Journal of Plastic, Reconstructive & Aesthetic Surgery (2015) 68, 1171e1183

REVIEW

Bilateral hand transplantation: Functionalbenefits assessment in five patients with amean follow-up of 7.6 years(range 4e13 years)

Laurence Bernardon a,1, Aram Gazarian b,c,*,1,Palmina Petruzzo c, Tara Packham d, Michel Guillot a,Vincent Guigal b, Emmanuel Morelon c, Hua Pan e,Jean-Michel Dubernard c, Christophe Rizzo b, Patrick Feugier c,Thibault Streichenberger c, Ludovic Bincaz f,Jean-Pierre Urien g, Guillaume Mezzadri f, Thibault Rousselon h,Franck Plotard i, Christian Seulin c, Fabienne Braye c,Ali Mojallal c, Guillaume Herzberg c, Jean Kanitakis c,Davit Abrahamyan j, Simon Kay k, Lionel Badet c

a Romans Ferrari Rehabilitation Centre, Miribel, Franceb Clinique du Parc, Lyon, Francec Hopital Edouard Herriot, Hospices Civils de Lyon, Lyon, Franced McMaster University, Hamilton, Canadae Xijing Hospital, Xi’an, Chinaf Clinique Kennedy, Montelimar, Franceg Clinique Medipole de Savoie, Challes-les-Eaux, Franceh Centre de l’Hospitalisation Privee de la Loire, Saint Etienne, Francei Hopital Nord-Ouest, Villefranche-sur-Saone, Francej Arabkir Joint Medical Centre, Yerevan, Armeniak Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom

Received 26 May 2015; accepted 12 July 2015

* Corresponding author. Clinique du Parc, 155 Blvd. Stalingrad, 69006 Lyon, France. Tel.: þ33 472 44 87 54.E-mail address: a.gazarian@cliniqueduparclyon.com (A. Gazarian).

1 Both authors contributed equally to this work and should be considered first author.

http://dx.doi.org/10.1016/j.bjps.2015.07.0071748-6815/ª 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

1172 L. Bernardon et al.

KEYWORDSBilateral handamputee;Bilateral handallotransplantation;Functional outcome;Quality of life

Summary Between January 2000 and July 2009, five adults who had suffered bilateral trau-matic below-elbow amputations, received bilateral hand-forearm allografts performed by theLyon team. We report the functional benefits achieved over a mean follow-up period of 7.6years (range 4e13 years), up to December 31st, 2013. Clinical measurement is hampered bythe lack of specific validated assessment tools, obliging us to use non-specific standardizedevaluation means. Our assessment shows that the restoration of motion, strength, and sensi-bility are fair. Functional results (Carroll upper extremity function test, 400-point test, Activ-ities of daily living) are good, as well as quality of life evaluation (RAND-36). Subjective andoverall results explored with questionnaires e Disabilities of the Arm Shoulder and Hand(DASH), Hand Transplantation Score System (HTSS), are very good. Improvement was seen tocontinue during the first three years, and then tend to become stable. Continued effortsshould be directed at designing comprehensive, condition-specific, reliable outcome measure-ment tools. Continuous monitoring and evaluation of patients is required to assess the long-term risk-benefit balance.ª 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published byElsevier Ltd. All rights reserved.

Introduction

The traumatic amputation of both hands is devastating.1

Bilateral hand allotransplantation is a therapeutic op-tion,2,3 but the outcomes are still under study. We reportthe outcomes in five consecutive patients, and identify alack of validated specific assessment tools.

Our patients had suffered bilateral below-elbow ampu-tations and received bilateral allografts between January2000 and July 2009. They were followed up for a mean of7.6 years (4e13 years), until December 31st, 2013.

Patients and methods

Recipients

The study includes four males and one female, mean age26.2 years (range 21e33 years) who underwent bilateral

Picture 1 The recipients be

hand and forearm allotransplantation following trauma(Picture 1, Table 1). The interval from amputation totransplantation was 3e5 years. All were originally right-hand dominant. Four patients used myoelectric prosthesesprior to allotransplantation with poor satisfaction.

Surgery

Details of technique have been reported.2,4,5

Individual management requirements and complicationsPatient 2 returned to theatre at day one for subacuteischemia in the right hand; at 4 months sepsis of the leftulna required removal of the fixation and antibiotics.6 Pa-tient 3 required a right end-to-end anastomosis betweenradial recipient and brachial donor arteries because ofarterial length difference, and debridement of skin necrosisat the tips of donor skin flaps. Patient 4 had previouslysuffered burn injury, and therefore underwent bone biopsy

fore hand transplantation.

Table 1 Recipient and donor characteristics.

Recipient: Sex Patient 1: M Patient 2: M Patient 3: F Patient 4: M Patient 5: M

Amputation date 12.01.1996 14.09.2000 28.08.2004 13.04.2003 11.07.2004Amputation cause explosion crush electrocution burn explosionAmputation level R: wrist R: mid-forearm R: mid-forearm R: MP joints R: distal forearm

L: wrist L: distal forearm L: mid-forearm L: MP joints L: wristOccupation before

amputationgardener manual worker kindergarten teacher,

sailing instructorengineer trainee chef

Age at Tx, yrs 33 21 27 29 21Donor’s age, yrs 18 45 40 29 18Tx date 13.01.2000 30.04.2003 19.02.2007 4.07.2008 11.07.2009Side R: L: R: L: R: L: R: L: R: L:Cold ischemia time 9 h20 8 h40 7 h04 6 h52 7 h00 7 h00 7 h30 6 h00 4 h00 4 h00Cold+warm ischemia 13 h 14 h 13 h 11 h 10 h 11h 10 h 9 h 16 h 20 hProcedure duration 19 h 14 h 12 h 19 h 20 h

R: right; L: left; M: male; F: female; Tx: transplantation.

Bilateral hand transplantation 1173

to exclude sepsis, and preparation of subcutaneous chan-nels to place donor veins.5 Patient 5 sustained frostbite ofthe donor thenar eminence from an ice pack during prep-aration, which required debridement and healed second-arily. At day fifteen, he developed ischemia of the left handand required vein grafting from the brachial artery to thedistal radial artery. A burn occurred on the left metacarpalregion from a hot pack, requiring cover with a pedicledgroin flap.

Secondary reconstructive proceduresPatient 1 underwent opponensplasty for the left thumb,without appreciable benefit.

In patient 2, FDP to index and long fingers were short-ened to improve flexion, with benefit; localised pus on thedorsum of the right middle finger was drained under anti-biotic therapy. He had two skin revisions for cosmesis.Although outside the timeframe of this report, in July 2014patient 2 suffered multifocal skin necrosis of the same rightmiddle finger attributed to chronic rejection (graft vascul-opathy), treated by amputation through the proximalphalanx. In November 2014, the left third finger wasamputated at the same level for similar reasons. The rightindex and the fourth left finger have been amputatedrecently. The prognosis for the hands of patient 2 is indoubt.

In patient 3, an active extension deficit at the PIPJ of theleft fourth finger resulted in arthrodesis.

In patient 5, intrinsic release in the right hand increasedmotion and function, but resulted in decreased grip.Arthrodesis of the right CMC joint provided better positionin the absence of intrinsic muscle recovery. On the lefthand, a tendon release and tendon transfer improvedthumb extension. The groin flap (above) was seriallydebulked.

Medical complications

The patients developed some complications related toimmunosuppressive treatment as solid organ grafted re-cipients.4 They were: 1) diabetes mellitus (PTDM) whichoccurred in the first post-operative period and was

transient in patients 1 and 5, while in patient 3 PTDMoccurred 6 years after the transplantation and requiredinsulin treatment; 2) transient increase in creatinine serumvalues in patient 5; 3) osteoporosis in patients 1, 2 and 4,while patient 5 developed hip avascular necrosis requiringhip prosthesis; 4) serum sickness in patient 1 due toantithymocyte globulins used as induction treatment; 5)herpes zoster infection in patient 5 and asymptomaticEpsteineBarr infection in patient 3.

Rehabilitation program

The multidisciplinary rehabilitation started 12e24 h aftersurgery twice a day for the first month, then in a Rehabil-itation Centre working 4e5 h daily for a period of 12months. Patient 3 spent 9 months in therapy, and patients 1and 4 continued for 18e24 months after transplantation.Patients transitioned from inpatient to outpatient care at 6months (range 2e18 months) while on this program.

In the first period (6 weeks), rehabilitation lasts 6 h/dayand focuses on three domains: Firstly, lymphatic drainageto reduce swelling and minimize adhesions. Secondly, alljoints are passively mobilised and early active controlledmovements encouraged. Thirdly, electrostimulation ofintrinsic muscles, commencing after the first week. Pro-tective static splints are used continuously, and ensurecorrect joint position and tendon balance.

Healed tendons at 8 weeks permit active mobilization ofwrist and fingers, and dynamic splints achieve a balancebetween extensors and flexors.

After 3 months, bony consolidation permits activeresisted mobilization, for mobility and strengthening.

At 6 months, sensory re-education is begun under pro-fessional guidance.

After 9 months, the program works on the balance ofextrinsic and intrinsic muscles, fine-motor coordination anda progressively complex program of somatosensory stimu-lation and retraining.

At 12 months, rehabilitation focuses on all daily activ-ities, aiming for autonomy, whilst further recovery ofdiscriminative and tactile gnosis is still possible, as aregains in skilled motor coordination.

1174 L. Bernardon et al.

Evaluation procedures

Pre- and post-transplantation testing allowed assessment ofrecovery of motion, strength and sensibility, as well asglobal functional recovery and quality of life (QoL). Theseassessments can be categorized as assessments of bodystructures and functions, activities, participation, andcontextual factors such as the environment and the person(ICF7) (Table 2).

Motion recovery was evaluated measuring active ROM ofthe wrist and long finger joints.8 Thumb active oppositionwas assessed with the modified Kapandji index.9 Gripstrength was evaluated with the Baseline� Hydraulic HandDynamometer, pinch strength using the Jamar� pinch gaugedynamometer10 and manual muscle testing.11,12 Sensibilityrecovery was evaluated on the basis of pain and thermalstimuli, Semmes-Weinstein,13 and two-point discrimination(TPD)14,15 static tests. Tactile gnosis assessment wasintroduced (2012) so as to assess functional sensitivity.Patients were provided with 8 different objects (woodenclothes peg, cork ball, wooden cube, bolt, toothbrush,

Table 2 Assessment tool categories.

ICF category Assessments Reference(development and ps

Body structuresand functions

TAM ASSH, 19838

Composite thumbmotion

Lefevre-Colau et al.,

Dynamometry Mathiowetz et al., 1MRC Scale MRC, 197611

Paternostro-Sluga etSWMF Bell-Krotoski et al.,Modified Highet scale Dellon et al., 197414

TPD Jerosch-Herold, 2005SDT Standardized unpubl

evaluationCarroll UEFT Carroll, 196519

Russell et al., 198420

400-point HFT Gable et al, 199721

Purdue pegboard Tiffin and Asher, 194Schoneveld et al, 20

HTSS Lanzetta, Petruzzo,

Activities DASH (English original)F-DASH(French translation)

Hudak et al, 199628

Beaton et al, 200126

Durand et al, 200527

Observation of 65 tasks No data available

Participation HTSS Lanzetta, Petruzzo,RAND-36 Hays et al, 199329

Contextual factors SSGE No data available

ICF: International Classification of Functioning, Disability and HealthMedical Research Council; SWMF: Semmes-Weinstein monofilamentsnation test; UEFT: upper extremity function test; HFT: hand function tArm, Shoulder and Hand; RAND-36: 36-Item Short Form Health Survey

gum, teaspoon, and pen) to be recognized vision occluded.The unknown objects are presented in a standardizedformat, placed first in the less functional hand and then themore functional one, in random sequence, without timelimit. This procedure was developed as other tactile gnosisevaluations have limitations for our population. TheWynneParryeDellon test is limited to 30 s for objectidentification,16 the Moberg pickup test often requiredmore motion and dexterity than some of our patients wereable to achieve17 and the Shape/Texture Identification testis limited to only three shapes and textures.18

The Carroll upper extremity function test (UEFT)19,20

and the 400-point test21 were chosen to assess hand func-tion. The Carroll was selected as a familiar “gold standard”.Despite limited validation, the newer 400-point test21e23

was also included for its unique focus on bimanual handfunction. It is scored out of 100, and is interpreted as apercentage of normal hand function. Hand dexterity wasevaluated by the Purdue pegboard test24,25 as of 2010.

Activities of daily living (ADL) were assessed both byusing the DASH questionnaire26e28 for patient self-

ychometrics)Components and constructs

Goniometry, aROM summed across the jointsof individual digits

20039 Modified Kapandji index

98410 Grip and pinch strengthManual muscle testing

al., 200812

199313 Light touch thresholdSensory recovery

15 Receptor densityished Tactile gnosis: scored 0-8

Task-based evaluation of grip, grasp/release,pinch, placing, and positioning of upper limbMotor skills, strength, bimanual coordination

824 Dexterity0925

200730 Appearance, sensibility, movement, dailyactivities and work status, psychological andsocial acceptance, patient satisfaction andgeneral well beingSelf-report of bimanual disabilities for specificactivities

Non-standardized observation of functionaltasks

200730 Global outcomes after hand transplantationHealth-related quality of lifeSelf-reported satisfaction with motion,strength, sensation, pain and aesthetics

; TAM: total active motion; aROM: active range of motion; MRC:testing; TPD: two-point discrimination test; SDT: shape discrimi-est; HTSS: Hand Transplant Score System; DASH: Disabilities of the; SSGE: Self-subjective global evaluation.

Picture 2 Functional outcome. Long finger active motion:the worst (A) and the best (B) results (patients 1 and 4,respectively). Thumb opposition: the worst (C) and the best (D)results (patient 4, right and left hands, respectively).

Bilateral hand transplantation 1175

evaluation, and through direct observation by the handtherapist of 65 tasks selected to represent the essentialfunctions of the upper limbs, designed by the rehabilitationCentre of Val Rosay (France) including:

� personal care (i.e. shaving or applying make-up, hairwashing, tooth-brushing);

� dressing (i.e. putting on trousers, a sweat-shirt, ajacket, fastening a zipper or buttons);

� eating (i.e. cutting meat and bread, opening a yogurtpot);

� housework;� instrumental tasks, such as using a phone, plugging in apower outlet, and writing.

Prior to the transplantation, patients were asked tocomplete these tasks twice: first with no prostheses ortechnical aids, using only the stumps; and secondly, withthe use of prosthesis or the technical aid. The tasks wererated on a 4-point categorical scale as completed easily,with difficulty, partially, or not completed.

The RAND-36 questionnaire29 was administered post-transplantation only, for evaluation of QoL. We also useda Self-Subjective Global Evaluation (SSGE) to evaluateoverall satisfaction with hand function and appearance.Patients were asked to evaluate their hand using a scale of0e10, with 10 being the performance of a normal hand.They were then asked to rate their loss for each of thefollowing areas: ROM, strength, sensibility, pain, and aes-thetics. Finally, all the recipients were evaluated on thebasis of the Hand Transplantation Score System (HTSS),30

which is the score adopted by the International Registryof Hand and Composite Tissue Transplantation (IRHCTT),31

ranging from 0 to 100 and based on 10 subjective andobjective items such as sensitivity and motion recovery,ability to perform daily activities and to work, social re-integration, well-being and patient satisfaction.

Although the psychopathological evaluation of patientsis of paramount importance, it is not reported in this study,but will be the subject of a future publication.

Results

Mobility

FingersThe fingers reached 31e93% of their preoperative range(Table 3 and Picture 2A,B). Eighty percent of the final range

Table 3 TAM of the fingers (long digits) at the latest time poinextreme values.

Dominant hand

Mean (D2 + D3 + D4 + D5)/4 Range (worstebest dig

Patient 1 37.5% 27%e46%Patient 2 64% 58%e73%Patient 3 52.4% 44%e62%Patient 4 91% 83%e96%Patient 5 81% 75%e85%

had been achieved by one year and was at its maximum bythree years.

ThumbAll patients achieved some active opposition by the end ofthe first year and reached their maximal level within twoyears. The poorest outcomes were only able to achievemid-range movements of 2 grades (on the modifiedKapandji) while the best (in patient 4) was able to movefrom 0 to 6 in his dominant left hand (Table 4 and Picture2C,D).

Wrist and forearmThe average arc of active wrist flexion was 32� (range0e70�) and extension 53� (range 25e70�). The average

t of the follow-up expressed as mean % of normal ROM and

Non-dominant hand

it) Mean (D2 + D3 + D4 + D5)/4 Range (worstebest digit)

31% 8%e52%63% 58%e70%50.5% 38%e58%40.4% 35%e52%93% 90%e98%

Table 4 Kapandji score at the latest time point of thefollow-up. Achieved opposition grades are bold andunderlined.

Dominant hand Non-dominant hand

Patient 1 0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10Patient 2 0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10Patient 3 0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10Patient 4 0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10Patient 5 0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10

Figure 2 Key grip strength evolution on dominant hand(Jamar� Pinch Gauge Dynamometer).

1176 L. Bernardon et al.

pronation and supination was 50� (range 5e80�) and 63�

(range �5e90�), respectively.

Strength

The grip strength for all hands was between 2.0 and16.3 kg, or 4%e28% of age and gender norms. Digital pinchstrength ranged from 0 to 4.6 kg, or 0e36% of normal force

Figure 1 Grip strength evolution on dominant hand (Base-line� Hydraulic Hand Dynamometer).

Table 5 Tactile and discriminative sensibility at the latest follo

Sensibility Dominant hand

Thumb Index Middle Ring

Patient 1 SWMF 2.83 4.31 4.31 4.31TPD 15 >15 >15 >15Grade S3þ S3 S3 S3

Patient 2 SWMF 2.83 2.83 2.83 2.83TPD 6 9 12 >15Grade S4 S3þ S3þ S3

Patient 3 SWMF 4.31 4.31 3.61 3.61TPD 10 9 7 9Grade S3þ S3þ S3þ S3þ

Patient 4 SWMF 2.83 2.83 2.83 4.31TPD 13 15 >15 >15Grade S3þ S3þ S3 S3

Patient 5 SWMF 4.31 3.61 3.61 3.61TPD 8 7 8 >15Grade S3þ S3þ S3þ S3

SWMF: Semmes-Weinstein monofilaments testing; TPD: two-point discscale, modified by Dellon (1988).16

(Figures 1 and 2). Grip strength progressively increased over3e4 years before stabilising. Patients 2 and 4 showed asubstantial difference between hands.

Unlike sensory return, there was no difference inintrinsic muscle strength between the median and ulnarinnervations: the mean score for median-innervated mus-cles was 2.9 (range 0.7e4.7) for dominant hands and 2.3(range 0.7e3.3) for non-dominant hands; and the meanscore for ulnar-innervated intrinsic muscles was similarly2.9 (range 1.3e4.7) for dominant hands and 2.8 (range2.0e3.3) for non-dominant hands.

Sensibility

All patients acquired protective sensation to hot and coldby one year, and were able to appreciate at least the 4.31calibre SemmeseWeinstein filament (corresponding to2.1 g/cm2 pressure) on any digits at one year (Table 5) andwent on to achieve 0.4e0.1 g/cm2 (filaments 3.61e2.83).All regained static TPD between 6 and 15 mm (in 23 of 50

w-up.

Non-dominant hand

Little Thumb Index Middle Ring Little

3.61 4.31 4.31 3.61 2.83 2.83>15 14 13 >15 >15 >15S3 S3þ S3þ S3 S3 S32.83 2.83 2.83 2.83 2.83 2.8312 14 14 >15 15 10S3þ S3þ S3þ S3 S3þ S3þ4.31 3.61 2.83 2.83 2.83 2.8311 >15 >15 >15 >15 >15S3þ S3 S3 S3 S3 S32.83 4.31 3.61 4.31 4.31 3.61>15 >15 >15 13 >15 >15S3 S3 S3 S3þ S3 S33.61 3.61 3.61 3.61 4.31 4.31>15 >15 >15 >15 15 >15S3 S3 S3 S3 S3þ S3

rimination test; the Grade is expressed on the basis of the Highet

Bilateral hand transplantation 1177

digits), with better results on the dominant thumb andindex fingers. Maximal recovery appeared between 2 yearsand 5 years. All achieved sensibility of at least S3 on alldigits. In the median nerve S3þ was present in 56.6% of thefingers, dropping to 30% in the ulnar nerve. On our test ofstereognosis, scores varied widely from 1 to 8 (mean 5.2),with no difference between the dominant and non-dominant hands. Stereognosis generally appeared abouttwo years after surgery, and progressed for another twoyears.

Figure 4 400-point test. Results at the latest follow-up.

Hand function and dexterity

With the Carroll UEFT, for their dominant hand at the latestreview (a follow-up period ranging from 4 to 13 years), thescores averaged 68/99 (range 57e87; see Figure 3 for agraphical representation of the recovery over time). Theaverage score of the non-dominant hands at the latestevaluation was 52.8/96 (range 37e78). Most function wasregained in the first year. However, patients 3, 4, and 5improved beyond this time interval.

Higher 400-point test scores were achieved by thedominant hand. Patients averaged 55.8% (43e66%) on theirdominant hand and 49.4% (40e64%) on the non-dominant

Figure 3 Carroll’s test scores evolution on dominant hands.

Picture 3 Eating alone before (A) a

one (Figure 4). On the bimanual function subscale, themean score was 74% (range 53e87%). The results (includingthe bimanual subscale) continued to improve beyond threeyears.

With the Purdue pegboard dexterity test, at the latestreview, all patients continued to score well below the firstpercentile of the time-dependent population norms.

Activities of daily living (ADL) and return to work

Preoperative ability to perform 65 ADL tasks were assessedin the three latest patients (3, 4, and 5) with or withouttheir prosthesis (patient 3 used right side prosthesis only;patient 4 used assisting devices; and patient 5 used his twostumps almost exclusively). The average percentage ofeasily-completed tasks rose from 38% (range 5e63%) pre-operatively to 81% (range 74e91%). Twenty two percent oftasks were failed preoperatively (range 11e43%) droppingto 2% (range 0e3%) at final evaluation (Picture 3).

The DASH questionnaire was used since it becameavailable in French in 2005,27 so no preoperative data areavailable for patients 1 and 2. The latest average DASHscore across all 5 patients was 15 (range 4e42). Thesescores showed progressive valuable improvement for 2years, after which they stabilized (Figure 5).

Two out of five patients returned to work. Patient 1returned to a modified position with his previous employer.Patients 2, 3, and 4 were not able to return to work. Patient5 had worked as a construction foreman following his am-putations, but resumed his original vocation as a cheffollowing allografts.

nd after (B) hand transplantation.

Table 6 RAND-36 measure of health-related quality of life. Detailed subscales results at the latest time point of the follow-up.

RAND-36 subscale Patient 1 Patient 2 Patient 3 Patient 4 Patient 5

Physical functioning 95 80 70 75 90Role limitations due to physical health 100 100 0 75 50Role limitations due to emotional problems 100 100 0 66.6 100Energy/Fatigue 60 70 20 40 65Emotional well-being 40 68 48 48 92Social functioning 100 75 62.5 50 100Pain 100 100 65 45 55General health 60 65 15 30 70

Figure 5 DASH score evolution.Figure 7 Hand Transplantation Score System (HTSS) scoreevolution.

1178 L. Bernardon et al.

Satisfaction and QoL

Using the SSGE scale, patients subjectively rated theoverall outcome of their hands at an average of 7.7/10(range 3e10) at the latest follow-up. In order of impor-tance, they ascribed the residual deficits to lack ofmobility, lack of power, lack of sensitivity and lastly, aes-thetics. None of the patients ascribed residual deficit to thepain.

After one year, patients 2 to 5 (no data for patient 1 onthe first years) have rated an average of 6.7/10 (range4e9). There is an average improvement of one point

Figure 6 RAND-36 measure of health-related quality of lifesurvey. Summary scales scores (MCS: Mental Component Sum-mary; PCS: Physical Component Summary).

between their first postoperative year evaluation and thelatest review.

The RAND-36 scores of health related QoL are shown inFigure 6, including the two components, physical andmental, summary scores. The mean physical and mentalscores of the five patients are 67/100 and 65.25/100,respectively. The scores are detailed in Table 6.

The HTSS summary score of IHRCTT (Figure 7) showed aglobal improvement in the first three years after trans-plantation, then the results became stable, especially in thefirst two patients (13 and 10 years after transplantation).

Discussion

About the method

Selection of instruments for the evaluation of hand functionshould be based on the evidence for clinical utility, stan-dardization, purpose, psychometric properties, and inclu-sion of the patient perspective.32,33

The ideal outcome measurement tool for bilateral handtransplantation should be comprehensive, condition-specific,reliable for comparisons across different patients, differentcentres and time; reliable and valid for longitudinal compar-isons for the same patient before and after transplantation;and validated for assessment of impairments, activities andparticipation. Such a tool is not yet available for this new andunusual procedure. These challenges are compounded as wefound no validated tool for upper limb bilateral (or even uni-lateral) amputee evaluation.34

Bilateral hand transplantation 1179

In all areas of rehabilitation, the field of allo-transplantation faces evaluation difficulties.

A scoring system compares retrospectively results acrossthis heterogeneous population,30 but there are currently nostandardized evaluation tools (with psychometrics) for thispatient group.35

We therefore used validated general assessment tools(Carroll UEFT, DASH, 400-point test), and employed stan-dardized tools when necessary (HTSS, SSGE, tasks of ADL,stereognosis).

Evaluation of video is particularly useful for capturingcomplexities of hand use during the Carroll UEFT and 400-point test.

About the results

Mobility and strengthStrength was reduced in all patients, and patients 2 and 4changed dominance toward the stronger hand and differ-ences between the right and left stumps may explain theoutcome discrepancy.

Extrinsic mobility of fingers and the grip force arecorrelated, and preservation of muscle in distal amputa-tions with good soft-tissue quality appears to contribute torecovery of strength. The best mobility and strength werein patient 2 left side, patient 4 left side and patient 5 bothsides, each having distal amputation. However, a distal lossdid not guarantee good strength and mobility as in patient4, whose burn injuries were associated with limited mus-culotendinous gliding and ankylosis of the elbow.

The quality of opposition correlated with recovery ofthumb intrinsic muscles and key-pinch strength.

Intrinsic muscle recovery began with the hypothenargroup by the end of the first year, and continued to improveuntil three years post-graft. The best intrinsic power wasachieved by patient 4 with the shortest duration ofischemia, whilst conversely, the lowest intrinsic recoverywas seen in patient 5 with the longest duration of ischemia.

SensibilityOur patients identified absent sensibility as the major lim-itation of their myoelectric prostheses.

We formed the impression that nerve repair results werebetter in allotransplantation than replantation, but couldnot confirm this when comparing them with forearmreplantation in the literature,36e39 because of the poordata from past sensibility assessments. However, after bothmedian and ulnar nerve laceration “according to the S0eS4grading, only 26.5% (ulnar) and 31% (median) of direct su-ture cases achieved S3þ or more”.40 We observed betterresults in our transplanted patients with values of 30% and56.6% respectively.

We cannot explain this finding, but there are two majordifferences between replantation and transplantation.Firstly, the quality of the tissues is clean cut and withouttension. Second, is the attention to the re-education processin this innovative procedure. In addition, tacrolimus prob-ably exerts a positive effect on nerve regeneration.41e43

The use of the radial digits for precise, discriminativeprehension may partly explain why the ulnar nerve shows

poorer sensibility but equivalent muscle recovery comparedto the median territory.

We found that recovery of stereognosis is disappointingas our patients continue to need visual feedback in dailylife. Patients needed both good discriminative sensibilityand good extrinsic and intrinsic muscle recovery to showthe best stereognosis corroborating previous contributionsin this field.44,45

Functional assessmentsCarroll UEFT. Half the Carroll score relates to thumb op-position and our results strongly correlated with motionrecovery of the fingers and thumb. The Carroll UEFT normalscore is 99 for the dominant hands and 96 for non-dominantones, and so the score of the grafted hands approximates apercentage function of a normal hand. Dominant handsachieved 69% (range 58e88%) and non-dominant hands 55%(range 39e81%) of normal function.

Other authors have reported similar Carroll UEFT forunilateral allografts.46,47

The 400-point assessment. In all patients the scoreexpressing bimanual ability was always proportionally bet-ter than for a single hand, as if each hand were potentiatedduring bimanual use. Other units have mentioned the scorebut not reported results.35

Dexterity. The Purdue pegboard test recommended byNinkovic et al.,35 in our experience is too demanding for ourpopulation, given the primary focus on time to completethe required actions.

ActivitiesDASH. DASH scores are not directly correlated with thephysical and functional tests results and there is a markedvariation between patients. Patient 4 who had the beststrength outcome (of the 10 hands) on the left side and theleast performing on the right, reported the poorest DASHscore. Conversely, patient 1 whose results were among thepoorest had one of the best DASH scores. This may be dueto a poor fit between satisfaction, functional capacity andfunctional demands.

ADL. The graft allowed patients to do things they wereunable to pre-transplant and to perform more easily thatwhich could already be done. All our patients could liveindependently when they had previously been (with theexception of patient 5) dependent on help in everyday life.

During their pre-transplant evaluation, the five bilateralamputees could easily perform 38% (range 5e63%) of the 65tasks of ADL requiring the use of the upper limbs proposedin our evaluation. For the remaining tasks (62%), they wereeither unable or performed them with difficulty, slowlyand/or with the use of compensations such as shoulderabduction, trunk inclination and rotation, use of the mouthor teeth.

They had been physically dependent on assistance andappropriate adaptations for ADLs, including bathroom useand personal hygiene, use of kitchen devices, and driving acar. Dressing was a particular issue with clothing choicesbeing determined by physical abilities rather than personalpreference or social settings. Patients expressed howabnormal postures or unusual gestures damaged their sociallife. For four of them (patient 5 excepted) the ADL assess-ment highlighted how dependence drove a loss of autonomy.

1180 L. Bernardon et al.

It appears that in the case of bilateral amputation of hands,the anatomical and functional loss is associated with the lossof physical integrity and causes major disability in social,family and professional roles. This is the edge between thefunctional and psychological aspects of the hand allograft:while we have elected not to explore this fully in this article,our patients and our observations have confirmed our beliefthat there was a life-preserving quality in the non-life savingtransplant requests.

The ADL evaluation was designed by the rehabilitationCentre of Val Rosay (France) because such measures as theFunctional Independence Measure (FIM� instrument),48

include transfers, sphincter control, locomotion, commu-nication, awareness and memory that are not relevant toour group. The validated KleineBell ADL scale49 may be analternative in the future, but is much more time-consuming. Further improvement could introduce contem-porary observations such as the use of smartphones, com-puter, credit card and cash machines.

ParticipationHTSS. Being multifactorial, the accuracy of the HTSS couldbe improved with weighting using the principle of sifting50;the rationale being that a good overall result cannot beachieved if specific items, considered of importance, areunderrepresented in the measurements, or diluted throughthe blending with many less important constructs.

RAND-36: Health-related QoL. In our series, patientsscored an average of 67/100 on the physical summary scale(range 37.5e88.75). The very large range of scores (over 50points) is concordant with the care team’s perception ofthe patients’ physical status. For reference, the averagescore of the US population average is 90/100.51 Comparedto the US our patients’ average physical scale is similar topatients affected by diabetes or depression. Similarly, themean mental summary scale of 65.25/100 (range32.6e89.25) also demonstrates wide score variability. Incomparison, the US population average mental scale scoreis 75/100. Our patients’ average mental scale is similar tothat observed in multiple sclerosis and asymptomatic AIDSpopulations.51

On both Physical and Mental scales, the important dif-ferences between our patients does not seem to be relatedwith performance and function, but more with the abilityto be satisfied with a given result, reflecting our earliercomments on DASH scores.

Unfortunately,wedo not have relevant preoperative dataand are therefore unable to measure the improvement ourpatient should have gained. Furthermore, we did not findRAND-36 or SF-36 data on pre- or post-operative evaluationsin amputees versus grafted patients in the literature.

Similar to functional recovery, QoL should probably beappreciated as a multidimensional construct integratingsensibility and motion recovery as well as re-appropriationand use of the grafted hands.52

Contextual factors, self subjective global evaluationWith an average score of 6.7/10 at one-year post-graft, it isevident that patients are pleased with their hands from arelatively early stage, even though they have not reachedtheir maximum capacity. Over time, the SSGE improves anaverage of only one more point (from 6.7 to 7.7/10),

according to a similar progress in analytical and functionalfields. These data could reflect the patients’ early satis-faction at retrieving lost physical integrity, but also shows apersisting satisfaction despite analytical and functionalperformances inferior to those of a normal hand.

Overall results and influencing factors

Level and mechanism of amputation and associatedlesionsIn major replantation better outcomes are expected inmore distal transplants and in guillotine-typeamputation.38,39,53e55 This is attributed to the quality oftissue repairs, especially for the nerves, with earlier re-covery of sensation and earlier reanimation of intrinsicmusculature given the shorter distance of nerve re-growth. In our small series, the mechanisms of amputa-tion were always unfavourable. Even though the best re-sults were achieved in distally amputated patients, thisfactor did not directly predict final function and the smallnumber of cases prevents any robust conclusion in thismatter.

Associated injuries also influenced the outcome asillustrated by patient 4, whose amputations followed burnsof 70% of the body surface, resulting in ankylosis of theright elbow thus reducing the potential for optimal posi-tioning of the transplanted hand during functional activ-ities. In patient 3, the original electrocution injury may bethe source of reported pain.

Primary and secondary surgical managementThe average ischemia time, including both cold and warmischemia totalled 12.7 h (range 9e20 h). This point ischallenging for future transplantation. Ischemia timecontributed to the intrinsic muscles atrophy, most clearlyseen in patient 5 (although this patient who experiencedthe longest warm ischemia time achieved one of the bestfunctional results).

The majority of complications in the primary surgerieswere vascular, and were resolved successfully.

Except for patient 1 (who did not benefit from his leftthumb opposition transfer), secondary surgeries improvedpatients’ functional recovery.

Comparison to other series

There are no other series in the literature focussingexclusively on bilateral hand transplantation, and itproved difficult to compare our results to those of otherseries, because of discrepancies in the materials, thechoice of evaluation tools, the way of the evaluation toolsare used and the way results are presented.46,47,56,57 Weused eight assessments (TAM, Kapandji opposition, Grip,Key pinch, TPD, Intrinsic muscle testing, DASH, HTSS) incommon with the study of Ninkovic et al.35 (who includedthree bilateral amputees) and our results are at least asgood.

Landin et al.57 published a systematic review of 28 handtransplant patients and the five patients with bilateralbelow-elbow transplants presented an average pre-op DASHscore of 64.5 (range 29e98), and an average post-op DASH

Bilateral hand transplantation 1181

score of 44.8 (range 18e71) with an average improvementof 20 points.

The score of our three more recent patients (no preop-erative data for patients 1 and 2) shows an averageimprovement of 30 points.

Allograft versus previous functional status

Comparing the allografted hands with the presurgical statusis very difficult because of the great variety of the lattercircumstances.

The transplant recipients showed better mobilities thanpermitted by the prostheses they wore in which mobilitywas restricted to the second and third fingers, allowing tip-to-tip opposition with the thumb, (which required passivepositioning). No prosthesis provided wrist flexion or exten-sion. Only one had prono-supination.

The greatest grip strength exerted by the prostheses(10 kg) was less than the average of the dominant graftedhand (10.82 kg (2.6e16.3 kg)).

Sensation is one of the major benefits of hand allograft,and all patients reported that one of the major limits of themyoelectric was the absence of sensibility.

We were able to compare pre- and post-transplantationscores for the DASH and Carroll’s test for the three mostrecent patients in our series: Carroll improved by anaverage of 46 points on dominant sides, and 31 points onnon-dominant sides after the transplantation, and the DASHscore showed a 30-point average improvement (range18e39).

Literature reviewThe studies reviewed58e61 consider unilateral amputation,which is not comparable with bilateral amputation. Thereare no reports focussing exclusively on the use of bilateralprosthetics.

This lack of robust comparative data from the literaturehas prompted ongoing studies, including the ARMEDICstudy in Lyon (France) designed to compare prostheses andgrafts in bilateral cases, on medical, social and economicaspects.

An economic analysis of hand transplantation in the USAin 2010 concluded that in bilateral amputation, doublehand transplantation was favoured over the use of pros-thesis but exceeded the societally acceptable threshold forgeneral adoption because of cost.62

Delivered information and prerequisites forallografts

Our team deals only with bilateral traumatic adultamputees.

The amputee patients are expected to predict howsurgery would impact their lives. We verify that the patienthas correctly evaluated the benefits, not idealizing them,and is able to fully understand the constraints and risksinherent to the care.

They are informed of the expected benefits bydescribing the results one can hope to obtain, in theabsence of complications. We present the results obtained

in previously operated patients demonstrating the handsobtained are by no means normal.

The applicant is invited to meet a transplant patient whoexperienced an equivalent level of amputation. The appli-cant is informed about the constraints and also the risksassociated with this procedure. Therapeutic constraintsassociated with the transplant are the severity of the sur-gery, duration and intensity of rehabilitation requiringactive participation, the need for lifelong rigorous medi-cation compliance. The side effects of the immunosup-pressive regimen are carefully detailed. We emphasize theimportance of the immunological and functional moni-toring, requiring frequent testing, including skin biopsies.An annual 10-day hospitalization is also expected forfurther investigations, sometimes invasive, and for detailedhand functional assessment.

The main risks are summarised: first, the risks associatedwith immunosuppressive therapy, including metabolic dis-orders (diabetes), infection and cancer. We also explain therisk of chronic rejection, which may occur despiteadequate treatment, which can lead to amputation of thegrafted hand(s).

This information is issued and repeated separately byspecialist practitioners: surgeons, transplant physicians,therapists, psychiatrists. Ethicists and philosophers arehelping the team for ethical questions in the process ofmedical care. A plenary meeting of the patient with allstakeholders often complements these consultations.

One way to emphasize the constraints and risks to thepatient is to express the idea that if he can live withouthands, it is better for him to not have hand allografts. So farwe also require a previous prolonged prosthesis use.

In order to verify the understanding of the informationprovided, we ask the patient to write us a letter in whichhe explains what he understood, and what his motivationsare.

So, the candidates admitted for a transplant, are verymotivated, and dissatisfied with prostheses for reasons offunction and social acceptability (aesthetics, self-confidence, other people’s opinions, and physical integ-rity). We feel that the prostheses and the transplants aredifferent answers to different care requests, arising fromclinically comparable subjects. Our interpretation,garnered from collective experience is that the choice ofallograft versus prostheses is a matter of a personal eval-uation of the benefit-risk balance in favour of the allograft.We accept the idea very often expressed by the patients:“Quality of life is more important than the duration of thelife”.

Conclusion

We reviewed five adult patients, bilateral traumatic am-putees that our team treated in Lyon between 2000 and2009, with bilateral allograft at the forearm level, with anaverage follow-up of 7.6 years (range 4e13 years) endingDecember 31st, 2013. The physical results (motion,strength, sensibility) achieved are considered fair; func-tional results are considered good, and subjective resultsconsidered very good. These results progress dramaticallyduring the first year, significantly during the first three

1182 L. Bernardon et al.

years, even later, especially for sensitivity, then becomestable. The overall results are effective, unequalled byprosthesis so far, and lasting for the duration of this follow-up.

The procedure is demanding both for the patient(especially psychologically) and for the healthcare pro-viders, especially the rehabilitation team, and carries allthe risks of major surgery, immunosuppressive-regimen sideeffects and complications, and the risk of graft loss becauseof chronic rejection.

Conflict of interest

None declared.

Funding

This study was funded by a National grant (PHRC).

Ethical approval

The study was approved by the Comite consultatif de pro-tection des personnes dans la recherche biomedicale(CCPPRB).

Acknowledgements

This paper is dedicated to the donors and their families. Wethank the whole team of anesthesiologists, nurses, reha-bilitation, as well as the Agence de la biomedecine (ABM).Each member of the team made possible the results ach-ieved in our patients. We also thank Mr. Mickael Hugues(Lyon, France) for the photos of patients 1 and 2. Weexpress our gratitude to professors Jean-Jacques Comtet,Guy Foucher and Graham D. Lister - our teachers andmentors in hand surgery.

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