Evidence-Based Approach to Timing of Nerve Surgery: A Review.

ABSTRACT: 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.

The circumstances created by the COVID-19 pandemic have shed light on a number of unanswered questions, particularly with regard to the acuity of conditions and urgency of surgical procedures. In the context of nerve surgery, the need for expedited decisions has revealed a lack of consolidated evidence, as there is currently no published article presenting clinical data on timing considerations of nerve surgery across a wide variety of injury patterns. Surgery remains necessary for many patients, even amid resource diversion, and all procedures exist within a timing hierarchy. An evidence-based approach is needed to adequately distinguish the relative acuity of different conditions, particularly within broad (and often misunderstood) categories such as “elective” surgery, which is frequently conflated with “optional.”[1]

Published recommendations not created or endorsed by expert subspecialty groups are often vague and fail to address the nuances of clinical decision making (Tables 1, 2; Fig. 1). Overly simplified 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.

TABLE 1

Orthopedic surgery case triage

Emergent—within 6 h

• Compartment syndrome

• Open fracture

• Joint dislocations

• Fracture-dislocations

• Dysvacular limb/ex fix

• Traumatic amp/replant

• Septic joint

• Abscess

• Cauda Equina syndrome

Urgent—within 24–48 h

• Hip and femur fractures

• Pelvis and acetabulum fractures

• Long bone (femur, tibia, humerus) fractures

• Multiple fractures

• Unstable spine fractures or progressive neurologic deficits

Acute—within 7 d

• Factures in general

• Hand/UE

• Ankle/tibial plateau, etc

• Spine fractures without gross

• Instability/cord compromise or neurologic symptoms

• Mutliligamentous knee dislocation (s/p initial stabilization [ex fix] if necessary)

Semielective

• Incarcerated meniscus

• Biceps tear/tendon repairs

• Nerve transection

Elective

• Total joint replacement (hip/knee/shoulder/ankle)

• Degenerative spine without cord/neurologic compromise

• Nonunion without hardware compromise/unstable extremity

• Degenerative hand/foot/ankle

• Isolated knee ligament/meniscus etc

• Hardware removal

Dr Ficke, AAOS Board of Directors, Johns Hopkins Hospital.

ex fix, external fixation; s/p, status post; UE, upper extremity.

TABLE 2

Selected Sections From the American College of Surgeons “Guidelines for Triage of Orthopedic Patients”

	Phase II		Phase III
	Schedule	Reschedule	Schedule	Reschedule
Trauma	All new fractures	Fractures >4 wk old	All new fractures	“Soft tissue injury”
	Acute traumatic injury		Quad tendon rupture	Patients without a diagnosis
	Nonunions, malunions, infections		Patellar tendon rupture	Malunions, nonunions
			Acute change of a chronic injury	Chronic infections
Orthopedic oncology	Infection including infected joints	Benign soft tissue masses	Infection including infected joints
	Sarcoma/other primary malignancy in a “chemo or radiation” window	Benign bone tumors that can wait	Sarcoma/other primary malignancy in a “chemo or radiation” window
	Aggressive benign tumors (GCT)	Elective joint replacement	Aggressive benign tumors (GCT)
	Impending pathologic fracture (including periprosthetic)		Impending pathologic fracture (including periprosthetic)
	Pathologic fracture		Pathologic fracture
Shoulder and elbow	Acute severe pain	Shoulder/elbow arthritis	Falls with inability to move shoulder or elbow	New-onset shoulder or elbow pain without trauma
	Falls with loss of function	Unchanged chronic pain with retained function	Proximal humerus fracture, humeral shaft fracture, distal humerus fracture	Shoulder/elbow arthritis
	Any fracture	Hospital discharge without impatient consult	Elbow fracture dislocation, elbow or shoulder dislocation	Chronic shoulder pain with function intact
	Any acute changes in function of shoulder or elbow	Hospital consultation, shoulder triaged	Olecranon fracture, clavicle fracture	Self-scheduling without screening
	Any neurological issues. Any infection	Chronic cuff disease with unchanged function	New loss of function. Acute-onset neurological complaints. Any infection	Chronic shoulder or elbow dislocations with joint reduced
Hand	Laceration with tendon, nerve injury	Healed lacerations with no tendon, nerve injury. Chronic and resolved infections	Acute laceration with tendon, nerve injury within 2 wk	Lacerations over 2 wk. Chronic infection, chronic osteomyelitis
	Acute infection	Tendonitis hand, wrist, elbow, trigger finger, DeQuervain's, epicondylitis (tennis/golfer's elbow)	Acute infection	Tendonitis hand, wrist, elbow, trigger finger, DeQuervain's, epicondylitis (tennis/golfer's elbow)
	Acute fractures hand, wrist, elbow requiring surgical treatment	Nerve compression syndromes carpal tunnel, cubital tunnel, etc	Acute fractures requiring surgical management	Nerve compression syndromes carpal tunnel, cubital tunnel, etc
	Acute injury hand, wrist, elbow within 2 wk	Chronic fracture over 6 wk. Injury hand, wrist, elbow over 2 wk	Acute high-energy hand, wrist, elbow pain without prior evaluation	Nonoperative fractures and fractures over 2 wk. Injury hand, wrist, elbow pain over 2 wk

GCT, giant cell tumor.

FIGURE 1

Treatment algorithm for elective cases currently in use by some centers. Piedmont Healthcare System, Georgia.

METHODS

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.

TABLE 3

Search Terms Used in PubMed for Each Section

Delayed treatment of injured nerves	Delayed nerve surgery, delayed vs immediate nerve repair, nerve surgery, prognostic factors affecting nerve recovery, outcomes of peripheral nerve surgery, functional outcomes nerve, timing of nerve repair, late reconstruction nerve, immediate reconstruction nerve, acute reconstruction nerve, poor functional recovery nerve, peripheral nerve regeneration, mechanism of nerve injury, mechanism of nerve regeneration, mechanism of nerve recovery
Sensory vs motor nerves	Sensory nerve repair, motor nerve repair, sensory nerve prognostic factors, motor nerve prognostic factors, sensory nerve outcomes, motor nerve outcomes, mixed nerve outcomes, sensory vs motor nerve repair, sensory vs motor nerve outcomes, timing sensory nerves, timing motor nerves, timing mixed nerves, delay sensory nerve repair, delay motor nerve repair, delay mixed nerve repair, delay vs immediate sensory nerve, delay vs immediate motor nerve, delay vs immediate mixed nerve, repair techniques sensory nerve, repair techniques motor nerve, repair techniques mixed nerve
Digital nerves	Digital nerve repair, digital nerve prognostic factors, digital nerve outcomes, digital nerve sensory outcomes, digital nerve motor outcomes, timing digital nerves, delay digital nerve repair, immediate digital nerve repair, delay vs immediate digital nerve, repair techniques digital nerve
Compartment syndrome	Compartment syndrome peripheral nerve, compartment syndrome nerve changes, compartment syndrome neuropathy, compartment syndrome timing nerve, compartment syndrome timing, compartment syndrome delay, compartment syndrome delayed vs immediate, compartment syndrome irreversible nerve changes, compartment syndrome ischemia, compartment syndrome pediatric, compartment syndrome adult, compartment syndrome pressure
Acute nerve compression/dysfunction	Acute compressive neuropathy, acute ulnar nerve compression, acute median nerve compression, acute carpal tunnel, acute cubital tunnel, posttraumatic compressive neuropathy, pressure acute nerve compression, timing acute nerve compression, timing acute nerve decompression, timing traumatic nerve compression, normal healthy carpal tunnel pressure, normal healthy cubital tunnel pressure, acute nerve compression changes, acute nerve compression irreversible nerve changes, acute nerve compression timing, acute nerve release timing, acute carpal tunnel release timing, acute cubital tunnel release timing, acute vs delayed traumatic decompression, acute vs delayed traumatic compressive neuropathy, compressive neuropathy cyst, compressive neuropathy ischemia, posttraumatic neuropathy, postsurgical neuropathy, surgery neuropraxia, timing posttraumatic neuropathy, timing postsurgical neuropathy, timing surgery neuropraxia
Chronic nerve compression	Compressive neuropathy, carpal tunnel syndrome, cubital tunnel syndrome, radial tunnel syndrome, ulnar nerve compression, median nerve compression, Guyon's canal decompression, timing acute nerve compression, timing nerve decompression, timing carpal tunnel release, timing cubital tunnel, timing ulnar nerve transposition, delayed nerve decompression, delayed carpal tunnel release, delayed cubital tunnel, delayed ulnar nerve transposition, prolonged nerve compression, prognostic factors carpal tunnel, prognostic factors cubital tunnel, prognostic factors nerve decompression, prognostic factors median nerve decompression, prognostic factors ulnar nerve decompression, time changes peripheral neuropathy, irreversible changes compressive neuropathy, revision* nerve decompression, revision carpal tunnel, revision cubital tunnel, revision radial tunnel, timing revision nerve decompression, timing revision carpal tunnel, timing revision cubital tunnel, timing revision radial tunnel, prognostic factors revision nerve decompression, prognostic factors revision carpal tunnel, prognostic factors revision cubital tunnel
Blunt trauma and gunshot wounds	Blunt trauma peripheral nerve, blunt trauma nerve changes, blunt trauma neuropathy, blunt trauma timing nerve, blunt trauma timing, blunt trauma delay, blunt trauma delayed vs immediate, blunt trauma irreversible nerve changes, gunshot wound peripheral nerve, gunshot wound nerve changes, gunshot wound neuropathy, gunshot wound timing nerve, gunshot wound timing, gunshot wound delay, gunshot wound delayed vs immediate, gunshot wound irreversible nerve changes, gunshot wound delayed exploration, gunshot wound immediate exploration, gunshot wound treatment, penetrating wound delay, penetrating wound immediate, penetrating wound exploration, penetrating wound timing

*All terms including “revision” were also searched using “recurrent” and “recalcitrant.”

DELAYED TREATMENT OF INJURED NERVES

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]

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, Ca2+/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-ERK1/2, 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.

TABLE 4

Classifications of Nerve Injuries

Degree of Nerve Injury	Definition of Nerve Injury	Prognosis	Tinel Sign	Surgical Intervention
First (neurapraxia)	Segmental demyelination Axonal continuity maintained;  endoneurium, perineurium and epineurium, intact	Favorable	None	None, distal decompression
Second (axonotmesis)	Discontinuity of axon and myelin;  endoneurium, perineurium, and epineurium intact	Favorable	Present, progressive	None, distal decompression,  supercharge procedure
Third	Discontinuity of axon, myelin and endoneurium;  perineurium and epineurium intact	Favorable	Present, progressive	None, distal decompression,  supercharge procedure
Fourth	Only the epineurium remains intact	Unfavorable	Present; no progression	Nerve repair, graft, transfer
Fifth (neurotmesis)	Complete nerve transection	Unfavorable	Present; no progression	Nerve repair, graft, transfer
Sixth	Mixed injury pattern	Variable	Variable	All options may be appropriate

Table adapted from Moore et al.[5]

In large nerve defects with greater regeneration times, denervated distal targets may not be successfully regenerated.[9-12] 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.[16-19]

FIGURE 3

Effect of Schwann cell insufficiency on distal nerve segments after prolonged discontinuity.

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[21-26] (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]

TABLE 5

Comparison of Patient-Reported Outcomes in Untreated Peripheral Nerve Injuries (Novak et al[27]) Versus Those Having Undergone Operative Intervention

SF-36 Scores	Physical Function	Role Limit to Physical Health	Role Limit to Emotional Problems	Energy/Fatigue	Emotional Well-Being	Social Function
Novak et al[27] >6 mo after injury without operative intervention (n = 57)
Mean ± SD	60.0 ± 23.0	23.0 ± 33.0	45.0 ± 43.0	49.0 ± 24.0	58.0 ± 23.0	57.0 ± 30.0

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]

SENSORY VERSUS MOTOR NERVES

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]

TABLE 6

Outcomes of Sensory-Only Peripheral Nerve Repairs

Predictor	Group	Satisfactory (Good-Excellent) Sensory Recovery
Age	≤16 y	100% (7/7)
	16–25 y	75.0% (24/32)
	26–40 y	88.5% (23/26)
	>40 y	75.0% (18/24
	Total (n)	n = 89
	Univariate odds ratio per year (95% CI)	0.98 (0.95–1.02), P = 0.31
Sex	Male	67.4% (29/43)
	Female	95.5% (21/22)
	Total (n)	n = 65
	Univariate odds ratio (95% CI): female vs male	10.14 (1.24–83.18), P = 0.03
Nerve	Digital	80.7% (71/88)
	Total (n)	n = 88
Graft length	No graft	100% (2/2)
	≤30 mm	76.2% (45/54)
	30–50 mm	33.3% (2/6)
	>50 mm	33.3% (1/3)
	Total (n)	n = 65
	Univariate odds ratio (95% CI), gap/cm	0.49 (0.30–0.80), P < 0.01
Delay	No delay (<24 h)	78.6% (33/42)
	1–30 d	75.0% (3/4)
	1–3 mo	100% (5/5)
	3–6 mo	84.6% (1/13)
	6–12 mo	75.0% (3/4)
	>12 mo	100% (2/2)
	Total (n)	n = 70
	Univariate odds ratio per month (95% CI)	1.04 (0.88–1.23), P = 0.64

Table adapted from He et al.[32]

In a systematic review of 270 mixed nerve injuries (150 ulnar, 75 median, 45 radial), good to excellent sensory recovery (scoring scales in Table 7) occurred in 90.9% of immediate repairs (<24 hours from time of injury), 58.3% with a delay of <1 month, 73.3% with a delay of 1 to 3 months, and 46.2% with a delay of ≥3 months[35] (Table 8).[32,36-93] Although aggregate data show declines at monthly intervals, individual studies have reported increments as small as 14 days for progressive functional decline.[54,58,65]

TABLE 7

Sensory and Range of Motion Recovery Scoring Scales

Mackinnon-Dellon Scale (modified from British Medical Research Council Score of Sensory Recovery)	S0 (failure): absence of sensibility in the autonomous area of the nerve
	S0 (none): no recovery of sensibility in the autonomous zone of the nerve
	S1 (poor): recovery of deep cutaneous pain and tactile sensibility
	S1+ (poor): recovery of superficial pain sensibility
	S2 (poor): recovery of some degree of superficial cutaneous pain and tactile sensibility
	S2+ (poor): as in s2, but with overresponse
	S3 (poor): return of pain and tactile sensibility with disappearance of over response, s2PD >15 mm, m2PD >7 mm
	S3+ (good): return of sensibility as in s3 with some recovery of 2-point discrimination: s2PD, 7–15 mm; m2PD, 4–7 mm
	S4 (excellent): complete recovery: s2PD, 2–6 mm; m2PD, 2–3 mm
ASSH classification of total active motion (TAM) recovery	Excellent	TAM equal to normal side
	Good	TAM >75% of normal side
	Fair	TAM >50% of normal side
	Poor	TAM <50% of normal side

TABLE 8

Outcomes of Mixed Motor Peripheral Nerve Repairs

Predictor	Group	Satisfactory (Good-Excellent) Sensory Recovery	Satisfactory (Good-Excellent) Motor Recovery
Age	≤16 y	60.9% (56/92)	66.7% (54/81)
	16–25 y	64.7% (44/68)	63.6% (35/55)
	26–40 y	57.8% (38/66)	60.4% (32/53)
	>40 y	40.9% (18/44)	47.6% (20/42)
	Total (n)	n = 270	n = 231
	Univariate odds ratio per year (95% CI)	0.98 (0.96–0.99), P = 0.02	0.97 (0.96–0.99), P = 0.02
Sex	Male	51.0% (77/151)	55.8% (72/129)
	Female	61.4% (35/57)	73.5% (36/49)
	Total (n)	n = 208	n = 178
	Univariate odds ratio (95% CI), female vs male	1.53 (0.82–2.85), P = 0.18	2.19 (1.06–4.52), P = 0.03
Nerve	Ulnar	52.7% (79/150)	47.5% (56/118)
	Median	57.3% (43/75)	75.0% (39/52)
	Radial	75.6% (34/45)	75.4% (46/61)
	Total (n)	n = 270	n = 231
Univariate	Univariate odds ratio (95% CI), median vs radial	0.44 (0.19–0.99), P < 0.05	0.98 (0.42–2.30), P > 0.05
	Univariate odds ratio (95% CI), ulnar vs radial	0.36 (0.17–0.76), P < 0.05	0.30 (0.15–0.59), P < 0.05
Graft length	No graft	59.4% (63/106)	73.8% (59/80)
	≤30 mm	53.8% (14/26)	48.0% (12/25)
	30–50 mm	39.3% (11/28)	28.9% (11/38)
	>50 mm	18.2% (4/22)	64.9% (37/57)
	Total (n)	n = 182	n = 200
	Univariate odds ratio (95% CI), graft used vs none	0.48 (0.28–0.82), P = 0.01	0.40 (0.22–0.73), P < 0.01
	Univariate odds ratio (95% CI), gap/cm	0.91 (0.83–0.99), P = 0.04	0.93 (0.84–1.03), P = 0.15
Delay	No delay (<24 h)	10/11 (90.9%)	6/7 (85.7%)
	1–30 d	21/36 (58.3%)	56/70 (80.0%)
	1–3 mo	22/30 (73.3%)	23/32 (71.9%)
	3–6 mo	17/39 (43.6%)	18/34 (52.9%)
	6–12 mo	11/24 (45.8%)	5/21 (23.8%)
	>12 mo	25/52 (48.1%)	10/39 (25.6%)
	Total (n)	n = 192	n = 203
	Odds ratio per month (95% CI)	1.00 (0.99–1.01), P = 0.73	0.93 (0.90–0.97), P < 0.01

Table adapted from He et al.[32]

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).[36-94] 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).

Take-Home Messages

Sensory-Only

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 nerves include gap length, injury level, ability to identify proximal and distal stumps, and concomitant vessel or tendon injuries (Table 6).[32]

Mixed/Motor

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 should be considered in mixed nerves include the following: age, nerve injured, level of injury, concomitant vessel or tendon injuries, and gap length (Table 8).[36-94]

DIGITAL NERVES

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).[32,97,100,101,103-119,121-123] Another study including 254 digital nerve repairs reported significantly improved outcomes in repairs performed within 3 months of injury.[124]

TABLE 9

Outcomes of Digital Nerve Repair With Varying Delay Times

Author(s)	Mean Time to Repair in Days	Primary Repair	Nerve Graft	Synthetic Conduit	Vein Conduit	Muscle/Muscle-in-Vein	s2PD Mean, mm	m2PD Mean, mm	SWMT Mean
McFarlane and Mayer[100]	170.8		13				14.9
Hirasawa et al[101]	186.1	10	4				7.9	4.7	5.7
Sullivan[102]	41.02	42					11	5.6
Walton et al[103]	61				115			4.5	4.02
Rose et al[104]	256.2						8.3	5.8
Pereira et al[105]	42.7	24				12	9.4
Tang et al[106]					16			3.2
Segalman et al[107]		19					5.5	5.0	3.74
Battiston et al[99]	112.85			18		13		9.1
Vipond et al[108]	1						3
Lohmeyer et al[109]	115.9			12			9.6
Marcoccio and Vigasio[110]						18	10.7	9.2
Taras et al[111]	6			22			5.2	5
Rinker and Laiu[112]	3			36	32		8.4	6.8
Laveaux et al[113]	1				11		11
Chen et al[114]	24		26				6.7		3.62
Taras et al[115]	29		18				7.1	5.4
Stang et al[116]			28				9
Pilanci et al[117]	55.8		12				7.4		3.1
He et al[32]	23.7		100				12.81		3.57
Kim et al[97]							5.9	5.1	3.81
Rinker et al[118]	13		37				7.1	6.7
Wong et al[119]							14.7		5.09
Fakin et al[120]		93					10.6		2.7
Klein et al[121]	5	81					4

Table adapted from Kim et al.[97]

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 sensory-only nerves include gap length, ability to identify proximal and distal stumps, and concomitant vessel or tendon injuries (Table 6).[32]

ACUTE NERVE COMPRESSION/DYSFUNCTION

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.[125-128] Although early decompression has been recommended, the literature lacks algorithms for timing of intervention.[126-129]

Treatment algorithms have been described in the literature for acute median nerve compression, which is frequently associated with distal radius fractures.[130-134] 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.[123,137-141]

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,[146-150] or ulnar nerve complications after medial or collateral ligament reconstruction of the elbow.[151-153] 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]

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 be considered within 8 hours of symptom onset.[129,154] Although the literature indicates that long-term changes may develop within this time window, clinical symptoms must be evaluated on a case-by-case basis. 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 nerve blocks) with serial measures to determine the appropriate course of treatment and/or assess recovery.

CHRONIC NERVE COMPRESSION

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.

TABLE 10

Carpal Tunnel Surgery: Outcomes Predictors Based on SSS and FSS

Variables Predicting Change in SSS
Predictors	B	SE	P	Standard Coefficient β	95% CI
Age	0.002	0.001	0.134	0.077	−0.001 to 0.004
Duration of symptoms	0.056	0. 20	0.007	0.137	0.015–0.096
Electrophysiological severity	0.231	0.016	<0.001	0.767	0.199 to 0.263
Thenar muscle atrophy	−0.003	0.028	0.908	−0.006	−0.58 to 0.052

BMI, body mass index; FSS, Functional Status Scale; SSS, Symptom Severity Scale.

Table adapted from Alimohammadi et al.[159]

TABLE 12

Risk Factors for Postoperative Infection Following Open Cubital Tunnel Release

Variable	Odds Ratio	95% CI	P
Significant risk factors for infection after open cubital tunnel release
Demographics
Age <65 y	2.08	1.52–2.85	<0.001
Tobacco use	1.65	1.31–2.07	<0.001
Body mass index, kg/m2
30–40 (obesity)	1.52	1.18–1.94	<0.001
≥40 (morbid obesity)	1.53	1.16–2.01	0.002
Male sex	1.32	1.07–1.63	0.008
Comorbidity
Hemodialysis use	2.47	1.19–5.16	0.016
Chronic anemia	2.24	1.72–2.90	<0.001
Inflammatory arthritis	1.43	1.08–1.88	0.012
Depression	1.36	1.09–1.70	0.007
Hyperlipidemia	1.33	1.00–1.76	0.049
Chronic lung disease	1.29	1.04–1.60	0.022
Factors not increasing the risk for infection after open cubital tunnel release
Demographics
Low body mass index (<19 kg/m2)	0.97	0.31–3.07	0.962
Comorbidity
Hypercoagulable state	1.16	0.78–1.72	0.459
Alcohol abuse	1.12	0.83–1.50	0.468
Diabetes mellitus	1.08	0.87–1.34	0.507
Chronic kidney disease	1.06	0.81–1.40	0.675
Peripheral vascular disease	1.06	0.82–1.39	0.648
Hypothyroidism	1.05	0.84–1.31	0.668
Hypertension	1.03	0.75–1.41	0.852
Chronic liver disease	1.01	0.75–1.36	0.942
Congestive heart failure	0.82	0.63–1.08	0.159
Coronary artery disease	0.77	0.61–0.97	0.011

Table adapted from Camp et al.[161]

Although published reports are variable, revision decompression has shown to provide comparable benefits in many outcome dimensions (Tables 13, 14).[165-175,177,178,181-183,186,188-199] 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]

TABLE 13

Primary Versus Revision Cubital Tunnel Syndrome

	Primary	Revisions	P
Final subjective symptoms according to patient group
Relief after primary surgery	27 (96%)	14 (50%)	<0.001
Relief after revision surgery	—	22 (79%)
Symptoms currently	22 (79%)	24 (85%)	0.48
• Paresthesias	17 (61%)	20 (71%)	0.39
Symptoms constant, intermittent, or absent			0.03
• Constant	5 (18%)	15 (53%)
• Intermittent	17 (61%)	9 (32%)
• Absent	6 (21%)	4 (15%)
Physical examination findings according to patient group
Elbow extension, °	2 (0–20)	12 (0–35)	<0.001
Elbow flexion, °	142 (120–145)	137 (125–150)	0.09
Positive Tinel sign	15 (54%)	14 (50%)	0.79
Nerve tender at elbow	4 (14%)	12 (43%)	0.02
1st DI strength (out of 5)	4.5 (2–5)	4.4 (3–5)	0.87
Grip strength, kg	33 (11–54)	28 (8–63)	0.13
Key pinch strength, kg	8 (4–15)	5 (3–16)	0.03
Ring/little finger 2-point discrimination, mm	6 (5–15)	7 (6–15)	0.02
Wartenberg sign	2 (7%)	9 (32%)	0.02
Froment sign	4 (14%)	7 (25%)	0.31
McGowan grading according to patient group
Final McGowan grade			0.01
0	10 (36%)	6 (21%)
I	12 (43%)	5 (18%)
IIA	2 (7%)	12 (43%)
IIB	3 (11%)	3 (11%)
III	1 (3%)	2 (7%)
Change in McGowan grade after surgery			0.003
Improved	18 (64%)	7 (25%)
No change	8 (29%)	15 (54%)
Worse	2 (7%)	6 (21%)

Table adapted from Aleem et al.[164]

TABLE 14

Outcomes After Revision Carpal Tunnel Surgery

		Study	Level of Evidence	No. of Hands	Method/Follow-Up	Resolved or Improved, n (%)	Complications and Patient-Reported Outcomes
Recurrent or persistent CTS	Endoscopic revision CTR	Teoh and Tan[165]	IV Retrospective	9	Endoscopic revision 24-mo avg follow-up	9 (100)	0 complications PRO: NR
		Luria et al[166]	IV Prospective	41	Endoscopic revision 12-mo follow-up (all)	37 (90)	0 complications CTSSS improved from 3.3 to 2.0* CTSFSS improved from 3.1 to 2.1* UWSS improved from 68 to 86* Mean RTW 25 d
		Total		50		46 (92)	0 (0%) complications
	Open revision CTR and neurolysis	Langloh and Linscheid[167]	IV Retrospective	33	External neurolysis 24-mo avg follow-up	28 (85)	Complications: NR PRO: NR
		Wadstroem and Nigst[168]	IV Retrospective	27	External and internal neurolysis	22 (81)	NA
		O'Malley et al[169]	IV Retrospective	20	External neurolysis 31-mo avg follow-up	12 (60)	1 superficial wound infection 1 RSD PRO: NR
		Chang and Dellon[170]	IV Retrospective	35	External and internal neurolysis 23.5-mo avg follow-up	29 (83)	Complications: NR PRO: NR
		Cobb et al[171]	IV Retrospective	131	External and internal neurolysis 11-y avg follow-up	87 (66)	9 delayed wound healing 4 postoperative infections 3 RSD Mean RTW 7.8 wk Mean RTA 8 wk
		Duclos and Sokolow[172]	IV Retrospective	13	External neurolysis 27.5-mo avg follow-up	12 (92)	NA
		Hulsizer et al[173]	IV Retrospective	30	External neurolysis 30-mo avg follow-up	18 (60)	Complications: NR PRO: NR
		Forman et al[174]	IV Retrospective	22	External neurolysis 19-mo avg follow-up	21 (95)	2 scar tenderness and stiffness PRO: NR
		Beck et al[175]	III Retrospective	28	External neurolysis 12-mo avg follow-up	23 (82)	Complications: NR Mean DASH 29 at follow-up
		Total		339		252 (74)	20 (6%) complications
	Vein wrap	Sotereanos et al.[6] Sotereanos and Xu[177]	IV Retrospective	6	Saphenous vein wrap 18-mo avg follow-up	6 (100)	1 transient venous insufficiency PRO: NR
		Varitimidis et al[178]	IV Retrospective	15	Saphenous vein wrap 43-mo avg follow-up	15 (100)	1 transient local swelling at leg PRO: NR
		Total		21		21 (100)	2 (10%) complications, transient
	Synthetic wrap	Soltani et al.[179]	IV Retrospective	9	Collagen synthetic wrap 13.7-mo avg follow-up	8 (89)	Complications: NR PRO: NR
		Kokkalis et al.[180]	IV Retrospective	2	Collagen synthetic wrap 19-mo avg follow-up	2 (100)	0 complications PRO: NR
		Kokkalis et al[181]	IV Retrospective	10	Collagen synthetic wrap 24-mo avg follow-up	10 (100)	0 complications
		Total		21		21 (95)	0 (0%) complications
Recurrent or persistent CTS	Hypothenar fat flap	Strickland et al[182]	IV Retrospective	62	Hypothenar fat flap (62) + internal neurolysis (7) 33-mo avg follow-up	55 (89)	1 ulnar digital nerve paresthesias 1 hypothenar numbness 1 superficial cellulitis Mean RTW 37 wk (work comp) Mean RTW 12 wk (nonwork comp)
		Giunta et al[183]	IV Retrospective	9	Hypothenar fat flap	8 (89)	NA
		Mathoulin et al[184]	IV Retrospective	45	Hypothenar fat flap 45 mo median follow-up	43 (96)	2 scar pain and edema, transient PRO: NR 100% RTW
		Craft et al[185]	IV Retrospective	28	Hypothenar fat flap 10.5-mo avg follow-up	26 (93)	Complications: NR PRO: NR
		Stutz et al[186]	III Retrospective comparative	11	Hypothenar fat flap 11-mo avg follow-up	8 (73)	2 hypertrophic scar DASH 31 at follow-up
		Fusetti et al[187]	IV Retrospective	20	Hypothenar fat flap 6 mo minimum follow-up	18 (90)	16 two-point discrimination resolved to normal DASH improved significantly in all patients
		Karthik et al[188]	IV Retrospective	27	Hypothenar fat flap 22-mo avg follow-up	24 (89)	Complications: NR PRO: NR
		Wichelhaus et al[189]	IV Retrospective	18	Hypothenar fat flap 22-mo avg follow-up	16 (89)	2 hypertrophic scar DASH 42.2 to 17.6 (P < 0.01)
		Athlani and Haloua[190]	IV Prospective	34	Hypothenar fat flap 24 mo minimum follow-up 60 mo follow-up in 13 patients	34 (100)	VAS decreased from 6.4 to 1.4 (P < 0.05) Grip strength improved from 72% to 86% of the contralateral side (P < 0.05) QuickDASH 60.7 to 19.8 (P < 0.05)
		Total		254		232 (91)	9 (4%) complications
	Synovial flap	Wulle[191]	IV Retrospective	27	Synovial flap Follow-up range 1 mo to 14 y	25 (93)	NA
		Stutz et al[186]	III Retrospective comparative	16	Synovial flap 11-mo avg follow-up	9 (56)	1 delayed wound healing DASH 37 at follow-up
		Murthy et al[192]	IV Retrospective	45	Synovial flap 11-mo avg follow-up	43 (96)	1 scar pain PRO: NR
		Total		88		77 (88)	2 (2%) complications
	Multiple surgical methods (outcomes not reported separately)	Strasberg et al[193]	IV Retrospective	45	External and internal neurolysis Median nerve release forearm Ulnar nerve submuscular transposition Median nerve repair Common dig nerve graft Abductor muscle flap 31-mo avg follow-up	24 (53)	Complications: NR PRO: NR
		Varitimidis et al[194]	IV Retrospective	24	External neurolysis alone (7) Hypothenar flap (15) Saphenous vein wrap (1) Neurorrhaphy and hypothenar flap (1) 19-mo avg follow-up	24 (100)	Complications: NR RTW 92%
		Jones et al[195]	IV Retrospective	55	External neurolysis (41) Epineurectomy (15) Synovial or hypothenar flap (8) Reverse radial forearm flap (3) Minimum 1 year follow-up Avg follow-up NR	45 (82)	Complications: NR PRO: NR
Recurrent or persistent CTS		Zieske et al[196]	III Retrospective	97 Persistent (42) Recurrent (19) New (36)	External neurolysis (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) 3.4–4.1 mo follow-up dependent on subgroup	NR	All groups had decreases in VAS pain scores postop Persistent and new subgroups had improvement in pinch and grip strength postop Recurrent subgroup had a higher prevalence of diabetes and did not have significant change in postoperative grip or pinch
		Djerbi et al[197]	IV Retrospective	38	Neurolysis (22) Hypothenar fat flap (11) Pronator quadratus flap (1) Synovial flap (2) Vein wrap (1) Silicone sheet (1) 51-mo avg follow-up	26 (68)	Complications: NR DASH 35 if no fibrosis present at revision surgery DASH 28.7 if perineural fibrosis present at revision surgery DASH 58.6 if perineural and intraneural fibrosis present at revision surgery
		Total		162		119 (73)

*P < 0.01.

Avg, average; CTR, carpal tunnel release; CTS, carpal tunnel syndrome; CTSFSS, Carpal Tunnel Syndrome Functional Status Score; CTSSS, Carpal Tunnel Syndrome Symptom Severity Score; DASH, Disabilities of the Arm, Shoulder, and Hand Score; NA, not available; NR, not reported; PRO, patient self-reported outcomes, validated outcomes include DASH, PRWE; RSD, reflex sympathetic dystrophy (ie, chronic regional pain syndrome); RTA, return to recreational activities; RTW, return to work; UWSS, University of Washington patient satisfaction score; VAS, visual analog scale.

Table adapted from Lauder et al.[198]

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.

CHRONIC PAIN DUE TO NERVE INJURY-INDUCED PAINFUL NEUROMA

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.[25,208-212] 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]

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.

ADDITIONAL REPAIR CONSIDERATIONS

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:

FIGURE 4

Management of peripheral nerve transection.

Ability to achieve a tension-free repair

Operative time required for each repair approach

Ability to reduce anesthesia acuity and duration

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.

Management of nerve gap (Fig. 4)[95,124,215-217]

Ability to reduce resource utilization by performing a single surgery versus staged reconstruction

Insurance, socioeconomic status, and likelihood of returning for secondary procedures should be considered.

Management plan for concomitant injuries/procedures

Extent and timing of rehabilitative plan

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 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.

DISCUSSION

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 procedures (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.

TABLE 15

Medically Necessary, Time-Sensitive Procedures

Procedure Factors	1	2	3	4	5	Score (1–5)
OR time, min	<30	30–60	60–120	120–180	≥180
Estimated length of stay	Outpatient	23 h	24–48 h	≤3 d	>4 d
Postoperative ICU need, %	Very unlikely	<5	5–10	10–25	≥25
Anticipated blood loss, cc	<100	100–250	250–500	500–750	≥75
Surgical team size	1	2	3	4	>4
Intubation probability	≤1%	1%–5%	5%–10%	10%–25%	≥25%
Surgical site	None of the following	Abdominopelvic MIS surgery	Abdominopelvic open surgery, infraumbilical	Abdominopelvic open surgery, supraumbilical	OHNS/upper GI/thoracic
Disease factors	1	2	3	4	5	Score (1–5)
Nonoperative treatment option effectiveness	None available	Available, <40% as effective as surgery	Available, 40%–60% as effective as surgery	Available, 60%–95% as effective as surgery	Available, equally effective
Nonoperative treatment option resource/exposure risk	Significantly worse/not applicable	Somewhat worse	Equivalent	Somewhat better	Significantly better
Impact of 2-wk delay in disease outcome	Significantly worse	Worse	Moderately worse	Slightly worse	No worse
Impact of 2-wk Delay in surgical difficulty/risk	Significantly worse	Worse	Moderately worse	Slightly worse	No worse
Impact of 6-wk delay in disease outcome	Significantly worse	Worse	Moderately worse	Slightly worse	No worse
Impact of 6-wk delay in surgical difficulty/risk	Significantly worse	Worse	Moderately worse	Slightly worse	No worse
Patient factors	1	2	3	4	5	Score (1–5)
Age, y	<20	20–40	40–50	50–65	>65
Lung disease (asthma, COPD, CF1)	None			Minimal (rare inhaler)	>Minimal
Obstructive sleep apnea	Not present			Mild/Moderate (no CPAP)	On CPAP
CV disease (HTN, CHF, CAD)	None	Minimal (no meds)	Mild (≤1 med)	Moderate (2 meds)	Severe (≥3 meds)
Diabetes	None		Mild (no meds)	Moderate (PO meds only)	>Moderate (insulin)
Immunocompromised2	No			Moderate	Severe
ILI3 Sx's (fever, cough, sore throat, body aches, diarrhea)	None, asymptomatic				Yes
Exposure to known COVID-19–positive person in the past 14 d	No	Probably not	Possibly	Probably	Yes
					Total Score:

Each row is scored, and all scores are added to produce a cumulative score (range, 21–105). 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.

Table adapted from Prachand et al.[1]

TABLE 16

MeNTS Possible Score Ranges for Common Nerve Procedures

Procedure Factors	Sharp Laceration of Digital Nerve	Ulnar Elbow (MM)		Carpal Tunnel	Neuroma (Palmar Nerve)
OR time	1–2	2–3		1	2
Estimated length of stay	1	1		1	1
Postoperative ICU need	1	1		1	1
Anticipated blood loss	1	1		1	1
Surgical team size	4	4		4	4
Intubation probability	1	1		1	1
Surgical site	1	1		1	1
Disease factors
Nonoperative treatment, pain medication	2	1		2	2
Nonoperative treatment, pain medication	5	1		5	5
Impact of 2-wk delay End-organ viability, painful neuroma formation, amount of scarring in the nerve results in more trimming and longer gap	3	3		5	3
Impact of 2-wk delay Adhesions, ability to find distal stump	2	2		5	5
Impact of 6-wk delay End-organ viability, painful neuroma formation	2	1		4	3
Impact of 6-wk delay Adhesions, ability to find distal stump	2	2		5	5
Score (+ possible scores from factors below)	27 (+8 → 40)	22 (+8 → 40)		36 (+8 → 40)	34 (+8 → 40)
Patient factors	1	2	3	4	5
Age, y	<20	20–40	40–50	50–65	>65
Lung disease (asthma, COPD, CF1)	None			Minimal (rare inhaler)	> Minimal
Obstructive sleep apnea	Not present			Mild/moderate (no CPAP)	On CPAP
CV disease (HTN, CHF, CAD)	None	Minimal (no meds)	Mild (≤1 med)	Moderate (2 meds)	Severe (≥3 meds)
Diabetes	None		Mild (no meds)	Moderate (PO meds only)	>Moderate (insulin)
Immunocompromised2	No			Moderate	Severe
ILI3 Sx's (fever, cough, sore throat, body aches, diarrhea)	None, asymptomatic				Yes
Exposure to known COVID-19–positive person in the past 14 d	No	Probably not	Possibly	Probably	Yes

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; CPAP, continuous positive airway pressure; CV, cardiovascular; COPD, chronic obstructive pulmonary disease; HTN, hypertension; ICU, intensive care unit; MeNTS, Medically Necessary, Time-Sensitive Procedures; PO, per os (oral administration).

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.

TABLE 11

Outcomes Predictors for in Situ Ulnar Nerve Decompression

Variable	Unsatisfactory Group (n = 27)	Satisfactory Group (n = 208)	P
Age (y)	54.1 ± 11.3	53.2 ± 10.6	0.681
Sex			0.83
Male	17	137
Female	10	71
BMI, kg/m2	24.1 ± 3.1	23.5 ± 2.7	0.287
Tobacco use			0.649
Yes	6	59
No	21	149
Alcohol use			0.614
Yes	4	42
No	23	166
Hypertension			0.438
Yes	7	39
No	20	169
Diabetes mellitus			0.748
Yes	2	23
No	25	185
Disease duration, mo	17.1 ± 6.7	13.8 ± 7.4	0.029
Preoperative severity			0.004
Severe	25	137
Not severe	2	71
MCV, m/s	28.2 ± 10.5	34.1 ± 12.8	0.023
SCV, m/s	23.4 ± 11.7	27.6 ± 8.4	0.021

BMI, body mass index; MCV, motor conduction velocity; SCV sensory conduction velocity.

Table adapted from Kong et al.[160]