Neurostimulation has been used for over 30 years to treat several chronic pain syndromes that are intractable to other treatment modalities.[1] The term encompasses a variety of techniques, including transcutaneous electrical nerve stimulation (TENS), peripheral nerve stimulation (PNS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and cortical stimulation.[1] This update concentrates on the most recent developments in SCS and PNS. SCS and PNS have experienced a resurgence in popularity because of their status as reversible treatments for chronic pain, with no addiction issues or systemic side effects.[2] Careful patient selection, sufficient preimplantation trials, and recent innovations in the design of the implanted devices have allowed the more effective use of these techniques.
In neurostimulation, precise targeted electrical stimulation is applied to nociceptive pathways, both inside and outside the central nervous system (CNS). In the CNS, there are nociceptive pathways in the spinal cord and brain, specifically the dorsal roots, dorsal ganglion, dorsal horn, spinothalamic tracts, and all ascending neural tracts to the cerebrum. The peripheral nervous system includes pathways outside the spinal cord, specifically various plexuses and peripheral nerves.
There is a long tradition of using electricity to relieve pain, but there was little understanding of the exact mechanism or physiological effect. Then, in 1965, the "gate theory" of Melzak and Wall[3] and simultaneous advances in electronics gave the targeted use of electricity a theoretical and practical underpinning. The gate theory proposes that activating large, myelinated afferent nerve fibers will affect the dorsal horn and inhibit transmission in small, unmyelinated primary afferent nerve fibers.[3,4] Strategically placed epidural electrodes stimulate the dorsal columns to inhibit or modulate incoming nociceptive input through the smaller fibers.[5]
The first electrical stimulation method that developed from this theory, TENS, offered a method of providing an appropriate pattern of nerve activity in an affected area, without the systemic side effects of other analgesics. However, some pain was clearly more widespread or deep-seated, and required a different approach, namely, controlled stimulation of the CNS with implanted electrodes.[4] SCS involves the placement of an electrical system to block nociception through the surgical placement of epidural electrodes, cables, and an RF transmitter or battery-powered generator along the dorsal columns. In 1967, Shealy and colleagues[6] were the first to experiment with implanted electrodes to stimulate the dorsal columns for the treatment of chronic, intractable pain.[7] As it became clear that spinal stimulation activates dorsal horn neurons and spinal roots as well as dorsal columns, or a combination, the term "spinal cord stimulation" became prevalent.[4] Ongoing research suggests that SCS may act by inhibiting transmission in the spinothalamic tract by activating central inhibitory mechanisms that influence sympathetic efferent neurons and through the release of various inhibitory neurotransmitters.
PNS began as silicone cuff electrodes that were placed around the affected peripheral nerves and attached to a subcutaneous RF receiver.[8] The technology has since been refined to multiarray percutaneous wire electrodes, with power sources that range from RF receivers in combination with external transmitters (currently US Food and Drug Administration [FDA]-approved) to implanted lithium ion battery packs (used off-label), as well as an FDA-approved implanted power source.[8]
The current techniques for SCS and PNS are minimally invasive. Electrodes can generally be placed during an outpatient procedure, with local anesthesia and sedation. One essential step toward effective use of neurostimulation in potential patients is a trial of the system through percutaneous lead placement. No incision is necessary and the procedure is performed with only local anesthesia. The purpose of the trial is to determine the effectiveness of the stimulation for relieving pain and improving the patient's quality of life. If this temporary placement of the stimulation system provides sufficient analgesia (often measured as > 50% pain relief), allows the patient to sleep better, and uses less pain medication, then permanent placement of the system is considered. The advantages of SCS (neuroaugmentation) over ablative surgeries include reversibility, a removable device, and a nonmedication modality. There are also none of the long-term systemic side effects associated with opiate use.[7]
SCS is generally indicated for failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), peripheral neuropathies, angina, and peripheral vascular disease (PVD) as well as postherpetic neuralgia, occipital neuralgia, and chronic pelvic pain (particularly interstitial cystitis) (Table 1). The most common conditions indicated for the use of SCS are FBSS in the United States and PVD in Europe.[9] PNS has been shown to be useful for intractable pain from transformed migraine, peripheral mononeuropathies, such as peripheral nerve trauma and chronic entrapment syndromes (failed carpal tunnel syndrome), and posttherapeutic neuritis and extremity burns.[8,9]
Table 1. Indications for Neurostimulation
|
Condition |
Type of Neurostimulation |
|
FBSS |
SCS |
|
CRPS |
SCS and PNS |
|
PVD |
SCS |
|
Refractory angina |
SCS |
|
Postherpetic neuralgia |
SCS and PNS |
|
Occipital neuralgia |
PNS |
|
Pelvic pain and urge incontinence |
SCS |
|
Peripheral neuropathies |
SCS and PNS |
|
Radiculopathies |
SCS and PNS |
FBSS = failed back surgery syndrome; CRPS = complex regional pain syndrome; PVD = peripheral vascular disease; SCS = spinal cord stimulation; PNS = peripheral nerve stimulation
In choosing a mode of neurostimulation, clinicians may be guided by the nature of the pain. For pain associated with a single peripheral nerve injury, PNS may be appropriate, whereas SCS is most appropriate for pain that encompasses several adjoining dermatomes.[10] The nature of SCS and PNS -- invasive modalities with inherent risks -- makes it difficult to conduct large-scale, prospective, controlled, double-blind studies of the techniques and their effects. However, there are a few controlled trials as well as many prospective studies and small-scale randomized trials of the treatments. Also, the lack of a placebo effect is observed when lead displacement or battery depletion occurs. In a study of SCS in severe PVD, 70% of the patients who had achieved significant pain relief lost this benefit immediately upon lead displacement or generator failure.[11]
Neuropathic pain syndromes. Neuropathic pain covers many different diagnoses, and patients with one disease entity may have different types of pain. It is likely that chronic pain patients exhibit neuropathic pain via central sensitization and experience a nociceptive deafferentation pain that differ in their mechanisms.[5] Nociceptive pain is typically the result of a musculoskeletal or visceral injury. It is localized, constant, and often has an aching or throbbing quality. It usually resolves when the initial tissue damage heals and tends to respond well to treatment with opioids. Neuropathic pain is the result of an injury or malfunction in the peripheral or CNS. The pain is often triggered by an injury, but this injury may or may not involve actual damage to the nervous system. The pain frequently has qualities of burning, lancinating, or electrical shock.[2] Persistent allodynia, ie, pain resulting from a nonpainful stimulus, such as a light touch, is also a common characteristic of neuropathic pain.[7] The pain may persist for months or years beyond the apparent healing of any damaged tissues. Neuropathic pain is frequently chronic and tends to have a less robust response to treatment with opioids. Neuropathic problems are often not fully reversible, but partial improvement commonly results with proper treatment.
In some conditions, pain appears to be caused by a complex mixture of nociceptive and neuropathic factors. In these cases, an initial nervous system dysfunction or injury may trigger the neural release of inflammatory mediators and subsequent neurogenic inflammation -- migraine headaches, for example, are most likely a mixture of neuropathic and nociceptive pain.
Complex Regional Pain Syndrome (CRPS). CRPS remains a clinical diagnosis with no specific diagnostic tests and encompasses several different states.[5] Patients with both types of CRPS -- CRPS I and CRPS II -- respond well to SCS, including those with upper or lower extremity pain.[9] In a 1998 retrospective study of 15 years of experience with SCS for neuropathic pain, Kumar and associates[12] reported a 100% success rate in the 13 patients treated for reflex sympathetic dystrophy (also known as CRPS I) or causalgia (CRPS 2), both during the trial and in the long-term follow-up.
In a prospective, randomized trial by Kemler and colleagues,[13] patients with CRPS I who received both SCS and physical therapy fared better than those who were given physical therapy alone, with a success rate of 56%. The investigators used the VAS and McGill Pain Questionnaire for outcome measures in pain as well as the Nottingham Health Profile (NHP) and the Sickness Impact Profile to measure outcomes for quality of life. In an intention-to-treat analysis, the group assigned to receive SCS with physical therapy had a mean reduction of 2.4 cm in the intensity of pain at 6 months as compared with an increase of .2 cm in the group assigned to receive physical therapy alone (P < .001). Also, 39% of patients who received SCS reported "much improved" global perceived effect, whereas only 6% of the physical therapy group reported this result (P = .01). Health-related quality of life improved only in the 24 patients who actually underwent implantation of a spinal cord stimulator. However, overall, the investigators reported no clinically important improvement in functional status for either group. A recent follow-up of these patients demonstrated sustained, significant pain relief in the SCS and PT group as compared with the PT-alone group (VAS change of 2.0 vs 0, respectively) (P < .05).[14]
For CRPS patients with a partial response to SCS, a multidisciplinary approach with other regimens may be the most beneficial. A study by van Hilten and colleagues[15] showed good results with intrathecal baclofen in patients with CRPS. Given that Intrathecal Baclofen also augments the effects of SCS (see the subsequent "Mechanisms of Action" section), the combined therapies may be quite effective for treating selected patients with CRPS.[9,16]
Peripheral neuropathy and postherpetic neuralgia. Various forms of peripheral neuropathy respond well to SCS, but the reports on its effectiveness for phantom limb pain, stump pain, and spinal cord injury are varied. In these syndromes, the remapping that takes place in the CNS may result in poor coverage for deafferentation pain. Diabetic neuropathy and postherpetic neuralgia are the 2 most common neuropathic pain syndromes.[9] For patients with diabetic neuropathy, SCS appears to offer analgesia and the possibility of limb salvage when there is associated limb ischemia. Patients who show an increase in transcutaneous oxygen pressure (TcPO2) during the SCS trial period are more likely to experience positive results with SCS.[17] However, because there is a higher risk of infection for patients with diabetic neuropathy, special precaution should be used during the implantation procedure.[9]
Data on the efficacy of SCS in postherpetic neuralgia are limited, but some investigators have reported good results. A study from Spain by Sanchez-Ledesma and colleagues[18] examining SCS in causalgia, phantom limb pain, plexus and nerve root avulsion, postherpetic neuralgia, reflex sympathetic dystrophy, and amputation found that 57% of the patients experienced satisfactory pain relief (ie, over 75% pain relief).
More recently, Harke and colleagues[19] in
Diabetic neuropathy also responds well to SCS, although, as noted above, care should be taken to avoid infection. Kumar and colleagues[12] had a success rate of 75% in treating patients with diabetic neuropathy. Tesfaye and colleagues,[20] in a trial of diabetics with no PVD, neurotoxic drugs, or alcohol, and normal renal function, found that all patients with normal dorsal column function experienced increased function.
Cancer pain. Although there have been no formal studies on the use of SCS or PNS in cancer patients, there are several neuropathic pain syndromes that are common in this population. Neuropathic pain states seen elsewhere, such as in postherpetic neuralgia, radiculopathy, and other neuralgias, are present in cancer patients, and tumor-related mononeuropathies particular to the cancer state are also a documented problem.[21] Cancer survivors often experience neuropathic pain as a consequence of cancer treatment. Those patients who are stable at presentation often fare better with SCS than patients whose pain has been further complicated by disease progression.
In FBSS, patients experience persistent low back pain even after surgical intervention. Twenty percent to 40% of the more than 200,000 people who have lumbar spine surgery each year are prone to FBSS.[9,22] People with FBSS are often more responsive to SCS than reoperation. SCS has demonstrated widely varying levels of efficacy, but in more recent studies is showing a consistently high rate of success.[9] Several literature reviews indicate that an average of 59% of patients with FBSS who are treated with SCS experience at least 50% pain relief, and improved functioning (as measured by the return-to-work rate), improved activities of daily living, and reduced consumption of analgesics.[12, 23-26] Two prospective controlled studies found positive results for SCS in FBSS. One, by Marchand and colleagues[27] that measured pain scores after patients received either placebo stimulation or normal stimulation, found that the pain scores were significantly lower (P = .03) after treatment with SCS as compared with placebo. In a study by North and coworkers,[28] patients randomized to either additional surgery or SCS were given the opportunity to cross over into the alternative group for inadequate analgesia. Patients randomized to SCS were much less likely to request crossover for further surgery. SCS generally seems to be most effective in patients who have chronic low back pain with a radiating pattern to the legs rather than isolated axial low back pain, even in those patients without previous surgery.[9]
Over 2 million people in the
In angina, there is generally an insufficient supply of blood to the myocardium, often due to atherosclerosis of the coronary arteries.[30] Angina that does not respond to pharmacologic or surgical intervention may merit a trial of SCS.[9,31] The first report of the use of SCS to treat angina was a study by Murphy and Giles[32] in 1987, which demonstrated a reduction in the severity and frequency of anginal attacks, and reduced use of nitrate tablets. Several groups of patients have a higher risk of complication with revascularization procedures, such as coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty : patients whose coronary anatomy requires extended surgical procedures; patients with low ejection fractions or concomitant diseases, such as diabetes mellitus, renal dysfunction, cerebrovascular disease, or peripheral vascular disease; and patients who have previously undergone CABG.[31] Because the SCS device is implanted under local anesthesia, the complication risk is likely to be lower than in CABG. SCS has been used with some success in treating severe angina pectoris in patients who cannot undergo revascularization.[33] Patients treated with SCS for ischemic heart disease often show an increased capacity for exercise, improved quality of life, reduced anginal complaints, and use fewer short-acting nitrates.[9]
In the ESBY study, by Mannheimer and colleagues,[33] a total of 104 patients, mostly men, were randomized to either CABG (n = 51) or SCS (n = 53). Although the CABG group showed an increase in exercise capacity, lower ST-segment depression, and comparable workloads when compared with the SCS group, both treatment methods caused a decrease in the frequency of anginal attacks (P < .0001) and consumption of short-acting nitrates (P < .0001). The mortality in the CABG group was significantly higher on an intent-to-treat basis. The study authors note that the lack of effect of SCS on exercise capacity and ST-segment depression in their study was contrasted with previous studies of the immediate effects of electrostimulation on experimentally induced myocardial ischemia. In these studies, SCS demonstrated a consistent and highly reproducible anti-ischemic effect. The study authors concluded that SCS may be a therapeutic alternative for patients with an increased risk of surgical complications and no prognostic benefit from surgery.[9]
SCS also appears to have a durable effect in many patients with angina. In a prospective, randomized, controlled study, by de Jongste and colleagues,[34] 60% of the patients with SCS still experienced positive effects from the treatment after 1 year. In the study, 17 patients were randomly assigned to implantation, with 8 patients receiving treatment within 2 weeks and 9 patients receiving implantation after 8 weeks. After the 8-week study period, the control group was also implanted, and all patients were followed for 12 months. During the 8 weeks, the treatment but not the control group demonstrated a significant increase in exercise duration (P < .02), rate-pressure product (P < .03), and time to angina (P < .04), with a decrease in ST-segment depression (P < .05). These effects were associated with an increase in daily life and social activity scores (P < .008 and P < .005) as well as reduced nitrate intake and episodes of angina pectoris (P < .004 and P < .003). During the 1-year follow-up, quality-of-life variables improved in a linear fashion for the entire group as compared to baseline, with results also holding steady in the time to angina, exercise duration, and ST-segment depression. On the basis of these results, the study authors concluded that SCS significantly improves exercise capacity and quality of life for patients with intractable angina.[34]
Several other studies (conducted without controls) have found a variety of positive effects with SCS for refractory angina, including a reduction in the number of angina attacks, improvement in New York Heart Association (NYHA) grade, reduced nitrate intake, decreased hospital admission rates, and long-lasting effects in 57% to 78% of patients.[7,31] Despite the antianginal effects and analgesic properties, SCS does not seem to decrease the warning signals from an actual myocardial ischemic attack.[7,22]
Severe PVD is usually characterized as critical limb ischemia (CLI). Patients with inoperable severe leg ischemia or CLI are considered candidates for SCS. CLI can be characterized by its involvement of major arteries or small vessels, and changes in these can be used as outcome measures.[5] Patients with ischemic pain are often categorized according to Fontaine classification. SCS is usually recommended to patients in Fontaine groups III and IV (Table 2).
Table 2. Fontaine Classification of Peripheral Vascular Disease
|
Class |
Symptoms |
|
I |
No symptoms |
|
II |
Claudication but no rest pain Intermittent, moderate claudication Intermittent, severe claudication |
|
III |
Rest and pain at night, but no tissue involvement |
|
IV |
Pain and ulceration With local inflammation With widespread inflammation |
Adapted from: Carter ML. Spinal cord stimulation in chronic pain: a review of the evidence. Anaesth Intensive Care. 2004;32:11-21
In a prospective, randomized, controlled study of the effect of SCS on CLI, Klomp and colleagues[35] found that in 120 patients treated with best medical treatment or best medical treatment and SCS, there was no significant difference in pain scores, but the short-term use of pain medication was greatly reduced in the SCS group. Also, there was no difference in rates of amputation over time.
Jivegard and colleagues[36] found different results in a study of 51 patients: 25 patients randomized to SCS and 26 to analgesic treatment. Long-term pain relief was observed only in the SCS group, although macrocirculatory parameters did not differ between the 2 groups during follow-up. After 18 months, limb salvage rates between the 2 groups were not significantly different -- 62% in the SCS group and 45% in the control group, with lower tissue loss (P = .05) in the SCS group. However, a subgroup of patients without arterial hypertension had a significantly lower amputation rate in the SCS than in the control group, leading the study authors to conclude that SCS did provide long-term pain relief for CLI, and may be effective in reducing the likelihood of amputation in patients without arterial hypertension.[36] Several studies, prospective and retrospective without matched controls, found that 76% to 78% of the patients treated for CLI with SCS reported successful pain relief.[7] Although there has been little evidence for an increase in overall limb salvage over the long term with SCS treatment in CLI, several studies have found a significant reduction in analgesic use.[5]
Following an analysis of data from several trials, Huber and associates[37] found that the indications for SCS in CLI include chronic intractable pain due to ischemia in which surgical revascularization is not an option and ulcers < 3 cm in diameter. Others have found that measuring microcirculation can be a good predictor of success with SCS. Claeys[11] and Ubbink and associates[38] both found that CLI patients who have a TcPO2 of 10-30 mm Hg on the affected extremity did well with SCS, whereas patients with a TcPO2 of < 10 mm Hg did not respond as well.
Retrograde lead placement can be used to treat pain or other nerve-related difficulties in the lower part of the trunk. The use of SCS at the sacral nerve root for urge incontinence was approved by the FDA in 1995, and retrograde lead placement has also been used to treat pelvic (particularly patients with interstitial cystitis) and rectal pain. In the case of chronic nonspecific pelvic pain, patients should be carefully screened for sexual abuse before selection.[2]
For SCS, 2 main modes of action bring about pain relief for
the different conditions that respond to treatment. For neuropathic pain, the
gate control pain theory proposes that stimulating the large fibers reduces the
nociceptive input from peripheral nerves by
modulating the dorsal horn "gate," and there are studies that
demonstrate that stimulating the dorsal columns can inhibit neuronal activity
in the dorsal horn.[9] However,
there may be other mechanisms that are more influential in determining the
action of SCS. According to a study in rats by Cui and colleagues[39]
in
In PVD, several studies so far have shown no change in peripheral blood flow, and it seems most likely that SCS may act by rebalancing the oxygen supply and preventing ischemia.[42,43] After measuring coronary blood flow, one study postulated that the analgesic effects of SCS in myocardial ischemia are most likely achieved through the redistribution of coronary blood flow from regions with normal perfusion to regions with impaired myocardial infusion.[44] SCS may also be instrumental in modulating the cardiac nervous system by directly suppressing the excitatory effects of cardiac neurons.[45] For angina, de Jongste and colleagues[34] also postulated that the basis of an increase in exercise capacity and rate-pressure product they observed in their treatment group implied that SCS may act to improve oxygen supply to the heart. A recent study by Moore and colleagues[46] studied the influence of SCS on cardiac autonomic balance by testing heart-rate variability. In 16 patients with refractory angina, treatment with SCS significantly altered the spectral power parameter in heart-rate variability, implying that SCS reduces cardiac sympathetic activity. The possible complication of this mechanism, however, is that there could be a rebound if neurostimulation is lost, as may be the case with lead migration or battery failure. Jessurun and colleagues[47] tested the likelihood of adverse cardiac events after cessation of SCS in 24 patients, and found that there was no higher likelihood of recurring ischemia, number of anginal attacks, nitroglycerin intake, or ischemic episodes in patients who were suddenly removed from SCS.
SCS systems can be implanted through percutaneous
leads, which is now the most common method, or through the original method of placing
plate electrodes via a laminectomy.[5,7]
The typical SCS hardware is an SCS lead, an extension cable, and a pulse
generator. The lead design varies from 4 to 8 electrodes (Medtronic,
One innovation that has influenced the success of SCS is the
development of the multipolar lead, often leading to
greater effectiveness for the procedure. Over the 15 years covered by their
analysis, Kumar and colleagues[12]
found that multipolar systems were significantly more
reliable (P < .001) than unipolar systems,
and concluded that the advent of multipolar systems
had significantly improved the clinical reliability of SCS. At the 2004 Annual
Meeting of the
PNS is commonly used as a flat-paddle array placed through dissection of the affected nerve, and sometimes percutaneously. Subcutaneous impulses may also be useful; Weiner[8] observed that electrical impulses are conducted by subcutaneous tissues throughout the body that are not necessarily close to major peripheral nerves. These impulses can result in a dermatomal and possibly myotomal pattern of paresthesias that are especially useful in treating transformed migraine headaches and occipital neuralgia.
Chronic pain is a complex experience, and it includes physical, psychological, and emotional factors, all of which play a part in a patient's response to any treatment modality.[10] It has become apparent through years of experience that careful patient selection is one of the best predictors of success with neurostimulation, especially SCS.[5] All factors encompassing the experience of long-term chronic pain must be taken into account. Many chronic pain sufferers have been the victims of childhood abuse or traumatic stress, and chronic pain is often intertwined with depression, anxiety, and somatoform disorder.[10] Despite the fact that 2 studies have stated that psychological factors were not significant in predicting outcome, patient screening for potential treatment with SCS should consider a detailed psychological profile as well as a thorough medical history.[5,10,51,52]
Table 3 summarizes patient selection criteria and contraindications for neurostimulation. Most patients who are candidates for neurostimulation are likely to have a long and complicated medical history. The first step in evaluation must be to examine this history, and include patient questionnaires that investigate pain history, current medication and other therapies, disability status, and a VAS measurement of their pain. A thorough physical examination, including neurologic assessment, should be used to document the patient's current symptoms, and any underlying reversible components of the pain should be addressed.[10] The cooperation of the patient is essential to the success of a self-regulated therapy like SCS. The evaluation process before implantation should include a discussion with the patient of what they expect from the procedure, stressing that complete pain relief is unlikely, regular follow-up appointments are necessary, and there can be complications after the implantation has been completed.[9,22] Many patients benefit from a detailed psychological evaluation with a professional psychologist. To avoid misunderstandings, this evaluation should be discussed with patients before the meeting with the psychologist, so that patients do not feel that they are being told they are "crazy," or their pain is not legitimate. The evaluation can address the subjective experience of pain, the patient's emotional state, expectations about the implantation procedure, and psychological tests for an objective measure.[10]
Table 3. Patient-Selection Criteria and Contraindications for Neurostimulation
|
Selection Criteria |
|
Sufficient dorsal column function |
|
No stimulating or sensing devices (eg, pacemakers) |
|
Normal coagulation |
|
Normal immune status |
|
Incomplete response to conservative therapies |
|
No further surgery planned |
|
Few or no surgeries before implantation* |
|
Sufficient cognition to understand function and operation of device |
|
Good response to trial |
|
Contraindications |
|
Major psychiatric disorder |
|
Poor comprehension |
|
Lack of compliance |
|
Lack of social support |
|
Drug or alcohol abuse or drug-seeking behavior |
|
Tendency to litigation |
|
Poor response to trial |
*Optimizes response, but does not exclude patient
The European Federation of the International Association for the Study of Pain Chapters (IASP) recommends treatment with SCS for chronic pain patients, with some dorsal column function, no other stimulating or sensing devices, and normal coagulation and immune status, who have not responded to conservative therapies and in whom no further surgery is contemplated.[53] Kumar and associates[12] found, in their retrospective study, that patients whose pain did not follow a surgical procedure were more likely to respond well to SCS than patients who had multiple surgical procedures before their first implant. The consensus statement stipulates that the patient must be able to understand the function of the implanted device and be able to use it within acceptable guidelines. Factors that make informed consent impossible are considered a contraindication for implantation and may include issues, such as major psychiatric disorder, poor comprehension, lack of compliance, lack of social support, drug or alcohol abuse, and drug-seeking behavior.[5,10]
The selection criteria for PNS are similar to that for SCS, with the added stipulations of a demonstrated injury for the pain and identification of the injured nerve through selective blocking techniques at the nerve root. The nerves most commonly treated with PNS are the ulnar, median, radial, posterior tibial, and common peroneal nerves (Table 3).[8]
Trials before permanent implantation allow the patient and the physician time to assess the effectiveness of the technique. The trial tests the patient's response to the treatment, both in terms of pain treatment and tolerability.[10,49] North and Wetzel[48] connected the information garnered through the results of a trial stimulation with an external pulse generator to the efficacy of the procedure of the long run. Before the trial period, the patient and the physician should agree on the goals of the trial and outcome measures.[10] The patient should experience a pain reduction of at least 50% and show evidence of improved function and reduced analgesic intake before contemplating permanent implantation.[5] There is no current consensus on a trial period for SCS. The trial period should be at least 24 hours, and many centers perform 3-5-day trials.[9] The trial period can be extended if the patient does not have a sufficient degree of pain relief or cannot tolerate the paresthesias that stimulation causes.[5] A shorter trial, or "trial on the table" in which the electrode is inserted, tested and permanently implanted in 1 session may sometimes be desirable in patients at particular risk for infection.[22] In a study of SCS in angina by Di Pede and colleagues,[54] the only infections that occurred took place in the patients who went through the implantation procedure in 2 steps.
Before the trial placement, a prophylactic intravenous antibiotic is commonly administered and proper patient position is ascertained. Lead placement is performed under local anesthesia, with intravenous sedation. The patient is prone and fluoroscopic imaging is used to facilitate lead placement. A 15-gauge Tuohy needle should enter the intralaminal space via a paramedian approach at an angle of 30ƒ to 45ƒ, with the loss-of-resistance technique. If needed, an epidurogram can be used to confirm the epidural space. The final lead position is based on handheld programming and should be a minimum of 1 or 2 levels above the epidural entry point. Once the needle is confirmed in the epidural space, the lead is passed to the appropriate (desired) spinal level. The proximal end of the electrode lead is optimally tunneled ipsilateral to the pocket generator site. Factors that may influence lead placement include manipulating the needle bevel and rotating the lead. Resistance to lead placement should be minimal, and if paresthesias are encountered, adjustments should be made.[2,9] New technology advances, including leads, curved tips, and specialized stylets, allow for enhanced steering under live fluoroscopic guidance.
It is sometimes necessary to use a retrograde placement technique, in which the lead is placed in the inferior aspect of the epidural space. In this technique, the physician stands opposite the normal position. The needle angle during this technique is generally 40ƒ to 70ƒ in the caudal orientation, and the entry site ranges from the L1-L2 level to the L5-S1 level.[2]
Once the lead is in place, sedation is decreased so that communication with the patient is facilitated, and an electrode is connected to a screening wire. When the paresthesia is correctly located and at an acceptable level for the patient, the lead can be secured,[2] tunneled, and connected to the pulse generator or RF transmitter.
Where the electrodes for SCS are placed depends on the location and nature of the pain. For pain in the trunk and limbs, electrodes have been placed anywhere from C1 to L2.[55] Leads placed inferior to the termination of the spinal cord are stimulating nerve roots and are not technically considered as SCS leads. Placement for treating chronic pelvic pain and urge incontinence are often placed retrograde in the lower lumbar and sacral areas.[2]
FBSS: A dual-lead system with electrodes positioned near T9-T10 seems to be more effective in relieving axial low back pain than a single lead, although there is some evidence to the contrary.[9] Rarely, patients with lumbar radiculopathy experience better coverage and pain relief with retrograde lead placement through the neural foramina.[56] Above T9, patients may experience nerve root irritation that spreads into the abdomen or the intercostal nerves. For foot pain, positioning at T10-11 may be more effective, and buttock or axial back pain is more likely to respond at T9.[2]
Angina: In the ESBY study, the skin incision was made paramedian in the midthoracic region, and the epidural space was punctured at the level of T6. A Tuohy-type needle was advanced into the epidural space, and the electrode tip was placed at the level of T1-T2. The pulse generator was placed in a subcutaneous pouch below the left costal arch. An extension lead was tunneled subcutaneously from the back incision to the pocket site and subsequently connected to the generator.[57] Oosterga and colleagues[30] implanted by puncturing the epidural space at the level of T4-T5 and positioning the proximal electrode of the lead at the C7-T1 level.
CLI: Huber and associates[37] recommends implanting the electrode between T10 and L1, with the tip directed toward the painful side.
Other spine stimulation: Cervical spine stimulation is most effectively obtained by entering the skin at T2 or T3, entering the intralaminal space at C7-T1 or T1-T2, and placing the electrode at C3-C7. To treat thoracic nerve root injuries, the lead must often be placed more laterally than usual, and it is often difficult to balance stimulation and overintense paresthesia. Sacral nerve root leads are placed at the S2-S4 neural foramina, with either a unilateral or bilateral distribution, and are often placed with a retrograde technique. Treatment for urge incontinence can be placed peripherally through the sacral foramen.[2]
PNS for transformed migraine occipital headache: Popenay and Alo[29] placed 2 quadripolar electrodes transversely through a subcutaneous midline incision over C1, superficial to the cervical muscular fascia and transverse to the affected C1 though C3 nerves, under fluoroscopic control.
Power sources: The power source for stimulation may be externally placed or totally implantable. The FDA has approved implantable generators that can control > 1 lead, and many power sources are now of this type. With an implanted power generator, patient acceptance is increased; it is possible to change programming without wearing an external power source; and software upgrades are available to improve programming. With external power sources, changing the battery does not require surgery, but the mechanical complications of wearing an external power source at all times may be daunting to most patients.[2] In Mannheimer and associates'[33] angina study, as an example of how a power source is customized to the procedure, the pulse generator was telemetrically programmed with 2 preset stimulation strengths. The stronger one was used in the case of established anginal pain, whereas the weaker setting was used as a prophylactic treatment. The pulse generator was controlled with a quick touch by the patient placing an external magnet on the skin over the pulse generator. The patient was also able to use the magnet to switch between the 2 preset stimulation strengths.
Permanent placement: Once the trial phase has been completed with satisfactory results, permanent placement is possible. A sterile surgical technique should be followed for permanent implantation. If the original trial is anchored in the deep fascial tissue of the back and tunneled laterally, this lead can be exposed during permanent implantation and connected to an extension set that is tunneled to the pocket site. Final connections to the generator or RF transmitters are made and the wound closed.
Commonly, the trial lead is anchored only to the skin. Following a successful trial, the temporary lead is removed and the patient returns for permanent implantation 7-21 days later. The lead is reintroduced and stimulated to mimic the successful trial, connected to a tunneled extension set, and a pocket is made for the generator or RF transmitter. After all connections are secured, the wounds are closed.
PNS: A flat-paddle array is the most frequently used surgical lead, which incorporates a mesh apron to facilitate anchoring into the surrounding tissue When implanting leads adjacent to peripheral nerves, intravenous sedation and local anesthesia are usually well tolerated and leave the patient alert enough to respond to intraoperative stimulation.[8]
The electrode is placed by exposing a 5-cm segment of peripheral nerve proximal to the injury site and free of surrounding tissues. Nearby fascial tissue or a fascial graft is used to create a flap that covers the electrode to avoid direct contact with the nerve. The electrode lead is longitudinally inserted under the dissected section of the nerve, making sure that all 4 electrode contacts remain close to the nerve. Once the electrode is placed, temporary electrode stimulation can be used to confirm proper lead position. As in SCS, the distal electrode wiring can be kept external so that there may be a prolonged screening stimulation before permanent implantation.
Power sources are most commonly situated subcutaneously in the anterior chest or abdominal wall, midaxillary midthoracic region, or posterior superior buttock region. Power sources for PNS in the lower extremities can be placed in the lateral thigh or extended into the abdomen. If appropriate, the electrode and the power source can be implanted by tunneling the lead extension wire to the receiver/generator pocket. The voltage requirements for PNS are generally much lower than for SCS, ranging from .2 to 3.0 V. Pulse widths range from 120 to 400 mcseconds, with a frequency of 40-100 Hz. However, some pain is frequency-dependent, and this often requires frequencies of 1000 Hz.[8]
Use of PNS has been limited in the past in some patients by the need for extensive surgical dissection in the affected region. However, the more current percutaneous electrode-placement techniques developed for SCS may make this less of an issue. Simple percutaneous perineural electrodes can be placed parallel to a major peripheral nerve quickly and easily, making more extensive nerve-dissection surgery unnecessary. This has been reported effective in treating failed carpal tunnel syndrome and failed ulnar transposition in which the nerve segment in the midforearm or the midhumerus, respectively, can be approached at an angle of approximately 20ƒ to 30ƒ.[8]
Complications from treatment with SCS have been both technical and biological.[7] The most common technical complications are lead migration, electrode breakage, and failure of the pulse generator or battery. The most common biological complications are infection, cerebrospinal fluid leakage, and pain at the incision electrode or receiver site. Skin erosion can be a problem in some diabetic patients. There has been 1 case of paralysis reported as a result of a bacterial infection at the lead tip, but most complications are not life-threatening and can usually be resolved by removing the device.[5,7] In a study of FBSS, Burchiel and colleagues[58] found a complication rate of 4% at lead implantation, 16% nonsurgical, and 17% surgical. In a study of CLI, Klomp and colleagues[35] found that 3 of the 60 patients implanted required lead repositioning within 30 days, with 11 more repositionings and a replacement during follow-up.
Although there are no systemic side effects, there have been reports of dizziness, headache, asthenia, and muscle spasms and twitches.[7]
Law[59] noted that after 625 operations for SCS electrode insertion, 1.8% of the patients experienced temporary paralysis, whereas 4.2% experienced multidermatomal, painful allodynia. Diagnostic testing yielded no anatomic explanation, and in patients who were awake during the operation, these deficits were noted to begin immediately after pain caused by mechanical deformation of the dura. The study author hypothesized that cord ischemia from a vasospasm that is triggered by pain within or near the spinal canal may cause myelopathy and proposed selective epidural anesthesia to prevent these complications. Many centers do not use epidural anesthesia, as this can interfere with stimulation patterns.
One of the more recent complications reported is interference from electromagnetic fields in security systems. There has been only 1 report of such an incident, in which the patient alleged permanent neurologic injury from the uncontrolled activation of a cervical SCS device.[60]
Infection can occur, and Deer[2] recommends using a third-generation cephalosporin prophylactically during lead placement. If the patient is allergic to cephalosporin, an alternate drug (eg, vancomycin) that acts on local pathogens can be given. For patients who are at higher risk of infection, such as those with diabetes, it may be useful to consult with a specialist in internal medicine or infectious disease.[2]
If infections occur following the procedure, they can
usually be resolved by antibiotic therapy or by removing the SCS system. Severe
infections are rare, but there has been at least 1 reported case of methicillin-resistant Staphylococcus aureus
(MRSA).
Andersen,[62] working with 60 patients treated with long-term SCS for angina, recorded the complications of the procedure in detail. Twenty-two had monopolar leads and 38 had quadripolar leads positioned percutaneously. The patients were followed at 1-4-month intervals over a period of 4 years, and all complications were recorded, including electrode fracture, infection, electrode migration, and technical equipment failure. There was infection in 5% and electrode fracture in 3% of the patients. The most frequent complication --in 23% of patients -- was electrode displacement requiring surgery. The incidence of this complication was 11% less in patients with quadripolar electrodes than in patients with monopolar electrodes (P < .003, and all displacements occurred within a year of implantation. There was no significant difference between the frequency of migration for patients with monopolar or quadripolar epidural stimulation electrodes (P = .31), but reoperation among patients with multipolar electrodes was less likely because it was possible to change electrode combinations and optimize stimulation noninvasively. Changing electrode combinations related to small migrations was necessary in 29% of the patients with multipolar electrodes. The study authors concluded that when SCS was used for treatment of anginal pain, the frequency of electrode tip migrations was high, but the use of multipolar electrodes gave the possibility to compensate for the migration and to avoid surgical replacement. North and colleagues[63] also found that surgical revision was necessary in 23% of patients with dual leads treated for chronic pain with SCS. This was reduced to 16% in patients with multichannel devices.[7]
In PNS, anchoring the electrode with silicone medical adhesive, suffused between the anchor and electrode just before suture tightening, may reduce the tendency to lead migration. Also, looping the lead and securing in a pocket adjacent to the incision may reduce the migration potential.[8]
SCS and other implantation devices are expensive, complex technologies. However, given other factors, successful SCS can pay for the expense of the device within 2.5 years by improving pain control, quality of life, and increased work rehabilitation.[64] The Canadian study, by Kumar and associates,[64] compared the cost of 60 patients with failed back syndrome treated with SCS with a control group of 44 patients. Over 5 years, the study authors tabulated costs from diagnostic imaging, physicians' fees, implantation (including the costs for hardware), nursing visits for maintenance of the stimulators, physical therapy, chiropractic treatments, massage therapy, and hospitalization for treatment of breakthrough pain. They found that the mean cumulative cost for SCS therapy over a 5-year period was $29,123/patient as compared with $38,029 for the control group. Costs were greater for the SCS group in the first 2.5 years, then became lower, and remained lower during the rest of the follow-up period. Also, 15% of the SCS-treated patients were able to resume work because of superior pain control and lower drug intake, but none of the patients in the control group were able to return to employment of any kind.[64]
Taylor and colleagues[65]
also found that across a range of medical indications, the initial costs of SCS
implantation were consistently offset by reduced postimplant
costs and a lower need for healthcare resources. In another cost analysis of
SCS for FBSS,
Neurostimulation can be very useful as an alternative to
more invasive surgery and systemic pharmacological pain-control techniques in
patients with intractable pain. New technologies of neurostimulation
and more refined knowledge of the mechanisms of its action have honed the
effectiveness of neurostimulation as a pain-control
technique. Greater knowledge of the patient populations to target has also
allowed the techniques to be applied more effectively. After many years of use
in Europe SCS is gaining acceptance in the
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