Severity of Neuropathy Is Associated With Long-term Spinal Cord Stimulation Outcome in Painful Diabetic Peripheral Neuropathy: Five-Year Follow-up of a Prospective Two-Center Clinical Trial.

OBJECTIVE: Evidence from prospective studies for long-term treatment efficacy of spinal cord stimulation (SCS) in painful diabetic peripheral neuropathy (PDPN) is not available. We report prospective data on the effect of SCS on pain ratings, treatment success and failure, and complications during a 5-year follow-up in patients with PDPN. RESEARCH DESIGN AND METHODS: Patients with PDPN (n = 48) were included in this prospective multicenter study. The Michigan Diabetic Neuropathy Score (MDNS) was used to assess the severity of neuropathy. Numerical rating scale (NRS) score for pain, Patient's Global Impression of Change (PGIC), and treatment success (50% reduction of NRS score or significant PGIC) during 5 years of follow-up were evaluated. Complications of SCS were reported, and associations between baseline characteristics and SCS trial success or failure during a 5-year follow-up were investigated by using survival analyses. RESULTS: Treatment success was observed in 55% of patients after 5 years. Median duration of SCS treatment was 60 months (minimum 1 month, maximum 60 months), and 80% of patients with a permanent implant still used their SCS device after 5 years. Higher MDNS was associated with treatment failure during the 5-year follow-up (hazard ratio 3.9 [95% CI 1.3-11.6]; P = 0.014). CONCLUSIONS: SCS is successful in reducing chronic pain symptoms in the lower extremities of patients with PDPN up to 5 years after initiation of treatment. Furthermore, 80% of patients with PDPN still use their SCS device after 5 years. Moreover, the severity of neuropathy is associated with a higher chance of long-term treatment failure during a 5-year follow-up.

A Trial-Based Economic Evaluation Comparing Spinal Cord Stimulation With Best Medical Treatment in Painful Diabetic Peripheral Neuropathy.

The objective was to perform an economic evaluation comparing spinal cord stimulation (SCS) in combination with best medical treatment (BMT) with BMT in painful diabetic peripheral neuropathy patients. Alongside a prospective 2-center randomized controlled trial, involving 36 painful diabetic peripheral neuropathy patients with severe lower limb pain not responding to conventional therapy, an economic evaluation was performed. Incremental cost-effectiveness ratios were based on: 1) societal costs and quality-adjusted life years (QALYs), and 2) direct health care costs and the number of successfully treated patients, respectively, both with a time horizon of 12 months. Bootstrap and secondary analyses were performed to address uncertainty. Total societal cost amounted to €26,539.18 versus €5,313.45 per patient in the SCS and BMT group, respectively. QALYs were .58 versus .36 and the number of successfully treated patients was 55% versus 7% for the SCS and BMT group, respectively. This resulted in incremental cost-effectiveness ratios of €94,159.56 per QALY and €34,518.85 per successfully treated patient, respectively. Bootstrap analyses showed that the probability of SCS being cost-effective ranges from 0 to 46% with willingness to pay threshold values ranging between €20,000 and €80,000 for a QALY. Secondary analyses showed that cost-effectiveness of SCS became more favorable after correcting for baseline cost imbalance between the 2 groups, extending the depreciation period of SCS material to 4 years, and extrapolation of the data up to 4 years. Although SCS was considerably more effective compared with BMT, the substantial initial investment that is required resulted in SCS not being cost-effective in the short term. Cost-effectiveness results were sensitive to baseline cost imbalances between the groups and the depreciation period of the SCS material. PERSPECTIVE: Painful diabetic peripheral neuropathy is a common complication of diabetes mellitus and the humanistic and economic burden is high. This article presents the cost-effectiveness of SCS in patients suffering from painful diabetic peripheral neuropathy from a societal and health care perspective with a time horizon of 12 months.

Increased contact heat evoked potential stimulation latencies in responders to spinal cord stimulation for painful diabetic polyneuropathy.

OBJECTIVES: To analyze sensory characteristics and small nerve fiber function in patients suffering from painful diabetic polyneuropathy (PDP) and compare outcomes in responders and nonresponders to SCS treatment. METHODS: Fifteen patients with intractable PDP in the legs were recruited. If trial stimulation resulted in clinically relevant pain relief, a pulse generator was implanted and pain scores were measured after 12 months. Sensory characteristics (modified Inflammatory Neuropathy Cause and Treatment [md-INCAT] sum score) and small nerve fiber function (contact heat evoked potentials, CHEPs) were measured before implantation (D1), and CHEP measurement was repeated after two weeks of trial stimulation (D2). Outcomes in responders (N = 10) and nonresponders (N = 5) to SCS treatment were compared. Data were analyzed using nonparametric statistics. RESULTS: At one year, clinically relevant pain relief was achieved in 10 out of 15 patients. The md-INCAT score did not differ between SCS responders and nonresponders (8.0 vs. 5.0; p = 0.59). No differences were found in CHEP outcomes at D1 vs. D2, except for dorsal forearm P2 latency, and the correlation between D1 and D2 CHEP outcomes was high. Volar N2 forearm latency (0.492 vs. 0.434; p < 0.01), dorsal forearm N2 latency (0.518 vs. 0.453; p = 0.04), and dorsal forearm P2 latency (0.660 vs. 0.589; p = 0.04) were increased in SCS responders as compared with SCS nonresponders. CONCLUSIONS: From this small-scale clinical pilot study we conclude that forearm CHEP latencies are increased in PDP patients who respond to SCS therapy as compared with SCS nonresponders. Before the CHEP latency can be used as a predictor of SCS outcome in PDP patients, a large-scale study is needed.

Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-center randomized controlled trial.

OBJECTIVE: Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes mellitus. Unfortunately, pharmacological treatment is often partially effective or accompanied by unacceptable side effects, and new treatments are urgently needed. Small observational studies suggested that spinal cord stimulation (SCS) may have positive effects. RESEARCH DESIGN AND METHODS: We performed a multicenter randomized clinical trial in 36 PDPN patients with severe lower limb pain not responding to conventional therapy. Twenty-two patients were randomly assigned to SCS in combination with the best medical treatment (BMT) (SCS group) and 14 to BMT only (BMT group). The SCS system was implanted only if trial stimulation was successful. Treatment success was defined as ≥50% pain relief during daytime or nighttime or "(very) much improved" for pain and sleep on the patient global impression of change (PGIC) scale at 6 months. RESULTS: Trial stimulation was successful in 77% of the SCS patients. Treatment success was observed in 59% of the SCS and in 7% of the BMT patients (P < 0.01). Pain relief during daytime and during nighttime was reported by 41 and 36% in the SCS group and 0 and 7% in the BMT group, respectively (P < 0.05). Pain and sleep were "(very) much improved" in 55 and 36% in the SCS group, whereas no changes were seen in the BMT group, respectively (P < 0.001 and P < 0.05). One SCS patient died because of a subdural hematoma. CONCLUSIONS: Treatment success was shown in 59% of patients with PDPN who were treated with SCS over a 6-month period, although this treatment is not without risks.

Electrical spinal cord stimulation in painful diabetic polyneuropathy, a systematic review on treatment efficacy and safety.

INTRODUCTION: Painful diabetic polyneuropathy is a common complication of diabetes mellitus. Drug therapies are ineffective in many patients. Therefore other treatment modalities should be considered, including spinal cord stimulation. We performed a systematic review to evaluate treatment efficacy and safety of spinal cord stimulation in painful diabetic polyneuropathy. SEARCH STRATEGY AND SELECTION CRITERIA: A systematic search with reference tracing was conducted in Pubmed and Embase from January 1980 to March 2010 to determine possible eligible articles. Reports were identified using the following keywords: (1) "diabetic neuropathies" AND "electric stimulation"; (2) "diabetic neuropathies" AND "spinal cord" and (3) "pain" AND "electric stimulation" AND "spinal cord". Subsequently, data were recruited on the efficacy and safety of spinal cord stimulation in this disorder. DATA COLLECTION AND ANALYSIS: The search strategy was designed by one reviewer. Study selection and data extraction were performed by two reviewers. Data for individual studies was reported and pooled data analysis was performed if appropriate. RESULTS: Three prospective case series and one retrospective cohort study were identified (including 25 patients). At 1 year spinal cord stimulation resulted in ≥ 50% pain relief in 63% of patients. After 1 year analgesics usage was reduced in most SCS-treated patients with complete withdrawal in 60%. No major adverse events were reported. CONCLUSION: Available literature shows promising results for the pain-relieving effect of spinal cord stimulation in painful diabetic polyneuropathy. The outcome of a randomized clinical trial is needed before spinal cord stimulation can be considered to be integrated in the standardized treatment algorithm.