Spinal cord stimulation: Background and clinical application

2.1 A short history of neurostimulation before 1965

For at least two millennia, humans have used electricity to treat chronic pain. The first written account of electrical stimulation as pain treatment dates back to AD 46 when the Roman physician Scribonius Largus recommended the use of the electric fish torpedo ray (Fig. 1) as a – rather crude – remedy for gout and headache [9]. He also warned that prolonged use of electric jolts could cause permanent damage and should thus be used with caution.

Fig. 1

Torpedo panthera, Gulf of Aqaba, Egypt. Picture by Kaare Meier.

Man-made electricity was introduced several centuries later with the German scientist Otto von Guericke’s Elektrisiermaschine (1672), followed by the German bishop Ewald Georg von Kleist and the Dutch physicist Pieter van Musschenbroek’s Leyden Jar (1745). The new-found power was immediately put to therapeutical use, most famously by the American scientist Benjamin Franklin, who, around 1756 unfortunately used very strong voltage and thus caused burns in his patients [10], and by the British cleric John Wesley, who in 1760 published a famous treatise, humbly titled “The desideratum: or, electricity made plain and useful. By a lover of mankind, and of common sense”.

The invention of the Voltaic Pile by the Italian physicist Alessandro Giuseppe Antonio Anastasio Volta in 1800, and later the twin discoveries of electromagnetism in 1821 by the Danish physicist Hans Christian Ørsted and electrical induction in 1831 by the British scientist Michael Faraday, gave rise to a whole new industry of electrotherapy with results varying from apparently miraculous pain relief to burns and sometimes cardiac arrests. In 1855 French neurologist Guillaume-Benjamin-Amand Duchenne published the book De l’electrisation localisée et de son application a la physiologie, a la pathologie, et a la thérapeutique, further encouraging the use of treatment with electrical current.

S. Gaiffe’s device from 1863 and C. W. Kent’s “Electreat” from 1919 bear strong resemblance to modern devices for transcutaneous electrical nerve stimulation (TENS) and were commercially successful, and by the end of the 19th century, various forms of electrotherapy were widespread in clinical practice. Still, no one had provided a sound theoretical foundation for the therapy.

2.2 The gate control theory of pain

In 1965, the Canadian psychologist Ronald Melzack and the British neuroscientist Patrick David Wall published a groundbreaking theory in the Science journal, “The Gate Control Theory of Pain” [11].

Central to the theory was the postulate that activation of large myelinated A-fibres can diminish the transmission of pain via an integrative centre (the gate) in the spinal cord. The centre, which was also postulated to be tightly regulated by the brain in a complex interplay between afferent and efferent fibres, was proposed to be located in the complex interneuron network in Rexed lamina II (substantia gelatinosa) of the dorsal horn in the spinal cord.

The theory provided a theoretical framework for neurostimulation as a treatment for pain and stimulated immediate interest. In 1967, Patrick Wall and the American neurosurgeon William Sweet published a case series of eight patients suffering from various pain conditions [12]. They were all treated with electrical impulses, either delivered to the skin (similar to modern TENS), with a subcutaneously implanted electrode comparable to modern peripheral nerve stimulation (PNS), or as a combination of both. The aim was to prove that the practical application of the gate control theory was indeed effective. The patients showed improvement of their otherwise intractable pain, attracting further attention to the Gate Control Theory.

The same year, the American neurosurgeon C. Norman Shealy published a case report with a 70-year old patient suffering from intractable pain related to a bronchial carcinoma [13]. Shealy had previously proposed that instead of stimulating the peripheral nerves directly, it might be more effective to stimulate the part of the spinal cord where the majority of the proprioceptive impulses are transmitted to the brain, i.e. the dorsal column part of the white substance [14].

For that purpose, the engineer J. Thomas Mortimer constructed an electrode that Shealy implanted subdurally above the dorsal column in the patient. Shealy named the treatment dorsal column stimulation, and as the patient experienced significant pain relief, the treatment gained instant attention. Unfortunately the patient died 6 days later (from a supposedly unrelated bacterial endocarditis with cerebral embolism), but the encouraging short-term effects spawned great interest in the new treatment.

2.3 Mechanisms of action of spinal cord stimulation

While the Gate Control Theory provided an initial explanation for the mechanism of action of neurostimulation on pain perception, subsequent work failed to explain how SCS exerts its pain relieving effect. It became clear that a remarkable aspect of SCS treatment is that the effect on purely nociceptive pain appears to be very limited. Another issue is that while TENS and PNS stimulate peripheral nerves, SCS activates transmission pathways central to the gate, i.e. the stimulating contacts are placed more centrally than the proposed integrative centre in the dorsal horn. This may also serve to explain why success with TENS treatment is not generally considered a good predictor for a positive SCS treatment outcome, in contrast to what was originally assumed [15].

Finally, and importantly, it is to be noted that even in the best selected cases there is a relatively high percentage of patients (around 25–50%, depending on indication) who have no beneficial effect of SCS. Attempts at identifying clinically important and reliably reproducible predictors for success have so far proved unsuccessful.

The Karolinska group has demonstrated in several rat studies that the effect of SCS may be related to the release of inhibitory neurotransmitters within the dorsal horn, notably γ-aminobutyric acid (GABA) [16,17], acetylcholine [18,19], and serotonin [20]. Involvement of the GABA system seems to be supported by a recent small randomized trial that successfully used intrathecal treatment with the GABA agonist baclofen as an adjuvant to unsuccessful SCS treatment (where the α₂ receptor agonist clonidine also proved effective) [21].

Recent rat studies from Johns Hopkins have suggested that the effect of SCS in part is related to activation of both ascending and descending fibre systems in the spinal cord as well as a direct root stimulation effect [22]. The result is an attenuation of hyperexcitability in the wide dynamic range (WDR) fibres in the dorsal horn [23]. Antidromic activation has previously been shown in a human study [24].

In contrast to these findings, a new study demonstrated that in sciatic nerve lesioned rats, SCS electrodes that are placed at the level where the injured fibres enter the spinal cord are more effective at attenuating allodynia-like behaviour than electrodes placed more rostrally [25], suggesting a segmental spinal site of action.

While most studies have primarily investigated changes in the spinal cord as the result of SCS treatment, the Beirut group has pointed to the existence of a signalling loop between the spinal cord and the brainstem [26,27].

Other studies using positron emission tomography (PET) [28,29], single-photon emission computed tomography (SPECT) [30], and functional magnetic resonance imaging (fMRI) [31] have shown that SCS alters the activity in a series of brain regions. With the limited evidence available, no attempts have so far been made at assessing the relative importance, role, and possible connections for each region.

2.4 Modern spinal cord stimulation

Shealy’s decision to place the electrode subdurally gave rise to a number of complications In addition, very vaguely defined patient selection criteria unfortunately led to a large number of treatment failures. The poor outcome and multiple complications discouraged all but a few determined implanters after the initial enthusiasm, and Shealy himself implanted his last patient in 1973 [32].

Despite the quickly cooling interest among physicians, advances were continuously being made in the quality and sophistication of equipment. Moreover, implanters realized that the electrode could be implanted in the epidural space, drastically lowering the rate of neurological complications and greatly easing the implantation procedure. This eventually led to the development of the percutaneous implantation technique, allowing also non-neurosurgeons (primarily anesthesiologists) to perform the procedure.

Combined with further improvements of equipment quality (largely as a spill-over from advances in cardiac pacemaker therapy), the foundation was laid for a rekindled interest in the technique in the late 80s. No official figures exist for the annual number of implants performed, but estimates of 28,000 in US alone (2007) [33] and 30,000 worldwide (2010) [34] have been quoted, the majority of systems being manufactured by Medtronic (Minneapolis, Minnesota, USA), St. Jude Medical (St. Paul, Minnesota, USA), Boston Scientific (Natick, Massachusetts, USA), and Nevro (Menlo Park, California, USA).

Recent developments include the use of high-frequency stimulation with frequencies in the kilohertz range [35,36] (as opposed to conventional stimulation which normally occurs in the 30–300 Hz range), stimulation patterns relying on burst of impulses rather than a tonic stimulation pattern [37], and stimulation of the dorsal root ganglion with customized leads [38]. Although the initial results seem promising, particularly in complicated cases, the effect of those new treatment paradigms still need to be documented in larger studies.

2.5 Implantation procedure

The treatment consists of an electrode implanted in the epidural space of the spinal canal, either via a percutaneous approach (using the so-called percutaneous leads) or via a surgical (hemi-) laminectomy (using the so-called surgical leads or plate leads). Most modern percutaneous leads have 8 independent contacts, whereas more recent plate leads often have 16.

Percutaneous leads are generally inserted directly via a modified Tuohy cannula or, in the case of a recently marketed hybrid lead, via a broader plastic introducer inserted via the Seldinger technique [39]. Once placed in the epidural space, the lead is advanced under fluoroscopic guidance, and steered using a removable stylet.

The lead is implanted close to the dorsal column at the spinal cord segmental level that corresponds to the area of pain. The choice of placement is largely based on empirical data (with Giancarlo Barolat’s SCS atlas acting as a key reference [40]) combined with the knowledge of electrical fields in the spinal cord provided by the pioneering work by the Dutch physicist Jan Holsheimer [41,42,43,44].

When the lead is positioned, it is activated via an external stimulation device, evoking peripheral paresthesias (a sensation often described as “buzzing” or “tingling”), and the patient describes where and how the paresthesia is felt. Empirical evidence has shown that in order to obtain optimal pain relief, a complete overlap with the evoked paresthesia and the patient’s painful areas must be achieved.

When the lead(s) is estimated to be in the optimal position, it is fixated in the deep tissue with an anchor. It may then either be directly connected to a subcutaneously implanted pulse generator (IPG) or externalized and connected to an external stimulation device for a trial period ranging from a few days to 4 weeks. In the latter case, the IPG is later implanted if the test stimulation period yields significant improvement of the pain condition.

An example of equipment used for SCS is inserted as Figs. 2 (leads) and 3 (IPGs). An illustration of a percutaneous implantation procedure can be found in Fig. 4.1–4.9.

Fig. 2

Example of leads used for spinal cord stimulation. Leads manufactured by St. Jude Medical. A 2-Euro coin is used for size comparison. From left to right: 14G Tuohy needle used for implantation of percutaneous leads, conventional 8-contact percutaneous lead (Octrode), percutaneous 8-contact hybrid lead (S8 Lamitrode), surgical 20-contact lead (Penta). Photo by Kristian Bang, Aarhus University Hospital.

Fig. 3

Example of IPGs used for spinal cord stimulation. IPGs manufactured by St. Jude Medical. A 2-Euro coin is used for size comparison. From left to right: 8-channel non-rechargeable IPG (Genesis), 16-channel non-rechargeable IPG (EonC), 16-channel rechargeable IPG (Eon). Photo by Kristian Bang, Aarhus University Hospital.

Fig. 4.1–4.9

Description of percutaneous SCS procedure (complete implantation). Male patient with pain from CRPS II in his left hand. Permission to use the pictures has been obtained from the patient. Implanted with an 8-contact percutaneous lead and a non-rechargeable IPG. Some differences exist in technical specifications and implantation procedure between each manufacturer’s equipment but the figures illustrate the general principle. Procedure performed by Kaare Meier and Jens Christian Sørensen at the Centre for Ambulatory Surgery, Aarhus University Hospital. Fig. 4.1. A short incision is made in the midline. A pocket is then created by carefully dissecting the subcutaneous tissue just above the muscle fascia. Fig. 4.2. A modified Tuohy cannula is inserted into the epidural space via a paramedian approach. The exact localization is confirmed by a combination of fluoroscopy and loss-of-resistance technique. Fig. 4.3. The lead is inserted through the Tuohy cannula. Fig. 4.4. Using fluoroscopy, the implanted lead is advanced cranially inside the epidural space. The lead can be steered as it is advanced through careful manipulation of an inserted, curved stylet. Fig. 4.5. Once the electrode is in place, an anatomical landmark or an instrument fixed to the draping can be used to verify a stable position. Fig. 4.6. The lead is connected to the programming device via a cable interface. By activating the various contacts at different settings, the aim is to obtain parasthesia coverage of the entire painful area. Lead repositioning is often needed. Fig. 4.7. When a satisfactory position of the lead is obtained, it is anchored to the fascia. Strain relief loops are made and hidden in the prepared pocket, and an extension (not shown here) is attached. The extension is then tunnelled subcutaneously to a deep pocket dissected in the subcutis in a suitable location. Fig. 4.8. The lead is connected to the IPG. Fig. 4.9. Excess lead is wound up into a loop hidden behind the IPG. The IPG is implanted in the pocket, and incisions are closed in minimum two layers.

2.6 Indications for spinal cord stimulation

SCS is being used to treat a wide range of pain conditions but unfortunately there is a marked lack of randomized controlled trials; indications that have been evaluated as amenable for SCS in randomized trials are so far limited to complex regional pain syndrome (CRPS I) [45], angina pectoris [46,47], and radicular pain after failed back surgery syndrome (FBSS) [48,49].

Other conditions that are generally considered good indications for SCS include pain due to peripheral nerve injury, stump pain [50], peripheral vascular disease [51,52] and diabetic neuropathy [53,54]; whereas phantom pain [55], postherpetic neuralgia [56,57], chronic visceral pain [58], and pain after partial spinal cord injury [59] remain more controversial. For some indications like pain after root avulsion, pain after complete spinal cord injury, or perineal pain only anecdotal material is available. The general opinion is that SCS is not effective in relieving central neuropathic pain states.

A remarkable effect of SCS treatment of peripheral vascular disease and angina pectoris is that some clinical and experimental evidence points to improvement in the ischaemic condition in addition to the purely pain-relieving effect [60,61].

Commonly recommended contraindications for the treatment include pregnancy, coagulopathy, severe addiction to psychoactive substances, and lack of ability to cooperate (e.g. due to active psychosis or cognitive impairment).

2.7 Controversies in spinal cord stimulation

Most implanters agree that careful patient selection prior to implantation is essential to achieve a good outcome. However, despite rather extensive research into possible factors predicting the outcome of the treatment, there is still a marked disagreement on the constituents of a proper patient screening. Professional psychological evaluation, MR imaging of the spinal canal, quantitative sensory testing (QST), neuropathic pain questionnaire scoring, and screening with TENS are examples of policies that are being strongly advocated by some implanters and discouraged by others [62,63,64].

The most generally agreed key factor in patient selection is evaluation of the outcome of a short period of trial stimulation, although a few authors have questioned the universal value of trial stimulation [15]. Unfortunately, there is no general agreement on the definition of a passed trial. Most clinical studies rate a 50% pain reduction on either a 0–100 Visual Analogue Scale (VAS) or a 0–10 Numerical Rating Scale (NRS) as the minimum requirement for proceeding from a trial implantation to a full implantation. However, in everyday practice experienced implanters recommend a plethora of follow-up tools ranging from reductions in pain scores to improvements in various questionnaires, patient feedback (often using the Patient’s Global Impression of Change, PGIC), the physician’s own gut feeling, reduction in analgesics, or a combination of those. It is important to note that even a successful trial implantation (no matter the success criteria) is no guarantee for a successful long-term treatment outcome.

The lack of a definition for treatment success also hampers evaluation of long-term treatment effect. Often-quoted figures are in the 50–75% range, but the numbers depend heavily on indication, experience of implanters, and certainly success criteria. Many clinical studies and published case series also lack proper handling of missing data due to patient dropouts when calculating success rates.

A final issue receiving substantial attention is the complication rates of the treatment. An often-quoted reference work is the extensive 2004 review by Tracy Cameron [65], listing lead migration rates at 13.2%, lead breakage at 9.1%, infection at 3.4%, pain over implant at 0.9%, and dural puncture at a mere 0.3%. The complication rates listed in various reports vary considerably; and it is this author’s impression from personal communication with experienced European colleagues that in general practice particularly lead migration, pain over implant, and dural tear is a much more common occurrence than these figures show, whereas lead breakage is a rather rare event when using modern implants.

Spinal cord stimulation is a therapy with high initial cost, potential surgical complications, and large demand for follow-up, yet vital parameters concerning patient selection, complications, and outcomes are still largely based on relatively few clinical trials and single-centre case series. The Aarhus Neuromodulation Database Project represents an attempt to gather high-quality treatment data in the general SCS patient population [66]. The database covers core SCS treatment parameters, including procedure-related details and complications, and features recording of key success parameters such as pain intensity, work status, and quality of life. Designed for international collaboration, it is intended to contribute vital data to answer three central questions in neuromodulation surgery: Whom should we treat, how should we optimally proceed, and what outcome can we realistically expect?