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Restoration and protection of brachial plexus injury: hot topics in the last decade

Brachial plexus injury is frequently induced by injuries, accidents or birth trauma. Upper limb function may be partially or totally lost after injury, or left permanently disabled. With the development of various medical technologies, different types of interventions are used, but their effectiveness is wide ranging. Many repair methods have phasic characteristics, i.e., repairs are done in different phases. This study explored research progress and hot topic methods for protection after brachial plexus injury, by analyzing 1,797 articles concerning the repair of brachial plexus injuries, published between 2004 and 2013 and indexed by the Science Citation Index database. Results revealed that there are many methods used to repair brachial plexus injury, and their effects are varied. Intervention methods include nerve transfer surgery, electrical stimulation, cell transplantation, neurotrophic factor therapy and drug treatment. Therapeutic methods in this field change according to the hot topic of research.


Introduction
Brachial plexus injury is a disabling condition. In particular, total brachial plexus root avulsion is a most severe disability in the upper extremity, and the prognosis is poor. Therefore, the accurate diagnosis and effective treatment of brachial plexus injuries is an ongoing issue (Lao, 2010). Methods of rehabilitation for conserving and restoring function after brachial plexus injuries are still being standardized. In active exploration whether independent movement can be effectively restored after injury, whether brain plasticity is accelerated and reforms to regulate the injured nerves, and whether rehabilitation involving human brain plasticity is effective are yet to be explored (Xu et al., 2010).
With the progress of medical technology and the attention of professional rehabilitation personnel to brachial plexus injury research, neural function can be restored to a certain degree in patients with brachial plexus injuries. Various intervention methods are often simultaneously and effectively used in clinic settings. Based on information from the Science Citation Index (SCI) database, this study summarized international developments in addressing brachial plexus injury and analyzed the hot topics in treating brachial plexus injury.

Data and methods
Data source 1,797 articles published between January 2004 and June 2013 were retrieved from the SCI database. The key words used were brachial plexus injury, repair, surgery, protection, nerve trans-fer, cell, acupuncture, neurotrophic factors, and medicine.

Inclusion criteria
(1) Peer reviewed articles related to brachial plexus injury; (2) methodological studies of brachial plexus injury.

Exclusion criteria
(1) Articles unrelated to the study aim; (2) unpublished articles; (3) news articles unrelated to the study aim; (4) articles that needed to be traced by telephone or manual search.

Analysis of when articles on brachial plexus injury were published during the period from 2004 to 2013
Between 2004 and 2013, 1,797 articles addressing brachial plexus injury were indexed by SCI, as shown in Figure 1. The highest annual number of published articles was more than 180. The number of articles showed a stable increasing trend, but the increase was not apparent. From 2008, the number of articles about brachial plexus injury exceeded 160 annually and was gradually increasing, until a decline in 2013.

Citations of a paper
In bibliometrics, one of the main criteria to measure the quality of a publication is its citation rate. This is a key index to assess the academic value of the literature to fellow scholars. 1,797 articles addressing brachial plexus injury were indexed by SCI in 2004-2013. In both 2004 and 2006 two "classic" articles were found, with one "classic" article found in each of the years 2005, 2007 and 2009. This indicates that the repair and protection of brachial plexus injuries was a hot topic in the field of hand surgery in these years ( Table 2).

Publication distribution for articles addressing brachial plexus injury
Most of the articles on brachial plexus injury were published in neurosurgery journals. A total of 80 articles were published in the Journal of Hand Surgery (American Volume), accounting for 4.452%, 73 by Journal of Neurosurgery, 71 by Neurosurgery, and less than 50 by other journals ( Table 3).

Number of articles on brachial plexus injury treatment by intervention method
As illustrated in Figure 2, nerve transfer was the most frequently reported choice for the repair of brachial plexus injury. Cell transplantation, electroacupuncture combined with exercise therapy, nerve growth factor therapy, and other nutritional medicine approaches have become therapies in the repair of brachial plexus injury in recent years, and have been increasing selected since 2011.             The fourth was written by Ilfeld and published in Anesthesia And Analgesia in 2011, entitled Continuous peripheral nerve blocks: a review of the published evidence. This article mainly discussed the application of a continuous peripheral nerve block during nerve transfer, concluding that avoiding intraoperative complications by using continuous peripheral nerve block was an area that anesthesiologists should focus on.
The fifth most highly cited article was by Leechavengvongs et al and published in Journal of Hand Surgery (American Volume) in 2006, entitled Combined nerve transfers for C 5 and C 6 brachial news avulsion injury. This study explored combined nerve transfer in the treatment of C 5 and C 6 root avulsion.
The sixth was written by Belzberg et al in 2004 and published in the Journal of Neurosurgery, entitled Surgical repair of brachial plexus injury: a multinational survey of experienced peripheral nerve surgeons. Belzberg et al suggested that the identification of which patients with brachial plexus injury had a better prognosis after surgery was well defined, but that the practical repair methods of specific lesions required standardization. They stated that among experienced hand surgeons, different methods for the repair of brachial plexus injury were used. Areas of difference included diagnostic methods, the definition of the injury, surgical intervention time and indications, position of nerve transfer at the elbow and shoulder abduction sites, and neuroma treatment.
In these six articles, we found that the most highly cited manuscripts mainly focused on nerve transfer for brachial plexus injury. Most of these were published in 2004, with the most recent highly cited paper published in 2011.

Institutions publishing articles on surgery for brachial plexus injury
Among the articles addressing surgery for brachial plexus injury published between 2004 and 2013 (Figure 3), there were 47 articles from Fudan University in China, 23 articles from the Mayo Clinic in the USA, 19 articles from the Governador Celso Ramos Hospital in Brazil, 17 articles from Washington University in the USA, amongst others. Two of the 10 institutions were from China: Fudan University (first) and the Second Military Medical Hospital (sixth).

Citations of articles using cell transplantation for brachial plexus injury
Two of the five highly cited articles were published in 2007. The repair method described in these was not cell transplantation alone, but a combination of materials and cells. The highest cited article was written by Facer et al. in 2007 and published in BMC Neurology, entitled Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy. At the time of this study, it had been cited 89 times ( Table 5).

Citations of articles using electroacupuncture for brachial plexus
The most highly cited articles about electroacupuncture for brachial plexus injury were published between 2007 and 2009. The highest ranking of these had been cited 124 times at the time of this study, and is entitled Ultrasound guidance improves success rate of axillary brachial plexus block, written by Chan, Vincent W. S. et al. in 2007, and published in Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie. Each of the other four articles on this topic has also been cited more than 58 times ( Table 6).

Citations of articles investigating neurotrophic factor for brachial plexus injury treatment
The most highly cited articles using neurotrophic factor therapy for brachial plexus injury were mainly published in neurology journals and involved basic research. The repair method described mainly involves remodeling nerves. These publications suggest that neurotrophic factor for the treatment of brachial plexus injury has been gradually gaining attention ( Table 7).

Citations of articles concerning drug treatment for brachial plexus injury
When sorted by citation rates, drug treatment for brachial plexus injury was ranked in third place, behind surgery (first), and electroacupuncture (second). As shown in Table 8, the highest cited article discussing drug treatment was written by Berman et al and published in Pain in 2004, entitled Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. This article demonstrated the effect of marijuana on chronic pain related to brachial plexus root avulsion, using a clinical randomized, double-blind, and placebo-controlled crossover methodology. The results showed that marijuana was generally well tolerated with the most adverse indications being mild to moderate intoxication-type reactions, which quickly resolved.

Discussion
After a long period of basic and clinical investigation, the study of brachial plexus injury repair has undergone a long and difficult development process characterized by several stages of 'hot topics' in the area.
Using bibliometrics to investigate the literature on this topic, this study explored various intervention methods in the treatment of brachial plexus injury, and concludes as follows: (1) Nerve transfer is always the first choice for the treatment of brachial plexus injury. Studies mainly focus on transfer after C 5-6 brachial plexus avulsion. Recently, the number of articles on nerve transfer for brachial plexus injury has plateaued. However, this remains a hot topic. In regards to the institutions publishing in this area, organizations in China ranked first.
(2) The number of articles on cell transplantation and the use of neurotrophic factor for brachial plexus injury is low, but these articles were published more recently, and the number is gradually increasing. Although these articles were basic research, rather than surgery, the aims and results of cell transplantation and neurotrophic factor therapies are more focused on restorative and remodeling functions. Also, the combination of these and other therapies has recently become an area of focus for hand surgeons.
(3) The major new trend in the use of electroacupuncture for brachial plexus injury concerns the inhibitory effects of electroacupuncture on pain, according to the number of highly cited articles on this topic published between 2004 and 2013. In recent years, drug intervention has also obtained satisfactory outcomes and entered Phase III clinical trials.
(4) The analysis of countries showed that articles on repairing and protecting brachial plexus injuries were mainly from the USA. The number of papers far exceeded those from other countries, and lead the way in the study of this field.
(5) Articles concerning the repair and protection of brachial plexus injuries in China focused on surgical treatment, and are high in number and academic quality. Nevertheless, a few articles addressing electroacupuncture, drug treatment, cell transplantation and neurotrophic factor therapy were from China, so the number and quality of these could be improved.
It is hoped that this bibliometric and qualitative content analysis provides valuable information for hand surgery experts and researchers in the study of the repair and protection of brachial plexus injuries.