PM R 10 (2018) 1173-1184 www.pmrjournal.org Original Research The Use of Transfers to Restore Upper Extremity Function in Cervical Spinal Cord Injury

Ida K. Fox, MD, Christine B. Novak, PhD, Emily M. Krauss, MD, Gwendolyn M. Hoben, MD, PhD, Craig M. Zaidman, MD, Rimma Ruvinskaya, MD, Neringa Juknis, MD, Anke C. Winter, MD, MSc, Susan E. Mackinnon, MD

Abstract

Background: Nerve transfer to restore upper extremity function in cervical spinal cord injury (SCI) is novel and may transform treatment. Determining candidacy even years post-SCI is ill defined and deserves investigation. Objective: To develop a diagnostic algorithm, focusing on electrodiagnostic (EDX) studies, to determine eligibility for nerve transfer surgery. Design: Retrospective descriptive case series. Setting: Tertiary university-based institution. Patients: Individuals with cervical SCI (n ¼ 45). Methods: The electronic medical records of people referred to the Multidisciplinary Upper Extremity Surgery in SCI from 2010-2015 were reviewed. People were considered for nerve transfers to restore elbow extension or finger flexion and/or extension. Data including demographic, clinical evaluation, EDX results, surgery, and outcomes were collected and analyzed. Main Outcome Measurements: EDX data, including nerve conduction studies and , for bilateral upper ex- tremities of each patient examined was used to assess for the presence of lower motor injury, which would preclude late nerve transfer. Results: Based on our criteria and the results of EDX testing, a substantial number of patients presenting even years post-SCI were candidates for nerve transfers. Clinical outcome results are heterogeneous but promising and suggest that further refinement of eligibility, long-term follow-up, and standardized assessment will improve our understanding of the role of nerve transfer surgery to restore function in people with midcervical SCI. Conclusions: Many patients living with SCI are candidates for nerve transfer surgery to restore upper extremity function. Although the ultimate efficacy of these is not yet determined, this study attempts to report the criteria we are using and may ultimately determine the timing for intervention and which transfers are most useful for this heterogeneous population. Level of Evidence: IV

Introduction such as nerve transfer surgery [1-3,5-13] could improve eligibility or desirability for reconstructive Cervical-level spinal cord injury (SCI) can result in a surgery. devastating loss of function. Reconstruc- A motor nerve transfer surgically coapts an expend- tive surgery, traditionally tendon transfer techniques able donor nerve that innervates a muscle under voli- [1-3], can improve function and yet as few as 14% of tional control, to a nonfunctional recipient nerve to eligible people with cervical SCI in the United States) provide return of function. This has revolutionized the receive upper limb reconstructive surgery [4].The field of brachial plexus and peripheral nerve injury limitations of tendon transfers include limited treatment [14,15]. In midlevel SCI, there are numerous tendon/muscle donors and a long duration of post- potential donor and recipient that could be operative immobilization. Newer treatment options coapted to restore function (Table 1).

1934-1482/$ - see front matter ª 2018 by the American Academy of Physical and Rehabilitation https://doi.org/10.1016/j.pmrj.2018.03.013 1174 Use of Nerve Transfers

Table 1 Nerve Transfer Options to Restore Function in SCI Missing function Reconstructive options Other information Elbow extension Posterior deltoid nerve branch The posterior deltoid muscle often has dual innervation from the axillary nerve to triceps nerve branch (one of the 2 branches is therefore expendable). transfer extension Brachialis nerve branch to ECRL The brachialis muscle is an elbow flexor as are the biceps and BR. The brachialis nerve branch transfer is expendable if the biceps function is normal and retained. Brachialis nerve branch is a useful donor for nerve transfer; the brachialis muscle is not very useful as a donor in tendon transfer surgery for biomechanical reasons. The ECRL nerve branch recipient is in relative proximity to the brachialis donor. Re- innervation of ECRB muscle would provide central wrist extension (preferable) but the distance between donor and recipient precludes doing this transfer. opening (thumb and Supinator nerve branch to PIN The supinator nerve branch is expendable because the biceps muscle is actually finger extension) nerve branch transfer the primary supinator of the forearm and can be preserved to retain this function. Supinator nerve branch is a useful donor for nerve transfer; the supinator muscle is not useful as a donor in tendon transfer surgery for biomechanical reasons. Hand closing Brachialis nerve branch to AIN The brachialis muscle is expendable as noted above. (prehension and grasp) and FDS nerve branch The branches of the median nerve to the AIN and FDS can be separated from transfer other functioning or nonfunctioning components incuding nerve branches to PT, FCR, sensory, thenar musculature. Other transfer Teres minor nerve branch to The teres minor nerve branch of the axillary nerve is expendable as the optionsdshoulder level Triceps nerve branch transfer infraspinatus muscle also provides shoulder external rotation. However this is located relatively far from the triceps muscle recipient. Other transfer BR nerve branch to Other nerve The BR nerve branch is, theoretically, an expendable donor. However, BR serves optionsdBR N donor branch transfer (not as useful additional elbow flexor in users of manual wheelchairs who do not recommended) have normal triceps function. BR is also useful as a donor for the tendon transfer to restore power pinch (BR to FPL), which can be done in addition to or instead of nerve transfer surgery. Other transfer optionsdto Supinator nerve branch to ECU The supinator nerve is expendable as noted above. However the ECU nerve augment wrist extension nerve branch transfer branch recipient is difficult to separate from the PIN proper and ECU muscle (not recommended) function alone does not provide much additional wrist function in the absence of ECRL and B function. Other transfer Expendable donor nerve to The ulnar nerve recipient is located further from putative donors (brachialis, optionsdfor more hand ulnar innervated musculature supinator or BR Ns) and provides less function; therefore nerve transfers in SCI closing (grip) function (flexor digitorum profundus) are preferentially routed into the median nerve branches (see above). Other transfer Expendable donor nerve to Because the intrinsic muscles are in the hand, they are far from the putative optionsdfor hand ulnar and/or median donor nerves (such as nerves to FCR, FCU, or other forearm-level function (power pinch, innervated intrinsic musculature); the transferred nerve would fail to reach target within w1 year opposition, abduction, musculature of the hand and reinnervation would fail. dexterity) (not recommended) Other caveats Theoretical risks and Use of the deltoid posterior head nerve branch as a donor likely precludes downstream effects subsequent posterior deltoid to triceps tendon transfer surgery to restore elbow extension as the remaining posterior deltoid function (while retained) may be suboptimal for tendon transfer. Use of brachialis nerve branch as a donor precludes the biceps to triceps tendon transfer surgery to restore elbow extension as no elbow flexors would be preserved. Use of supinator nerve branch as a donor also precludes use of the the biceps to triceps tendon transfer surgery to restore elbow extension as no forearm supinators would be preserved. This table includes a list of putative donor and recipient nerves in midlevel cervical spinal cord injury. The specific combinations are based on decades of work in brachial plexus and peripheral nerve injury surgery as well as more recent work describing nerve transfers in SCI. The missing function and nerve transfer surgery reconstructive optionsdincluding the putative donor and recipient nerve branchesdare listed. Further in- formation about why the donor is considered relatively expendable, caveats, and other relevant technical information is provided. Use of bra- chialis and supinator as donor nerves for nerve transfer procedures is advantageous as these muscles are not effective for use in tendon transfer surgery because of their anatomy and other biomechanical characteristics. Therefore, people with midlevel SCI, who are not candidates for traditional tendon transfer surgeries, may be candidates for some of the above tabulated nerve transfer surgeries. The AIN innervates the flexor pollicis longus and flexor digitorum profundus muscles to the index þ/- long finger, and the PIN innervates the extensor pollicis longus, the extensor digitorum communis to index, long, ring and small finger, the extensor indicis proprius, the extensor digiti minimi, extensor carpi ulnaris and the abductor pollicis longus muscles. ECRL ¼ extensor carpi radialis longus; BR ¼ brachioradialis; ECRB ¼ extensor carpi radialis brevis; PIN ¼ posterior interosseous nerve; AIN ¼ anterior interosseous nerve; FDS ¼ flexor digitorum superficialis; PT ¼ pronator teres; FCR ¼ flexor carpi radialis; N ¼ nerve; FPL ¼ flexor pollicis longus; ECU ¼ extensor carpi ulnaris. Reproduced with permission from nervesurgery.wustl.edu, 2017. I.K. Fox et al. / PM R 10 (2018) 1173-1184 1175

People ineligible for tendon transfer surgery could from disruption of UMN control, a nerve transfer be eligible for nerve transfers [11] as nerve transfers could be theoretically performed even decades after do not have the same biomechanical limitations of SCI (Figure 1). Although muscles may atrophy, they tendon transfers. Also, a single donor nerve can should not become fibrotic without concomitant LMN reinnervate multiple muscles, and thus restore mul- injury [20-22]. However, in the cases of SCI, with loss tiple functions [15]. Finally, nerve transfers do not of UMN control and a zone of direct LMN damage in require the immobilization and perioperative strin- the spinal cord [20] (Figure 2), candidacy for nerve gent activity restrictions required of tendon transfer transfer is dependent on the time from injury; surgery. By eliminating some of the barriers to concomitant LMN damage at the level of desired reconstructive surgery, the addition of nerve trans- reinnervation must be addressed before terminal fers may transform the current treatment paradigm in muscle atrophy occurs. Differentiating these sub- cervical SCI. populations is critical to appropriate surgical decision Candidacy for nerve transfer surgery in SCI is unique making. Patients with concomitant LMN injury will and differs from that of people with isolated lower not be eligible for nerve transfer surgery unless it can (LMN) injury (such as brachial plexus and restore both UMN and LMN innervation to the recip- peripheral nerve injuries). In isolated LMN injuries, a ient muscle within approximately 1 year of injury. In nerve transfer is used to reroute expendable functional our clinic, we test for continuity of the LMN at the peripheral nerves to reinnervate the affected, dener- level of the putative recipient using electrodiagnostic vated muscle. Restoration of function to denervated (EDX) studies. muscle is time sensitive. If muscle innervation is not The purpose of this retrospective descriptive case restored within approximately 1 year, irreversible ter- series was to describe an integrated diagnostic process, minal muscle atrophy will occur and function will not be focusing on EDX studies, to determine eligibility for restored [16-19]. nerve transfer surgery in the setting of cervical SCI. Our By contrast, in SCI the injury patterns are hetero- specific focus was to define the subgroups that had geneous and may include (1) loss of upper motor time-sensitive, extensive LMN loss patterns of SCI. By neuron (UMN) function alone or (2) a combination of incorporating electrophysiology into the presurgical UMN and LMN dysfunction [20]. The nerve transfer evaluation, we hypothesize that we can identify which technique is used to bypass the damaged spinal cord patients are candidates for delayed SCI nerve transfer area and restore muscle function by restoring UMN surgery from within those with similar physical exami- control. In injury patterns with loss of function purely nations and functional loss.

Figure 1. In SCI, a peripheral nerve transfer surgery is typically used to bypass an area of spinal cord injury to deliver a signal via the upper motor neuron (UMN) from the brain to a muscle that became disconnected following that injury. A donor peripheral nerve, (lower motor neuron [LMN]) is taken from a less essential uninjured muscle and transferred to provide a more critical function. (Reproduced with permission from nervesurgery. wustl.edu, 2016.) 1176 Use of Nerve Transfers

Figure 2. However, some people with SCI will have a more extensive zone of LMN injury within the cord, and the nerve transfer will be required to restore volitional upper motor neuron control and continuity of the lower motor unit. In this injury pattern, after 1 year of denervation from lower motor neuron damage, irreversible muscle atrophy has occurred, and function cannot be restored with a nerve transfer (a tendon transfer may still be performed). (Reproduced with permission from nervesurgery.wustl.edu, 2016.)

Methods assistance) were elicited by the surgeon. A detailed physical examination by the surgeon and a certified hand The study was approved by the Washington University and physical therapist was used to assess for the presence School of Medicine Institutional Review Board. of adequate motor donors (MRC grade >4 strength). Pu- tative nerve transfer recipient muscles were also dis- Patients and Record Review cussed based on absent function and patient preference. Patients who had (1) lack of expendable motor donors by For this retrospective review, we included all physical examination; (2) significant medical comorbid- consecutive patients (age 18 years) referred to the ities; and/or (3) psychosocial contraindications were Plastic Surgery Multidisciplinary Upper Extremity Sur- deemed ineligible for nerve transfer surgery. Those pa- gery in SCI clinic from 2010-2015. Our institution is a tients considered eligible for nerve transfer surgery were tertiary care academic center in the Midwest. The pa- referred for EDX testing. tient population presenting at this clinic was diverse, with referrals from within our academic center by the Electrodiagnostic Testing Physical and Rehabilitation Medicine and SCI Medicine specialists who practice at the same institution, by Overview therapists and providers from a nearby affiliated reha- Six neuromuscular neurologists with American Board of bilitation and self-referral after reading news Electrodiagnostic Medicine certification per- and articles online. formed the EDX testing in the electrophysiology laboratory Demographic, health history (including mechanism using standard techniques, equipment (Nicolet, Natus and date of SCI), physical examination, and EDX testing Medical Incorporated, Pleasanton, CA), and normal values data were collected from the electronic medical records as defined by the laboratory (see below). Nerve conduc- and coded for analysis. Each was also tion studies (NCS) and electromyography (EMG) were reviewed by the principal investigator, and a standard- performed with some variability depending on the nerve ized data collection form was used to collect informa- transfer surgical procedure(s) under consideration. Po- tion regarding the individualized patient assessment, tential donor and recipient nerves and the muscles that plan of care, and outcomes. they innervate were tested based on the tentative surgical plan, patient tolerance, and testing time available. Some Initial Assessment patients had EDX testing of the bilateral upper extremities and others had unilateral testing. The biologic (major comorbidities that might preclude semi-elective surgery under general ) and psy- Nerve Conduction Studies chosocial history (expectations regarding return of func- We collected and recorded the motor compound tion, social support such as transport/perioperative muscle action potential (CMAP) amplitudes and I.K. Fox et al. / PM R 10 (2018) 1173-1184 1177 antidromic sensory nerve action potential (SNAP) am- surgical procedure(s), postoperative course and plitudes. We chose the following specific motor seg- outcome (as reported by the treating hand therapist and ments as the most relevant and reliable (normal values the surgeon). Research team members met to review are provided in parentheses): (1) Radial CMAP, extensor the information and, using standardized score sheets, indicis proprius (EIP) to forearm segment (normal 2 provided a post hoc score regarding the appropriateness millivolts); (2) Median CMAP, abductor pollicis brevis of the determination of candidacy and the success of (APB) to wrist segment (normal 4 millivolts); and (3) the surgery on a scale from 0 (poor) to 10 (excellent). Ulnar CMAP, abductor digit minimi (ADM) to wrist Based on this, a review of reasons for success and segment (normal 6 millivolts). CMAPs were coded as conjecture regarding the lack of success were also absent, reduced, or normal. Sensory NCS results were discussed. reviewed to assess for superimposed peripheral nerve abnormalities (such as brachial plexus injury or cubital Statistical Analysis tunnel syndrome). Normal and abnormal values were collected per segment tested or percentage of segments Descriptive statistics, including the number and per- tested rather than per patient. centages of tested limbs, were determined for the data. Not all patients had both Electromyography limbs tested across each segment. Similarly for the EMG, EMG test results of the potential recipient muscles data for all muscles were provided and not all patients as well as other muscles with the same cervical root underwent EMG for each muscle tested. Therefore, level innervation were collected to assess for the when providing the descriptive data, all limbs and presence or absence of UMN control and the presence muscles were analyzed independently for the NCS and or absence of direct LMN injury and muscle denerva- EMG respectively. tion. We defined LMN injury to these muscles based on the presence of either abnormal spontaneous activity (fibrillations [Fibs] and positive sharp waves [PSWs]) or Results abnormal motor unit morphology and recruitment patterns consistent with chronic denervation (large, Patient Sample and Demographics broad, polyphasic motor unit potentials [MUPs], and reduced recruitment). We assessed 45 adult patients with cervical SCI from 2010 to 2015. Thirty-six patients completed EDX testing. Surgical Procedure and Outcomes Of the patients not referred for EDX testing, the most frequent reasons included: 1) inadequate donors; 2) Surgical intervention details were documented and suboptimal recipient muscles; and 3) contractures included data regarding laterality of surgery and goal of (Figure 3). The cause and type of SCI and demographic surgery (restore elbow extension, wrist extension, finger data are presented in Table 2. extension, finger flexion, or other function). Details of the intraoperative direct nerve stimulation findings that Electrodiagnostic Test Results were used to confirm and finalize the selection of donor and recipient nerve branches were recorded. The Overview electronic medical record was reviewed, and results For patients with more than one date of EDX testing, from manual muscle testing of the exact recipient we used the first testing date to calculate the time since muscles were recorded and categorized by the most SCI. An abnormal (absent) CMAP, suggests that there is a common transfer surgeries performed. In this manu- LMN injury at that cervical level and/or within that script, we have chosen to use the name of the recipient specific nerve segment. Those patients with abnormal and donor muscles to indicate the branches of the CMAPs would not be considered candidates for nerve nerve that were used. These included the (1) brachialis transfer surgery if they presented at >1 year post-SCI. to anterior interosseous nerve (AIN) / FDS transfer to Our analysis was focused on the CMAP amplitude of restore hand closing; (2) supinator to PIN transfer to the radial and median nerves which provided putative or restore hand opening; and (3) deltoid to triceps transfer surrogate information for the potential recipient to restore elbow extension. Qualitative descriptions of nerves. Specifically, we considered patients candidates gains in function were also collected from the outpa- for the hand opening supinator to posterior interosseous tient electronic medical record and included both the nerve (PIN) surgery if the radial CMAP recorded from the surgeon and notes. Postoperative EMG testing EIP muscle was present and similarly determined can- was not performed. didacy for the hand-closing brachialis to anterior inter- A multidisciplinary research team reviewed the in- osseous nerve (AIN)/flexor digitorum superficialis (FDS) formation of all patients who underwent transfer sur- transfer surgery if the median CMAP from the APB gery. This included data on the initial evaluation, muscle was present. EMG testing results of the recipient 1178 Use of Nerve Transfers

Figure 3. This schematic illustrates the process of consideration of cervical spinal cord injury (SCI) patients for upper extremity nerve transfer surgery. This cohort consisted of consecutive patients (age 18 years, from 2010-2015) referred to the Plastic Surgery Multidisciplinary Upper Extremity Surgery in SCI clinic. Surgical candidacy was determined by comprehensive evaluation through history, physical examination, elec- trodiagnostic testing and, later, intraoperative direct nerve stimulation. Some patients had more than one finding that contributed to not being considered a surgical candidate; the total number of reasons may be greater than the total number of subjects.

musculature and other musculature deriving innervation with mild incongruence between these two CMAPs seen at the same cervical root level were also reviewed. on rare occasion (Table 3). Patient candidacy for the elbow extension posterior CMAPs were completely absent in a proportion of the deltoid to triceps branch nerve transfer was based on tested radial, median, or ulnar nerves. A larger propor- solely on EMG findings. NCS of the radial and axillary tion of the tested segments had variably reduced CMAPS nerves at the shoulder and proximal arm are theo- indicating heterogeneous patterns of LMN involvement retically possible but technically difficult and prone to (Table 3). We found a normal median nerve CMAP in an error because of challenging surface anatomy and individual who was greater than 12 years post-SCI. course of the nerves at this level [23].NoNCSwere Results of the sensory NCS were reported using SNAP performed to evaluate candidacy for this transfer amplitudes as these provide quantitative information procedure. about the number of intact sensory LMNs. This infor- mation further confirms the central nervous system of the disease process related to SCI. Sub- NCS Results: For Evaluation of Supinator to PIN stantial sensory NCS abnormalities, which would suggest and Brachialis to AIN/FDS/FCR Transfer a superimposed brachial plexus or peripheral nerve injury, were not seen even in the subpopulation with a NCS results are presented in Table 3. Results are severe mechanism of injury (motor vehicle crash, etc) categorized by the duration of time since SCI because (Appendix A). patients referred for evaluation, testing, and surgery within 1 year of injury had different eligibility charac- teristics for surgery compared to those presenting >1 EMG Test Results: For Evaluation of the Deltoid year postinjury. to Triceps Nerve Transfer Our analysis was focused on results of the motor NCS of the radial and median which provided putative or Nineteen patients had EMG of at least one head of surrogate information for the potential recipient nerve. the triceps muscle recipient, with 72 discrete muscles Ulnar NCS were also recorded in most patients; the tested. In these 72 muscles, 60 showed EMG evidence median and ulnar CMAP amplitude results were similar, of LMN injury as indicated by abnormal spontaneous I.K. Fox et al. / PM R 10 (2018) 1173-1184 1179

Table 2 EMG Test Results: For Evaluation of Other Patient Characteristics According to Time Since SCI (N ¼ 36) Musculature Time since SCI n (%) <1 year 1 year In our study population, nearly 400 muscles were tested. Characteristics n ¼ 9n¼ 27 These included the following putative donor nerve mus- cles: brachialis, biceps, supinator and BR. Recipient nerve Mean age years (SD) 36.1 (16) 38.8 (17) Gender muscles tested included the following groups: (1) extensor Male 7 (78) 22 (82) carpi radialis muscle (ECRdas differentiation between Female 2 (22) 5 (18) ECRB and ECRL is difficult, EMG of these wrist extensors Race were as grouped together in EDX reports); (2) AIN inner- White 6 (67) 24 (89) vated (FPL and FDP to index and long); (3) FDS muscle; and African American/Black 2 (22) 2 (7) American Indian/Alaska Native 1 (11) 0 (0) (4) PIN innervated (EPL, APL, EDC, EIP, EDQ, and ECU). Cause of injury Testing of the APB and first dorsal interosseous muscles Sport/leisure 3 (33) 9 (33) provided additional information about the C8/T1 nerve Assault 0 (0) 1 (4) root level musculature although these muscles were not Transport 5 (56) 12 (44) the direct target of the nerve transfer surgery. Fall 1 (11) 3 (11) Nontraumatic spinal cord lesion 0 (0) 2 (7) Relevant EMG data for all of the study subjects who Type of Injury underwent EDX testing has been organized and reported Blunt 9 (100) 24 (89) along with the corresponding NCS data. For each patient Penetrating 0 (0) 1 (4) limb tested, EMG results were categorized by the corre- Unknown 0 (0) 2 (7) sponding CMAP. Median CMAPS (recorded from the APB) Current employment status Working part-time 1 (11) 2 (7) with absent, low, and normal values were reported along Working full-time 1 (11) 3 (11) with the EMG of the median innervated musculature of On disability 5 (56) 13 (48) interest(FDS,FPL,FDP,andAPB).RadialnerveCMAPS Unemployed/looking for work 0 (0) 0 (0) (recorded from the EIP) with absent, low, and normal Unemployed/not looking for work 0 (0) 4 (15) values were reported along with the EMG of the radial Not reported 2 (22) 5 (18) Comorbidities innervated musculature of interest (EIP, EPL, APL, EDC, History of autonomic dysreflexia 3 (33) 14 (54) EDQ, and ECU). Details of the EMG testing stratified by NCS History of heart attack 1 (11) 1 (4) test results are presented in Appendix B. Overall, there History of hypertension 1 (11) 4 (15) were 35 corresponding muscles tested in individuals who History of stroke 0 (0) 1 (4) had a median NCS completed on the corresponding limb. History of diabetes 0 (0) 3 (11) History of seizures/black outs 0 (0) 2 (7) There were 7 muscles tested in individuals who had a History of neurodegenerative disorder 0 (0) 0 (0) radial NCS completed on the corresponding limb. The History of congenital spine deformity 0 (0) 1 (4) paucity of muscles tested and heterogeneity make it History of degenerative spine disorders 1 (11) 1 (4) difficult to identify clear correlates between NCS and History of 0 (0) 1 (4) EMG. Overall, the majority of median innervated muscu- History of asthma 0 (0) 1 (4) History of lung disease/COPD 0 (0) 0 (0) lature corresponding to normal median CMAPs had EMG Previous upper extremity/hand surgery 1 (11) 3 (11) findings that corroborated a lack of direct LMN injury Presence of any spasticity 7 (78) 22 (82) (absence of spontaneous activity) and loss of UMN control Presence of upper extremity spasticity 3 (33) 5 (18) (absent MUPs and no recruitment). Similar trends were SCI ¼ spinal cord injury; SD ¼ standard deviation; COPD ¼ chronic identified in the radial innervated musculature tested in obstructive pulmonary disease. those with normal radial CMAPs.

Electrodiagnostic Test Results Stratified by activity (Fibs and PSWs). An additional 6 of 72 had Duration of Time Since SCI abnormal MUP morphology indicating denervation with chronic reinnervation. In summary, 66 of 72 (92%) Our EDX testing results indicated that there were a ofalltricepsmusclestestedshowedevidenceofLMN substantial number of patients who presented more than injury. 1 year post-SCI with no LMN injury at the level of putative MUPS were absent in 47 of the 72 tested muscles recipient and were eligible for delayed nerve transfer (65%) demonstrating a concomitant lack of UMN control. surgery to restore hand function. More than half of these In some cases, the MUPS pattern in a single extremity patients were eligible for a brachialis to AIN/FDS nerve was different for the different heads of the triceps transfer (indicated by a preserved median CMAP) to (medial, long, lateral); for example, evidence of restore thumb/finger flexion and approximately half ongoing denervation/reinnervation with preserved UMN were eligible for a supinator to PIN nerve transfer (indi- control in one triceps head was seen with evidence of cated by a preserved radial CMAP) to restore thumb/ denervation with absent MUPs in another. finger extension. Because nerve transfers can be used to 1180 Use of Nerve Transfers

Table 3 Results of Motor Nerve Conduction Studies Time since Spinal Cord Injury For all limbs tested (n ¼ 36) < 1 year (n ¼ 9) 1 year (n ¼ 27) Segment Number of limbs (%) Number of limbs (%) Number of limbs (%) Radial CMAP (EIP to forearm)dtotal limbs tested 28 5 23 Absent (0 millivolts) 6 (21) 2 (40) 4 (17) Reduced (>0 but <2 millivolts) 10 (36) 2 (40) 8 (35) Normal (2 millivolts) 12 (43) 1 (20) 11 (48) Median CMAP (APB to wrist)dtotal limbs tested 54 15 39 Absent (0 millivolts) 12 (22) 2 (13) 10 (26) Reduced (>0 but <4 millivolts) 8 (15) 3 (20) 5 (13) Normal (4 millivolts) 34 (63) 10 (67) 24 (62) Ulnar CMAP (ADM to wrist)dtotal limbs tested 52 16 36 Absent (0 millivolts) 12 (23) 3 (19) 9 (25) Reduced (>0 but <6 millivolts) 26 (50) 12 (75) 14 (39) Normal (6 millivolts) 14 (27) 1 (6) 13 (36) The results for the electrodiagnostic testing are reported per segment/limb tested. The first line in each section indicates the total number of limbs that were tested over the corresponding nerve segment (radial, median, and ulnar nerves). The subsequent rows in each section display the number of limbs that have absent, reduced, or normal compound muscle action potentials (CMAPs) values in millivolts. The segment tested is indicated EIP (extensor indicis proprius), APB (abductor pollicis brevis), and ADM (abductor digiti minimi). restore UMN control and to reinnervate denervated long) fingertip flexion, this nerve was included as a muscles by restoring LMN continuity in patients who recipient; (2) if FDS nerve stimulation produced digit present within 1 year of SCI, different criteria for surgical flexion at the proximal interphalangeal joint, this nerve eligibility were used. We report these data based on was also included as a recipient; (3) if volitional FCR number who would be eligible if they were to wait (not function was absent and FCR stimulation produced wrist time-sensitive transfer scenario). More than half of the flexion, this nerve was included as a recipient (if addi- patients were eligible for the brachialis to AIN/FDS nerve tional donor nerve branches were available). transfer (to restore thumb/finger flexion) at any time Additional detailed results, which include the rele- post-SCI, and approximately 25% were eligible for the vant preoperative electrodiagnostic testing results (NCS supinator to PIN transfer (to restore thumb/finger and EMG) and clinical outcome for each patient who extension) at any time post-SCI. No patients presenting underwent surgery are presented in Appendixes A and more than 1 year post-SCI were eligible for the deltoid to C. This includes the results of detailed manual muscles triceps nerve transfer (to restore elbow extension) testing for the exact recipient nerve muscles and de- because of a mixed pattern of LMN injury showing scriptions of qualitative gains in function. ongoing muscle denervation/reinnervation with vari- Overall, the majority of surgical patients had gains in ability in the presence and absence of UMN control. Some function on isolated manual muscle testing of recipient of the patients might have been eligible for the deltoid to musculature (observed gains in MRC grade from 0 pre- triceps transfer (to restore elbow extension) but only if operatively to 1þ to 3 post-operatively). This translated the nerve transfer was performed within 1 year after SCI. to augmented tenodesis effect hand function (for the For these patients, nerve transfers could have been hand-specific transfers) and qualitative improvement in offered to provide both restoration of volitional activities of daily living. Results for the transfer to UMN control and reinnervation (restoration of LMN restore elbow extension were more variable. continuity). After the research team review and scoring, conjecture regarding the potential reasons for subop- Surgical Decision Making and Outcomes timal outcomes were discussed. These findings are as follows: (1) In one case, ingrained adaptive successful Details of the patient population and surgeries strategies (successful bimanual use of extremities to completed are presented in Figure 3. complete activities of daily living) and upper extremity Nuances of the surgical decision making regarding positioning (profound forearm supination and wrist donor and recipient nerve combinations were noted extension at baseline) precluded successful integration particularly for the brachialis to AIN/FDS/FCR nerve of the new function provided by the nerve transfer; transfer. For example, direct intraoperative stimulation of and (2) in the second case, later histologic analysis the FCR, FDS, and AIN permitted the final selection of the of the donor and recipient nerve tissue revealed recipient nerves. The intraoperative decision-making pri- extensive scar within the recipient radial nerve branch orities for this transfer (brachialis to AIN/FDS/FCR ) were to triceps that likely precluded successful nerve (1) if AIN stimulation produced thumb and index (þ/e regeneration. I.K. Fox et al. / PM R 10 (2018) 1173-1184 1181

Discussion contribute to successful restoration of elbow extension. Nerve transfer surgery can restore function to un- Limitations of this study include the retrospective damaged anterior horn cells, LMNs, that are below the analysis, the select patient sample from a single surgeon’s level of the cervical SCI. The extent of LMN injury dif- practice, and the referral patterns in our local environ- fers between patients, and muscle atrophy and fibrosis ment that may not be representative of the general can be difficult to differentiate using physical exami- population. Candidacy for nerve transfer surgery has yet nation alone. This study shows how EDX testing can be to be definitively outlined. Our previous work [9,10,24],as used to help determine eligibility for nerve transfer well as contributions from others [6-8,11-13,25,26],sug- surgery. Our outcomes suggest that clinically useful gest that results after nerve transfer surgery are prom- function can be derived from the nerve transfer surgery, ising, although studies [27,28] show variable outcomes. which serves as an alternative to tendon transfer or This emphasizes the need for careful and comprehensive other more experimental procedures. preoperative patient evaluation using standardized func- There are numerous factors that contribute to pa- tional assessments to better define surgical candidacy and tient candidacy for a successful surgical procedure and outcomes of nerve transfer surgery in patients with SCI. outcome. In this particular patient population, biologic The main aim of this study was to evaluate the preoper- factors such as overall cardiovascular, respiratory, skin, ative evaluation particularly the EDX studies in patients and infectious concerns can preclude safe general with SCI to identify those patients who had extensive LMN anesthetic and elective surgery. Inalterable joint con- loss patterns and thus a time-sensitive case for early (<1 tractures, indoctrinated substitutions and patterns of year) nerve transfer surgery. In many of the patients re- upper extremity use, and the lack of adequate and ported in this study, the follow-up time was insufficient to expendable motor nerve donors may also make surgery report the final outcomes and the source of the recovery to improve upper extremity function contraindicated. (nerve transfer surgery, late regeneration, or zone of Once these prerequisite conditions are met, additional partial preservation). However, in nerve transfers such as preoperative workup with EDX testing provides some the supinator to PIN transfer, the recipient PIN is preliminary data about the continuity of the LMN below completely transected surgically with complete disconti- the level of the SCI. Intraoperative nerve stimulation is nuity of the lower motor neuron to allow the nerve then used to finalize the appropriate recipient nerve coaptation of the donor supinator nerve branch to the branches for transfer. recipient PIN nerve. The original innervation pattern to Our study shows that many of the patients presenting the PIN is therefore disrupted and this precludes recovery within 1 year of SCI, and some even decades after as a result of late regeneration or a zone of partial pres- injury, are potential candidates for nerve transfer sur- ervation. In these cases, the gain in function must be due gery, and thus improved hand function and increased to reinnervation via the nerve transfer surgery. By independence. Candidates are identified by the pres- contrast, for the deltoid branch to triceps branch and ence of intact CMAPs in the median and radial nerve brachialis branch to AIN/branch FDS transfer, some fasci- recipient branches, which is corroborated by intra- cles may be left intact and the source of recovery is not as operative stimulation results in those patients who did clear and deserves further investigation. Future prospec- undergo surgery. Outcomes in our cohort were generally tive studies with standardized pre- and postsurgical eval- positive, though in some cases subtle, with gains in uation are planned to determine which factors best Medical Research Council (MRC) grades from 0 to 3 when predict a successful outcome of nerve transfer surgeries in isolated manual muscle testing was performed. This these complex patients with SCI. translated to augmented tenodesis function and the Cervical SCI is a heterogeneous disease process; ability to pinch and grip small, light items (food, uten- approaches to care and outcomes assessment should sils, and urinary catheters). Based on these results, we be individualized. Nerve transfers may be an accept- have provided a working guide to the performance of able alternative for those hoping for incremental EDX for preoperative evaluation of suitability for nerve functional gains with minimal postoperative immobi- transfer surgery in SCI (Table 4). lization. This contrasts to the other available proced- Importantly, we found that none of the patients ures to improve function: (1) tendon transfers, which presenting more than 1 year post-SCI were candidates require substantial immobilization; and (2) experi- for the posterior deltoid to triceps nerve transfer mental implanted neuroprostheses, which are not procedure to restore elbow extension. EMG testing of commercially available. the triceps musculature showed extensive, mixed UMN and LMN injury. Of the 3 patients who presented Conclusion within 1 year of SCI and underwent a deltoid to triceps nerve transfer surgery to restore both UMN and LMN Adaptation of the use of nerve transfer surgery to restore function, results were variable. This suggests that function in people with cervical SCI is an exciting develop- further work is needed to determine factors that may ment. Many patients with SCI, including those who are 1182 Use of Nerve Transfers

Table 4 Working Protocol for the Exam and Electrodiagnostic (EDX) Evaluation of People with Cervical Spinal Cord Injury Considering Nerve Transfer Surgery Functional and EDX Criteria For Hand Closing Nerve TransferdBrachialis Nerve Branch to AIN/FDS Nerve Transfer Donor function Examine for normal brachialis function (MRC 5) Redundant function Examine for normal biceps (MRC 5) (will maintain elbow flexion after nerve transfer is done) Donor EMG testing Consider testing brachialis, biceps, and brachioradialis muscles Recipient function Examine for absent thumb, finger flexion (MRC 0) Recipient CMAP CMAP median (recording done from the APB) Recipient (in millivolts): CMAP > 4: best outcome CMAP >0 and <4: unclear CMAP absent: not a candidate for late nerve transfer Recipient EMG testing Consider testing FPL, FDP, FDS muscles (note intraoperative nerve stimulation is also used to confirm the presence or absence of FDS LMN integrity) Surrogate EMG Consider testing APB and FDI muscles (provides information about the continuity of the LMN at the C8/T1 cervical root level) For Hand Opening Nerve TransferdSupinator N to PIN transfer Donor function Examine for normal supinator function (MRC 5) Redundant function Examine for normal biceps (MRC 5) (will maintain forearm supination after nerve transfer is done) Donor EMG testing For the Supinator N donor, consider testing supinator and biceps muscles Recipient function Examine for Absent Thumb, Finger Extension (MRC 0) Recipient CMAP CMAP Radial (recording done from the EIP) Recipient in millivolts: CMAP >2: best outcome CMAP 1e2: suboptimal (intraoperative stimulation required to make final decision) CMAP absent: not a candidate for late nerve transfer Recipient EMG testing Consider testing EPL, EDC, EIP, EDQ, ECU muscles For Other TransfersdThe details of the examination and testing are described For wrist extension nerve transferdbrachialis to ECRL nerve transfer Goal of surgery For people with no wrist extension and no tenodesis function, this transfer may be used to restore wrist extension and secondary tenodesis driven hand function Relevant examination Examine for normal brachialis and biceps function (MRC 5) and absent wrist extension (MRC O) Relevant EDX EMG of the donor brachialis and recipient ECR musculature may be performed For elbow extension nerve transferdposterior deltoid N to triceps (medial, long, or lateral head) nerve transfer Goal of surgery For people with no elbow extension, this transfer may be used to restore elbow extension; however, this transfer must typically be performed within 1 year of SCI Relevant examination Examine for normal deltoid function (MRC 5) and absent triceps function (MRC 0) Relevant testing EMG of the donor (anterior, middle, and posterior deltoid) and recipient (long, lateral, and medial head of triceps) musculature should be performed AIN (anterior interosseous nerve) innervates the flexor pollicis longus and flexor digitorum profundus muscles to the index þ/e long finger, and PIN (posterior interosseous nerve) innervates the extensor pollicis longus, the extensor digitorum communis to index, long, ring and small finger, the extensor indicis proprius, the extensor digiti minimi, extensor carpi ulnaris, and the abductor pollicis longus muscles. For most people considering nerve transfer surgery, function will be present at the shoulder, elbow, and wrist level. Hand function is generally absent (aside from that due to the tenodesis effect hand function) and the goal of the nerve transfer surgery is to restore hand closing and opening. Of note, less common transfers to restore elbow extension and (if absent) wrist extension may also be considered. The following tests provide either direct or surrogate information regarding potential donor and recipient nerves. This information includes physical examination findings and EDX, which may be used to augment the physical examination; further intraoperative direct nerve stimulation, clinical judgement, and intraoperative decision making are also necessary. On all patients, motor and sensory nerve conduction studies (NCS) of the radial, median, and ulnar nerves are also performed. This allows for assessment of superimposed compressive or other neuropathy, concomitant brachial plexus injury, and other disease processes. Further details of the NCS findings are noted in the table below. Ideal candidates for late nerve transfer should have the following EMG findings: (1) EMG of donors should reveal intact normal musculature without denervation; (2) EMG of recipients or surrogate muscles should show an absence of denervation (no spontaneous activity) and a lack of UMN control (no MUPs and no recruitment). Caveat 1: for patients presenting <1 year postinjury, this information is not as relevant, because even in the presence of abnormal NCS or CMAPs, function may be restored. Caveat 2: Donor muscle electrodiagnostic testing may not be necessary for muscles with normal Medical Research Council (MRC) 5 strength on physical examination. CMAPs are reported in millivolts. MRC ¼ medial research council; EMG ¼ electromyography; CMAP ¼ compound muscle action potential; APB ¼ abductor pollicis brevis; FPL ¼ flexor pollicis longus; FDP ¼ flexor digitorum profundus; FDS ¼ flexor digitorum superficialis; LMN ¼ lower motor neuron; FDI ¼ first dorsal interosseous; N ¼ nerve; EPL ¼ extensor pollicis muscle; EDC ¼ extensor digitorum communis; EIP ¼ extensor indicis proprius; EDQ ¼ extensor digitorum quinti minimi; ECU ¼ extensor carpi ulnaris; ECRL ¼ extensor carpi radialis longus; ECR ¼ extensor carpi radialis brevis and/or longus muscle; SCI ¼ spinal cord injury. Reproduced with permission from nervesurgery.wustl.edu, 2017. I.K. Fox et al. / PM R 10 (2018) 1173-1184 1183 decades after injury, are candidates for nerve transfer 10. Fox IK, Davidge KM, Novak CB, et al. Nerve transfers to restore surgery to restore hand function. In contrast, patients upper extremity function in cervical spinal cord injury: Update and greater than 1 year after SCI are likely not candidates for preliminary outcomes. Plast Reconstr Surg 2015;136:780-792. 11. Friden J, Gohritz A. Brachialis-to-extensor carpi radialis longus nerve transfers from the deltoid to triceps as the triceps selective nerve transfer to restore wrist extension in tetraplegia: musculature often showed extensive LMN injury. There- Case report. J Hand Surg Am 2012;37:1606-1608. fore, early referral of patients (within 6 months of SCI) who 12. Mackinnon SE, Yee A, Ray WZ. Nerve transfers for the restoration lack antigravity elbow extension is essential to optimize of hand function after spinal cord injury. J Neurosurg 2012;117: functional outcome. Although the ultimate efficacy of 176-185. 13. van Zyl N, Hahn JB, Cooper CA, Weymouth MD, Flood SJ, Galea MP. these surgeries is not yet determined, this study attempts Upper limb reinnervation in C6 tetraplegia using a triple nerve to report the criteria we are using and may ultimately transfer: Case report. J Hand Surg Am 2014;39:1779-1783. determine the timing for intervention and which transfers 14. Lee SK, Wolfe SW. Nerve transfers for the upper extremity: New are most useful for this heterogeneous population. Future horizons in nerve reconstruction. J Am Acad Orthop Surg 2012;20: studies will better define the outcomes to be gained from 506-517. 15. Tung TH, Mackinnon SE. Nerve transfers: Indications, techniques, nerve transfer procedures for individuals living with cervi- and outcomes. J Hand Surg Am 2010;35:332-341. cal SCI. 16. Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: Prolonged axotomy. J Neurosci 1995; 15(5, pt 2):3876-3885. Acknowledgments 17. Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J Neurosci The authors acknowledge Carie Kennedy, RN, Joel 1995;15(5, pt 2):3886-3895. Vetter, MS, Jessica Carter, RN, Rebecca Hamm, OT, 18. Gordon T, Yang JF, Ayer K, Stein RB, Tyreman N. Recovery po- tential of muscle after partial denervation: a comparison between Lorna Kahn, PT, and Meredith Whitehead, PT, for rats and humans. Brain Res Bull 1993;30:477-482. assistance with manuscript review, study data analysis, 19. Omer GE Jr. Injuries to nerves of the upper extremity. J Joint organization, and patient assessment including partici- Surg Am 1974;56:1615-1624. pation in the comprehensive research study meetings. 20. Coulet B, Allieu Y, Chammas M. Injured metamere and func- tional surgery of the tetraplegic upper limb. Hand Clin 2002;18: 399-412, vi. References 21. Ho CH, Triolo RJ, Elias AL, et al. Functional electrical stimulation and spinal cord injury. Phys Med Rehabil Clin N Am 2014;25:631- 1. Zlotolow DA. The role of the upper extremity surgeon in the man- 654, ix. agement of tetraplegia. J Hand Surg Am 2011;36:929-935; quiz 935. 22. Mulcahey MJ, Smith BT, Betz RR. Evaluation of the lower motor 2. Kozin SH. Biceps-to-triceps transfer for restoration of elbow neuron integrity of upper extremity muscles in high level spinal extension in tetraplegia. Tech Hand Up Extrem Surg 2003;7:43-51. cord injury. Spinal Cord 1999;37:585-591. 3. Hentz VR, Ladd AL. Functional Reconstruction of the Upper Ex- 23. Preston DC, Shapiro BE. Electromyography and Neuromuscular tremity in Tetraplegia, Vol 1. New York: McGraw Hill; 1996. Disorders: Clinical-Electrophysiologic Correlations. Saint Louis, 4. Curtin CM, Gater DR, Chung KC. Upper extremity reconstruction in MO: Elsevier Saunders; 2012. the tetraplegic population, a national epidemiologic study. J Hand 24. Fox IK. Nerve transfers in tetraplegia. Hand Clin 2016;32:227- Surg Am 2005;30:94-99. 242. 5. Bertelli JA, Ghizoni MF. Transfer of nerve branch to the brachialis 25. Bertelli JA, Tacca CP, Winkelmann Duarte EC, Ghizoni MF, to reconstruct elbow extension in incomplete tetraplegia: Case Duarte H. Transfer of axillary nerve branches to reconstruct elbow report. J Hand Surg Am 2012;37:1990-1993. extension in tetraplegics: A laboratory investigation of surgical 6. Bertelli JA, Ghizoni MF. Nerve transfers for elbow and finger feasibility. 2011;31:376-381. extension reconstruction in midcervical spinal cord injuries. J 26. Bertelli JA, Mendes Lehm VL, Tacca CP, Winkelmann Duarte EC, Neurosurg 2015;122:121-127. Ghizoni MF, Duarte H. Transfer of the distal terminal motor branch 7. Bertelli JA, Ghizoni MF, Tacca CP. Transfer of the teres minor of the extensor carpi radialis brevis to the nerve of the flexor motor branch for triceps reinnervation in tetraplegia. J Neurosurg pollicis longus: An anatomic study and clinical application in a 2011;114:1457-1460. tetraplegic patient. 2012;70:1011-1016; discussion 8. Bertelli JA, Tacca CP, Ghizoni MF, Kechele PR, Santos MA. Transfer 1016. of supinator motor branches to the posterior interosseous nerve to 27. Bertelli JA, Ghizoni MF. Nerve transfers for restoration of finger reconstruct thumb and finger extension in tetraplegia: Case flexion in patients with tetraplegia. J Neurosurg Spine 2017;26: report. J Hand Surg Am 2010;35:1647-1651. 55-61. 9. Fox IK, Davidge KM, Novak CB, et al. Use of peripheral nerve 28. Cain SA, Gohritz A, Fride´n J, van Zyl N. Review of upper extremity transfers in tetraplegia: Evaluation of feasibility and morbidity. nerve transfer in cervical spinal cord injury. J Brachial Plex Hand (N Y) 2015;10:60-67. Peripher Nerve Inj 2015;10:e34-e42.

Disclosure

I.K.F. Division of Plastic & Reconstructive Surgery, Washington University School C.B.N. Division of Plastic & Reconstructive Surgery, University of Toronto, Tor- of Medicine, 660 South Euclid Avenue, Box 8238, St Louis, MO 63110. Address onto, ON, Canada correspondence to: I.K.F.; e-mail: [email protected] Disclosures related to this publication: grant, Craig H. Neilsen Foundation Grant Disclosures related to this publication: grant, Craig H. Neilsen Foundation pro- paid to corresponding author institution (money to institution) vided funding for this work (money to institution) 1184 Use of Nerve Transfers

E.M.K. Division of Plastic Surgery, University of British Columbia Island Medical N.J. Department of , Washington University School of Medicine, St Program, Victoria, BC, Canada Louis, MO Disclosures related to this publication: grant, Craig H. Neilsen Foundation Grant Disclosures related to this publication: grant, Craig H. Neilsen Foundation paid to corresponding author institution (money to institution) (money to institution)

G.M.H. Division of Plastic & Reconstructive Surgery, Washington University A.C.W. Division of Sciences, Washington University School of School of Medicine, St Louis, MO Medicine, St Louis, MO Disclosure: nothing to disclose Disclosures related to this publication: grant, Craig H. Neilsen Foundation (money to institution) C.M.Z. Department of Neurology, Washington University School of Medicine, St Louis, MO S.E.M. Division of Plastic & Reconstructive Surgery, Washington University School Disclosures related to this publication: grant, Craig H. Neilsen Foundation of Medicine, St Louis, MO (money to institution) Disclosures related to this publication: grant, Craig H. Neilsen Foundation Spinal Cord Injury Research on the Translation Spectrum (SCIRTS) (PI: Ida K. Fox) R.R. Department of Neurology, Washington University School of Medicine, St (money to institution); Disclosures outside this publication: expert testimony, Louis, MO for legal cases (money to author); grants/grants pending, NIH (money to insti- Disclosures related to this publication: grant, Craig H. Neilsen Foundation tution); royalties, Thieme Medical Publishers, Inc (money to author) (money to institution) Funding to support this project from the Craig H. Neilsen Foundation Spinal Cord Injury Research on the Translation Spectrum (SCIRTS) Grant: “Nerve Transfers to Restore Hand Function in Cervical Spinal Cord Injury.” Submitted for publication May 11, 2017; accepted March 2, 2018. I.K. Fox et al. / PM R 10 (2018) 1173-1184 1184.e1

Appendix A Appendix B

Results of the Sensory Nerve Conduction Studies Results of Motor Nerve Conduction Studies (NCS) and Corresponding Electromyography (EMG) The results for the electrodiagnostics testing are reported per segment/limb tested and are reported The results for the electrodiagnostics testing are forallofthetestedsegments.Thefirstlineineach reported per limb tested. Of the tested muscles, re- section indicates the total number of limbs that were sults are stratified by the ipsilateral limb’s compound tested over the corresponding nerve segment (radial: muscle action potentials (CMAP) values for the tested wrist to the snuffbox; median: wrist to digit 2 or 3; nerve segment. The median CMAP was recorded at the and ulnar: wrist to digit 5); the subsequent rows in abductor pollicis brevis (APB) to wrist segment and each section display the numbers of limbs that have the corresponding tested muscles included the flexor nonrecordable, reduced or normal sensory nerve ac- digitorum superficialis (FDS), flexor digitorum pro- tion potentials (SNAP) values in microvolts. Results of fundus (FDP), and APB. The radial CMAP was recorded the sensory NCS were reported using SNAP ampli- at the extensor indicis proprius (EIP) to forearm tudes as these provide quantitative information segment and the corresponding tested muscles about the number of intact sensory LMNs. This in- included the extensor pollicis muscle (EPL), EIP, formation further confirms the central nervous sys- extensor digitorum communis (EDC), and extensor tem pathology of the disease process related to SCI. carpi ulnaris (ECU). Substantial sensory NCS abnormalities, which would Overall there were 35 corresponding muscles tested in suggest a superimposed brachial plexus or peripheral individuals that had a median NCS completed on the nerve injury, were not seen even in the subpopula- corresponding limb. There were 7 muscles tested in in- tion with a severe mechanism of injury (motor dividuals that had a radial NCS completed on the cor- vehicle crash, etc). Overall, the majority of the responding limb. The numerical values listed in each row examined radial, median, or ulnar SNAPs were below indicated the numbers of muscles in the ipsilat- normal. None of the examined radial or median eral limb that had the described spontaneous activity SNAPs were absent and only 7% of the ulnar SNAPs (fibrillations and/or insertional activity), motor unit were absent. In patients <1yearfrominjury,mostof potentials (MUPs) and recruitment patterns. This per- the examined SNAPS were normal (82%-100%). Absent mits characterization of the musculature associated ulnar SNAPs were only found in patients >1year with a specific normal or abnormal motor neve conduc- after SCI. tion study value.

Time Since Spinal Cord Injury <1 year (n ¼ 9) 1 year (n ¼ 27) For all limbs Segment tested (n ¼ 36) Number of limbs (%) Number of limbs (%) Radial SNAP: total limbs tested 27 4 23 Absent (0) 0 (0) 0 (0) 0 (0) Reduced (>0to<10 microvolt) 5 (19) 0 (0) 5 (22) Normal (10 microvolt) 22 (81) 4 (100) 18 (78) Median SNAP: total limbs tested 58 17 41 Absent (0) 0 (0) 0 (0) 0 (0) Reduced (>0 but <7 microvolt) 7 (12) 0 (0) 7 (17) Normal (7 microvolt) 51 (88) 17 (100) 34 (83) Ulnar SNAP: total limbs tested 57 17 40 Absent (0) 4 (7) 0 (0) 4 (10) Reduced (>0 but <5 microvolt) 8 (14) 3 (18) 5 (13) Normal (5 microvolt) 45 (79) 14 (82) 31 (78) SNAP ¼ sensory nerve action potential. 1184.e2 Use of Nerve Transfers

Appendix C Of note, all EDX data were obtained prior to the relevant surgery. We report the EDX test results for both Detailed Electrodiagnostic (EDX) and Surgical Procedure the donor and recipient nerve branches that were Outcomes Data for the Nerve Transfer Surgery Subset tested. To provide as much relevant information as possible, the EMG for each relevant muscle tested is As described in the manuscript, for this retrospective provided as EMG results 1, 2, etc For the most part, cohort study, testing was heterogeneous particularly these tests were done on the same day; the results for with respect to the electromyography (EMG). Detailed each muscle tested are reported in separate columns for information on the nerve transfer surgery completed and clarity. The relevant nerve conduction study is reported corresponding EDX including nerve conduction studies in millivolts and is the compound muscle action potential (NCS) and relevant EMG is provided. In reporting the for the median or radial nerve segment to abductor time interval between the date of spinal cord injury pollicis brevis (APB) or extensor indicis proprius (EIP), (SCI) and surgery, we delineate if the interval is >1 year respectively. As delineated in the manuscript, these or <1 year post-SCI to parallel information in the other segments are tested when considering transfers to the tables and the body of the manuscript. Of note, several median (branches to anterior interosseous nerve [AIN] subjects underwent more than one procedure. For the and/or flexor digitorum superficialis [FDS]) or posterior sake of brevity, details regarding the date of the specific interosseous nerve (PIN) recipient nerves. Corresponding procedures are not included, and the date of the first sensory nerve action potential data for each segment surgery is used to determine the time interval. tested is also reported.

Median CMAP Results EMG Results (median innervated muscles) Absent (0 mV) Reduced (<4 mV) Normal (4 mV) Spontaneous Activity No 6 5 11 Yes 4 2 7 MUPS Normal MUPS 1 1 4 Abnormal MUPS 1 2 1 Absent MUPS 8 4 13 Recruitment pattern None 7 3 12 Normal recruitment 0 0 1 Reduced recruitment 2 1 1 Reduced activation 0 0 4 Not tested 1 3 0 EMG Results Radial CMAP Results (radial innervated muscles) Absent (0 mV) Reduced (<2 mV) Normal (2) Spontaneous Activity No 0 1 2 Yes 0 4 0 MUPS Normal MUPS 0 2 1 Abnormal MUPS 0 0 1 Absent MUPS 0 3 0 Recruitment Pattern None 0 3 0 Normal recruitment 0 0 0 Reduced recruitment 0 1 1 Reduced activation 0 1 1 Not tested 0 0 0