Epineurial repair

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Epineurial repair
Epineurial Repair.jpg
Repair to epineurium via epineurial repair
Specialty neurology

Epineurial repair is a common surgical procedure to repair a nerve laceration via the epineurium, the connective tissue surrounding nerve fibers originating from the spinal cord. It is intended to allow the restoration of sensory function. When a nerve is lacerated or cut, repair is done by sewing the cut ends together through the epineurium to increase the potential of the proximal part growing correctly along the route the degrading distal part leaves behind. Usual sensation and mobility will not be an immediate result because nerves grow at a rate of approximately 1 millimeter per day, so it will take a few months to notice the final outcome. [1] Research in use of nerve grafts and nerve growth factors is being done to speed recovery time.

Contents

Reasons

A nerve injury in continuity results when axonal function is nonexistent but the structure of the connective tissue is preserved. More severe nerve injury like axonotmesis or neurotmesis warrant the repair of the epineurium because the connective tissue is damaged. The epineurium is preserved in a nerve injury in continuity by definition and the severity of the injury varies with the amount of the connective tissue preserved. [2] Typical indications for surgery are if the patient who presented with a laceration has no conduction along the axon, signal transmitted across the nerve, or does not recover within a week. Numbness and paralysis varies depending on the amount of functional loss due to the axonal interruption. The lack of signal being sent from the brain across the gap is caused by the laceration. The procedure can be applied to any nerve epineurium. [1] [3] The procedure is used to repair different-sized fascicles and non-grouped fascicles compared to group fascicular and perinuerial repair.[ citation needed ]

Challenges

Glial scars can have detrimental effects to neuronal regrowth to aide in the restoration of sensory function. Astrocytes form a barrier preventing further growth by forming gap junctions along with producing molecules that chemically prevent axon extension.[ citation needed ]

Tension in the rejoined nerve may stretch the epineurium and rip the two parts from each other again. Even tension along the sutured joint is necessary for an even repair.[ citation needed ]

The results of gaining motor function cannot guarantee results. The amount of scarring and size of the gap influences the results of the repair. The larger the gap, the less likelihood of recovery because more axon would have to grow further and astrocytes could develop over the longer length of time it takes to grow than with a shorter gap. In order to reduce the length of time for regeneration, further research is being conducted to speed regeneration such as nerve grafts and stem cells.

Approach

Detailed descriptions of epineural repair focus on removal of scar and apposition of healthy tissue. [3] [ additional citation(s) needed ] After removal of scarred nerve tissue, the nerve is freed from surrounding soft tissues and its course may be shifted to allow the free ends to meet more easily. Initial sutures are placed on opposite sides of the joint, through the epineurium and slightly into the subepineurial neural structure to anchor the two nerves together. Suturing continues 180 degrees from each initial suture. The position of the lateral sutures is reversed to expose the opposite side and sutured the same way. Glue can be used in the place of some sutures to limit scarring, resulting in better axonal growth, and speed up the surgery. If it is needed to bend the body part in any position to bring the nerve ends together, the patient is instructed to maintain this position for 10–14 days in order not to disrupt the repair. [1]

Recovery

The length and efficiency of recovery is depended on the regenerative process that may require 6 to 18 months. The length of the nerve and site of the injury influences the recovery time. To avoid tension during recovery (generally 10–14 days), minimizing movement of the nerve may reduce risk of further damage. [1] Regaining motor function is the intended result. Typical axon regrowth amounts to approximately 1 millimeter per day. Signs of recovery may present quickly, which is thought to be due to so-called "pioneer axons", axons that arrive at the recovery site along the pathway ahead of the rest of the nerve fibers. [4] Nerve growth factors and nerve grafts can also be used to increase the speed of the regenerative process.

Cross Section of Epineurium
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Transverse section of human tibial nerve. (Epineurium labeled at upper right.)
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Nerve structure
Anatomical terminology

Perineurial repair involves the individual fascicles and placing sutures through the perineurium, the protective sheath surrounding fascicles, the nerve fibers enclosed by the perineurium. Trauma to the nerve by cutting out each fascicle and fibrosis, a build up of tissue as a reaction, that develops due to the dissections and number of sutures is a problem. [5] Group fasicular repair involves suturing group fascicles in the intraneural epineurium to line up the groups of fascicles. This is only applicable when fascicles are grouped. [5] Intraneural scarring due to the amount of dissection and manipulation of the repair is a potential result that may counteract the advantage of alignment of the fascicles. [2]

Epineurial repair was shown to be as good as perineurial repair in acute nerve laceration, a small cut to the nerve, in cats by evaluating the ambulation pattern, fanning of claws and sensation. The objective measures were efficiency, absolute strength and weight of the flexor carpi ulnaris muscle. [6] The anterior tibial nerves of dogs were cut to determine which of fascicular, interfascicular and epineural suture techniques were best. There was not a significant difference between the results of fascicular and epineural, but a significant difference between the two and interfascicular. [7] In a study of 18 children with a 2:1 ratio of male to female, the children showed a recovery of motor and sensory functions assessed by the Bruininks–Oseretsky test, a test used to measure motor skills such as balance or cutting out a circle from a piece of paper. [8] [9]

Perspectives

Growth factors

Research for the use of neurotrophic factors such as N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) to aide in the nerve regeneration was started in 2011. Assessments using a grasp test (a test to measure how well an object is grab) were performed weekly for 12 weeks in order to know functional recovery of the flexor muscle (the muscle that is flexed when the end of the finger is brought to the palm) in fingers along with median nerve regeneration. The results showed that MDP with fibrin tissue adhesive (FTA) and epineurial sutures were the best performing group among the sutures and sutures combined with FTA. [10]

Artificial nerve grafts

When nerve repair cannot be performed without tension, nerve grafting can be used and is considered the most suitable treatment of peripheral nerve injuries, injuries to nerves outside of the brain and spinal cord. Nerve grafts are used to avoid tension at the proximal and distal ends, to reduce the likelihood of postoperative distraction. A nerve graft will be about 10 percent longer than the gap between the nerves, and the cross-section of the nerve end will be a quite larger than the diameter of the nerve graft to allow for growth. The use of harvested nerve grafts from a donor nerve provider contain Schwann cells and basal lamina endoneurial tubes that provide growth factors and surfaces for molecules to regenerate the axons. [11]

Sensory loss, scarring and neuroma formation can cause morbidity to the donor site of the patient the nerve is harvested from. Therefore, alloplastic nerve graft research is being conducted for nerve repair. Silicone has been used previously, but long-term use of tubes produces compression and decreased conduction, requiring surgery to remove the tube. Conduits made from polyglycolic acid, a bioabsorbable substance used for dissolvable sutures, reduce the problems associated with silicone and eliminate problems associated with nerve grafts taken from donors. In a study on nerve repair comparing nerve grafts and polyglycolic acid conduits, there was no statistical differences, but 2-point discrimination showed that the conduit group was better at eliminating donor-site morbidity as a result of the graft. [5]

Stem cells

Nerve tissue loss is associated with the more severe nerve injuries. 50-60% of sensory and motor neurons has been calculated from experiments after the use of nerve grafts Schwann cells form myelin, insulation to the nerve to allow better conduction along the axon, around the nerve fibers and secrete growth factors that play a major role in the regeneration process. The cells can align themselves to provide directional support to the regrowth of axons after injury and possibly increase the level of secretion of growth factors by being modified genetically. The time needed to grow and harvest the cells may be too long for less severe injury because it takes 10 weeks to culture or grow enough. [12]

Cell therapy to improve nerve regeneration is also being researched. In one study mononuclear cells, cells with one nucleus, were used to repair the sciatic nerve, a large nerve running through the leg to the butt, followed by epineurial repair. Wistar rats were divided into groups of a control, epineurial sutures, medium after suture and injection of 10 microliters of medium into the nerve to allow for growth of cells still there, and mononuclear cells combined with medium after structure in the epineurium region. Results of sciatic functional index, histological and morphometric analyzes showed that the mononuclear group was the best. [13]

Related Research Articles

Axon Long projection on a neuron that conducts signals to other neurons

An axon, or nerve fiber, is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction has caused many inherited and acquired neurological disorders which can affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.

Nerve Enclosed, cable-like bundle of axons in the peripheral nervous system

A nerve is an enclosed, cable-like bundle of nerve fibers in the peripheral nervous system.

Schwann cell

Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle. The two types of Schwann cells are myelinating and nonmyelinating. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. The Schwann cell promoter is present in the downstream region of the human dystrophin gene that gives shortened transcript that are again synthesized in a tissue-specific manner.

Motor nerve

A motor nerve is a nerve located in the central nervous system (CNS), usually the spinal cord, that sends motor signals from the CNS to the muscles of the body. This is different from the motor neuron, which includes a cell body and branching of dendrites, while the nerve is made up of a bundle of axons. Motor nerves act as efferent nerves which carry information out from the CNS to muscles, as opposed to afferent nerves, which send signals from sensory receptors in the periphery to the CNS. Efferent nerves can also connect to glands or other organs/issues instead of muscles. In addition, there are nerves that serve as both sensory and motor nerves called mixed nerves.

Wallerian degeneration Biological process of axonal degeneration

Wallerian degeneration is an active process of degeneration that results when a nerve fiber is cut or crushed and the part of the axon distal to the injury degenerates. A related process of dying back or retrograde degeneration known as 'Wallerian-like degeneration' occurs in many neurodegenerative diseases, especially those where axonal transport is impaired such as ALS and Alzheimer's disease. Primary culture studies suggest that a failure to deliver sufficient quantities of the essential axonal protein NMNAT2 is a key initiating event.

Neurotmesis is part of Seddon's classification scheme used to classify nerve damage. It is the most serious nerve injury in the scheme. In this type of injury, both the nerve and the nerve sheath are disrupted. While partial recovery may occur, complete recovery is impossible.

Axonotmesis is an injury to the peripheral nerve of one of the extremities of the body. The axons and their myelin sheath are damaged in this kind of injury, but the endoneurium, perineurium and epineurium remain intact. Motor and sensory functions distal to the point of injury are completely lost over time leading to Wallerian degeneration due to ischemia, or loss of blood supply. Axonotmesis is usually the result of a more severe crush or contusion than neurapraxia.

Epineurium Outermost layer of a nerve

The epineurium is the outermost layer of dense irregular connective tissue surrounding a peripheral nerve. It usually surrounds multiple nerve fascicles as well as blood vessels which supply the nerve. Smaller branches of these blood vessels penetrate into the perineurium. In addition to blood vessels which supply the nerve, lymphocytes and fibroblasts are also present and contribute to the production of collagen fibers that form the backbone of the epineurium. In addition to providing structural support, lymphocytes and fibroblasts also play a vital role in maintenance and repair of the surrounding tissues.

Neural engineering is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs.

Endoneurium Connective tissue layer around myelinated nerve fibers in peripheral nervous system

The endoneurium is a layer of delicate connective tissue around the myelin sheath of each myelinated nerve fiber in the peripheral nervous system. Its component cells are called endoneurial cells. The endoneuria with their enclosed nerve fibers are bundled into groups called nerve fascicles, each fascicle within its own protective sheath called a perineurium. In sufficiently large nerves multiple fascicles, each with its blood supply and fatty tissue, may be bundled within yet another sheath, the epineurium.

Nerve injury Medical condition

Nerve injury is an injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve fiber injury and whether there is continuity of the nerve. Usually, however, peripheral nerve injuries are classified in five stages, based on the extent of damage to both the nerve and the surrounding connective tissue, since supporting glial cells may be involved.

Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system (PNS) and the central nervous system (CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelin sheath. The proximal segment can either die by apoptosis or undergo the chromatolytic reaction, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.

Neural tissue engineering is a specific sub-field of tissue engineering. Neural tissue engineering is primarily a search for strategies to eliminate inflammation and fibrosis upon implantation of foreign substances. Often foreign substances in the form of grafts and scaffolds are implanted to promote nerve regeneration and to repair damage caused to nerves of both the central nervous system (CNS) and peripheral nervous system (PNS) by an injury.

Glial scar Mass formed in response to injury to the nervous system

Glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.

Peripheral nerve injury classification

Classification of peripheral nerve injury assists in prognosis and determination of treatment strategy. Classification of nerve injury was described by Seddon in 1943 and by Sunderland in 1951. The lowest degree of nerve injury in which the nerve remains intact but signaling ability is damaged is called neurapraxia. The second degree in which the axon is damaged but the surrounding connecting tissue remains intact is called axonotmesis. The last degree in which both the axon and connective tissue are damaged is called neurotmesis.

Olfactory ensheathing cell Type of macroglia that ensheath unmyelinated olfactory neurons

Olfactory ensheathing cells (OECs), also known as olfactory ensheathing glia or olfactory ensheathing glial cells, are a type of macroglia found in the nervous system. They are also known as olfactory Schwann cells, because they ensheath the non-myelinated axons of olfactory neurons in a similar way to which Schwann cells ensheath non-myelinated peripheral neurons. They also share the property of assisting axonal regeneration.

Nerve allotransplantation is the transplantation of a nerve to a receiver from a donor of the same species. For example, nerve tissue is transplanted from one person to another. Allotransplantation is a commonly used type of transplantation of which nerve repair is one specific aspect.

Cryoneurolysis, also referred to as cryoanalgesia, is a medical procedure that temporarily blocks nerve conduction along peripheral nerve pathways. The procedure, which inserts a small probe to freeze the target nerve, can facilitate complete regeneration of the structure and function of the affected nerve. Cryoneurolysis has been used to treat a variety of painful conditions.

Preferential motor reinnervation (PMR) refers to the tendency of a regenerating axon in the peripheral nervous system (PNS) to reinnervate a motor pathway as opposed to a somatosensory pathway. PMR affects how nerves regenerate and reinnervate within the PNS after surgical procedures or traumatic injuries. It is important to understand in order to further develop axonal regrowth surgical techniques. Further research of preferential motor reinnervation will lead to a better understanding of peripheral nervous system function in the human body regarding cell roles and abilities.

Spinal cord injury research seeks new ways to cure or treat spinal cord injury in order to lessen the debilitating effects of the injury in the short or long term. There is no cure for SCI, and current treatments are mostly focused on spinal cord injury rehabilitation and management of the secondary effects of the condition. Two major areas of research include neuroprotection, ways to prevent damage to cells caused by biological processes that take place in the body after the insult, and neuroregeneration, regrowing or replacing damaged neural circuits.

References

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  3. 1 2 Wheeless, C. (2011, September 8). Epineural nerve repair. Retrieved from http://www.wheelessonline.com/ortho/epineural_nerve_repair
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  8. Hudson DA, Bolitho DG, Hodgetts K. Primary epineural repair of the median nerve in children. J Hand Surg Br Vol. 1997 Feb;22(1):54-6. PubMed PMID   9061526.
  9. Bolitho DG, Boustred M, Hudson DA, Hodgetts K. Primary epineural repair of the ulnar nerve in children. J Hand Surg Am Vol. 1999 Jan;24(1):16-20. PubMed PMID   10048511.
  10. Fornazari AA, Rezende MR, Mattar Jr R, Taira RI, Santos GB, Paulos RG. Effect of neurotrophic factor, MDP, on rats' nerve regeneration. Braz J Med Biol Res. 2011 Apr;44(4):327-31. Epub 2011 Feb 25. PubMed PMID   21344131.
  11. Santin, Matteo. "Nerve Autografts." Strategies in Regenerative Medicine: Integrating Biology with Materials Design. New York: Springer, 2009. 325. Print.
  12. Geuna, Stefano, Pierluigi Tos, and Bruno Battiston. Multipotent stem cells, cells with the ability to grow into an restricted number of cell types specific to a tissue, are believed to be able to change into cells for other tissues, which has created interest in the use for nerve regeneration. Cells from bone marrow, mesenchymal stem cells, have been shown to secrete growth factors and produce myelin genes when grown with neuronal cells. Stem cells from adipose tissue have a higher frequency of about 100 to 1000 more than mesenchymal stem cells, which reduces the delay between the injury and transplantation of the cells and can express the same markers found in Schwann cells for axonal growth. "Use of Stem Cells for Improving Nerve Regeneration." Essays on Peripheral Nerve Repair and Regeneration. New York: Academic, 2009. 393-99. Print.
  13. Lopes-Filho JD, Caldas HC, Santos FC, Mazzer N, Simões GF, Kawasaki-Oyama RS, Abbud-Filho M, Oliveira AR, Toboga SR, Chueire AG. Microscopic evidences that bone marrow mononuclear cell treatment improves sciatic nerve regeneration after neurorrhaphy. Microsc Res Tech. 2010 Aug 23. [Epub ahead of print] PubMed PMID   20734409.