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The Painful Neuroma: The Regenerating the Epineural Sheath
Axon versus
A. WENDELL NELSON, D.V.M.,PH.D. Surgical Laboratory, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80521 Submitted for publication September 9, 1976
The painful neuroma has been a critical problem as long as amputations and peripheral nerve surgery has been practiced. Historically, the relatively high incidence (2030%) of this lesion occurring after neurectomy has been experienced by clinician and investigator no matter which technique of cutting, injection, implanting, or ligating the nerve end was employed [l-3, 6- 121. Normally, the intact peripheral nerve is encased in an organized fibrous connective tissue sheath. This and other encasing sheaths keep the axon appendages of the neuron in their proper place. After severe nerve injury, the regenerating axons find discontinuities in their regenerating sheaths and aimlessly wander in the proliferating connective tissue. Thus, the basic structure of an organized sheath system is missing in the unsuccessful attempts to stop painful neuroma formation. Several techniques have been used for the purpose of confining the regrowth of axons after neurectomy. The proximal nerve end has been implanted in a biologic (i.e., bone or vein) or synthetic (i.e., tantalum cap) confine in an attempt to keep free axons from escaping into the loosely organized scar tissue. These techniques have given varied results until more versatile materials have been developed. The technique of covering the transected nerve with silicone rubber tubing proved effective in reducing the incidence of painful neuroma [5]. However, this technique required meticulous preparation of the silicone tubing and considerable time in
surgery. Also, the need for a relatively long free nerve segment to encase in the tube precludes its use where short segments are encountered (i.e., neuroma resections). This method does result in fulfillment of the basic criterion for painful neuroma prevention, axon confinement. The plastic sheath protects the cut nerve from the general disorganized scar tissue bed and provides a smooth surface conducive to the formation of an organized fibrous connective tissue sheet between the nerve and the plastic. The connective tissue sheet is continuous with the proliferating epineurium and forms a viable encasement for the proliferating Schwann cells and axons. A more physiologic method of nerve encasement after neurectomy has been the utilization of the epineural sheath. The current technique in use at Colorado State University entails the reflection of the epineural sheath of the proximal nerve segment for a distance of approximately 2 cm. Careful atraumatic technique is needed to ensure complete survival of an absolute intact sheath. The exposed nerve is hemisected in two places proximad to the complete transection. The nerve is transected approximately 1.0 cm from the site of initial neurectomy leaving the nerve shorter than the sheath. The epineural sheath is slid back over the transected nerve stump and circumferentially ligated approximately 0.5 cm distad to the reensheathed proximal nerve stump. This provides a ready-made, viable, organized connective tissue encasement of the regenerating nerve. Although tedious
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FIG. 1. Photograph of posterior digital nerve with the silk suture in place and ready for capping.
and time consuming, this is the procedure of choice when it can be utilized. However, an alternate method is needed in cases where the usable nerve segment is too short for this technique or the sheath is not completely intact. The subject of this report is the utilization of a Silastic elastomer (Silicone elastomer No. 382, Dow Corning Chemical Corp., Midland, Michigan) as an encasement material for problem cases of nerve capping. The effective use of silicone elastomer in nerve anastomosis in dogs and primates is a significant improvement in previous methods of anastomotic site encasement to prevent neuroma development and to enhance the chances of nerve regeneration [4]. This elastomer was well tolerated by the
FIG. 2. Photograph of modified allis tissue forceps (a) and Silastic mold (b).
VOL. 23, NO. 3, SEPJYEMBER 1977
FIG. 3. Photograph of modified allis tissue forceps holding the two halves of the Silastic elastomer-filled molds together around the exposed posterior digital nerve. The silk suture holding the nerve end can be seen emerging from the mold.
tissues and prevented axons from escaping to form a neuroma. The elastomer is an easily handled viscous fluid with a rapid, nonexothermic catalyzed setting. This allows for on-the-spot molding of custon caps for any nerve length or diameter. METHODOLOGY Ten mature ponies weighing between 300 and 550 lb were used in this study. Each pony was prepared for bilateral posterior digital neurectomy on each leg. The
FIG. 4. Photograph of the capped nerve immediately after the mold was removed.
A. WENDELL
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FIG. 5. Photograph of the capped nerve ready for embedding.
hair was clipped from the coronary band to the carpus or the tarsus with a No. 40 blade. The ponies were then placed under general anesthetic using atropine sulfate (2 mg/lOO lb body weight) and acetylpromazine (10 mg/100 lb body weight) as preanesthetic agents, thiamylal sodium (1- 1.5 g iv; Surital, Parke- Davis, Detroit, Michigan) to induce general anesthesia, and halothane (Fluothane, Ayerst Laboratories, New
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York, New York) to maintain anesthesia. The animal was placed in lateral recumbency and the distal limbs prepared for aseptic surgery. Each postdigital nerve was exposed through a skin incision (3 cm long) beginning approximately 1.5 cm distad to the fetlock joint. Approximately 1.5 cm of nerve was dissected free and transected at its distal end. Hemostasis was maintained throughout the entire procedure. This is particularly important for the intraneural vessels in order to maintain a dry field. A simple interrupted silk suture (4-O) was placed in the proximal nerve stump 1 mm proximad to the cut edge; it pierced both sides of the epineurium so that when tied it would essentially close the end of the nerve without encirclement. The ends of this suture material were left approximately 8 cm long so that they could be used for traction during the capping procedure. Each nerve, whether it was capped or not, was treated in this similar manner and was exposed for the same length of time (approximately 5 min). The nerve stump that was to be capped
FIG. 6. Micrograph of a capped nerve (a) that partially migrated out of the Silastic cap (b). Note suture (c) in tissue at mouth of cap (x7).
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FIG. 7. Micrograph of nerve and surrounding tissue from which the Silastic cap was extruded; within the first week after implantation the nerve end (a) is heavily encased in connective tissue (b) (x6.0).
with the elastomer was stabilized by the use of the silk suture material (Fig. 1). The elastomer was mixed with a sufficient amount of catalyst to provide setting of the elastomer in approximately 2 min. After the
catalyst and elastomer had been thoroughly mixed (30 set), the mixture was poured into the two sides of the cap mold. The two sides of the mold were placed around the nerve stump and held in place for 3 min with pair
FIG. 8. Micrograph of capped nerve in which the distal one-third of the nerve stump has degenerated
(x7.7).
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9. Micrograph utilizing polarized light to define mature collagen. A thin layer of collagen (a) can be surrounding the Silastic cap (~7.7).
of forceps (Figs. 2 and 3). The mold was removed. This left the nerve capped with a Silastic coating and the end of the silk suture extending out through the distal end of the cap (Fig. 4). The silk suture was then cut off next to the cap and sealed over with additional elastomer to prevent axons from growing along the suture and into surrounding tissue. After this final coating of elastomer had solidified, the nerve was replaced into its original bed (Fig. 5). The initial closure of the connective tissue surrounding the capped nerve was done so that all dead space was closed and a viable tissue barrier was placed between the Silastic and the skin incision. The skin was then closed with simple interrupted sutures. A sterile gauze pack was placed on the skin wounds and the leg was wrapped from the coronary band to the mid-metacarpus or metatarsus with cotton gauze. This was overwrapped with elastic tape starting at the hoof wall and carrying up to a point proximal to the gauze bandage. Ponies were confined to a box stall for 48 hr after surgery. The bandage was left in place for approximately
5 days, at which time it was removed. The incision sites were examined for seepage or extrusion of the cap. The skin sutures were removed at 10 days. The ponies were held in a dry corral or on pasture until tissues were harvested for histologic examination. Ponies were sacrified between 3 months and 1 year following the neurectomy. The digital nerve segments and surrounding tissue were removed immediately and placed in cold (4°C) buffered formalin. The fixed tissue was imbedded in paraffin and sectioned at 6 pm. The sections were stained with hematoxylin and eosin for cellular detail. RESULTS
A total of 80 posterior digital nerves was transected during this project. Forty of these were capped with Silastic elastomer and the other 40 were left uncapped. Although varying degrees of sensitivity remained over the neurectomy site during the early postoperative period, painful neuromas were not detected in either the
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capped or the uncapped sites. The duration of sensitivity varied between ponies (3-6 weeks), yet seemed to be of longer duration in those with Silastic caps on the nerve. This was probably due to the relatively large bulk of plastic that was placed in the tissue. Three results occurred in the capped nerves. Approximately 60% of these underwent a migration of the encased nerve segment out of the cap until the distal end lay at the open end of the cap (Fig. 6). This was detected by the shape of the nerve stump and the presence of the silk suture material in the nerve end. The nerve stump formed a sigmoid shape and was covered by a layer of connective tissue. Twenty-five percent of the caps were extruded through the skin during the first 7 days after surgery. At the end of the experiment these nerve segments were found adhered to the subcutaneous tissue and surrounded by a layer of connective tissue. The nerve stump was essentially the same size and shape as when it was originally encapsulated (Fig. 7). Fifteen percent of the nerve segments
remained inside the elastomer capsule and underwent necrosis of the distal one-third of the stump. The viable nerve end was encased in a thin fibrous capsule (Fig. 8). The traditional “neuroma” normally observed in the distal end of severed nerves developed only slightly in the capped nerves. The distal end of the nerve gradually tapered into a connective tissue scar. Microscopic examination of the tissues surrounding the capped nerves revealed a mild inflammatory reaction which gradually organized by the fifth postsurgical month and matured to a thin connective tissue sheath by 1 year (Fig. 9). The uncapped nerve ends formed the traditional neuroma (Fig. IO), which seemed to be randomly encased in connective tissue. The unexpected lack of painful neuroma formation in the uncapped nerves may have been due to the closing of the epineural sheath by the single silk suture placed at the end of the nerve. Although this did not prevent completely outgrowth of axons from the nerve stump, it may have retarded axon regrowth sufficiently to allow time for some connective tissue encasement (Figure 10).
FIG. 10. Micrograph of a noncapped nerve end encased in a collagen sheath (a). A small neuroma (b) has developed at the distal end (x7.7).
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This attempt at uniform treatment of all nerve stumps may have inadvertently led to a reduction in the possibility of painful neuroma formation. These results provide a greater insight into the actual procedures necessary to prevent painful neuroma formations, as well as further evidence of the tissue compatibility of this elastomer. In all cases of Silastic capping, the encased nerve end was surrounded completely in a smooth, organized connective tissue mass which prevented the wandering of axons into the surrounding tissues. DISCUSSION
The basic concept of a viable connective tissue sheath encasing the distal end of the transected nerve has been obtained through the atraumatic handling of the tissues, while using the two aforementioned Silastic capping and epineural capping procedures. Other previous methods have utilized some traumatic procedure in an attempt to curtail the regrowth of the nerve. Under circumstances which preclude epineural sheath capping, the liquid elastomer (No. 382) could be easily used for “custom” capping. This technique provides the same advantages as the Silastic tube for capping, yet does not have its disadvantages. The development of simple instrumentation for cap molding would reduce the capping time to l-3 min per nerve. The need for only 0.5 cm of nerve end to carry out this procedure is a strict advantage. SUMMARY
The basic concepts of nerve capping for the prevention of painful neuroma production were discussed. The need for an organized fibrous connective tissue sheath encasing the transected nerve end to pre-
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vent painful neuroma formation was stressed. A modification of the silastic tubing capping technique using a Silastic elastomer (No. 382, Dow Corning Chemical Corp., Midland, Michigan) in ponies was presented and discussed. This method has the decided advantage of needing only 0.5 cm of nerve stump to carry out the capping procedure. REFERENCES 1. Adams, 0. R. Lameness in Horses,
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2nd ed., p. 58. Lea and Febiger, Philadelphia, 1966. Boldrey, E. E. Amputation neuroma in nerves implanted in bone. Ann. Surg. 118~1052, 1943. Campbell, J. B., Bassett, C. A. L., Husby, J.. Thulin, C. A., and Feringa, E. R. Microfilter sheaths in peripheral nerve surgery: A laboratory report and preliminary clinical study. J. Trauma 1: 139, 1%1. Ducker, T. B. and Hayes, G. J. Experimental Improvements in the use of Silastic cuff for peripheral nerve repair. J. Neurosurg. 28: 582, 1968. Evans, L. H., Campbell, J. B., Pinner-Poole, B., and Jenny, J. Prevention and painful neuromas in horses. J. Amer. Vet. Med. Assoc. 153: 313, 1%8. Farley, H. H. Painful stump neuroma, treatment of. Minn. Med. 48: 679, 1%5. Gorman, T. N., Nold, M. M., and King, J. M. Radioactive ligatures in neurectomy. Cornell Ver. 52: 542, 1962. Hirasawa, Y., and Marmor, L. The protective effect of irradiation combined with sheathing methods on experimental nerve heterografts: Silastic, autogenous veins, and heterogenous arteries. J. Neurosurg. 27: 401, 1%7. Schebitz, H. Podotrochlosis in the horse. In Pro-
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Denver, December 1964, pp. 49-53. 10. Weir, M. S. Injuries of Nerves and Their Consequences, p. 343. J. B. Lippincott, Philadelphia, 1973. 11. White, J. C., and Hamlin, H. New uses of tantalum in nerve suture; control of neuroma formation. J. Neurosurg.
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12. Unpublished review of 565 clinic cases from the files of Colorado State University, Large Animal Clinic.