the brachial plexus consists of nerve roots c5t1 , which mainly innervate the muscles of the upper arm , and control the normal activities of these muscles .
brachial plexus injury , particularly total root avulsion , is one of the most serious disabilities of the extremities .
it has an unfavorable prognosis and may cause paralysis of part of or even the entire upper arm . therefore , treatment of brachial plexus injury is a major topic of study in the field of peripheral nerve injury .
nerve transfer is currently the optimal clinic strategy for the treatment of brachial plexus injury . to achieve good results from treatment ,
one major goal of this literature review is to provide a comprehensive survey on the numerous intra and extra - plexal nerves that have been used in transfer procedures , both within china and overseas , to repair brachial plexus injury .
the other goal is to discuss the role of candidate nerves for transfer in the surgical management of common severe brachial plexus problems encountered clinically .
nerve transfer involves the reconstruction of a distal de - innervated nerve by using a proximal foreign nerve as the donor of neurons and axons to re - innervate the distal targets ( chen et al . , 1994 ) .
two types of nerves can be used : extra - plexal donor nerves and intra - plexal donor nerves ( addas and midha , 2009 ) .
extra - plexal donor nerves include the intercostal nerve ( icn ) , spinal accessory nerve , cervical plexus , phrenic nerve and contralateral c7 root .
intra - plexal donor nerves include the ipsilateral nerve trunk and the bundle branch of the medial or ulnar nerves .
nerve transfer is indicated in the following situations ( hems , 2011 ) : ( 1 ) brachial plexus root avulsion or proximal intra - foraminal injury close to the spinal cord with no , or poor , nerve stump available for nerve grafting ; ( 2 ) proximal injury with a long distance to the target muscle ; ( 3 ) significant vascular or bony injuries in the region of the brachial plexus ; ( 4 ) previously failed attempts at brachial plexus or proximal nerve repair .
a review of the historical precedents as well as the anatomical basis and rationale for nerve transfers in brachial plexus surgery was clearly presented 30 years ago ( gu , 2005 ) . since then
, nerve transfer procedures have been increasingly performed to treat severe brachial plexus injury , and the methods of treatment for total brachial plexus root avulsion have continued to improve ( mcguiness and kay , 2002 ; bertelli and ghizoni , 2003 ) . according to the site of injury , lesions of the brachial plexus are classified as either preganglionic or postganglionic . for a postganglionic lesion , conservative treatment or nerve grafting , including nerve suture or neurolysis , can often achieve good results .
extra - plexal or intra - plexal donor nerve transfer or an alternative reconstructive procedure should be considered without delay .
the former involves the following nerve transfers : icn transfer to the axillary nerves , and accessory nerve transfer to the suprascapular nerves , phrenic nerve transfer to the musculocutaneous nerves , and contralateral c7 nerve transfer to the median nerves or radial nerves . in intra - plexal nerve transfer , part of the bundle branch of the ulnar or median nerves is transferred to the musculocutaneous nerves , or the branch of the radial nerve supplying the long head of the triceps brachii is transferred to the axillary nerves .
the first is to re - innervate the recipient nerve as closely as possible to the target organ .
the outcome of nerve transfers is enhanced when the donor and recipient are properly selected , as cortical re - adaptation is the physiological basis of functional recovery .
the concept of icn transfer for repairing brachial plexus injury can be credited to seddon , tsuyama and nagano .
he used the ulnar nerve as a nerve graft to connect the icns to the musculocutaneous nerve .
six years later , tsuyama improved seddon 's method by directly splicing icns to the musculocutaneous nerve , thus achieving satisfactory results . after reviewing 159 cases , nagano et al .
( 1989 ) concluded that using the fish - mouth technique during suturing achieved the highest efficacy in nerve transfer procedures .
based on these principles , gu ( 2005 ) made the following conclusions based on his own clinical practice : ( 1 ) when cutting out icns , the fourth icn should be used as the center ; ( 2 ) when transferring to the musculocutaneous nerve , at least two icns should be sutured ; ( 3 ) when cutting out three icns , transverse incisions should be made along the intercostal spaces ; ( 4 ) while cutting out at least four icns , a longitudinal incision should be made along the anterior axillary line . with innovations based on these principles ,
the efficacy of nerve transfer has increased to 67.39% . since then , icns have been commonly used as extra - plexal donor nerves .
they are commonly transferred to the thoracodorsal nerves and the branch of the radial nerve supplying the long head of the triceps brachii to restore shoulder abduction and external rotation ( terzis and kokkalis , 2008 ) .
this is of great significance for patients who have severe brachial plexus injury involving the c5t1 roots , where the sources of the donor nerves are limited ( midha , 2004 ) .
better results can be achieved in patients younger than 30 years old who receive the operation within 6 months of injury ( nagona , 1998 ) .
classified as an extra - plexal nerve , sans are rarely injured in patients who have brachial plexus injury ( samardzi et al . , 2000 ) . when they were first used in 1972
since then , sans have been transferred to suprascapular and musculocutaneous nerves to restore shoulder abduction and elbow flexion , respectively .
brunelli and brunelli ( 1991 ) showed that san transfer to the suprascapular nerves was the best solution because the supraspinatus and infraspinatus muscles are supplied by similar nerves . in 1987
, gu proved that the efficacy of directly suturing sans to suprascapular nerves was higher than that of using a nerve graft .
the closer the transfer is to the target muscle , the shorter the distance the regenerating axons have to travel and the better the functional re - innervation ( addas and midha , 2009 ) .
traditionally , accessory to suprascapular nerve transfer has been accomplished through an anterior supraclavicular approach . however , there are some disadvantages of this method , such as scarring , nerve retraction or displacement , and nerve tumor .
each of these complications may cause difficulties when searching for the suprascapular and accessory nerves .
consequently , clinicians have started to use a posterior approach , particularly when transfer of the triceps branch of the axillary nerve is considered in combination to accessory nerve transfer ( rui et al . , 2013 ) .
colbert and mackinnon ( 2006 ) used the posterior approach , and achieved better protection to the nerves supplying the trapezius as well as better recovery of shoulder abduction in comparison to the anterior approach .
plate et al . ( 2011 ) came to the same conclusion after treating nine patients using combined nerve transfer .
the posterior approach offers the following advantages : ( 1 ) it is better for functional recovery as the anastomosis lies next to the target muscles ; ( 2 ) anatomically , the scapular nerve and accessory nerve can be easily tracked , maintaining a fixed location when descending to shoulder level ; ( 3 ) this operation relieves nerve compression syndrome of the suprascapular nerve caused by the transverse ligament
. a larger number of cases will be needed to evaluate its efficacy compared with the traditional method , because the number of distal fibers of the accessory nerve is substantially low ( lao , 2010 ) .
the phrenic nerve originates mainly from the fourth cervical root , while both c3 and c5 roots contribute to and augment the nerve . as a result
, it contains more pure motor axons than other nerves , allowing for the possibility of partial or complete nerve transfer with great success ( viterbo et al . , 1995 ) .
injury to both c4 and c5 is uncommon as both nerve roots are strongly bound by fibrous tissue forming a chute - like structure .
liu et al . ( 2014 ) compared the vascularized phrenic nerve transfers of 14 patients with the non - vascularized phrenic nerve transfers of 19 patients .
no statistically significant difference was found between the two groups after a 3-year follow up .
this is most likely because the nerve itself has a small diameter and a well - vascularized bed . in recent years
, the thoracoscope has been widely used in cutting out the phrenic nerve . in 1999 ,
preliminary results showed that this method was used to transfer the phrenic nerve to the ulnar nerve , successfully restoring thumb flexion in 20 patients . compared with traditional methods used in cutting out the phrenic nerve , the length of the excised nerve
2002 ) successfully cut out the full length of the phrenic nerve with the aid of a thoracoscope and transferred it to the musculocutaneous nerve .
this method reduced the recovery time for elbow flexion to an average of just 5 months .
( 1995 ) showed that the lower icns of rats also participated in the innervation of the diaphragm .
when the phrenic nerve is sacrificed for nerve transfer , respiratory function decreases by an average of 10% ( luedemann et al . , 2002 ) .
this can produce symptoms in high oxygen demand situations , particularly in infants and children with respiratory infections . in 2006 , jiang et al .
( 2006 ) found a statistically significant drop in vital capacity when using the right phrenic nerve compared with the left .
he demonstrated that transposition of the left phrenic nerve does not lead to severe respiratory dysfunction .
consequently , clinicians should be cautious when using the right phrenic nerve if maximal inspiratory pressure is low preoperatively . until a long - term follow - up study is completed
the contralateral c7 root has a large number of nerve fibers ( approximately 420,00 ) , and it was first used for nerve transfer in 1986 ( gu et al . , 1992 ) .
since then , many clinical cases and experiments have demonstrated that transfer using this root can achieve very good outcomes ( kim et al . , 2003 ) .
also , there is little risk to function by harvesting the c7 spinal nerve , providing additional sources of donor nerves ( gu et al . ,
contralateral c7 nerve transfer has been widely used , both within china and overseas , for shoulder and elbow restoration
. this method returns grasp function and achieves sensory recovery , and is considered a major breakthrough in the treatment of brachial plexus injury .
contralateral c7 nerve transfer is an optimal strategy for treating brachial plexus injury ( dubuisson and kline , 2002 ; friedman et al . ,
1990 ) , especially when root avulsion and phrenic and accessory nerve damage is encountered simultaneously .
in this situation , contralateral c7 transfer is the only solution ( terzis and kokkalis , 2010 ) .
the procedure for contralateral c7 nerve transfer can be divided into two stages ; stage i and stage ii ( gu et al , 1992 ) . in stage
i , the contralateral c7 root is transferred to the nerve graft ( ulnar nerve with vessel pedicle is frequently used ) , and in stage ii , the other part of the nerve graft is transferred to the recipient nerve , including the median nerve and radial nerve .
there are numerous follow - up patient reports , providing evidence of the importance of such a division .
( 1999 ) reported that only 20% of the 96 patients who underwent contralateral c7 nerve root transfer regained forearm and hand flexor muscle strength to grade 3 or 4 , measured using the modified mrc scale , within period i. lao ( 2010 ) concluded that different methods contributed to the large disparity in the proportion of patients who achieved strength recovery during periods i and ii36% and 63% , respectively .
cortical plasticity appears to play an important physiological role in the functional recovery of the re - innervated muscles .
recently , an increasing number of investigators have focused their attention on cerebral plasticity following contralateral cervical nerve transfer in humans .
2001 ) have shown that the brain is capable of extensive reorganization after the peripheral nervous system is injured ( wang et al . , 2010 ) .
contralateral c7 nerve transfer provides an ideal opportunity to study the relationship between brachial plexus injury and cortical reorganization ( florence et al . , 1996 ) .
peripheral nerve conduction testing shows that degeneration and regeneration after peripheral nerve injury are complex processes .
physiological changes occur not only at the site of injury , but also upstream ( brain and spinal cord ) and downstream ( muscles and effectors ) of the damage ( kemp et al . , 2010 ) .
peripheral nerve injuries block the flow of output from the motor cortex to the denervated muscles , thereby resulting in paralysis .
however , with the gradual maturation of regenerating axons , the dominant functions of the muscles eventually recover ( muetn - gmez et al . , 2004 ;
( 2004 , 2005 ) showed that plastic changes indeed take place in the contralateral motor cortex of adult rats with total brachial plexus root avulsion .
( 2005 ) demonstrated changes within the primary motor cortex of patients who underwent contralateral c7 nerve translocation following brachial plexus injury using functional mri .
he also proposed that earlier rehabilitation of the affected limb results in better and more extensive cortical reorganization . in 2012 , liu et al .
( 2012 ) used contralateral c7 nerve transfer to treat six patients with central spastic hemiplegia .
after a 2-year follow - up , they concluded that functional recovery of the affected limb , particularly of the wrist and elbow , was satisfactory . in patients with total root avulsion of the brachial plexus ,
elbow flexion is restored by icn transfer , and shoulder function is restored by shoulder arthrodesis .
hand function is restored by an icn transfer for the median nerve , or by free muscle transplantation in combination with nerve transfer ( nagano , 1998 ) .
different neural transplantation approaches for the treatment of brachial plexus injury provide differential outcomes , but direct transplantation of collateral branches are associated with better outcome compared with the use of other nerve plexuses , especially in patients with delayed treatment ( bertelli and ghizoni , 2010 ) .
the concept of icn transfer for repairing brachial plexus injury can be credited to seddon , tsuyama and nagano .
he used the ulnar nerve as a nerve graft to connect the icns to the musculocutaneous nerve .
six years later , tsuyama improved seddon 's method by directly splicing icns to the musculocutaneous nerve , thus achieving satisfactory results . after reviewing 159 cases , nagano et al .
( 1989 ) concluded that using the fish - mouth technique during suturing achieved the highest efficacy in nerve transfer procedures .
based on these principles , gu ( 2005 ) made the following conclusions based on his own clinical practice : ( 1 ) when cutting out icns , the fourth icn should be used as the center ; ( 2 ) when transferring to the musculocutaneous nerve , at least two icns should be sutured ; ( 3 ) when cutting out three icns , transverse incisions should be made along the intercostal spaces ; ( 4 ) while cutting out at least four icns , a longitudinal incision should be made along the anterior axillary line . with innovations based on these principles ,
the efficacy of nerve transfer has increased to 67.39% . since then , icns have been commonly used as extra - plexal donor nerves .
they are commonly transferred to the thoracodorsal nerves and the branch of the radial nerve supplying the long head of the triceps brachii to restore shoulder abduction and external rotation ( terzis and kokkalis , 2008 ) .
this is of great significance for patients who have severe brachial plexus injury involving the c5t1 roots , where the sources of the donor nerves are limited ( midha , 2004 ) .
better results can be achieved in patients younger than 30 years old who receive the operation within 6 months of injury ( nagona , 1998 ) .
classified as an extra - plexal nerve , sans are rarely injured in patients who have brachial plexus injury ( samardzi et al . , 2000 ) . when they were first used in 1972
since then , sans have been transferred to suprascapular and musculocutaneous nerves to restore shoulder abduction and elbow flexion , respectively .
brunelli and brunelli ( 1991 ) showed that san transfer to the suprascapular nerves was the best solution because the supraspinatus and infraspinatus muscles are supplied by similar nerves . in 1987
, gu proved that the efficacy of directly suturing sans to suprascapular nerves was higher than that of using a nerve graft .
the closer the transfer is to the target muscle , the shorter the distance the regenerating axons have to travel and the better the functional re - innervation ( addas and midha , 2009 ) .
traditionally , accessory to suprascapular nerve transfer has been accomplished through an anterior supraclavicular approach . however , there are some disadvantages of this method , such as scarring , nerve retraction or displacement , and nerve tumor .
each of these complications may cause difficulties when searching for the suprascapular and accessory nerves .
consequently , clinicians have started to use a posterior approach , particularly when transfer of the triceps branch of the axillary nerve is considered in combination to accessory nerve transfer ( rui et al .
colbert and mackinnon ( 2006 ) used the posterior approach , and achieved better protection to the nerves supplying the trapezius as well as better recovery of shoulder abduction in comparison to the anterior approach .
plate et al . ( 2011 ) came to the same conclusion after treating nine patients using combined nerve transfer .
the posterior approach offers the following advantages : ( 1 ) it is better for functional recovery as the anastomosis lies next to the target muscles ; ( 2 ) anatomically , the scapular nerve and accessory nerve can be easily tracked , maintaining a fixed location when descending to shoulder level ; ( 3 ) this operation relieves nerve compression syndrome of the suprascapular nerve caused by the transverse ligament
. a larger number of cases will be needed to evaluate its efficacy compared with the traditional method , because the number of distal fibers of the accessory nerve is substantially low ( lao , 2010 ) .
the phrenic nerve originates mainly from the fourth cervical root , while both c3 and c5 roots contribute to and augment the nerve . as a result
, it contains more pure motor axons than other nerves , allowing for the possibility of partial or complete nerve transfer with great success ( viterbo et al . , 1995 ) . for a complete phrenic nerve ,
injury to both c4 and c5 is uncommon as both nerve roots are strongly bound by fibrous tissue forming a chute - like structure .
liu et al . ( 2014 ) compared the vascularized phrenic nerve transfers of 14 patients with the non - vascularized phrenic nerve transfers of 19 patients .
no statistically significant difference was found between the two groups after a 3-year follow up .
this is most likely because the nerve itself has a small diameter and a well - vascularized bed . in recent years
, the thoracoscope has been widely used in cutting out the phrenic nerve . in 1999 ,
preliminary results showed that this method was used to transfer the phrenic nerve to the ulnar nerve , successfully restoring thumb flexion in 20 patients . compared with traditional methods used in cutting out the phrenic nerve ,
the length of the excised nerve can be increased by using a thoracoscope . in 2002 ,
xu et al . ( 2002 ) successfully cut out the full length of the phrenic nerve with the aid of a thoracoscope and transferred it to the musculocutaneous nerve .
this method reduced the recovery time for elbow flexion to an average of just 5 months .
( 1995 ) showed that the lower icns of rats also participated in the innervation of the diaphragm . when the phrenic nerve is sacrificed for nerve transfer , respiratory function decreases by an average of 10% ( luedemann et al . , 2002 ) .
this can produce symptoms in high oxygen demand situations , particularly in infants and children with respiratory infections . in 2006 , jiang et al .
( 2006 ) found a statistically significant drop in vital capacity when using the right phrenic nerve compared with the left .
he demonstrated that transposition of the left phrenic nerve does not lead to severe respiratory dysfunction .
consequently , clinicians should be cautious when using the right phrenic nerve if maximal inspiratory pressure is low preoperatively . until a long - term follow - up study is completed
the contralateral c7 root has a large number of nerve fibers ( approximately 420,00 ) , and it was first used for nerve transfer in 1986 ( gu et al . , 1992 ) .
since then , many clinical cases and experiments have demonstrated that transfer using this root can achieve very good outcomes ( kim et al . , 2003 ) .
also , there is little risk to function by harvesting the c7 spinal nerve , providing additional sources of donor nerves ( gu et al . , 2003 ) .
contralateral c7 nerve transfer has been widely used , both within china and overseas , for shoulder and elbow restoration
. this method returns grasp function and achieves sensory recovery , and is considered a major breakthrough in the treatment of brachial plexus injury .
contralateral c7 nerve transfer is an optimal strategy for treating brachial plexus injury ( dubuisson and kline , 2002 ; friedman et al . ,
1990 ) , especially when root avulsion and phrenic and accessory nerve damage is encountered simultaneously .
in this situation , contralateral c7 transfer is the only solution ( terzis and kokkalis , 2010 ) .
the procedure for contralateral c7 nerve transfer can be divided into two stages ; stage i and stage ii ( gu et al , 1992 ) . in stage
i , the contralateral c7 root is transferred to the nerve graft ( ulnar nerve with vessel pedicle is frequently used ) , and in stage ii , the other part of the nerve graft is transferred to the recipient nerve , including the median nerve and radial nerve .
there are numerous follow - up patient reports , providing evidence of the importance of such a division .
( 1999 ) reported that only 20% of the 96 patients who underwent contralateral c7 nerve root transfer regained forearm and hand flexor muscle strength to grade 3 or 4 , measured using the modified mrc scale , within period i. lao ( 2010 ) concluded that different methods contributed to the large disparity in the proportion of patients who achieved strength recovery during periods i and ii36% and 63% , respectively .
cortical plasticity appears to play an important physiological role in the functional recovery of the re - innervated muscles .
recently , an increasing number of investigators have focused their attention on cerebral plasticity following contralateral cervical nerve transfer in humans .
2001 ) have shown that the brain is capable of extensive reorganization after the peripheral nervous system is injured ( wang et al . , 2010 ) .
contralateral c7 nerve transfer provides an ideal opportunity to study the relationship between brachial plexus injury and cortical reorganization ( florence et al . , 1996 ) .
peripheral nerve conduction testing shows that degeneration and regeneration after peripheral nerve injury are complex processes .
physiological changes occur not only at the site of injury , but also upstream ( brain and spinal cord ) and downstream ( muscles and effectors ) of the damage ( kemp et al . , 2010 ) .
peripheral nerve injuries block the flow of output from the motor cortex to the denervated muscles , thereby resulting in paralysis .
however , with the gradual maturation of regenerating axons , the dominant functions of the muscles eventually recover ( muetn - gmez et al .
( 2004 , 2005 ) showed that plastic changes indeed take place in the contralateral motor cortex of adult rats with total brachial plexus root avulsion .
( 2005 ) demonstrated changes within the primary motor cortex of patients who underwent contralateral c7 nerve translocation following brachial plexus injury using functional mri .
he also proposed that earlier rehabilitation of the affected limb results in better and more extensive cortical reorganization . in 2012 , liu et al .
( 2012 ) used contralateral c7 nerve transfer to treat six patients with central spastic hemiplegia .
after a 2-year follow - up , they concluded that functional recovery of the affected limb , particularly of the wrist and elbow , was satisfactory .
in patients with total root avulsion of the brachial plexus , elbow flexion is restored by icn transfer , and shoulder function is restored by shoulder arthrodesis .
hand function is restored by an icn transfer for the median nerve , or by free muscle transplantation in combination with nerve transfer ( nagano , 1998 ) .
different neural transplantation approaches for the treatment of brachial plexus injury provide differential outcomes , but direct transplantation of collateral branches are associated with better outcome compared with the use of other nerve plexuses , especially in patients with delayed treatment ( bertelli and ghizoni , 2010 ) .
the use of nerve transfers has been a major advancement in the field of brachial plexus nerve reconstructive surgery .
many different and ingenious transfer strategies have been developed and have helped enhance functional recovery .
root avulsion of the brachial plexus should be treated with comprehensive treatment and rehabilitation ( korak et al . , 2004 ) .
the efficacy of treatment is strongly impacted by the following factors : ( 1 ) type of involved roots ; ( 2 ) time period between injury and operation ; ( 3 ) degree of damage ; ( 4 ) restorative exercises post - operation ; and ( 5 ) co - therapy of the central nerves . a large number of clinical and animal experiments have shown that a combined treatment approach involving the brain , spinal cord and effectors that control muscle movement is required to obtain satisfactory clinical results in the rehabilitation of brachial plexus root avulsion .
 in the treatment of brachial plexus injury , nerves that are functionally less important are transferred onto the distal ends of damaged crucial nerves to help recover neuromuscular function in the target region . 
 for example , intercostal nerves are transferred onto axillary nerves , and accessory nerves are transferred onto suprascapular nerves , the phrenic nerve is transferred onto the musculocutaneous nerves , and the contralateral c7 nerve is transferred onto the median or radial nerves . 
 nerve transfer has become a major method for reconstructing the brachial plexus after avulsion injury . 
 many experiments have shown that nerve transfers for treatment of brachial plexus injury can help reconstruct cerebral cortical function and increase cortical plasticity . in this review article , we summarize the recent progress in the use of diverse nerve transfer methods for the repair of brachial plexus injury , and we discuss the impact of nerve transfer on cerebral cortical plasticity after brachial plexus injury . 
Introduction
Treatment Options for Brachial Plexus Injury
Intercostal nerves
Spinal accessory nerve (SAN)
Phrenic nerve
Contralateral C
Combined application
Expectations