4. Surgical technique of human NR reimplantation

Surgical techniques can be useful, particularly in complete BPA and with a delay between the injury and the surgical repair of no longer than 4 weeks [45]. Some significant problems are that MN apoptosis is greater as the time goes by [20, 27, 91, 93, 101–103] and that by 4 weeks, there is a dense scar around the BP as well as the avulsed NRs and in their intervertebral foramina that hinders any surgical manoeuvres [45, 74].

The surgical approaches described can be summarized into posterior subscapular [192], lateral [193], anterolateral [194, 195] and single-stage combined anterior (first) and posterior (second) [33].

#### 4.1. Posterior subscapular approach

this drug—increase in erythrocyte production and a prothrombotic state—are not problematic because this drug is only administered for 3 days [118]. Perhaps administering this drug for a longer period of time could provide additional neuroprotective effects, but 3 days are enough to prolong the period in which a successful NR reimplantation can be performed [118].

FK506-tacrolimus improved the amount of regenerating posterior NR axons penetrating the

Acamprosate is a taurine analogue used to prevent relapse in alcoholic patients that acts as

Ribavirin is a nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis that

N-Acetyl cysteine administered intraperitoneally and intrathecally in rats enhances the rate of

Glatiramer is a polymer of L-alanine, L-glutamic acid, L-lysine and L-tyrosine that structurally resembles the myelin basic protein and that when administered daily reduces the gliosis and

To summarize, in NRA reimplantation GDGF applied directly to the anterior SC—to the point where the motor rootlets go out—associated with oral riluzole provides the highest rate of MN survival and axonal regeneration [8]. For the dorsal root, CNTF [87] applied directly to the section of the posterior SC where the sensory rootlets get in combined with oral N-acetyl cysteine [155] allows maximal sensory neuron survival. Other agents could be added, such as oral minocycline [106, 120], tacrolimus [151] or recombinant erythropoietin [118, 165]to reduce the reactive glial proliferation that impairs the axonal regeneration. ISP should be administered subcutaneously to minimize astrocyte inhibition of axonal regeneration [126, 167]. The

Another strategy has been to apply pluripotent cells at the SC avulsion site to improve MN survival and axonal regeneration. These have been particularly useful in minimizing neuronal apoptosis. Among them are induced pluripotent stem cells (iPSC) [143], mesenchymal stem cells (MSCs) [168–170], olfactory ensheathing glial cells (OECs) [85, 171], bone marrow stem cells (BMC) [172], human fibroblast growth factor 2 (FGG2) [95], neuroectodermal stem cells (ESC) [143], murine neural crest stem cells (MNCSC) [173], embryonic stem cell-derived neuron precursors (ESCDNP) [173] and neural progenitor cells (NPC) [140, 141, 168, 174]. The human embryonic stem cells overexpressing human fibroblast growth factor 2 (FGG2) applied at the injury site improved MN survival and reduced the glial reactivity, thus improving the regenerating capacities [95]. However, it has unknown effectivity, only shown in animal

experimental studies, and its application in the human being creates ethical issues.

Some researchers have found in vivo that a week time gap between NG harvest and its subsequent use in nerve repair improves the regenerating capacities [175] by increasing the number of Schwann cells and macrophages inside the NG [145, 176, 177] as well as by inducing the local GDNF release [145, 178, 179]. This is another possibility but difficult to use

is administered together with acamprosate to encourage axonal regeneration [154].

MN survival and facilitates regeneration in case of NR reimplantation [155].

SC and reaching the posterior horn [151].

54 Treatment of Brachial Plexus Injuries

the avulsed MN synaptic stripping [156].

data are summarized in Table 1.

in clinical practice.

neuroprotective and accelerates axonal regeneration [154, 166].

With the patient in the prone position, a longitudinal incision is made halfway between the spine and the scapula [39, 192, 196]. The trapezius muscle is sectioned transversally in the direction of its fibers. The rhomboid major and minor muscles are also divided following the direction of their fibers. The T1 transverse process is identified and removed with the aid of a drill. A section of the first rib is also removed. A laminectomy and facetectomy are needed to access the spinal canal. The dura is opened and the dentate ligaments sectioned to rotate the SC to reach the implantation site of the ventral roots. As no access to the anterior structures is possible, another anterior approach to the BP is needed to identify and mobilize it and to pass the NGs from one surgical field to the other [7]. Depending on the degree of bone removal, a posterior cervical fusion might be required. This approach only allows access to the avulsed NRs that lie inside the spinal canal or outside it but very close to the foramina [39]. Only one case was reported in 1995 [39], which did not spark much interest within the BP surgical community. Currently this technique is not used for NR reimplantation.

and laminae. The transverse processes and the anterior and posterior tubercles are exposed by removing all the muscles attaching to them. These bone structures plus a section of the lateral mass are removed and a C5-C7 hemilaminectomy performed. The removed bone pieces are

Nerve Root Reimplantation in Brachial Plexus Injuries http://dx.doi.org/10.5772/intechopen.82431 57

Care must be taken with the vertebral artery, as it does not need to be mobilized. As most of the lateral mass, the disc and the contralateral facet joints are spared; the procedure usually does not induce spine instability. The avulsed NRs can be identified by pseudomeningoceles. The C5–C7 foramina are exposed with ease, while the C8 and T1 are much more difficult, and some surgeons refuse to do it to concentrate in repairing only the C5–C7 NRs, even if the lower ones are also damaged [45]. This is important because no improvement can be expected in roots that have never been reimplanted and explains one of the reasons why the distal muscles of the hand are seldom reinnervated [15, 45]. Some researchers have proven in rat experimental studies that a single reimplanted NR can attract regenerating axonal sprouts from nearby

The dura mater is exposed and opened longitudinally and the dentate ligaments sectioned. Intraoperative neurophysiological monitoring is recommended particularly on rotating the SC and when performing the longitudinal myelotomy and inserting the NGs inside it [45].

The SC is rotated, pulling from the dentate ligaments to expose its anterior aspect. Serial 2– 3 mm-long stab incisions are done at the same place where the anterior NRs formerly stood. Peripheral nerve sensory NGs (medial antebrachial cutaneous nerve, superficial radial nerve, saphenous nerve) are introduced 1 mm inside the SC tissue [201] and secured with Tisseel fibrin glue (Immuno AG, Vienna, Austria). The distal stumps of these NGs are sutured with the corresponding avulsed NR remnant. The dura mater is repaired with a dural substitute

Some anatomical studies have found that the best spot where to insert the NGs in the SC is where the anterior NRs formerly stood and not in the lateral SC side [201]. This latter place is technically easier and achieves some regeneration by lateral MN axon sprouting, but the results are inadequate [201]. As the NG implantation inside the SC will cause a further damage to it [26], suturing the NGs to the SC pial surface in an experimental avulsion model has been tried, finding that it allows adequate MN survival and axonal regeneration [27]. This ventral

This was first reported in 1997 in an experimental rat NRA model [202]. Peripheral NGs were used to cover the gap between the remaining dorsal NR and the SC. A DREZ longitudinal myelotomy was performed to insert the NGs 2 mm inside the posterior horn. Some regeneration was seen with peroxidase staining [202]. The addition of olfactory ensheathing cells at the DREZ in 2003 did not improve the results [171]. In 2004, Tang et al. [188] also in rats used bioresorbable nerve conduits to repair a 6 mm dorsal NR gap, showing signs of recovery. This

and the suture reinforced with fibrin glue to prevent CSF leaks.

root pial reimplantation is not only less risky but technically easier [26, 33].

saved for later use.

levels [200].

4.2.1. Ventral root repair

4.2.2. Dorsal rootlet repair

#### 4.2. Lateral approach

This has been well described in the publications of Carlstedt and co-authors [7, 44, 45, 193]. The patient is placed on the lateral decubitus position with the affected arm at the highest position and slightly rotated outwards with the hand in supination. The head is supported in a Mayfield head clamp (Integra LifeSciences, Austin, Texas, USA) and, slightly laterally, bent towards the healthy side. The idea is not only to allow surgical access to the whole BP but also to the possible donor sensory nerves (median antebrachial cutaneous and radial sensory nerves). The ipsilateral lower limb saphenous nerve can also be accessed with ease. The surgical table is placed in a 15% head-up position to reduce venous bleeding. A skin incision is performed from the mastoid to the clavicle following the posterior border of the sternocleidomastoid muscle [7, 44, 45],or by incising from the sternocleidomastoid muscle-clavicular incision and running parallel to the clavicle about 2 cm above it in the direction of the C7 spinous process [193]. After dissecting the platysma and sternocleidomastoid muscles, the spinal accessory and cervical plexus nerves are identified and referenced with loops. Care has to be taken not to damage the spinal accessory nerve at the junction between the upper and middle-third sternocleidomastoid muscle posterior border. After careful subcutaneous fat dissection, the transverse processes of the cervical vertebrae can be felt deep to the sternocleidomastoid muscle with the tip of the finger. The scalene muscles anterior, middle and posterior as well as the levator scapula muscle are identified. Next, the transverse cervical artery and vein are isolated and referenced. It is best not to sacrifice them as they can be used in the future to vascularise a possible gracilis muscle graft [197]. The BP is fully exposed and the avulsed NRs identified. The avulsed NRs are trimmed until normalappearing nervous tissue is seen. Many surgeons remove the dorsal root including its ganglion [15, 45]. Unless the NR reimplantation is attempted in the first 2 weeks post-avulsion injury, the BP retracts distally and undergoes fibrotic changes adhering to the nearby structures [1, 26, 33, 198, 199], so the BP has to be completely freed to be able to move it upwards. This maneuver can be troublesome at times due to dense fibrotic tissue, particularly when surgical reimplantation has been delayed over 4 weeks [15, 45]. When this is not possible or the BP cannot regain its former position in contralateral C7 NR transfer, some have shortened the humerus shaft by 4 cm [198]. The alternative is to use long autologous NGs that cover the gap between the SC and the NR remnants [15, 26, 45, 109].

The C5-T1 NR foramina and zygapophyseal joints are approached between the elevator scapula and the middle and posterior scalene muscles. Then the longissimus muscle is split longitudinally to expose the spine. The multifidus muscles are detached from the zygapophyseal joints and laminae. The transverse processes and the anterior and posterior tubercles are exposed by removing all the muscles attaching to them. These bone structures plus a section of the lateral mass are removed and a C5-C7 hemilaminectomy performed. The removed bone pieces are saved for later use.

Care must be taken with the vertebral artery, as it does not need to be mobilized. As most of the lateral mass, the disc and the contralateral facet joints are spared; the procedure usually does not induce spine instability. The avulsed NRs can be identified by pseudomeningoceles. The C5–C7 foramina are exposed with ease, while the C8 and T1 are much more difficult, and some surgeons refuse to do it to concentrate in repairing only the C5–C7 NRs, even if the lower ones are also damaged [45]. This is important because no improvement can be expected in roots that have never been reimplanted and explains one of the reasons why the distal muscles of the hand are seldom reinnervated [15, 45]. Some researchers have proven in rat experimental studies that a single reimplanted NR can attract regenerating axonal sprouts from nearby levels [200].

The dura mater is exposed and opened longitudinally and the dentate ligaments sectioned. Intraoperative neurophysiological monitoring is recommended particularly on rotating the SC and when performing the longitudinal myelotomy and inserting the NGs inside it [45].

#### 4.2.1. Ventral root repair

access the spinal canal. The dura is opened and the dentate ligaments sectioned to rotate the SC to reach the implantation site of the ventral roots. As no access to the anterior structures is possible, another anterior approach to the BP is needed to identify and mobilize it and to pass the NGs from one surgical field to the other [7]. Depending on the degree of bone removal, a posterior cervical fusion might be required. This approach only allows access to the avulsed NRs that lie inside the spinal canal or outside it but very close to the foramina [39]. Only one case was reported in 1995 [39], which did not spark much interest within the BP surgical

This has been well described in the publications of Carlstedt and co-authors [7, 44, 45, 193]. The patient is placed on the lateral decubitus position with the affected arm at the highest position and slightly rotated outwards with the hand in supination. The head is supported in a Mayfield head clamp (Integra LifeSciences, Austin, Texas, USA) and, slightly laterally, bent towards the healthy side. The idea is not only to allow surgical access to the whole BP but also to the possible donor sensory nerves (median antebrachial cutaneous and radial sensory nerves). The ipsilateral lower limb saphenous nerve can also be accessed with ease. The surgical table is placed in a 15% head-up position to reduce venous bleeding. A skin incision is performed from the mastoid to the clavicle following the posterior border of the sternocleidomastoid muscle [7, 44, 45],or by incising from the sternocleidomastoid muscle-clavicular incision and running parallel to the clavicle about 2 cm above it in the direction of the C7 spinous process [193]. After dissecting the platysma and sternocleidomastoid muscles, the spinal accessory and cervical plexus nerves are identified and referenced with loops. Care has to be taken not to damage the spinal accessory nerve at the junction between the upper and middle-third sternocleidomastoid muscle posterior border. After careful subcutaneous fat dissection, the transverse processes of the cervical vertebrae can be felt deep to the sternocleidomastoid muscle with the tip of the finger. The scalene muscles anterior, middle and posterior as well as the levator scapula muscle are identified. Next, the transverse cervical artery and vein are isolated and referenced. It is best not to sacrifice them as they can be used in the future to vascularise a possible gracilis muscle graft [197]. The BP is fully exposed and the avulsed NRs identified. The avulsed NRs are trimmed until normalappearing nervous tissue is seen. Many surgeons remove the dorsal root including its ganglion [15, 45]. Unless the NR reimplantation is attempted in the first 2 weeks post-avulsion injury, the BP retracts distally and undergoes fibrotic changes adhering to the nearby structures [1, 26, 33, 198, 199], so the BP has to be completely freed to be able to move it upwards. This maneuver can be troublesome at times due to dense fibrotic tissue, particularly when surgical reimplantation has been delayed over 4 weeks [15, 45]. When this is not possible or the BP cannot regain its former position in contralateral C7 NR transfer, some have shortened the humerus shaft by 4 cm [198]. The alternative is to use long autologous NGs that cover the gap between the SC and the

The C5-T1 NR foramina and zygapophyseal joints are approached between the elevator scapula and the middle and posterior scalene muscles. Then the longissimus muscle is split longitudinally to expose the spine. The multifidus muscles are detached from the zygapophyseal joints

community. Currently this technique is not used for NR reimplantation.

4.2. Lateral approach

56 Treatment of Brachial Plexus Injuries

NR remnants [15, 26, 45, 109].

The SC is rotated, pulling from the dentate ligaments to expose its anterior aspect. Serial 2– 3 mm-long stab incisions are done at the same place where the anterior NRs formerly stood. Peripheral nerve sensory NGs (medial antebrachial cutaneous nerve, superficial radial nerve, saphenous nerve) are introduced 1 mm inside the SC tissue [201] and secured with Tisseel fibrin glue (Immuno AG, Vienna, Austria). The distal stumps of these NGs are sutured with the corresponding avulsed NR remnant. The dura mater is repaired with a dural substitute and the suture reinforced with fibrin glue to prevent CSF leaks.

Some anatomical studies have found that the best spot where to insert the NGs in the SC is where the anterior NRs formerly stood and not in the lateral SC side [201]. This latter place is technically easier and achieves some regeneration by lateral MN axon sprouting, but the results are inadequate [201]. As the NG implantation inside the SC will cause a further damage to it [26], suturing the NGs to the SC pial surface in an experimental avulsion model has been tried, finding that it allows adequate MN survival and axonal regeneration [27]. This ventral root pial reimplantation is not only less risky but technically easier [26, 33].

#### 4.2.2. Dorsal rootlet repair

This was first reported in 1997 in an experimental rat NRA model [202]. Peripheral NGs were used to cover the gap between the remaining dorsal NR and the SC. A DREZ longitudinal myelotomy was performed to insert the NGs 2 mm inside the posterior horn. Some regeneration was seen with peroxidase staining [202]. The addition of olfactory ensheathing cells at the DREZ in 2003 did not improve the results [171]. In 2004, Tang et al. [188] also in rats used bioresorbable nerve conduits to repair a 6 mm dorsal NR gap, showing signs of recovery. This repair was enhanced by injecting a viral vector inside the DRG [203]. In 2017, Konig et al. [173] reported the application of murine neural crest stem cells and embryonic stem cell-derived neuron precursors at the DREZ in an experimental rat cervical dorsal NRA showing differentiation into neurons and their migration, transforming into interneurons and facilitating the creation of synapsis with the regenerating axons coming from the reimplanted dorsal NR.

corpectomy of the affected levels that can be C4 to T1 when the whole BP is involved. This involves an extensive anterior cervical fusion, not optimal for younger individuals due to its possible long-term consequences [206]. The anterolateral approach provides good access to the BP and ventral NR, but the dorsal NR cannot be reimplanted [195]. This approach has been reported in research animals—cats [207, 208]—in ten cadavers and four clinical cases [194], but

Nerve Root Reimplantation in Brachial Plexus Injuries http://dx.doi.org/10.5772/intechopen.82431 59

The antecedent of this approach is the two-stage combined approach posterior (first) and anterior (some days later) [185]. In the first stage, the cervical spinal canal was approached with the patient prone. A C4–T1 laminectomy with medial-third facetectomy was performed and the SC inspected after longitudinal dural opening. The dentate ligaments were sectioned and SC rotated and inspected looking for avulsed NR. In case the avulsed NRts were inside the dura mater, they were reimplanted where they formerly stood. Both ventral and dorsal NRs were reimplanted. When the NRs were outside the spinal canal, NGs were inserted and sutured to the SC tissue through small myelotomies and their distal end tunneled through the paraspinal muscles and placed in the supraclavicular area with two metallic hemoclips to facilitate their identification in the future. The dura mater was sutured and sealed with fibrin glue. A posterior mass cervical fusion was performed to prevent postoperative kyphotic deformities. Some days later the patient was taken back to the operating room and in the supine position the BP identified and isolated in the supraclavicular region. The NG distal ends were localized through the hemoclips with X-ray guidance and sutured to the corresponding BP cords. Apart from the original report [116], no further publications on this

The single-stage combined anterior (first) and posterior (second) approach was reported by Amr el al. in 2009 [33]. The patient is placed in the lateral decubitus position and the skin sterilized front and back of neck and chest as well as the whole affected upper limb and both lower limbs. Then the patient is rotated backwards and placed supine. In this position a traditional BP exploration is done through a transverse supraclavicular incision. If needed, a second incision perpendicular to it can be done following the delto-pectoral groove. This allows exploration of the infra-clavicular BP, particularly when it has migrated distally. Once the whole BP is dissected free and the damages evaluated, several peripheral sensory NGs are obtained from the affected upper limb and both lower limbs. These grafts are sutured to the

Next, the patient is placed again in the lateral position. Through a posterior midline incision from occiput to T2, the whole cervical spine is exposed. The spinal muscles are detached from the spinous process and separated laterally. A laminectomy and partial medial facetectomy C4–T1 are performed on the affected side. The dura is opened through a longitudinal incision and the dentate ligaments sectioned. The NG that had been previously sutured to the BP cords in an end-to-side versus end-to-end technique [33, 209] is passed subcutaneously from the anterior surgical field to the laminectomy area. These NG needs to be long enough to cover the distance between the SC and the BP. Then the proximal ends of the NGs are sutured subpially

4.4. Single-stage combined anterior (first) and posterior (second) approach

no long-term clinical results have been reported.

seem to exist.

cords of the avulsed NR.

In humans, dorsal rootlet repair has been recently attempted by Carlstedt et al. [97]. As they noticed the extreme difficulty for the growing axons coming from the DRG to cross the glial scar at the surface of the posterior horn, they sectioned the avulsed NR distal to the DRG and sutured the peripheral sensory stump to the posterior horn by means of NGs introduced in the SC through a longitudinal myelotomy. The rationale was to get some sensory recovery from the growing axons of the posterior horn neurons that are expected to grow distally inside the implanted NG [99]. As the neuronal bodies of the DRG are removed, the regeneration has to depend on the neuronal plasticity of neurons coming from the posterior horn that have to stretch their axons to reach the skin though the NGs and peripheral nerves. The results are poor [99, 100], but it is the first strategy that has provided some success in humans. This is not ideal as sensation could be recovered if the dorsal rootlets were replaced by NGs and the tip of those grafts inserted inside the posterior SC horn through a longitudinal myelotomy while maintaining the neuronal bodies that lie at the DRG. This technique proved effective in rats [202], but no attempts in humans have been found in the literature. To improve the results, CNTF [87] should apply locally to the posterior SC at the DREZ associated with N-acetyl cysteine [155] orally to allow maximal sensory neuron survival. Oral minocycline [106, 120], oral tacrolimus [151] or subcutaneous recombinant erythropoietin [118, 165] could be also administered to reduce the reactive glial proliferation that acts as a barrier against dorsal root axonal regeneration.

#### 4.2.3. Wound closure

The dura mater is closed with a dural substitute and reinforced with fibrin glue to prevent CSF leaks. The morcellized bone obtained from the transverse processes and lateral masses supplemented together with demineralized bone matrix is laid on the cervical spinal column defect to enhance bone fusion. A lumbar drain is inserted and kept for 5 days to prevent CSF leaks.

Postoperatively, patients are kept with a sling for 6 weeks before starting any passive movements, to prevent NG dislodgement [45]. Cervical X-rays are taken every 3 months for a year to detect any possible instability that might require a cervical fusion.

The most important disadvantage of this approach is that it entails extensive muscular damage, particularly at the scalene muscles [33]. The most significant advantage is that the NGs needed for the repair are the shortest of all the NRA reimplantation approaches [45, 193].

#### 4.3. Anterolateral approach

It is first described by George et al. for the treatment of cervical spinal spondylosis and tumors [204, 205]. This approach is much more direct but demands a partial multilevel oblique partial corpectomy of the affected levels that can be C4 to T1 when the whole BP is involved. This involves an extensive anterior cervical fusion, not optimal for younger individuals due to its possible long-term consequences [206]. The anterolateral approach provides good access to the BP and ventral NR, but the dorsal NR cannot be reimplanted [195]. This approach has been reported in research animals—cats [207, 208]—in ten cadavers and four clinical cases [194], but no long-term clinical results have been reported.

#### 4.4. Single-stage combined anterior (first) and posterior (second) approach

repair was enhanced by injecting a viral vector inside the DRG [203]. In 2017, Konig et al. [173] reported the application of murine neural crest stem cells and embryonic stem cell-derived neuron precursors at the DREZ in an experimental rat cervical dorsal NRA showing differentiation into neurons and their migration, transforming into interneurons and facilitating the creation of synapsis with the regenerating axons coming from the reimplanted dorsal NR.

In humans, dorsal rootlet repair has been recently attempted by Carlstedt et al. [97]. As they noticed the extreme difficulty for the growing axons coming from the DRG to cross the glial scar at the surface of the posterior horn, they sectioned the avulsed NR distal to the DRG and sutured the peripheral sensory stump to the posterior horn by means of NGs introduced in the SC through a longitudinal myelotomy. The rationale was to get some sensory recovery from the growing axons of the posterior horn neurons that are expected to grow distally inside the implanted NG [99]. As the neuronal bodies of the DRG are removed, the regeneration has to depend on the neuronal plasticity of neurons coming from the posterior horn that have to stretch their axons to reach the skin though the NGs and peripheral nerves. The results are poor [99, 100], but it is the first strategy that has provided some success in humans. This is not ideal as sensation could be recovered if the dorsal rootlets were replaced by NGs and the tip of those grafts inserted inside the posterior SC horn through a longitudinal myelotomy while maintaining the neuronal bodies that lie at the DRG. This technique proved effective in rats [202], but no attempts in humans have been found in the literature. To improve the results, CNTF [87] should apply locally to the posterior SC at the DREZ associated with N-acetyl cysteine [155] orally to allow maximal sensory neuron survival. Oral minocycline [106, 120], oral tacrolimus [151] or subcutaneous recombinant erythropoietin [118, 165] could be also administered to reduce the reactive glial proliferation that acts as a barrier against dorsal root

The dura mater is closed with a dural substitute and reinforced with fibrin glue to prevent CSF leaks. The morcellized bone obtained from the transverse processes and lateral masses supplemented together with demineralized bone matrix is laid on the cervical spinal column defect to enhance bone fusion. A lumbar drain is inserted and kept for 5 days to prevent CSF

Postoperatively, patients are kept with a sling for 6 weeks before starting any passive movements, to prevent NG dislodgement [45]. Cervical X-rays are taken every 3 months for a year

The most important disadvantage of this approach is that it entails extensive muscular damage, particularly at the scalene muscles [33]. The most significant advantage is that the NGs needed for the repair are the shortest of all the NRA reimplantation approaches [45, 193].

It is first described by George et al. for the treatment of cervical spinal spondylosis and tumors [204, 205]. This approach is much more direct but demands a partial multilevel oblique partial

to detect any possible instability that might require a cervical fusion.

axonal regeneration.

58 Treatment of Brachial Plexus Injuries

4.2.3. Wound closure

4.3. Anterolateral approach

leaks.

The antecedent of this approach is the two-stage combined approach posterior (first) and anterior (some days later) [185]. In the first stage, the cervical spinal canal was approached with the patient prone. A C4–T1 laminectomy with medial-third facetectomy was performed and the SC inspected after longitudinal dural opening. The dentate ligaments were sectioned and SC rotated and inspected looking for avulsed NR. In case the avulsed NRts were inside the dura mater, they were reimplanted where they formerly stood. Both ventral and dorsal NRs were reimplanted. When the NRs were outside the spinal canal, NGs were inserted and sutured to the SC tissue through small myelotomies and their distal end tunneled through the paraspinal muscles and placed in the supraclavicular area with two metallic hemoclips to facilitate their identification in the future. The dura mater was sutured and sealed with fibrin glue. A posterior mass cervical fusion was performed to prevent postoperative kyphotic deformities. Some days later the patient was taken back to the operating room and in the supine position the BP identified and isolated in the supraclavicular region. The NG distal ends were localized through the hemoclips with X-ray guidance and sutured to the corresponding BP cords. Apart from the original report [116], no further publications on this seem to exist.

The single-stage combined anterior (first) and posterior (second) approach was reported by Amr el al. in 2009 [33]. The patient is placed in the lateral decubitus position and the skin sterilized front and back of neck and chest as well as the whole affected upper limb and both lower limbs. Then the patient is rotated backwards and placed supine. In this position a traditional BP exploration is done through a transverse supraclavicular incision. If needed, a second incision perpendicular to it can be done following the delto-pectoral groove. This allows exploration of the infra-clavicular BP, particularly when it has migrated distally. Once the whole BP is dissected free and the damages evaluated, several peripheral sensory NGs are obtained from the affected upper limb and both lower limbs. These grafts are sutured to the cords of the avulsed NR.

Next, the patient is placed again in the lateral position. Through a posterior midline incision from occiput to T2, the whole cervical spine is exposed. The spinal muscles are detached from the spinous process and separated laterally. A laminectomy and partial medial facetectomy C4–T1 are performed on the affected side. The dura is opened through a longitudinal incision and the dentate ligaments sectioned. The NG that had been previously sutured to the BP cords in an end-to-side versus end-to-end technique [33, 209] is passed subcutaneously from the anterior surgical field to the laminectomy area. These NG needs to be long enough to cover the distance between the SC and the BP. Then the proximal ends of the NGs are sutured subpially in a longitudinal fashion, parallel to the side where the ventral roots stood. No SC incisions are performed. The proximal ends of the NGs are sutured intradurally to C4 above and to T1 below. In the only publication that we have found, the dorsal NRs are not repaired [33]. The dura is closed with interrupted stitches reinforced with fibrin glue. No cervical fusion is applied.

Abbreviations

BDNF brain-derived neurotrophic factor

GDNF glial-derived neurotrophic factor

iPSC induced pluripotent stem cells

ISP intracellular sigma peptide

MSCs mesenchymal stem cells

NF neurotrophic factor

NPC neural progenitor cells

NRA nerve root avulsion

NSC neuroectodermal stem cells

OECs olfactory ensheathing glial cells

\*Address all correspondence to: vvanaclo@hotmail.com

3 Universidad Católica San Vicente Mártir, Valencia, Spain

4 Medical School, University College London, London, United Kingdom

1 Hospital General Universitario Valencia, Spain

2 Hospital 9 de Octubre, Valencia, Spain

\*, Nieves Saiz-Sapena<sup>2</sup>

, José María Ortiz-Criado<sup>3</sup>

Nerve Root Reimplantation in Brachial Plexus Injuries http://dx.doi.org/10.5772/intechopen.82431 61

BMC bone marrow stem cells

BPA brachial plexus avulsion CNF ciliary neurotrophic factor

BP brachial plexus

MN motor neuron

NGs nerve grafts

NR nerve root

NRts nerve rootlets

SC spinal cord

Vicente Vanaclocha-Vanaclocha<sup>1</sup>

Author details

and Leyre Vanaclocha<sup>4</sup>

The advantage of this double approach is that it is more conservative to the muscles. The disadvantage is that long NGs are needed, making the distance between the motoneuron and the muscular end plates still larger. To the best of our knowledge, there is only a single publication attesting the validity of this technique [33]. It is of particular interest that ventral NR regeneration can be achieved by laying the NGs subpially at the SC without having to insert them inside the SC tissue through myelotomies [33].

## 5. Clinical results in human beings

Some clinical studies have reported definitive although limited motor and sensory improvements particularly in the proximal limb areas after NR reimplantation in complete BPAs [15, 30, 32, 33, 45, 185]. The best motor recovery was seen at the deltoid, pectoralis, infraspinatus, biceps and triceps muscles [15, 30, 45, 185, 209]. One patient showed signs of partial recovery of the flexor digitorum superficialis and another of the first dorsal interosseous muscle [45]. A functional recovery of the hand has only been reported in a 9-year-old child with a complete BPA [29]. Hand intrinsic muscle motor grade 2 recovery was reported by Amr et al. [33]. The best sensory improvement was patent at dermatomes C5, C6 and T1, particularly at C5 [33, 45]. One of the reasons by which only proximal muscles show signs of reinnervation in the work of Kachramanoglou et al. is because only the C5–C7 NRs are reimplanted as C8 and T1 are more technically demanding and they were reluctant to risk neurological complications on handling the SC at these levels [45]. This could also be the reason by which Amr et al. [33] report hand intrinsic muscle grade 2 motor recovery, as they did repair the C8 and T1 roots. Another extremely important reason is that when the regenerating axons reach the distal limb muscles, they are already atrophied and fibrotic [72, 73]. The C5 and T1 sensory recovery can in part be due to overlapping sensory covering from nearby dermatomes (C4 for C5 and T2 for T1) [32, 45].

#### 6. Conclusions

NRA keeps being in an area in which improvement is desperately needed, particularly in complete BPAs in which not many alternatives are possible. As clinical results in humans keep being dismal, further research is needed. The administration of drugs, preferably orally, has to be pursued to find a combination of them that helps to achieve a successful limb recovery. NR reimplantation has to be undertaken as soon as the patients' clinical condition allows it. Ventral NRt implantation provides better results than its posterior counterparts.
