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PubMed2006

Estimations of topographically correct regeneration to nerve branches and skin after peripheral nerve injury and repair.

Peripheral nerve injury is typically associated with long-term disturbances in sensory localization, despite nerve repair and regeneration. Here, we investigate the extent of correct reinnervation by back-labeling neuronal soma with fluorescent tracers applied in the target area before and after sciatic nerve injury and repair in the rat. The subpopulations of sensory or motor neurons that had regenerated their axons to either the tibial branch or the skin of the third hindlimb digit were calculated from the number of cell bodies labeled by the first and/or second tracer. Compared to the normal control side, 81% of the sensory and 66% of the motor tibial nerve cells regenerated their axons back to this nerve, while 22% of the afferent cells from the third digit reinnervated this digit. Corresponding percentages based on quantification of the surviving population on the experimental side showed 91%, 87%, and 56%, respectively. The results show that nerve injury followed by nerve repair by epineurial suture results in a high but variable amount of topographically correct regeneration, and that proportionally more neurons regenerate into the correct proximal nerve branch than into the correct innervation territory in the skin.

Algorithms↗
PubMed1987

Assessment of central and peripheral nerve functions in chain-saw operators: a study of short-latency somatosensory evoked potential and peripheral nerve conduction.

In order to clarify the effects of local vibration on the peripheral and central nervous system, peripheral (median) nerve conduction velocities and short-latency somatosensory evoked potentials (SSEP) following stimulation of the median nerve at the wrist were measured in 15 male forest workers in 1986. They had engaged in chain-saw operation for 16-34 (mean 22) years; their working days in 1985 averaged 124 days with a range of 50-203 days. The results indicated significant delays in maximal motor and sensory nerve conduction velocities followed by prolongation of all 4 peak latencies of SSEP up to the sensory cortex of the brain (N9, N13, N20 and P23 latencies) in chain-saw operators; their N9 and P23 latencies were significantly correlated with total working days per year. On the other hand, no significant prolongation of the interpeak latencies of SSEP (i.e., cervico-spinobulbar and central conduction times) was found in the workers. It is concluded that local vibration predominantly affects peripheral nerve conduction; cervico-spinobulbar and central nerve conduction may not be significantly affected.

Adult↗
PubMed2004

Sciatic nerve sarcoidosis: utility of magnetic resonance peripheral nerve imaging and treatment with radiation therapy.

Sarcoidosis may involve both the central and peripheral nervous system, although peripheral nerve manifestations are usually seen late in the disease. In this report, the authors describe a case of sarcoidosis in a 22-year-old woman who presented with a foot drop. Although results of conventional lumbar magnetic resonance (MR) imaging were normal, MR peripheral nerve imaging of the thigh showed a mass in the sciatic nerve indicating tumor. An intraoperative biopsy sample revealed noncaseating granulomas consistent with sarcoid. The patient was treated with steroid drugs to control the manifestations of her disease but exhibited early signs of femoral bone necrosis, which required discontinuation of the steroids. She was then treated with local radiation therapy. At her 2-year follow-up visit the patient demonstrated relief of her symptoms and improvement on MR peripheral nerve imaging. This case demonstrates that sarcoidosis may present with peripheral nerve manifestations. The appearance of a diffusely swollen nerve on MR imaging should prompt clinicians to include sarcoidosis in the differential diagnosis and plan surgery accordingly. Patients who are not responsive to or who are unable to tolerate medical therapy may be treated with radiation therapy.

Adult↗
PubMed2003

Recovery of muscle contractile function following nerve gap repair with chemically acellularized peripheral nerve grafts.

Acellular nerve grafts have emerged as a possible alternative for reconstruction of short (<2 cm) peripheral nerve gaps. Axonal regeneration has been demonstrated within the nerve constructs. However, very little work has been done to demonstrate both axonal regeneration and recovery of motor function following peripheral nerve gap repair with acellular nerve constructs. The authors hypothesized that chemically acellularized nerve grafts can support axonal regeneration and provide functional reinnervation of rat hindlimb muscles with equivalent efficiency to peripheral nerve autografts. Peroneal nerves were harvested from adult rats and chemically acellularized. Two- and 4-cm peroneal nerve gaps were reconstructed with either a cellular autograft or an acellular isograft. Functional recovery was evaluated with walking-track analyses and measurement of maximum tetanic isometric force (F 0 ) of the extensor digitorum longus (EDL) muscle. Walking-track analysis revealed no statistically significant difference in functional recovery in rats undergoing reconstruction of 2-cm nerve gaps with acellular isografts or cellular autografts. Maximum tetanic isometric force measurements revealed a 60 percent force deficit in EDL muscles reinnervated by 2-cm acellular nerve grafts, compared to cellular autografts. Four-centimeter acellular grafts failed to support any significant EDL muscle reinnervation. This study demonstrates that chemically acellularized peripheral nerve supports axonal regeneration and functional reinnervation across 2-cm nerve gaps, and may potentially serve as an appropriate scaffold for reintroducing cellular elements, adhesion molecules, or growth factors for repair of longer nerve gaps.

Animals↗
PubMed2000

CNTF promotes the regrowth of retinal ganglion cell axons into murine peripheral nerve grafts.

Autologous peripheral nerves were transplanted onto transected optic nerves of adult mice. We examined whether intraocular CNTF injections increased retinal ganglion cell (RGC) axon regeneration, and what types of RGCs regrew axons into grafts. After temporal CNTF eye injections there were more fluorogold-labelled regenerating RGCs (mean +/- s.e.m. 342+/-113.1; n=6) than in sham eye-injected mice (133+/-27.6; n=8). Greater numbers of regenerating RGCs (1198+/-367.6; n=6) were seen in mice receiving both nasal and temporal CNTF injections. The range of soma areas in regenerate and normal retinas was similar but the average size of regenerating RGCs was greater (212 microm2 vs 111 microm2). Most regenerating RGCs had large dendritic fields. The data suggest a heterogeneous response to axotomy in adult mice, large RGCs preferentially regrowing axons into PN grafts.

Animals↗
PubMed1985

Effects of capsaicin applied to a peripheral nerve on the responses of primate spinothalamic tract cells.

Capsaicin is a neurotoxin that appears to affect unmyelinated nociceptive sensory fibers selectively. We examined the effects of capsaicin applied topically to the sural nerve on peripheral nerve volleys and on the responses of neurons belonging to the spinothalamic tract (STT) in the monkey. The responses examined included those following electrical stimulation of the sural nerve and also those produced by more natural forms of noxious and innocuous stimuli applied to the skin. Capsaicin (1% solution) applied onto the sural nerve for 15 min resulted in a reduction of the sizes of A delta- and C-fiber afferent volleys. These changes paralleled the reduction of A- and C-fiber responses of the STT cells elicited by electrical stimulation of the sural nerve. During capsaicin application onto the sural nerve, the background activity of STT cells increased for 5-10 min. After capsaicin treatment, the responses of STT cells to innocuous mechanical stimuli applied to the cutaneous receptive field were increased, whereas the responses to noxious mechanical stimuli were decreased. However, topical capsaicin application almost eliminated the responses of STT cells to noxious heat stimuli. The results of the present study suggest that topical capsaicin application onto a peripheral nerve produces a transient nociceptive response followed by a decrease in sensitivity to noxious stimuli, particularly to noxious heat. These changes are due to conduction block of the nerve fibers at the site of capsaicin application.

Animals↗
PubMed2004

Selection of biomaterials for peripheral nerve regeneration using data from the nerve chamber model.

Peripheral nerve regeneration has been studied in a variety of animal models. Of these, the nerve chamber model has clearly dominated. It has been used to generate a large base of data that, however, cannot be analyzed usefully due to lack of standardization of experimental conditions and assays. Lack of standardization of critical experimental parameters of the model has, however, greatly limited the opportunity to compare directly data from independent investigators; as a result, progress in understanding conditions for optimal nerve regeneration has been stunted. In this article, we provide an overview of the major experimental parameters that must be controlled in order to generate data from independent investigators that can be compared directly (normalized data). Such parameters include the gap length, animal species, and the identity of assays used to evaluate the product of the regenerative process. Use of the recently introduced concept of critical axon elongation, the gap length at which the probability of axonal outgrowth (reinnervation) across the gap is 50%, leads to generation of a normalized database that includes data from several independent investigators. Conclusions are drawn about the relative efficacy of the various biomaterials and devices employed. Nerve chamber configurations that had the highest regenerative activity were those in which the tube wall comprised collagen and certain synthetic biodegradable polymers rather than silicone, and was cell-permeable rather than protein-permeable. In addition, the following tube fillings showed very high regenerative activity: suspensions of Schwann cells; a solution either of acidic or basic fibroblast growth factor; insoluble ECM substrates rather than solutions or gels; polyamide filaments oriented along the tube axis; highly porous, insoluble analogs of the ECM with specific structure and controlled degradation rate.

Absorbable Implants↗
PubMed2001

The role of basic fibroblast growth factor in peripheral nerve regeneration.

In the peripheral nervous system regeneration and gradual functional restoration occur following peripheral nerve injury. Growth of regenerating axons depends on the presence of diffusible neurotrophic factors, in addition to the substratum. Neurotrophic factors that are involved in peripheral nerve regeneration include nerve growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor, glial cell line-derived neurotrophic factor, and interleukin-6. Recent functional and expression studies of basic fibroblast growth factor and its receptors have emphasized a physiological role of these molecules in the peripheral nervous system. Basic fibroblast growth factor and its receptors are constitutively expressed in dorsal root ganglia and the peripheral nerve. These molecules display an upregulation in dorsal root ganglia and in the proximal and distal nerve stumps following peripheral nerve injury. In the ganglia these molecules show a mainly neuronal expression, whereas at the lesion site of the nerve, Schwann cells and invading macrophages represent the main cellular sources of basic fibroblast growth factor and the receptors 1-3. Exogenously applied basic fibroblast growth factor mediates rescue effects on injured sensory neurons and supports neurite outgrowth of transectioned nerves. Regarding the expression patterm and the effects after exogenous administration of basic fibroblast growth factor, this molecule seems to play a physiological role during nerve regeneration. Thus, basic fibroblast growth factor could be a promising candidate to contribute to the development of new therapeutic strategies for the treatment of peripheral nerve injuries.

Animals↗
PubMed2005

Artificial nerve conduits in peripheral-nerve repair.

Injuries to the nervous system are the result of mechanical, thermal, chemical or congenital pathologies and, if function is not restored, they lead to loss of muscle function, pain and impaired sensation. Current treatment modalities essentially coapt the two nerves ends together or place a nerve graft between the cut ends. However, clinical results have never been optimal, and therefore a quest for better options has taken place. In this review article we look at the synthetic and biomimetic options currently being tested as potential nerve grafts.

Animals↗
PubMed2002

Combination of gonadal steroid treatment and peripheral nerve grafting results in a peripheral motoneuron-like pattern of beta II-tubulin mRNA expression in axotomized hamster rubrospinal motoneurons.

Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-containing central motoneurons in rodents. In this study, the ability of testosterone propionate (TP), alone or in conjunction with a peripheral nerve graft (PNG), to alter the molecular program of injured RSMN was accomplished using betaII-tubulin cDNA probes and quantitative in situ hybridization (ISH). Initial fluoro-gold labeling experiments following a T1 hemisection established that, as in the rat, the hamster rubrospinal system is essentially crossed and that injured RSMN concentrate in the ventrolateral region of the red nucleus. In the second experimental series, adult gonadectomized male hamsters were subjected to a right T1 hemisection, with half of the operated animals immediately subcutaneously implanted with 1 10 mm TP Silastic capsule and the other half sham implanted. In a third experimental series, animals were subjected to T1 hemisection, followed by transplantation of a predegenerated autologous segment of peripheral nerve. Half of the animals in each group received TP implants at the time of spinal cord injury and PNG. Postoperative times were 2, 7, and 14 days (dpo). Quantitative ISH was performed using a betaII-tubulin-specific (33)P-labeled cDNA probe, emulsion autoradiography, and computerized image analysis for grain counting. Injury alone resulted in a short-lived increase in betaII-tubulin mRNA expression in the RSMN at 2 dpo, with a significant decline to well below control values at 7 and 14 dpo. TP treatment or PNG alone attenuated, but did not prevent, the down-regulation of betaII-tubulin mRNA. In contrast, the combination of TP with a PNG sustained the injury-induced increase in betaII-tubulin mRNA levels throughout the postoperative period of 2, 7, and 14 dpo. The synergistic effects of the two treatment strategies confirm the importance of targeting multiple aspects of the injury response for therapeutic intervention.

Animals↗
PubMed1997

Peripheral nerve injuries in the athlete.

Peripheral nerves are susceptible to injury in the athlete because of the excessive physiological demands that are made on both the neurological structures and the soft tissues that protect them. The common mechanisms of injury are compression, traction, ischaemia and laceration. Seddon's original classification system for nerve injuries based on neurophysiological changes is the most widely used. Grade 1 nerve injury is a neuropraxic condition, grade 2 is axonal degeneration and grade 3 is nerve transection. Peripheral nerve injuries are more common in the upper extremities than the lower extremities, tend to be sport specific, and often have a biomechanical component. While the more acute and catastrophic neurological injuries are usually obvious, many remain subclinical and are not recognised before neurological damage is permanent. Early detection allows initiation of a proper rehabilitation programme and modification of biomechanics before the nerve injury becomes irreversible. Recognition of nerve injuries requires an understanding of peripheral neuroanatomy, knowledge of common sites of nerve injury and an awareness of the types of peripheral nerve injuries that are common and unique to each sport. The electrodiagnostic exam, usually referred to as the 'EMG', consists of nerve conduction studies and the needle electrode examination. It is used to determine the site and degree of neurological injury and to predict outcome. It should be performed by a neurologist or physiatrist (physician specialising in physical medicine and rehabilitation), trained and skilled in this procedure. Timing is essential if the study is to provide maximal information. Findings such as decreased recruitment after injury and conduction block at the site of injury may be apparent immediately after injury but other findings such as abnormal spontaneous activity may take several weeks to develop. The electrodiagnostic test assists with both diagnosis of the injury and in predicting outcome. Proximal nerve injuries have a poorer prognosis for neurological recovery. The most common peripheral nerve injury in the athlete is the burner syndrome. Though primarily a football injury, burners have been reported in wrestling, hockey, basketball and weight-lifting as a result of acute head, neck and/or shoulder trauma. Most burners are self-limiting, but they occasionally produce permanent neurological deficits. The axillary nerve is commonly injured with shoulder dislocations but is also susceptible to injury by direct compression. The sciatic and common peroneal nerves can be injured by trauma. The suprascapular, musculocutaneous, ulnar, median and tibial nerves are susceptible to entrapment. The long thoracic and femoral nerves can be injured by severe traction.

Athletic Injuries↗
PubMed2001

Tracing axons in the peripheral nerve using lacZ gene recombinant adenovirus and its application to regeneration of the peripheral nerve.

The usefulness of recombinant adenovirus with LacZ to trace axons in the peripheral nervous system was investigated. Recombinant adenovirus with LacZ was applied to the cut end of the tibial nerve in rats. The LacZ gene product (B-galactosidase) filled axons of the tibial nerve, which permitted the continuous long-range tracing of axons. Further, the branching and the direction of the branches could also be examined. Labeled axons in the tibial nerves ran parallel to each other without branching and kept this relative position in the tibial and the sciatic nerve. When the virus was introduced to the regenerating nerve using a silicon tube, the regenerating fibers grew tortuously with short branches in the bulge at the proximal end of the silicon tube. The fibers grew straight in the tube and passed through the bulge at the distal end of the tube without branching. These observations indicate that the LacZ gene recombinant adenovirus is a useful tracer for the study of the peripheral nervous system and of the regeneration processes.

Adenoviridae↗
PubMed1992

Innervator NS 252, a new, constant current and programmable peripheral nerve stimulator.

A peripheral nerve stimulator should be able to deliver a constant current to provide supramaximal nerve stimulation even under conditions of increasing resistance. We tested a new programmable peripheral nerve stimulator, the Innervator NS 252. It was able to maintain a constant current of 80 mA up to a resistance of 3.9 kohm. The pulse appearance was correct and there were only small variations in stimulation time intervals. The different type of double burst stimulation and the lack of synchronization with the previously applied stimulus pattern may be regarded as slight disadvantages.

Electric Impedance↗
PubMed1997

Structural and physiological properties of peripheral nerves after intraoperative irradiation.

Peripheral nerve appears to be a dose-limiting normal tissue in the clinical application of intraoperative radiation therapy (IORT). The objectives of this review are to study structural and physiological changes peripheral nerves undergo after intraoperative irradiation through the evaluation of clinical and experimental studies. Clinically significant peripheral nerve injury will most likely occur if the dose of IORT exceeds 20 Gy. Tolerance of peripheral nerve will also depend on the volume of irradiated nerve and surrounding tissues, such as muscle and vasculature, or the combination of IORT with other therapeutic modalities, such as hyperthermia and chemotherapy. Evaluation of the histomorphometric findings showed a significant decrease in nerve fiber density, particularly in the central portion of the nerve and especially affecting large nerve fibers after doses higher than 20 Gy. Electron microscopic analysis have shown an increase in microtubule density and neurofilament accumulation in axons of irradiated nerves while changes in myelin were not present. These findings are suggestive of radiation induced hypoxia (damage to the vasculature) resulting in axon damage and subsequent nerve fiber loss as a mechanism of late radiation injury to the peripheral nerve.

Combined Modality Therapy↗
PubMedDate not supplied

[Tumors of nerve sheaths of the peripheral nerves].

Objectives of this paper are the analysis of the confidence in the complementary investigation for the differential diagnostic between schwannoma and neurofibroma, and the retrospective evaluation of the therapy based on the consequent follow-up. The study has been conducted on 36 patients, most of them observed by University Clinic of Navarra (Pamplona), and the others by N. Picardi, all with preoperative diagnosis of schwannoma and neurofibroma, localized in 13 cases in peripheral nerves. Diagnostic iter, pathologic definition, therapy and evolution has been evaluated for all of them. In conclusion we feel that this pathology has to be suspected every time we find a tumor with neurologic symptomatology and that surgical indication of exeresis is the most correct in the majority of cases; moreover imaging investigations is rather useful, but if any doubt occurs we must proceed to biopsy or directly to exeresis of the tumor. Our experience shows that schwannoma, thanks to its anatomic patterns, can be treated less radically toward the nerve continuity than neurofibroma, and that the technique of nerve graft could be a useful alternative in this kind of surgery.

Adolescent↗