The Use of Nerve Caps after Nerve Transection in Headache Surgery: Cadaver and Case Reports

Abstract

Background:

Nerve transection with nerve reconstruction is part of the treatment algorithm for patients with refractory pain after greater occipital nerve (GON) and lesser occipital nerve (LON) decompression or during primary decompression when severe nerve injury or neuroma formation is present. Importantly, the residual nerve stump is often best addressed via contemporary nerve reconstruction techniques to avoid recurrent pain. As a primary aim of this study, nerve capping is explored as a potential viable alternative that can be utilized in certain headache cases to mitigate pain.

Methods:

The technical feasibility of nerve capping after GON/LON transection was evaluated in cadaver dissections and intraoperatively. Patient-reported outcomes in the 3- to 4-month period were compiled from clinic visits. At 1-year follow-up, subjective outcomes and Migraine Headache Index scores were tabulated.

Results:

Two patients underwent nerve capping as a treatment for headaches refractory to medical therapy and surgical decompressions with significant improvement to total resolution of pain without postoperative complications. These improvements on pain frequency, intensity, and duration remained stable at a 1-year time point (Migraine Headache Index score reductions of –180 to –205).

Conclusions:

Surgeons should be equipped to address the proximal nerve stump to prevent neuroma and neuropathic pain recurrence. Next to known contemporary nerve reconstruction techniques such as targeted muscle reinnervation/regenerative peripheral nerve interface and relocation nerve grafting, nerve capping is another viable method for surgeons to address the proximal nerve stump in settings of GON and LON pain. This option exhibits short operative time, requires only limited dissection, and yields significant clinical improvement in pain symptoms.

Takeaways

Question: Is nerve capping a viable modality for greater occipital nerve/lesser occipital nerve headache surgery?

Findings: Two patients underwent nerve capping and experienced significant to total resolution of pain (Migraine Headache Index score reductions of –180 to –205).

Meaning: Nerve capping is a promising treatment for refractory occipital neuralgia.

INTRODUCTION

Occipital neuralgia, typically driven by greater occipital nerve (GON) involvement,¹ comprises nearly 10% of presentations for undifferentiated facial pain.² Although frequently treated medically, patients refractory to these therapeutics exhibit an unmet need for alternative modalities. Headache surgery has become a viable treatment method for patients with occipital neuralgia in whom conservative treatment has failed.^3–5 The success of the procedure is fundamentally rooted in “decompression of extracranial sensory nerves from surrounding structures” with the goal of improving quality of life and alleviating intractable pain.⁶ The current surgical gold standard treatment for occipital headaches is decompression of the GON, lesser occipital nerve (LON), and third occipital nerve to alleviate neuropathic pain.⁶ If primary decompression fails, then secondary transection of the GON/LON for occipital neuralgia is considered.⁷ Furthermore, GON/LON excision during the index case can be considered if the nerve appears severely damaged or in patients presenting with painful neuromas from either iatrogenic or traumatic injury, an observed phenomenon in 15%–25% of postamputation-pain patients.^8–11

Nerve capping was introduced by Tupper and Booth in 1976 in an attempt to control immature sprouting of axons after nerve transection.¹² The initial experience of the nerve cap involved primarily silicone caps in a rat sciatic nerve model, which were placed over the cut end of the nerve to down-regulate nerve growth and inflammatory markers. This intervention yielded significantly reduced autotomy (of 50% absolute reduction or greater) and pain-associated behaviors from 3 days to 2 weeks with correlating inhibition of inflammatory infiltrate and neurotrophins.¹³ Recently, capping of the terminal nerve ends with biocompatible materials, including vein and nerve allograft, have superseded silicone caps with their increased longevity in limiting autotomy for up to 12 weeks in animal models.^14–16 Onode et al reported effective use of bioabsorbable nerve conduit caps to limit perineural inflammation, scar formation, and neuropathic pain in a rat model.¹⁵ We have recently described our experience in managing the proximal nerve segment after transection in headache surgery for neuroma prevention with regenerative peripheral nerve interfaces (RPNIs), targeted muscle reinnervation (TMR), and neurectomy with relocation nerve grafting.⁸ However, in certain situations when the nerve stump is short, there are no easily accessible motor targets, and/ or there is limited space to perform nerve reconstruction, alternative options are required. The aim of this article was to describe nerve capping with a proprietary nerve cap derived from porcine small intestine (Axoguard; Axogen) of the proximal GON/LON stump to minimize headache pain in patients with refractory symptoms despite previous nerve decompression. Secondarily, with longitudinal follow-up, the effects of these caps on headache are also described. These cases will illustrate the efficacy and durability of nerve caps as a therapy for refractory headache pain.

SURGICAL TECHNIQUE TO ADDRESS THE PROXIMAL NERVE STUMP AFTER NERVE TRANSECTION

The procedure was optimized via simulation with cadaveric specimens. Planning included minimizing incisional burden while permitting sufficient access for identification of structures and space to perform coaptations.

GON: A 5-cm vertical midline incision was marked extending inferiorly from the occipital protuberance to above the hairline. The incision was carried from the skin and subcutaneous tissue through the trapezius fascia and muscle to the semispinalis capitis muscle. The GON was identified at its exit point from the semispinalis capitis muscle 3 cm distal to the occipital protuberance and 1.5 cm lateral to the midline and was meticulously dissected with Jacobson forceps (Fig. 1). The nerve was sharply transected with iris scissors. The proximal stump was subsequently telescoped into to the nerve cap, secured with 8-0 nylon. Importantly, the construct was buried under the semispinalis muscle to avoid superficial positioning of the nerve.

Fig. 1.

Cadaver dissection identifying intact GON exiting from semispinalis capitis muscle. Top of image: cephalad.

LON: A 3-cm oblique incision was marked along the posterior edge of the sternocleidomastoid (SCM) muscle superior to Erb’s point. Skin was sharply incised, and blunt dissection with Jacobson forceps through the subcutaneous plane was performed to identify the LON. Once identified, the course was followed superiorly and sharply transected. The proximal stump was similarly capped as described with the GON (Fig. 2) and buried under nearby SCM. (See Video [online], which highlights the incisional design and dissection/implementation of GON/LON capping in cadaver and intraoperative patients).

Fig. 2.

Cadaver dissection and nerve capping of the LON. This construct was placed beneath the adjacent SCM. Instrument handles point to cadaver’s left side.

Video 1. This video highlights the incisional design and dissection/implementation of GON/LON nerve capping in cadaver and intraoperative patients.

Download video file ^{(59.5MB, mp4)}

Outcomes Methods

In pre- and postoperative follow-up surveillance, patients were interviewed for subjective reported outcomes (reported as a perceived global percent reduction in pain symptoms) as well as a calculated Migraine Headache Index (MHI), as previously described.^17,18 Briefly, patients were asked to report their number of days with headache within a month, average intensity, and the average number of hours per day (reported as a fraction over 24 hours). These variables were multiplied together to generate an MHI score. The difference between pre- and postoperative scores are reported as the MHI score reflecting the degree of resolution.

Case Report 1

This 37-year-old woman underwent a previous right GON decompression and left GON transection 4 years before presentation. She continued to experience daily right-sided occipital pain, which was not responsive to medications but had resolution of pain with nerve blocks. The decision was made to proceed with GON exploration and possible transection.

The area of maximum pain in the right occipital region was marked preoperatively. A midline incision was made, and dissection carried down to the midline raphe. The GON was dissected from surrounding scar tissue at the nuchal ridge (Fig. 3 and Video [online]). The GON appeared diffuse, discolored, and flattened, with absence of vasa vasorum at the exit point from the semispinalis capitis muscle. The GON was dissected until a healthy nerve segment was noted intramuscularly. The decision was made to transect and reconstruct the GON. The short proximal GON stump was telescoped into a 3-mm porcine small intestine nerve cap (Axoguard; Axogen) and buried in the semispinalis capitis muscle (Figure 4 and Video [online]). The LON was also decompressed from surrounding scar tissue. At 3 months follow-up, solicited patient-reported outcomes included significant subjective improvements from her baseline pain without any wound healing issues or other postoperative complications. At 1 year after her operation, she still experiences some pain, but reports a 40%–50% improvement compared with before surgery with an MHI score change of –205 (85% reduction). Although her pain used to be constant before surgery, her pain now lasts on average 4 hours. When she takes medication, duration of pain is reduced to 30 minutes. She also reports reduction in medication use, including discontinuation of preventive and antiemetics medication (Table 1).

Fig. 3.

Dissection and exposure of GON. Throughout the dissection, extensive scar was encountered, as expected, through the previous operative site. Careful neurolysis yielded inflamed and edematous GON with surrounding muscles of poor quality. The compromised region of nerve was resected with proximal stump prepared for nerve cap implantation. Top of image: cephalad.

Fig. 4.

Nerve cap implantation. Nerve cap construct was carefully telescoped over the proximal stump and parachuted with 8-0 nylon suture. Top of image: cephalad.

Table 1.

Pain Data Summary for Case Report 1

Pain Data	Preoperative	12 Months Postoperative	Resolution
Pain frequency, pain days per month	30	30	0
Average pain intensity, 1–10/10	8	7	–1
Average pain duration, hours/24 h	24	4	–20
MHI score	240	35	–205

Percent improvement of pain (subjective global report): 45%.

Case Report 2

This 20-year-old woman underwent a previous bilateral GON decompression for occipital neuralgia 9 months before presentation. She had relief of her daily occipital pain for 3 months after her initial GON decompression. Afterward, she started experiencing occipital pain, which was response to nerve blocks. The decision was made to proceed with bilateral GON exploration, possible avulsion, and possible nerve cap.

Preoperatively, the area of maximum pain in the occipital region was marked. Previous midline incision was opened, and dissection was carried down to midline raphae. The right GON seemed quite inflamed; so further dissection of the nerve was carried proximally into the semispinalis capitis muscle until the nerve appeared healthy for transection. The GON was transected proximally with the proximal GON stump telescoped into a 4-mm porcine small intestine nerve cap (Axoguard; Axogen), which was buried within the semispinalis capitis muscle. On 4 months follow-up, she reported complete resolution on the right side with healed, intact incisions and no signs of infection. On susbsequent follow-up 1 year after surgery, she continued to report complete resolution of pain, with an MHI score change of –180 (Table 2).

Table 2.

Pain Data Summary for Case Report 2

Pain	Preoperative	12 Months Postoperative	Resolution
Pain frequency, pain days per month	30	0	–30
Average pain intensity, 1–10/10	6	0	–6
Average pain duration, hours/24 h	24	0	–24
MHI score	180	0	–180

Percent improvement of pain at 12 months (subjective global report): 100%.

DISCUSSION

Several contemporary techniques of peripheral nerve surgery have been incorporated into headache surgery to manage the proximal nerve stump after transection. In 1985, Mackinnon et al performed histological analyses of primate neuroma repairs, observing implantation within nearby muscle yielded less neuroma.¹⁹ Since then, several studies have further investigated various surgical techniques to prevent symptomatic neuroma formation and pain. Management of the proximal nerve stump has undergone several iterations from the early approaches of burying nerve stumps in surrounding soft tissue or bone to prevent neuromas.^20,21 RPNI, TMR, and nerve autograft have emerged as promising contemporary techniques to prevent symptomatic neuroma formation in the setting of peripheral nerve injury within the head and neck, trunk, and upper and lower extremity regions. Implementation of nerve transection and reconstruction in headache surgery via RPNI, TMR, and reset neurectomy with relocation nerve grafting have been demonstrated in previous case reports.⁸

Limitations in Simple Transection of Problematic Nerves

Transection of the GON/LON has been shown to alleviate neuropathic pain.⁷ However, existing literature has well delineated the risk for symptomatic neuroma formation in the setting of injured or transected peripheral nerves due to the unorganized axon growth²² and scar deposition,²³ along with additional regulatory programs undergoing active investigation.^24,25 Regenerating nerves lacking a distal target or impeded by scar, aberrant tissue, or debris have been empirically demonstrated to result in sprouting axons that deteriorate into a disorganized bundle of immature axons and connective tissue known as a neuroma.^26–28 This aberrant nerve healing may cause severe neuropathic pain, temperature intolerance, paresthesia, and/or sensitivity.^20,21 Contemporary treatment modalities for the management of symptomatic neuroma all iterate on a convergent goal: inhibition of disorganized axonal outgrowth and scarring. To achieve this goal, strategies include physical barriers to potential immunologic and neurotrophic stimuli, coaptation with tissues with receptive neural targets (ie, target end organs receptive to nerve reinnervation and/or ingrowth), or possibly both. Peripheral nerve injuries in limb amputation patients have been successfully treated for neuroma via coaptation with harvested distal motor nerve stumps (TMR^29–31), wrapping with free muscle grafts (RPNIs^32,33), interposing nerve graft between stump and muscle (graft to nowhere³⁴ or relocation nerve grafting³⁵), and capping with both biologic³⁶ and synthetic constructs.^14,15,37,38

Nerve Re-routing Techniques

In the field of neuroma prevention, several candidate targets for nerves have been described, including implantation into veins and nearby tissues.³⁹ TMR and RPNI have emerged as champions in the prevention of symptomatic neuroma formation and are conceptualized as effective options for focal nerve damage at or distal to the exit point of the GON from the semispinalis capitis muscle.⁸ Both TMR and RPNI inherently contribute to, albeit typically minor, morbidity to the patient via sacrifice of muscle innervation or tissue itself in an environment with already limited musculature. Furthermore, these techniques require larger surgical dissection and theoretically could precipitate greater pain in the acute postoperative period. In settings of extensive chronic damage to the surrounding environment, suboptimal donor tissues or injury location; inadequate length of proximal nerve stumps; or anatomic variations geometrically prohibiting tension-free coaptation, TMR, and RPNI may be untenable.

Pharmacological Inhibition of Axonal Regrowth

Other purported strategies have included direct inhibition of axonal regrowth by introduction of ablative substances, including formaldehyde, alcohol, phenol,⁴⁰ doxorubicin,⁴¹ and nerve growth factor inhibitors,⁴² but all remain clinically difficult or impossible to implement in patients due to their postoperative risk, including hematoma and diffuse inflammation.

Nerve Capping

Nerve capping is a novel, alternative technique that has also been shown to prevent neuroma formation, but the exact mechanism remains unknown. Putative mechanisms include facilitation of epineural healing over fascicles and prevention of irregular regeneration of fibers. Both contact guidance via scaffold and shielding from potential inflammatory and neurotrophic factors have been proposed as possible pathways.¹⁴ Since the initial description of silicone nerve capping by Tupper and Booth, various biocompatible materials have been described, including acellular nerve allografts, porcine small intestinal submucosa, polygycolic acid conduit, and photosealed caps with human amniotic membrane or autologous vein.^12,43–45While an ideal material for nerve capping has yet to be firmly established, the utility of nerve capping in preventing neuroma formation has been increasingly established in the literature.^{14,15,36–38} These include early human applications via lactide and caprolactone copolymers (NEUROCAP; Polyganics)^46,47 currently undergoing clinical trials (NCT02993276). This work also describes the first human application of another nerve cap product derived from porcine small intestine submucosa (AXOGUARD; Axogen) with promising results in rat models.⁴³

Nerve capping is another tool in headache surgery to manage the proximal GON stump, especially in environments suboptimal for TMR/RPNI. These patients had previously undergone decompression surgery to manage bilateral occipital pain with high a priori suspicion for scarring and hostile surgical sites. Given this preoperative environment, nerve capping provided an alternative solution compatible with restricted dissection and short proximal nerve stump and led to reduced operative time with no donor site morbidity. Furthermore, these procedures produced significant improvements to complete resolution of pain that remained stable at 1 year follow-up.

Our study is limited by patient numbers and long-term follow-up to make direct comparisons with other techniques. Larger patient cohorts as well as longer follow-up timepoints will be necessary to further delineate the clinical impacts of this intervention. As we continue to gain experience and illustrate successful treatment of neuropathic pain, we hope to formulate an algorithm with various techniques for management of proximal nerve stumps in the context of headache surgery.

CONCLUSIONS

Advances in peripheral nerve surgery have shown that transected nerve endings are prone to painful neuroma formation, and surgeons should be equipped to address the proximal nerve stump. Nerve capping is another method for surgeons to limit operative time, extent of dissection, and donor morbidity in patient cohorts that present with limitations in their candidacy for TMR/RPNI or relocation nerve grafting.

DISCLOSURES

ILV is a consultant for Axogen Corporation, Checkpoint Surgical Inc., and Integra LifeSciences Corporation. All the other authors have no financial interest to declare in relation to the content of this article.