Spinal Cord Stimulation in Refractory Diabetic Peripheral Neuropathy

CME INDIA Presentation by Dr. R. Ramnarayan, M. Ch (Neurosurgery), FRCS, IFAANS, Functional Fellowship (UK), Functional/ restorative neurosurgeon, Chennai. +91 9003022445; r.ramnarayan65@gmail.com; www.lakshmineuroclinic.com.

Quick Take Away

Spinal cord stimulation is currently approved by the FDA for chronic pain of the trunk and limbs, intractable low back pain, leg pain, and pain from failed back surgery syndrome. In Europe, it has additional approval for refractory angina pectoris and peripheral limb ischemia.
In January 2022, it was also approved for severe diabetic neuropathy pain

Spinal Cord Stimulation can safely and effectively treat patients with refractory Diabetic Peripheral Neuropathy

Functional/ restorative neurosurgery includes:

Spinal Cord Stimulation in Refractory Diabetic Peripheral Neuropathy

Role of Spinal Cord Stimulation (SCS) in Diabetic Peripheral Neuropathy (DPN)

U.S. Food and Drug Administration approval of its Intellis™ rechargeable neurostimulator and Vanta™ recharge-free neurostimulator for the treatment of chronic pain associated with diabetic peripheral neuropathy (DPN) is making wave in treating DPN. (Diabetic peripheral neuropathy)

It is well known that DPN is a debilitating and progressive neurological disorder
It affects approximately 30% of people with diabetes, significantly impacting both quality of life and functional ability, including mood, social relationships, and sleep.
In some patients, the pain can become progressively worse and excruciating. Patients may be treated with medications, but they are often only partially effective and can result in serious side effects.
This new indication by FDA offers new hope to patients with DPN
Independent studies (1,2) have shown that patients with DPN achieve significant pain relief when treated with SCS compared to conventional treatments alone.
70% of patients receiving treatment with SCS experienced relief of their pain symptoms compared to 6% of patients receiving only conventional treatments.
SCS treated patients experienced a 53% average reduction in pain, compared to 0% among patients receiving only conventional treatments.
A meta-analysis by Duarte RV, Nevitt S, Maden M, et al. (2021) showed a significant improvement in health-related quality of life in patients treated with SCS compared to those receiving only conventional treatments. (4)
A Long-term Spinal Cord Stimulation Outcome in Painful Diabetic Peripheral Neuropathy is available. It shows that patients treated using Medtronic SCS technology continued to use their devices at five years to treat their pain in 80%. (5)

Looking back: Journey of SCS

Spinal Cord Stimulation in severe intractable painful diabetic neuropathy

Surg Neurol. 1996 Oct; 46(4):363-9. Spinal cord stimulation for chronic pain in peripheral neuropathy.Kumar K, Toth C, Nath RK.
- An analysis of a series of 276 patients revealed 30 patients diagnosed with peripheral neuropathy- Causes of intractable pain included postherpetic neuralgia, intercostal neuralgia, causalgic pain, diabetic neuropathy, and idiopathic neuropathy.
- Nineteen patients reported relief of pain on trial stimulation and had their systems permanently implanted. At an average of 87 months’ follow-up, 14 of these patients achieved long-term success in control of chronic pain (47% of all patients included in this study).
- Six patients reported excellent pain relief (> 75% pain relief), eight described good results (> 50% pain relief), and six had poor pain relief (< 50% pain relief).
- Study concluded: SCS is an effective therapy for pain syndromes associated with peripheral neuropathy. Causalgic and diabetic neuropathic pain seem to respond relatively well. whereas postherpetic pain and intercostal neuralgia syndromes seem to respond less favorably to the long-term beneficial effects of SCS. This information will be useful in the selection of patients with peripheral neuropathic pain who could be helped by SCS.
Lancet. 1996 Dec 21-28; 348(9043):1698-701. Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy. Tesfaye S, Watt J, Benbow SJ, Pang KA, Miles J, MacFarlane IA. Walton Diabetes Centre, Walton Hospital, Liverpool, UK. Comment in: Lancet. 1997 Mar 8;349(9053):729. Lancet. 1996 Dec 21-28;348(9043):1672-3.
- Ten diabetic patients who did not respond to conventional treatment were studied.
- The electrode was implanted in the thoracic/lumbar epidural space. Immediate neuropathic pain relief was assessed by visual analogue scale (VAS) after connecting the electrode, in a random order, to a percutaneous electrical stimulator or to a placebo stimulator. Exercise tolerance was assessed on a treadmill.
- This study concluded: Electrical spinal-cord stimulation offers a new and effective way of relieving chronic diabetic neuropathic pain and improves exercise tolerance. The technique should be considered in patients with neuropathic pain who do not respond to conventional treatment.
Surg Neurol. 2000 Feb; 53(2):182-8; discussion 188-9. Does autonomic neuropathy influence spinal cord stimulation therapy success in diabetic patients with critical lower limb ischemia?Petrakis IE, Sciacca V.
- This study concluded: Diabetic patients with peripheral arterial occlusive disease presenting with intractable pain may be successfully treated with spinal cord stimulation unless they have associated severe autonomic neuropathy.
Int Angiol. 2000 Mar;19(1):18-25. Prospective study of transcutaneous oxygen tension (TcPO2) measurement in the testing period of spinal cord stimulation in diabetic patients with critical lower limb ischemia.Petrakis E, Sciacca V.
- This study aimed to evaluate whether transcutaneous oxygen tension (TcPO2) measurements can be used as a specific prognostic parameter in the assessment of suitability for permanent device implantation in a prospective controlled study on diabetic patients with peripheral arterial occlusive disease
- It concluded: A two-week testing period should be performed in all diabetic patients treated with spinal cord stimulation for peripheral arterial occlusive disease to identify the candidates for permanent implantation. Only diabetic patients with significant increases of TcPO2 and clinical improvement, during the test period, should be considered for permanent implantation and not merely all patients with pain relief. TcPO2 changes could be used as a predictive index of the therapy success and should be considered in terms of cost effectiveness before the final decision to permanent implantation.
Anesth Analg. 2004 Mar;98(3):745-6, Decreased insulin requirements with spinal cord stimulation in a patient with diabetes.
- They described a case of type-2 diabetes mellitus with significant improvement in blood glucose control and significant decrease in insulin requirements after initiation of spinal cord stimulation
- They concluded: Spinal cord stimulation when used for control of chronic pain in diabetics may provide additional benefits of improving glycemic control and insulin requirements.
Diabet Med. 2005 Apr;22(4):393-8. Electrical spinal cord stimulation in the long-term treatment of chronic painful diabetic neuropathy. Daousi C, Benbow SJ, MacFarlane IA. Diabetes and Endocrinology Clinical Research Group, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK.
- They assessed the efficacy and complication rate of ESCS implanted at least 7 years previously in eight patients
- They concluded: SCS can continue to provide significant pain relief over a prolonged period of time with little associated morbidity.
Neurosurgery. 2006 Mar;58(3):481-96; discussion 481-96. Spinal cord stimulation in treatment of chronic benign pain: challenges in treatment planning and present status, a 22-year experience.
- They concluded: Spinal cord stimulation can provide significant long-term pain relief with improved quality of life and employment. Results of this study will be effective in better defining prognostic factors and reducing complications leading to higher success rates with spinal cord stimulation.
J Diabetes Complications. 2009 Jan-Feb;23(1):40-5. Epub 2008 Apr 16. Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy.
- This study concluded: Spinal cord stimulation offers an effective and safe therapy for chronic diabetic neuropathic pain.
Pain Pract. 2011 Mar; 11(2): 191-8. Evidence-based interventional pain medicine according to clinical diagnoses. 18. Painful diabetic polyneuropathy. Pluijms W, Huygen F, Cheng J, Mekhail N, van Kleef M, Van Zundert J, van Dongen R.
- Authors concluded: Based on the recently published National Institute for Health and Clinical Excellence guidelines, treatment of painful diabetic neuropathy should start with duloxetine or amitriptyline if duloxetine is contraindicated.
- If pain relief is inadequate, monotherapy with amitriptyline or pregabalin, or combination therapy with amitriptyline and pregabalin should be considered.
- If pain relief is still insufficient, tramadol instead of or in combination with a second-line agent should be considered. In patients who are unable to take oral medication, topical lidocaine can be considered for localized pain.
- There are currently four studies showing that spinal cord stimulation can potentially provide pain alleviation for the longer term in patients with painful diabetic polyneuropathy.
- Complications are mainly implant related, though infections also occur. The available evidence (2 C+) justifies spinal cord stimulation to be considered, preferably study related.
Diabetes Metab Res Rev. 2011 Jun 21. Painful Diabetic Peripheral Neuropathy: Consensus Recommendations on Diagnosis, Assessment and Management. Tesfaye S, Vileikyte L, Rayman G, Sindrup S, Perkins B, Baconja M, Vinik A, Boulton A; on behalf of the Toronto Expert Panel on Diabetic Neuropathy
- In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated.
Eur J Pain. 2011 Sep; 15(8):783-8. Electrical spinal cord stimulation in painful diabetic polyneuropathy, a systematic review on treatment efficacy and safety.
- It concluded: 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.
Curr Pain Headache Rep. 2011 Nov 10. Contemporary Insights into Painful Diabetic Neuropathy and Treatment with Spinal Cord Stimulation. McGreevy K, Williams KA.
- Authors commented: For over 30 years, spinal cord stimulation (SCS) has been used extensively for the management of various chronic neuropathic pain states. In the past decade, interest in the use of SCS for treatment of PDPN has increased.
Br J Anaesth. 2012 Oct;109(4):623-9. Pain relief and quality-of-life improvement after spinal cord stimulation in painful diabetic polyneuropathy: a pilot study.
- Study opined: SCS seems to be an efficacious and feasible treatment for intractable PDP. In this exploratory study, it was not possible to predict the treatment outcome using clinical sensory testing. These results justify performing a randomized clinical trial.
Br J Anaesth. 2013 Dec; 111(6):1030-1. Sustained effect of spinal cord stimulation on pain and quality of life in painful diabetic peripheral neuropathy.
- They studied the long-term effectiveness of SCS on pain and QoL in patients with PDPN. The short-term results of SCS were reported earlier in a prospective open-label cohort study. Besides the effect of SCS on pain, effect on patients’ QoL was also significant.
Eur J Pain. 2013 Oct; 17(9):1338-46. The effect of spinal cord stimulation frequency in experimental painful diabetic polyneuropathy
- The study concluded: The pain-relieving effect of SCS in PDP was studied in an experimental model. Our study shows that SCS on mechanical hypersensitivity in PDP rats is equally effective when applied at low, mid and high frequency.
Pain. 2013 Nov; 154(11):2249-61. Interventional management of neuropathic pain: NeuPSIG recommendations
- Based on the available data, authors recommend not to use sympathetic blocks for PHN nor radiofrequency lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available data
Neuromodulation. 2014 Feb; 17(2):152-9. Burst spinal cord stimulation evaluated in patients with failed back surgery syndrome and painful diabetic neuropathy
- This study concluded: About 60% of the patients with tonic SCS experienced further pain reduction upon application of burst stimulation.
Pain. 2014 Aug 29 2014. Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomised clinical trial
- 5D questionnaires showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after six months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduces pain and improves quality of life.
Diabetes Care. 2014 Nov; 37(11):3016-24. Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-centre randomized controlled trial.
- This study concluded: 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.
Scand J Pain. 2014 Jul 1; 5(3):175-181. Spinal cord stimulation: Background and clinical application.
Qual Life Res. 2016 Jul; 25(7):1771-7. Quality of life increases in patients with painful diabetic neuropathy following treatment with spinal cord stimulation.
- It concluded: SCS resulted in significant improvement in pain intensity and QoL in patients with PDN, offering further support for SCS as an effective treatment for patients suffering from PDN
J Neurol Surg A Cent Eur Neurosurg. 2016 Mar; 77(2):176-8.
- They presented a chronic pain syndrome due to combined Prinzmetal angina and diabetic neuropathy of the lower limbs with sustained pain relief utilizing a single SCS lead.
J Clin Anesth. 2016 Feb; 28: 74-7. Efficacy of spinal cord stimulators in treating peripheral neuropathy: a case series
- They presented 3 cases with chronic painful peripheral neuropathy secondary to HIV, diabetes mellitus, and chemotherapy that was resistant to conservative pain management and procedures that was successfully treated with neurostimulation.
J Pain. 2017 Apr; 18(4):405-414. A Trial-Based Economic Evaluation Comparing Spinal Cord Stimulation with Best Medical Treatment in Painful Diabetic Peripheral Neuropathy.
- They showed 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.
Eur J Pain. 2017 May; 21(5):795-803. Spinal cord stimulation in experimental chronic painful diabetic polyneuropathy: Delayed effect of High-frequency stimulation.
- They demonstrated that High frequency (500 Hz) – SCS resulted in a delayed effect- on pain-related behavioural outcome in chronic PDPN.
Reg Anesth Pain Med. 2018 May; 43(4):391-406. Spinal Cord Stimulation 50 Years Later: Clinical Outcomes of Spinal Cord Stimulation Based on Randomized Clinical Trials-A Systematic Review.
- The evidence presented by authors has broad applicability as it encompasses a breadth of patient populations, variations of SCS therapy, and comparable controls that, together, reflect comprehensive clinical decision making.
Curr Med Res Opin. 2018 Aug 17:1-11. Non-pharmacologic treatments for symptoms of diabetic peripheral neuropathy: a systematic review
- It showed: Alpha-lipoic acid and spinal cord stimulation were effective for pain; studies were short-term with quality deficits. Spinal cord stimulation had serious adverse events. Further research should address long-term outcomes and other non-pharmacologic treatments.
Front Neurol. 2019 Mar 18;10: 222. Lumbar Spinal Cord Activity and Blood Biochemical Changes in Individuals with Diabetic Peripheral Neuropathy During Electrical Stimulation
- Activation in the DPN patients was primarily observed in the T12 (10/13) vertebral level. The percentage of signal changes in DPN patients was higher than that in the control group (Z = -2.757, P < 0.05).
J Pain Res. 2019 Apr 30; 12: 1311-1324. The effect of spinal cord stimulation on pain medication reduction in intractable spine and limb pain: a systematic review of randomized controlled trials and meta-analysis
- In the high-frequency SCS group, average MED decreased by 24.8 mg vs average MED decrease of 7.3 mg in the conventional SCS group.
Neurologia. 2019 Jul 20. pii: S0213-4853(19)30089-1. Spinal cord stimulation: Beyond pain management.
- It concluded: In its 50-year history, SCS has progressed enormously. The perfection of hardware and software may improve its effectiveness and reduce the rate of complications. Indications for SCS could include other diseases, and its use could be expanded, if the costs of the technology are reduced.
Postgrad Med. 2020 Mar 9:1-6. Treatment of painful polyneuropathies of diabetic and other origins with 10 kHz SCS: a case series.
- In conclusion, 10 kHz SCS treatment resulted in significant pain relief in all the patients, decreased reliance on pain medication, and improved lower limb sensory function in the majority of patients.
Value Health 2020 May;23(5):656-665. A Systematic Review of Economic Evaluations Reporting the Cost-Effectiveness of Spinal Cord Stimulation.
- It concluded: The results consistently suggest that SCS is cost-effective when considering a long-term time horizon, particularly for the management of FBSS and CRPS. Further studies are needed to assess the cost-effectiveness of SCS for ischemic pain and DPN.
Postgrad Med. 2020 May;132(4):352-357. Treatment of painful polyneuropathies of diabetic and other origins with 10 kHz SCS: a case series
- In conclusion, 10 kHz SCS treatment resulted in significant pain relief in all the patients, decreased reliance on pain medication, and improved lower limb sensory function in the majority of patients.
J Diabetes Sci Technol. 2020 Aug 28;1932296820951829. Current Strategies for the Management of Painful Diabetic Neuropathy
- There is an emerging role for neuromodulation treatment modalities including intrathecal drug delivery, spinal cord stimulation, and dorsal root ganglion stimulation.
Pain Manag. 2020 Sep;10(5):291-300. 10-kHz spinal cord stimulation treatment for painful diabetic neuropathy: results from post-hoc analysis of the SENZA-PPN study.
- Results & conclusion: At 12 months, 6/7 subjects were treatment responders (≥50% pain relief) and had pain remission (visual analog scale ≤ 3.0 cm). Worsening of neurologic deficits was not reported in any subject. Instead, 5/7 subjects showed improvements in sensory testing and/or reflexes.
Adv Ther. 2020 Oct;37(10):4096-4106. Non-Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review
- Future RCTs should be conducted to shed more light in the use of non-pharmacological approaches in patients with PNP.
Neuromodulation. 2021 Jan;24(1):13-21. Invasive Electrical Neuromodulation for the Treatment of Painful Diabetic Neuropathy: Systematic Review and Meta-Analysis.
- It concluded: Efficacious, lasting and safe surgical pain management options are available to diabetic patients suffering from PDN. Tonic-SCS is the established standard of treatment; however, other SCS paradigms and DRGS are emerging as promising treatments offering comparable pain benefits, but with few cases published to date. Randomized controlled trials are ongoing to assess their relative merits.
JAMA Neurol 2021 Apr 5. Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients with Painful Diabetic Neuropathy: A Randomized Clinical Trial.
- Conclusions and relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN

References:

de Vos CC, Meier K, Zaalberg PB, et al. Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial. Pain. 2014 Nov;155(11):2426-31.
Slangen R, Schaper N, Faber C, et al. Spinal Cord Stimulation and Pain Relief in Painful Diabetic Peripheral Neuropathy: A Prospective Two-Center Randomized Controlled Trial. Diabetes Care. 2014;37:3016-3024.
Medtronic announces FDA approval of spinal cord stimulation therapy for treating chronic pain resulting from diabetic peripheral neuropathy – Jan 24, 2022
Duarte RV, Nevitt S, Maden M, et al. Spinal cord stimulation for the management of painful diabetic neuropathy: a systematic review and meta-analysis of individual patient and aggregate data. Pain. March 2021
Van Beek M, Geurts J, Slangen R, et al. 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. Diabetes Care. 2018;41:32–38.