Spinal Cord Stimulation and Pain Relief in Painful Diabetic Peripheral Neuropathy

A Prospective Two-Center Randomized Controlled Trial

Rachel Slangen; Nicolaas C. Schaper; Catharina G. Faber; Elbert A. Joosten; Carmen D. Dirksen; Robert T. van Dongen; Alfons G. Kessels; Maarten van Kleef

Disclosures

Diabetes Care. 2014;37(11):3016-3024. 

In This Article

Conclusions

This prospective multicenter RCT involving patients with moderate to severe PDPN in the lower limbs showed that after 6 months, SCS treatment reduces pain more effectively compared with BMT only. SCS reduced both daytime and nighttime pain. No differences were observed in HRQoL after SCS treatment. Finally, SCS treatment was not without any risk as two serious adverse events, which were both treatment related, occurred. Significant pain relief during daytime was shown in 41%, as compared with 55–60% in previous pilot studies, at 6 months.[10–12] Furthermore, 55% of the SCS group showed a clinically important difference on the PGIC score for pain. The larger number of patients with an effect on PCIC can be explained by the fact that an increase of ≥6 score on the PGIC scale is associated with 30% pain reduction on the NRS scale and is experienced as clinically relevant.[17,29,30] In this study, 11 out of 22 patients (50%) reported ≥30% pain relief on the NRS during daytime. During nighttime, ≥50% pain relief was noted in 36%, which was accompanied by a nonsignificant 1-h increase in sleeping time in the SCS patients. No differences were observed in HRQoL after SCS treatment.

As expected, our patients showed a poor HRQoL, and the participants reported utility scores of 0.25 (SCS group) and 0.33 (BMT group) at baseline, which were substantially lower compared with other studies that reported higher utility scores in PDPN patients (with a mean 0.61 [95% CI 0.56–0.66]).[31,32] In the SCS patients, the utility score improved from 0.25 to 0.50, which was mainly due to improvements on three dimensions of the EQ-5D: daily activities, pain, and mood. As pain and mood both have a relatively large weight in the regression-based calculation of the utility score, they largely accounted for the observed major improvement in the SCS group. Nevertheless, probably due to the large variability in the data, the differences between the SCS and BMT patients were not significantly different. Remarkably, patients' valuation of their current health state on the VAS of the EQ-5D showed no differences between the two groups. Patients in the SCS group showed hardly any improvements, despite reported pain relief and improved functioning in daily activities and mood at 6 months as compared with baseline. The difference between the general population (i.e., the utility scores) and patients' valuations (i.e., the VAS) has been explained by the adaptation phenomenon.[33] Where PDPN patients are likely to adapt to changes in their health state, healthy individuals usually do not anticipate adaptation effects and thus value those health states differently.[33,34] Another explanation for the discrepancy between the utility scores and VAS in PDPN patients is that they may have included dimensions in the valuation of their current health state other than those included in the descriptive system of the EQ-5D and subsequently weighted them differently.[35] This also explains the nonsignificant change in MCS and PCS of the MOS SF-36. As discussed below, the number of participants in this RCT was limited; therefore studies with a larger number of participants are necessary to determine the effects of SCS on HRQoL.

Success of SCS seems highly dependent on the use of strict selection criteria and the use of a 2-week trial stimulation with predefined criteria to evaluate the efficacy of the trial stimulation. We used strict selection criteria[36] to include patients, including an NRS pain intensity ≥5 measured on an NRS at the lower extremities for at least 6 months, treated with best medical therapy and patients with a clear history of PDPN. Causes other than diabetic peripheral neuropathy were excluded, and if necessary, a psychological assessment prior to inclusion was performed. A 2-week trial stimulation with predefined criteria was used to evaluate the efficacy of SCS. A negative trial stimulation was noted in 23% of the SCS patients, which is in line with previously published studies.[10–12] These patients reported <10% pain relief during daytime and nighttime, as well as no change on the PGIC scale. As summarized by Tesfaye et al.,[37] several anatomical or pathophysiological changes, including both peripheral and central mechanisms, have been implicated in the development of pain in diabetic peripheral neuropathy. A possible explanation for the substantial number of negative trial stimulations might be the presence of permanent central changes in the spinal cord. Three observational studies reported a smaller mean spinal cord area index at the cervical and thoracic level in patients with diabetic peripheral neuropathy as compared with control patients without DM.[38–40] Whether involvement of the spinal cord is a primary or secondary event in diabetic peripheral neuropathy is not yet clear.[39] In cases of spinal cord atrophy, we would expect differences in various neurological tests between patients with a positive and those with a negative trial stimulation. However, no differences in muscle strength, reflexes (knee and achilles tendon reflex), vibration sense, and joint position in the lower extremities were found. Thus, our data indicate that given the number of negative trial stimulations, a trial stimulation should always be performed when SCS is considered.

Although SCS is effective in most patients, the treatment is not without risks. Review studies report SCS to be a safe intervention in neuropathic pain patients.[41,42] The most common complications related to SCS are hardware related (lead migration, lead fracturing, connection failure, and discomfort), infection, subcutaneous hematomas, and cerebrospinal fluid leak.[41–43] In our study, severe complications were noted in two patients (9%) during a period of 6 months following implantation. In one patient, an infection occurred 6 weeks after SCS system implantation, and the patient responded to antibiotic management and removal of the SCS system. In the second patient, however, a dural puncture during the trial phase resulted in postdural puncture headache and subsequent development of a subdural hematoma with lethal outcome. To the best of our knowledge, a subdural hematoma is an extremely rare complication of SCS. After extensive review of the literature, we found one case report of a subdural hematoma after an SCS implant, where the patient suffered from minor head injury within 24 h before dural tearing and showed full neurological recovery after emergent craniotomy.[44] Although extensive examination of our patient's record was performed, no predictors for this devastating serious adverse event could be found. Except for this lethal complication, the complication rate in this study is comparable to that reported in literature.[41–43] Nevertheless, given the invasive nature of SCS, our data underscore that SCS reduced pain but should be applied as a last resort treatment and only should be carried out in specialized centers by a specialist with excellent experience in performing SCS treatment.

Our study has some limitations that need to be discussed. Patients with failure of pharmacological treatment and with high pain levels were screened and included. Therefore, the results cannot be generalized to patients with less pain. Some of the screened patients were referred to our clinic because of failure of previous treatment. Although some of the referring centers used a somewhat different treatment algorithm, all patients had been treated with pharmacological treatment as described in the current guidelines, including antidepressants, anticonvulsants, and/or opioids. As pain severity is not always related to the extent of neurologic abnormalities on clinical examination, the MDNS score was evenly distributed in our patients, leading to the possibility of referral of more severely affected patients. A major limitation of the study, like all studies using conventional SCS, was the fact that this study was not blinded, since paraesthesia accompanies SCS. Moreover, it is unethical and too invasive to implant a SCS system that is subsequently not used. Finally, PDPN is a progressive disease in which symptoms will be present in not only the feet and legs but will gradually progress proximally toward the hands and arms. We excluded patients with pain in the upper extremities as only the lower extremities were stimulated. Hence, it remains to be determined if SCS at both cervical and thoracal/lumbar spinal levels will be effective.

These limitations notwithstanding and including the risks, our findings show that in PDPN patients, SCS in combination with BMT results in clinically relevant pain relief over a 6-month period.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....