Spinal-Cord Stimulation 'Last Resort' for Diabetic Nerve Pain

Miriam E. Tucker

September 30, 2014

Spinal-cord stimulation may represent a "last-resort" treatment for some patients with severe painful diabetic neuropathy when pharmacologic therapy has failed, a new 2-center study suggests.

The results were published online September 11 in Diabetes Care by Rachel Slangen, a PhD student at Maastricht University Medical Center, the Netherlands, and colleagues.

Spinal-cord stimulation produced significant pain relief in more than half of 22 patients with severe refractory lower-limb pain due to diabetic peripheral neuropathy. But the treatment is invasive, and there were 2 severe complications, including 1 death, suggesting that the modality is appropriate only for "end-of-line patients with severe diabetic peripheral neuropathy pain not responding to medication," study principal investigator Maarten van Kleef, MD, PhD, head of the pain clinic at Maastricht University Medical Center, told Medscape Medical News.

Asked to comment, A. Gordon Smith, MD, director of the Peripheral Neuropathy Clinic and Cutaneous Innervation Laboratory at the University of Utah, Salt Lake City, agreed.

"[Spinal-cord stimulation] is going to be reserved for patients with severe, refractory pain that has not responded to traditional pharmacologic therapy. In that setting, you have to have a frank discussion with the patient about the risks of the procedure….The risk of death is incredibly low, but the risk of an infection or other procedure-related risk is somewhat higher. Patients need to be made aware of that," Dr. Smith told Medscape Medical News.

Medtronic's implantable neurostimulation system used in the study is indicated for the treatment of chronic, intractable pain of the trunk or limbs due to a variety of conditions such as failed back syndrome, unsuccessful disc surgery, and postlaminectomy pain. It is not currently indicated for diabetic peripheral neuropathy.

"The indication for diabetic peripheral neuropathy was always questioned. It was labeled before as a bad indication, which it is not," Dr. van Kleef told Medscape Medical News, noting that another recent multicenter trial had produced similar findings to his study (Pain. 2014. Abstract).

Pain Relief When Nothing Else Works

The Dutch study included a total of 36 patients, 22 of whom were randomized to spinal-cord stimulation along with best medical treatment and 14 to best medical treatment alone.

Those randomized to spinal-cord stimulation first underwent a 2-week trial stimulation period in which the device's lead (Octad, Medtronic) was implanted into the spine but was connected to an external stimulator (External Neurostimulator Trialing System, Medtronic). After implantation, patients were admitted to the hospital for 24 hours. They were discharged if no change in position of the lead was seen after X-ray verification.

Improvement in the 2-week trial stimulation, or 'treatment success,' was defined as a numeric rating scale score for the intensity of pain during daytime or nighttime for the past 4 days of at least 50% lower than baseline or a score of 6 or higher ("much improved" or "very much improved") on the Patient Global Impression of Change scales for pain and sleep. Such improvement occurred in 17 of the 22 patients.

One of the patients withdrew due to an infection and, following removal of the system, was still included in the intention-to-treat analysis as a treatment failure. In the 17 who responded to the initial trial, a different stimulator was implanted (Synergy Versitrel or Prime Advanced) near the gluteal muscle or in the anterior abdominal wall.

At 6 months, treatment success (same definition as before) for the spinal-cord stimulation occurred in 13 of the 22 patients (59%), vs just 1 of the 14 controls (7%), a significant difference (P < .009).

Nine of the 22 spinal-cord-stimulation patients (41%) reported 50% or more pain relief during the daytime, vs 0% of the controls (P < .001). For nighttime pain, those proportions were 8 (36%) vs 1 of the 14 controls (7%).

Of the 22 with spinal-cord stimulation, 12 (55%) scored 6 or higher ("much improved") on the Patient Global Impression of Change Scale for pain (P < .001) and 8 (36%) did so for sleep (P < .011), whereas none of the controls reported that level of improvement on either the pain or sleep measure.

After adjustment for baseline characteristics, the odds ratio for treatment success was 18.8.

Scores on the Pain Severity Index and the Pain Interference Index were significantly improved with the spinal-cord stimulation compared with controls ( P < .001 and < .008, respectively).

Seeming Contradiction: Pain and Sleep Improved, but QoL Wasn't

However, there was no significant difference between the 2 groups overall in the 5 dimensions of health-related quality-of-life scores on the EuroQol, although there were slight improvements in daily activities, pain, and mood (P < .776).

Patients' self-rated health as measured by the Medical Outcome Study-36 also did not improve. Sleep quality was poor in both groups, and spinal-cord stimulation didn't appear to help.

Those with severe diabetic peripheral neuropathy may have included other dimensions in their health status not captured in the health-related quality-of-life scales, the authors suggest.

Dr. Smith told Medscape Medical News, "Even though there was a significant change in pain in the treated group, the average pain still was quite severe, and I suspect that's what is underlying the seeming dichotomy between change in pain and change in quality of life."

Of course, he added, one problem with spinal-cord stimulation studies is that it's impossible to blind them. "You'd need to do a sham surgery, and when the device is working patients can tell."

Dr. Smith praised the authors for including quality-of-life measures in their study. This was a good effort "to try to understand how it actually affected patients….Clearly, the goal isn't just reducing pain but also improving function and quality of life. I think that was a real strength."

Use of pain medications was reduced in 7 of the 22 spinal-cord-stimulation patients (32%), and 2 stopped pharmacologic treatment while continuing with the stimulation. In contrast, 4 controls (29%) increased their medication use, 1 changed to a different medication class, and 9 (64%) did not change their drug use.

Complications: Infection Risk Is the One to Watch

One patient developed an infection 6 weeks after the stimulator implantation and responded to antibiotics after the device was removed but didn't completely recover.

The other patient had a dural puncture during the trial phase that caused a postdural puncture headache and was found to have a subdural hematoma. He died despite surgery.

"To our knowledge, a subdural hematoma is an extremely rare complication of [spinal-cord stimulation]," the authors write.

Indeed, Dr. Smith said that he has never had a patient die from spinal-cord stimulation. "I see an occasional stimulator misplaced, but have never seen someone die….There are some risks associated with this, but I think the risk of death is incredibly low. Infections are the risks you really worry about."

Dr Slangen and colleagues conclude, "These limitations notwithstanding and including the risks, our findings show that in painful diabetic peripheral neuropathy patients, spinal-cord simulation in combination with best medical treatment results in clinically relevant pain relief over a 6-month period."

This study was supported by Medtronic, which provided a grant for Rachel Slangen's employment for 3 years. Dr. van Kleef has reported no further relevant financial relationships. Dr. Smith has received grants from the National Institute of Diabetes, Digestive, and Kidney Diseases and the American Diabetes Association .

Diabetes Care. Published online September 11, 2014. Abstract


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