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Azoury et al. Plast Aesthet Res 2020;7:4 I http://dx.doi.org/10.20517/2347-9264.2019.44 Page 15 of 20

Structural brain MRI and magnetoencephalography to record neural correlates of sensory responses
and hand movement, motor cortex mapping with transcranial magnetic stimulation and motor evoked
potentials from intrinsic muscles, and functional MRI (fMRI) before and after transplantation are used
to track progress. Psychological and social assessments are made through semi-structured interviews to
support coping with transplantation and rehabilitation.

Reported outcomes following hand-forearm transplantation have been promising and follow-up now
extends over a decade [82,99] . It is well known that more proximal amputations fair poorer with transplantation
when compared to distal ones given the distance for regeneration. However, continual yearly improvement
[92]
is seen in the majority of patients . An international registry observed that all transplant recipients
develop protective sensibility against pain, 90% regained tactile sensibility, 82.3% achieved discriminative
[16]
fine sensibility, and 75% reported overall improved quality of life . A review of five recipients of bilateral
hand allotransplantation performed in Lyon France (Follow-up 3-13 years) demonstrated 100% patient
and graft survival, adequate sensorimotor recovery (protective/tactile sensitivity), an ability to perform the
[99]
majority of daily living activities (e.g., eating, shaving, and using the telephone), and normal social lives .
In fact, a return of sensation, albeit to varying degrees and timing, can generally be expected in upper
extremity VCA patients. Follow-up has also demonstrated normal appearance (i.e., color, temperature,
texture, and hair and nail growth) and uneventful bone healing, with normal structure of the recipient
and transplanted bones. Motion recovery started at 3-6 months for these patients, with extrinsic recovery
allowing the patients to grasp large objects, whereas the intrinsic activity started later (9-12 months),
increasing in the first fiveyears post-transplant. Patients experienced at least one episode of acute rejections
(range 1-6) . The Louisville group reported intrinsic function recovery after at least two years of follow-
[99]
up in three of five patients [110] . The Innsbruck group recently reported on an 18-year experience, with
outcomes demonstrating improvement in hand function and sensibility in the first five years and stability
thereafter [100] . This same group also reported that one of the five patients, a unilateral hand transplant
recipient, suffered from recurrent and unmanageable antibody mediated rejections, which eventually led to
chronic rejection vasculopathy, necessitating amputation seven years postoperatively. Although bias cannot
be excluded based on inherent differences in patient populations, a comparison of prosthetic and upper
extremity transplant recipients noted improved quality of life in the transplanted group [111] .

Aside from wound healing complications, risks of upper extremity VCA include vessel thrombosis,
rejection and possible graft loss, hematoma, and deep venous thrombosis. Aside from side effects of
immunosuppression, medication side effects include neurotoxicity and nephrotoxicity. Although graft loss
was reported in 22.4% of patients in a 2015 review, graft loss may be estimated at < 1% in patients who are
compliant with medications [112] . Combined vascularized composite allotransplantation of multiple anatomic
areas (e.g., face and hand) has demonstrated an unacceptably high risk of complications, including graft
[92]
loss and death . It is estimated that up to 85% of hand transplant recipients may experience acute rejection
within the first year, which manifests as cutaneous lesions [16,113] . Acute rejection is typically reversed
successfully with intravenous steroids or increasing oral steroid dose. Other complications included
transient hyperglycemia, renal toxicity related to immunosuppressive drugs, osteopenia, and infectious
complications. Vascular thrombosis, when it occurs, may be successfully treated with embolectomy and
bypass procedures. To our knowledge, there have been no reported cases of malignancies [99,100] .

CONCLUSION
OI, TMR, and VCA are just a few ways by which our reconstructive ladder is changing. With regards to
prosthetic technology, amputees continue to experience high levels of disability, distress, dependency,
and overall dissatisfaction. Bionic limbs still do not replicate the complex function of the upper extremity
muscles. It is important to recognize that amputation does not necessarily denote failure, but we have