**Conflict of interest**

**2.6. Relevance**

34 Treatment of Brachial Plexus Injuries

**3. Conclusions**

**Acknowledgements**

Improving knowledge on TBPI and its treatment is also an opportunity to reduce its social and economic impacts, the main victims being in general male in working age. Since Narakas' report in 1985 [50], subsequent series on brachial plexus injury around the world reaffirmed the importance of motor vehicle accidents, especially motorcycle, as its main cause [83–89]. The

However, traffic accidents as a whole, including motorcycle ones, impact more intensely in developing countries [94]. As an example of this situation, in Brazil, a huge increase by 400% in motorcycle fleet was observed from 2003 to 2015 [95]. In recent years, there grew up from 20 million in 2012 to more than 25 million in 2017 [96]. A consequent increase in motorcycle accidents reports should be naturally expected. However, official data show that the relative contribution to traffic accidents by motorcycle is much higher than could be previously imagined. In the first 6 months of 2017, motorcycles represented 27% of total Brazilian vehicular fleet, but were responsible for 74% of total indemnity paid by traffic accidents in the same period. Since traffic accidents involving motorcycles represent the most frequent cause of TBPI [83–89], an increase in TBPI in the Brazil, and in other developing countries, can be predicted in the near future.

There is mounting evidence that the brain is capable of recognizing and incorporating new information after a peripheral lesion followed by its surgical reconstruction. Frequently, these plastic processes are associated with persisting pain, a phenomenon that has been shown to correlate with the degree of cortical reorganization. However, the mechanisms underlying these phenomena are still only partially uncovered. TBPI is an interesting model of brain plasticity due to its incidence, the large variety of injury levels and the available surgical reconstructive procedures. For instance, studies with TBPI have shown changes in cortical representation after surgical transfer. Shortcomings in interpreting the results from studies relating brain changes after TBPI and its reconstruction are the paucity of systematic correlation of TBPI with detailed clinical evaluation protocols and the need of further investigation of physical therapy outcomes after TBPI. New venues in this domain shall be opened through the development of approaches allowing putting together more detailed clinical investigation

This work is part of the ABRAÇO Initiative for the Brachial Plexus Injury (http://abraco.numec. prp.usp.br/) of the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)'s Research, Innovation and Dissemination Center for Neuromathematics (grant 2013/07699-0, http://neuromat.numec.prp.usp.br/). It was also supported by the Conselho Nacional de Pesquisa (CNPq) (grants 306817/2014-4 and 309560/2017-9) and the Fundação de Amparo à Pesquisa do Rio de Janeiro FAPERJ (grants E-26/111.655/ 2012, E26/010.002902/2014 and E-26/010.002474/2016).

protocols and that of brain mechanisms associated to plasticity after TBPI.

same trend is observed in series covering peripheral nerve injury in general [90–93].

The authors declare that there is no conflict of interest.

## **Author details**

Fernanda F. Torres1,2, Bia L. Ramalho1,2, Cristiane B. Patroclo1,2, Lidiane Souza1,2, Fernanda Guimaraes2,3, José Vicente Martins2 , Maria Luíza Rangel1,2 and Claudia D. Vargas1,2\*

\*Address all correspondence to: claudiadvargas@gmail.com

1 Laboratory of Neurobiology of movement, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

2 Laboratory of Neuroscience and Rehabilitation, Institute of Neurology Deolindo Couto, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

3 Federal Institute of Rio de Janeiro, Rio de Janeiro, Brazil

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42 Treatment of Brachial Plexus Injuries

600.59365.41

112.28212015.2016

**Chapter 4**

Provisional chapter

**Nerve Root Reimplantation in Brachial Plexus Injuries**

DOI: 10.5772/intechopen.82431

Nerve root avulsion is the most severe form of brachial or lumbosacral plexus injury. Spontaneous recovery is extremely rare, and when all the nerve roots of the affected plexus are avulsed, the therapeutic options are very limited. Nerve root reimplantation has been attempted since the 1990s, first in experimental animal models and afterwards in human beings. Currently, only partial recovery of the proximal limb muscles has been achieved. New therapeutic strategies have been developed to improve motor neuron survival and axonal regeneration, with promising results. Neurotrophic factors and some drugs have been used successfully to improve the regenerating ability, but long-term studies in humans are needed to develop complete recovery of the affected limb. Keywords: brachial plexus injury, nerve root avulsion, nerve root reimplantation, motor neuron death, muscle atrophy, neurotrophic factor, axonal regeneration, motor and

A common event in brachial plexus (BP) injury is nerve root avulsion (NRA) in which the nerve rootlets (NRts) are torn from the spinal cord (SC) [1–3]. Once avulsed, the NRts retract towards the nerve root (NR) sleeve [4]. The most common cause is traumatic NR stretching due to road accidents or parturitions [3, 5]. These injuries can also happen but are much rarer at the lumbosacral plexus [6]. The ventral rootlets (motor) are weaker and thus get injured

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

more often and more seriously than their posterior counterparts [7].

Nerve Root Reimplantation in Brachial Plexus Injuries

Vicente Vanaclocha-Vanaclocha,

Vicente Vanaclocha-Vanaclocha,

http://dx.doi.org/10.5772/intechopen.82431

Leyre Vanaclocha

Abstract

sensory recovery

1. Introduction

and Leyre Vanaclocha

Nieves Saiz-Sapena, José María Ortiz-Criado and

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

Nieves Saiz-Sapena, José María Ortiz-Criado

#### **Nerve Root Reimplantation in Brachial Plexus Injuries** Nerve Root Reimplantation in Brachial Plexus Injuries

DOI: 10.5772/intechopen.82431

Vicente Vanaclocha-Vanaclocha, Nieves Saiz-Sapena, José María Ortiz-Criado and Leyre Vanaclocha Vicente Vanaclocha-Vanaclocha, Nieves Saiz-Sapena, José María Ortiz-Criado and Leyre Vanaclocha

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.82431

#### Abstract

Nerve root avulsion is the most severe form of brachial or lumbosacral plexus injury. Spontaneous recovery is extremely rare, and when all the nerve roots of the affected plexus are avulsed, the therapeutic options are very limited. Nerve root reimplantation has been attempted since the 1990s, first in experimental animal models and afterwards in human beings. Currently, only partial recovery of the proximal limb muscles has been achieved. New therapeutic strategies have been developed to improve motor neuron survival and axonal regeneration, with promising results. Neurotrophic factors and some drugs have been used successfully to improve the regenerating ability, but long-term studies in humans are needed to develop complete recovery of the affected limb.

Keywords: brachial plexus injury, nerve root avulsion, nerve root reimplantation, motor neuron death, muscle atrophy, neurotrophic factor, axonal regeneration, motor and sensory recovery

#### 1. Introduction

A common event in brachial plexus (BP) injury is nerve root avulsion (NRA) in which the nerve rootlets (NRts) are torn from the spinal cord (SC) [1–3]. Once avulsed, the NRts retract towards the nerve root (NR) sleeve [4]. The most common cause is traumatic NR stretching due to road accidents or parturitions [3, 5]. These injuries can also happen but are much rarer at the lumbosacral plexus [6]. The ventral rootlets (motor) are weaker and thus get injured more often and more seriously than their posterior counterparts [7].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Soon after avulsion anterior horn motor neurons (MN) and sensory neurons at the dorsal root ganglion (DRG) undergo apoptosis [8–17]. Inside the avulsed NR itself, there is a Wallerian degeneration with axonal and myelin loss [18]. The muscles, devoid of nervous impulses, undergo atrophy and fibrous transformation [19, 20]. At the SC, the neurons suffer loss of synapses with destruction of previous neuronal networks and creation of new anomalous ones that will lead to abnormal nerve impulses which might induce chronic neuropathic pain [21–24].

the DRG neurons from the bulbar and thalamic sensory nuclei [48]. NRA also induces loss of synapses and dendritic arborisation, fiber degeneration, neuronal death, posterior spinal column degeneration and glial proliferation [23, 48]. The synaptic and neuronal changes in the

Nerve Root Reimplantation in Brachial Plexus Injuries http://dx.doi.org/10.5772/intechopen.82431 47

NRA is followed by an intense inflammatory SC reaction [50] with microglia, macrophage and glial proliferations [51]. At the TZ a dense scar tissue and a neuroma from the avulsed MN develop [15, 46, 52–55]. In the normal situation, the central nervous system is rich in astrocytes that create channels through which the nerve fibers pass [15]. After NRA, astrocytes proliferate and rearrange, blocking those channels and making it difficult for the regenerating nerve fibers to grow [15, 46, 56]. Axonal and dendrite regeneration is inhibited by the secretion of some substances by the astrocytes (chondroitin sulphate proteoglycans or CSPGs) [57–59] and oligodendrocytes (myelin protein [60–62] and semaphorin-3 [63]). Additionally, the glia secrete neurotoxic products like glutamate [15] and free radicals [64] that induce massive neuronal death among motor [8], sympathetic [12], parasympathetic [12] and posterior horn sensory

About 80% of the MNs die in the following weeks [13, 65, 66], but this death does not happen immediately after NRA [13, 67, 68]. Instead, there is a 12-day period in which different treatment strategies can reduce this MN loss [65, 69]. The chemical compounds that counteract the glutamate toxic effects can reduce the MN loss by 70%, provided that they are adminis-

The closer the axonal injury to the neuronal body [55], the smaller the regenerating capacity of the axon and the higher the chance that the neuron will die. Four millimeters is the minimum

The surviving MNs develop axonal sprouts within 1 month after the NRA [41], but to achieve a successful regeneration, the axons must cross the gliotic TZ, grow inside the distal peripheral nerves, and reach the motor end plates [71]. The long distance to cover is a big impediment to a successful functional recovery [72, 73]. By the time the muscles get reinnervated, they are atrophic and with fibrotic changes, particularly the most distal ones [74]. The regeneration is not privative to the axon, and the dendrites can also regenerate as axon, creating what has been called a dendraxon. These also have the capacity to grow into the peripheral nerves and

Although the MN regenerating axon has a chance to cross the anterior SC white matter to reach its surface and then attempt to grow in a possible reimplanted NR [77, 78] for the DRG growing axon, the same is almost impossible as they have to cross a very hostile and gliotic

In the human being, the avulsion damages more frequently the ventral NRts as they are more

NRA creates four problems that have to be addressed to achieve a successful repair. First, if the axon is torn closer than 4 mm to the cell body, motor and preganglionic parasympathetic neurons undergo apoptosis [10–13, 23, 67, 68, 70, 82–84]. Second, muscles are fibrotic by the

amount of peripheral nerve that should remain to avoid MN death [70].

posterior horn produce neuropathic pain [24, 48, 49].

tered in the first 2 weeks after the NRA [16, 65, 69].

posterior SC Dorsal Root Entry Zone (DREZ) [79–81].

fragile than their posterior counterparts [15].

neurons [17].

reinnervate muscles [75, 76].

After complete NRA, spontaneous regeneration is impossible [9]. In case of a single NRA, recovery coming from nearby healthy ones can be expected in neonates but not in adult patients [25]. Ventral root surgical reimplantation has been attempted both in experimental animals and in human beings with partial recovery [26, 27].

Axonal regeneration is stronger in direct ventral NR reimplantation [26, 28]. This is rarely possible [4, 7, 29, 30], so peripheral nerve grafts (NGs) are used to cover the gap between the SC and the remains of the avulsed NR [31–33]. These NGs are usually taken from a peripheral sensory nerve (medial antebrachial cutaneous, radial cutaneous, and saphenous), which is not the ideal situation as motor nerve regeneration is worse if sensory nerves are used as donors compared to mixed or pure motor nerves [34–36]. Acellular conduits have also been used, but the regeneration does not grow further than 2 cm [37, 38].

#### 1.1. Historical background

Surgical repair of spinal NRs after traumatic avulsion in live human beings was considered technically impossible until the pioneering work of Carlstedt et al. [39]. The first studies were done in rats [40], then in cats [41] and finally in primates [42, 43], before attempting NR reimplantation in humans [44]. Initially, the efforts were directed at repairing the ventral rootlets (motor), but in adult human beings, it provided only mild improvement in shoulder and elbow movements [45]. In children, some hand movement was recovered but with limited function [29]. In addition, it was found that the number of surviving MNs and the number of axons that regenerated after NR reimplantation had a direct relationship with the final functional recovery [7, 30]. Ever since, many research groups have focussed on understanding the underlying pathophysiology and to find surgical strategies and drugs that can enhance regenerating capacities.
