Systematic review of targeted muscle reinnervation and regenerative peripheral nerve interfaces for the treatment of residual limb pain following major limb amputation
Genevieve Dostaler, MD, MHA, University of Alberta, Edmonton, AB, Canada, Adil Ladak, MD, MSc, Division of Plastic Surgery, University of Alberta, Edmonton, AB, Canada and Hollie Power, MD, Department of Plastic and Reconstructive Surgery, University of Alberta, Edmonton, AB, Canada
Background:The symptomatic neuroma is a major contributor to post-amputation residual limb pain (RLP). Numerous surgical approaches to treat this pain exist but consensus on the most effective is lacking. Conventional methods aim to protect the nerve end from pressure or mechanical irritation. Emerging approaches exploit the physiologic process of nerve regeneration and include targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI). The aim of this study is to review the published outcomes of TMR and RPNI for the prevention and treatment of RLPfollowing major limb amputation.
Methods:A systematic review was performed according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Studies from the last two decades were identified through Cochrane, PubMed, and EMBASE databases using the search terms: amputation, neuroma pain, TMR, neuroma and RPNI. Human studies published in English or French with RLP outcomes and a minimum of 1 year follow-up were included.
Results:Eleven studies met inclusion criteria. Meta-analysis was not possible as the studies had small sample sizes, heterogenous inclusion criteria, and variability in the patient-reported outcome measures. Regarding prevention of RLP, 100% of patients who had RPNI performed at the time of major limb amputation (n=95) reported no pain at 1 year, compared to 13.3% of control patients (n=45). TMR was performed in 103 patients in 4 studies. Patient-reported Outcome Measurement Information System(PROMIS) RLP scoreswere significantly lower in the TMR group (n=78) compared to controls (n=109). In two of the included studies, all patients undergoing TMR (n=25) reported no neuroma pain at 7-18 months follow up.Regarding the treatment of established RLP, 16 patients who underwent RPNI 1-29 years post-amputation were 71% lower. For TMR, 67-100% of patients reported complete pain resolution at 4-25 months follow-up. Two studies (n=44) reported clinically significant decreases in RLP VAS and/or PROMIS scores with TMR treatment even in long term amputees (1-37 years).
Conclusion: Both RPNI and TMR are effective in the prevention and treatment of RLP following major limb amputation. Comparative studies and long-term outcomes are lacking and will be an important area for future investigation.
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