantom limb pain (PLP) is a chronic condition in which patients experience a sensation of itching,
3
ACCEPTED MANUSCRIPT Corporation, Menlo Park, CA., USA) were placed in median peridural space for the treatment
67
of monolateral critical limb ischemia and phantom limb pain. (Fig.1)
68
The electrodes were connected to the test stimulator, and the stimulation was profound in the areas
69
with pain. After the test stimulation, the pain was reduced by 50% on both the right and the left
70
side. During 1 week of test stimulation, the patient’s pain was maintained to within 20-30/100 mm
71
on VAS, the use of opiate analgesics was decreased by 50% and the increase in TcPO2 >75% on
72
the right foot was recorded. These parameters represented the main indications for permanent SCS
73
therapy.
74
RESULTS
75
The first patient was a 72 year-old man affected by hypertension, diabetes mellitus, dyslipidemia,
76
heart failure, chronic obstructive pulmonary disease, and lower limbs critical ischemia that came to
77
our Institution approximately two years ago, complaining rest pain on the right foot and rest pain
78
and cyanosis of the left foot. He was submitted to left prosthetic iliac-deep femoral artery bypass
79
and one year ago to right superficial femoral artery and anterior tibial artery percutaneous
80
transluminal angioplasty (PTA), with pain relief of both feet. Six months ago the left iliac-deep
81
femoral artery bypass occlusion occurred, with severe ischemia of the left foot, recurrence of rest
82
pain and gangrene of all toes of the foot. Subsequently, he underwent to above the knee amputation
83
and presented phantom limb pain. Also a recurrence of rest pain on the right foot occurred:
84
ultrasonography showed the restenosis of the right vessels previously submitted to PTA.
85
The patient received intravenous prostanoids infusion, low weight molecular heparin (LWMH),
86
oxycodone 40 mg twice a day and gabapentin started at 300 mg 3 times day, increased every 3 days
87
in order to tritation the effect up to 3600 mg 3 times a day.
88
Although a number of treatments were tried, the patient complained extreme pain at the level of
89
amputation greater than 90/100 mm on the visual analogue scale (VAS) and rest pain on the right
90
foot, 60/100 mm on VAS.
AC C
EP
TE D
M AN U
SC
RI PT
66
4
ACCEPTED MANUSCRIPT After three weeks of intensive pharmacological therapy he did not experienced improvement of his
92
clinical status and the surgeon proposed the implantation of a SCS, as a last resort strategy for pain
93
control.
94
At the level of the right foot, in baseline conditions the preoperative TcPO2 value was 18 in supine
95
position and 26 with dependent limb. The regional perfusion index (RPI), the ratio between the foot
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and chest transcutaneous oxygen pressure, at baseline was 0.27.
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Three months later the RPI increased to 0.41 on the right side, the pain was maintained within
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30/100 mm on VAS on both right and left side, and the use of opioid analgesics was decreased
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more than 50% compared with the pre-procedure stage.
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The second patient was a 77 years-old man affected by hypertension, dyslipidemia and diabetes
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mellitus. Six months ago he received a right superficial femoral artery and posterior tibial artery
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successful PTA, with rest pain relief. On the left lower limb, he was submitted to above the knee
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amputation after failure of many attempts of revascularization, with consequently PLP. Five months
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later, the rest pain on the right foot recurred after the restenosis of the vessels previously submitted
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to endovascular treatment. Also this patient was submitted to intensive pharmacological treatment
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without pain resolution after three weeks of therapy, and the surgeon proposed the SCS
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implantation.
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In baseline conditions, on the right foot the preoperative TcPO2 value was 17 in supine position and
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24 with dependent limb, while the RPI was 0.25.
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After 1 week of test stimulation, the patient’s pain was maintained to within 30-40/100 mm on
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VAS, the use of opiate analgesics was decreased by 40% and the increase in TcPO2 >75% on the
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right foot was recorded. Three weeks later the permanent SCS was implanted in this patient.
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Three months later, the RPI increased to 0.40 on the right side, the pain was maintained within
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30/100 mm on VAS on both right and left side, and the use of opioid analgesics was completely
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stopped.
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ACCEPTED MANUSCRIPT The third patient was a 75 years-old woman suffering from diabetes mellitus, hypertension, atrial
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fibrillation, end stage renal disease on hemodialysis and chronic pulmonary obstructive disease.
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She presented a calcaneal lesion with an area > 2 cm2 on her left foot, accompanied by rest pain
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(Rutherford 6); four months ago she was submitted to surgical revascularization of the lower limb,
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through a femoro-peroneal artery bypass in great saphenous vein. During the following months she
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obtain a rest pain reduction, with a slow and difficult wound healing, even if the bypass was well
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functioning.
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On the right side the patient presented an extensive lesion with severe rest pain (Rutherford 6) and
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after failure of surgical revascularization, she received an above the knee amputation with PLP. The
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patient was treated through medical therapy but after two weeks of treatment she didn’t present an
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improvement of her clinical status and the surgeon proposed the SCS implantation, as adjuvant
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therapy to promote wound healing of the left foot and to obtain PLP relief.
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The preoperative TcPO2 value was 14 in supine position and 22 with dependent limb, while the RPI
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was 0.21 on the left foot.
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Three months later the RPI increased to 0.40 on the left side, the pain was maintained within 30/100
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mm on VAS on both right and left side, and the use of opioid analgesics was stopped. The trophic
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calcaneal lesion decreased to 0.3 cm2.
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DISCUSSION
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Phantom limb pain is a chronic condition affecting the majority of patients submitted to lower limb
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amputation and pain before amputation seems to increase the risk of phantom limb. The treatment
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of PLP can be divided into pharmacological, surgical, anesthetic, and psychological modalities.
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Pharmacotherapy plays an important role in the management of PLP. In the past decades, a range of
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pharmacological interventions appeared in the literature, few with conclusive efficacy and safety
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that can meet clinical needs. In fact, clinicians have been restricted by the lack of well-designed
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clinical trials and by the absence of evidence-based consensus guidelines.[2]
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ACCEPTED MANUSCRIPT Although, the Authors recommend many different drugs as the rational options for the treatment of
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PLP, such as tricyclic antidepressants, gabapentin, tramadol, opioids, local anaesthetics and N-
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methyl-D-aspartate receptor antagonists.[3]
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The best treatment, however, seems to be a multimodal approach that combines pharmacotherapy
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and surgical methods.
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Spinal cord stimulation does not represent a new method for the treatment of PLP and critical lower
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limb ischemia.
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Many reports about the application of SCS in patients affected by peripheral arterial disease are
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reported in literature.[4-12]
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About the treatment of PLP, SCS has been used since 1969, with the first series being published in
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1975 by Nielson et al.[13] Of the six patients treated through SCS, four patients were felt to have
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excellent outcomes and one patient had a good outcome.
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In 1980, Krainick et al.[14] reported their experience in 61 patients with PLP treated with SCS: one
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patient reported pain relief greater than 75%, 13 had pain relief greater than 50% and 12 greater
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than 25% pain relief while 28 patients did not receive benefit from their SCS.
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In their Italian multicentric study, Broggi et al.[15] treated 26 patients with SCS for PLP: 23
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patients were satisfied with the SCS trial and subsequently received permanent SCS therapy.
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Most recently, Katayama et al.[16] treated with SCS 19 patients suffering from PLP. For this group
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of patients, satisfactory pain control was determined by greater than 80% reduction in their visual
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analog scale. Using this criterion, six of 19 (32%) patients had satisfactory long-term pain control
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with SCS.
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Miles et al.[17] reported their experience about PLP treated by electrical stimulation with excellent
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results in 7 cases and partial relief of pain in 3 cases.
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Viswanathan et al.[18] reported 4 cases of SCS implantation for the treatment of PLP, reporting an
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excellent pain relief (>80%).
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ACCEPTED MANUSCRIPT Our experience differs from the others reported in literature until now, because the SCS therapy was
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proposed not only to obtain pain relief in patients affected by PLP, but also to promote pain control
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on the controlateral lower limb, delaying a more invasive treatment of revascularization. In
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addition, in one case the SCS was adopted as adjuvant therapy, to speed a calcaneal wound healing,
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in presence of a functioning distal bypass.
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CONCLUSIONS
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SCS does not represent a new method for the treatment of PLP and critical lower limb ischemia.
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However, for patients in whom medical management has proven inadequate, SCS is a low-risk
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intervention which can lead to decreased pain, decreased overall symptoms, and improved
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functional outcome. In particular, in patients already submitted to amputation with concomitant
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lower limb critical ischemia on the other side, SCS therapy could represent a valid option to treat
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rest pain, delaying an endovascular or surgical revascularization.
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REFERENCES
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[1] Flor H, Nikolajsen L, Jensen TS. Phantom limb pain: a case of CNS plasticity? Nat Rev
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Neurosci 2006;7:873–881.
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[2] Halbert J, Crotty M, Cameron ID. Evidence for the optimal management of acute and chronic
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phantom pain: a systematic review Clin J Pain 2002;18:84-92.
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[3] Fang J, Lian YH, Xie KJ, et al. Pharmacological interventions for phantom limb pain Chin Med
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J 2013;126:542-549.
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[4] Brümmer U, Condini V, Cappelli P, et al. Spinal cord stimulation in hemodialysis patients with
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critical lower-limb ischemia Am J Kidney Dis 2006 May;47:842-7.
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[5] Petrakis IE, Sciacca V. Spinal cord stimulation in critical limb ischemia of the lower
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extremities: our experience J Neurosurg Sci 1999 Dec;43:285-93.
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ACCEPTED MANUSCRIPT [6] Ubbink DT, Spincemaille GH, Prins MH, et al. Microcirculatory investigations to determine the
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effect of spinal cord stimulation for critical leg ischemia: the Dutch multicenter randomized
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controlled trial J Vasc Surg 1999 Aug;30:236-44.
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[7] De Caridi G, Massara M, David A, et al. Spinal cord stimulation to achieve wound healing in a
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primary lower limb critical ischemia referral center Int Wound J 2014 Apr 8. doi:
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10.1111/iwj.12272.
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[8] Horsch S, Schulte S, Hess S. Spinal cord stimulation in the treatment of peripheral vascular
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disease: results of a single-center study of 258 patients Angiology 2004 Mar-Apr;55:111-18.
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[9] Spincemaille GH, de Vet HC, Ubbink DT, et al. The results of spinal cord stimulation in critical
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limb ischemia: a review Eur J Vasc Endovasc Surg 2001 Feb;21:99-105.
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[10] Amann W, Berg P, Gersbach P, et al. European Peripheral Vascular Disease Outcome Study
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SCS-EPOS. Spinal cord stimulation in the treatment of nonreconstructable stable critical leg
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ischaemia: results of the European Peripheral Vascular Outcome Study (SCS-EPOS) Eur J Vasc
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Endovasc Surg 2003 Sep;26:280-6.
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[11] Ubbink DT, Vermeulen H. Spinal cord stimulation for critical leg ischemia: a review of
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effectiveness and optimal patient selection J Pain Symptom Manage 2006 Apr;31:S30-5.
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[12] De Caridi G, Massara M, Benedetto F, et al. Adjuvant Spinal Cord Stimulation improves
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wound healing of peripheral tissue loss due to a steal syndrome of the hand. Clinical challenge
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treating a difficult case Int Wound J 2014 Feb 17. doi: 10.1111/iwj.12233.
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[13] Nielson KD, Adams JE, Hosobuchi Y. Phantom limb pain: treatment with dorsal column
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stimulation J Neurosurg 1975;42:301–307.
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[14] Krainick JU, Thoden U, Riechert T. Pain reduction in amputees by long-term spinal cord
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stimulation: long term follow-up study over 5 years J Neurosurg 1980;52:346–350.
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[15] Broggi G, Servello D, Dones I, et al. Italian multicenter study on pain treatment with epidural
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spinal cord stimulation Stereotact Funct Neurosurg 1994;62:273–278.
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ACCEPTED MANUSCRIPT [16] Katayama Y, Yamamoto T, Kobayashi K, et al. Motor cortex stimulation for phantom limb
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pain: comprehensive therapy with spinal cord and thalamic stimulation Stereotact Funct Neurosurg
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2001;77:159–162.
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[17] Miles J, Lipton S. Phantom limb pain treated by electrical stimulation Pain 1978 Dec;5:373-82.
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[18] Viswanathan A, Phan PC, Burton AW. Use of spinal cord stimulation in the treatment of
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phantom limb pain: case series and review of the literature Pain Pract 2010 Sep-Oct;10:479-84.
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FIGURE LEGENDS 10
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FIG. 1 Double octopolar leads positioned between T9 and T12
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FIG. 2 Trophic calcaneal lesion
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