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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 34
| Issue : 3 | Page : 167-171 |
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A clinical study of single intraneural platelet-rich plasma injection in peripheral nerve repair
Saugat Das, Akoijam Ibohal Singh, Nehar Sinam, Laishram Oken Singh, Nepram Sanjib Singh
Department of Plastic Surgery, Regional Institute of Medical Sciences, Imphal, Manipur, India
| Date of Submission | 31-Jan-2021 |
| Date of Acceptance | 31-Jan-2021 |
| Date of Web Publication | 29-Apr-2021 |
Correspondence Address:
Akoijam Ibohal Singh
Department of Plastic Surgery, Regional Institute of Medical Sciences, Imphal West - 795 004, Manipur
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jms.jms_26_21
Background: Peripheral nerve injuries cause great morbidity leaving many with long-term disabilities with high societal costs. Direct tension-free microsurgical repair and/or the transplantation of a nerve autograft to bridge the gap are the gold standard treatments. However, such treatments may not recreate the suitable cellular and molecular microenvironment and in some cases, the functional recovery of nerve injuries is incomplete.
Aims and Objectives: The purpose of the study is to investigate if, and to what extent, PRP can improve the clinical condition after nerve repair. To study the effects and therapeutic potential of platelet rich plasma in traumatic nerve injury.
Materials and Methods: A hospital based Non-Randomized control trial was conducted in a tertiary hospital setup in Manipur, India, for a period of 2 years. This study was done on 12 patients who underwent peripheral nerve repair. Materials and method The selected sample will be divided into two groups. Control group was treated with direct tension-free epineural microsurgical repair and the treatment group was treated with direct tension-free epineural microsurgical repair along with intraoperative infiltrating the nerve stumps perineurally and intraneurally with a single dose of autologous PRP injection. Comparison was done on the basis of subjective and objective outcomes between the groups over a period of 1 year. Statistical analysis Statistical analysis was done by using IBM SPSS Version 21 for windows. Descriptive statistics such as mean, proportion, percentage were used to present the result. Chi square test was used to see the association of proportions. Student's t- test and repeated ANOVA were used for the continuous variables. P-value <0.05 was taken as significant.
Results: A total of 12 patients were included in the study, who were divided into 2 groups i.e., Case group and Control group, with 6 patients in each. The two groups were comparable with regards to patient characteristics, nerve injured and time interval to surgery. The patients in the case group, had significant improved outcome, when compare to control group, in terms of subjective (quickDASH) and objective tests (2-point discrimination, sensory recovery, motor strength and nerve conduction studies).
Conclusion: In this study we found that intraoperative PRP injection can improve the clinical outcome after nerve repair in traumatic nerve injury.
Keywords: Nerve injury, peripheral nerve repair, platelet-rich plasma
How to cite this article:
Das S, Singh AI, Sinam N, Singh LO, Singh NS. A clinical study of single intraneural platelet-rich plasma injection in peripheral nerve repair. J Med Soc 2020;34:167-71 |
How to cite this URL:
Das S, Singh AI, Sinam N, Singh LO, Singh NS. A clinical study of single intraneural platelet-rich plasma injection in peripheral nerve repair. J Med Soc [serial online] 2020 [cited 2023 Jun 9];34:167-71. Available from: https://www.jmedsoc.org/text.asp?2020/34/3/167/315102 |
| Introduction | |  |
Peripheral nerve injuries (PNIs) cause morbidity in 2.8% of all trauma patients, leaving many with long-term disabilities with high societal costs.[1] Every year, 350,000 patients are affected by traumatic PNIs, which accounts for $150 billion in annual health care costs. Direct tension-free microsurgical repair and/or the transplantation of a nerve autograft to bridge the gap are the gold standard treatments aimed at enhancing the intrinsic regenerative potential of injured axons. However, such treatments do not recreate the suitable cellular and molecular microenvironment, and in some cases, the functional recovery of nerve injuries is incomplete.
Platelet-rich plasma (PRP) products hold an important therapeutic potential as a neuroprotective, neurogenic, and neuroinflammatory therapeutic modulator system and as an enhancer of sensory and motor functional nerve-muscle unit recovery, emerging as a biological adjuvant in PNIs and neuropathies. These autologous products are applied, as a filler of nerve conduits or vein-muscle grafts across nerve gaps post trauma by infiltrating the nerve stumps perineurally and intraneurally which is guided with ultrasound probes, or as scaffolds to bridge or wrap the injured nerve stumps. Moreover, it can be used in nontraumatic peripheral injuries such as compression, adhesion, and fibrosis where this novel approach applied may additionally diminish undesirable consequences such as fibrotic scars and denervated organ atrophy since this adjuvant therapy can speed up the functional recovery of the nerve-muscle unit. Therefore, PRPs may be applied to assist and synergize with the gold standard therapies in nerve regeneration and neuropathies.[2],[3]
PRP is a new approach to tissue regeneration: it is widely used in various surgical fields, including head-and-neck surgery, otolaryngology, cardiovascular surgery, and maxillofacial surgery.[4] During wound healing, platelets are among the first cells to respond at a wound site, being critical to the initiation of this process. Besides their procoagulant effects, platelets form a rich source of important growth factors, such as platelet-derived growth factor, transforming growth factor-b 1 and 2, and vascular endothelial growth factor; all of these are involved in the angiogenic cascade which assists in hard- and soft-tissue wound healing.[5]
PRP can be prepared from autologous blood isolated by puncture as an entirely safe procedure. The clinical use of PRP causes no adverse events or postoperative complication. Meanwhile, the preparation of PRP is rapid, simple, convenient, and economical.
Depending on the device and technique used, PRP can contain variable amounts of plasma, erythrocytes, white blood cells, and platelets. The platelet concentration should be increased above baseline or whole blood concentration. It is generally agreed upon that PRP should have a minimum of five times the number of platelets compared to baseline values for whole blood to be considered “platelet rich.”[6] The purpose of the study is to investigate if, and to what extent, PRP can improve the clinical condition after nerve repair and to study the effects and therapeutic potential of PRP in traumatic nerve injury.
| Materials and Methods | | |
This hospital-based nonrandomized control trial was conducted in a tertiary hospital in Imphal, Manipur, for a period of 2 years from December 2018 to November 2020. The study was done on all the patients who were operated for PNI. Inclusion criteria were patients between the ages of 18 and 60 years. Exclusion criteria were (a) unwilling patients, (b) diabetes mellitus patients, (c) immunocompromised patients where wound healing may be affected, (d) mentally ill patients. A total of 12 cases were selected as sample size.
The selected sample will be divided into two groups. Control group patients were treated with direct tension-free epineural microsurgical repair, and case group patients were treated with direct tension-free epineural microsurgical repair along with intraoperative infiltration of the nerve stumps perineurally and intraneurally with a single dose of autologous PRP injection [Figure 1] and [Figure 2]. The patients were assigned to case and control groups according to the convenience of sampling. Study variables (independent) were age, sex, place of residence, religion, and nerve involved. Outcome measures were the procedure done, time interval between injury and repair, postoperative complications, subjective clinical improvement (pain and discomfort) using QuickDASH questionnaire, objective clinical improvement using study tools like two-point discrimination (2-PD) static (S2-PD) and dynamic (D2-PD), Medical Research Council scale for sensory outcome and muscle strength, and electroneurography ENG study (nerve conduction study [NCS]). Preparation and activation of PRP was done by the method described by Zheng et al.[1] The repaired nerves were injected intraneurally intraoperatively using a 22G needle of the autologous preparation. Around 0.4–0.5 ml of PRP was injected softly within the epineurium and around the injured nerve. Clinical evaluation was done at 1-month, 3-month, 6-month, and 12-month follow-up. | Figure 1: Platelet-rich plasma injective administration in and around the repaired Minerve
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Statistical analysis
Statistical analysis was done using IBM SPSS version 21, New Orchard Road Armonk, New York, USA. Descriptive statistics such as mean, proportion, and percentage were used to present result. Chi-square test was used to see the association of proportions. Student's t-test and repeated ANOVA were used for the continuous variables. P < 0.05 was taken as statistically significant.
Ethics issues
The study was taken up after getting clearance from the Research Ethics Board, Regional Institute of Medical Sciences, Imphal. All the participants were informed about the nature of the study.
| Results | | |
A total of 12 patients were included in the study, who were divided into 2 groups, i.e., case group and control group, with 6 patients in each. The patient characteristics were found to be not significantly different with regard to age distribution (P = 0.857; independent t-test), gender distribution (P = 1.000; Fisher's exact test), place of residence (P = 1.000; Fisher's exact test), and religion (P = 0.368; Chi-square) [Table 1]. | Table 1: Comparison of patient demographics of the case and control groups
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In the case group, three patients had median nerve injury and three patients had ulnar nerve injury, whereas in the control group, patients having median and ulnar nerve injury were 4 and 2, respectively. However, this difference was not significantly different. The two groups also did not have significantly different intervals between the time of injury and surgery. Therefore, the two groups were comparable with regard to patient characteristics, nerve injured, and time interval to surgery, as shown in [Table 2] and [Table 3], respectively. | Table 2: Comparison of nerve injured in the case and control groups (Fisher's exact test)
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 | Table 3: Comparison of time interval between injury and surgery (independent t-test)
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The patients in the case group had a significantly lower score of subjective assessment by Quick- Disabilities of the Arm, Shoulder and Hand score questionnaire, as shown in [Table 4]. The lower scores indicate a lower disability, i.e., better outcome. | Table 4: Comparison of subjective assessment by quick disabilities of the arm, shoulder, and hand questionnaire (independent t-test)
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For the assessment of two-point discrimination ability, the measurements were categorized into four groups of 1–5 mm (which is the best score), 6–10 mm, 11–15 mm, and >15 mm (which is the worst score). At 1 month and 3 months, all patients of the case and control groups had no two-point discrimination ability, both static and dynamic. At 6 months, the case group patients had a better static and dynamic two-point discrimination measurement, however, this difference was not significantly different for the static two-point discrimination, but a significant difference was noted for the dynamic two-point discrimination. At 12 months, the case group had a significantly better static two-point discrimination measurement, and a better measurement of dynamic two-point discrimination, although not statistically significant [Table 5] and [Table 6]. | Table 5: Comparison of static two-point discrimination at 1, 3, 6, and 12 months (Pearson χ2)
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 | Table 6: Comparison of dynamic two-point discrimination at 1, 3, 6, and 12 months (Pearson χ2)
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For assessment of sensory recovery, the scores of the British Medical Research Council (BMRC) were grouped as S0, S1/S1+, S2/S2+, S3/S3+, and S4, as shown in [Table 7]. All patients had an S0 score at 1 month; scores at 3 and 6 months were not statistically different, but at 12 months, the sensory scores of case group patients were significantly better than that of the control group (P = 0.046). | Table 7: Comparison of British Medical Research Council score of sensory recovery at 1, 3, 6, and 12 months (Pearson χ2)
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For assessment of muscle strength recovery, BMRC muscle strength grading system was used (M0–M5) and the scores of two muscles supplied by the particular injured nerve were summed to derive a score ranging from 0 to 10, and the scores were grouped as 0, 1–3, 4–6, and 7–10. All patients had a score of 0 at 1 month. The patients in the case group had a significantly higher score at 3, 6, and 12 months (P = 0.014, 0.013, and 0.002, respectively), as shown in [Table 8]. At 6 months, NCS motor velocity measurements were done. | Table 8: Comparison of muscle strength recovery British Medical Research Council muscle strength grading system (Pearson χ2)
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For the case group, the mean motor velocity was 41.938 m/s, which was significantly higher than the mean velocity of 16.770 m/s of the control group. The mean sensory velocity of the case group was also significantly higher than that of the control group, as shown in [Table 9]. | Table 9: Comparison of nerve conduction study motor and sensory velocities at 6 months (independent t-test)
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| Discussion | | |
PRP is an autologous cell therapy containing many bioactive factors that are involved in wound healing and tissue repair, which has several advantages compared with other products and techniques
The ultimate goal of any peripheral nerve repair strategy is the restoration of nerve-target organ function while minimizing therapeutic side effects. PRPs are versatile and safe biological products to be harnessed by surgeons and clinicians as an adjuvant therapeutic tool to enhance the robust intrinsic nerve repair processes and overcome posttraumatic and neuropathic inhibitory microenvironment by combinatorial strategy of delivering neurotrophic and neurotropic factors. They may assist nerve conduit guidance and grafts as a filler, as a liquid in intraneural and perineural ultrasound-guided injections in nerve entrapments and fibrosis, and as a scaffold to bridge or wrap the injured nerve gap.
This study was done to compare the nerve regeneration after PNI repair between primary repair and primary repair with PRP injection. The patients and injury characteristics of both the groups were similar. It was noted that there is a significant improvement in subjective assessment by qDASH questionnaire for patients receiving PRP therapy and also better static and dynamic two-point discrimination. It was also observed that the sensory recovery was significantly better at 12 months, and motor strength recovery was better at 3, 6, and 12 months in patients receiving PRP therapy. PRP therapy also resulted in significantly better NCS motor and sensory velocities at 6 months after surgery.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Zheng C, Zhu Q, Liu X, Huang X, He C, Jiang L, et al. Improved peripheral nerve regeneration using acellular nerve allografts loaded with platelet-rich plasma. Tissue Eng Part A 2014;20:3228-40.  |
| 2. | Sánchez M, Garate A, Delgado D, Padilla S. Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair. Neural Regen Res 2017;12:47-52. |
| 3. | Alcaraz J, Oliver A, Sánchez JM. Platelet-rich plasma in a patient with cerebral palsy. Am J Case Rep 2015;16:469-72. |
| 4. | Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:638-46. |
| 5. | Albanese A, Licata ME, Polizzi B, Campisi G. Platelet-rich plasma (PRP) in dental and oral surgery: From the wound healing to bone regeneration. Immun Ageing 2013;10:23. |
| 6. | Anjayani S, Wirohadidjojo YW, Adam AM, Suwandi D, Seweng A, Amiruddin MD. Sensory improvement of leprosy peripheral neuropathy in patients treated with perineural injection of platelet-rich plasma. Int J Dermatol 2014;53:109-13. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]
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