Intraneural Fibrosis Research Articles

Interdigital neuroma: clinical examination and histopathologic results in 63 cases treated with excision.

Between November 1993 and September 1999, 60 patients (three bilateral) were consecutively treated with excision of interdigital neuroma. The clinical examination was preoperatively performed and a personal interview, physical examination, and routine radiographs were included. A specific clinical rating system was developed. The clinical results were excellent or good in 49 (78%) feet, fair in 12 (19%), and poor in two (3%). Prior to surgery, the clinical evaluation score was an average of 16 points. Postoperative average score was 67 points, with an average improvement of 50 points. Histopathologically, intraneural fibrosis and sclerohyalinosis were observed, as in the interstitium; furthermore, an increase of the elastic fibers in the stroma was also observed. The precise etiology of interdigital neuroma remains obscure.

Effects of Hyaluronic Acid-Carboxymethylcellulose Membrane on Extraneural Adhesion Formation and Peripheral Nerve Regeneration

The goal of nerve repair in the peripheral nervous system is to increase the number of axons passing from proximal to distal stump, and to enable the regenerated axons to reach the end organ as soon as possible. In the present study, the effect of the membrane formed by a mixture of hyaluronic acid and carboxymethylcellulose (HA-CMC) on nerve regeneration and perineurial scar formation was investigated. Eighteen New Zealand rabbits were allocated into control (n = 9) and experimental groups (n = 9). In the control group, conventional nerve repair was carried out following the transection of the sciatic nerve, while in the experimental group, following repair of the nerve, the repair line was covered by HA-CMC membrane extending 1 cm beyond the distal and proximal ends. Nerve regeneration and extraneurial adhesion formation were compared between the two groups 3 months later. It was observed that adhesion in the surrounding tissues was significantly less in the experimental group than in the control group. Furthermore, morphometric analysis of specimens obtained from the distal parts of nerves showed that the number of axons with myelin was higher in the experimental group than in the control group, with a statistically significant difference. Histologic sections obtained from the nerve repair line demonstrated that extraneural and intraneural fibrosis was significantly lower in the experimental group. It was concluded that HA-CMC membrane had a favorable effect on nerve regeneration, as well as extraneural scar formation, encouraging the clinical application of HA-CMC following nerve injuries.

Prevention of damage caused by sural nerve withdrawal for nerve grafting.

Sural nerve withdrawal in peripheral nerve surgery is commonly performed for grafting nerve lesions with gap. Notwithstanding its popular use, this procedure is not entirely without fault as painful neuromas can occur after the withdrawal. We have treated 24 cases of painful neuromas of sural nerve after withdrawal; 11 of which were treated surgically. A safe procedure to cure and to prevent such neuromas is described - the electrical coagulation of the stump of the nerve by slowly increasing the intensity of the current. This procedure has been devised based on the fact that electrically burnt patients do not produce painful neuromas. An experimental histological study performed on rats demonstrated that slow electrical burning of the stump of a severed nerve prevents the formation of intraneural fibrosis which, on the contrary, forms abundantly when the cut nerve is not coagulated.

Preliminary study for prevention of neural adhesion using an absorbable oxidised regenerated cellulose sheet.

The purpose of this study was to clarify the effect of an absorbable oxidised regenerated cellulose sheet (AORCS) for prevention of neural adhesion. Rabbit sciatic nerve was exposed at the middle of the thigh and the neural bed was coagulated by a bipolar coagulator to establish an adhesion model. Coagulation only was Group A (n = 8), coagulation and wrapping the sciatic nerve with an AORCS was Group B (n = 8), and an intact nerve was Group C (n = 16). Six weeks later, each group was estimated. Adhesion between the nerve and neural bed, and intraneural fibrosis were seen in Group A. However, there was little adhesion and fibrosis in Group B. Although the electrophysiological study showed a small significant difference, AORCS clearly prevented the adhesion in the histological study. Hence, AORCS might be useful as an additional treatment during nerve surgery.

Considerations on rehabilitation of cervicothoracobrachial outlet syndrome

The conservative treatment of the thoracic outlet syndrome (TOS) as proposed by Peet in 1956 prevailed a long time and still remains, for many physiotherapists, the technique of reference. However, during these last 20 years, many authors have published improvements to this technique. The Walsh program, published in 1996, is advantageous on the one hand because it utilizes all the evaluation data, and on the other hand, it separates compressive TOS from entrapment TOS, with the latter limiting plexus mobility in proportion to extraneural and/or intraneural fibrosis. The treatment program includes three stages. The goal of the first stage is to control the symptomatology and to obtain comfort. The second stage concerns more directly the pathological tissues: musculoskeletal surroundings for compressive components and mobilization of the nervous system according to Butler, Totten and Hunter protocols for entrapment components. The third stage aims to condition and strengthen the postural muscles. A home rehabilitation program is also addressed. The patient's ability to tolerate daily living and professional activities depends on the pursuit of the home program in accordance with evolution.

Arthroscopic discectomy of the lumbar spine.

Although open laminotomy remains an acceptable and, at times, necessary method of treatment for herniated intervertebral discs, spinal stenosis, and various intracanal spinal disorders, arthroscopic disc surgery is emerging as an alternative method of treatment for contained and nonmigrated sequestered herniated discs. Successful performance of arthroscopic disc surgery requires technical skill and a learning curve. Prudent patient selection, adherence to inclusion and exclusion criteria, and avoidance of entry into the spinal canal when possible will reduce the incidence of perineural and intraneural fibrosis and will ensure a satisfactory outcome. Although the incidence of complications has been acceptable, a satisfactory outcome ranging from 75% to 87% has been reported after arthroscopic microdiscectomy. In contrast to nuclear debulking procedures, the objective imaging confirmation of decompression of the nerve root may be shown by immediate postoperative computed tomography or magnetic resonance imaging studies.

Herniated intervertebral disc-associated periradicular fibrosis and vascular abnormalities occur without inflammatory cell infiltration.

Prospective histologic comparison of perineural tissues from patients requiring decompression surgery for herniated intervertebral disc with those from cadaveric controls. To examine the significance of herniated intervertebral-disc-associated perineural vascular and fibrotic abnormalities with respect to back pain symptom generation. Previous cadaveric studies have demonstrated perineural vascular congestion, dilatation, and thrombosis and perineural and intraneural fibrosis occurring in association with herniated intervertebral disc. It was suggested that these neural abnormalities were the result of ischemia, due to venous outflow obstruction, and also represented a possible cause of ongoing back pain symptoms. Criticisms of such a conclusion arose, however, because the possibility could not be excluded that these abnormalities were the result of postmortem artifact. Histologic and immunohistochemical comparison of discal and peridiscal tissues removed from 11 patients with radiographically proven herniated intervertebral disc requiring decompressive surgery and from 6 fresh cadavers without history of back pain in life. Histology and immunohistochemistry of perineural and extraneural tissues from patients revealed vascular congestion, neovascularization, and endothelial abnormalities including luminal platelet adhesion, in association with reductions in von Willebrand factor levels, together with perivascular and perineural fibrosis. Elevated fibrogenic cytokine concentrations were also detected in patients' tissues. These changes occurred without evidence of inflammation and were absent in cadaveric control tissues. The vascular abnormalities detected in patients may represent an important etiopathologic factor predisposing to intraneural and perineural fibrosis, and hence to chronic pain symptoms, after disc herniation. It seems important to preserve the perineural microcirculation following disc herniation.

Intervertebral foramen venous obstruction. A cause of periradicular fibrosis?

Disc herniation into the intervertebral foramen (IVF) or osteophytic outgrowths from the margins of the apophyseal joints that project into the IVF may compress the neural structures, but in this cadaveric study of 160 lumbar foramens (age range, 35-91 years), the authors have found that they were much more commonly associated with compression and distortion of the large venous plexus within the IVF. In the absence of direct nerve compression (seen in only eight specimens), the most severe neural changes were associated with compression, congestion, and resultant dilatation of foraminal veins. Pathologic changes within and around the nerve root complex included peri- and intraneural fibrosis, edema of nerve roots, and focal demyelination. Inflammatory cells were notably absent. Vascular changes within the thickened fibrous sheath about damaged nerves, namely, basement membrane thickening, suggestive of endothelial cell injury also were observed. The association between vascular compression, tissue fibrosis, and endothelial injury distant from the compression may be causal--probably due to ischemia as a result of reduced venous outflow. Such observations have led the authors to propose that venous obstruction may be an important pathogenic mechanism in the development of perineural and intraneural fibrosis.

Vascular damage, fibrosis, and chronic inflammation in mechanical back pain problems

Our current hypothesis is that mechanical damage in the spine such as a disc prolapse can lead directly to pain. However, pain arising for this reason is usually of short duration. In many subjects, however, the mechanical problems lead to vascular damage and, in particular, venous obstruction and dilatation with endothelial damage, fibrin deposition, and intravascular thromboses. In turn, this is associated with perineural and intraneural fibrosis. There is a defect in the fibrinolytic system in the peripheral blood that may be the result of vascular damage but in turn may contribute to the persistence of this problem. Therefore, it seems likely that in many patients with chronic mechanical back pain there are important vascular, fibrotic, and inflammatory components to the problem. Treatment in the future should be directed specifically at these aspects of the disorder and hopefully can lead to better control of symptoms.

Intraneural Microcirculation

Peripheral nerve trunks are well-vascularized structures where a well-developed collateral system may compensate for local vascular damage. Interference with intraneural blood flow is reflected rapidly in disturbances in nerve function. In compression lesions and nerve entrapments, the microvascular factor plays an important pathophysiologic role for development of symptoms. Although endoneurial capillaries normally constitute a BNB helping to optimize endoneurial environment, damage to the vessels may induce a miniature closed compartment syndrome by increasing the permeability, thereby contributing to increased endoneurial fluid pressure and development of an intrafascicular edema. Surgeons, performing intraneural dissections, should be aware of the potential risks associated with intraneural bleedings, edema, and intraneural fibrosis.

Effects of high-peak pulsed electromagnetic field on the degeneration and regeneration of the common peroneal nerve in rats

Apart from preliminary notices of present work, previous reports of experimental and clinical trials of the effects of a high-peak pulsed electromagnetic field (PEMF) on degeneration and regeneration of peripheral nerves lacked statistical analysis. Therefore, we designed experiments with standardised operative, histological, cytological and morphometric techniques to assess the effect of PEMF on lesions of the common peroneal nerves in paired male rats matched for age, environmental conditions and level and type of lesion. One of two types of lesion was induced in the left common peroneal nerve: in 12 pairs of rats the nerve was crushed just above the knee and in the remaining 12 pairs the nerve was cut and immediately sutured at the same level. The right common peroneal nerve of each rat served as a control. Animals received 15 minutes of PEMF produced by a Diapulse machine or sham treatment daily for periods ranging from three and a half days to eight weeks after injury. Healthy nerves were unaffected, but after damage there were statistically significant differences between PEMF treated and sham treated rats. PEMF accelerated the recovery of injured limbs and the degeneration, regeneration and maturation of myelinated axons; epineural, perineural and intraneural fibrosis was reduced; and the luminal cross-sectional area of intraneural vessels increased after both types of lesion. Findings are discussed and the need for clinical trials is stressed.

Effects of high-peak pulsed electromagnetic field on the degeneration and regeneration of the common peroneal nerve in rats.

Apart from preliminary notices of present work, previous reports of experimental and clinical trials of the effects of a high-peak pulsed electromagnetic field (PEMF) on degeneration and regeneration of peripheral nerves lacked statistical analysis. Therefore, we designed experiments with standardised operative, histological, cytological and morphometric techniques to assess the effect of PEMF on lesions of the common peroneal nerves in paired male rats matched for age, environmental conditions and level and type of lesion. One of two types of lesion was induced in the left common peroneal nerve: in 12 pairs of rats the nerve was crushed just above the knee and in the remaining 12 pairs the nerve was cut and immediately sutured at the same level. The right common peroneal nerve of each rat served as a control. Animals received 15 minutes of PEMF produced by a Diapulse machine or sham treatment daily for periods ranging from three and a half days to eight weeks after injury. Healthy nerves were unaffected, but after damage there were statistically significant differences between PEMF treated and sham treated rats. PEMF accelerated the recovery of injured limbs and the degeneration, regeneration and maturation of myelinated axons; epineural, perineural and intraneural fibrosis was reduced; and the luminal cross-sectional area of intraneural vessels increased after both types of lesion. Findings are discussed and the need for clinical trials is stressed.

Factors related to the outcome of surgically managed compressive ulnar neuropathy at the elbow level

Forty-eight of 59 patients who had undergone initial and no secondary treatment of compressive ulnar neuropathy at the level of the elbow during the period of January, 1968, to December, 1977, were reviewed by personal follow-up examination. Cubital tunnel decompression and anterior subcutaneous transposition of the ulnar nerve gave equal results as to the relief of pain and dysesthesia. However, anterior subcutaneous transposition gave better total relief of paresthesias and better return of intrinsic muscle function than did cubital tunnel decompression. Submuscular transposition was not evaluated in this study. The presence of intraoperative intraneural fibrosis or preoperative intrinsic muscle weakness were factors associated with a poor result. Prolonged duration of symptoms and advanced age were relative factors associated with a poor outcome. The presence of preoperative pain, paresthesias, or a widened two-point discrimination had no association with the eventual outcome.

Effects of Chymopapain on Nerve Tissue An Experimental Study on the Structure and Function of Peripheral Nerve Tissue in Rabbits After Local Application of Chymopapain

An experimental model is described, which has been used for evaluating effects of clinically used concentrations of chymopapain on peripheral nerve tissue. Chymopapain does not acutely block impulse conduction or axonal transport of proteins. However, chymopapain induces impairment of the barrier function of the perineurial sheath and increases permeability of the intraneural microvessels resulting in intraneural edema formation. The long-term consequences are degeneration of nerve fibers and formation of intraneural fibrosis, requiring an increased threshold voltage for eliciting action potentials. The results are discussed in relation to the clinical use of chymopapain in the treatment of intervertebral disc disease.

Intraneural Tissue Reactions Induced by Internal Neurolysis

Surgical treatment of peripheral nerve lesions associated with intraneural fibrosis is sometimes extended to include internal neurolysis. This procedure is performed in order to release the individual nerve fascicles from interfascicular scar tissue which is believed to constrict nerve fibres and thereby interfere with their function and regenerative capacity. However, an internal neurolysis per se implies a significant trauma to the nerve and may induce microvascular damage and formation of new intraneural scar tissue. Considering this, such a procedure appears justified only when the preoperative intraneural fibrosis is more severe than the scarring which might be induced by the surgical procedure as such. In order to evaluate the tissue reactions following internal neurolysis an experimental investigation was carried out: internal neurolysis was performed on normal rabbit tibial nerve. After varying postoperative periods up to 6 months specimens of nerves were analysed. Reactive changes of connective tissue and myelin sheath lesions, indicating nerve fibre damage, were investigated in histological sections studied by light microscopy. Barrier function of perineurial membrane and endoneurial vessels was investigated by fluorescent microscopic tracing of locally applied or intravenously injected albumin labelled with Evans' blue. The results indicate that an experimental internal neurolysis per se may induce fibrosis in all layers of the nerve and may cause some nerve fibre damage. However, the barrier function of the perineurium and the endoneurial vessels seems to be generally well preserved. The findings are discussed in relation to indications for internal neurolysis.

Effect of "R'and "S'Forms of Chromogenic Acid-Fast Bacillus from Human Leprous Lesion on Rabbits

The writer isolated a “rough'and “smooth'form of a chromogenic acid-fast bacillus which was recovered from the human leprous lesion. The 2 forms differed both morphologically and culturally. A study was made to determine any difference in pathogenicity. Inoculations of rabbits began about a year ago. Large doses of the 2 forms were given at frequent intervals over a considerable length of time. Three rabbits were respectively injected with the “R'form subcutaneously, intraäbdominally and intranasally, and 3 other animals received the “S'form by the same routes. Preliminary to the injections of living bacilli, all 6 rabbits received several injections of a lepra broth-filtrate to produce, if possible, an allergic condition which would enhance the growth of the acid-fast bacilli in vivo. The “S'form produced the most striking results. The rabbits became markedly emaciated after approximately 7 months. Several subcutaneous nodules were noted at the sites of inoculations in the rabbits receiving the subcutaneous injections. Microscopic examination of ulcerated nodules revealed many acid-fast bacilli. The internal organs, especially the liver, spleen and kidneys, showed many large phagocytic cells, simulating lepra cells, containing acid-fast bacilli. Fibrosis and generalized thickening of the blood vessels was marked. Two rabbits showed paralysis of 2 or more extremities which probably was the result of extra- and intraneural fibrosis. Less conspicuous changes were noted in the rabbits injected with the “R'form. Emaciation was present but not to the degree seen in the rabbits that had received the “S'injections. Subcutaneous nodules developed but gradually disappeared without ulceration. Careful microscopic examination of the internal organs of the “R'animals revealed nothing characteristic of leprosy. No acid-fast bacilli were detected in any of the organs. One of the objects of this investigation was to determine whether it is possible to induce in rabbits. by means of the chromogenic acidfast bacillus isolated from the human leprous nodule, a disease comparable to human leprosy.