key: cord-0974996-4u4b3qxc
authors: MacKay, Brendan J.; Cox, Cameron T.; Valerio, Ian L.; Greenberg, Jeffrey A.; Buncke, Gregory M.; Evans, Peter J.; Mercer, Deana M.; McKee, Desirae M.; Ducic, Ivica
title: Evidence-Based Approach to Timing of Nerve Surgery: A Review
date: 2021-09-01
journal: Ann Plast Surg
DOI: 10.1097/sap.0000000000002767
sha: 41984bccb72758e269d93808070d3a9d5f239da6
doc_id: 974996
cord_uid: 4u4b3qxc

Events causing acute stress to the health care system, such as the COVID-19 pandemic, place clinical decisions under increased scrutiny. The priority and timing of surgical procedures are critically evaluated under these conditions, yet the optimal timing of procedures is a key consideration in any clinical setting. There is currently no single article consolidating a large body of current evidence on timing of nerve surgery. MEDLINE and EMBASE databases were systematically reviewed for clinical data on nerve repair and reconstruction to define the current understanding of timing and other factors affecting outcomes. Special attention was given to sensory, mixed/motor, nerve compression syndromes, and nerve pain. The data presented in this review may assist surgeons in making sound, evidence-based clinical decisions regarding timing of nerve surgery.

algorithms will do little to assist surgeons and may even give a false sense of security when further deliberation is warranted. Physicians should always operate by best practices aligned with current evidence. A misstep in clinical judgment can leave patients and surgeons vulnerable to poor outcomes. A condensed view of the relevant data could assist physicians advocating for patients' timely treatment. The following review may ultimately serve as a resource to positively impact outcomes in patients with peripheral nerve injuries.

The authors performed a systematic review of the MEDLINE and EMBASE databases using a comprehensive combination of keywords and search algorithm according to PRISMA guidelines. The literature search focused on clinical evidence-based data on nerve repair and reconstruction and was undertaken to define the current understanding of nerve repair timing and outcomes. Particular emphasis was made evaluating sensory, mixed/motor, nerve compression syndromes, and nerve pain. Search terms are listed in Table 3 .

When peripheral nerves are injured, a coordinated response involving both neurons and nonneuronal cells is initiated 2,3 (Fig. 2) . Inflammatory changes increase blood-nerve barrier permeability, activating Schwann cells and macrophages. 4 Nerve injuries present with varying degrees of involvement, which often dictate treatment and expected outcomes (Table 4 ). In less severe injuries, natural processes are often successful in regenerating the injured portion of a nerve, and full functional recovery may be achieved without intervention. 6 However, with more severe injury, prolonged neuronal input deficiency distal to the site of injury can significantly reduce the regenerative success of nerves. 4, 7, 8 In large nerve defects with greater regeneration times, denervated distal targets may not be successfully regenerated. [9] [10] [11] [12] In the distal stump of a severed nerve, endoneurial tubes progressively and permanently shrink in diameter, and Schwann cells lose their capacity to support axonal growth when left transected 13, 14 (Figs. 2, 3) . Target sensory and motor end-organs deteriorate irreversibly over time. Another cause for suboptimal recovery in peripheral nerve injury is upstream degeneration. When nerve injuries are incurred, neuronal cell death commences in the dorsal root ganglia (distal sensory nerve injuries) and/or the spinal motor neurons (proximal nerve injuries, eg, brachial plexus). 15 Cortical changes are known to develop in cases of prolonged neuronal deficiency, and neural plasticity should be considered when making decisions related to timing of intervention. [16] [17] [18] [19] Peripheral nerve injuries are known to result in poor sensory and/ or motor function if left untreated. 8, 20 Significant declines in postoperative function and chronic pain may lead to long-term disabilities for patients who do not receive timely operative treatment [21] [22] [23] [24] [25] [26] (Table 5) . This could impact more than patient outcomes, as both proximal and distal nerve injuries may contribute to high costs, lost work or medical disabilities, increased pharmacologic dependencies and expenses, and substantial lost function. 28 In a study of 66 median and/or ulnar nerve lesions, Dumont and Alnot 26 found that the time from injury to repair was the most significant prognostic factor in functional nerve recovery. Multiple reports in the literature describe the negative implications of delayed repair on sensory and motor outcomes in a variety of injury patterns, with one study indicating the critical window lies within 3 months. 3, 10, 29, 30 Considering the implications of prolonged nervous deficiency, timing is critical for treatment algorithms involving the peripheral nerves. 31, 32 

Clinical data indicate that sensory nerves may be less affected by prolonged denervation than motor nerves 19, 33 (Table 6 ). 32 However, the histologic response to prolonged denervation seems to be amplified for sensory when compared with motor nerves. 3 The recovery of mixed motor nerves degrades dramatically over time, as repairs delayed more than 1 month exhibit significant functional declines. This is especially pronounced in motor outcomes, as the functional loss is even more amplified the longer the muscle is denervated because the end-target organ (eg, muscle supplied by an injured nerve) may not regenerate. 32, 34 In a systematic review of 270 mixed nerve injuries (150 ulnar, 75 median, 45 radial), good to excellent sensory recovery (scoring scales in Timing of Nerve Surgery 54, 58, 65 In the same group, good to excellent motor recovery was achieved in 85.7% of immediate repairs, 80.0% with a delay of <1 month, 71.9% with a delay of 1 to 3 months, 52.9% with a delay of 3 to 6 months, and 25.0% with a delay of >6 months 35 (Table 8) . For each month of delay to repair, there was a significant decrease in the odds of good-excellent motor recovery (odds ratio, 0.93; 95% confidence interval [CI], 0.90-0.97; P < 0.01). 32 In one study of 260 radial and posterior interosseous nerves, 49% of nerves repaired within 14 days achieved good-excellent results, whereas only 28% of late repairs (mean, 190 days; range, 15-440 days) produced good-excellent outcomes. 58 One study involving 82 musculocutaneous nerve injuries reported 78% (21/27) good-excellent results when repaired within 14 days and 62% (34/55) when performed >14 days after injury. 54 When making decisions for timing of nerve procedures, it is critical to use a multifactorial approach. The trends described previously are broad and do not account for variables such as gap length, mechanism of injury, proximal versus distal location, and other considerations to be discussed in later sections, which may have a compound negative effect on delayed repairs (Tables 6, 8) .

Sensory-only nerve injuries should be considered acutely (within 14 days of injury) when possible to prevent painful neuroma formation. Once a neuroma occurs, it becomes an additional task to overcome the psychological impairment and, in some instances, narcotic dependency in order to return patients to a healthy return to functional activities. In cases where the initial presentation is delayed, it is suggested to repair within 14 days of clinical presentation if the injury occurred <6 months prior. After 6 months, reconstruction may still be undertaken but with consideration for possible adjunctive techniques to optimize outcomes based on individual prognostic factors.

Functional sensory return is not as time sensitive as muscle reinnervation. Although sooner is better, evidence points to functional sensory return being achievable for several years after complete transection, yet the quality of such delayed recovery might remain less predictable. 32 Additional preoperative factors that should be considered in sensory-only 

For mixed/motor nerve injuries, immediate repair (within 24 hours of injury) is suggested when possible. In cases where the initial presentation is delayed, it is suggested to repair within 14 days of clinical presentation if the injury occurred <6 months prior. After 6 months, a multifactorial approach including but not limited to nerve grafting, nerve transfer, and/or tendon transfer may be necessary to restore function.

Motor endplate degradation may limit the amount of time available for any functional motor return. Typically, efforts should be taken to provide axons to the muscle endplates no later than 1 year after complete transections. 95, 96 Because of the slow rate (~1 mm/d) and unidirectional nature (neuronal outgrowth only occurs distally from proximal end), irreversible motor endplate degradation has been observed as early as 12 months after injury. 3, 95, 96 Additional preoperative factors that FIGURE 2. Peripheral nerve injury cascade of events leading to the unidirectional regeneration from proximal to distal stump. ATF2, activating transcription factor 2; ATF3, activating transcription factor 3; ERK, extracellular signal-regulated kinase; CaMKII, Ca 2+ / calmodulin-dependent protein kinase II; CNTF, ciliary neurotrophic factor; Fra-2, transcription factor; IL-6, interleukin 6; Islet-1, transcription factor; JNK, c-Jun N-terminal kinase; JunD, transcription factor; LIF, leukemia inhibitory factor; NCAM, neural cell adhesion molecule; NfKB, nuclear factor κB; NRG1, neuregulin 1; p-ERK 1/2 , phosphorylated extracellular signal-regulated kinase; P311, 8-kDa protein with several PEST-like motifs found in neurons and muscle; SC, Scwhann cell; Sox11, transcription factor; STAT3, signal transducer and activator of transcription 3. 

Digital nerve injuries are a unique subset of sensory nerve injuries and should be considered independently with respect to timing of operative intervention. Although digital nerves primarily supply sensation to the hand, abnormal sensory outcomes have been shown to have an effect on motor function. 94 Patients with good active range of motion may not use the affected digit because of the lack of sensation or pain with movement, resulting in lasting stiffness and/or weakness. 97 Pain secondary to symptomatic neuroma formation has been shown to interfere with rehabilitation and functional outcomes, especially in the thumb and index finger, as both are critical for normal pinch and grip function. 98 A time to repair of <15 days has been associated with significantly improved sensory outcomes 99 (Table 9) . 32, 97, 100, 101, [103] [104] [105] [106] [107] [108] [109] [110] [111] [112] [113] [114] [115] [116] [117] [118] [119] [121] [122] [123] Another study including 254 digital nerve repairs reported significantly improved outcomes in repairs performed within 3 months of injury. 124 

For digital nerves, acute repair (within 14 days of injury) is suggested when possible. In cases where the initial presentation is delayed, repair is suggested within 3 months after injury to prevent painful neuroma formation. Once a neuroma occurs, it becomes an additional task to overcome the psychological impairment and, in some instances, narcotic dependency in order to return patients to a healthy return to functional activities. After 3 months, reconstruction may still be undertaken but with consideration for possible adjunctive techniques to optimize outcomes based on individual prognostic factors.

Functional sensory return is not as time sensitive as muscle reinnervation. Although sooner is better, evidence points to functional sensory return being achievable for several years after complete transection, although the extent of such recovery might be incomplete or less predictable. Additional preoperative factors that should be considered in 19.75 ± 20.5 n/a sensory-only nerves include gap length, ability to identify proximal and distal stumps, and concomitant vessel or tendon injuries (Table 6 ). 32

In cases of acute compressive neuropathy, prompt diagnosis is particularly important because symptoms and functional outcomes deteriorate more quickly due to severe ischemic conditions and/or intraneural scarring. 125 Acute compressive neuropathy in the ulnar nerve is rare, with the majority of cases occurring in Guyon's canal secondary to ganglion cyst. [125] [126] [127] [128] Although early decompression has been recommended, the literature lacks algorithms for timing of intervention. [126] [127] [128] [129] Treatment algorithms have been described in the literature for acute median nerve compression, which is frequently associated with distal radius fractures. [130] [131] [132] [133] [134] In healthy patients, carpal tunnel pressure has been reported from 5 to 14 mm Hg. Although carpal tunnel pressure has been reported from 12 to 43 mm Hg in patients with chronic carpal tunnel syndrome, acute cases may be elevated between 40 and 60 mm Hg. 129, 135 Although the exact threshold for irreversible damage is unknown, the literature has indicated that irreversible damage may be incurred at pressures as low as 30 mm Hg. 129 Given the amplified sequelae of acute compression, pressure measurements may be taken after 2 hours of nonsurgical intervention (eg, elevation or dressing release) using a wick catheter or STIC device. 131 The current literature on compartment syndrome indicates delayed intervention may lead to additional operations and/or permanent ischemic nerve damage. 136 Although it is difficult to pinpoint the delay time because the exact time of onset is often not known, earlier intervention has been associated with significantly improved functional recovery. 123, [137] [138] [139] [140] [141] In a study of 22 patients, 68% of those treated within 12 hours recovered normal function, compared with only 8% in patients treated >12 hours from time of onset. 136, 138 Nerve conduction velocity returned to normal if compartment release was performed within 4 hours. 138, 142 Of note, patient age seems to play a role in functional outcomes of compartment release. In a review of 39 pediatric cases with a mean time to diagnosis of 48 hours, 54% returned to normal function. 142 Another review reported that 85% of pediatric patients achieved full functional recovery when treated within a mean of 24.5 hours after the onset of symptoms. 131, 143 Frequently, patients present with postsurgical nerve dysfunction such as radial nerve palsy after open reduction and internal fixation of humeral fractures, 144, 145 peroneal and/or saphenous nerve palsy after knee ligament reconstruction and/or dislocation, [146] [147] [148] [149] [150] or ulnar nerve complications after medial or collateral ligament reconstruction of the elbow. [151] [152] [153] The literature addressing timing in these contexts is highly variable. 144, 145, 148, 150, 151 Generally, symptom severity and duration are thought to be indicators of potential for spontaneous recovery or need for operative intervention. Although the literature lacks consensus recommendations, close monitoring of nerve symptoms is recommended in the early postoperative period (up to 12 weeks). 144, 145, 148, 150, 151 Take-Home Messages

In the case of posttraumatic compressive neuropathy, if symptoms persist and/or elevated pressure remains in the affected tunnel/ canal at 2 hours after injury, exploration with possible release should Given the lack of consensus and high-quality data, published timing recommendations should be included as one part of the clinical decision-making process rather than a sole determining factor. In cases of compressive neuropathy secondary to cyst formation, decompression should be considered within 3 months of symptom onset if the patient's symptoms are minimal and nonprogressive. If symptoms progress rapidly and/or the patient has already incurred significant functional deficits, decompression may be performed acutely.

When treating injuries frequently associated with posttraumatic compressive neuropathy, the potential for compression should be considered when planning initial treatment. For example, in distal radius fractures, different fixation methods have been linked to varying rates of posttraumatic carpal tunnel syndrome. 133, 134 Given the high variability of postsurgical neuropraxia, even in similar injury/repair patterns, patients with neuropathic symptoms should be closely monitored in the first several weeks postoperatively. At approximately 6 weeks, nerve conduction study (NCS) and electromyography (EMG) may further clarify etiology and serve as a baseline for future comparison if symptoms persist. At this time, surgeons may decide to schedule surgery or continue observation with a possible second NCS/EMG at 12 weeks. Although some have questioned the sensitivity of electrophysiologic testing in chronic carpal tunnel syndrome, the same studies show that symptom severity is significantly associated with positive NCS findings. 155, 156 In cases of acute, traumatic, or postsurgical compression, compartment pressure is often elevated above typical chronic compression values, 129, 135 indicating that NCS/EMG may have greater utility for monitoring suspected neuropathy in acute compression.

Ultimately, multiple modalities must be considered (eg, patient complaints, physical examination, NCS/EMG, radiological studies, and 

Compressive neuropathies vary in severity beginning with deterioration of the blood-nerve barrier, followed by subperineurial edema and demyelination, and ending in axonal loss. 154 Although mild cases involving dynamic ischemia may be improved with nonoperative treatment such as therapy, activity modifications, or bracing, patients with a long history of compression may progress to axonal loss. 154 Severity can be confirmed by serial EMG and NCS. 157 Given the progressive nature of severe compression neuropathy, 157 operative intervention is indicated, and early intervention is preferred to avoid further changes in sensation and/or motor weakness and atrophy.

Both duration and severity of symptoms have been shown to impact pain, sensation, and functional outcomes in carpal and cubital tunnel decompression procedures 158, 159 (Tables 10-12) . 158, 160, 161 Masud et al 157 reported that normal grip strength was not achieved in carpal tunnel procedures performed on patients with symptom duration >6 months. At preoperative symptom duration >12 months, patients in this cohort were more likely to have persisting night pain and a lower rate of return to activities. These findings are consistent with the findings by Eisenhardt et al 163 in a similar patient population. In a 12-year study of 14,722 patients with carpal tunnel release, Hankins et al 164 suggested that these effects are likely due to the progressive nature of long-term compressive neuropathy.

Although published reports are variable, revision decompression has shown to provide comparable benefits in many outcome dimensions (Tables 13, 14) . [165] [166] [167] [168] [169] [170] [171] [172] [173] [174] [175] 177, 178, [181] [182] [183] 186, [188] [189] [190] [191] [192] [193] [194] [195] [196] [197] [198] [199] Differences in revision decompression outcomes have not been associated with duration of symptoms in the literature. 200 However, severity of symptoms has been identified as a correlating factor and should be taken into account if recurrent symptoms are rapidly progressing. 201, 202 Take-Home Messages

In cases of chronic compressive neuropathy, the role of nerve surgery is to address the cause of ongoing symptoms (eg, a peripheral injury that has led to central sensitization). Multiple assessment methods are recommended to evaluate the status of a symptomatic nerve and determine the potential benefit of surgical intervention.

If operative intervention is indicated, it is suggested that nerve decompression procedures be optimally performed within 3 to 6 months of onset of symptoms. If functional deficits, pain, or atrophy are rapidly progressing, acute intervention should be considered. Revision decompression procedures may be planned with considerations for symptom severity speed of symptom progression. Additional preoperative factors that should be considered include the following: age, muscle atrophy, grip strength, electrophysiological severity, tobacco use, body mass index, anemia, depression, chronic lung disease, and inflammatory arthritis (Tables 10-12) . 158, 160, 161 BLUNT TRAUMA AND GUNSHOT WOUNDS In cases of blunt trauma or gunshot wounds, a wait time of 2 to 3 weeks for zone of injury demarcation may be recommended for peripheral nerve repair. 5 During the time between injury and potential operative intervention, serial physical examinations may be accompanied by EMG and NCS. 203 Once the extent of injury has been determined, treatment should be initiated as early as possible to avoid long-term nervous insufficiency. Although penetrating wounds have historically been treated via delayed exploration, there is no clear consensus for optimal timing of exploration and repair. 34, 204 Advocates of early exploration point to improved outcomes and shorter graft length requirements for early exploration, which may be attributable to avoiding dense scar tissue formation and intraneural edema (by performing early epineural release), as well as preventing retraction by suturing to local structures. 72, 74, 82, 205, 206 Histologic data also support a favorable regenerative environment in the acute setting. 10, 207 At this time, clinical data remain inconclusive, and a risk-benefit analysis is necessary to determine the optimal course of treatment for each patient.

If the zone of injury is clearly established, immediate exploration may be warranted. In these cases, the decision to explore immediately or wait is ultimately subject to clinical judgment and individual patient/ injury characteristics. When the zone of injury is unclear, a wait time of 2 to 3 weeks is recommended.

The term "chronic pain" can be misleading, and the need for timely surgical intervention is often mistakenly dismissed in these cases. Such delays and assumptions can lead to significant impairment and/or inability to return to work and may have even more devastating outcomes, especially if suicidal ideation is present. 25, [208] [209] [210] [211] [212] Although a variety of treatment options are currently used for pain secondary to neuroma formation, most are focused on treatment of symptoms. Nonsurgical or symptomatic treatments are often unsuccessful, as they fail to address the root cause of pain. 210, 213 When pain persists despite reasonable treatment via supportive symptomatic modalities, surgical intervention targeting the source of the pain is indicated. 209, 214 Take-Home Messages If chronic pain persists 3 to 6 months after nerve injury, it is recommended that surgical exploration/treatment be electively scheduled, with patient goals and rate of symptom progression taken into consideration. Although the literature is unclear regarding exact timing, increased duration of symptoms has been associated with unfavorable outcomes. 210 If a patient presents with uncontrolled pain that is severe, progressing, or incapacitating despite nonoperative management, acute exploration/intervention should be considered. Ultimately, intervention must be determined using clinical judgment for each patient regardless of whether pain has persisted for 3 months.

In addition to timing of repair, factors may play a role in both planning the operative case and the repair methodology used. Availability of personal protective equipment, sterile surgical supplies, anesthesia supplies, and staffing will influence the ability to achieve appropriate timing in nerve repair. Exposure risks for the both the clinical team and patient should also be taken into consideration. Scope and scale or exposure risks should not be limited to just the surgery, but should include efforts to minimize recovery room time, days of hospitalization, rehabilitation, and any steps that can be appropriately taken to reduce staging of procedures and the overall episodes of care.

There is evidence to support a variety of reconstructive options. Optimal treatment is determined using available clinical data on safety, efficacy, and utility. Common repair methods for peripheral nerve injuries include direct suture, autograft, allograft, conduit, or nerve transfer (Fig. 4) . In addition to clinical outcomes data, additional factors should be considered for each approach, including: 1. Ability to achieve a tension-free repair 2. Operative time required for each repair approach 3. Ability to reduce anesthesia acuity and duration a. For example, although local regional anesthesia and monitored anesthesia care carry less risk of airway irritation, they may increase aerosol production (and viral spread in the present scenario) compared with tracheal intubation or laryngeal mask airway. Patient risk and the risk of viral spread should be discussed with an anesthesiologist. 4. Management of nerve gap (Fig. 4) 95, 124, [215] [216] [217] 5. Ability to reduce resource utilization by performing a single surgery versus staged reconstruction a. Insurance, socioeconomic status, and likelihood of returning for secondary procedures should be considered. 6. Management plan for concomitant injuries/procedures 7. Extent and timing of rehabilitative plan 8. Proximity to a tertiary referral center and/or available transportation Each of these factors plays a role in resource utilization, ability to schedule the procedure, and exposure risk to the patient and clinical teams. Patient desires may not always align with scientific evidence (97) Internal neurolysis (NA) Ulnar tunnel release (63) Proximal median n release (7) Median n reconstruction (6) Ulnar n reconstruction (3) Opponensplasty (2) Hypothenar flap (22) 3. Each row is scored, and all scores are added to produce a cumulative score (range, . A higher total score is associated with poorer perioperative outcomes, increased COVID-19 transmission, and/or increased hospital resource requirements.

CAD, coronary artery disease; CHF, congestive heart failure; CV, cardiovascular; COPD, chronic obstructive pulmonary disease; HTN, hypertension; ICU, intensive care unit. for optimal timing. In practice, decisions are made by engaging patients in an informed discussion of near-and long-term goals of recovery, as well as how these may be affected by different treatment options. Developing a shared understanding of the factors listed previously is crucial when creating a management plan and determining appropriate repair methods.

Appropriate timing of repair is a key consideration for the management of patients with nerve injuries. Injuries to peripheral nerves initiate a series of regenerative and degenerative processes. When these processes fail to proceed in a synchronous, organized manner, neuroma formation and/or nervous deficiency may occur, both of which are progressive in nature. 218 Untreated nerve injuries can result in serial remodeling in the sensorimotor, frontoparietal, and executive control networks. 219 Postinjury neuropathic pain has been linked to adverse cortical changes and psychosocial factors such as pain catastrophizing. 220 Successful nerve procedures can improve or eliminate neuropathic pain symptoms as well as restore connectivity in the brain's sensorimotor and salience networks. 219, 221 Timely intervention may reduce the risk of patients progressing to dependence on narcotics or neuromodulators. 222 As a critical component of the nerve treatment algorithm, the issue of timing must be addressed to optimize outcomes. A concise view of relevant clinical data may assist physicians making decisions and advocating for the appropriate timing of intervention for patients. Although most of the existing recommendations are too broad to be useful in a clinical setting with high variability between cases, Prachand et al 1 recently proposed a scoring system that integrates procedure, disease, and patient factors to justify the scheduling of (Table 15) . This system provides a template that may be adapted to subspecialties. As a thought experiment, we scored four common nerve procedures using an adapted version of Prachand's scale to briefly assess whether their Medically Necessary, Time-Sensitive procedure scale may be applicable in nerve practice (Table 16) . Preliminary analysis shows some promise in nerve procedures, and further research is needed to determine the utility of this scoring system. In the case of the COVID-19 pandemic, the initial response of many institutions was to cancel or reschedule all "elective" surgeries. Unfortunately, many nerve surgeries must be performed within a critical time window to avoid permanent sensory and/or functional deficits. Postponing these serious but nonemergency cases can result in rescheduled surgeries performed in a more unfavorable environment if ideal conditions do not materialize within the time frame for effective operative intervention. In routine practice conditions, procedures are often delayed because of inopportune surrounding circumstances such as patients' work or social commitments. When planning surgery with patients, the appropriate data must be used to weigh potential risks of delaying treatment.

Crisis scenarios can be a catalyst but are not the focus of discussions surrounding optimal treatment algorithms. Timing decisions are always critical to patient outcomes and are made by surgeons daily, regardless external circumstances. Although the current literature remains limited in many situations, the authors believe this review serves as a suitably condensed resource to allow surgeons to make educated assessments for individual patients with any type of nerve pathology. Although further investigation will be necessary to parse out nuances in clinical decision making, the authors believe that these data will allow physicians to better advocate for patients regarding the timing of nerve procedures and may ultimately lead to more optimal outcomes.

Medically necessary, time-sensitive procedures: scoring system to ethically and efficiently manage resource scarcity and provider risk during the COVID-19 pandemic

Quantitative changes of schwann and mast cells in the process of peripheral nerve regeneration

The role of timing in nerve reconstruction

Traumatic nerve damage: causes, approaches and prognosis

Principles of nerve repair in complex wounds of the upper extremity

Mechanisms of disease: what factors limit the success of peripheral nerve regeneration in humans?

The physiology of neural injury and regeneration: the role of neurotrophic factors

The basis for diminished functional recovery after delayed peripheral nerve repair

Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation

Effect of delayed peripheral nerve repair on nerve regeneration, Schwann cell function and target muscle recovery

Surgical repair in humans after traumatic nerve injury provides limited functional neural regeneration in adults

Effects of short-and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size

Irreversible changes occurring in long-term denervated Schwann cells affect delayed nerve repair

The nerve injury and the dying neurons: diagnosis and prevention

Chapter 27: neural plasticity after nerve injury and regeneration

Neural plasticity after peripheral nerve injury and regeneration

Cortical plasticity in rehabilitation for upper extremity peripheral nerve injury: a scoping review

Cerebral changes after injury to the median nerve: a long-term follow up

Nerve regeneration: understanding biology and its influence on return of function after nerve transfers

Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy

Evaluation of nerve injury and nerve compression in the upper quadrant

Ulnar nerve transposition using a mini-invasive approach: case series of 30 patients

Surgical treatment of neuromas improves patient-reported pain, depression, and quality of life

Postoperative improvement in DASH score, clinical findings, and nerve conduction velocity in patients with cubital tunnel syndrome

Outcomes of the surgical treatment of peripheral neuromas of the hand and forearm: a 25-year comparative outcome study

Proximal median and ulnar resections. Results of primary and secondary repairs

Patient-reported outcome after peripheral nerve injury

Acute and long-term costs of 268 peripheral nerve injuries in the upper extremity

Comparison of ulnar nerve repair according to injury level and type

Comparative study between primary versus delayed peripheral nerve repair after various types of injury

Traumatic peripheral nerve lesions: diagnosis and treatment

Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries

Results of treatment of the extensive volar wrist lacerations: 'the spaghetti wrist'

The clinical, electrophysiologic, and surgical characteristics of peripheral nerve injuries caused by gunshot wounds in adults: a 40-year experience

Secondary repair of ulnar nerve injury. 44 cases followed for 2 years

Surgical management of nerve injuries of the upper extremity in children: a 15-year survey

Repair of median and ulnar nerves

Correlation of two-point discrimination and hand function following median nerve injury

The results of secondary microsurgical repair of ulnar nerve injury

The results of secondary microsurgical repair of radial nerve in 33 patients

Peripheral nerve repair in the hand with and without motor sensory differentiation

An analysis of the results of late reconstruction of 132 median nerves

Repair of mixed peripheral nerves using muscle autografts: a preliminary communication

Tubular versus conventional repair of median and ulnar nerves in the human forearm: early results from a prospective, randomized, clinical study

Contralateral median nerve autograft

A technique to quantitate motor recovery following nerve grafting

Results of interfascicular nerve grafting for radial nerve lesions

Primary epineural repair of the median nerve in children

Tubular repair of the median nerve in the human forearm. Preliminary findings

Results of suture of the radial, median, and ulnar nerves after missile injury below the axilla

Functional results of low median and ulnar nerve repair with intraneural fascicular dissection and electrical fascicular orientation

The use of silicone tubing in the late repair of the median and ulnar nerves in the forearm

Primary epineural repair of the ulnar nerve in children

The musculocutaneous nerve

Machete injuries in Haiti

Results of nerve transfer techniques for restoration of shoulder and elbow function in the context of a meta-analysis of the English literature

Surgical management and outcome in patients with radial nerve lesions

The radial and posterior interosseous nerves. Results fo 260 repairs

The long term recovery curve in adults after median or ulnar nerve repair: a reference interval

Restoration of sensibility in irreparable ulnar and median nerve lesions with use of sensory nerve transfer: long-term follow-up of 20 cases

A comparison between clinical results and electromyographic analysis after median or ulnar nerve injuries in children's wrists

Surgical treatment of peripheral nerve injuries in upper extremities

The harvest and clinical application of the superficial peroneal sensory nerve for grafting motor and sensory nerve defects

Poor results after nerve grafting in the upper extremity: quo vadis? Microsurgery

Surgical outcomes of 654 ulnar nerve lesions

Surgical treatment of traumatic lesions of the axillary nerve. A retrospective study of 33 cases

Vascularized nerve grafts for the treatment of large nerve gap after severe trauma to an upper extremity

Clinical evaluation of ulnar nerve repair at wrist level

Long-term outcome of muscle strength in ulnar and median nerve injury: comparing manual muscle strength testing, grip and pinch strength dynamometers and a new intrinsic muscle strength dynamometer

Missile-caused ulnar nerve injuries: outcomes of 128 repairs

Surgical outcomes of ulnar nerve lesions in children. A retrospective clinical study

Missile-caused median nerve injuries: results of 81 repairs

Tubular repair of the median or ulnar nerve in the human forearm: a 5-year follow-up

Missile severances of the radial nerve. Results of 131 repairs

Injury to the human median and ulnar nerves in the forearm-analysis of costs for treatment and rehabilitation of 69 patients in southern Sweden

Median and ulnar nerve injuries: a meta-analysis of predictors of motor and sensory recovery after modern microsurgical nerve repair

Difference in recovery potential of peripheral nerves after graft repairs

Microsurgical treatment of injury to peripheral nerves in upper and lower limbs: a critical review of the last 8 years. Microsurgery

A novel technique leading to complete sensory and motor recovery across a long peripheral nerve gap

Reconstruction of the human median nerve in the forearm with the Neurotube

Regimen and results of physiotherapy in patients following surgical treatment of ulnar nerve injury

Surgical repair of ulnar nerve lesions caused by gunshot and shrapnel: results in 407 lesions

Radial nerve repair using an autologous denatured muscle graft: comparison with outcomes of nerve graft repair

Long-term functional results of primary reconstruction of severe forearm injuries

Long-term results after primary microsurgical repair of ulnar and median nerve injuries: a comparison of common score systems

Early surgical exploration of radial nerve injury associated with fracture shaft humerus

Outcomes of secondary reconstruction of ulnar nerve lesions: our experience

Sural nerve autografts for high radial nerve injury with nine centimeter or greater defects

Effect of sensory re-education after low median nerve complete transection and repair

Repair of electrically injured median nerve with the aid of somatosensory evoked potential

Primary and delayed repair and nerve grafting for treatment of cut median and ulnar nerves

Outcomes of nerve reconstruction for radial nerve injuries based on the level of injury in 244 operative cases

Cognitive capacity: no association with recovery of sensibility by Semmes Weinstein test score after peripheral nerve injury of the forearm

Prognostic factors in sensory recovery after digital nerve repair

Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies

Nerve physiology: mechanisms of injury and recovery

A systematic review of prognostic factors for sensory recovery after digital nerve reconstruction

Digital nerve injuries: a review of predictors of sensory recovery after microsurgical digital nerve repair

Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair

Digital nerve grafts with the lateral antebrachial cutaneous nerve

Evaluation of sensibility after sensory reconstruction of the thumb

Results of digital neurorrhaphy in adults

Autogenous vein graft repair of digital nerve defects in the finger: a retrospective clinical study

The reversed venous arterialized nerve graft in digital nerve reconstruction across scarred beds

Comparison of results of repair of digital nerves by denatured muscle grafts and end-to-end sutures

Repair of digital nerve defect with autogenous vein graft during flexor tendon surgery in zone 2

Digital neurorrhaphy after the age of 60 years

Postoperative splinting for isolated digital nerve injuries in the hand

Nerve injuries of the upper extremity-expected outcome and clinical examination

Muscle-in-vein nerve guide for secondary reconstruction in digital nerve lesions

Allograft reconstruction for digital nerve loss

A prospective randomized study comparing woven polyglycolic acid and autogenous vein conduits for reconstruction of digital nerve gaps

Emergency management of traumatic collateral palmar digital nerve defect inferior to 30 mm by venous grafting

Reconstruction of proper digital nerve defects in the thumb using a pedicle nerve graft

Reconstruction of digital nerves with collagen conduits

Posterior interosseus nerve vs. medial cutaneous nerve of the forearm: differences in digital nerve reconstruction

Is there a profit to use the lateral antebrachial cutaneous nerve as a graft source in digital nerve reconstruction? Microsurgery

Outcomes of short-gap sensory nerve injuries reconstructed with processed nerve allografts from a multicenter registry study

Electrical stimulation enhances sensory recovery: a randomized controlled trial

Long-term clinical outcome after epineural coaptation of digital nerves

Evaluation of cutaneous spatial resolution and pressure threshold secondary to digital nerve repair

Innervated reverse digital artery island flap through bilateral neurorrhaphy using direct small branches of the proper digital nerve

Compartment syndrome: diagnosis, management, and unique concerns in the twenty-first century

The results of secondary repair of 254 digital nerves

Ulnar nerve entrapment in Guyon's canal caused by a ganglion cyst: two case reports and review of the literature

Acute ulnar neuropathy at the wrist: a case report and review of the literature

Ulnar nerve deep branch compression by a ganglion: a review of nine cases

Compression of the deep branch of the ulnar nerve in Guyon's canal by a ganglion: two cases

Acute median neuropathy after wrist trauma. The role of emergent carpal tunnel release

Case report: acute cubital tunnel syndrome in a hemophiliac patient

Acute carpal tunnel syndrome

Carpal tunnel syndrome and distal radius fractures

A network meta-analysis of outcomes of 7 surgical treatments for distal radius fractures

Comparison of risk of carpal tunnel syndrome in patients with distal radius fractures after 7 treatments

Pressure measurement in carpal tunnel syndrome: correlation with electrodiagnostic and ultrasonographic findings

Fasciotomy in the treatment of the acute compartment syndrome

Lower limb compartment syndrome: course after delayed fasciotomy

Acute compartment syndrome: cause, diagnosis, and new viewpoint

Histologic determination of the ischemic threshold of muscle in the canine compartment syndrome model

Acute compartment syndrome: update on diagnosis and treatment

The extent and distribution of skeletal muscle necrosis after graded periods of complete ischemia

Pediatric acute compartment syndrome: a systematic review and meta-analysis

Acute compartment syndrome of the upper extremity in children: diagnosis, management, and outcomes

Causes of secondary radial nerve palsy and results of treatment

Radial nerve palsy in humeral shaft fractures with internal fixation: analysis of management and outcome

Nerve injury during anterior cruciate ligament reconstruction: a comparison between patellar and hamstring tendon grafts harvest

Common peroneal nerve palsy with multiple-ligament knee injury and distal avulsion of the biceps femoris tendon

Prevalence and clinical implications of nerve injury during bone patellar tendon bone harvesting for anterior cruciate ligament reconstruction

Complications following harvesting of patellar tendon or hamstring tendon grafts for anterior cruciate ligament reconstruction: systematic review of literature

The sequelae of drop foot after knee dislocation: evaluation and treatment

Ulnar nerve complications after ulnar collateral ligament reconstruction of the elbow: a systematic review

Stress sonography of the ulnar collateral ligament of the elbow in professional baseball pitchers: a 10-year study

Ulnar collateral ligament reconstruction: anatomy, indications, techniques, and outcomes

Ulnar neuropathy: evaluation and management

Suspected carpal tunnel syndrome: do nerve conduction study results and symptoms match?

The value added by electrodiagnostic testing in the diagnosis of carpal tunnel syndrome

Does the duration and severity of symptoms have an impact on relief of symptoms after carpal tunnel release?

Relationship between the duration and severity of symptoms and the outcome of carpal tunnel surgery

Carpal tunnel surgery: predictors of clinical outcomes and patients' satisfaction

Predictors of surgical outcomes after in situ ulnar nerve decompression for cubital tunnel syndrome

Patient-related risk factors for infection following ulnar nerve release at the cubital tunnel: an analysis of 15,188 cases

Retrospective analysis of 242 patients whose carpal tunnels were released using a one-port endoscopic procedure: superior results of early intervention

A 12-year experience using the Brown two-portal endoscopic procedure of transverse carpal ligament release in 14,722 patients: defining a new paradigm in the treatment of carpal tunnel syndrome

Outcomes of revision surgery for cubital tunnel syndrome

Endoscopic carpal tunnel release for recurrent carpal tunnel syndrome after previous open release

Endoscopic revision of carpal tunnel release

Recurrent and unrelieved carpal-tunnel syndrome

Reoperation for carpal tunnel syndrome. A retrospective analysis of forty cases

Factors that determine reexploration treatment of carpal tunnel syndrome

Surgical management of recurrent carpal tunnel syndrome

Outcome of reoperation for carpal tunnel syndrome

Management of true recurrent carpal tunnel syndrome: is it worthwhile to bring vascularized tissue?

The results of revision carpal tunnel release following previous open versus endoscopic surgery

Persistent or recurrent carpal tunnel syndrome following prior endoscopic carpal tunnel release

Predicting the outcome of revision carpal tunnel release

Vein-graft wrapping for the treatment of recurrent compression of the median nerve

Vein wrapping for the treatment of recurrent carpal tunnel syndrome

Recalcitrant post-surgical neuropathy of the ulnar nerve at the elbow: treatment with autogenous saphenous vein wrapping

Revision decompression and collagen nerve wrap for recurrent and persistent compression neuropathies of the upper extremity

Collagen nerve wrap for median nerve scarring

Median nerve biodegradable wrapping: clinical outcome of 10 patients

The hypothenar fat pad flap for management of recalcitrant carpal tunnel syndrome

The hypothenar fat-pad flap for reconstructive repair after scarring of the median nerve at the wrist joint

Pedicled hypothenar fat flap for median nerve coverage in recalcitrant carpal tunnel syndrome

Management of recurrent carpal tunnel syndrome with microneurolysis and the hypothenar fat pad flap

Clinical and electrophysiological comparison of different methods of soft tissue coverage of the median nerve in recurrent carpal tunnel syndrome

A reliable and simple solution for recalcitrant carpal tunnel syndrome: the hypothenar fat pad flap

Recurrent carpal tunnel syndrome-analysis of the impact of patient personality in altering functional outcome following a vascularised hypothenar fat pad flap surgery

Vascularized hypothenar fat pad flap in revision surgery for carpal tunnel syndrome

Strickland's hypothenar fat pad flap for revision surgery in carpal tunnel syndrome: prospective study of 34 cases

The synovial flap as treatment of the recurrent carpal tunnel syndrome

The tenosynovial flap for recalcitrant carpal tunnel syndrome

Subjective and employment outcome following secondary carpal tunnel surgery

Failed endoscopic carpal tunnel release. Operative findings and results of open revision surgery

Revision surgery for persistent and recurrent carpal tunnel syndrome and for failed carpal tunnel release

Revision carpal tunnel surgery: a 10-year review of intraoperative findings and outcomes

Revision surgery for recurrent and persistent carpal tunnel syndrome: clinical results and factors affecting outcomes

Management of recalcitrant carpal tunnel syndrome

The surgical management of nerve gaps: present and future

Anterior submuscular transposition of the ulnar nerve. For post-operative focal neuropathy at the elbow

The failed ulnar nerve transposition. Etiology and treatment

Revision surgery for refractory cubital tunnel syndrome: a systematic review

Clinical characteristics of coronavirus disease 2019 in China

Predictors of nerve injury after gunshot wounds to the upper extremity

Management and complications of traumatic peripheral nerve injuries

Gunshot wounds to the extremities

Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair

Surgical algorithm for neuroma management: a changing treatment paradigm

Treatment of neuroma-induced chronic pain and management of nerve defects with processed nerve allografts

Surgical interventions for the treatment of painful neuroma: a comparative meta-analysis

Obstacles to returning to work with chronic pain: in-depth interviews with people who are off work due to chronic pain and employers

findings from the National Violent Death Reporting System

Treatment of foot and ankle neuroma pain with processed nerve allografts

Nerve Surgery

Use of long autologous nerve grafts in brachial plexus reconstruction: factors that affect the outcome

Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions

Recovery of motor function after mixed and motor nerve repair with processed nerve allograft

Time course of traumatic neuroma development

Cortical plasticity after brachial plexus injury and repair: a resting-state functional MRI study

A longitudinal study of pain, personality, and brain plasticity following peripheral nerve injury

Targeted muscle reinnervation at the time of upper-extremity amputation for the treatment of pain severity and symptoms

Surgically induced neuropathic pain: understanding the perioperative process