Assessment, management, and rehabilitation of traumatic peripheral nerve injuries for non-surgeons.

Electrodiagnostic evaluation is often requested for persons with peripheral nerve injuries and plays an important role in their diagnosis, prognosis, and management. Peripheral nerve injuries are common and can have devastating effects on patients' physical, psychological, and socioeconomic well-being; alongside surgeons, electrodiagnostic medicine specialists serve a central function in ensuring patients receive optimal treatment for these injuries. Surgical intervention-nerve grafting, nerve transfers, and tendon transfers-often plays a critical role in the management of these injuries and the restoration of patients' function. Increasingly, nerve transfers are becoming the standard of care for some types of peripheral nerve injury due to two significant advantages: first, they shorten the time to reinnervation of denervated muscles; and second, they confer greater specificity in directing motor and sensory axons toward their respective targets. As the indications for, and use of, nerve transfers expand, so too does the role of the electrodiagnostic medicine specialist in establishing or confirming the diagnosis, determining the injury's prognosis, recommending treatment, aiding in surgical planning, and supporting rehabilitation. Having a working knowledge of nerve and/or tendon transfer options allows the electrodiagnostic medicine specialist to not only arrive at the diagnosis and prognosticate, but also to clarify which nerves and/or muscles might be suitable donors, such as confirming whether the branch to supinator could be a nerve transfer donor to restore distal posterior interosseous nerve function. Moreover, post-operative testing can determine if nerve transfer reinnervation is occurring and progress patients' rehabilitation and/or direct surgeons to consider tendon transfers.

The hand diagram: A novel outcome measure following supercharged end-to-side anterior interosseous nerve to ulnar nerve transfer in severe compressive ulnar neuropathy.

BACKGROUND: With advances in the surgical management for severe ulnar neuropathy with the introduction of the super charged-end-to-side (SETS) anterior interosseous nerve (AIN) to ulnar nerve transfer, a simple and reliable outcome measure is required. There is currently not "one" standardized outcome measure used to represent and compare results. PURPOSE: To present the abduction hand diagram as a "novel", reproducible, and simple outcome measure for patients with severe ulnar neuropathy. STUDY DESIGN: Retrospective case series. METHODS: Nine patients with severe entrapment/compressive ulnar neuropathy at the elbow were reviewed. Clinical parameters included preoperative and postoperative abduction tracings, Medical Research Grade (MRC) muscle strength, key pinch strength, Disability of the Hand Arm and Shoulder (DASH) score, and crossed finger test. Electrodiagnostic data included change in compound muscle action potentials (CMAP) amplitude of the first dorsal interosseous (FDI), and abductor digiti minimi (ADM). Summary statistics were used for demographic and clinical data. RESULTS: Average follow-up was 22.8 ± 9.3 months. At 18-months of follow up, 44% had ADM MRC grade 3 strength or higher, mean key pinch strength improved to 72 ± 19.3%, and mean DASH was 33 ± 28.7. There was a mean increase of 16.7 ± 9.1 mm and 31.5 ± 12 mm in total and summed hand abduction tracing measurements respectively. CONCLUSIONS: Hand abduction tracings are a quantitative outcome measure to follow recovery over time for intrinsic hand function and can be used in patients with severe ulnar neuropathy following surgical intervention.

Postoperative management and rehabilitation after the supercharged end-to-side anterior interosseous nerve to ulnar motor nerve transfer: A report of 3 cases.

INTRODUCTION: Compressive ulnar neuropathy at the elbow is the second most common compressive neuropathy. Nerve transfers are used for severe ulnar neuropathies as a means of facilitating recovery. Hand therapy and rehabilitation after nerve transfers have not been extensively explored. PURPOSE OF THE STUDY: The aim of this repeated case study was to describe the responses, functional outcome, and neuromuscular health of three participants after the supercharged end-to-side (SETS) anterior interosseous nerve (AIN) to ulnar motor nerve transfer do describe the hand therapy and recovery of 3 cases reflecting different recovery potential mediators, trajectories, and outcomes. STUDY DESIGN: Repeated case study. METHODS: Three participants of similar age (76-80 years) that had severe ulnar neuropathy who underwent surgical treatment including a SETS AIN to ulnar motor nerve surgery were purposively selected from an ongoing clinical trial, based on their response to the surgical and the rehabilitation intervention (large, moderate, and small improvements). Clinical evaluations included measuring range of motion, strength testing, and clinical tests (ie, Egawa's sign) and, subjective assessment of rehabilitation adherence., Quick Disability of Arm, Shoulder and Hand and decomposition-based quantitative electromyography were performed at >23 months to evaluate patients. RESULTS: All the three participants completed the surgical and hand therapy interventions, demonstrating a variable course of recovery and functional outcomes. The Quick Disability of Arm, Shoulder and Hand scores (>23 months) for participants A, B, and C were 68, 30, and 18, respectively. The person with the least improvement had idiopathic Parkinson's disease, dyslipidemia, history of depression, and gout. Comparison across cases suggested that the comorbidities, longer time from neuropathy to the surgical intervention, and psychosocial barriers to exercise and rehabilitation adherence influenced the recovery process. The participants with the best outcomes demonstrated improvements in his lower motor neurons or motor unit counts (109 and 18 motor units in the abductor digiti minimi (ADM) and first dorsal interosseous, respectively) and motor unit stability (39.5% and 37.6% near-fiber jiggle in the ADM and first dorsal interosseous, respectively). The participant with moderate response to the interventions had a motor unit count of 93 for the ADM muscle. We were unable to determine motor unit counts and measurements from the participant with the poorest outcomes due to his physical limitations. CONCLUSIONS: SETS AIN to ulnar motor nerve followed by multimodal hand therapy provides measurable improvements in neurophysiology and function, although engagement in hand therapy and outcomes appear to be mediated by comorbid physical and psychosocial health.

Treatment of Cervical Spondylotic Amyotrophy With Nerve Transfers.

Cervical spondylotic amyotrophy is characterized by severe, proximal upper extremity weakness including an inability to abduct the shoulder and flex the elbow. Treatment using both medical and surgical decompression approaches has produced variable results. This paper reports the use of nerve transfers (spinal accessory to suprascapular, flexor carpi ulnaris fascicle of ulnar to biceps motor branch, radial nerve branch to triceps to axillary) to restore shoulder and elbow function in a case of unilateral cervical spondylotic amyotrophy involving C5 and C6 myotomes. Evidence of regeneration was observed on electromyography as well as clinically at 5 months postoperatively. At 3 years after surgery, recovery of elbow flexion and shoulder abduction was Medical Research Council grade 4/5 with improved external rotation and considerably improved patient-rated Disabilities of the Arm, Shoulder and Hand scores. We propose that nerve transfers be considered along with other reconstruction modalities in the treatment of cervical spondylotic amyotrophy.

Nerve transfers and neurotization in peripheral nerve injury, from surgery to rehabilitation.

Peripheral nerve injury (PNI) and recent advances in nerve reconstruction (such as neurotization with nerve transfers) have improved outcomes for patients suffering peripheral nerve trauma. The purpose of this paper is to bridge the gap between the electromyographer/clinical neurophysiologist and the peripheral nerve surgeon. Whereas the preceding literature focuses on either the basic science behind nerve injury and reconstruction, or the surgical options and algorithms, this paper demonstrates how electromyography is not just a 'decision tool' when deciding whether to operate but is also essential to all phases of PNI management including surgery and rehabilitation. The recent advances in the reconstruction and rehabilitation of PNI is demonstrated using case examples to assist the electromyographer to understand modern surgical techniques and the unique demands they ask from electrodiagnostic testing.

Sciatic and tibial neuropathies.

The sciatic nerve is the body's largest peripheral nerve. Along with their two terminal divisions (tibial and fibular), their anatomic location makes them particularly vulnerable to trauma and iatrogenic injuries. A thorough understanding of the functional anatomy is required to adequately localize lesions in this lengthy neural pathway. Proximal disorders of the nerve can be challenging to precisely localize among a range of possibilities including lumbosacral pathology, radiculopathy, or piriformis syndrome. A correct diagnosis is based upon a thorough history and physical examination, which will then appropriately direct adjunctive investigations such as imaging and electrodiagnostic testing. Disorders of the sciatic nerve and its terminal branches are disabling for patients, and expert assessment by rehabilitation professionals is important in limiting their impact. Applying techniques established in the upper extremity, surgical reconstruction of lower extremity nerve dysfunction is rapidly improving and evolving. These new techniques, such as nerve transfers, require electrodiagnostic assessment of both the injured nerve(s) as well as healthy, potential donor nerves as part of a complete neurophysiological examination.

Anterior Interosseus to Ulnar Motor Nerve Transfers: A Canadian Perspective.

BACKGROUND: The anterior interosseus nerve (AIN) to ulnar motor nerve transfer has been popularized as an adjunct to surgical decompression in patients with severe cubital tunnel syndrome (CuTS) and high ulnar nerve injuries. The factors influencing its implementation in Canada have yet to be described. METHODS: An electronic survey was distributed to all members of the Canadian Society of Plastic Surgery (CSPS) using REDCap software. The survey examined 4 themes: previous training/experience, practice volume of nerve pathologies, experience with nerve transfers, and approach to the treatment of CuTS and high ulnar nerve injuries. RESULTS: A total of 49 responses were collected (12% response rate). Of all, 62% of surgeons would use an AIN to ulnar motor supercharge end-to-side (SETS) transfer for a high ulnar nerve injury. For patients with CuTS and signs of intrinsic atrophy, 75% of surgeons would add an AIN-SETS transfer to a cubital tunnel decompression. Sixty-five percent would also release Guyon's canal, and the majority (56%) use a perineurial window for their end-to-side repair. Eighteen percent of surgeons did not believe the transfer would improve outcomes, 3% cited lack of training, and 3% would preferentially use tendon transfers. Surgeons with hand fellowship training and those less than 30 years in practice were more likely to use nerve transfers in the treatment of CuTS (P < .05). CONCLUSIONS: Most CSPS members would use an AIN-SETS transfer in the treatment of both a high ulnar nerve injury and severe CuTS with intrinsic atrophy.

Assessment, patient selection, and rehabilitation of nerve transfers.

Peripheral nerve injuries are common and can have a devastating effect on physical, psychological, and socioeconomic wellbeing. Peripheral nerve transfers have become the standard of care for many types of peripheral nerve injury due to their superior outcomes relative to conventional techniques. As the indications for, and use of, nerve transfers expand, the importance of pre-operative assessment and post-operative optimization increases. There are two principal advantages of nerve transfers: (1) their ability to shorten the time to reinnervation of muscles undergoing denervation because of peripheral nerve injury; and (2) their specificity in ensuring proximal motor and sensory axons are directed towards appropriate motor and sensory targets. Compared to conventional nerve grafting, nerve transfers offer opportunities to reinnervate muscles affected by cervical spinal cord injury and to augment natural reinnervation potential for very proximal injuries. This article provides a narrative review of the current scientific knowledge and clinical understanding of nerve transfers including peripheral nerve injury assessment and pre- and post-operative electrodiagnostic testing, adjuvant therapies, and post-operative rehabilitation for optimizing nerve transfer outcomes.

Rehabilitation Following Nerve Transfer Surgery.

Nerve transfer surgery is an important new addition to the treatment paradigm following nerve trauma. The following rehabilitation plan has been developed over the past 15 years, in an interdisciplinary, tertiary peripheral nerve program at the "Roth|McFarlane Hand and Upper Limb Centre." This center evaluates more than 400 patients with complex nerve injuries annually and has been routinely using nerve transfers since 2005. The described rehabilitation program includes input from patients, therapists, physiatrists, and surgeons and has evolved based on experience and updated science. The plan is comprised of phases which are practical, reproducible and will serve as a framework to allow other peripheral nerve programs to adapt and improve the "Roth|McFarlane Hand and Upper Limb Centre" paradigm to enhance patient outcomes.

Development of a breast reconstruction satisfaction questionnaire (BRECON): dimensionality and clinical importance of breast symptoms, donor site issues, patient expectations, and relationships.

OBJECTIVES: To develop a valid, reliable and responsive, self-administered questionnaire to assess women's satisfaction with breast reconstruction. METHODS: Item generation: Three sources for item inventory were utilized: focus groups, expert panel, and literature review.Item reduction: Item impact scores were derived from patients and experts each ranking the importance and frequency of each item. Correlation between patient and expert scores was calculated. The highest impact questions were maintained. RESULTS: Four focus groups comprising 20 women generated 515 items, 10 experts developed 171 items, and literature review produced 227 items. These 913 potential items were reduced to 183 by combining redundancy. The 183 items underwent formal reduction by assessing importance and frequency of each item. Thirty-two of 40 reconstructed women and 19 of 19 experts responded to the mail-out. Seventy-seven items of the women's top 100 also made the experts' top 100 list. Intraclass correlation between patients and experts was 0.71 [0.62 0.77], indicating "good" but not "excellent" agreement, reinforcing the importance of patient involvement in questionnaire development. Women rated abdominal donor site issues higher than experts, and experts rated breast softness and symmetry higher than women. CONCLUSIONS: A 100-item pilot questionnaire for breast reconstruction satisfaction was developed for psychometric testing.

Refining perforator selection for DIEP breast reconstruction using transit time flow volume measurements.

Transit time flow volume has been used in cardiac surgery to assess small vessel flow characteristics. This study examines the usefulness of transit time flow volume (TTFV) in assessing perforator vessels in deep inferior epigastric artery perforator (DIEP) flap harvesting. The purpose of this study was to evaluate the correlation among computed tomographic angiography (CTA), intraoperative TTFV measurements, and hand-held Doppler signals in identifying perforators. Ten consecutive free DIEP breast reconstructions were prospectively evaluated using CTA to identify abdominal wall perforators. Intraoperatively, perforating vessels >1 mm in diameter were evaluated with a conventional hand-held 8-MHz Doppler and a TTFV measurement device. Vessel location was correlated with preoperative CTA . Waveform patterns and TTFV measurements were recorded for each vessel and correlated with both CTA and hand-held Doppler signals. Of the 54 perforators identified, TTFV showed arterial flow waveforms in 15 of 16 perforators identified by CTA and in 2 of the remaining 38 vessels. The sensitivity and specificity of TTFV in identifying arterial perforators were 94 and 95%, respectively. In contradistinction, hand-held Doppler was misleading in 70% of vessels. TTFV distinguishes arterial from venous waveforms in vessels that appear arterial by hand-held Doppler signals. CTA and TTFV are highly correlated, and the use of TTFV may prevent poor perfusion seen in some DIEP flaps.

Assessment of age-related differences in decomposition-based quantitative EMG in the intrinsic hand muscles: A multivariate approach.

OBJECTIVE: Decomposition-based quantitative electromyography (DQEMG) is one method of measuring neuromuscular physiology in human muscles. The objective of the current study is to compare the neuromuscular physiology of a typical aging population in the intrinsic hand muscles. METHODS: Measurements of DQEMG were detected with a standard concentric needle and surface EMG from the intrinsic hand muscles. DQEMG was obtained from the first dorsal interosseous (FDI), the abductor digiti minimi (ADM) and fourth dorsal interosseous (4DI). Multivariate analysis of variance (MANOVA) were performed for the surface and intramuscular EMG measures to identify age differences in motor unit properties. RESULTS: Large differences were observed between the age groups for the canonical intramuscular and surface EMG variables. Older adults demonstrated a large decrease in motor unit number estimation in the ADM and FDI. Likewise, medium to large decreases in motor unit stability were observed in the FDI, ADM and 4DI. CONCLUSIONS: With aging, there are decreases in motor unit number estimation and stability in the intrinsic hand muscles. Using a multivariate approach allows for age-related differences and the relationship between the variables to be further elucidated. SIGNIFICANCE: Multivariate analysis of DQEMG may be useful for identifying patterns of change in neuromuscular physiology with age-related changes to hand musculature. This may potentially lead to future prognostic biomarkers of age-related changes to hand muscles.

Reverse End-to-Side Anterior Interosseous Nerve-to-Ulnar Motor Transfer for Severe Ulnar Neuropathy.

BACKGROUND: Reverse end-to-side anterior interosseous nerve transfer has been reported to enhance treatment of severe, proximal ulnar neuropathy. The authors report on patients with severe neuropathy treated with ulnar nerve transposition and distal reverse end-to-side anterior interosseous nerve transfer. METHODS: Thirty patients with severe ulnar neuropathy at the elbow were reviewed. Clinical parameters included preoperative and postoperative Medical Research Council muscle strength, clawing, and degree of wasting. Electrodiagnostic data included compound motor action potential and sensory nerve action potential amplitudes. Summary statistics were used for demographic and clinical data. The t test and Wilcoxon signed rank test were used where appropriate. RESULTS: Average follow-up was 18.6 months. Preoperatively, 20 patients had Medical Research Council less than or equal to grade 1 in hand intrinsics, small finger sensory nerve action potentials were absent in all patients except for three, and average compound motor action potentials were severely reduced (absent in nearly 40 percent) confirming severity. All groups had a statistically significant increase in strength. More than three-quarters of patients noted partial or complete resolution of clawing and intrinsic muscle wasting. Seventy-three percent of patients regained Medical Research Council greater than or equal to grade 3 and 47 percent achieved Medical Research Council greater than or equal to grade 4. Mean time to observation of nascent units was 8.5 months, and 77 percent of patients demonstrated an augmentation of motor unit numbers with forearm pronation on needle electromyography CONCLUSION:: Proximal subcutaneous ulnar nerve transposition when combined with reverse end-to-side anterior interosseous nerve-to-ulnar nerve transfer demonstrates significant clinical and electrodiagnostic improvement of intrinsic muscle function. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Test-retest reliability of near-fibre jiggle in the ulnar intrinsic hand muscles.

OBJECTIVE: Near-fibre (NF) jiggle is one method of measuring the shape variability of motor unit potentials (MUPs) from successive firings during voluntary contractions. MUP shape variability has been associated with neuromuscular stability and health. The purpose of this study was to analyze the test-retest reliability of NF jiggle in the ulnar nerve innervated intrinsic hand muscles of healthy subjects. METHODS: Twenty healthy adult were tested (Mean age = 23.2 ±â€¯1.9; 8 females). Measurements of NF jiggle were assessed with a standard concentric needle during mild-moderate contractions from the first dorsal interosseous (FDI), the abductor digiti minimi (ADM), and the forth dorsal interosseous (4DI) muscles. Test-retest reliability were evaluated using intraclass-correlation coefficient (ICC). RESULTS: NF jiggle showed good test-retest reliability in the FDI, ADM and 4DI muscles with ICC values of 0.86, 0.85, and 0.87, respectively. The SEM for the FDI, ADM, and 4DI were 1.9%, 2.1%, and 2.5%. Finally, the MDC of the FDI, ADM and 4DI were 4.4%, 5.0%, and 7.1%. CONCLUSION: To date, this is the first investigation to explore NF jiggle in the intrinsic hand muscles. NF Jiggle demonstrates good test-retest reliability coefficients and with low measurement error.

Long-term limb allograft survival using a short course of anti-CD45RB monoclonal antibody, LF 15-0195, and rapamycin in a mouse model.

BACKGROUND: The purpose of this study was to determine if a short course of monoclonal antibody (mAb) against CD45RB, LF 15-0195, and rapamycin would achieve long-term survival by inducing tolerance in a mouse limb transplant model. METHODS: Group 1 (n=9) consisted of nine isogenic (C57BL/6) transplants. Group 2 (n=3) included C57BL/6-to-BALB/c transplants receiving no drug therapy. Group 3 mice (n=4) were treated with mAb (3 mg/kg) and LF (2 mg/kg), and Group 4 (n=13) was treated with mAb, LF, and rapamycin (2 mg/kg). Both treatment groups received drug treatment for only 14 days posttransplantation. Animals were sacrificed if they displayed evidence of rejection or when deemed to be tolerant (defined as >day 100). RESULTS: All isografts had normal histology and graft function on day 100. Untreated C57BL/6-to-BALB/c allografts developed acute rejection within 10 days. The combination of mAb and LF prolonged allograft survival to a mean of 39+/-7 days. In Group 4, two animals had to be sacrificed at days 28 and 76 due to acute urinary retention. Transplant tolerance was achieved in 8 of the remaining 11 animals with a mean survival time of 100+/-12 days. Donor specific tolerance was demonstrated through permanent acceptance of skin grafts from the donor strain and rejection of skin grafts from C3H mice. Three Group 4 animals showed clinical and histological signs of mild, chronic rejection. Dendritic cells isolated from tolerant recipients exerted a suppressive effect in mixed lymphocyte reaction. CONCLUSION: A short course of anti-CD45RB mAb and LF 15-0195 prolonged limb allograft survival. The addition of rapamycin induced limb allograft tolerance which is associated with the generation of tolerogenic dendritic cells that suppressed T-cell proliferation.

The Effect of Isolated Finger Stiffness on Adjacent Digit Function.

BACKGROUND: Isolated stiffness in a single finger can affect the function of adjacent digits and decrease overall hand function due to the quadriga phenomenon. This study objectively quantifies the dysfunctional impact of each individual stiff finger upon the remaining digits. METHODS: Twenty-five individuals (10 men and 15 women) with a mean age of 31 years (range, 18-58 years) without any upper limb pathology, neuropathy, or systemic illness were recruited. Volar-based finger splints were used to hold individual digits of the dominant hand (24 right and 1 left) sequentially in full extension at the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints. Motion of the remaining 3 nonsplinted digits was assessed using a finger goniometer and linear scale to measure the total active range of motion (TAM) and fingertip-to-distal palmar crease (DPC) distance. TAM before and after splinting for each digit was compared using 1-way analysis of variance (ANOVA). RESULTS: Splinting of any individual finger resulted in a significant reduction in the TAM of all adjacent fingers, regardless of which finger was splinted ( P < .001). Digits immediately adjacent to the splinted finger were more heavily impacted compared with nonadjacent digits. Splinting of the ring finger produced the greatest detriment, with a 26% to 47% reduction in the TAM and a DPC distance greater than 40 mm in a third of participants. The index finger caused the least disturbance to remaining digital motion. CONCLUSIONS: Isolated finger stiffness causes a variable degree of dysfunction on adjacent normal digits. This emphasizes the need for a focused and proactive approach to restore full active motion following isolated finger injuries to prevent persistent functional sequelae of the hand.

Spinal accessory nerve injury: A potentially missed cause of a painful, droopy shoulder.

BACKGROUND: Spinal accessory nerve (SAN) injury can be an overlooked cause of scapular winging and shoulder dysfunction. The most common etiology is iatrogenic injury following surgical procedures at the posterior triangle of the neck. We present three cases of isolated injury to the SAN following trauma. OBJECTIVE: To improve detection of SAN injuries through highlighting the clinical presentation, diagnosis and treatment via three cases in which the injuries were initially missed. METHODS: Clinical case series and narrative review. RESULTS: Three (3) patients were evaluated by history, physical exam and electrodiagnostic study (EMG). Clinical symptoms included, a painful, droopy shoulder and difficulties with overhead activities. Clinical signs included the observation of scapular winging, and focal atrophy of the trapezius and in some cases the sternocleidomastoid (SCM). Novel clinical signs such as the active elevation lag sign and triangle sign were also helpful clinically to highlight the SAN as the site of pathology. EMG revealed denervation and reduced motor unit recruitment in the trapezius and SCM. CONCLUSIONS: Early detection of SAN injuries can be improved through appropriate clinical suspicion, a detailed history and careful physical exam. EMG testing can help guide prognosis, direct conservative and surgical treatment, and reduce patient morbidity.

Beta-catenin expression in Dupuytren's disease: potential role for cell-matrix interactions in modulating beta-catenin levels in vivo and in vitro.

Dupuytren's disease (DD) is a superficial fibromatosis of the hand. Although the molecular mechanisms responsible for this disease are unknown, recent studies suggest that beta-catenin may be a key factor involved in fibromatosis. In this study, we analysed the in vivo and in vitro expression levels of beta-catenin in DD, using surgical specimens and primary cell lines. Although no somatic mutations (exon 3) of beta-catenin were detected, Western blot analysis revealed high levels of beta-catenin in diseased palmar fascia, and low to undetectable levels of beta-catenin in patient-matched normal palmar fascia. Immunohistochemistry analysis showed high levels of beta-catenin expression within the disease fascia, as well as cytoplasmic and nuclear accumulations of the protein. Immunoprecipitation of beta-catenin from seven patient lesions showed the protein to be tyrosine phosphorylated. Lastly, Western analysis of three patient-matched (disease and normal fascia) primary cell cultures showed significantly elevated levels of beta-catenin in disease cells cultured in three-dimensional collagen lattices. This is the first extensive in vivo and in vitro characterization of beta-catenin in DD, and the first to suggest that the extracellular matrix may play an important role in modulating beta-catenin stability in DD.