Neuromodulation: Technology at the Neural Interface Received: October 6, 2013
Revised: March 18, 2014
Accepted: April 18, 2014
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12205
Spinal Cord Stimulation for Intractable Pain Evaluated by a Collision Study Using Somatosensory Evoked Potentials: A Preliminary Report Eiichirou Urasaki, MD, PhD*; Mami Tsuda, CE†; Shunya Nakane, MD, PhD‡; Keisuke Toyoda, MD, PhD*; Tetsuya Umeno, MD*; Yuzo Yamakawa, MD, PhD* Objective: Appropriate stimulation of the dorsal column is required in order to achieve optimal control over pain by way of spinal cord stimulation (SCS). In this study, we objectively evaluated changes in somatosensory evoked potentials (SEPs) during a collision test in order to investigate whether paresthetic sensation or amount of pain reduction was correlated with the degree of dorsal column stimulation. Materials and Methods: We studied 12 patients with intractable pain who underwent permanent SCS implantation. SEP collision was examined while recording the cortical SEP components elicited by posterior tibial nerve stimulation. A positive collision effect was observed when the SEP amplitude was clearly reduced by the SCS. Results: Based on the SEP collision findings, the effects of SCS were classified into four patterns: positive collision with pain reduction (Type 1), positive collision without pain reduction (Type 2), negative collision with pain reduction (Type 3), and negative collision without pain reduction (Type 4). Type 1 was observed for well-known diseases in which SCS was very effective, whereas Type 2 was seen in poor candidates for dorsal column stimulation. Patients with poststroke pain exhibited various patterns including types 1, 2, and 3. One patient showed Type 4 patterning, and we recommended further SCS trials before the abandonment of SCS therapy for this patient. Conclusions: We show that SEP collision is useful for evaluating the degree of dorsal column stimulation needed as well as in considering factors related to differences between responders and nonresponders to SCS therapy. Keywords: Collision study, dorsal column stimulation, pain, somatosensory evoked potentials (SEP), spinal cord stimulation (SCS) Conflict of Interest: Eiichirou Urasaki received an honorarium as a speaker for St Jude Medical. The other authors reported no conflicts of interest.
INTRODUCTION
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Spinal cord stimulation (SCS) is widely used to control various intractable forms of neuropathic pain (1–3). The first step in controlling pain via SCS is to appropriately stimulate the dorsal column of the spinal cord. In clinical practice, the location of the painful area, distribution of paresthetic sensations elicited by SCS, and degree of pain reduction must be evaluated; all of these factors are evaluated using subjective information provided by the patient. As paresthetic sensation is dependent on various factors, including stimulus frequency, this sensation may not necessarily be correlated with the degree of pain relief and amount of dorsal column stimulation. From the standpoint of physicians, the relation between these parameters is an ongoing question. Objective electrophysiological measurement of dorsal column stimulation would, therefore, be useful to 1) investigate whether the SCS method actually stimulates the dorsal column of the spinal cord, 2) determine what kinds of neuropathic pain are responsive to dorsal column stimulation, and 3) assess whether stimulation of the extralemniscal pathway modulates neuropathic pain. We selected both patients with common www.neuromodulationjournal.com
indications of SCS and patients with several pain conditions generally classified as uncommon responders to SCS (e.g., post-stroke pain or fibromyalgia) (2,3), so it was possible to evaluate the change of somatosensory evoked potential (SEP) collision in different patient populations. One important finding of this study was that
Address corresponding to: Eiichirou Urasaki, MD, PhD, Department of Neurosurgery, Nagasaki Kawatana Medical Center, Nishi-kyusyu Brain and Nerve Center, Shimokumigo 2005-1, Kawatana-cho, Higashi-sonogigun, Nagasaki 859-3615, Japan. Email: [email protected] * Department of Neurosurgery, Nagasaki Kawatana Medical Center, Nishi-kyusyu Brain and Nerve Center, Nagasaki, Japan; † Department of Clinical Engineering, Nagasaki Kawatana Medical Center, Nishikyusyu Brain and Nerve Center, Nagasaki, Japan; and ‡ Department of Neurology, Nagasaki Kawatana Medical Center, Nishi-kyusyu Brain and Nerve Center, Nagasaki, Japan For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http:// www.wiley.com/bw/submit.asp?ref=1094-7159&site=1
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 746–752
SCS AND SEP COLLISION
Table 1. Summary of Patient Clinical Data. Case
Age/Sex
Pain location
Disease
Electrode position
SCS effect (Trial)
SCS parameters: PW (μsec)/frequency (Hz)
SEP collision
1 2 3 4 5 6 7 8 9 10 11 12
56/M 44/M 67/M 66/F 73/F 77/F 69/M 53/M 64/M 72/F 44/F 50/M
Right leg Right arm and leg Lumbar and legs Lumbar and right leg Bilateral legs Right leg Right arm and chest Leftt leg Right leg Lumbar and legs Lumbar and legs Lumbar
Complex regional pain syndrome Failed neck surgery syndrome Failed back surgery syndrome Parkinson’s disease Parkinson’s disease Left thalamic hemorrhage Left thalamic infarction Right putaminal hemorrhage Wallenberg syndrome HAM Fibromyalgia Parkinson’s disease
L1-2 C4-6 T10-12 T8-9 T7-10 T12-L1 C3-T3 T7-8 T10-L2 T7-9 T8-9 T8-11
(G) G (G) G (G) G (G) G (F) F (F) F (F) F (F) P (F) P (P) P (G) P (F) P
300/20 210/20 200/50 210/10 450/100 350/40 250/200 210/100 200/10 450/60 200/50 450/30
+ + + + + + − + + + + −
G, pain reduction more than 50%; F, pain reduction between 30 and 50%; P, pain reduction less than 30%. SCS, spinal cord stimulation; PW, pulse width; SEP, somatosensory evoked potential; HAM, human T-lymphotropic virus 1–associated myelopathy.
sufficient dorsal column stimulation with negligible pain relief indicated a poor candidate for SCS. In this preliminary study we demonstrated that the relation between dorsal column stimulation and pain reduction could be evaluated by the SEP collision method and that this method might be a useful tool in categorizing various forms of neuropathic pain into subtypes with respect to their responsiveness to dorsal column stimulation.
PATIENTS AND METHODS
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We evaluated 12 patients with intractable pain who underwent permanent SCS (see Table 1 for a summary of the clinical data of these patients). The degree of pain reduction was calculated as a percentage by comparing pre- and post-SCS scores on a visual analogue scale (VAS). When VAS score was reduced more than 50%, the SCS effect was judged as good (displayed as G in Table 1); less than 50% but above 30% was deemed fair (F), and less than 30% was listed as poor (P). Patients with pain reduction more than 30% (G and F in Table 1) were categorized in the positive pain reduction group, and those with pain reduction less than 30% (P in Table 1) were categorized in the poor pain reduction group. Although no consensus has been reached regarding the definition of good outcome in chronic pain, the criterion of more than 50% pain relief has been used in many studies (4). Because our study included patients with poststroke pain, fibromyalgia, or pain related to human T-lymphotropic virus 1–associated myelopathy (HAM), more than 30% pain reduction (less than 50%) was regarded as meaningful, considering the severity of pain these patients typically experience (4). Table 1 shows that some patients, except for those with failed back surgery syndrome or complex regional pain syndrome (CRPS), were not good candidates for SCS, but their chronic pain might accompany neuropathic pain, which was often not distinguishable from the pain caused by the primary disease. In these cases, we routinely performed SCS trials, and if the patient strongly desired to receive permanent implantation, we performed surgery several months after the trial. All patients in this study received the SCS trial examination and experienced some reduction of their pain. The test period of the SCS
trial lasted from 4–7 days, and the degree of pain reduction experienced during this trial can be seen in Table 1. Although pain reduction was not over 50% in some patients, permanent implantation surgery was still performed when it was strongly desired by the patient. Furthermore, we determined that certain patients with central neuropathic pain such as poststroke pain (cases 6–9) were eligible for motor cortex stimulation; however, these patients preferred SCS therapy, as they did not wish to receive brain surgery. Case 11, a case of fibromyalgia, exhibited more than 50% pain reduction during the SCS trial and 3 months after permanent implantation. However, the effect of pain control gradually diminished, and at the time of the SEP collision study, the patient’s pain reduction was determined to be less than 30%. Cycle mode stimulation or a change of stimulus frequency was effective in slightly improving this patient’s pain reduction (between 30% and 50%); however, within several months the patient’s pain reduction was again less than 30%. Three patients with Parkinson’s disease (PD) underwent deep brain surgery in the bilateral subthalamic nuclei, and this was found to remarkably improve the majority of their PD-related symptoms, with the exception of lumbago and/or leg pain. One of these two patients (Case 4), classified as having a Type 1 pattern SCS effect (positive collision with pain reduction), was found to have degenerative lumbar spondylosis and scoliosis, while the other Type 1 patient (Case 5) had scoliosis and camptocormia. Finally, the third patient with PD (Case 12), showing severe camptocormia and lumbago, underwent lumbar fixation surgery with the diagnosis of L4/5 facet/discogenic pain before SCS therapy; however, this patient’s pain persisted. The degree of pain control in these three patients varied from good to poor and is described in Table 1. SEP collision was examined by stimulating the dorsal column while recording cortical SEPs elicited by posterior tibial nerve (PTN) stimulation in the awake state. All patients except for one (Case 7 in Table 1) had lower limb pain, and electrode placement varied from lumbar to cervical regions (Table 1). Although the SCS electrode was placed in the cervical region in two cases, SEP collision using PTN stimulation could be evaluated. These two cases are reported elsewhere (5). Figure 1 shows a schematic illustrating the fundamental hypothesis of the SEP collision study. Briefly, ascending electrical impulses
URASAKI ET AL. N50
SEP collision findings and Pain reducƟon PTN sm.
Pain reducƟon (+)
Spinal Dorsal Column
SEP collision (+) P39
Scalp-recorded SEP
SCS
Pain reducƟon (-)
Poststroke pain (2) Fibromyalgia (1) HAM-related pain (1)
Pain reducƟon (+)
Poststroke pain (1)
Pain reducƟon (-)
Parkinson's and lumbago (1)
PTN sm. Spinal Dorsal Column
Failed back surgery syndrome (2) Parkinson's and lumbago (2) CRPS (1) Poststroke pain (1)
SEP collision (-) Figure 1. Schematic illustration of the somatosensory evoked potential (SEP) collision study. Electrical impulses from the posterior tibial nerve (PTN) travel along the dorsal column of the spinal cord and elicit scalp SEPs (P39/N50). Due to the collision between ascending SEP impulses and antidromic descending electrical impulses from the spinal cord stimulation (SCS), the amplitude of the scalp-recorded SEP is reduced when the SCS is applied over the dorsal column.
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from the PTN travel along the dorsal column of the spinal cord and elicit scalp SEPs. Amplitudes of the scalp-recorded SEPs decrease when SCS is applied to the dorsal column due to the collision between the ascending SEP volleys and descending antidromic SCS volleys. SCS intensity was increased up to the level at which patients reported paresthesia or described as being slightly beyond their individual comfort level but within tolerable limits. As individuals vary, pulse width and stimulus frequency differed between patients. Therefore, there is a possibility that the change of these parameters induced different SEP collision effects. However, because the purpose of this study was to investigate the correlation between the degree of dorsal column stimulation and pain reduction, the results reported here are meant to reflect only the patients’ states at the time of SEP collision examination. When the amplitude of the cortical response P39/N50 (6) was reduced to more than 40% of the pre-SCS control state, it was interpreted as a positive collision effect. The mean pre-SCS control P39/ N50 amplitude difference (fluctuation) was 15.4% (difference of two SEP amplitudes divided by the larger SEP amplitude), but it varied from 0% (minimum) to 32.3% (maximum). Based on these findings, we tentatively set a 40% reduction in amplitude as the cutoff value in this study. In other words, if we observed a more than 40% reduction in amplitude, we determined that this was clearly beyond the level of amplitude fluctuation. Lastly, a positive SEP collision effect indicated sufficient dorsal column stimulation by SCS, as early SEP components have been shown to be constructed mainly of ascending dorsal column volleys (when the peripheral nerve is electrically stimulated) (6). PTN-SEPs were obtained by delivering 0.2-ms square wave pulses over the medial side of the ankle, with cathodes being placed between the medial border of the Achilles tendon and the posterior border of the medial malleolus and the 3-cm distal anode (6). Stimulus intensity was adjusted to yield muscle twitches or twice the sensory threshold level, with a stimulation rate of 5 Hz. The scalp recording electrode was at Cz’ (2 cm posterior to Cz) and the reference electrode was at Fz, as defined by the international 10–20 system, where Cz is the central zero (midline) and Fz is the frontal zero (midline) (6). Evoked activity was amplified with a 10- to 300-Hz bandpass filter and averaged over 300–1000 trials. www.neuromodulationjournal.com
Figure 2. Correlation between somatosensory evoked potential (SEP) collision findings and pain reduction in patients with various pathological conditions. CRPS, complex regional pain syndrome; HAM, human T-lymphotropic virus 1–associated myelopathy.
The institutional review board of our hospital approved this study, and written informed consent was obtained from all patients and patient families.
RESULTS Analysis of the data obtained from all 12 patients showed that P39/N50 amplitudes were reduced from the pre-SCS control state (0.89 ± 0.51 μV [mean ± standard deviation]) to the SCS-on state (0.46 ± 0.33 μV), and that the difference was statistically significant (two-tailed p value < 0.0001, Wilcoxon matched-pairs signed-ranks test using InStat [GraphPad] Ver. 3.0). Based on SEP collision findings, the effects of SCS could be classified into four patterns: positive collision with pain reduction (Type 1), positive collision without pain reduction (Type 2), negative collision with pain reduction (Type 3), and negative collision without pain reduction (Type 4) (see Fig. 2). The Type 1 pattern group included two patients with failed back surgery syndrome, two patients with lumbago accompanied by PD, and one patient with CRPS (Fig. 2). All patients in this pattern group were afflicted with well-known pathological conditions, and SCS was generally effective (2,3,7). Figure 3 shows an SEP collision study performed on a patient with lumbago and lower limb pain associated with PD (Case 4). SCS reduced this patient’s pain over 60% compared with her preoperative state. Clear amplitude reductions of the right and left PTN-SEPs were also seen when SCS strength was increased to the paresthesia threshold level as well as to a more comfortable level, indicating sufficient stimulation of the bilateral dorsal columns. Figure 4a also demonstrates positive collision findings of a patient with CRPS who was relieved from pain by SCS (Case 1). Because of pain in his right hip and leg, this patient was restricted to the use of a wheelchair preoperatively, but achieved independent walking after SCS implantation. Clear SEP amplitude reduction by SCS was shown when the SCS strength was increased above his comfort level (Fig. 4a). Figure 4b shows the SEP collision study with various stimulus electrode combinations. Clear SEP amplitude reduction was obtained when the three SCS electrode combinations were stimulated. Interestingly, the patient had
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 746–752
SCS AND SEP COLLISION 5 Th8
Cz′(−)/Fz(+) 5 μV
SCS 6(+)/7(−)/8(+) 210 μsec 10 Hz
500 × 2
15 10
0
4
N50
SCS off R
P39
L
SCS 2.1V Paresthesia threshold
100 msec
SCS 2.7V Paresthesia (+) comfortable SCS off
Rt. PTN stim.
Lt. PTN stim.
Figure 3. Somatosensory evoked potential (SEP) collision study in a patient (Case 4) with lumbago and right leg pain associated with Parkinson’s disease. Note the clear amplitude reduction of right and left posterior tibial nerve (PTN) SEPs. Two SEP waveforms are superimposed.
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DISCUSSION In order to determine the best stimulus position over the dorsal extent of the spinal cord for treatment of neuropathic pain, the following electrophysiological examinations were conducted: 1. Analysis of amplitude laterality of scalp SEP waveforms elicited by epidural stimulation of the spinal cord (12,13). SEPs were simultaneously recorded from the right and left scalp, and the side of the scalp that yielded larger amplitudes indicated that the contralateral side of the dorsal column was the side that was dominantly stimulated (13). 2. Recording spinal SEPs from SCS electrodes by stimulation of the peripheral nerve (14,15). SEP mapping studies were carried out along SCS electrodes to capture the site where the maximum SEP amplitude was obtained. When the spinal electrode showing the maximum SEP was stimulated, sufficient paresthesia could be induced in the corresponding peripheral body area (14). 3. Evaluation of electromyograms (16,17) or peripheral nerve activities (18–20) after spinal cord stimulation. The relation between the side of the spinal cord and SCS electrode position was determined by detecting the laterality of these activities. 4. Evaluation of the SCS interference on SEPs or “SEP collision” (5,21–24). The present study demonstrated the usefulness of SEP collision for evaluating the degree of dorsal column stimulation, especially in patients who have undergone permanent SCS implantation. For total obliteration of an ascending volley via collision with a descending volley, synchronization of the two reciprocally directed volleys is necessary (25). This can generally be achieved by performing a strictly planned experiment and by preferentially adjusting stimulus conditions such as frequency and impulse duration (19). On the other hand, it is also true that the neurophysiological mechanism of impulse collision implies that two action potentials
© 2014 International Neuromodulation Society
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already selected two out of the three electrode combinations before completion of the collision study (Fig. 4b). The Type 2 pattern group included one patient with fibromyalgia and one patient with HAM-related pain. Although a more than 50% SEP reduction was obtained in these two patients, pain relief was less than 30% of the preoperative state. In the patient with HAM, SCS was continued for more than 3 years without side effect; however, only warming sensations in the lower extremities were observed. In the patient with fibromyalgia, her pain recurred after SCS surgery. Thus, we inferred that patients with these types of pain might not be good candidates for dorsal column stimulation (Table 1, Fig. 2) (2,3). One poststroke patient (Case 7) reported pain reduction with no SEP collision effect (Type 3), implying that extralemniscal stimulation might induce a central pain suppression mechanism (Table 1, Fig. 2) (4,8–11). The result of SEP in this patient has been reported elsewhere (5). The other three poststroke patients showed various pain patterns, including one patient with Type 1 patterning and two patients with Type 2 (Table 1, Fig. 2). This suggests that the long-term effect of SCS on pain reduction for poststroke patients could be difficult to predict using only the evaluations obtained from the degree of dorsal column stimulation. There was one patient (Case 12) with lumbago associated with PD who showed no SEP collision effect without pain reduction. Furthermore, lumbar fixation surgery and SCS on Th8–11 failed to reduce his severe lumbago. Unpleasant electrical sensation spread to regions outside of the lumbar area, and the back and abdominal muscles twitched when SCS strength was increased. All of these factors precluded increasing the intensity of SCS to a level where it would cover up the painful lumbar area. Additionally, various combinations of SCS electrodes with tolerable stimulus intensity could not induce SEP amplitude reduction more than 40%, indicating insufficient stimulation of the dorsal columns. All of these findings suggest the need for a further trial to obtain sufficient dorsal column stimulation before making the final judgment of SCS as ineffective.
URASAKI ET AL. Cz′(−)/Fz(+)
a
SCS 300 μs 20 Hz
300 × 1 N50
SCS 1.0V
P39
SCS 1.5V Paresthesia threshold
SCS 2.0V Pain map SCS 2.5V SCS stim. 1(−)/2(+)
Comfortable
SCS 3.0V R
SCS off 100 msec 5 μV
b
Rt. PTN stim.
Lt. PTN stim.
Cz′(−)/Fz(+)
5 μV
0 1 4 2 5 3 6 7
L L1
Paresthesia Bil. hips, legs (R>L)
SCS 300 μs 20 Hz
500 × 2 (superimposed) N50
Pre-SCS
P39 100 msec
1(−)/2(+) 3.5V Rt. hip & back thigh
2(−)/3(+) 2.5V Bil. hips
4(−)/5(+) 2.2V Rt. leg
5(−)/6(+) 2.3V Rt. ankle
6(−)/7(+) 2.4V Rt. back leg
Rt. PTN stim.
Lt. PTN stim.
Figure 4. Patient with complex regional pain syndrome (Case 1) demonstrating remarkable effects of spinal cord stimulation (SCS). a. A clear somatosensory evoked potential (SEP) amplitude reduction could be seen (arrows) when SCS was administered at a strength that was above the reported comfort level. The first control SEP waveform is superimposed on subsequent SEP waveforms. b. SEP collision study using various SCS electrode combinations. Two SEP waveforms are superimposed over each SCS electrode combination. Paresthesia sites on the patient’s body elicited by SCS are described under the numbers of combined stimulus electrodes. A clear SEP amplitude reduction was obtained by the stimuli of three SCS electrode combinations (arrows), which decreased the patient’s right hip and leg pain. Interestingly, two out of the three electrode combinations, specifically 1(−)/2(+) and 4(−)/5(+), had already been selected by the patient before the SEP collision study.
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travelling in the opposite direction on the same fiber cancel each other at the moment of their collision (23,25). This definition does not indicate that these two ascending and descending signals must be completely synchronized. In the current study, it seems apparent that there was a collision between the ascending SEP www.neuromodulationjournal.com
volley and descending SCS volley in the same dorsal column fiber, even though no attempt was made to synchronize the two signals. Moreover, if we adjusted both ascending and descending volleys to be more synchronized, a more apparent reduction in SEP amplitude would be obtained (19); however, this is beyond the scope of
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Neuromodulation 2014; 17: 746–752
SCS AND SEP COLLISION
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SEP collision with pain reduction also suggests that clinical responsiveness to preimplantation tests is of the highest importance in selecting patients for SCS. In order to properly categorize the relationship between different patterns of pain and the effectiveness of dorsal column stimulation, more data collection from patients with neuropathic pain will be required. According to recent evidence-based guidelines (2,3), SCS is recommended in patients with failed back surgery syndrome and CRPS (Grade B recommendation) and in patients with traumatic neuropathy and brachial plexopathy (Grade C), but residual patients with other neuropathic pain syndromes are deemed Grade I, meaning the benefits and drawbacks of SCS cannot be determined. It is, however, also true that there are certain patients who belong to good indication groups who have poor results or who fall into a poor indication group but have good results. In order to determine the difference between responders and nonresponders, objective neurophysiological evaluations of dorsal column stimulation will be one of the most important steps in developing pain control using SCS technology.
Authorship Statements Dr. Urasaki and CE. Tsuda designed and conducted the study, including patient recruitment, data collection and data analysis. Dr. Urasaki prepared the manuscript draft with important intellectual input from Drs. Toyoda, Umeno, Nakane, and Yamakawa. All authors approved the final manuscript.
How to Cite this Article: Urasaki E., Tsuda M., Nakane S., Toyoda K., Umeno T., Yamakawa Y. 2014. Spinal Cord Stimulation for Intractable Pain Evaluated by a Collision Study Using Somatosensory Evoked Potentials: A Preliminary Report. Neuromodulation 2014; 17: 746–752
REFERENCES 1. Meyerson BA, Cui JG, Yakhnitsa V et al. Modulation of spinal pain mechanisms by spinal cord stimulation and the potential role of adjuvant pharmacotherapy. Stereotact Funct Neurosurg 1997;68:129–140. 2. Mailis A, Taenzer P. Evidence-based guideline for neuropathic pain interventional treatments: spinal cord stimulation, intravenous infusions, epidural injections and nerve blocks. Pain Res Manag 2012;17:150–158. 3. Cruccu G, Aziz TZ, Garcia-Larrea L et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007;14:952–970. 4. Ali MM, Saitoh Y, Hosomi K, Oshino S, Kishima H, Yoshimine T. Spinal cord stimulation for central poststroke pain. Neurosurgery 2010;67 (3 Suppl. Operative):ons206– ons212. 5. Urasaki E, Tsuda M, Nakane S, Toyoda K, Umeno T, Yamakawa Y. Evaluation of spinal dorsal column stimulation using the SEP collision method. Functional Neurosurgery (Kioutekinousinkeigeka in Japanese), 2013;52:5–13. (In Japanese). 6. Cruccu G, Aminoff MJ, Curio G et al. Recommendation of the clinical use of somatosensory-evoked potentials. Clin Neurophysiol 2008;119:1705–1719. 7. Agari T, Date I. Spinal cord stimulation for the treatment of abnormal posture and gait disorder in patients with Parkinson’s disease. Neurol Med Chir (Tokyo) 2012;52:470–474. 8. Bantli H, Bloedel JR, Thienprasit P. Supraspinal interactions resulting from experimental dorsal column stimulation. J Neurosurg 1975;42:296–300. 9. Kishima H, Saitoh Y, Oshino S et al. Modulation of neural activity after spinal cord stimulation for neuropathic pain: H215O PET study. Neuroimage 2010;49:2564–2569. 10. Larson SJ, Sances A, Riegel DH, Meyer GA, Dallmann DE, Swiontek T. Neurophysiological effects of dorsal column stimulation in man and monkey. J Neurosurg 1974;41:217–223. 11. Nagamachi S, Fujita S, Nishii R et al. Alteration of regional cerebral blood flow in patients with chronic pain—evaluation before and after epidural spinal cord stimulation. Ann Nucl Med 2006;20:303–310.
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the current study. We, therefore, use the term “SEP collision” in accordance with several previous studies (1,5,23). It should be noted that the reduction in scalp SEP amplitude during SCS could be induced by several other mechanisms aside from spike collision in the dorsal column. For example, saturation in the sensory cortex by SCS could prevent production of synchronous large-amplitude SEP, or there could be a gating mechanism in the dorsal horn (24). Further studies will need to be carried out to determine the main mechanism responsible for the SEP changes that we observed during SCS. An intraoperative SEP collision study reported by Balser et al. was aimed at determining SCS electrode positioning on the spinal cord (21). If a larger trial reproduced their results, this method could prove to be intraoperatively useful and could allow singlestage SCS surgery. We confirmed the usefulness of this method during surgery (5) and, furthermore, we developed this method to evaluate a patient who underwent permanent implantation of an SCS system. It is well known that PD-related pain (dystonic and central pain) and PD-unrelated pain (musculoskeletal, neuronal, and radicular pains) are often mixed in the types of pain that are perceived by patients with PD. SCS is generally effective for neuropathic pain but not for nonneuropathic pain such as nociceptive pain. As suggested by Agari and Date (7), pain reduction in patients with PD is probably achieved because lumbago and leg pain are partially caused by chronic neuropathic pathological conditions, which are factors even in musculoskeletal pain that comprises several nociceptive components (7). It is important to point out that following SCS, 4/12 patients demonstrated poor results, while 9/12 patients exhibited poor to fair results (
Revised: March 18, 2014
Accepted: April 18, 2014
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12205
Spinal Cord Stimulation for Intractable Pain Evaluated by a Collision Study Using Somatosensory Evoked Potentials: A Preliminary Report Eiichirou Urasaki, MD, PhD*; Mami Tsuda, CE†; Shunya Nakane, MD, PhD‡; Keisuke Toyoda, MD, PhD*; Tetsuya Umeno, MD*; Yuzo Yamakawa, MD, PhD* Objective: Appropriate stimulation of the dorsal column is required in order to achieve optimal control over pain by way of spinal cord stimulation (SCS). In this study, we objectively evaluated changes in somatosensory evoked potentials (SEPs) during a collision test in order to investigate whether paresthetic sensation or amount of pain reduction was correlated with the degree of dorsal column stimulation. Materials and Methods: We studied 12 patients with intractable pain who underwent permanent SCS implantation. SEP collision was examined while recording the cortical SEP components elicited by posterior tibial nerve stimulation. A positive collision effect was observed when the SEP amplitude was clearly reduced by the SCS. Results: Based on the SEP collision findings, the effects of SCS were classified into four patterns: positive collision with pain reduction (Type 1), positive collision without pain reduction (Type 2), negative collision with pain reduction (Type 3), and negative collision without pain reduction (Type 4). Type 1 was observed for well-known diseases in which SCS was very effective, whereas Type 2 was seen in poor candidates for dorsal column stimulation. Patients with poststroke pain exhibited various patterns including types 1, 2, and 3. One patient showed Type 4 patterning, and we recommended further SCS trials before the abandonment of SCS therapy for this patient. Conclusions: We show that SEP collision is useful for evaluating the degree of dorsal column stimulation needed as well as in considering factors related to differences between responders and nonresponders to SCS therapy. Keywords: Collision study, dorsal column stimulation, pain, somatosensory evoked potentials (SEP), spinal cord stimulation (SCS) Conflict of Interest: Eiichirou Urasaki received an honorarium as a speaker for St Jude Medical. The other authors reported no conflicts of interest.
INTRODUCTION
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Spinal cord stimulation (SCS) is widely used to control various intractable forms of neuropathic pain (1–3). The first step in controlling pain via SCS is to appropriately stimulate the dorsal column of the spinal cord. In clinical practice, the location of the painful area, distribution of paresthetic sensations elicited by SCS, and degree of pain reduction must be evaluated; all of these factors are evaluated using subjective information provided by the patient. As paresthetic sensation is dependent on various factors, including stimulus frequency, this sensation may not necessarily be correlated with the degree of pain relief and amount of dorsal column stimulation. From the standpoint of physicians, the relation between these parameters is an ongoing question. Objective electrophysiological measurement of dorsal column stimulation would, therefore, be useful to 1) investigate whether the SCS method actually stimulates the dorsal column of the spinal cord, 2) determine what kinds of neuropathic pain are responsive to dorsal column stimulation, and 3) assess whether stimulation of the extralemniscal pathway modulates neuropathic pain. We selected both patients with common www.neuromodulationjournal.com
indications of SCS and patients with several pain conditions generally classified as uncommon responders to SCS (e.g., post-stroke pain or fibromyalgia) (2,3), so it was possible to evaluate the change of somatosensory evoked potential (SEP) collision in different patient populations. One important finding of this study was that
Address corresponding to: Eiichirou Urasaki, MD, PhD, Department of Neurosurgery, Nagasaki Kawatana Medical Center, Nishi-kyusyu Brain and Nerve Center, Shimokumigo 2005-1, Kawatana-cho, Higashi-sonogigun, Nagasaki 859-3615, Japan. Email: [email protected] * Department of Neurosurgery, Nagasaki Kawatana Medical Center, Nishi-kyusyu Brain and Nerve Center, Nagasaki, Japan; † Department of Clinical Engineering, Nagasaki Kawatana Medical Center, Nishikyusyu Brain and Nerve Center, Nagasaki, Japan; and ‡ Department of Neurology, Nagasaki Kawatana Medical Center, Nishi-kyusyu Brain and Nerve Center, Nagasaki, Japan For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http:// www.wiley.com/bw/submit.asp?ref=1094-7159&site=1
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 746–752
SCS AND SEP COLLISION
Table 1. Summary of Patient Clinical Data. Case
Age/Sex
Pain location
Disease
Electrode position
SCS effect (Trial)
SCS parameters: PW (μsec)/frequency (Hz)
SEP collision
1 2 3 4 5 6 7 8 9 10 11 12
56/M 44/M 67/M 66/F 73/F 77/F 69/M 53/M 64/M 72/F 44/F 50/M
Right leg Right arm and leg Lumbar and legs Lumbar and right leg Bilateral legs Right leg Right arm and chest Leftt leg Right leg Lumbar and legs Lumbar and legs Lumbar
Complex regional pain syndrome Failed neck surgery syndrome Failed back surgery syndrome Parkinson’s disease Parkinson’s disease Left thalamic hemorrhage Left thalamic infarction Right putaminal hemorrhage Wallenberg syndrome HAM Fibromyalgia Parkinson’s disease
L1-2 C4-6 T10-12 T8-9 T7-10 T12-L1 C3-T3 T7-8 T10-L2 T7-9 T8-9 T8-11
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G, pain reduction more than 50%; F, pain reduction between 30 and 50%; P, pain reduction less than 30%. SCS, spinal cord stimulation; PW, pulse width; SEP, somatosensory evoked potential; HAM, human T-lymphotropic virus 1–associated myelopathy.
sufficient dorsal column stimulation with negligible pain relief indicated a poor candidate for SCS. In this preliminary study we demonstrated that the relation between dorsal column stimulation and pain reduction could be evaluated by the SEP collision method and that this method might be a useful tool in categorizing various forms of neuropathic pain into subtypes with respect to their responsiveness to dorsal column stimulation.
PATIENTS AND METHODS
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We evaluated 12 patients with intractable pain who underwent permanent SCS (see Table 1 for a summary of the clinical data of these patients). The degree of pain reduction was calculated as a percentage by comparing pre- and post-SCS scores on a visual analogue scale (VAS). When VAS score was reduced more than 50%, the SCS effect was judged as good (displayed as G in Table 1); less than 50% but above 30% was deemed fair (F), and less than 30% was listed as poor (P). Patients with pain reduction more than 30% (G and F in Table 1) were categorized in the positive pain reduction group, and those with pain reduction less than 30% (P in Table 1) were categorized in the poor pain reduction group. Although no consensus has been reached regarding the definition of good outcome in chronic pain, the criterion of more than 50% pain relief has been used in many studies (4). Because our study included patients with poststroke pain, fibromyalgia, or pain related to human T-lymphotropic virus 1–associated myelopathy (HAM), more than 30% pain reduction (less than 50%) was regarded as meaningful, considering the severity of pain these patients typically experience (4). Table 1 shows that some patients, except for those with failed back surgery syndrome or complex regional pain syndrome (CRPS), were not good candidates for SCS, but their chronic pain might accompany neuropathic pain, which was often not distinguishable from the pain caused by the primary disease. In these cases, we routinely performed SCS trials, and if the patient strongly desired to receive permanent implantation, we performed surgery several months after the trial. All patients in this study received the SCS trial examination and experienced some reduction of their pain. The test period of the SCS
trial lasted from 4–7 days, and the degree of pain reduction experienced during this trial can be seen in Table 1. Although pain reduction was not over 50% in some patients, permanent implantation surgery was still performed when it was strongly desired by the patient. Furthermore, we determined that certain patients with central neuropathic pain such as poststroke pain (cases 6–9) were eligible for motor cortex stimulation; however, these patients preferred SCS therapy, as they did not wish to receive brain surgery. Case 11, a case of fibromyalgia, exhibited more than 50% pain reduction during the SCS trial and 3 months after permanent implantation. However, the effect of pain control gradually diminished, and at the time of the SEP collision study, the patient’s pain reduction was determined to be less than 30%. Cycle mode stimulation or a change of stimulus frequency was effective in slightly improving this patient’s pain reduction (between 30% and 50%); however, within several months the patient’s pain reduction was again less than 30%. Three patients with Parkinson’s disease (PD) underwent deep brain surgery in the bilateral subthalamic nuclei, and this was found to remarkably improve the majority of their PD-related symptoms, with the exception of lumbago and/or leg pain. One of these two patients (Case 4), classified as having a Type 1 pattern SCS effect (positive collision with pain reduction), was found to have degenerative lumbar spondylosis and scoliosis, while the other Type 1 patient (Case 5) had scoliosis and camptocormia. Finally, the third patient with PD (Case 12), showing severe camptocormia and lumbago, underwent lumbar fixation surgery with the diagnosis of L4/5 facet/discogenic pain before SCS therapy; however, this patient’s pain persisted. The degree of pain control in these three patients varied from good to poor and is described in Table 1. SEP collision was examined by stimulating the dorsal column while recording cortical SEPs elicited by posterior tibial nerve (PTN) stimulation in the awake state. All patients except for one (Case 7 in Table 1) had lower limb pain, and electrode placement varied from lumbar to cervical regions (Table 1). Although the SCS electrode was placed in the cervical region in two cases, SEP collision using PTN stimulation could be evaluated. These two cases are reported elsewhere (5). Figure 1 shows a schematic illustrating the fundamental hypothesis of the SEP collision study. Briefly, ascending electrical impulses
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SEP collision (-) Figure 1. Schematic illustration of the somatosensory evoked potential (SEP) collision study. Electrical impulses from the posterior tibial nerve (PTN) travel along the dorsal column of the spinal cord and elicit scalp SEPs (P39/N50). Due to the collision between ascending SEP impulses and antidromic descending electrical impulses from the spinal cord stimulation (SCS), the amplitude of the scalp-recorded SEP is reduced when the SCS is applied over the dorsal column.
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from the PTN travel along the dorsal column of the spinal cord and elicit scalp SEPs. Amplitudes of the scalp-recorded SEPs decrease when SCS is applied to the dorsal column due to the collision between the ascending SEP volleys and descending antidromic SCS volleys. SCS intensity was increased up to the level at which patients reported paresthesia or described as being slightly beyond their individual comfort level but within tolerable limits. As individuals vary, pulse width and stimulus frequency differed between patients. Therefore, there is a possibility that the change of these parameters induced different SEP collision effects. However, because the purpose of this study was to investigate the correlation between the degree of dorsal column stimulation and pain reduction, the results reported here are meant to reflect only the patients’ states at the time of SEP collision examination. When the amplitude of the cortical response P39/N50 (6) was reduced to more than 40% of the pre-SCS control state, it was interpreted as a positive collision effect. The mean pre-SCS control P39/ N50 amplitude difference (fluctuation) was 15.4% (difference of two SEP amplitudes divided by the larger SEP amplitude), but it varied from 0% (minimum) to 32.3% (maximum). Based on these findings, we tentatively set a 40% reduction in amplitude as the cutoff value in this study. In other words, if we observed a more than 40% reduction in amplitude, we determined that this was clearly beyond the level of amplitude fluctuation. Lastly, a positive SEP collision effect indicated sufficient dorsal column stimulation by SCS, as early SEP components have been shown to be constructed mainly of ascending dorsal column volleys (when the peripheral nerve is electrically stimulated) (6). PTN-SEPs were obtained by delivering 0.2-ms square wave pulses over the medial side of the ankle, with cathodes being placed between the medial border of the Achilles tendon and the posterior border of the medial malleolus and the 3-cm distal anode (6). Stimulus intensity was adjusted to yield muscle twitches or twice the sensory threshold level, with a stimulation rate of 5 Hz. The scalp recording electrode was at Cz’ (2 cm posterior to Cz) and the reference electrode was at Fz, as defined by the international 10–20 system, where Cz is the central zero (midline) and Fz is the frontal zero (midline) (6). Evoked activity was amplified with a 10- to 300-Hz bandpass filter and averaged over 300–1000 trials. www.neuromodulationjournal.com
Figure 2. Correlation between somatosensory evoked potential (SEP) collision findings and pain reduction in patients with various pathological conditions. CRPS, complex regional pain syndrome; HAM, human T-lymphotropic virus 1–associated myelopathy.
The institutional review board of our hospital approved this study, and written informed consent was obtained from all patients and patient families.
RESULTS Analysis of the data obtained from all 12 patients showed that P39/N50 amplitudes were reduced from the pre-SCS control state (0.89 ± 0.51 μV [mean ± standard deviation]) to the SCS-on state (0.46 ± 0.33 μV), and that the difference was statistically significant (two-tailed p value < 0.0001, Wilcoxon matched-pairs signed-ranks test using InStat [GraphPad] Ver. 3.0). Based on SEP collision findings, the effects of SCS could be classified into four patterns: positive collision with pain reduction (Type 1), positive collision without pain reduction (Type 2), negative collision with pain reduction (Type 3), and negative collision without pain reduction (Type 4) (see Fig. 2). The Type 1 pattern group included two patients with failed back surgery syndrome, two patients with lumbago accompanied by PD, and one patient with CRPS (Fig. 2). All patients in this pattern group were afflicted with well-known pathological conditions, and SCS was generally effective (2,3,7). Figure 3 shows an SEP collision study performed on a patient with lumbago and lower limb pain associated with PD (Case 4). SCS reduced this patient’s pain over 60% compared with her preoperative state. Clear amplitude reductions of the right and left PTN-SEPs were also seen when SCS strength was increased to the paresthesia threshold level as well as to a more comfortable level, indicating sufficient stimulation of the bilateral dorsal columns. Figure 4a also demonstrates positive collision findings of a patient with CRPS who was relieved from pain by SCS (Case 1). Because of pain in his right hip and leg, this patient was restricted to the use of a wheelchair preoperatively, but achieved independent walking after SCS implantation. Clear SEP amplitude reduction by SCS was shown when the SCS strength was increased above his comfort level (Fig. 4a). Figure 4b shows the SEP collision study with various stimulus electrode combinations. Clear SEP amplitude reduction was obtained when the three SCS electrode combinations were stimulated. Interestingly, the patient had
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Figure 3. Somatosensory evoked potential (SEP) collision study in a patient (Case 4) with lumbago and right leg pain associated with Parkinson’s disease. Note the clear amplitude reduction of right and left posterior tibial nerve (PTN) SEPs. Two SEP waveforms are superimposed.
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DISCUSSION In order to determine the best stimulus position over the dorsal extent of the spinal cord for treatment of neuropathic pain, the following electrophysiological examinations were conducted: 1. Analysis of amplitude laterality of scalp SEP waveforms elicited by epidural stimulation of the spinal cord (12,13). SEPs were simultaneously recorded from the right and left scalp, and the side of the scalp that yielded larger amplitudes indicated that the contralateral side of the dorsal column was the side that was dominantly stimulated (13). 2. Recording spinal SEPs from SCS electrodes by stimulation of the peripheral nerve (14,15). SEP mapping studies were carried out along SCS electrodes to capture the site where the maximum SEP amplitude was obtained. When the spinal electrode showing the maximum SEP was stimulated, sufficient paresthesia could be induced in the corresponding peripheral body area (14). 3. Evaluation of electromyograms (16,17) or peripheral nerve activities (18–20) after spinal cord stimulation. The relation between the side of the spinal cord and SCS electrode position was determined by detecting the laterality of these activities. 4. Evaluation of the SCS interference on SEPs or “SEP collision” (5,21–24). The present study demonstrated the usefulness of SEP collision for evaluating the degree of dorsal column stimulation, especially in patients who have undergone permanent SCS implantation. For total obliteration of an ascending volley via collision with a descending volley, synchronization of the two reciprocally directed volleys is necessary (25). This can generally be achieved by performing a strictly planned experiment and by preferentially adjusting stimulus conditions such as frequency and impulse duration (19). On the other hand, it is also true that the neurophysiological mechanism of impulse collision implies that two action potentials
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already selected two out of the three electrode combinations before completion of the collision study (Fig. 4b). The Type 2 pattern group included one patient with fibromyalgia and one patient with HAM-related pain. Although a more than 50% SEP reduction was obtained in these two patients, pain relief was less than 30% of the preoperative state. In the patient with HAM, SCS was continued for more than 3 years without side effect; however, only warming sensations in the lower extremities were observed. In the patient with fibromyalgia, her pain recurred after SCS surgery. Thus, we inferred that patients with these types of pain might not be good candidates for dorsal column stimulation (Table 1, Fig. 2) (2,3). One poststroke patient (Case 7) reported pain reduction with no SEP collision effect (Type 3), implying that extralemniscal stimulation might induce a central pain suppression mechanism (Table 1, Fig. 2) (4,8–11). The result of SEP in this patient has been reported elsewhere (5). The other three poststroke patients showed various pain patterns, including one patient with Type 1 patterning and two patients with Type 2 (Table 1, Fig. 2). This suggests that the long-term effect of SCS on pain reduction for poststroke patients could be difficult to predict using only the evaluations obtained from the degree of dorsal column stimulation. There was one patient (Case 12) with lumbago associated with PD who showed no SEP collision effect without pain reduction. Furthermore, lumbar fixation surgery and SCS on Th8–11 failed to reduce his severe lumbago. Unpleasant electrical sensation spread to regions outside of the lumbar area, and the back and abdominal muscles twitched when SCS strength was increased. All of these factors precluded increasing the intensity of SCS to a level where it would cover up the painful lumbar area. Additionally, various combinations of SCS electrodes with tolerable stimulus intensity could not induce SEP amplitude reduction more than 40%, indicating insufficient stimulation of the dorsal columns. All of these findings suggest the need for a further trial to obtain sufficient dorsal column stimulation before making the final judgment of SCS as ineffective.
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Figure 4. Patient with complex regional pain syndrome (Case 1) demonstrating remarkable effects of spinal cord stimulation (SCS). a. A clear somatosensory evoked potential (SEP) amplitude reduction could be seen (arrows) when SCS was administered at a strength that was above the reported comfort level. The first control SEP waveform is superimposed on subsequent SEP waveforms. b. SEP collision study using various SCS electrode combinations. Two SEP waveforms are superimposed over each SCS electrode combination. Paresthesia sites on the patient’s body elicited by SCS are described under the numbers of combined stimulus electrodes. A clear SEP amplitude reduction was obtained by the stimuli of three SCS electrode combinations (arrows), which decreased the patient’s right hip and leg pain. Interestingly, two out of the three electrode combinations, specifically 1(−)/2(+) and 4(−)/5(+), had already been selected by the patient before the SEP collision study.
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travelling in the opposite direction on the same fiber cancel each other at the moment of their collision (23,25). This definition does not indicate that these two ascending and descending signals must be completely synchronized. In the current study, it seems apparent that there was a collision between the ascending SEP www.neuromodulationjournal.com
volley and descending SCS volley in the same dorsal column fiber, even though no attempt was made to synchronize the two signals. Moreover, if we adjusted both ascending and descending volleys to be more synchronized, a more apparent reduction in SEP amplitude would be obtained (19); however, this is beyond the scope of
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SCS AND SEP COLLISION
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SEP collision with pain reduction also suggests that clinical responsiveness to preimplantation tests is of the highest importance in selecting patients for SCS. In order to properly categorize the relationship between different patterns of pain and the effectiveness of dorsal column stimulation, more data collection from patients with neuropathic pain will be required. According to recent evidence-based guidelines (2,3), SCS is recommended in patients with failed back surgery syndrome and CRPS (Grade B recommendation) and in patients with traumatic neuropathy and brachial plexopathy (Grade C), but residual patients with other neuropathic pain syndromes are deemed Grade I, meaning the benefits and drawbacks of SCS cannot be determined. It is, however, also true that there are certain patients who belong to good indication groups who have poor results or who fall into a poor indication group but have good results. In order to determine the difference between responders and nonresponders, objective neurophysiological evaluations of dorsal column stimulation will be one of the most important steps in developing pain control using SCS technology.
Authorship Statements Dr. Urasaki and CE. Tsuda designed and conducted the study, including patient recruitment, data collection and data analysis. Dr. Urasaki prepared the manuscript draft with important intellectual input from Drs. Toyoda, Umeno, Nakane, and Yamakawa. All authors approved the final manuscript.
How to Cite this Article: Urasaki E., Tsuda M., Nakane S., Toyoda K., Umeno T., Yamakawa Y. 2014. Spinal Cord Stimulation for Intractable Pain Evaluated by a Collision Study Using Somatosensory Evoked Potentials: A Preliminary Report. Neuromodulation 2014; 17: 746–752
REFERENCES 1. Meyerson BA, Cui JG, Yakhnitsa V et al. Modulation of spinal pain mechanisms by spinal cord stimulation and the potential role of adjuvant pharmacotherapy. Stereotact Funct Neurosurg 1997;68:129–140. 2. Mailis A, Taenzer P. Evidence-based guideline for neuropathic pain interventional treatments: spinal cord stimulation, intravenous infusions, epidural injections and nerve blocks. Pain Res Manag 2012;17:150–158. 3. Cruccu G, Aziz TZ, Garcia-Larrea L et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007;14:952–970. 4. Ali MM, Saitoh Y, Hosomi K, Oshino S, Kishima H, Yoshimine T. Spinal cord stimulation for central poststroke pain. Neurosurgery 2010;67 (3 Suppl. Operative):ons206– ons212. 5. Urasaki E, Tsuda M, Nakane S, Toyoda K, Umeno T, Yamakawa Y. Evaluation of spinal dorsal column stimulation using the SEP collision method. Functional Neurosurgery (Kioutekinousinkeigeka in Japanese), 2013;52:5–13. (In Japanese). 6. Cruccu G, Aminoff MJ, Curio G et al. Recommendation of the clinical use of somatosensory-evoked potentials. Clin Neurophysiol 2008;119:1705–1719. 7. Agari T, Date I. Spinal cord stimulation for the treatment of abnormal posture and gait disorder in patients with Parkinson’s disease. Neurol Med Chir (Tokyo) 2012;52:470–474. 8. Bantli H, Bloedel JR, Thienprasit P. Supraspinal interactions resulting from experimental dorsal column stimulation. J Neurosurg 1975;42:296–300. 9. Kishima H, Saitoh Y, Oshino S et al. Modulation of neural activity after spinal cord stimulation for neuropathic pain: H215O PET study. Neuroimage 2010;49:2564–2569. 10. Larson SJ, Sances A, Riegel DH, Meyer GA, Dallmann DE, Swiontek T. Neurophysiological effects of dorsal column stimulation in man and monkey. J Neurosurg 1974;41:217–223. 11. Nagamachi S, Fujita S, Nishii R et al. Alteration of regional cerebral blood flow in patients with chronic pain—evaluation before and after epidural spinal cord stimulation. Ann Nucl Med 2006;20:303–310.
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the current study. We, therefore, use the term “SEP collision” in accordance with several previous studies (1,5,23). It should be noted that the reduction in scalp SEP amplitude during SCS could be induced by several other mechanisms aside from spike collision in the dorsal column. For example, saturation in the sensory cortex by SCS could prevent production of synchronous large-amplitude SEP, or there could be a gating mechanism in the dorsal horn (24). Further studies will need to be carried out to determine the main mechanism responsible for the SEP changes that we observed during SCS. An intraoperative SEP collision study reported by Balser et al. was aimed at determining SCS electrode positioning on the spinal cord (21). If a larger trial reproduced their results, this method could prove to be intraoperatively useful and could allow singlestage SCS surgery. We confirmed the usefulness of this method during surgery (5) and, furthermore, we developed this method to evaluate a patient who underwent permanent implantation of an SCS system. It is well known that PD-related pain (dystonic and central pain) and PD-unrelated pain (musculoskeletal, neuronal, and radicular pains) are often mixed in the types of pain that are perceived by patients with PD. SCS is generally effective for neuropathic pain but not for nonneuropathic pain such as nociceptive pain. As suggested by Agari and Date (7), pain reduction in patients with PD is probably achieved because lumbago and leg pain are partially caused by chronic neuropathic pathological conditions, which are factors even in musculoskeletal pain that comprises several nociceptive components (7). It is important to point out that following SCS, 4/12 patients demonstrated poor results, while 9/12 patients exhibited poor to fair results (
