Decompression nerve surgery for diabetic neuropathy: a structured review of published clinical trials

Abstract

Aim

To assess lower extremity decompression nerve surgery (DNS) to treat the consequences of diabetic distal symmetric peripheral neuropathy (DPN).

Research design and methods

MEDLINE, PubMed, and related registries were searched through December 2017 to identify randomized, quasi-randomized or observational trials that evaluated the efficacy of lower extremity DNS on pain relief (primary outcome) or other secondary outcomes. Observational studies were included, given investigators’ reluctance to use sham surgery controls. Outcome effect size was estimated, and a weighted average was calculated.

Results

Eight of 23 studies evaluated pain relief, including a double-blind randomized controlled trial (with a sham surgery leg), an unblinded trial with a nonsurgical control leg, and 6 observational studies. All reported substantial pain relief post-DNS with average effect sizes between two and five. Unexpectedly, the double-blind trial showed improvement in the sham leg comparable to the DNS leg and exceeding the improvement observed in the nonsurgical leg in the unblinded study. Sensory testing showed generally favorable results supporting DNS, and nerve conduction velocities increased post-DNS relative to deterioration in controls. Ultrasound revealed fusiform nerve swelling near compression sites. Morphological results of DNS were generally favorable but inconsistent, whereas hemodynamic measures showed a positive effect on arterial parameters, as did transcutaneous oximetry (improved microcirculation). The incidence of initial and recurrent neuropathic diabetic foot ulcers appeared reduced post-DNS relative to the contralateral foot (borderline significant).

Conclusion

The data remain insufficient to recommend DNS for painful DPN, given conflicting and unexpectedly positive results involving sham surgery relative to unblinded controls. The generally supportive sensory and nerve conduction results are compromised by methodological issues, whereas more favorable results support DNS to prevent new or recurrent neuropathic foot ulcers. Future studies need to clarify subject selection vis-à-vis DPN vs superimposed compressed nerves, utilize appropriate validated instruments, and readdress use of sham surgical controls in light of recent results.

Keywords:

• diabetic neuropathy
• painful neuropathy
• neuropathy treatment

Supplementary material

MEDLINE (Ovid) search strategy

1. randomized.ab

2. placebo.ab

3. trial.ab

4. (diabetes mellitus or diabet$).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

5. exp diabetic neuropathies/ or diabetic peripheral neuropathy.mp

6. diabetic polyneuropathy.mp 7. exp diabetic foot/

7. exp decompression, surgical/

8. *tarsal tunnel syndrome/su [surgery]

9. exp foot/su [surgery]

10. or/1–3

11. or /6–7

12. or 8–10

13. and 12 and 13

Acknowledgments

We thank Michael Clark, PhD, for statistical assistance and Kenneth L Casey, MD, for critical review of published manuscripts.

Author contributions

JWA designed the protocol. JWA and RJ selected initial publications suitable for review and extracted data. JWA analyzed the data. JWA and RJ made substantial contributions to analysis and interpretation of data, participated in drafting and critically revising the manuscript, and approved the final version for publication. JWA is the guarantor of the present manuscript and takes full responsibility for the integrity of the results.

Disclosure

JWA serves on the Epidemiology of Diabetes Interventions and Complications Study (EDIC) Continuing Follow-up (NeuroEDIC) and is a member of the EDIC Mortality and Morbidity Review Committee. He has received personal compensation for activities with Alnylam Pharmaceuticals, Eli Lilly & Company, Lilly Research Laboratories, and Veristat, or by firms representing companies in litigation. These activities have been as a consultant, advisory board member, data monitoring committee member, mortality and morbidity review committee member, participating study investigator, or expert witness. None of the potential conflicts of interest relates directly to any of the material discussed in the current review. RJ reports no potential conflicts of interest.