Keywords
obstetrical brachial plexus palsy - nerve transfer - allogenic grafts
Introduction
Obstetric brachial plexus injury (OBPI) or obstetric brachial plexus palsy (OBPP)
is a rather common injury in newborns that can have a spontaneous recovery,[1] but it varies from 30% to 90%. This injury is caused by traction to the brachial
plexus during labor, and the extent of neural damage can only be assessed by evaluating
recovery in the course of time.[2] Its incidence varies between 0.15 and 3 cases per 1.000 live births.[2] The classical injury is a C5, C6 palsy, but all roots can be involved.[1]
Nerve grafting has been performed in neonatal population with brachial plexus palsy
for > 30 years, and it is recommended for patients who present with postganglionic
rupture of the upper nerve roots of the brachial plexus (C5 and C6).[3] On the other hand, nerve transfer surgery is usually indicated in cases of late
presentation, failed primary nerve reconstruction, isolated deficit, absence of proximal
root for grafting, and multiple nerve root avulsions.[3] Nerve transfer surgery involves taking nerve branches from a neighboring nerve and
redirecting them to the distal end of the injured nerve.[4] After the surgery, the body regenerates axons along the new path, and the motor
cortex rewires itself to relearn muscle functions.[4]
There are several experimental reports in which allograft nerve has been used as an
alternative to nerve autograft to bridge two ends of a nerve together, both in nonhuman
and human primates.[5] Allograft tissue would serve as a temporary scaffold in which it enhances neural
regeneration by providing the essential structural characteristics of the nerve tissue.[6] Restoration of elbow flexion is of great importance and it is one of the highest
priorities of brachial plexus reconstruction,[7] and one of the most commonly grading system to assess this recovery has been the
Medical Research Council (MRC) grading system.[8]
[9] In this context, with the present systematic review, we aimed to explore the use
of nerve graft and nerve transfer as procedures to improve elbow flexion in children
with OBPP.
Methods
The present systematic review was performed according to the Preferred Reporting Items
for Systematic reviews and Meta-Analyses (PRISMA).[10] We searched the MEDLINE, EMBASE, LILACS, The Cochrane Central Register of Controlled
Trials (CENTRAL), Web of Science, Wholis, and SCOPUS databases. In the search, we
included terms in English, Spanish and Portuguese using the search equation: E= (P1 AND P2 NOT (P3 OR P4)) AND I AND O. The Patient/Population, Intervention, Comparison and Outcomes (PICO) question was:
What is the evidence of elbow flexion improvement with the nerve graft or nerve transfer
technique in children with OBPP? We did not restrict the search by time ([Supplementary material 1]).
Table 1
|
Studies that compared nerve graft versus nerve transfer
|
|
Author, year
|
Country
|
Study design
|
(n) Nerve graft
|
(n) Nerve transfer
|
Age at sugery (nerve graft) (months old)
|
Age at sugery (nerve transfer) (months old)
|
Female %
|
Follow-up period (months)
|
|
Chang et al. 2018,[3]
|
USA
|
Retrospective cohort study
|
28
|
12
|
6
|
7
|
62%
|
12
|
|
Luszawski et al. 2017,[13]
|
Poland
|
Retrospective study
|
14
|
5
|
< 18
|
< 18
|
NS
|
> 12
|
|
Malessy et al. 2014,[14]
|
Netherlands
|
Retrospective study
|
17
|
17
|
5.7
|
5.7
|
56%
|
70
|
|
Studies that used nerve graft and nerve transfer combined
|
|
Author, year
|
Country
|
Study design
|
(n)
|
Age at sugery (months old)
|
Female %
|
Follow-up period (months)
|
|
|
|
Bhandari et al. 2015[16]
|
India
|
Retrospective study
|
32
|
3.5 to 23
|
NS
|
24.3
|
|
|
|
Birch et al. 2005[20]
|
England
|
Prospective study
|
100
|
7
|
45%
|
85
|
|
|
|
Terzis et al 2009[21]
|
USA
|
Retrospective study
|
23
|
14
|
44%
|
78
|
|
|
|
Xu et al. 2000[22]
|
China
|
Retrospective study
|
10
|
4.5
|
40%
|
44.3
|
|
|
Selection Criteria
Predetermined criteria defined the following requirements for inclusion of a study:
clinical trials, quasi-experiments, and cohort studies that performed nerve graft
and nerve transfer in children (≤ 3 years old) with diagnosis of OBPP. For all outcomes,
the studies had to have at least 6 months of follow-up. All comparative studies of
graft versus transfer reported relevant outcomes regarding the muscle strength measured
by the MRC.
Data Extraction
Independent and blinded reviewers extracted data from eligible studies. The variables
of abstraction included: author, year of the study, study design, number of patients
for either procedure, age at surgery, gender, injuries, follow-up period, and donor
nerve for either procedure. The primary outcome was to explore the use of nerve graft
and nerve transfer in children with OBPP, and the secondary outcome was the recovery
of elbow flexion following both procedures, assessed by strength by the MRC after
the procedure. The MRC grading system consists of 5 grades: 0 represents no contraction,
1 represents flicker or trace of contraction, 2 represents active movement with gravity
eliminated, 3 represents active movement against gravity, 4 represents active movement
against gravity and resistance, and 5 represents normal power.[8] Two researchers reviewed each study found in the databases by title and abstract,
selecting the more adequate ones. Subsequently, they reviewed the full texts of previously
selected articles and screened them according to the inclusion criteria. With the
studies finally selected, we extracted the data. Disagreements were resolved by consensus,
and where disagreement could not be solved, one of the two reviewers solved the conflict.
Risk of Bias Assessment
The Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) assessment
tool[11] was used for nonrandomized studies. This tool includes 7 specific bias domains:
1 - confounding; 2 - selection of participants; 3 - classification of intervention;
4 - deviation from interventions; 5 - missing outcome data; 6 - measurement of outcomes;
and 7 - selection of reported overall result. Risk of bias was rated as: 0 - no information;
1 - low risk; 2 - moderate risk; 3 - serious risk; and 4 - critical risk. Two authors
assessed independently the risk of bias of the included articles. Disagreements were
managed by consensus.
Strategy for Data Analysis
The statistical analysis for categorical variables consisted in percentages, frequencies
and measures of central tendency.
Results
From our literature search in the different databases, we found 344 records after
removal of duplicates. Following the screening of titles and abstracts, 44 studies
were eligible for full-text evaluation. Finally, seven studies were included in the
systematic review, as presented in the PRISMA Flow Diagram ([Fig. 1]). Disagreements were managed by consensus.
Fig. 1 PRISMA flow diagram of selected studies
Study Characteristics
Seven studies were selected, three of which compared the procedures of nerve graft
for 59 patients and of nerve transfer for 34 patients, having a total number of 93
patients ([Table 1]). On the other hand, four of them did not compare procedures, but used them as a
reconstructive method for children with OBPP ([Table 1]). For the studies that compared nerve graft with nerve transfer, the age at surgery
ranged from 5.7 to 18 months old, and the follow-up period ranged from 12 to 70 months.
Meanwhile, the age at surgery of the studies that combined both procedures ranged
from 3.5 to 23 months old, and the follow-up period ranged from 24.3 to 85 months.
Only two of the selected studies had all data necessary to compare the elbow flexion
outcome evaluated with the MRC after the nerve grafting or nerve transfer surgeries
([Table 2]).
Table 2
|
Author
|
Injury
|
MRC nerve transfer PO (%)
|
Injury
|
MRC nerve graft PO (%)
|
p-value
|
|
Chang et al. 2018[3]
|
C5-C6, C5-C7, C5-T1, C5-T1+ Horner sign
|
M3 (NS)
|
C5-C6, C5-C7, C5-T1, C5-T1+ Horner sign
|
M2 (NS)
|
0.77
|
|
Luszawski et al. 2017[13]
|
C5-C7
|
> M3 (100%)
|
C5-C6, C5-C7, C5-T1
|
> M3 (77%)
|
NS
|
|
Malessy & Pondaag, 2014[14]
|
C5-C6 anterior root filament
|
≥M4 (100%)
|
C5-anterior division of superior trunk
|
≥M4 (100%)
|
NS
|
|
C5-C6
|
≥M4 (100%)
|
Risk of Bias Assessment
Risk of bias assessment for the studies was evaluated using the ROBINS-I tool ([Supplementary material 2]). Only the three studies that compared the procedures of nerve graft with nerve
transfer were included in this assessment. In domains 3 and 6, 3 out of 3 studies
were rated as low risk; in domain 7, 3 out 3 studies were rated as moderate; in domains
2 and 4, one-third was rated as moderate; in domains 1 and 5, one-third was rated
as serious; overall, two studies were rated as presenting moderate, and one as presenting
serious risk of bias.
Discussion
Our objective was to explore the use of nerve graft and nerve transfer as procedures
to improve elbow flexion in children with OBPP. Here, we found seven studies that
used both procedures, three of them compared the procedures of nerve graft and nerve
transfer, as the other four combined them as a reconstructive method for children
with OBPP. According to the MRC scale, both methods equally improved the elbow flexion
in the children, which is coincident with previous studies.[12]
Chang et al.[3] found similar improvement for elbow flexion in abduction and adduction for both
groups of infants who underwent Oberlin transfer versus nerve grafting, with no statistical
significance. According to the authors, nerve transfer should be considered in cases
such as late presentation, failed primary nerve reconstruction, absence of proximal
root for grafting, and multiple nerve root avulsions (preganglionic lesion). Likewise,
Luszawski et al.[13] reported the results of children with OBPP lesions operated with the nerve graft
or nerve transfer technique. The authors do not show the results of all patients after
the follow-up period, but 100% of the patients submitted to nerve transfer (only 1
shown) had biceps muscle recovery to an MRC grade > M3. On the other hand, 77% of
the patients (10 out of 13 shown) submitted to nerve graft had biceps muscle recovery
to an MRC grade > M3. On the other hand, Malessy et al.,[14] in their study, divided patients into Group A and Group B, depending on the procedures
performed. In group A, 17 infants received transfer of either the C6 anterior root
filaments with direct coaptation in 15 of them, or the entire C6 nerve to C5. Likewise,
Group B comprised 17 infants; in this case, who received grafting from C5 to the anterior
division of the superior trunk. According to the authors, all infants, independently
of the type of surgery performed, had biceps muscle recovery to a, MRC grade > M4.
After this study, another study by Yang et al.[15] also proved the viability of restoring a C5 and C6 avulsion of the brachial plexus
with an extradural nerve anastomosis technique.
In the study by Bhandari et al.,[16] the authors used neurolysis and nerve graft combined with nerve transfer as surgical
procedures for nerve reconstruction in children with OBPP. Neurolysis was indicated
for neuroma-in-continuity,[17] and nerve grafts were used to bridge the nerve defects, once the nonconducting neuromas
were resected, and nerve transfers were indicated in avulsion and irreparable nerve
root injuries.[18] The patients with total palsy received nerve transfer and nerve graft when the nerve
to be transferred was insufficient in length, achieving 70% of biceps recovery. The
authors believe that indications for neurolysis in OBPP are very few, and the results
are far superior with resection of neuroma followed by nerve grafting in infants aged
between 3 and 4 months old. This statement has been widely confirmed by many studies
that showed better results of nerve reconstructions in younger children.[14]
[19] Furthermore, Birch et al.[20] found no statistical difference between a repair of C5 by graft or by nerve transfer.
Moreover, Terzis et al.[21] found that, overall, 78% of the extremities that underwent nerve reconstruction
surgery achieved good and excellent results (M3 + ). According to the authors, late
reconstruction (∼ 7 months) of the MCN resulted in inferior results, and infants with
C5-C6 palsy achieved significantly stronger elbow flexion than those with global palsy.
Xu et al.[22] selected patients that had no recovery of biceps contraction by the age of 3 months
old. The procedure of nerve transfer and grafting combined was performed in 10 patients
with OBPP; excellent and good results in elbow flexion were found in 70% of the patients
in the nerve transfer and grafting group. Also, 80% of the infants had biceps muscle
recovery to an MRC grade of M3 + . According to the authors, the results show that
nerve transfer combined with nerve graft is the best option to manage resection of
the neuroma and reconstruction of the brachial plexus, that infant nerves have more
regeneration capacity,[23] and that a shorter distance for axons to reach the end organ[24] results in a better surgery outcome.
Conclusions
Overall, our results showed that both techniques of nerve graft and nerve transfer
are good options for nerve reconstruction in cases of OBPP. The present study has
various limitations, one of them being that all included studies were nonrandomized
studies. In addition, the injury type, the surgical approach, and the follow-up time
were inconsistent in the selected studies. More studies approaching the nerve reconstruction
techniques in OBPP should be made, preferably randomized clinical trials to validate
the results of the present systematic review.
