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Page 10 of 17                                                                               Toyoda et al. Plast Aesthet Res 2022;9:17  https://dx.doi.org/10.20517/2347-9264.2021.118



                              RPNI
                                      [74]
                              Woo et al.   2016  Excision of post-amputation     Retrospective case series   16: 3 upper extremity, 14 lower   • Mean follow up 7.5 months        • 81% able to wear prosthesis after
                                                 symptomatic neuroma with RPNI                               extremity                       • Postoperative phone interviews with   RPNI (vs. 56% preoperatively)
                                                                                                                                             patient-reported pains cores adapted from  • Average pain score reduction 71%
                                                                                                                                             PROMIS                               • 56% reduced pain medication use
                                                                                                                                             • 100% response rate                 (none increased)
                                                                                                                                                                                  • Aggregate pain interference score
                                                                                                                                                                                  2.15 (vs. 4.6 preoperatively)
                                                                                                                                                                                  • 75% satisfied
                                                                                                                                                                                  • 94% would have surgery again
                                        [75]
                              Kubiak et al.   2019  Primary RPNI                 Retrospective case series   45 (52 limbs): 6 upper extremity,   • Mean follow up 357 days        • 13.3% of control patients developed
                                                                                                             46 lower extremity              • Pain outcomes binary               symptomatic neuromas
                                                                                                             45 control (52 limbs): 4 upper                                       • 0% of primary RPNI patients
                                                                                                             extremity, 48 lower extremity                                        developed symptomatic neuromas
                                                                                                                                                                                  • 51% of primary RPNI patients
                                                                                                                                                                                  developed PLP


                             TMR: Targeted muscle reinnervation; RPNI: regenerative peripheral nerve interfaces; secondary procedures: treatment of postamputation symptomatic neuromas; primary procedures: prophylactic treatment at time
                             of initial amputation; PROMIS: patient-reported outcomes measurement information system; PLP: phantom limb pain; NRS: numerical rating scale; OPUS: orthotics prosthetics users survey; QOL: quality of life;
                             vRPNI: pedicled vascularized RPNI.


                             interference scores demonstrated a significant decrease in residual limb and phantom limb pains at one-year follow-up compared to preoperatively. Quality of

                             life and functional assessment measures were also significantly improved after TMR for both upper and lower extremity amputees. The authors recommend
                                                                                                                                [62]
                             TMR as the first-line surgical treatment option for chronic amputation-related pain . Bowen et al.  are performing an ongoing prospective multicenter,
                                                                                                                                                  [63]
                             randomized study comparing the long-term success of TMR with the current standard of care. Preliminary results demonstrated that neuroma pain and PLP
                             might persist immediately after surgery, but by 3-6 months post-operation, patients can expect reduced pain, less inhibition from PLP, and improvement in
                             function and prosthesis use .
                                                            [63]


                             Effective treatment of existing symptomatic neuroma with TMR led teams across the country to assess its effect on neuroma pain prophylaxis by incorporating
                             it in the index amputation surgery. Researchers have hypothesized that primary TMR has the advantages of decreased muscle atrophy due to less muscle

                             denervation, improved nerve in-growth, and greater neuroplasticity . Thus far, primary TMR has demonstrated promising results. The first report of TMR in
                                                                                                           [63]
                             the acute setting at the time of traumatic shoulder disarticulation demonstrated multiple successful nerve transfers for myoelectric prosthesis control as well as
                             a complete lack of neuroma pain on the exam, which was corroborated with PROMIS at 8 months post-operation . The patient did not use a prosthesis due
                                                                                                                                                                 [64]
                                                                                                                                                                                                           [64]
                             to financial reasons, but distinct myoelectric control sites were seen on a clinical exam when she was able to trigger contraction under cortical control . She
                             did, however, report phantom sensations without pain, functional limitations, and mood depression . In another study by Alexander et al. , patients who
                                                                                                                                                                                                [65]
                                                                                                                                                  [64]
                             underwent major limb amputation for oncologic purposes with TMR at the time of amputation were compared to a cross-sectional sample of oncologic
                             amputees who were not treated at the research institution (who therefore presumably had amputations without TMR). At one year follow-up, those who had
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