Intraneural Fibrosis Research Articles

Intraneural fibrosis within ilioinguinal nerve in inguinal hernia patients with preoperative pain: it's the sign of irreversible nerve injury, isn't it?

Preoperative pain is known as one of the most powerful risk factors for chronic postoperative inguinal pain (CPIP), while its pathogenesis has not been fully elucidated. The aim of the present study was to evaluate patients with preoperative pain from the pathological perspective and discuss the potential pathogenesis of CPIP in those patients. This was a single-institutional retrospective study. The study population was inguinal hernia patients with preoperative pain who underwent open anterior hernia repair for primary inguinal hernia with pragmatic ilioinguinal neurectomy during surgery between March 2021 and March 2023. The primary and secondary outcomes were proportion of collagen deposition and mucus accumulation within ilioinguinal nerve in those patients, respectively, which were evaluated histologically using Image J software. Forty patients were evaluated. Median value of proportion of intraneural collagen deposition was 38.3% (27.7-95.9). These values were positively correlated with the duration of pain (r2=0.468, P<0.001). Median value of proportion of mucus accumulation in ilioinguinal nerve was 50.1% (0-82.0). These values had no correlation with any clinicopathological variables. In the present study population, all patients with preoperative pain had intraneural fibrosis within ilioinguinal nerve, and its degree had a positive correlation with the pain duration.

Correlation between histopathological nerve assessment and clinical recovery in brachial plexus birth injuries.

In the management of brachial plexus birth palsies, the quality of the roots eligible for reconstruction is thought to be a key issue. The aim of the present study was to evaluate the correlations between pathological root examination and motor recovery after brachial plexus reconstructions. Quantitative histopathological analysis of intraneural fibrosis was conducted on 72 nerve transections (40 roots, 18 trunks and 14 suprascapular nerves) in 20 patients. Clinical recovery of targeted muscles after surgery was assessed by standardized functional scores. After a mean follow-up of 32 months, patients with a lower fibrosis rate for the suprascapular nerve had greater global Mallet scores (r = -0.57; p = 0.042) as well as a greater active shoulder flexion (r = -0.66; p = 0.015). Correlations were also found between C6 root and upper trunk fibrosis rate and some of the subsections of the Mallet score, active movement scale for the biceps and active elbow flexion. These results seem to confirm the relevance of intraoperative pathological evaluation of the roots and nerves after neuroma resection to optimally define the reconstruction strategy.Level of evidence: IV.

Intraneural fibrosis and loss of microvascular architecture — Key findings investigating failed human nerve allografts

BackgroundProcessed nerve allografts are increasingly used in clinical nerve reconstruction with promising results. However, allograft failure has been reported, leading to chronic pain and persistent loss of function. In the present work, we performed a histological and immunohistochemical analysis of two failed allograft reconstructions of a sensory human nerve one year after primary surgery. MethodsTwo patients with a superficial radial nerve injury underwent nerve reconstruction with processed nerve allografts. The clinical follow-up was complicated by severe neuropathic pain and absent sensory reinnervation. Consequently, the failed allografts were excised with subsequent histological and immunohistochemical examinations. For that purpose, the collagen content and neurofilament network as well as the blood and lymphatic vasculature were analysed in the center of the specimens. ResultsHistology revealed increased fibrosis, fatty degeneration, and disorganised proliferation of nerve fibres. Moreover, the microvascular network within the allografts was characterised by increased numbers of microvessels, whereas no difference was found concerning the lymphatic vasculature. ConclusionThe herein presented histological and immunohistochemical findings indicate that the failure of human allografts is associated with loss of the physiological microvascular architecture. Future studies elucidating the complex interplay of angiogenesis, lymphangiogenesis and axonal regeneration are required to better understand the mechanisms of human allograft failure.

Histopathological nerve assessment in brachial plexus birth injuries

In children suffering from brachial plexus birth injuries (BPBI), one major difficulty concerns intraoperative selection of the roots to be used for reconstruction. Between November 2018 and August 2020, surgical qualitative evaluations and pathological quantitative analyses were conducted on 52 roots and 29 distal neural stumps (trunks, divisions, cords, and nerves distal to the neuroma) in 17 patients who underwent brachial plexus reconstruction. For each root, surgeons rated stump quality as “good”, “fair” or “avulsed”. Neural sections were then sent to pathology to determine percentage intraneural fibrosis under microscopy. Mean root intraneural fibrosis rates were 30.5% (SD 24.9; range, 0–80%), 46.3% (SD 32.6; range, 0–90%) and 24.6% (SD 23.5; range, 0–80%) in the “good quality”, “fair quality” and “avulsed” groups, respectively, with no significant differences between groups. In distal neural stumps, the mean intraneural fibrosis rate was 30.9% (SD 24.7). These findings raise the question of conducting frozen section biopsy of neural stumps after neuroma resection to determine surgical reconstruction strategy.

Nerve Ultrasound in Traumatic and Iatrogenic Peripheral Nerve Injury.

Peripheral nerve injury is a potentially debilitating disorder that occurs in an estimated 2–3% of all patients with major trauma, in a similar percentage of medical procedures. The workup of these injuries has traditionally been clinical, combined with electrodiagnostic testing. However, this has limitations, especially in the acute phase of the trauma or lack of any recovery, when it is very important to determine nerve continuity and perform surgical exploration and repair in the case of the complete transection or intraneural fibrosis. Ultrasound can help in those situations. It is a versatile imaging technique with a high sensitivity of 93% for detecting focal nerve lesions. Ultrasound can assess the structural integrity of the nerve, neuroma formation and other surrounding abnormalities of bone or foreign bodies impeding the nerve. In addition, this can help to prevent iatrogenic nerve injury by marking the nerve before the procedure. This narrative review gives an overview of why and how nerve ultrasound can play a role in the detection, management and prevention of peripheral nerve injury.

Scalpel edge roughness affects post-transection peripheral nerve regeneration

BackgroundGentle and precise tissue dissection reduces collateral tissue damage and preserves its structural quality for optimizing healing. This is particularly true for peripheral nerve neurorrhaphy. Axon regeneration kinetics across the repair is dependent on the amount of intraneural fibrosis. The purpose of this study was to determine whether scalpel blade smoothness was a deterministic factor in the kinetics of postneurorrhaphy peripheral axon regeneration. MethodsScalpel transection of the saphenous nerve was performed in 18 female Hartley guinea pigs either by a standard #15 stainless steel scalpel blade or a highly polished version of the same blade. Compound nerve action potential recordings and histochemical assay of neurofilament density proximal and 1 cm distal to the site of nerve transection were quantified postneurorrhaphy at postoperative weeks 5, 9, and 12. ResultsThere was no action potential transmission observed in the distal axons immediately after neurorrhaphy. A substantial acceleration of axonal conduction recovery was observed in nerves transected with polished scalpel blades observed by high compound nerve action potential amplitudes at postneurorrhaphy weeks 5 and 9 (P < .05). In addition, an increased recovery of intra-axonal neurofilament density in nerves transected with polished scalpel blades was observed by postoperative week 5 (P < .05). ConclusionThe quality of the scalpel blade is an important determinate of postsurgical healing. Gentle handling of tissue matters.

Effects of 4% Ethanol Sclerosing Injection on Morton's Neuroma: A Histologic Study.

Nonoperational treatments for Morton's neuroma remain controversial because it is believed that sclerosing injections do not change nerve fibers on a cellular level. Up to 80% success rates with 4% ethanol sclerosing have been documented, and the remainder required operational removal of the painful nerve. We sought to evaluate the histologic characteristics of Morton's neuromas treated with 4% ethanol sclerosing injection versus corticosteroid injection alone in patients who required removal of the nerve for pain relief. A retrospective histologic review was performed of 23 consecutive patients who were treated with either sclerosing injection or nonsclerosing injection and underwent nerve removal between September 1, 2012, and February 28, 2015. Of 19 patients who met the inclusion criteria, eight received sclerosing injections and 11 received nonsclerosing injections. Intraneural fibrosis was more severe in the nonsclerosing injection group (P = .008). Histologic changes are seen in Morton's neuroma with the use of 4% ethanol sclerosing injection, contrary to findings from previous studies.

Silicone tubes with thyroid hormone (Τ3) and BDNF as an alternative to autografts for bridging neural defects

The way thyroid hormone works in peripheral nerve regeneration has not been fully elucidated, although studies have shown that it has a strong positive effect on nerve regeneration. It is argued that its action is probably stronger than the neurotrophic factors that have been used for some time. It is hypothesized that the use of thyroid hormone in the nerve tubes has a beneficial effect on nerve regeneration to the extent that the results of its use are comparable to those of the autograft technique in bridging small nerve deficits. In this experimental study, we examined the effect of thyroid hormone and BDNF (Brain Derived Neurotrophic Factor) on the repair of 10 mm nerve defects when administered within silicone nerve tubes and compared the results with the autograft method. Thyroid hormone promotes nerve regeneration mainly by increasing its speed and its effect on the maturation of nerve fibers compared to the other groups where the nerve deficit was bridged by entubulation. Also, better organization and the absence of intraneural fibrosis, compared to the other groups, may argue for the action of thyroid hormone in regulating the inflammatory response. Functionally, the AG group showed better results compared to the other groups by the end of the study (16 weeks).

Clinical outcome after decompression of intraneural peroneal ganglion cyst and its morphologic correlation to postoperative nerve ultrasound.

Intraneural ganglion cysts are rare and benign mucinous lesions that affect peripheral nerves, most frequently the common peroneal nerve (CPN). The precise pathophysiological mechanisms of intraneural ganglion cyst development remain unclear. A well-established theory suggests the spread of mucinous fluid along the articular branch of the peroneal nerve as the underlying mechanism. Clinical outcome following decompression of intraneural ganglion cysts has been demonstrated to be excellent. The aim of this study was to evaluate the correlation between clinical outcome and ultrasound-detected morphological nerve features following decompression of intraneural ganglion cysts of the CPN. Data were retrospectively analyzed from 20 patients who underwent common peroneal nerve ganglion cyst decompression surgery at the Universität Ulm/Günzburg Neurosurgery Department between October 2003 and October 2017. Postoperative clinical outcome was evaluated by assessment of the muscular strength of the anterior tibial muscle, the extensor hallucis longus muscle, and the peroneus muscle according to the Medical Research Council grading system. Hypesthesia was measured by sensation testing. In all patients, postoperative morphological assessment of the peroneal nerve was conducted between October 2016 and October 2017 using the iU22 Philips Medical ultrasound system at the last routine follow-up appointment. Finally, the correlations between morphological changes in nerve ultrasound and postoperative clinical outcomes were evaluated. During the postoperative ultrasound scan an intraneural hypoechogenic ring structure located at the medial side of the peroneal nerve was detected in 15 (75%) of 20 patients, 14 of whom demonstrated an improvement in motor function. A regular intraneural fasicular structure was identified in 3 patients (15%), who also reported recovery. In 1 patient, a recurrent cyst was detected, and 1 patient showed intraneural fibrosis for which recovery did not occur in the year following the procedure. Two patients (10%) developed neuropathic pain that could not be explained by nerve ultrasound findings. The results of this study demonstrate significant recovery from preoperative weakness after decompression of intraneural ganglion cysts of the CPN. A favorable clinical outcome was highly correlated with an intraneural hypoechogenic ring-shaped structure on the medial side of the CPN identified during a follow-up postoperative ultrasound scan. These study results indicate the potential benefit of ultrasound scanning as a prognostic tool following decompression procedures for intraneural ganglion cysts of the CPN.

Results of Operative Treatment of Brachial Plexus Injury Resulting from Shoulder Dislocation: A Study with A Long-Term Follow-Up.

Injury to the infraclavicular brachial plexus is an uncommon but serious complication of shoulder dislocation. This work aims to determine the effectiveness of operative treatment in patients with this type of injury. Thirty-three patients (26 men and 7 women; mean age, 45 years and 3 months) treated operatively for brachial plexus injury resulting from shoulder dislocation between the years 2000 and 2013 were included in this retrospective case series. Motor function of affected limbs was assessed pre- and postoperatively with the use of the British Medical Research Council (BMRC) scale. Sensory function in the areas innervated by ulnar and median nerves was evaluated with the BMRC scale modified by Omer and Dellon and in the remaining areas with the Highet classification. Follow-up lasted 2-10 years (mean, 5.1 years). Good postoperative recovery of nerve function was observed in 100% of musculocutaneous, 93.3% of radial, 66.7% of median, 64% of axillary, and 50% of ulnar nerve injuries. No recovery was observed in 5.6% of median, 6.7% of radial, 10% of ulnar, and 20% of axillary nerve injuries. Injury to a single nerve was associated with worse treatment outcome than multiple nerve injury. Obtaining improvement in peripheral nerve function after injury resulting from shoulder dislocation may require operative intervention. The type of surgical procedure depends on intraoperative findings: sural nerve grafting in cases of neural elements' disruption, internal neurolysis when intraneural fibrosis is observed, and external neurolysis in the remaining cases. The outcomes of surgical treatment are good, and the risk of intra- and postoperative complications is low.

Anatomical Basis and Clinical Application of Synovial Flaps in the Wrist and Distal Forearm

Neuropathic symptoms after median nerve repair at the wrist or secondary to refractory carpal tunnel syndrome may become debilitating. These symptoms develop because of perineural adhesions, intraneural fibrosis, and fixation of the nerve to the transverse carpal ligament after surgery, and often require neurolysis. Interposition of vascularized soft tissue over the median nerve at the time of neurolysis prevents recurrence of such adhesions. The synovial flap, fashioned from the synovial lining of the flexor tendon sheath, is an ideal tissue for this purpose. Previous authors have described the surgical technique of the synovial flap, but the anatomical basis and design of the flap have not been previously discussed. Twenty fresh cadaver upper extremities were injected with Microfil to analyze the arterial anatomy, flap dimensions, and arc of rotation of the flexor tendon synovium mobilized as a flap suitable for coverage of the median nerve at the wrist. The authors determined that both radial and ulnar-based flaps are clinically useful for providing coverage in the wrist and distal forearm. This flap was used in 18 patients with complicated median nerve lesions in this region. All patients had an uncomplicated postoperative course. Of 13 patients treated for posttraumatic median nerve neuromas, all but two had significant resolution of symptoms. When used as a vascularized flap, the flexor tendon synovium provides adequate protection of the median nerve. Flap dimensions and vascularity of this tissue make it an ideal local flap option when performing reoperative surgery on the median nerve.

Revision surgery for recurrent and persistent carpal tunnel syndrome: Clinical results and factors affecting outcomes

Thirty-eight hands in 36 patients with recurrent or persistent carpal tunnel syndrome (CTS) were reviewed retrospectively after a mean of 51months (range 12–86) to identify factors that may lead to poor outcomes after surgical management. Clinical assessment focused on pain and sensitivity recovery, measured with a VAS and Weber's two-point discrimination test, respectively. At the latest follow-up, we found 11 excellent, 15 good, nine fair and three poor results. The risk of fair or poor results was significantly higher in the presence of intraneural fibrosis, severe preoperative sensory deficit, neuroma of the palmar cutaneous branch of the median nerve, workers compensation claims and number of previous surgeries. This last factor also significantly increased the risk of intraneural fibrosis. Despite disappointing outcomes, identification of these factors may improve our prognostic ability for revision surgery in cases of recurrent CTS.

Reduction of neural scarring after peripheral nerve suture: An experimental study about collagen membrane and autologous vein wrapping

The effects of a collagen membrane and a technique of autologous vein wrapping on scar formation after peripheral nerve suture are investigated. Forty-eight sciatic nerves from Wistar rats were transected and repaired, then allocated to a control group C (n=16) and two experimental groups: in group A (n=16) the repair line was covered by the collagen membrane, and in group B (n=16) the repair line was wrapped by an external jugular venous graft. Three months later, it was observed that adhesions in the surrounding tissues were significantly less in groups A and B compared to group C, and significantly less in group A than in the group B. Histological analysis revealed no significant reduction of extraneural or intraneural scar tissue in groups A or B compared to group C. However intraneural fibrosis was significantly less in the group A than in the group B. It was concluded that the collagen membrane was effective in reducing neural scar formation after peripheral nerve suture. Autologous vein wrapping also showed a favorable effect in this indication despite less successful histological outcomes.

Painful Nodules and Cords in Dupuytren Disease

The etiology of Dupuytren disease is unclear. Pain is seldom described in the literature. Patients are more often disturbed by impaired extension of the fingers. We recently treated a series of patients who had had painful nodules for more than 1 year, and we therefore decided to investigate them for a possible anatomical correlate. Biopsies were taken during surgery from patients with Dupuytren disease and stained to enable detection of neuronal tissue. We treated 17 fingers in 10 patients. Intraoperatively, 10 showed tiny nerve branches passing into or crossing the fibrous bands or nodules. Of 13 biopsies, 6 showed nerve fibers embedded in fibrous tissue, 3 showed perineural or intraneural fibrosis or both, and 3 showed true neuromas. Enlarged Pacinian corpuscles were isolated from 1 sample. All patients were pain free after surgery. Although Dupuytren disease is generally considered painless, we treated a series of early stage patients with painful disease. Intraoperative inspection and histological examination of tissue samples showed that nerve tissue was involved in all cases. The pain might have been due to local nerve compression by the fibromatosis or the Dupuytren disease itself. We, therefore, suggest that the indication for surgery in Dupuytren disease be extended to painful nodules for more than 1 year, even in the early stages of the disease in the absence of functional deficits, with assessment of tissue samples for histological changes in nerves.

Surgical Options for Recalcitrant Carpal Tunnel Syndrome with Perineural Fibrosis

Surgical release of the transverse carpal ligament for the treatment of carpal tunnel syndrome (CTS) is, in general, a very successful procedure. Some patients, however, fail this standard release and have persistent or recurrent symptoms. Such recalcitrance may relate to incomplete release but more often relates to perineural or intraneural fibrosis of the median nerve. While there is no good treatment for intraneural fibrosis, numerous procedures have evolved in an attempt to treat perineural fibrosis which restricts nerve gliding. These include procedures to isolate the nerve from scar as well as procedures to bring neovascularization to the median nerve. This review describes the various surgical treatment options for recalcitrant CTS as well as their reported outcomes.

Tratamento cirúrgico de dor neuropática em membro inferior por ferimento de arma de fogo: relato de caso

BACKGROUND AND OBJECTIVES: Neuropathic pain is difficult to treat and many patients have partial and incomplete pain relief with pharmacological treatment. When the neuropathic pain has traumatic origin one should consider the possibility of treating with surgical exploration because pain may be caused by nervous compression due to adjacent tissues fibrosis or sheath thickening. This study aimed at presenting a successful case of surgical treatment of neuropathic pain caused by sheath thickening of left sciatic nerve, caused by firearm injury. CASE REPORT: Male patient, reached by firearm shot in the left gluteus region, who evolved with burning pain in the posterior left thigh region, with irradiation to the posterior thigh face, leg and foot, which was partially controlled with pharmacological treatment with oxycodone, gabapentin and amitriptyline. As pain persisted, surgical exploration was performed at the bullet entry site, which has evidenced the presence of left sciatic nerve bulb and sheath thickening, being performed endoneurolysis for intraneural fibrosis decompression. After surgery, patient was treated with pregabalin, morphine and amitriptyline and 10 months after surgery he was asymptomatic and no longer having medication. CONCLUSION: Surgical treatment with endoneurolysis for intraneural fibrosis decompression in left sciatic nerve associated to treatment with amitriptyline and pregabalin has successfully controlled neuropathic pain caused by firearm injury.

Ulnar Nerve Palsy Following Closed Fracture of the Distal Radius: A Report of 2 Cases

Ulnar nerve palsy subsequent to a fracture of the distal radius is extremely rare compared to a median nerve injury. The lesion tends to occur in younger patents with a high-energy mechanism of injury and a severe injury pattern consisting of wide displacement, comminution, combined distal ulnar fracture and open fracture. The mechanism of injury can contribute to a direct contusion and traction, compression secondary to prolonged edema and tissue fibrosis, intraneural fibrosis and laceration. We report 2 cases of progressive ulnar nerve palsy subsequent to closed fractures of the distal radius. The neurological symptoms recovered in all cases who underwent nerve decompression and neurolysis at 2 or 3 months after the trauma. It is recommended that cases with high-energy, widely displaced or comminuted fractures of the distal radius be evaluated carefully for ulnar nerve as well as median nerve injury.

End-to-Side Neurorrhaphy: Past, Present,and Future

To the present day, nerve injuries still represent a challenge to the surgeon. With all the advances in microneural surgery, additional approaches need to be studied to improve functional results. End-to-side nerve repair is the newest tool in managing certain nerve injuries, especially where the surgeon is faced with long nerve gaps, when it becomes impractical to use nerve grafts. The use of long nerve grafts is associated with intraneural fibrosis and atrophy of the end organs because of the prolonged time of regrowth of axons. The authors present a full review of the history, experimental work, and clinical applications of end-to-side neurorrhaphy, such as facial palsy, brachial plexus repair, and solitary sensory nerve repair. After reading this article, the surgeon will be familiar with this newest technique available to the microneural surgeon and the situations where the technique can be used to yield good results. She or he will also be able to expand on the existing experimental work in the pursuit of best functional outcomes.

Preliminary Results of a Randomized, Equivalence Trial of Fluoroscopic Caudal Epidural Injections in Managing Chronic Low Back Pain: Part 3 – Post Surgery Syndrome

Background: Post surgery syndrome resulting in persistent pain following lumbar spine surgery is common. Speculated causes of post lumbar surgery syndrome include stenosis, degeneration of adjacent segments, internal disc disruption, recurrent disc herniation, retained disc fragment, epidural or intraneural fibrosis, radiculopathy, and various other causes. Epidural injections are most commonly used in post surgery syndrome. There is lack of evidence for the effectiveness of epidural injections in managing chronic low back pain with or without lower extremity pain secondary to post surgery syndrome. Study Design: A randomized, double-blind, equivalence trial. Setting: An interventional pain management practice, a specialty referral center, a private practice setting in the United States. Objectives: To evaluate the effectiveness of caudal epidural injections in patients with chronic low back and lower extremity pain after surgical intervention with post lumbar surgery syndrome. Methods: Patients were randomly assigned to one of 2 groups; Group I patients received caudal epidural injections with local anesthetic (lidocaine 0.5%), whereas Group II patients received caudal epidural injections with 0.5% lidocaine 9 mL mixed with 1 mL of 6 mg non-particulate Celestone. Randomization was performed by computer-generated random allocation sequence by simple randomization. Outcomes Assessment: Multiple outcome measures were utilized which included the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3 months, 6 months, and 12 months post-treatment. Significant pain relief was described as 50% or more, whereas significant improvement in the disability score was defined as a reduction of 40% or more. Results: Significant pain relief (≥ 50%) was recorded in 60% to 70% of the patients with no significant differences noted with or without steroid over a period of one-year. In addition, functional assessment measured by the ODI also showed significant improvement with at least 40% reduction in Oswestry scores in 40% to 55% of the patients. The average procedures per year were 3.4 with an average total relief per year of 31.7 ± 19.10 weeks in Group I and 26.2 ± 18.34 weeks in Group II over a period of 52 weeks. Limitations: The results of this study are limited by the lack of a placebo group and the preliminary report size of only 20 patients in each group. Conclusion: Caudal epidural injections in chronic function-limiting low back pain in post surgery syndrome without facet joint pain demonstrated effectiveness with over 55% of the patients showing improvement in functional status with significant pain relief in 60% to 70%. Key words: Post lumbar surgery syndrome, post lumbar laminectomy syndrome, chronic low back pain, epidural adhesions, epidural steroid injections, epidural fibrosis, recurrent disc herniation, spinal stenosis

An experimental model of peripheral nerve adhesion in rabbits

We studied the effects of peripheral nerve adhesion in a rabbit sciatic nerve model. After nerve exposure, its adventitial layer was sutured with 8–0 nylon to the nerve bed, which had been cauterised to promote adhesion. Nerve kinematics, electrophysiology, blood flow and histology were assessed. Rabbits in which Fontana's bands were visible as normal through the epineurium, classified as a nonadhesion group (group I), lacked intraneural fibrosis. In this group, nerve conduction and nerve blood flow were well maintained. Rabbits in which Fontana's bands could not be seen were classified as the adhesion group (group II). This group was classified into two levels pathologically; thickening of epineurium and perineurium was observed but no endoneurial fibrosis (group IIa), and endoneurial fibrosis (Wallerian degeneration, myelin sheath thinning and fibrosis between nerve fibers) was noted (group IIb). Compound muscle action potentials (CMAP) were reduced in amplitude and blood flow was significantly decreased at adhesion sites in group IIb. In conclusion, adhesion of peripheral nerve to surrounding tissues results in fibrosis in the nerve that contributes to peripheral nerve dysfunction.