Treatment Of Peripheral Nerve Lesions Research Articles

455 Distal Nerve Transfers in Treatment of Peripheral Nerve Lesions

INTRODUCTION: Distal nerve transfers can be used in treating patients with irreparable high nerve lesions, aiming to regain hand function. The indications for these transfers include upper (C5-C6) and lower (C8-T1) brachial plexus palsy, isolated proximal extensive radial, median, or ulnar nerve lesion, or isolated axillary or musculocutaneous nerve lesion. METHODS: The selected cases (n = 5) included lower brachial plexus injury (n = 2), and isolated radial (n = 1), ulnar (n = 1), and median (n = 1) nerve injuries. The MRC grading was used to examine postoperative muscle strength. The DASH and PNSQoL questionnaires were used to assess the postoperative quality of life. RESULTS: The useful functional recovery (MRC = 4-5) was achieved in all presented cases. The DASH and PNSQoL scores indicated a satisfying quality of life in terms of the absence of postoperative disability. CONCLUSIONS: Distal nerve transfers are a valuable technique for treatment of the patients with irreparable proximal nerve lesions. This technique reduces the path necessary for the regenerative nerve fibers to pass, provides direct nerve coaptation without additional suture line, and facilitates faster and better recovery, with the final outcome as an increase in the patients’ quality of life.

Strain-induced bands of Büngner formation promotes axon growth in 3D tissue-engineered constructs

Treatment of peripheral nerve lesions remains a major challenge due to poor functional recovery; hence, ongoing research efforts strive to enhance peripheral nerve repair. In this study, we aimed to establish three-dimensional tissue-engineered bands of Büngner constructs by subjecting Schwann cells (SCs) embedded in fibrin hydrogels to mechanical stimulation. We show for the first time that the application of strain induces (i) longitudinal alignment of SCs resembling bands of Büngner, and (ii) the expression of a pronounced repair SC phenotype as evidenced by upregulation of BDNF, NGF, and p75NTR. Furthermore, we show that mechanically aligned SCs provide physical guidance for migrating axons over several millimeters in vitro in a co-culture model with rat dorsal root ganglion explants. Consequently, these constructs hold great therapeutic potential for transplantation into patients and might also provide a physiologically relevant in vitro peripheral nerve model for drug screening or investigation of pathologic or regenerative processes.

The role of the reconstructive surgeon treating neuropathic pain after iatrogenic nerve lesions

The role of the reconstructive surgeon treating neuropathic pain after iatrogenic nerve lesions Abstract. Any surgical intervention bears the potential risk of iatrogenic nerve lesions with consecutive functional deficits and chronic neuropathic pain syndromes. These complications obviously result in patient dissatisfaction and frequently bear legal consequences. A broad experience in diagnosis and treatment of peripheral nerve lesions is needed to initiate the proper diagnostics and treatment modalities in an according time frame. The quick and appropriate response after any nerve trauma is an important criterion for success or failure of the reconstruction. Surgeons from other specialities, who do not deal with nerve lesions in their daily routine, need a distinct overview about diagnostics and treatment, to initiate the adequate therapy shortly after the injury. This review provides an overview of peripheral nerve lesions, the underlying pathomechanisms, the diagnosis and reconstructive treatment options. Even with highest accuracy and experience, nerve lesions are part of any surgical practice. However, we are convinced that with adequate and prompt action of the primary surgeon a good patient-doctor relationship may be maintained, often more favourable results may be achieved after reconstruction and legal trials avoided.

Traumatic peripheral nerve lesions : Diagnosis and treatment

Traumatic peripheral nerve lesions affect patients of all age groups. They are associated with functional deficits that have severe consequences for affected patients and prolonged or permanent inability to work has socioeconomic relevance. In order to improve prognoses and achieve the best possible outcome an early diagnosis and competent knowledge of the correct approach and treatment strategies are essential. Unfortunately, nerve lesions are often not detected in time, so that surgical treatment can only be initiated after a delay. Because of the relatively high proportion of iatrogenic nerve lesions, aprofound knowledge of the optimal care of patients with peripheral nerve lesions is compulsory for every doctor who works in the operative field. Surgical treatment of peripheral nerve lesions should remain in the hands of experienced peripheral nerve surgeons. The foundation of successful treatment, however, begins earlier at the initial referral when the patient receives the correct diagnostics and treatment.

Co-Culture Systems of Human Sweat Gland Derived Stem Cells and Peripheral Nerve Cells: An in Vitro Approach for Peripheral Nerve Regeneration

Background/Aims: The treatment of peripheral nerve lesions still represents a clinical challenge. Several approaches such as novel biomaterials for nerve guides, addition of growth factors or cellular supplements moved in the focus of research. Especially the application of autologous stem cells is highly promising for future applications. Human sweat gland derived stem cells (hSGSCs) represent an easy accessible source of autologous adult stem cells and did already show a beneficial effect in dermal wound healing. Methods: In this study, the effect of hSGSCs on neurite outgrowth of primary adult or prenatal Dorsal root ganglia (DRG) neurons was analysed in an indirect co-culture model. Additionally, direct co-cultures with hSGSCs as a feeder layer were performed. Results: Adult and prenatal DRG neurons showed increased neurite outgrowth after 24 h co-culture with hSGSCs. The outgrowth increased significantly by the factors 5.6 and 2.6 respectively. Direct co-cultures revealed neurite alignment along the hSGSCs orientation. Conclusion: The paracrine influence of hSGSCs on neurite outgrowth, but also their ability to operate as a feeder layer with guidance properties shows great potential for future applications in peripheral nerve regeneration.

Functionalization of Electrospun Poly(ε-Caprolactone) Fibers with the Extracellular Matrix-Derived Peptide GRGDS Improves Guidance of Schwann Cell Migration and Axonal Growth

The best available treatment of peripheral nerve lesions involves transplantation of an autologous nerve. This approach, however, entails sensory deficits at the donor site and requires additional surgery. Such limitations have motivated the search for a bioengineering solution to design artificial implants. For this purpose we are producing orientated biodegradable microfibers of poly(ε-caprolactone) (PCL) with electrospinning. The present study describes the functionalization of these electrospun fibers with biologically active peptides to produce guidance structures for Schwann cell migration and axonal regeneration. For the chemical modification PCL was blended with star-shaped NCO-poly(ethylene glycol)-stat-poly(propylene glycol) (PCL/sPEG) as a covalent linker for the peptide GRGDS, derived from extracellular matrix proteins. To test biological functions of electrospun fibers, Schwann cell migration and axonal growth from dorsal root ganglia explants were investigated with time lapse video microscopy. Migrating Schwann cells as well as growing sensory axons closely followed the electrospun fibers with occasional leaps between adjacent fibers. Cell migration was characterized by frequent changes in velocity and direction reversals. Comparison of substrates showed that functionalized fibers caused more Schwann cells to move out of the explants, supported faster cell migration and axonal growth than the nonfunctional fibers. Using inhibitors of intracellular signaling kinases, we found that these biological effects required activation of the phosphatidyl inositol-3-kinase pathway. Since sPEG-containing fibers also showed low levels of nonspecific protein adsorption, which is desirable in the context of artificial implant design, the peptide modification of fibers appears to provide good substrates for nerve repair.

Diagnosis and treatment of peripheral nerve lesions in children

Abstract Over the past decade, there have been significant improvements in neurophysiologic testing, imaging and microsurgical techniques applied to peripheral nerve(s). These have led to major changes in the possibilities for treatment and intervention for children and adolescents with monoparesis and/or identified peripheral nerve lesions. This review will present several illustrative case studies and demonstrate the utility of these techniques.

Basic fibroblast growth factor isoforms promote axonal elongation and branching of adult sensory neurons in vitro

Synthesis of the multifunctional cytokine basic fibroblast growth factor (FGF-2) is up-regulated after sciatic nerve lesion. In this study, the effects of low and high molecular weight FGF-2 isoforms on axonal elongation and branching of dissociated rat sensory neurons derived from adult lumbar dorsal root ganglia were investigated. These neurons express FGF receptor (FGFR) type I in the cytoplasmic/membrane compartment and in nuclear speckles. FGF-2 isoforms increase the number of axonal branches in cultures obtained from control rats, but do not promote axonal elongation. In response to a preconditioning lesion, i.e. transection of the sciatic nerve 1 week before culture, the axonal length of ipsilateral lumbar sensory neurons increases two-fold when compared with non-lesioned control rats, and this response is significantly enhanced by FGF-2 isoforms but not by nerve growth factor (NGF). Neurons dissociated from ganglia located contralaterally to the lesion exhibit a smaller increase in axon elongation (30%). The stimulating effects of FGF-2 isoforms on axon growth are fully blocked, and the enhanced regeneration of prelesioned neurons is reduced by the FGFR inhibitor SU5402 suggesting an involvement of endogenous FGF signaling in response to a lesion. The present data support a direct neurotrophic role of the 18 kD and 23 kD FGF-2 isoforms on adult axonal regeneration which may be of therapeutic value in the treatment of peripheral nerve lesions. Furthermore, evidence is provided for an enhanced regenerative capacity not only of preaxotomized neurons but also of homonymous non-axotomized neurons.

Differences in peripheral nerve degeneration/regeneration between wild-type and neuronal nitric oxide synthase knockout mice.

Nitric oxide (NO), a unique biological messenger molecule, is synthesized by three isoforms of the enzyme NO synthase (NOS) and diffuses from the site of production across cellular membranes. A postulated role for NO in degeneration and regeneration of peripheral nerves has been explored in a sciatic nerve model comparing wild-type mice and mice lacking neuronal NOS after transection and microsurgical repair. In NOS knockout mice, regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). In the regenerated nerve, pruning of uncontrolled sprouts was disturbed, leading to an enhanced number of axons, whereas remyelination seemed to be less affected. Delayed regeneration was associated with a delayed recovery of sensor and motor function. In such a context, possible NO targets are neurofilaments and myelin sheaths of the interrupted axon, filopodia of the growth cone, newly formed neuromuscular endplates, and Schwann cells in the distal nerve stump. The results presented suggest that 1) local release of NO following peripheral nerve injury is a crucial factor in degeneration/regeneration, 2) success of fiber regeneration in the peripheral nervous system depends on a regular WD, and 3) manipulation of NO supply may offer interesting therapeutic options for treatment of peripheral nerve lesions.

Review of some surgical concepts in the treatment of peripheral nerve lesions

Summary The treatment of peripheral nerve lesions still represents a challenge in spite of today's diagnostic and surgical sophistication. Clear anatomo-clinical and surgical notions must guide the treatment planning in this field which has been somewhat «neglected» by clinical neurosurgery. The results can be spectacular, nevertheless the decisive information will often be acquired only after surgical exposure that is in situ. The basic prerequisite or principIe is to be able to create optimal conditions for axonal regrowth.

頚部脊椎症と末梢神経障害の合併 運動神経伝導速度を中心に

Twenty-three patients with cervical spondylosis were confirmed by clinical symptoms and X-ray finding. We, then, measured their motor nerve conduction velocities (MCV) of the median and ulnar nerves. The delay of terminal latency in the median nerve (M-TL) and the ulnar nerve (U-TL) were detected in 35.7% and 15.2% of the patients, respectively. Delay of the ulnar nerve MCV (a cross section of the elbow) was recognized in 28.3% of the patients. Patients who showed a delayed M-TL had cervical lesions at the C5 or C6 root under radiculopathy. But patients who showed a delayed U-TL had no special level of cervical lesion. A high percentage of patients with cervical spondylosis showed a delayed M-TL, U-TL and of U-E. It seems that patients with cervical spondylosis may have peripheral nerve lesions. These cases which showed a delayed U-E had more clinical symptoms than did those cases with a delayed M-TL and U-TL. We believe that patients with severe cervical lesions will not obtain good results in the treatment of peripheral nerve lesions.

Elektrophysiologische Diagnostik bei peripheren Nervenläsionen

In the last two decades the surgical treatment of peripheral nerve lesions has improved considerably, mostly because of the introduction of the microsurgical technique. It was not until the introduction of microsurgery that the surgeon was able to achieve restoration at the level of the nerve fasciculi. The simultaneous use of electrophysiological techniques can improve the results of the reconstruction and especially the extent of functional outcome of nerve restoration. Electrophysiological methods allow detailed and objective assessment of the site, extent, and cause of the lesion and are therefore crucial for the decision upon the appropriate therapeutic procedure and for the success of the operation. The aim of the review is the demonstration of: 1. Today's understanding of peripheral nerve function/ 2. The neurophysiological mechanism of denervation and renervation/ 3. The different electrophysiological methods/ 4. The indications and 5. Application of these techniques in the context of reconstructive surgery.

New methods of treatment of severely injured sciatic nerve and spinal cord. An experimental study.

It has been demonstrated that low-energy laser irradiation (LELI) applied simultaneously to the injured sciatic nerve and the corresponding segment of the spinal cord, accelerates the process of regeneration of the injured peripheral nerve. A beneficial influence of LELI was also observed when it was applied to the spinal cord following transection and implantation of a segment of an autologous sciatic nerve, but further studies are necessary to evaluate if real regeneration or only earlier distal cord automatism occurred. Both methods are proposed for treatment of peripheral nerve lesions (PNS) and spinal cord injuries.

Morphological and functional effects of triiodothyronine on regenerating peripheral nerve

The functional and morphologic consequences of treatment of peripheral nerve lesions with exogenous 3,3′,5-triiodo- l-thyronine (T 3) are unclear. In this study adult wistar rats with sciatic nerve crush lesions were treated with 20 μg/kg/day of T 3. The treated animals gained weight though more slowly than vehicle-treated rats. Ten control and 10 experimental animals assessed 4 days postoperatively for sensory axon regeneration by the “pinch test” showed no significant difference in distance regenerated. Motor function recovery was monitored for 21 days after nerve crush lesions by the vestibular placing response and also showed no significant difference. Light microscopy of transverse epoxy sections of the sciatic nerve 5 mm distal to the lesion showed no significant difference in whole nerve area or myelinated fiber density but quantitative electron microscopy revealed a significant increase in axolemma, myelin spiral length, whole nerve fiber area, and nerve fiber perimeter in T 3-treated rats. Statistically non-significant increases in axonal area and myelin periodicity were also noted. These results are interpreted as indicating that although T 3 treatment is not functionally beneficial in the regeneration of adult mammalian peripheral nerve it nonetheless has subtle morphologic effects that indicate a stimulating effect on membrane synthesis.

Electrophysiological recordings in peripheral nerve surgery: A review

The use of electrophysiological techniques as an adjunct in the surgical repair of peripheral nerve injuries can improve the quality of the repair and thus the degree of functional recovery. These techniques provide objective information needed to assess the degree of injury and can assist the surgeon in making proper decisions regarding treatment of peripheral nerve lesions. The purposes of this paper are to review: (1) the current theories of the functions of peripheral nerves and their and organs, (2) the development of electrophysiological techniques, (3) the principles involved in their use, and (4) the present and possible future applications of these techniques in peripheral nerve surgery and to outline them.

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.