Spinal Cord Stimulation for Peripheral Vascular Disorders

Introduction

Peripheral arterial disease (PAD) includes a diverse group of disorders that lead to progressive stenosis or occlusion of the aorta and its noncoronary branch arteries, including the carotid, upper-extremity, visceral, and lower-extremity arteries. The most common cause of lower extremity PAD worldwide is atherosclerosis and thus the epidemiology and clinical consequences of PAD are closely associated with classic atherosclerosis risk factors (e.g., smoking, diabetes mellitus, hypertension, dyslipidemia, and family history).

The prevalence of lower extremity PAD has been defined by a series of epidemiological investigations that have used either claudication as a symptomatic marker of PAD or an abnormal ankle-to-brachial systolic blood pressure to define the population affected, which is in the range of 3%–10% in people younger than 60 years. The prevalence increases to 15%–20% in persons older than 70 years ( ).

The prognosis of the affected limb is determined by the extent of the arterial disease, the acuity of limb ischemia, and the feasibility and rapidity of restoring arterial circulation to the foot. For the patient with chronic peripheral arterial occlusive disease and continued progression of symptoms to critical limb ischemia (CLI) (e.g., development of ulcer, rest pain, or gangrene), the prognosis is very poor unless revascularization is established.

The management of patients with PAD is often challenging due to the fact that the therapy has to be planned, not only in the context of the natural history and epidemiology of the disease (including risk factors and markers predicting spontaneous deterioration), but also in the context of its high comorbidity and mortality rates. Despite ongoing progress in revascularization procedures such as distal bypasses and increasingly complex endovascular procedures, the fate of patients with CLI is still poor. It is estimated that 10%–30% of the patients with CLI will die within 6 months of its onset and another 25%–35% will undergo major amputation ( ).

Revascularization (surgical or percutaneous restoration of blood flow to the affected organ/limb) is the therapy of choice in patients with chronic CLI. The aim of these procedures is to relieve ischemic rest pain, to heal ischemic ulcers and to avoid major amputation ( ). Nevertheless, although technical advances in vascular and endovascular surgery may have resulted in a decrease of amputation rates, there remain patients in whom repeated vascular reconstructions do not have a realistic chance of success. In these patients, ischemic pain is often disabling, adversely affecting their quality of life (QOL) and severely limiting their activity level, and this, in turn, hinders treatment of their underlying disease. Such patients are at a high risk for amputation.

History of Electrical Stimulation for Peripheral Arterial Disease

In , Cook and Weinstein were the first to describe a significant increase in regional blood flow of the lower extremities in patients with multiple sclerosis treated by spinal cord stimulation (SCS) for limb pain and spasm. Three years later, this same group was the first to treat the ischemic pain of peripheral vascular disease (PVD) with SCS. They reported a significant relief of pain of the stimulated limbs, increased blood flow and skin temperature, and, moreover, a sustained healing of ischemic ulcers in nine patients with PAD. They postulated that SCS might slow or delay amputation of ischemic limbs and suggested further investigation ( ). In the ensuing years, other authors concordantly drew the same conclusions regarding the effects of SCS in PAD. SCS provides good pain relief in 60%–80% of patients, provides an improvement in claudication distance, and provides an improvement in activities of daily living (ADLs) ( ).

These apparent benefits of SCS in patients with PAD have been attributed to improvement of the microcirculation in the affected limb. In several studies, the status of the microcirculation was obtained using different variables such as capillary blood flow, capillary density ( ), skin temperature, transcutaneous oxygen tension (TcpO ₂ ), and laser Doppler flowmetry ( ), measured on the dorsum of the foot. Most of these studies were clinical retrospective data collections and only a few were randomized or controlled. For a long time, the overall effects on limb salvage and other endpoints for SCS were not sufficiently established.

During the 1990s, the first randomized controlled studies were conducted comparing the results of SCS treatment to the results of “optimal medical management” (see Table 105.1 ). The “Swedish prospective randomized controlled study” published by tested the hypothesis that SCS improves limb salvage in patients with non-reconstructible CLI. During a 5-year period, 51 patients, including 10 patients with diabetes having ischemic rest pain and/or ulcerations, were randomized to either SCS plus per-oral analgesic treatment (n = 25) or per-oral analgesic treatment alone (n = 26). The endpoints for this study were pain relief, tissue loss, and limb salvage. Long-term pain relief occurred only in the group treated with SCS and tissue loss was less. Limb salvage after 18 and 60 months tended to be higher in the SCS than in the control group (62% vs. 45% and 51% vs. 35%, respectively) ( ). The randomized controlled multicenter trial in Belgium included 38 patients with severe limb ischemia unsuitable for surgery ( ). All patients received optimal medical treatment consisting of platelet antiaggregation therapy, rheological therapy (to improve flow characteristics), and analgesic medication. Twenty patients were randomized to receive additional SCS treatment. There were no significant differences regarding forefoot salvage during the 24 months of study in either group. However, when evaluating “clinical success,” defined as pain relief, ability to walk, and QOL, life-table analysis did show a significantly better result in favor of the SCS group ( ). In a study by , 86 inoperable patients with ischemic ulcers, including 13 patients with diabetes, were randomized into two groups receiving intravenous prostaglandin E ₁ (PGE ₁ ), with or without adjunctive SCS treatment. Ulcer healing occurred significantly more in the SCS group (69%) when compared to the PGE ₁ group (17%). Pain relief was also more frequently seen in the group with the additional SCS treatment (40% vs. 10%). There was, however, no difference in major amputation frequency when comparing the two groups (15% vs. 20%). After a follow-up of 12 months, TcpO ₂ values increased significantly in the group treated with PGE ₁ and SCS. A TcpO ₂ increase above 26 mmHg correlated with ulcer healing, whereas a TcpO ₂ less than or equal to 10 mmHg predicted poor outcome ( ).

The Dutch randomized controlled multicenter trial studying SCS, enrolled 120 patients with nonreconstructible chronic CLI ( ). Treatment strategies in this study included optimal medical treatment versus optimal medical treatment plus SCS. The primary endpoints of the study were limb salvage, pain relief, QOL, and cost-effectiveness. The secondary endpoints of the study included healing of ischemic lesions, level of amputation, effects on the macro- and microcirculation, and complications of the therapies. An additional strategy of this study was the evaluation of the prognostic value of microcirculatory data. A 2-year follow up revealed significant pain relief, but no differences in limb salvage. A subgroup analysis, dividing the patients according to their microcirculatory status, showed better results in a group of patients with an “intermediate” microcirculatory function ( ).

The results of the randomized studies are summarized in Table 105.1 .

Table 105.1

Results of Reported Randomized Controlled Trials (RCT)

Authors and Treatment	Patients (Control vs. Spinal Cord Stimulation (SCS)-Treated) [Fontaine Stage]	Follow-Up (mth)	Pain Relief at Follow-Up (Control vs. SCS-Treated)	Limb Salvage at Follow-Up (Control vs. SCS-Treated)
	n = 26 vs. 25 [14 vs. 15 stage IV]	18	Significant reduction of VAS only in SCS-treated group (6–12 months)	45% vs. 62% (n.s.)
Peroral analgesic vs. SCS + peroral analgesic treatment	n = 26 vs. 25 [14 vs. 15 stage IV]	18		45% vs. 62% (n.s.)
	n = 18 vs. 20 [13 vs. 13 stage IV]	20	28% vs. 70% painlessness	n.s.
Medical treatment vs. SCS + medical treatment	n = 18 vs. 20 [13 vs. 13 stage IV]	20	28% vs. 70% painlessness	n.s.
	n = 41 vs. 45 [41 vs. 45 stage IV]	12	10% vs. 40% achieved outcome of stage II (no rest pain, no ulcers)	65% vs. 68% (n.s.)
PGE ₁ vs. SCS + PGE ₁	n = 41 vs. 45 [41 vs. 45 stage IV]	12		65% vs. 68% (n.s.)
	n = 18 vs. 19 [14 vs. 14 stage IV]	24	Significant pain relief in the SCS group	39% vs. 61% (n.s.)
BMT vs. SCS + BMT	n = 18 vs. 19 [14 vs. 14 stage IV]	24	Significant pain relief in the SCS group	39% vs. 61% (n.s.)
, ESES Study BMT vs. SCS + BMT	n = 60 vs. 60 [41 vs. 38 stage IV]	18	Difference of pain reduction between control and SCS group not significant, but significant less pain medication in SCS group	24% vs. 48% (significant increase in limb salvage in patients' subgroup with “intermediate” skin microcirculation and SCS)
, SCS–EPOS Study BMT vs. SCS + BMT	n = 39 vs. 32 (SCS No-Match) + 41 (SCS Match ^a ) [14 vs. 17 (23 ^a ) stage IV]	18	Significant improvement in pain relief ( P < .005) in the SCS Match ^a group	45% vs. 55% (SCS No-Match) + 78% (SCS Match ^a ) at 12 months (significant increase in limb salvage in the SCS Match group)

BMT , best medical treatment: analgesics, anticoagulants, vasoactive agents, local wound care, and antibiotics if indicated; PGE ₁ , prostaglandin E1 therapy; EPOS , European Peripheral Vascular Disease Outcome Study; ESES , Epidural Spinal Cord Electrical Stimulation; VAS , Visual Analogue Scale.

a SCS-match group: defined as patients with a baseline forefoot TcpO ₂ of >30 mmHg and both sufficient pain relief and sufficient paresthesia coverage (>75%) after a test stimulation period of at least 72 h.

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