0% found this document useful (0 votes)
13 views5 pages

bhandari2019 (1)

Uploaded by

nadatox20
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
0% found this document useful (0 votes)
13 views5 pages

bhandari2019 (1)

Uploaded by

nadatox20
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 5

Journal of Clinical Orthopaedics and Trauma 10 (2019) 862e866

Contents lists available at ScienceDirect

Journal of Clinical Orthopaedics and Trauma


journal homepage: www.elsevier.com/locate/jcot

Management of peripheral nerve injury


P.S. Bhandari
Department and Institution, Department of Plastic Surgery, Brijlal Superspeciality Hospital Haldawni, Nainital, PIN 263139, India

a r t i c l e i n f o

Article history:
Received 8 July 2019
Accepted 8 August 2019
Available online 13 August 2019

various degrees of nerve injury.


1. Introduction

1.2. Pathophysiology of nerve injury e


Peripheral nerve injuries are frequently encountered in clinical
practice and often result in functional disability. In the past, due to
During first few days after axonal injury, local degenerative
poor understanding of pathophysiology, the results of nerve repair
events are accompanied by both retrograde and anterograde
were unpredictable. Sunderland1 in 1945 described the microsur-
degeneration of axon and myelin. During the intermediate phase (a
gical techniques which improved the results of nerve repairs. In the
few days to weeks), the anterograde pattern of Wallerian degen-
past few decades an understanding of nerve regeneration, advances
eration proceeds to completion with infiltrating macrophages
in microsurgical techniques, along with ongoing research in mo-
contributing to the removal of tissue debris and Schwann cells
lecular biology has helped in improving the results in peripheral
undergoing mitosis.4 The axotomised neuronal cell body undergoes
nerve surgery.
reactive, chromatolytic changes and the severed proximal end of
the axon develops regenerative axonal sprouts. Of the numerous
1.1. Classification of nerve injuries
axonal sprouts that successfully traverse the injury site (during the
first few weeks to months), some re-enter appropriate endoneurial
Seddon2 classified nerve injuries into three broad categories;
tubes and continue to extend through the distal nerve stump.
neurapraxia, axonotmesis, and neurotmesis. In neurapraxia, tran-
Failure of regenerating axonal sprouts to cross the injury site
sient functional loss is observed without affecting loss of nerve
(possibly due to the formation of a physical scarring barrier or the
continuity. A complete disruption of the nerve axon and sur-
loss of a large segment of nerve) results in neuroma formation. In
rounding myelin along with preservation of perineurium and
the proximal stump, the shortening of axon and myelin occurs due
epineurium is observed in axonotmesis. Neurotmesis causes com-
to degradative action by Schwann cells. Either the proximal
plete functional loss because of disconnection of a nerve. Sunder-
degradation can be negligible covering the injury site till the next
land's classification system classifies nerve injuries to five
node of Ranvier or it can entirely extend up to the cellular body.
categories according to severity. A first-degree injury is comparable
to Seddon's neurapraxia. In second and third-degree there is
disruption of the axon and is equivalent to axonotmesis. In fourth- 1.3. Neurotrophic factor in nerve regeneration
degree injury there is disruption of axon, endoneurium and peri-
neurium. There is a complete loss of continuity of nerve in fifth- Nerve growth factor (NGF) was the first neurotrophic factor to
degree corresponding to neurotmesis. While Seddon classification be identified. Other neurotrophic factor like brain derived neuro-
is simpler to follow, Sunderland grading is more often used by trophic factor, ciliary neurotrophic factor and glial derived neuro-
surgeons to take a decision on nerve repair. In 1989, Mackinnon3 trophic factor (GDNF) are important factors in nerve repair. They
has added a sixth-degree injury, which is a combination of are released from the target organs and Schwann cells which are
believed to be transferred to cell body in a retrograde fashion by the
axon.5 Any disruption of the transport of NGF is a trigger factor for
E-mail address: [email protected]. the repair process. The neurotrophic factors provide continuous

https://doi.org/10.1016/j.jcot.2019.08.003
0976-5662/© 2019 Delhi Orthopedic Association. All rights reserved.
P.S. Bhandari / Journal of Clinical Orthopaedics and Trauma 10 (2019) 862e866 863

stimulus for growth as well guide for advancing axons. Whitworth


et al. observed that administration of exogenous NGF resulted in
sustained axon regeneration which has been related to reduction in
the incidence of neuronal cell death.6 Similarly GDNF has a bene-
ficial effect on axonal regeneration and improves the conduction
velocity of motor neurons following regeneration and that of small
diameter sensory neurons.7,8

1.4. Diagnosis of nerve injury

Nerve injury clinically manifests as loss of motor (Fig. 1), sensory


(Fig. 2) and autonomic functions. These must be evaluated at the
time of nerve injury and findings meticulously documented. It is
important to distinguish between neuropraxia, axonotmesis and
neurotmesis. While complete recovery is expected in neuropraxia
and axonotmesis, neurotmesis will not recover without surgical
intervention. This distinction may be difficult at times and hence Fig. 2. Sensory impairment in ulnar nerve injury.
there is a role for electrophysiological studies in the diagnosis of
nerve injuries. They are also helpful in documenting recovery and
in the diagnosis of compressive neuropathies. studies are helpful in deciding the timing of surgery in these
patients.
1.5. Electromyography (EMG)
1.8. Surgical repair
The recording of muscle action potential can help in doc-
umenting the extent of denervation as well as its distribution.9 The core issue in a peripheral nerve surgery is tension free
EMG studies should be done after 2e3 weeks of injury for the coaptation of nerve ends with minimum number of nonabsorbable
muscle to show denervation changes. Complete denervation is monofilament sutures. The tension in the suture line is associated
characterized by low amplitude sharp waves or fibrillation poten- with increased fibrotic reaction and poor regeneration.11 Best re-
tial with muscle at rest and absent evoked muscle action potential sults of nerve repair are possible with correct matching of motor
(MUAP). With reinnervation these changes begin to reverse. and sensory component. Intraoperative motor-sensory differenti-
ation is possible with immunohistochemical and electrophysio-
1.6. Nerve conduction studies (NCS) logical methods.12 A divided nerve gap can be bridged by number of
means which include direct repair, nerve grafts and nerve conduits.
They play an important role in identifying the type and age of However, in cases where these are not feasible, nerve transfers and
peripheral nerve injury. In neuropraxia compound muscle action neurotization can be performed to achieve good functional
potential (CMAP) amplitude remains normal distal to the site of outcome.
injury and drops to zero with proximal site stimulation. In axonal
injury the CAMP is present in the first week and thereafter falls 1.9. Basic principles in nerve repair
rapidly after Wallerian degeneration has occurred.10
A meticulously performed nerve repair allows the growth of the
1.7. Management of nerve injuries regenerating axons into the endoneurial tubes of the distal nerve
stump with minimal loss of regenerating axons.
When a nerve injury is identified, the dilemma is when to Certain basic principles are followed in nerve repair-
operate, and what kind of repair should be undertaken. If the nerve
injury is due to penetrating trauma with neurological deficit, im- 1. A good illumination is essential
mediate exploration and repair of nerve is indicated. However, if 2. A bloodless field is achieved, either with a proximal tourniquet
the mechanism is due to blunt trauma the serial examination is or local tumescent infiltration
necessary for allowing spontaneous recovery to occur. In these 3. Nerve repairs are performed under magnification. Nerve
circumstances delayed repair can be done. Electrophysiological dissection is performed under loupe magnification and coap-
tation is done under an operating microscope
4. Appropriate microsurgical instrumentation with suture mate-
rials and/or tissue glue
5. Nerve are manipulated with microinstruments and repaired
with microsutures
6. Keyhole surgery is avoided. Incision is extended both proximally
and distally to get a good exposure of nerve ends (Fig. 3)

1.10. Direct nerve repair

A direct repair is recommended if two nerve ends can be held


without tension by a single 8-0 suture.13 Three techniques are
described for direct nerve repair viz epineural repair, perineural
repair and group fascicular repair. The epineural repair is the
Fig. 1. Clawing of ring and little fingers in ulnar nerve injury. commonest form of nerve repair and is associated with certain
864 P.S. Bhandari / Journal of Clinical Orthopaedics and Trauma 10 (2019) 862e866

Fig. 3. Skin flaps raised both proximally and distally to get a good exposure of nerve
ends.
Fig. 5. Graft coaptation with fibrin glue.

advantages in terms of short operating time, technical ease and


consists of an entire nerve with its vascular pedicle used to restore
avoids injury to intraneural tissues and fascicles. The perineural
nerve functions. Doi et al.17 in their series of vascularised vs non
repair is indicated in nerve grafting and nerves with less than 5
vascularised nerve grafts concluded that vascularised nerve grafts
fascicles. The group fascicular repair can be performed at a site
are indicated when the nerve gap is more than 6 cms and associ-
where nerve has given branches and individual fascicles can be
ated with massive skin loss and poor tissue bed vascularity.
identified in the main trunk. Theoretically motor and sensory fas-
cicles can be matched and hence motor-sensory cross innervations
1.12. Nerve transfers
avoided.
Neurotization involves use of proximal functioning nerve as
donor nerve to repair the distal denervated nerve element (Fig. 6).
1.11. Repair by nerve grafts
The procedure therefore reinnervates the target organ from healthy
functional nerve. The technique popularised by Narakas has been
When nerve gap exceeds 2 cms and direct nerve repair is under
used extensively in brachial plexus injuries to reinnervate the distal
tension nerve grafts are indicated to bridge the divided nerve
muscles in cases of root avulsion or roots not found repairable.18
ends.14,15 Three common types of nerve grafts are cable grafts,
trunk grafts and vascularised nerve grafts. Cable grafts are multiple
2. Emerging concepts in peripheral nerve surgery
small caliber grafts from relatively dispensable nerves. The
commonly used nerves are sural, superficial radial sensory nerve,
2.1. End to side neurorraphy
anterior branch of median antebrachial cutaneous nerve and lateral
femoral cutaneous nerve.16 The graft length should be 10e20%
This technique of nerve coaptation was described by Letrevant
longer than the nerve gap to allow for shortening due to fibrosis
in 1893 in a case of nerves with loss of significant length. This was
(Fig. 4). The micro neural sutures or fibrin glue (Fig. 5) are used to
however abandoned due to poor results. In 1992 Viterbo et al.19
co-apt the multiple cables to match the diameter of the nerve.
reintroduced this technique which consists of coaptation of distal
Reversal of nerve grafts reduces the axonal disruption through the
stump of transected nerve to the trunk of adjacent donor nerve.
distal nerve branches.
This is considered as an alternative technique when the proximal
The trunk grafts are whole nerve grafts in a non functional nerve
stump is unavailable or the nerve gap is too long to be bridged by a
which can be used to reconstruct a nerve likely to function. How-
nerve graft.20
ever due to its thickness and ability to vascularise from the bed,
The nerve regeneration in end to side neurorraphy takes place
they are associated with poor results. Vascularised nerve grafts
by collateral sprouting. The regenerated axons emerge from the
most proximal node of Ranvier and travel in the epineurium of
donor nerve.21,22 In 1993 Viterbo used cross facial nerve graft

Fig. 4. Nerve gaps bridged with sural nerve grafts. Fig. 6. Distal nerve transfer in isolated musculocutaneous nerve injury.
P.S. Bhandari / Journal of Clinical Orthopaedics and Trauma 10 (2019) 862e866 865

transplantation using end to side neurorraphy in facial palsy.23 Amr advances there remains limited indications for its application
et al. reported satisfactory results in 11 cases of brachial plexus which include insufficient nerve autografts,34 limb transplantation
injury managed with end to side neurorraphy.24 Other authors25 and pre-existing immunesuppression. The duration of immune
have also reported promising results with this technique. Never- suppression required for nerve allograft remains undetermined.
theless this is an interesting technique and in the future it may be a Mackinnon reported return of motor and sensory functions in 6 out
viable option in peripheral nerve injuries. of 7 nerve allograft transplants to upper and lower limbs.35

2.2. Nerve conduits 2.4. Immune modulators in nerve repair

Use of cylindrical tube to bridge a gap between nerve ends has The use of immunosuppressant FK 506 (Tacrolimus) has been
been widely reported in current literature. Through neurotrophism shown to accelerate the nerve regeneration and functional recov-
the regeneration of axons occurs within this tube. Axons regener- ery. It acts via FK 506 binding protein (FKBP) receptors. The FKBP 12
ating from proximal stump grow through the conduit and selec- in receptor is responsible for immune suppression.36 The current
tively find their original pathways in the distal stump by application of FK 506 is in enhancing the nerve regeneration after
chemotactic attraction. This would negate the problem of cross nerve repair but its role as an adjunct to nerve allografting is
innervation of motor and sensory bundles. promising. Yan et al. in their experimental study on rat demon-
It avoids the morbidity associated with nerve graft. The semi strated significant therapeutic impact in short term use of FK 506 in
rigid tube prevents the soft tissue coming in between the nerve nerve regeneration. In future, the use of FK 506 is likely to play an
ends. Several studies have indicated the comparable results to important role in nerve regeneration.37
direct nerve repair and nerve grafts when nerve conduit was used
to reconstruct a short segment of nerve26,27(Fig. 7). The limitation 2.5. Results after peripheral nerve repair
of nerve conduits is the distance between the divided ends which
can be bridged. The 3e4 cms is the defining upper limit of nerve The outcomes of nerve reconstruction are influenced by multi-
gap which can be bridged with comparable results.28,29 Conduits factorial variables. In 1991, Sunderland made certain observations
from various biological and synthetic sources have been used. The regarding nerve repair. He found that outcomes in younger pa-
biological tubes include the use of arteries, veins, muscles and tients, early repair, repair close to target muscle, repair of single
modified biological tissues such as laminin and collagen. The lim- function nerve and short nerve graft had better outcomes. Kallio
itations of biological conduits in terms of early fibrosis, scar infil- et al.38 reported their results of 132 median nerve reconstruction
tration and tissue reaction have led to emergence of conduits made which were managed with nerve grafting and secondary neuror-
from synthetic materials. Commonly used synthetic conduits are raphy. They reported good to excellent results in 49%, fair results in
polyester such as polyglycolic acid, polylactic acid and poly- 11% and poor results in 40% of patients. The poor results were
galactin.30 In order to enhance nerve regeneration in these conduits associated with injury proximal to the elbow, age more than 54
the use of exogenous growth factors and neurotrophic factors have years, graft length of more than 7 cms and delayed surgery of more
been used.31 However for digital nerve repair excellent to good than 23 months. Similar results were published by Vastamaki
sensory function in 75% has been reported and for larger mixed et al.39 in reconstruction of ulnar nerve with 52% of patients
nerves functional recovery was obtained in 75% of patients with achieving useful recovery.
1e4 cms nerve gap reconstructed with conduits. Therefore the use
of nerve conduits in selected patients can produce comparable 3. Conclusion
results obviating the need for donor nerves and its resultant
morbidity. Despite advances in understanding of pathophysiology of nerve
injuries and advent of microsurgical techniques, the outcomes of
2.3. Nerve allografts repair have still not reached its zenith, with about 50% of patients
achieving useful nerve function. Current research in nerve injuries
The use of nerve allografts have been reported in primates by is challenging and newer modalities are under evaluation to further
Bain et al..32 The immunosuppressant FK 506 (Tacrolimus) has improve the results of nerve reconstruction.
benefitted the experimental allografting results which are compa-
rable with autografting in animal studies.33 However despite these Conflicts of interest

The author reports no conflict of interest. The author is


responsible for the content and writing of the paper.

References

1. Sunderland S. The anatomy and physiology of nerve injury. Muscle Nerve.


1990;13:771e784.
2. Seddon HJ. Three types of nerve injury. Brain. 1943;66:237e288.
3. Mackinnon SE. New directions in peripheral nerve surgery. Ann Plast Surg.
1989;22:257e273.
4. Menorca RM, Fussell TS, Elfar JC. Nerve physiology: mechanisms of injury and
recovery. Hand Clin. 2013;29:317e330.
5. Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief re-
view. Neurosurg Focus. 2004;16(5):1e7.
6. Taniuchi M, Clarke HB, Schweiter JB, et al. Expression of nerve growth factors
receptors by Schwann cells of axotomised peripheral nerves: ultra structure
location, suppression by axonal contact and binding providing properties.
Neuroscience. 1988;8:664e681.
7. Whitworth IH, Terenghiti G, Green CJ, Brown RA, Stevens E, Tomlinson DR.
Fig. 7. Use of a biodegradable nerve conduit to bridge a short nerve defect. Targeted delivery of nerve growth factor via fibronectin conduits assists nerve
866 P.S. Bhandari / Journal of Clinical Orthopaedics and Trauma 10 (2019) 862e866

regeneration in control and diabetic rats. Eur J Neurosci. 1995;7:2220e2225. 25. Menner U. Side to side nerve suture in clinical practice. Hand Surg. 2003;8:
8. Munson JB, McMahon SB. Effects of GDNF on axotomised sensory and motor 33e42.
neurons in adult rats. Eur J Neurosci. 1997;9:1126e1129. 26. Lundberg G, Rosen B, Dahlin L, Holmberger J, Rosen I. Tubular repair of median
9. Bennett DLH, Micheal GJ, Ramachandran N, et al. A distinct subgroup of small or ulnar nerve in human forearm: a 5 year follow up. J Hand Surg. 2004;29(3):
DRG cells express GDNF receptor components and GDNF is protective for these 100e107.
neurons after nerve injury. J Neurosci. 1998;18:3059e3072. 27. Weber RA, Breindenbach WC, Brown RE, Jabaley ME, Mass DP. A randomized
10. Bauwens P. Electrodiagnostic definition of the site and nature of peripheral prospective study of polyglycolic conduits for digital nerve reconstruction in
nerve lesions. Ann Phys Med. 1960;5:149e152. humans. Plast Reconstr Surg. 2000;106:1035e1045.
11. Chaudhary V, Gornblath DR. Wallerian degeneration in human nerves: serial 28. Dellon AL, Mackinnon SE. An alternative to classical nerve graft for the man-
electrophysiological studies. Muscle Nerve. 1992;15:687e693. agement of short nerve gap. Plast Reconstr Surg. 1988;82:849e856.
12. Terzis JK, Faibisoff BA, Williams HB. The nerve gap: suture under tension vs 29. Hung V, Dellon AL. Reconstruction of 4 cms human median nerve gap by
graft. Plast Reconstr Surg. 1975;56:166e170. including an autogenous nerve slice in a bioabsorbable nerve conduit: a case
13. Ramachandran S, Midha R. Recent advances in nerve repair. Neurol India. report. J Hand Surg. 2008;33(A):313e315.
2019;67:106e114. 30. Belkas JS, Schoichet MS, Midha R. Peripheral nerve regeneration through
14. Mackinnon SE. Surgical management of peripheral nerve gap. Clin Plast Surg. guidance tube. Neurol Res. 2004;26(2):151e160.
1989;16(3):587e603. 31. Daly W, Yao L, Zeugolis D, Windebank A, Pandit A. A biological approach to
15. Millesi H, Meissl G, Berger A. The interfasicular nerve grafting of median and peripheral nerve regeneration: bridging the peripheral nerve gap and
ulnar nerve. J Bone Joint Surg Am. 1972;54(4):727e750. enhancing functional recovery. J R Soc Interface. 2012;9:202e221.
16. Berger A, Millesi H. Nerve grafting. Clin Orthop Relat Res. 1978;133:49e55. 32. Bain JR, Mackinnon SE, Hudson AR, Wade J, Evans P, et al. The peripheral nerve
17. Doi K, Tamaru K, Sakai K, Kuwata N, Kurafuji Y, Kawai S. A comparison of allografts in primate immunosuppressed with cyclosporine A. Histologic and
vascularised and conventional sural nerve grafts. J Hand Surg. 1992;17A: electrophysiologic assessment. Plast Reconstr Surg. 1992;90:1036e1046.
670e676. 33. Weizwerg N, Grindel S, Gonzalez M, Kky D, Fang J, Sahani B. Peripheral nerve
18. Narakas AO, Hentz VR. Neurotization in brachial plexus injuries: indications allotransplantation in rats immunosuppressed with transient or long term FK
and results. Clin Orthop Relat Res. 1988;237:43e56. 506. J Reconstr Microsurg. 1996;12:451e459.
19. Viterbo F, Trindade JC, Hoshino K, Mazzoni NA. Latero-terminal neurorraphy 34. Siemionow M, Sonmez E. Nerve allograft transplantation: a review. J Reconstr
without removal of epineural sheath. Experimental study in rats. Rev Paul Med. Microsurg. 2007;23(8):511e520.
1992;110:267e275. 35. Mackinnon SE, Doolabh VB, Novak CB, Trulock EP. Clinical outcome following
20. Lykissas MG. Current concepts in the end to side neurorraphy. World J Orthop. nerve allograft transplantation. Plast Reconstr Surg. 2001;107:1419e1429.
2011;2(11):102e106. 36. Gold B. Neuroimmunophilin ligands: evaluation of their therapeutic potential
21. Tham SK, Morrison WA. Motor collateral sprouting through an end to side for the treatment of neurological disorder. Expert Opin Investig Drugs. 2000;9:
nerve repair. J Hand Surg. Am. 1998;23:844e845. 2331e2342.
22. Zhang Z, Soucacos PN, Beris AE, Bo J, Iaachim E, Johnson EO. Long term eval- 37. Yan Y, Sun HH, Hunter DA, Mackinnon SE, Johnson PJ. Efficacy of short term FK
uation of rat peripheral nerve repair with end to side neurorraphy. J Reconstr 506 administration on accelerating nerve regeneration. Neurorehabilitation
Microsurg. 2000;16:303e311. Neural Repair. 2012;26(6):570e580.
23. Viterbo P. A new method for treatment of facial palsy: the cross face nerve 38. Kallio PK, Vadtamaki M. An analysis of the results of late reconstruction of 132
transplantation with end to side neurorraphy. Rev Soc Bras Cir Plast Estet median nerve. J Hand Surg. 1993;18:97e105.
Reconstr. 1993;8:29e38. 39. Vastamaki PK, Kallio PK, Solomem KA. The results of ulnar nerve repair. J Hand
24. Amr SM, Moharram AN. Repair of brachial plexus lesion by end to side grafting Surg. 1993;18:323e326.
neurorraphy: experience based on 11 cases. Microsurgery. 2005;25:126e146.

You might also like