Recovery of mechanical detection thresholds after direct digital nerve repair versus conduit implantation

Abstract

The purpose of this study was to assess sensory and functional nerve recovery after digital nerve injury in patients with an end-to-end suture (S) or with implantation of a collagen conduit (C) to bridge a nerve gap. Fifteen S and 11 C with a follow-up of 6–36 months and 28 healthy control participants were enrolled. Methods of assessments were quantitative sensory testing, the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), range of motion and the painDetect questionnaire. After both procedures, sensory profiles showed largely recovered function of C and Aδ fibres but severe loss of Aβ-fibre function leading to increased mechanical detection thresholds. There was only minimal allodynia. Severe pain was absent. Patients with conduits reported more functional impairment, especially in work performance, which correlated with the assessed loss of Aß-fibre function.

Level of evidence: III

Keywords

Nerve conduit digital nerve injury nerve recovery quantitative sensory testing somatosensory profiles

Introduction

Digital nerve injuries can severely affect everyday life. Patients can experience pain, paraesthesia, numbness and loss of tactile perception. These shortcomings limit the ability to perform household chores, sporting activities or to play musical instruments and can lead to major disability in participating in everyday work life (Dienstknecht et al., 2013).

The reference standard for treatment of peripheral nerve injuries (PNI) is tensionless primary end-to-end suture; but due to retraction of the nerve stumps, necessary intraoperative debridement, and tissue loss, this may not always be feasible (Archibald et al., 1995; Bertleff et al., 2005; Dienstknecht et al., 2013; Taras et al., 2011). In cases of injuries with a nerve gap, there is currently no consensus regarding the preferred treatment (Dienstknecht et al., 2013; Rinker and Vyas, 2014).

Previous studies have reported satisfactory sensory and functional nerve regeneration after implantation of a synthetic nerve conduit after PNI (Bushnell et al., 2008; Dienstknecht et al., 2013; Lohmeyer et al., 2009; Taras et al., 2011; Thomsen et al., 2010; Wangensteen and Kalliainen, 2010), which are comparable outcomes to those after end-to-end suture (Bertleff et al., 2005; Boeckstyns et al., 2013; Lundborg et al., 2004; Weber et al., 2000). Measurements applied in the abovenamed studies were two-point discrimination (2PD) and Semmes-Weinstein monofilament testing (SWM). However, both measurements have some methodical limitations, e.g. the lack of standardization (Bell-Krotoski et al., 1995; Lee et al., 2003; Lundborg and Rosen, 2004; Novak et al., 1993), a low inter-observer reliability for SWM (Collins et al., 2010; Marx et al., 1998) and the assessment of only the large, myelinated Aβ fibres.

In contrast, quantitative sensory testing (QST) is nowadays the reference standard to describe somatosensory profiles in painful and painless neuropathies (Backonja et al., 2013). A standardized protocol of the German Research Network on Neuropathic Pain (DFNS) along with reference to a large database (Magerl et al., 2010; Pfau et al., 2014) allows evaluating both large- and small-fibre function and additionally to identify signs of peripheral and central sensitization and cutaneous and deep pain sensitivity (Rolke et al., 2006). With QST, both negative (hypoesthesia, hypoalgesia) and positive sensory signs (hyperesthesia, hyperalgesia, allodynia) can be captured (Krumova et al., 2012; Rolke et al., 2006).

The purpose of the present study was to evaluate whether the recovery of somatosensory function in patients after digital nerve injury was adequate when compared with a healthy control group, taking into account both large- and small-fibre function. We also analysed whether disability assessed by the Disability of the Arm, Shoulder and Hand (DASH) Outcome Measure correlated with pain and the sensory loss of function.

Materials and methods

Written informed consent was obtained from all participants according to the Declaration of Helsinki. This study was approved by the local ethics committee (registry number: 4966-14).

A total of 106 patients with unilateral PNI of sensory nerves in the upper extremity treated with end-to-end suture or implantation of a collagen conduit from January 2011 to February 2014 were invited to participate. The NeuraGen® nerve guide (Integra LifeSciences Corporations, Plainsboro, NJ, USA), a biocompatible, semi-permeable, Type I bovine collagen tube, was used in all patients receiving nerve conduits. Exclusion criteria were incomplete transection of the nerve, additional nerve injuries of the contralateral upper extremity and psychiatric or neurological disorders (e.g. polyneuropathy).

Seventy-four patients were lost to follow-up assessment. The most frequent reasons were change of address and a long travel distance and/or sacrificing time for this study without any effect on further treatment. Two patients were excluded because they met one of the abovementioned exclusion criteria.

Initially, 30 healthy participants matching the patients in age (± 7 years), sex and testing area were recruited according to the recommendations for the selection of healthy participants for QST studies (Gierthmuhlen et al., 2015).

In favour of a better homogeneity of groups, we later decided to include only patients with a transection of a digital nerve which was primarily repaired. Therefore, five further patients, who had undergone secondary repair (n = 3) or presented with an injury of a nerve other than a digital nerve (n = 2) and two healthy participants were excluded from data collection after having been examined. One patient who presented with both a suture and a conduit in one hand was also excluded after examination. If a patient presented with two affected nerves, both nerves were examined separately. We examined 11 conduits in ten patients and 15 sutures in 14 patients; thus, there was one patient with two affected nerves in each group.

Quantitative sensory testing

QST was performed in a certified QST laboratory (Geber et al., 2009; Vollert et al., 2015) by one examiner after training according to the standardized protocol of the DFNS. The testing area for QST was determined as appropriate regarding the innervation area of the affected nerve. This was on the lateral side of the finger in the innervation area of the affected digital nerve at the level of the distal interphalangeal joint (DIP). The contralateral mirror area was assessed first, followed by assessment of the affected area (Rolke et al., 2006).

The DFNS-QST protocol comprised the assessment of:

Large nerve-fibre function (Aβ fibres) and corresponding central pathways by testing the mechanical (MDT) and vibration detection threshold (VDT) using a standardized set of von-Frey-Hairs (Marstock nervtest, Optihair 2, 0.25-512 mN) and a conventional tuning fork (128 Hz) with a grading scale in the range of 0–8.

Small nerve-fibre function (C and Aδ fibres) and corresponding central pathways by testing the

cold and warm detection threshold (CDT, WDT), the thermal sensory limen (TSL), paradoxical heat sensations (PHS) and the cold and heat pain threshold (CPT, HPT) using a TSA 2001-II (MEDOC, Israel) thermal sensory testing device with a contact area of 16 × 16 mm.

mechanical pain threshold (MPT) using a set of seven custom-made weighted pinprick stimulators (8–512 mN, contact area of 0.2 mm diameter).

C-fibre-mediated deep pain sensitivity by testing of the joint pressure pain threshold (PPT) using a hand-held pressure algometer (Somedic, Sweden, algometer type II) with a stimulus area of 1 cm² (Mainka et al., 2014).

Mechanical pain sensitivity (MPS) and dynamic mechanical allodynia (DMA) to test the reaction to sharp stimuli (Aδ fibres) and pain sensitivity to light touch (Aβ fibres) using the pinprick set, a cotton wisp (~3 mN), a cotton wool tip on an elastic strip (~100 mN) and a standardized brush (Somedic, Sweden, ~200–400 mN).

Temporal summation of pain (wind-up ratio [WUR]) using a single pinprick of 256 mN (or 128 mN if the pain intensity of the first stimulus was not tolerated and 512 mN if the first stimulus was rated as not painful, respectively). The WUR could not be calculated if the first rating is 0. The latter occurred in one patient in each group. Thus, those values were not included for these two patients.

VDT and PPT were measured at the DIP.

Questionnaires

The painDetect is a validated self-report questionnaire evaluating intensity, quality, location and temporal characteristics of pain (Freynhagen et al., 2006). The DASH outcome measure is a validated, self-report questionnaire (Germann et al., 2003) describing disabilities in everyday activities (30 items), work performance (four items) and sport/music performance (four items), as well as symptoms due to the injury. The work and sport/music modules have only been assessed in those patients currently working and/or performing a sport or music. The Short Form 12 health survey (sf12) is a self-report 12-item questionnaire evaluating quality of life with a subdomain in physical and in mental health. A summarizing score with a mean of 50 (SD 10) in healthy participants is calculated (Gandek et al., 1998). The lower the score, the lower the subjective quality of life. Additionally, the Edinburgh Handedness inventory was used to determine the patient’s handedness (Oldfield, 1971).

Correlation between disability, pain and loss of function

The intensity of current pain and thermal and mechanical detection thresholds (CDT, WDT, MDT) were correlated with the scores of the DASH questionnaire. The length of the nerve gap in the conduit group was correlated with the outcome of QST and the DASH score.

Clinical assessment

A thorough medical history was taken. A clinical examination of the affected and unaffected upper extremity was performed including movement in the glenohumeral and elbow joints. The range of motion was measured in the wrist. Then, patients were instructed to make a fist. If the fist was incomplete, the range of motion in the finger joints was measured. The function of extrinsic and intrinsic muscles was examined by observing whether the patient was able to perform pinch grip, power grip, key grip and pencil grip.

Statistical analysis

All QST parameters, except PHS, CPT, HPT and VDT, were normally distributed in logarithmic space and transformed logarithmically before statistical analysis (Rolke et al., 2006). To present the data in this study in their original units, QST values were retransformed. Z-transformation (Magerl et al., 2010; Rolke et al., 2006) was performed using the data of the group of healthy participants as reference values, as there are no published reference data for digital nerves. Z-transformation allows the presentation of a somatosensory profile in a dimensionless scale. Values above zero indicate a gain of function, while values below zero represent a loss of function. Abnormal values are values outside of the 95% confidence interval (CI) of the reference group (z-scores <–1.96 or >1.96). Abnormal side differences are defined as side-to-side differences beyond the 95% CI of the side-to-side differences of the reference group (Magerl et al., 2010; Rolke et al., 2006).

Univariate analysis of variance (ANOVA) and t-test were used to detect differences between the groups with least squares difference (LSD) and Scheffé as post-hoc tests. Pearson correlation was applied to determine associations between sensory parameters, pain intensity and DASH score. P values < 0.05 were considered significant.

Results

Clinical data

Fifteen sutures in 14 patients and 11 conduits in ten patients were examined. The location of the injured nerves is shown in Figure 1. The clinical data of both groups were comparable except for the extent of trauma and the length of the nerve gap (C: median: 1.5 cm [range, 0.8–2.7 cm], documented only in n = 9/11; S: no nerve gap). In cases of an extensive trauma (e.g. crush, circular saw or high-pressure cleaner injuries) intraoperative debridement of the nerve stumps was performed. If a tensionless end-to-end coaptation of the nerve stumps was not possible, a conduit was implanted. There was a significantly higher number of tendon and vessel injuries in the suture group; however, 10/14 nerve injuries were due to lacerations on sharp objects with the wounds being mostly clean and the nerve and tendon stumps easily opposed. In the conduit group, the nerve stumps were frayed or retracted and/or the wounds were dirty, which necessitated intraoperative debridement that resulted in a nerve gap. Thus, the nerve injury was more extensive in the conduit group. One patient in the conduit group presented with a fracture of the proximal phalanx due to a crush injury. This resulted in an arthrodesis of the proximal and distal interphalangeal joints of the affected finger. Another patient presented with an amputation of the distal phalanx of an unaffected finger of the contralateral hand. In the suture group, one patient had an accompanying tendon injury with a long gap between the tendon stumps that necessitated an arthrodesis of the distal interphalangeal joint. This limitation of motor function did not affect the results of QST of the purely sensory digital nerves, although it might have affected the results of the DASH score. However, the individual DASH scores of the affected patients showed only minor limitations compared with the other patients in the respective groups. Five patients in the conduit group and 12 patients in the suture group were operated on the day of or the day after the accident. The remaining patients were treated in the following months (median: C: 60 days, S: 26 days). Thirty-two digital nerves in 28 healthy participants were examined (Table 1).

Table 1.

Clinical data of all patients after implantation of a collagen conduit (C), after end-to-end suture (S) and in the healthy control group (H).

	Collagen conduit (C)	End-to-end suture (S)	Healthy participants (H)
Patients (n)	10	14	28
Age (years) (mean)	45.6 (SD 16.4)	38.6 (SD 13.9)	42.9 (SD 14.6)
Male (n (%))	10 (100)	11 (79)	24 (86)
BMI (kg/m²) (mean)	25.9 (SD 4.9)	28.2 (SD 5.0)	26.2 (SD 5.4)
Smokers (n (%))	6 (60)	5 (36)	5 (18)
Right-handedness (n (%))	10 (100)	14 (100)	26 (93)
Profession: skilled manual work (n (%))	5 (50)	4 (29)	1 (4)
Co-morbidities (n) (multiple answer)
- Cardiovascular disease	1	2	–
- Metabolic disease	2	1	–
- Other	4	2	–
Other surgical interventions of the upper extremities (n (%))	2 (20)	4 (29)	–
Data concerning the injury
Dominant hand affected (n (%))*	7 (70)	3 (21)
Pattern of primary injury (n (%))
- Crush injury	1 (10)	–
- Tear	2 (20)	1 (7)
Cut	5 (50)	10 (71)
- Injury by circular saw	1 (10)	2 (14)
- Injury by high-pressure cleaner	–	1 (7)
- Iatrogenic	1 (10)	–
Accompanying injuries n (multiple answer)
- Bone fracture	1
- Tendon injury (multiple answer)	3	12
◦ Flexor digitorum superficialis	1	5
◦ Flexor digitorum profundus	1	7
◦ Extensor digitorum	1	–
- Vessel injury	7	11
Time interval between surgery and examination (months) (n (%))
- 6–15	5 (50)	8 (57)
- 15–24^†	3 (40)	–
- > 24	1 (10)	6 (43)

Significant with P < 0.05.

†

Significant with P < 0.01.

n, number of patients; %, percentage of all patients in respective group; SD, standard deviation.

Quantitative sensory testing

The mechanical detection threshold was abnormally increased in 91% of the conduit group and 73% of the suture group, respectively (Table 2). There was a loss of sensory function for the thermal detection (CDT, WDT, TSL) and thermal pain thresholds (CPT, HPT) with significantly decreased z-values in the conduit group compared with the contralateral side (P < 0.01, but WDT P < 0.05) and to the healthy participants (P < 0.01). In the suture group, z-values were significantly decreased compared with the contralateral side only in WDT, TSL and HPT (P < 0.05) and to the healthy participants in TSL and HPT (P < 0.05). The MPT, MPS, PPT and WUR were comparable to the healthy participants in both patient groups. Low-intensity allodynia was found in two patients in each group. PHS were present in eight cases in the conduit group and five cases in the suture group (P < 0.05). Overall, the somatosensory profiles in both groups were mainly characterized by a loss of function. A minor abnormal gain of function was observed only regarding the PPT in the suture group and the WUR in both groups (Table 2, Figure 2, see also supplementary data for absolute values).

Table 2.

QST values (mean ± standard deviation) after z-transformation of affected side and unaffected side and indication of absolute abnormal values and abnormal side differences of all patients after implantation of a conduit (C), after end-to-end suture (S) and in the healthy control group (H).

	Conduit (C)				End-to-end suture (S)				Healthy participants (H)
	Affected	Unaffected	AAV	ASD	Affected	Unaffected	AAV	ASD	Affected	Unaffected	AAV	ASD
CDT	−1.75 (SD 1.28)aa **◦◦	0.15 (SD 1.08)	5 (45)	2 (18)	−0.41 (SD 1.45)	0.17 (SD 1.18)	3 (20)	2 (13)	−0.07 (SD 1.05)	0.07 (SD 0.96)	2 (6)	2 (6)
WDT	−1.35 (SD 0.94)a◦◦	0.01 (SD 1.27)	3 (27)	2 (18)	−0.63 (SD 1.23)a	0.35 (SD 0.77)	3 (20)	2 (13)	0.00 (SD 1.33)	0.15 (SD 1.26)	4 (13)	2 (6)
TSL	−1.90 (SD 0.52)aa**◦◦	−0.56 (SD 0.87)	7 (64)	1 (9)	−0.68 (SD 1.29)a ▪	0.07 (SD 1.05)	3 (20)	3 (20)	−0.01 (SD 1.05)	0.05 (SD 1.15)	2 (6)	1 (3)
CPT	−1.19 (SD 0.75)aa *◦◦	−0.03 (SD 1.03)	1 (9)	3 (27)	−0.12 (SD 1.08)	0.03 (SD 0.85)	0 (0)	0 (0)	0.01 (SD 1.09)	−0.13 (SD 1.13)	1 (3)	2 (6)
HPT	−1.28 (SD 0.81)aa ◦◦	−0.67 (SD 1.06)	2 (18)	1 (9)	−1.02 (SD 1.28)a ▪	−0.31 (SD 1.22)	7 (47)	1 (7)	−0.01 (SD 1.35)	−0.07 (SD 1.28)	5 (16)	4 (13)
MDT	−4.14 (SD 2.12)aa **◦◦	−0.66 (SD 1.17)	10 (91)	0 (0)	−2.81 (SD 1.60)aa ▪▪	−0.76 (SD 1.05)	11 (73)	0 (0)	0.05 (SD 0.43)	0.02 (SD 0.60)	0 (0)	1 (3)
MPT	−0.13 (SD 1.53)	0.66 (SD 1.52)	2 (18)	3 (27)	−0.40 (SD 1.77)	0.04 (SD 1.68)	5 (33)	1 (7)	0.10 (SD 1.14)	0.00 (SD 1.04)	2 (6)	5 (16)
MPS	−0.66 (SD 0.81)	−0.46 (SD 0.92)	0 (0)	1 (9)	−0.46 (SD 2.12)	−0.55 (SD 1.78)	5 (33)	3 (20)	0.10 (SD 1.21)	0.06 (SD 1.09)	3 (9)	2 (6)
WUR	0.22 (SD 0.74)	−0.01 (SD 0.75)	0 (0)	1 (9)	0.59 (SD 1.19)▪	0.53 (SD 1.09)	1 (7)	0 (0)	−0.02 (SD 0.71)	−0.04 (SD 0.69)	0 (0)	3 (9)
VDT	−2.06 (SD 2.69)a ◦◦	−0.61 (SD 1.39)	5 (45)	3 (27)	−1.15 (SD 1.68)▪	−0.57 (SD 1.36)	4 (27)	1 (7)	−0.01 (SD 1.10)	−0.01 (SD 1.05)	2 (6)	1 (3)
PPT	−0.05 (SD 0.72)	−1.14 (SD 1.32)	0 (0)	4 (36)	0.34 (SD 1.50)a	−0.53 (SD 1.57)	2 (13)	5 (3)	−0.09 (SD 1.06)	0.04 (SD 1.21)	3 (9)	2 (6)

Affected and Unaffected: all data given in mean ± standard deviation.

AAV (absolute abnormal values) and ASD (abnormal side differences): all data given in n (%) = number of patients with abnormal values (percentage of all patients in respective group); C: n = 11, S: n = 15 and H: n = 32 in all parameters, but in WUR: C: n = 10 and S: n = 14.

**,*: significant difference to S with P < 0.01 and P < 0.05.

▪▪,▪ and ◦◦,◦: significant difference to H with P < 0.01 and P < 0.05.

aa,a: significant difference to contralateral side with P < 0.01 and P < 0.05.

AAV, absolute abnormal values; ASD, abnormal side differences; CDT, cold detection threshold; CPT, cold pain threshold; HPT, heat pain threshold; MDT, mechanical detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; PPT, pressure pain threshold; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold; WUR, wind-up ratio.

Questionnaires

Eight conduit patients and three suture patients reported low intensity pain (P < 0.01, Table 3). None of the patients required analgesics. The intensity of different pain descriptors (Figure 3) showed no significant differences between the groups.

Table 3.

Pain characteristics of all patients after implantation of a collagen conduit (C) and after end-to-end suture (S).

	Collagen conduit (C)	End-to-end suture (S)
Patients (n)	10	14
Current pain n (%)^†	8 (80)	3 (21)
Pain on joints evoked by pressure n (%)^†	4 (40)	–
No pain n (%)^†	2 (20)	11 (79)
Total number of patients with pain (n (%))	8 (100)	3 (100)
Localization of pain (multiple answers) (n (%))
- Pain only in affected area	6 (75)	2 (67)
- Proximal spread of pain	2 (25)	1 (33)
- Superficial pain	2 (25)	1 (33)
- Deep pain	6 (75)	2 (67)
PainDetect (n (%))
Current pain (mean ± SD, NRS 0–10)	2.3 (SD 1.4)	2.0 (SD 1.0)
Mild	7 (88)	3 (100)
Moderate	1 (13)	–
Severe	–	–
Maximal pain during the last 4 weeks (mean ± SD, NRS 0–10)	4.4 (SD 2.1)	4.3 (SD 2.5)
Mild	3 (38)	1 (33)
Moderate	4 (50)	1 (33)
Severe	1 (13)	1 (33)
Average pain during the last 4 weeks (mean ± SD, NRS 0–10)	2.8 (SD 1.3)	3.0 (SD 1.7)
Mild	6 (75)	2 (67)
Moderate	2 (25)	1 (33)
Severe	–	–
Temporal characteristics of pain (n (%)
Persistent pain with slight fluctuations	3 (38)	1 (33)
Persistent pain with pain attacks	2 (25)	1 (33)
Pain attacks without pain in-between	3 (38)	1 (33)
Pain attacks with pain in-between	–	–

n, number of patients; %, percentage of all patients in respective group; SD, standard deviation; NRS, numerous rating scale; mild, NRS 1–3; moderate, NRS 4–6; severe, NRS 7–10.

Significant with P < 0.05.

†

Significant with P < 0.01.

In the conduit group, the DASH score was significantly higher, which was pronounced for the work section (all P < 0.01). Also, the physical section of the sf12 showed severe impairment in conduit patients compared with the suture patients and the healthy participants. Overall, there was no affectation on mental health as indicated by the subsection of the sf12 (Table 4).

Table 4.

Results of DASH and sf12 questionnaires of all patients after implantation of a collagen conduit (C), after end-to-end suture (S) and in the healthy control group (H).

	Collagen conduit (C)	End-to-end suture (S)	Healthy participants (H)
DASH total score	25.0 (SD 18.8)** ◦◦	5.6 (SD 6.8)	3.0 (SD 4.7)
DASH score performance sport/music	30.4 (SD 31.5)** ◦◦	8.0 (SD 15.3)	2.3 (SD 6.2)
DASH score work section	37.5 (SD 25.0)** ◦◦	9.1 (SD 15.0)	0.8 (SD 3.9)
sf12 score physical section	43.8 (SD 10.8)** ◦◦	51.6 (SD 5.2)	53.7 (SD 3.1)
sf12 score mental section	51.6 (SD 13.5)	56.6 (SD 8.4)	55.8 (SD 6.3)

All mean ± SD.

*,**: significant difference to S with P < 0.05 and P < 0.01.

◦,◦◦: significant difference to H with P < 0.05 and P < 0.01.

SD, standard deviation; DASH score performance sport/music: C: n = 7, S: n = 11, H: n = 25; DASH score work section: C: n = 7; S: n = 13; H: n = 23.

Correlation between disability, pain and loss of function

Pain adversely affected DASH scores in both groups (C: r = 0.836, P < 0.01; S: r = 0.817, P < 0.01), whereas MDT, CDT and WDT did not correlate with the DASH score (Figure 4). There was no correlation between the length of the nerve gap and the outcomes in the conduit group.

Functional assessment

There was no limitation of grip function or fist formation and no change in range of motion other than what can be ascribed to amputation (n = 1) and arthrodesis (n = 2).

Discussion

The somatosensory profiles of each group were similar, both in general were characterized by a loss of function, which was more pronounced in conduit patients. The small-fibre function was mostly recovered in both groups, but there was a remarkable loss of large-fibre function, manifesting itself in an impairment of the perception of touch and vibration. Overall pain was mild, but when reported, it correlated with a higher DASH score. Subjective functional impairment was more pronounced in the conduit group, especially in work performance. However, the decision regarding which surgical method was suitable in each case was made by the surgeon during the operation. Therefore, the authors want to emphasize that the aim of the study was not a comparison of the different surgical approaches.

In accordance with this study, pronounced mechanical and slight thermal hypoesthesia in patients after PNI mostly without surgical repair has been reported (Gierthmuhlen et al., 2012; Maier et al., 2010; Schuning et al., 2009). However, the somatosensory profiles described in those studies depicted hyperalgesia to all painful stimuli (Gierthmuhlen et al., 2012).

After implantation of a conduit, Chiriac et al. (2012) reported no sensory recovery in 17/28 patients while Haug et al. (2013) described fast recovery of protopathic functions (C fibres, Aδ fibres) and insufficient recovery of tactile detection (Aβ fibres), which reflects the results of our study. As in our study, Fakin et al. (2016) reported recovery of protective sensation in patients with an end-to-end suture but failure of recovery of normal functional sensibility. Sensory recovery of patients in our study corresponded to the recovery reported for injuries of other peripheral nerves, including nerves of larger calibre (Chiriac et al., 2012; Gierthmuhlen et al., 2012; Schuning et al., 2009).

In contrast, other studies have reported more favourable results with satisfactory sensory recovery after implantation of conduits (Bushnell et al., 2008; Dienstknecht et al., 2013; Lohmeyer et al., 2007; Lohmeyer et al., 2009; Taras et al., 2011; Thomsen et al., 2010; Wangensteen and Kalliainen, 2010), which resembled those after end-to-end suture (Bertleff et al., 2005; Boeckstyns et al., 2013; Lundborg et al., 2004; Weber et al., 2000). The 2PD and SWM testing applied in those studies have major limitations, e.g. neglected assessment of small-fibre function, insufficient standardization (Bell-Krotoski et al., 1995; Lee et al., 2003; Lundborg and Rosen, 2004; Novak et al., 1993) and low inter-observer reliability for SWM (Collins et al., 2010; Marx et al., 1998). Moreover, classification of a ‘good’ or ‘excellent’ outcome was inconsistent throughout the studies.

Meek and Coert (2013) provided a meta-analysis reclassifying sensory recovery assessed by 2PD in patients after implantation of a conduit according to the classification system used by Weber et al. (2000) and Bertleff et al. (2005). In this analysis, 73% of all cases presented good or excellent sensory recovery, whereby an excellent recovery for a 2PD is 3–6 mm and good is 7–15 mm. These values are not close to being normal and thus far away from being excellent or good when compared to healthy controls, who show a 2PD of 1.5 mm (SD 0.05 mm) in the index finger of young healthy participants and 3.4 mm (SD 0.13 mm) in elderly healthy participants (Kalisch et al., 2009). In healthy people, a 2PD above 2 mm resembles the spatial acuity of the shoulder, lower back, thigh, calf or dorsum of the foot and can thus be regarded as inadequate for a proper function of the hand (Mancini et al., 2014). Additionally, a 2PD which is twice as wide as in healthy participants does not necessarily indicate half the improvement of function considering the influence of the enhancement of cortical reorganization caused by loss of sensory input after PNI (Elbert et al., 1997; Merzenich et al., 1984; Pons et al., 1991; Schwenkreis et al., 2001).

Given the severe loss of Aß-fibre function and rather normal thermal detection thresholds and thus small-fibre function in our patients, we conclude that recovery of function in unmyelinated fibres is better than in myelinated fibres. Animal studies assessing nerve recovery after PNI show that there is little or no loss of myelinated axons proximal to the injury site (Horch and Lisney, 1981; Lisney, 1987; Pover and Lisney, 1988) and approximately 75% regenerate across the neuroma and form functional connections (Horch and Lisney, 1981). Even though only 45% of unmyelinated fibres regenerate across the injury site, sensory recovery is much better (Lisney, 1987). This could be ascribed to the higher frequency of skin terminations in regenerated polymodal nociceptors, or it could be due to an overlap of receptive fields, meaning a lower frequency of functional receptors in the skin does not automatically prompt a reduction of skin innervation (Lisney, 1987). However, especially the high incidence of paradoxical heat sensations as a sign of impaired Aδ-fibre function still points to not fully recovered small-nerve fibres (Craig and Bushnell, 1994; Hansen et al., 1996; Maier et al., 2010; Rolke et al., 2006; Vollert et al., 2015). Furthermore, multiple axon-sprouting has been observed in myelinated fibres leading to retraction and a failure to form functional connections (Horch and Lisney, 1981; Lisney, 1987; Pover and Lisney, 1988). Moreover, endoneurial tubes shrink during Wallerian degeneration, hence regenerating fibres are reduced in caliber and conduction velocity is decreased (Burnett and Zager, 2004; Horch and Lisney, 1981). Sensory nerve fibres show a tendency to cross-reinnervate and grow into functionally inappropriate endoneurial tubes or fail to re-enter completely (Brandt et al., 2015; Burnett and Zager, 2004; Dodd and Jessell, 1988; Fairbairn et al., 2015; Jacques and Kline, 2000).

Previously studied patients were mostly pain-free, which corresponds to our findings (Dienstknecht et al., 2013; Lohmeyer et al., 2009; Taras et al., 2011). The DASH questionnaire was applied in three studies reporting scores of 6–19 and a score of 5 in the work section (Bushnell et al., 2008; Dienstknecht et al., 2013; Thomsen et al., 2010). These results differ from the higher scores we assessed. This might be due to the considerable number of our patients performing a profession requiring skilled manual labour that were liable for injuries of the hand. Although pain was overall mild, we found a higher degree of disability in those patients reporting pain.

Being a single-centre, retrospective study, there are some limitations, e.g. lack of critical data in surgical reports, patients lost to follow-up and the small number of cases. We chose QST for sensory assessment as it provides much more information than 2PD testing, including the quantification of loss and also gain of function (hyperalgesia, allodynia) (Backonja et al., 2013; Krumova et al., 2012; Rolke et al., 2006). However, 2PD testing would have allowed better comparison with previous studies. As a psychophysical measure, QST is not as objective as nerve conduction studies. Nevertheless, due to the standardized protocol (Rolke et al., 2006) and training (Vollert et al., 2015), a high level of reliability is guaranteed (Geber et al., 2011). In patients with PNI, standardized QST provides stable results in certified laboratories across Europe (Vollert et al., 2016).

After both treatments, recovery of small-fibre function was satisfactory, whereas there was incomplete recovery of large nerve-fibres, especially resulting in an impaired perception of touch. Therefore, there is a need for further improvement of treatment. As proven in animal studies (Brandt et al., 2015; Goulart et al., 2014) and in treatment of other diseases (David et al., 2015), motor and sensory re-education seems to be a promising approach towards improving the results of nerve regeneration.

Footnotes

Acknowledgements

The authors thank Monika Pennekamp and Annette Kühl for training in QST and Elena Enax-Krumova for comments that improved the manuscript. This work is part of the doctoral thesis of Julika L. Huber.

Conflict of interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by research funds of the BG Trauma Center Duisburg, Germany. The sponsor had no role in the study design, collection, analysis or interpretation of data.

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