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Page 8 of 10 Di Valerio et al. Plast Aesthet Res 2022;9:62 https://dx.doi.org/10.20517/2347-9264.2022.50

Our investigation identified four studies meeting inclusion criteria assessing PLP/RLP; all of which showed
improvements in outcome parameters. Only one study, Dumanian et al, with limited patient enrollment
[7]
(n = 28), did not demonstrate statistical significance in improvements related to PROMIS specifically ;
however, the study did report significant change in PLP from baseline related to Numerical Rating Scale in 1
year post surgery . While this study represents randomized controlled data, its limited enrollment (with
[8]
diverse amputation locations, levels, and timing) likely affected outcomes trending in favor of TMR without
statistical significance. This study was unique in being the only one to assess patients with existing
amputations; thus, subjects likely were predisposed to longstanding behavioral adaptions, which possibly
prolonged calculable improvements in PROMIS parameters.

The remaining studies were retrospective cohort studies and demonstrated statistical significance across
PROMIS components including pain intensity, pain behavior, and pain interference. Alexander et al.
uniquely studied amputations related to oncologic treatment with concurrent TMR and incorporated
[6]
follow-up to 1 year . This study also had limited total patients (31 TMR). Although TMR was done at the
time of amputation, only 16 patients underwent TMR at index surgery. The remaining underwent
secondary amputation related to recurrence or infection. These patients were also affected by
neoadjuvant/adjuvant chemotherapy and radiation.

Valerio et al. focused on the general amputee population with larger patient numbers totaling 438 subjects,
51 of which had TMR performed at index procedure . Subjects represented diverse ages, levels of
[20]
amputation, and indications for amputation. The aggregate data perhaps favors a more generalized
representation, emphasizing marked improvements in PROMIS reporting across intensity, behavior, and
interference. The follow-up ranged 3 months to 5.3 years (> 1 year 64.7%). One limitation, however, is that
the follow-up survey of the non-TMR cohort was noted to be longer after surgery, given the retrospective
nature. Long-term data are needed to determine if TMR results are consistent over time without recurrence
of functional limitation. This likely introduced respondent reporting biases.

The latest 2021 study by O’Brien et al was also a retrospective cohort study, which included 16 patients who
underwent TMR at index amputation compared to 55 controls. 62% of the TMR patients had no PLP versus
24% of controls. Similarly, half of TMR patients were without RLP versus 36% of controls. PROMIS scores
across all parameters, with the exception of RLP interference, significantly favored TMR .
[21]

Although PROMIS scores offer a tremendous metric for assessing the debilitating pillars of RLP and PLP, it
is not without limitations. Its design remains predicated on an objective iteration of subjectively assigned
values in a presumably standardized manner. Moreover, the processes for all the above-mentioned studies
were reliant upon patients’ ability to distinguish PLP from RLP, which at times may be tenuous.

Limitations of this study include the lack of meta-analysis, which was not feasible given the wide variation
in data points collected among the different studies. Additionally, the information does not allow for
outcome conclusions comparing specific nerve transfers. Generally, target motor nerves in both upper and
lower extremity TMR are ideally those which have redundancy in motor function to maintain physiologic
continuity. The target nerve should be an expendable nerve preserving another nerve that has similar
functions. This is particularly relevant in below knee amputation, where the larger medial gastrocnemius is
preserved to provide adequate protective bulk for prosthesis fitting. Despite the statistical limitations and
inability to compare transfers across multiple studies, this review supports the use of TMR in the prevention
and treatment of RLP and PLP.