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Spinal Cord Stimulation for the Treatment of Vascular Pathology
Spinal Cord Stimulation for t he Tre a t m e n t o f Vas c u l a r Pathology Milind Deogaonkar, MDa, Zion Zibly, MDa, Konstantin V. Slavin, MD, FAANSb,* KEYWORDS Spinal neuromodulation Spinal cord stimulation Peripheral vascular disease Critical limb ischemia Peripheral arterial disease
KEY POINTS Spinal cord stimulation (SCS) in peripheral vascular disease (PVD) treatment can result in significant decrease in pain and improvements in limb salvage. Key patient selection criteria have been defined for SCS for PVD. Mechanisms of action are unknown but likely relate to direct modulation of factors that regulate vascular tone, including nitric oxide and prostaglandin production and sympathetic neuromodulation. Surgical techniques for SCS for PCD do not significantly differ from SCS techniques for pain.
Peripheral vascular disease (PVD) is a common disease mostly involving arteries of the extremities. It usually results from progressive narrowing of arteries in the lower extremities, caused by atherosclerosis.1 PVD prevalence in the United States has ranged as high as 30% in adult populations and is closely associated with elevated risk of cardiovascular disease morbidity and mortality.2,3 It is estimated that by 2020, 7 million people aged older than 40 years will suffer from PVD. Severe limb pain, claudication, ulcerations, and limb amputation are common complications of PVD, especially among patients with kidney disease and diabetes.4,5 The universal treatment approach for PVD includes risk-factor modification, pharmacologic therapy, and revascularization.6 Early in the 1980s, individuals with refractory ischemic pain attributed to PVD were treated with spinal cord stimulation (SCS).7 Since then, multiple studies have shown proved efficacy
of SCS in PVD. Other studies inquired into the pathophysiology and mechanism of action; the changes in tissue oxygenation and blood flow were considered as markers for response. It was also consistently shown that SCS significantly improved multiple outcomes, such as exercise tolerance, limb salvage, and pain level in patients presenting with critical leg ischemia.8 This article describes the role of SCS in the treatment of PVD, the patient selection criteria along with the outcomes, and mechanism by which SCS works in PVD.
REVIEW OF PUBLISHED LITERATURE Electrical stimulation of the posterior column (SCS) was first introduced in the late 1960s. It is thought to be based on the “gate-control” theory of pain described in 1965 by Melzack and Wall.9 It is generally used for the treatment of pain and is currently an established treatment of neurogenic pain. It was not until 1976 when Cook and
a
Department of Neurosurgery, Ohio State University, 480 Medical Center Drive, Columbus, OH 43210, USA; Department of Neurosurgery, University of Illinois, 912 South Wood Street, M/C 799, Chicago, IL 60612, USA * Corresponding author. E-mail address: [email protected] b
Neurosurg Clin N Am - (2013) -–http://dx.doi.org/10.1016/j.nec.2013.08.013 1042-3680/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
neurosurgery.theclinics.com
INTRODUCTION
Deogaonkar et al
2
colleagues10,11 introduced SCS as a therapeutic option for vascular disease of the limbs. Since then, multiple studies were done to prove and assess the efficacy of SCS for the treatment of PVD (Table 1). One of the large prospective, controlled studies was the Spinal Cord Stimulation European Peripheral Vascular Disease Outcome Study. The aim of the study was to evaluate the outcome of SCS on limb survival in individuals with critical leg ischemia. It concluded that SCS provided a significantly better limb survival rate than conservative treatment. In this study, the transcutaneous oxygen pressure (TcPO2), which is associated with high amputation rate, was assessed in 71 patients with PVD. Based on this prospective controlled study, the authors concluded that SCS provided a significantly better limb survival rate than conservative treatment. After a 12-month follow-up, limb survival was 33% higher in the patients treated with SCS. It was also shown that pain was significantly reduced in the SCS-treated group.8 Jivegard and colleagues12 studied 51 patients presenting with atherosclerotic and diabetic limb ischemia. In this prospective, randomized, controlled study that followed patients for 18 months, there was no difference in microcirculation
between the SCS and control groups. Nevertheless, the group of patients treated with SCS had better pain relief and significantly higher rate of limb salvage. In the same study, it was also noted that the most significant benefit from SCS was among those with inoperable limb ischemia and those presenting with arterial hypertension. Tallis and colleagues13 reported a case series of 10 patients presenting with severe, intractable symptoms of arteriographically proved arteriosclerosis and vascular ischemia. Some of the patients also demonstrated nonhealing ulcers and claudication. The authors measured cutaneous blood flow and muscle blood flow (by measuring Xenon 133 clearance). All patients had SCS trial before implantation of a permanent epidural SCS device. In this study all 10 patients showed improvement in mean claudication distance and improvement in the bicycle ergometer tolerance exercise. Most of the patients showed improvement in ischemic limb pain and ulcer healing. After SCS, there was a remarkable increase in the cutaneous blood flow and in the measured muscle blood flow within the group of patients that had positive clinical response to the SCS. Reig and Abejon14 reported their 20 years of experience with 98 SCS implants in patients
Table 1 Summary of SCS studies for the treatment of PVD Author, Year
Patient (N)
SCS Trial
Results
Amann et al, 2003
71
Yes
Reig & Abejon,14 2009
98
N/A
Jivegard et al,12 1995
51
N/A
Brummer et al,15 2006
8
N/A
Ubbink et al,16 1999
120
Yes
Claeys and Horsch,31 1996 Ubbink & Vermeulen,19 2013a Tallis et al,13 1983
86 450
No N/A
10
Yes
Petrakis and Sciacca,32 1999
150
Yes
Horsch et al,18 2004 kumar et al,17 1997
258 39
N/A Yes
significant improvement in limb survival rate, significant reduction of pain Significant reduction of pain, improvement in ischemic symptoms significant improvement in limb survival rate, significant reduction of pain significant improvement in limb survival rate, significant reduction of pain significant improvement in limb survival rate in a specific group of patients Major improvement in stage IV Fontaine significant improvement in limb survival rate, significant reduction of pain Significant reduction of pain, significant improvement of claudication and muscle blood flow Significant reduction of pain, improvement in ischemic symptoms and skin blood flow Significant increase in limb survival Significant reduction of pain, improvement in ischemic symptoms and blood flow
8
a
Review.
SCS in Vascular Pathology presenting with PVD. The authors measured clinical response, relief of pain, and ulcer healing. Almost 88% of the patients showed good clinical response with SCS. In this big retrospective cohort study, the authors concluded that SCS should be a therapeutic approach in treating PVD. Good pain relief was reported in more than 85% of the patients and most patients also reported improvement of their ischemic symptoms. An important study was done among a group of patients with end-stage renal disease by Brummer and colleagues.15 The importance of the study was defined by the fact that these patients were not candidates for limb-preservation surgeries and not considered to benefit from any revascularization procedures. Intensity of ischemic pain, quality of life, use of analgesic medications, limb survival, and outcome of skin ischemic lesions were evaluated before implantation of an SCS and at 6 and 12 months of follow-up. Of the eight patients that were studied, all showed significant improvement in pain, quality of life, limb survival, and absence of new skin ulcer development. This dynamic was most prominent in patients assessed at Fontaine stage III and IV. The Dutch multicenter randomized controlled study followed 120 patients presenting with critical leg ischemia. In this study, Ubbink and colleagues16 investigated the cutaneous microcirculation by means of capillary microscopy, laser Doppler perfusion, and transcutaneous oxygen measurements in the foot. The minimum followup period was 18 months. The authors reported that amputation frequency was higher in those patients with poor microcirculation and lower in those with good skin perfusion. In this important study, it was shown that in the group of patients with intermediate microcirculation SCS provided better chance for limb survival. Kumar and colleagues17 prospectively studied 39 patients with nonreconstructable ischemic vascular lower extremity disease. All patients had a successful SCS trial. The average follow-up was 21 months, and the analyzed parameters included pain control, microcirculatory changes measured by means of TcPO2, blood flow velocities, and pulse volumes. They concluded that SCS provides benefits as measured by TcPO2, blood flow velocities, and pulse volumes and improves microcirculation and macrocirculation. In their retrospective study of 258 patients treated with SCS, Horsch and colleagues18 followed the patients for a period of 18 months. All patients had to meet the following criteria: baseline TcPO2 less than 20 mm Hg, noncandidates for reconstructive surgery, and not treated with any medications for the PVD. The authors concluded
that among the group of patients presenting with a low baseline TcPO2 (<10 mm Hg), limb survival was significantly improved. They also showed that patients treated with SCS had ischemic pain relief and improvement in microcirculation. This study led to a conclusion that baseline TcPO2 could serve as a predictor for SCS treatment outcome. In their critical review of the literature, Ubbink and Vermeulen19 summarized reports of nearly 450 patients in six studies. Based on this, they concluded that limb salvage after 12 months follow-up period was higher within the group of patients that were treated with SCS. Pain relief was also higher in the SCS patient group, and the need for analgesics and other pain relief medications was significantly lower. However, there was no significant statistical difference in ulcer healing.
PROPOSED MECHANISMS OF ACTION The exact mechanism by which SCS acts in the treatment of PVD is not completely understood and several theories have been suggested. Because the SCS is implanted along the posterior epidural space, it stimulates mainly the dorsal columns of the spinal cord. Thus, SCS should stimulate sensory unmyelinated C fibers and myelinated A delta fibers that originate in the dorsal root ganglia.20–26 This, in turn, activates cell signaling cascade that leads to release and activation of different molecules. The end point of this cascade is the release of nitric oxide, which causes vasodilatation, decrease in vascular resistance, and relaxation of the vascular wall (smooth muscles) (Fig. 1). Suppression or modulation of the sympathetic nervous system is also achieved by inhibition of the nicotine transmission at the ganglion and postganglionic junction.21,27,28 In addition, reduction of pain is achieved by release of endogenous opioid-like peptides.29 The exact nature of neurohumoral effects mediated by dorsal root small-diameter afferents or the sympathetic fibers remains unclear. Prostaglandin-mediated vasodilatation caused by antidromic stimulation of dorsal root afferents has been suggested. It has also been suggested that pain relief in itself might relieve vasoconstriction. Speculation has also centered on the release of vasoactive substances with local and possibly systemic effects, including vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide.17 It may be possible that several mechanisms are active simultaneously, with inhibition of autonomically mediated vasoconstriction and activation of vasoactive substances participating in the efficacy of SCS.17,26
3
4
Deogaonkar et al Fig. 1. SCS proposed mechanism of action. AKT, protein kinase B; CGRP, calcitonin gene related protein; ERK, extracellular regulated kinase; NO, nitric oxide.
PATIENT SELECTION The selection of the right candidate for SCS among patients with PVD is based on certain basic criteria succinctly outlined by Kumar and colleagues17 in their study. They are as follows:
12. Patients report substantial pain relief after trial stimulation. 13. Patients have a life expectancy greater than 6 months. 14. Patients are able to give informed consent to the treatment.17
1. End-stage lower limb PVD with pain unresponsive to medical therapy. 2. Severe, nonreconstructable arterial obstruction. This is demonstrated by an ankle/ brachial index that is less than 0.4 (unless arteries were incompressible, as with diabetes), or by a great toe pressure less than 30 mm Hg. 3. Foot ulcers, if present, must be less than 2 cm in diameter and may not extend deep into the dermis. 4. Gangrene, if present, must be dry and must satisfy the ulcer conditions stated previously. 5. Patients with significant heart failure, pulmonary or renal insufficiency, or unstable angina are excluded. 6. A demonstrable pathology accounted for the pain. 7. Conservative therapies have failed or are contraindicated. 8. Untreated drug addiction problems do not exist. 9. Psychological assessment does not identify major barriers to treatment success. 10. Patients are motivated sufficiently to understand and cooperate with instructions on the use of the device and its adjustment, and are able to return for regular follow-up visits. 11. Patients are able to detect paresthesia in the painful area during the trial implantation screening period.
Some authors advocate not to perform an SCS trial because of a lack of objective response measures and also to reduce the risk of infection.12,30 Currently, it is considered a standard to treat patients with PVD with SCS based on their microcirculatory parameters. This has been shown to help with pain reduction, halt ulcer progression, and improve the chances of limb salvage. At present, patients are considered to be candidates for SCS if they are unable to have open or endovascular surgical procedures. Thus, this group includes patients with isolated resting limb pain (Fontaine stage III), and those with resting limb pain together with ulcers that are less than 3 cm in diameter (Fontaine IV). In addition, among the SCS candidates are those patients who had an unsuccessful revascularization and continue to present with limb pain or ischemia. The Dutch multicenter randomized controlled study, for example, showed that only patients who present with critical leg ischemia and intermediate cutaneous microcirculation could benefit from SCS treatment.16 Claeys and Horsch31 carried out a randomized controlled study where 81 Fontaine stage IV patients with end-stage PVD treated with prostaglandins were treated with SCS. After a 12-month follow-up the authors concluded that SCS provides a significant benefit for Fontaine stage IV patients especially if the initial TcPO2 is higher than
SCS in Vascular Pathology 10 mm Hg, making a case for this value to be considered as a parameter for patient selection. To decide whether the TcPO2 could serve as a prognostic parameter for SCS permanent implantation, Petrakis and Sciacca32 studied 150 patients with Fontaine stages III and IV. After a mean follow-up period of 71 months, SCS proved to improve skin blood flow and significantly reduce pain. They also concluded that TcPO2 increase after a 2-week SCS trial period is a good predictive index for subsequent successful treatment with permanent SCS. Kumar and coworkers17 suggested that trial stimulation parameters of excellent pain relief combined with an increase in TcPO2 of 10 mm Hg or greater, and an increase in peak flow velocity of 10 mm/s or more, give significant predilection for long-term success of SCS in the treatment of critical limb ischemia.
SURGICAL TECHNIQUE Standard surgical technique of SCS for chronic pain is described in various published articles. The same technique is used while implanting SCS for PVD. There are, however, some differences in SCS for PVD compared with SCS for chronic pain. 1. Need of trial: Some studies have done a preimplant trial17 but most studies do not comment on a preimplant trial. Rationale for skipping the trial is likely an inability to see clinical improvement in PVD during a short trial period. 2. Type of electrodes: Although very few studies comment on type of electrodes used for SCS, those who commented have used paddle lead implants more often. Nevertheless, the experience of the authors and personal communication with implanters worldwide suggest that percutaneous electrodes dominate in this surgical indication. 3. Placement of electrodes: All the SCS electrodes were placed in the dorsal epidural space with very few studies mentioning the exact location of the electrode contacts along the craniocaudal axis.
COMPLICATIONS The estimated overall complication rate is 17% and includes hardware failure (lead migration, generator failure) and infection at the epidural lead site or generator site.19 Based on metaanalysis of six studies comprising 450 patients that were treated with SCS for PVD, Ubbink and Vermeulen19 reported that the risk of infection of the lead or generator pocket is less than 3%.
The biggest study that examined the occurrence of SCS complications for all indications was done by Babu and colleagues.33 In their comparative analysis of 13,774 patients who were implanted with either percutaneous or paddle lead SCS the authors reported that SCS paddle leads had higher chance of complication than percutaneous leads at 90 days after surgery, but after 2 years the percutaneous group had a higher rate of reoperations.33,34 Kinfe and colleagues35 reported in their series of 81 patients with SCS implantation for the treatment of pain a 2.5% risk of lead migration, which clearly represents another kind of a surgical complication. Other complications that are possible with SCS are cerebrospinal fluid leak and hypotensive headache, and spinal cord injury. The assumed risk of all these complications is below 3%, and depends on surgeon experience.
SUMMARY Although there have been no masked studies to evaluate the benefit of SCS in the treatment of critical limb ischemia and end-stage PVD, there is plenty of evidence that supports its efficacy. It is clear that SCS, when done by an experienced functional neurosurgeon, is safe and effective. It is important to have clear criteria for patient selection and to understand that all patients should be therapeutically refractory (medication and revascularization) to qualify for SCS. It is safe to conclude that SCS improves limb survival in patients with critical limb ischemia, gives significant pain control, improves blood circulation, and improves patients’ quality of life by improving claudication.
REFERENCES 1. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation 2004;110: 738–43. 2. Newman AB, Shemanski L, Manolio TA, et al. Anklearm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group. Arterioscler Thromb Vasc Biol 1999;19:538–45. 3. Murabito JM, Evans JC, Nieto K, et al. Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. Am Heart J 2002;143:961–5. 4. Creager MA, Luscher TF, Cosentino F, et al. Diabetes and vascular disease: pathophysiology,
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clinical consequences, and medical therapy: part I. Circulation 2003;108:1527–32. Luscher TF, Creager MA, Beckman JA, et al. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Circulation 2003;108:1655–61. White C. Clinical practice. Intermittent claudication. N Engl J Med 2007;356:1241–50. De Vries J, De Jongste MJ, Spincemaille G, et al. Spinal cord stimulation for ischemic heart disease and peripheral vascular disease. Adv Tech Stand Neurosurg 2007;32:63–89. Amann W, Berg P, Gersbach P, et al. Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischaemia: results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS). Eur J Vasc Endovasc Surg 2003;26: 280–6. Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971–9. Cook AW. Epidural stimulation for vascular disease of extremities. J Neurosurg 1981;55:664. Cook AW, Oygar A, Baggenstos P, et al. Vascular disease of extremities. Electric stimulation of spinal cord and posterior roots. N Y State J Med 1976;76: 366–8. Jivegard LE, Augustinsson LE, Holm J, et al. Effects of spinal cord stimulation (SCS) in patients with inoperable severe lower limb ischaemia: a prospective randomised controlled study. Eur J Vasc Endovasc Surg 1995;9:421–5. Tallis RC, Illis LS, Sedgwick EM, et al. Spinal cord stimulation in peripheral vascular disease. J Neurol Neurosurg Psychiatry 1983;46:478–84. Reig E, Abejon D. Spinal cord stimulation: a 20-year retrospective analysis in 260 patients. Neuromodulation 2009;12:232–9. Brummer U, Condini V, Cappelli P, et al. Spinal cord stimulation in hemodialysis patients with critical lower-limb ischemia. Am J Kidney Dis 2006;47: 842–7. Ubbink DT, Spincemaille GH, Prins MH, et al. Microcirculatory investigations to determine the effect of spinal cord stimulation for critical leg ischemia: the Dutch multicenter randomized controlled trial. J Vasc Surg 1999;30:236–44. Kumar K, Toth C, Nath RK, et al. Improvement of limb circulation in peripheral vascular disease using epidural spinal cord stimulation: a prospective study. J Neurosurg 1997;86:662–9. Horsch S, Schulte S, Hess S. Spinal cord stimulation in the treatment of peripheral vascular disease: results of a single-center study of 258 patients. Angiology 2004;55:111–8. Ubbink DT, Vermeulen H. Spinal cord stimulation for non-reconstructable chronic critical leg ischaemia. Cochrane Database Syst Rev 2013;(2):CD004001.
20. Naoum JJ, Arbid EJ. Spinal cord stimulation for chronic limb ischemia. Methodist Debakey Cardiovasc J 2013;9:99–102. 21. Pedrini L, Magnoni F. Spinal cord stimulation for lower limb ischemic pain treatment. Interact Cardiovasc Thorac Surg 2007;6:495–500. 22. Tanaka S, Komori N, Barron KW, et al. Mechanisms of sustained cutaneous vasodilation induced by spinal cord stimulation. Auton Neurosci 2004;114:55–60. 23. Tanaka S, Barron KW, Chandler MJ, et al. Local cooling alters neural mechanisms producing changes in peripheral blood flow by spinal cord stimulation. Auton Neurosci 2003;104:117–27. 24. Tanaka S, Barron KW, Chandler MJ, et al. Role of primary afferents in spinal cord stimulation-induced vasodilation: characterization of fiber types. Brain Res 2003;959:191–8. 25. Provenzano DA, Nicholson L, Jarzabek G, et al. Spinal cord stimulation utilization to treat the microcirculatory vascular insufficiency and ulcers associated with scleroderma: a case report and review of the literature. Pain Med 2011;12:1331–5. 26. Provenzano DA, Jarzabek G, Georgevich P. The utilization of transcutaneous oxygen pressures to guide decision-making for spinal cord stimulation implantation for inoperable peripheral vascular disease: a report of two cases. Pain Physician 2008; 11:909–16. 27. Deer TR, Raso LJ. Spinal cord stimulation for refractory angina pectoris and peripheral vascular disease. Pain Physician 2006;9:347–52. 28. Reig E, Abejon D, del Pozo C, et al. Spinal cord stimulation in peripheral vascular disease: a retrospective analysis of 95 cases. Pain Pract 2001;1:324–31. 29. Wu M, Linderoth B, Foreman RD. Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: a review of experimental studies. Auton Neurosci 2008;138:9–23. 30. Klomp HM, Spincemaille GH, Steyerberg EW, et al. Spinal-cord stimulation in critical limb ischaemia: a randomised trial. ESES Study Group. Lancet 1999; 353:1040–4. 31. Claeys LG, Horsch S. Transcutaneous oxygen pressure as predictive parameter for ulcer healing in endstage vascular patients treated with spinal cord stimulation. Int Angiol 1996;15:344–9. 32. Petrakis E, Sciacca V. Prospective study of transcutaneous oxygen tension (TcPO2) measurement in the testing period of spinal cord stimulation in diabetic patients with critical lower limb ischaemia. Int Angiol 2000;19:18–25. 33. Babu R, Hazzard MA, Huang KT, et al. Outcomes of percutaneous and paddle lead implantation for spinal cord stimulation: a comparative analysis of complications, reoperation rates, and health-care costs. Neuromodulation 2013. http://dx.doi.org/10.1111/ ner.12065.
SCS in Vascular Pathology 34. Huang KT, Hazzard MA, Babu R, et al. Insurance disparities in the outcomes of spinal cord stimulation surgery. Neuromodulation 2013. http://dx.doi.org/ 10.1111/ner.12059.
35. Kinfe TM, Schu S, Quack FJ, et al. Percutaneous implanted paddle lead for spinal cord stimulation: technical considerations and long-term follow-up. Neuromodulation 2012;15:402–7.
7
KEY POINTS Spinal cord stimulation (SCS) in peripheral vascular disease (PVD) treatment can result in significant decrease in pain and improvements in limb salvage. Key patient selection criteria have been defined for SCS for PVD. Mechanisms of action are unknown but likely relate to direct modulation of factors that regulate vascular tone, including nitric oxide and prostaglandin production and sympathetic neuromodulation. Surgical techniques for SCS for PCD do not significantly differ from SCS techniques for pain.
Peripheral vascular disease (PVD) is a common disease mostly involving arteries of the extremities. It usually results from progressive narrowing of arteries in the lower extremities, caused by atherosclerosis.1 PVD prevalence in the United States has ranged as high as 30% in adult populations and is closely associated with elevated risk of cardiovascular disease morbidity and mortality.2,3 It is estimated that by 2020, 7 million people aged older than 40 years will suffer from PVD. Severe limb pain, claudication, ulcerations, and limb amputation are common complications of PVD, especially among patients with kidney disease and diabetes.4,5 The universal treatment approach for PVD includes risk-factor modification, pharmacologic therapy, and revascularization.6 Early in the 1980s, individuals with refractory ischemic pain attributed to PVD were treated with spinal cord stimulation (SCS).7 Since then, multiple studies have shown proved efficacy
of SCS in PVD. Other studies inquired into the pathophysiology and mechanism of action; the changes in tissue oxygenation and blood flow were considered as markers for response. It was also consistently shown that SCS significantly improved multiple outcomes, such as exercise tolerance, limb salvage, and pain level in patients presenting with critical leg ischemia.8 This article describes the role of SCS in the treatment of PVD, the patient selection criteria along with the outcomes, and mechanism by which SCS works in PVD.
REVIEW OF PUBLISHED LITERATURE Electrical stimulation of the posterior column (SCS) was first introduced in the late 1960s. It is thought to be based on the “gate-control” theory of pain described in 1965 by Melzack and Wall.9 It is generally used for the treatment of pain and is currently an established treatment of neurogenic pain. It was not until 1976 when Cook and
a
Department of Neurosurgery, Ohio State University, 480 Medical Center Drive, Columbus, OH 43210, USA; Department of Neurosurgery, University of Illinois, 912 South Wood Street, M/C 799, Chicago, IL 60612, USA * Corresponding author. E-mail address: [email protected] b
Neurosurg Clin N Am - (2013) -–http://dx.doi.org/10.1016/j.nec.2013.08.013 1042-3680/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
neurosurgery.theclinics.com
INTRODUCTION
Deogaonkar et al
2
colleagues10,11 introduced SCS as a therapeutic option for vascular disease of the limbs. Since then, multiple studies were done to prove and assess the efficacy of SCS for the treatment of PVD (Table 1). One of the large prospective, controlled studies was the Spinal Cord Stimulation European Peripheral Vascular Disease Outcome Study. The aim of the study was to evaluate the outcome of SCS on limb survival in individuals with critical leg ischemia. It concluded that SCS provided a significantly better limb survival rate than conservative treatment. In this study, the transcutaneous oxygen pressure (TcPO2), which is associated with high amputation rate, was assessed in 71 patients with PVD. Based on this prospective controlled study, the authors concluded that SCS provided a significantly better limb survival rate than conservative treatment. After a 12-month follow-up, limb survival was 33% higher in the patients treated with SCS. It was also shown that pain was significantly reduced in the SCS-treated group.8 Jivegard and colleagues12 studied 51 patients presenting with atherosclerotic and diabetic limb ischemia. In this prospective, randomized, controlled study that followed patients for 18 months, there was no difference in microcirculation
between the SCS and control groups. Nevertheless, the group of patients treated with SCS had better pain relief and significantly higher rate of limb salvage. In the same study, it was also noted that the most significant benefit from SCS was among those with inoperable limb ischemia and those presenting with arterial hypertension. Tallis and colleagues13 reported a case series of 10 patients presenting with severe, intractable symptoms of arteriographically proved arteriosclerosis and vascular ischemia. Some of the patients also demonstrated nonhealing ulcers and claudication. The authors measured cutaneous blood flow and muscle blood flow (by measuring Xenon 133 clearance). All patients had SCS trial before implantation of a permanent epidural SCS device. In this study all 10 patients showed improvement in mean claudication distance and improvement in the bicycle ergometer tolerance exercise. Most of the patients showed improvement in ischemic limb pain and ulcer healing. After SCS, there was a remarkable increase in the cutaneous blood flow and in the measured muscle blood flow within the group of patients that had positive clinical response to the SCS. Reig and Abejon14 reported their 20 years of experience with 98 SCS implants in patients
Table 1 Summary of SCS studies for the treatment of PVD Author, Year
Patient (N)
SCS Trial
Results
Amann et al, 2003
71
Yes
Reig & Abejon,14 2009
98
N/A
Jivegard et al,12 1995
51
N/A
Brummer et al,15 2006
8
N/A
Ubbink et al,16 1999
120
Yes
Claeys and Horsch,31 1996 Ubbink & Vermeulen,19 2013a Tallis et al,13 1983
86 450
No N/A
10
Yes
Petrakis and Sciacca,32 1999
150
Yes
Horsch et al,18 2004 kumar et al,17 1997
258 39
N/A Yes
significant improvement in limb survival rate, significant reduction of pain Significant reduction of pain, improvement in ischemic symptoms significant improvement in limb survival rate, significant reduction of pain significant improvement in limb survival rate, significant reduction of pain significant improvement in limb survival rate in a specific group of patients Major improvement in stage IV Fontaine significant improvement in limb survival rate, significant reduction of pain Significant reduction of pain, significant improvement of claudication and muscle blood flow Significant reduction of pain, improvement in ischemic symptoms and skin blood flow Significant increase in limb survival Significant reduction of pain, improvement in ischemic symptoms and blood flow
8
a
Review.
SCS in Vascular Pathology presenting with PVD. The authors measured clinical response, relief of pain, and ulcer healing. Almost 88% of the patients showed good clinical response with SCS. In this big retrospective cohort study, the authors concluded that SCS should be a therapeutic approach in treating PVD. Good pain relief was reported in more than 85% of the patients and most patients also reported improvement of their ischemic symptoms. An important study was done among a group of patients with end-stage renal disease by Brummer and colleagues.15 The importance of the study was defined by the fact that these patients were not candidates for limb-preservation surgeries and not considered to benefit from any revascularization procedures. Intensity of ischemic pain, quality of life, use of analgesic medications, limb survival, and outcome of skin ischemic lesions were evaluated before implantation of an SCS and at 6 and 12 months of follow-up. Of the eight patients that were studied, all showed significant improvement in pain, quality of life, limb survival, and absence of new skin ulcer development. This dynamic was most prominent in patients assessed at Fontaine stage III and IV. The Dutch multicenter randomized controlled study followed 120 patients presenting with critical leg ischemia. In this study, Ubbink and colleagues16 investigated the cutaneous microcirculation by means of capillary microscopy, laser Doppler perfusion, and transcutaneous oxygen measurements in the foot. The minimum followup period was 18 months. The authors reported that amputation frequency was higher in those patients with poor microcirculation and lower in those with good skin perfusion. In this important study, it was shown that in the group of patients with intermediate microcirculation SCS provided better chance for limb survival. Kumar and colleagues17 prospectively studied 39 patients with nonreconstructable ischemic vascular lower extremity disease. All patients had a successful SCS trial. The average follow-up was 21 months, and the analyzed parameters included pain control, microcirculatory changes measured by means of TcPO2, blood flow velocities, and pulse volumes. They concluded that SCS provides benefits as measured by TcPO2, blood flow velocities, and pulse volumes and improves microcirculation and macrocirculation. In their retrospective study of 258 patients treated with SCS, Horsch and colleagues18 followed the patients for a period of 18 months. All patients had to meet the following criteria: baseline TcPO2 less than 20 mm Hg, noncandidates for reconstructive surgery, and not treated with any medications for the PVD. The authors concluded
that among the group of patients presenting with a low baseline TcPO2 (<10 mm Hg), limb survival was significantly improved. They also showed that patients treated with SCS had ischemic pain relief and improvement in microcirculation. This study led to a conclusion that baseline TcPO2 could serve as a predictor for SCS treatment outcome. In their critical review of the literature, Ubbink and Vermeulen19 summarized reports of nearly 450 patients in six studies. Based on this, they concluded that limb salvage after 12 months follow-up period was higher within the group of patients that were treated with SCS. Pain relief was also higher in the SCS patient group, and the need for analgesics and other pain relief medications was significantly lower. However, there was no significant statistical difference in ulcer healing.
PROPOSED MECHANISMS OF ACTION The exact mechanism by which SCS acts in the treatment of PVD is not completely understood and several theories have been suggested. Because the SCS is implanted along the posterior epidural space, it stimulates mainly the dorsal columns of the spinal cord. Thus, SCS should stimulate sensory unmyelinated C fibers and myelinated A delta fibers that originate in the dorsal root ganglia.20–26 This, in turn, activates cell signaling cascade that leads to release and activation of different molecules. The end point of this cascade is the release of nitric oxide, which causes vasodilatation, decrease in vascular resistance, and relaxation of the vascular wall (smooth muscles) (Fig. 1). Suppression or modulation of the sympathetic nervous system is also achieved by inhibition of the nicotine transmission at the ganglion and postganglionic junction.21,27,28 In addition, reduction of pain is achieved by release of endogenous opioid-like peptides.29 The exact nature of neurohumoral effects mediated by dorsal root small-diameter afferents or the sympathetic fibers remains unclear. Prostaglandin-mediated vasodilatation caused by antidromic stimulation of dorsal root afferents has been suggested. It has also been suggested that pain relief in itself might relieve vasoconstriction. Speculation has also centered on the release of vasoactive substances with local and possibly systemic effects, including vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide.17 It may be possible that several mechanisms are active simultaneously, with inhibition of autonomically mediated vasoconstriction and activation of vasoactive substances participating in the efficacy of SCS.17,26
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Deogaonkar et al Fig. 1. SCS proposed mechanism of action. AKT, protein kinase B; CGRP, calcitonin gene related protein; ERK, extracellular regulated kinase; NO, nitric oxide.
PATIENT SELECTION The selection of the right candidate for SCS among patients with PVD is based on certain basic criteria succinctly outlined by Kumar and colleagues17 in their study. They are as follows:
12. Patients report substantial pain relief after trial stimulation. 13. Patients have a life expectancy greater than 6 months. 14. Patients are able to give informed consent to the treatment.17
1. End-stage lower limb PVD with pain unresponsive to medical therapy. 2. Severe, nonreconstructable arterial obstruction. This is demonstrated by an ankle/ brachial index that is less than 0.4 (unless arteries were incompressible, as with diabetes), or by a great toe pressure less than 30 mm Hg. 3. Foot ulcers, if present, must be less than 2 cm in diameter and may not extend deep into the dermis. 4. Gangrene, if present, must be dry and must satisfy the ulcer conditions stated previously. 5. Patients with significant heart failure, pulmonary or renal insufficiency, or unstable angina are excluded. 6. A demonstrable pathology accounted for the pain. 7. Conservative therapies have failed or are contraindicated. 8. Untreated drug addiction problems do not exist. 9. Psychological assessment does not identify major barriers to treatment success. 10. Patients are motivated sufficiently to understand and cooperate with instructions on the use of the device and its adjustment, and are able to return for regular follow-up visits. 11. Patients are able to detect paresthesia in the painful area during the trial implantation screening period.
Some authors advocate not to perform an SCS trial because of a lack of objective response measures and also to reduce the risk of infection.12,30 Currently, it is considered a standard to treat patients with PVD with SCS based on their microcirculatory parameters. This has been shown to help with pain reduction, halt ulcer progression, and improve the chances of limb salvage. At present, patients are considered to be candidates for SCS if they are unable to have open or endovascular surgical procedures. Thus, this group includes patients with isolated resting limb pain (Fontaine stage III), and those with resting limb pain together with ulcers that are less than 3 cm in diameter (Fontaine IV). In addition, among the SCS candidates are those patients who had an unsuccessful revascularization and continue to present with limb pain or ischemia. The Dutch multicenter randomized controlled study, for example, showed that only patients who present with critical leg ischemia and intermediate cutaneous microcirculation could benefit from SCS treatment.16 Claeys and Horsch31 carried out a randomized controlled study where 81 Fontaine stage IV patients with end-stage PVD treated with prostaglandins were treated with SCS. After a 12-month follow-up the authors concluded that SCS provides a significant benefit for Fontaine stage IV patients especially if the initial TcPO2 is higher than
SCS in Vascular Pathology 10 mm Hg, making a case for this value to be considered as a parameter for patient selection. To decide whether the TcPO2 could serve as a prognostic parameter for SCS permanent implantation, Petrakis and Sciacca32 studied 150 patients with Fontaine stages III and IV. After a mean follow-up period of 71 months, SCS proved to improve skin blood flow and significantly reduce pain. They also concluded that TcPO2 increase after a 2-week SCS trial period is a good predictive index for subsequent successful treatment with permanent SCS. Kumar and coworkers17 suggested that trial stimulation parameters of excellent pain relief combined with an increase in TcPO2 of 10 mm Hg or greater, and an increase in peak flow velocity of 10 mm/s or more, give significant predilection for long-term success of SCS in the treatment of critical limb ischemia.
SURGICAL TECHNIQUE Standard surgical technique of SCS for chronic pain is described in various published articles. The same technique is used while implanting SCS for PVD. There are, however, some differences in SCS for PVD compared with SCS for chronic pain. 1. Need of trial: Some studies have done a preimplant trial17 but most studies do not comment on a preimplant trial. Rationale for skipping the trial is likely an inability to see clinical improvement in PVD during a short trial period. 2. Type of electrodes: Although very few studies comment on type of electrodes used for SCS, those who commented have used paddle lead implants more often. Nevertheless, the experience of the authors and personal communication with implanters worldwide suggest that percutaneous electrodes dominate in this surgical indication. 3. Placement of electrodes: All the SCS electrodes were placed in the dorsal epidural space with very few studies mentioning the exact location of the electrode contacts along the craniocaudal axis.
COMPLICATIONS The estimated overall complication rate is 17% and includes hardware failure (lead migration, generator failure) and infection at the epidural lead site or generator site.19 Based on metaanalysis of six studies comprising 450 patients that were treated with SCS for PVD, Ubbink and Vermeulen19 reported that the risk of infection of the lead or generator pocket is less than 3%.
The biggest study that examined the occurrence of SCS complications for all indications was done by Babu and colleagues.33 In their comparative analysis of 13,774 patients who were implanted with either percutaneous or paddle lead SCS the authors reported that SCS paddle leads had higher chance of complication than percutaneous leads at 90 days after surgery, but after 2 years the percutaneous group had a higher rate of reoperations.33,34 Kinfe and colleagues35 reported in their series of 81 patients with SCS implantation for the treatment of pain a 2.5% risk of lead migration, which clearly represents another kind of a surgical complication. Other complications that are possible with SCS are cerebrospinal fluid leak and hypotensive headache, and spinal cord injury. The assumed risk of all these complications is below 3%, and depends on surgeon experience.
SUMMARY Although there have been no masked studies to evaluate the benefit of SCS in the treatment of critical limb ischemia and end-stage PVD, there is plenty of evidence that supports its efficacy. It is clear that SCS, when done by an experienced functional neurosurgeon, is safe and effective. It is important to have clear criteria for patient selection and to understand that all patients should be therapeutically refractory (medication and revascularization) to qualify for SCS. It is safe to conclude that SCS improves limb survival in patients with critical limb ischemia, gives significant pain control, improves blood circulation, and improves patients’ quality of life by improving claudication.
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