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Clinical study of magnetic stimulation of peripheral nerves.

Magnetic stimulation of the peripheral nerves is a recently developed technique and has exciting prospects in clinical neurophysiology. An experiment was performed comparing the conventional electric stimulation with magnetic stimulation of the median nerve of a normal population. Magnetic stimulation produced comparable results as far as latency, amplitudes and configuration of action potentials in most patients. The technique of magnetic stimulation is discussed. Its shortcomings are in locating the magnetic coil's point of stimulation on the nerve and difficulty in achieving supramaximal stimulation. Its great advantage is that it is painless and that deep nerves can be reached.

Humans↗

Glandular peripheral nerve sheath tumors.

BACKGROUND: Peripheral nerve tumors (PNT) containing glands are uncommon. Which types of PNT contain glands is a matter of controversy, a factor bearing on the prognosis of these tumors. METHODS: The authors reviewed the files of 11 patients with glandular PNT seen in their laboratory and 27 patients reported in the literature. RESULTS: The 11 instances of glandular PNT seen in their laboratory affected male and female patients equally; patients ages ranged from 8 to 68 years (mean, 28 years). Six patients had neurofibromatosis-1 (NF-1). Eleven of the tumors were histologically malignant PNT, and one was a benign neurofibroma. There were no schwannomas (neurilemomas). The glands were discrete, usually localized to a few areas and in every patient were lined by a keratin-positive epithelium, which in two patients was malignant. One tumor also contained areas of rhabdomyosarcoma, chondrosarcoma, and osteosarcoma (a pluridirectional malignant PNT). Treatment in all patients was some form of surgical resection, followed by radiation in three and chemotherapy in two. Follow-up data were available for nine patients; six of eight patients died with disease. Review of the literature revealed two purported glandular schwannomas (neurilemomas). The authors think these patients had schwannomas containing trapped skin adnexa. Overall, 74% of the patients had NF-1. Ninety-two percent of the tumors were histologically malignant, and 23% of the malignant tumors were pluridirectional malignant PNT. Of the 21 patients for whom follow-up was available, 71% died with tumor. CONCLUSION: Most glandular PNT are histologically malignant and often are fatal.

Adolescent↗

Changes in intercellular junctions during peripheral nerve regeneration in insects.

Peripheral nerves of the adult cockroach have been cut and the changes in glial cells followed during the subsequent process of regeneration. After three to four weeks of regrowth, the severed tips of nerves were examined by freeze-fracture to assess the state of intercellular junctions between the perineurial sheath cells as well as the underlying glial cells. Both pleated septate and gap junctions were found in the immature state; their intramembranous particle (IMP) distribution was characteristic of junctions in the process of assembly, since the IMPs were irregularly and loosely arrayed in contrast with the parallel septate junctional IMP rows and gap junctional plaques found in the fully regenerated or control tissues. These junctional stages resembled those occurring in developing embryonic or metamorphosing insect tissues.

Animals↗

Evidence for involvement of a tumor suppressor gene on 1p in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNST) are rare soft-tissue malignancies. The genetic basis of these tumors is still poorly understood. Cytogenetic analyses predominantly revealed complex karyotypes, precluding the identification of recurrent chromosomal changes. We report loss of 1p material in a near-diploid karyotype with few or no additional structural chromosome changes in two sporadic cases of MPNST, indicating an important role of 1p loss in MPNST development. In one of these two tumors, a distal 1p deletion (1p31.2 approximately pter) was detected suggesting involvement of a tumor suppressor gene located within this distal region of 1p. Further evidence for recurrent 1p loss in MPNST was obtained by interphase fluorescence in situ hybridization, which showed loss of 1p material in 3 out of 13 tumors. These findings together with data from the literature suggest that loss of a tumor suppressor gene located within distal 1p is implicated in the pathogenesis of MPNST.

Child↗

Cytogenetic characterization of three malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNST) are soft tissue sarcomas occurring frequently in patients with neurofibromatosis 1. We present three fully karyotyped cases of MPNST revealing aberrant near-triploid karyotypes. In all three cases we found deletions of chromosome arms or chromosomes 1p, 10q, 9, and 15, as well as gain of chromosome 7 in two NF1-associated cases and gain of chromosome 8 in an NF1-associated and a sporadic case. The chromosomal region of the NF1 gene was cytogenetically unchanged in all cases, whereas two MPNST cases showed losses of the region 22q harboring the locus of the NF2 gene.

Adult↗

Importance of soft tissue inhomogeneity in magnetic peripheral nerve stimulation.

In magnetic peripheral nerve stimulation with a figure-of-eight coil, a 'tangential-edge' coil orientation (the nerve is beneath the coil intersection and perpendicular to the coil wings) is ideal theoretically. However, some experimental results show that strong muscle responses are elicited with a 'symmetrical-tangential' coil orientation (the nerve is beneath the coil intersection and parallel to the coil wings), which is inconsistent with the cable theory. We hypothesized that the 10:1 conductivity difference between muscle and fat would cause inconsistent results during magnetic median nerve stimulation in the elbow, which was verified using an inhomogeneous volume conductor model. The induced electric fields were measured in a model composed of saline solutions of different concentrations divided by a cellophane sheet. A nerve was imagined along the boundary between the two solutions, and the coil was held in a 'symmetrical-tangential' position. Virtual cathodes, which were off the nerve in the homogeneous model, were on the nerve in the inhomogeneous model. The previous inconsistent results were explained by considering soft tissue inhomogeneity without any modification of the assumption in the cable theory that only the induced electric field component parallel to the nerve is responsible for nerve excitation.

Adult↗

Comparison of the fastest regenerating motor and sensory myelinated axons in the same peripheral nerve.

Functional outcome after peripheral nerve regeneration is often poor, particularly involving nerve injuries far from their targets. Comparison of sensory and motor axon regeneration before target reinnervation is not possible in the clinical setting, and previous experimental studies addressing the question of differences in growth rates of different nerve fibre populations led to conflicting results. We developed an animal model to compare growth and maturation of the fastest growing sensory and motor fibres within the same mixed nerve after Wallerian degeneration. Regeneration of cat tibial nerve after crush (n = 13) and section (n = 7) was monitored for up to 140 days, using implanted cuff electrodes placed around the sciatic and tibial nerves and wire electrodes at plantar muscles. To distinguish between sensory and motor fibres, recordings were carried out from L6-S2 spinal roots using cuff electrodes. The timing of laminectomy was based on the presence of regenerating fibres along the nerve within the tibial cuff. Stimulation of unlesioned tibial nerves (n = 6) evoked the largest motor response in S1 ventral root and the largest sensory response in L7 dorsal root. Growth rates were compared by mapping the regenerating nerve fibres within the tibial nerve cuff to all ventral or dorsal roots and, regardless of the lesion type, the fastest growth was similar in sensory and motor fibres. Maturation was assessed as recovery of the maximum motor and sensory conduction velocities (CVs) within the tibial nerve cuff. Throughout the observation period the CV was approximately 14% faster in regenerated sensory fibres than in motor fibres in accordance with the difference observed in control nerves. Recovery of amplitude was only partial after section, whereas the root distribution pattern was restored. Our data suggest that the fastest growth and maturation rates that can be achieved during regeneration are similar for motor and sensory myelinated fibres.

Action Potentials↗

Octyl 2-cyanoacrylate for repair of peripheral nerve.

The repair of peripheral nerves with sutures is time consuming. The aim of this study was to evaluate the benefits and functional outcome of repairing nerves with octyl 2-cyanoacrylate adhesive. The right peroneal nerve of 64 male, Lewis rats was sectioned and repaired. The rats were randomized into 3 experimental groups: A (n = 27), using only octyl 2-cyanoacrylate; B (n = 27), using 4, 10-0 nylon sutures; and C (n = 10), a sham operation. The recovery of nerve function was quantified through walking-track analyses; group A showed faster return of nerve function than B, especially at 15 days (P < 0.017). Histologic analysis showed a greater axonal regeneration in group A versus group B and no indication of tissue toxicity in group A. No dehiscence occurred during the 6-month study. Use of adhesive shortened the anastomosis time from 12 minutes to 4 minutes. These results indicate that the use of octyl 2-cyanoacrylate adhesive for nerve anastomoses is safe and effective and may have benefits compared with the use of sutures.

Anastomosis, Surgical↗

Gene expression profiling reveals unique molecular subtypes of Neurofibromatosis Type I-associated and sporadic malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell neoplasms that are frequently associated with Type I Neurofibromatosis (NF1) and respond poorly to current therapeutic regimens. To better understand the molecular heterogeneity of these tumors, we performed gene expression profiling on 25 NF1-associated and 17 sporadic MPNSTs using oligonucleotide microarrays representing approximately 8100 unique human gene transcripts. Using several previously reported statistical approaches, we were unable to identify a molecular signature that could reliably distinguish between NF1-associated and sporadic MPNSTs in independent training and test sample sets. However, using an unsupervised clustering approach, we identified an extensive gene expression signature that distinguished 9 of the 42 tumors analyzed. This signature corresponded to relative overexpression of transcripts associated with neuroglial differentiation (NCAM, MBP, L1CAM, P1P) and relative down-regulation of proliferation and growth factor associated transcripts (IGF2, FGFR1, MDK, Ki67). All tumors with this gene expression signature lacked expression of EGFR and all but one tumor were derived from patients with NF1. However, there were no other obvious associations with histological grade, tumor site, metastasis, recurrence, age, or patient survival. We conclude that distinct molecular classes of MPNST exist and that the ability to stratify these tumors based on unique and biologically relevant gene expression profiles may be important for future targeted therapeutics.

Adolescent↗

[Malignant peripheral nerve sheath tumor with divergent cartilage differentiation from the acoustic nerve: case report].

Malignant peripheral nerve sheath tumors(MPNSTs) of the acoustic nerve are very rare. Only seven cases of MPNST arising from the acoustic nerve have been reported. The authors present a case of MPNST with divergent cartilage and melanotic differentiation of the acoustic nerve. The patient was a 69 year old man admitted to our neurosurgical service in January 1999 complaining of left facial nerve palsy and hearing difficulty of his left ear. The initial CT showed a tumor at the left cerebellopontine angle region. On MRI the tumor was depicted as low intensity on T 1-weighted image and high intensity on T 2-weighted image, the mass was heterogeneously enhanced after administration of Gd-DTPA. The partial removal of the tumor was performed in January 1999. He was discharged February 1999. But he was admitted again because of progressive cerebellar ataxia. MRI showed the rapid regrowth of the residual tumor. In March 1999, complete removal of the tumor was performed. Histopathological analysis revealed a malignant spindle cell neoplasm with divergent cartilage and melanotic differentiation. We review the relevant literature concerning MPNST of the acoustic nerve and discuss the clinical features of malignant eighth cranial nerve tumor.

Aged↗

Peripheral nerve involvement in spinocerebellar ataxias.

BACKGROUND: In autosomal dominant cerebellar ataxias (ADCAs), it is unclear whether the associated peripheral nerve involvement is always a typical length-dependent axonopathy rather than primary neuronopathy due to neuronal degeneration in the spinal anterior horns and/or dorsal root ganglia. OBJECTIVE: To study the nature and extent of peripheral nerve involvement in patients with ADCA. PATIENTS AND METHODS: Standardized clinical and electrophysiologic studies of 27 genotyped patients with ADCA were conducted prospectively, with special emphasis on the distinction between primary neuronopathy and dying-back axonopathy. RESULTS: Electrophysiologic evidence of involvement of the peripheral nervous system was present in 70% of patients. Findings were compatible with dying-back axonopathy in 30%, while in 40% of patients, neuronopathy was diagnosed. Patients with spinocerebellar ataxia (SCA) 1 and SCA2 mostly displayed features of neuronopathy, while patients with SCA3 and SCA7 displayed both neuronopathy and axonopathy. In SCA6, no significant peripheral nerve involvement was demonstrated. We did not observe an influence of age, disease duration, or ataxia severity on the presence or type of peripheral nerve involvement. CONCLUSIONS: Peripheral nerve involvement in ADCA manifests not only as distal axonal neuropathy, but also as primary neuronopathy. Electrodiagnostic studies in this group of patients should be conducted in such a way that primary neuronopathy is detected.

Adult↗

Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury.

The mechanisms by which peripheral nerve injuries sometimes lead to causalgia, aberrant burning pain peripheral to the site of nerve damage, are uncertain, although the sympathetic nervous system is known to be involved. Whether such syndromes could be the result of the development of responsiveness by some cutaneous pain receptors (C-fiber nociceptors) to sympathetic efferent activity as a consequence of the nerve injury was tested in an animal model. After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nociceptors to tissue-damaging stimulation. These effects were demonstratable within days after nerve lesions, occurred at the cutaneous receptive terminal region, were manifest in sensory fibers that had not degenerated after the injury, and were mediated by alpha 2-adrenergic-like receptors.

Animals↗

Phenotypic analysis of migrant, efferent lymphocytes after implantation of cold preserved, peripheral nerve allografts.

Cold-preservation of peripheral nerve allografts in vitro (3 weeks, 5 degrees C) was performed to determine its effect on local lymphocyte migration patterns in vivo. Lymphocyte migration was assessed by continuously monitoring the cell output in the regional lymph for nearly 1 month. Cold-preservation delayed or prevented the typical biphasic increase in efferent lymphocyte output observed after fresh allograft implantation. It also decreased the output of activated lymphocytes (CD 5 and MHC class II positive) compared with that seen in the fresh allograft response. These changes suggest that the host immune response to preserved nerve allografts is altered over a prolonged period in vivo (3 weeks). Cold-preservation may be a useful method of reducing allograft immunogenicity, thereby limiting systemic immunosuppression requirements for the successful clinical utilization of peripheral nerve allografts.

Animals↗

Carbohydrate mimics promote functional recovery after peripheral nerve repair.

OBJECTIVE: The outcome of peripheral nerve repair is often unsatisfactory, and efficient therapies are not available. We tested the therapeutic potential of functional mimics of the human natural killer cell glycan (3-sulfoglucuronyl beta1-3 galactoside) (HNK-1) epitope, a carbohydrate indicated to favor specificity of motor reinnervation in mice. METHODS: We applied a linear HNK-1 mimic peptide, scrambled peptide, or vehicle substances in polyethylene cuffs used to reconstruct the severed femoral nerves of adult mice. We used video-based motion analysis and morphological and tracing techniques to monitor the outcome of nerve repair. RESULTS: After glycomimetic application, quadriceps muscle function recovered to 93% of normal within 3 months. Restoration of function was less complete (71-76%) in control groups. Better functional recovery was associated with larger motoneuron somata, better axonal myelination in the quadriceps nerve, and enhanced precision of target reinnervation. Lesion-induced death of motoneurons was reduced by 20 to 25%. The glycomimetic enhanced survival and neurite outgrowth of both mouse and human motoneurons in vitro by 30 to 75%. Application of a novel cyclic glycomimetic also enhanced functional recovery in vivo. INTERPRETATION: The improved outcome of nerve repair after glycomimetic application may be attributed to neurotrophic effects. Our results hold promise for therapeutic use in humans.

Animals↗

A newly synthesized neurotropic pyrimidine compound, MS-818, may activate migratory schwann cells in peripheral nerve regeneration.

Following transection of a peripheral nerve in mice, a newly synthesized neurotropic pyrimidine compound, MS-818 was administered intraperitoneally at a dose of 1 mg kg-1 b.wt. day-1. The film model experiments for analyzing the early growth of axonal regeneration suggested that MS-818 activated Schwann cells which migrate from the proximal stump, inducing axonal elongation in vivo.

Animals↗

Clinical application of peripheral nerve transplantation.

Surgical reconstruction of extensive peripheral nerve injuries frequently exhausts the patient's own source of expendable autogenous nerve grafts. Nerve allografts would offer a limitless supply of graft material. A 23-cm, 10-cable sciatic nerve allograft was performed in an 8-year-old boy in September of 1988. The patient was managed with Cyclosporin A for 2 years. Forty-four months after the transplant surgery and 19 months after the cessation of Cyclosporin A therapy, the patient has evidence of nerve regeneration across the allograft with recovery of functional sensibility in his foot. In the selected patient with an otherwise irreparable nerve injury, consideration can be given to the use of a nerve allograft.

Child↗

[Methodological considerations concerning peripheral nerve morphometry].

Morphometric studies of the peripheral nerve often present widely varying results which, in part at least, may be attributed to the different methodologies used. Two questions may be of importance with regard to the reliability of such results: the preselection of fibres according to their morphology and the method used in quantifying observations. In this work a morphological study was carried out on the myelinated fibres of the sciatic nerve of a rat in order to evaluate fibre selection criteria. A morphometric analysis was also performed using manual measurements, image digitalisation and surveying, and automatic image analysis. It was shown that morphological variability of transverse section fibres is considerable and that, really, the proportion of circular fibres with homogeneous compact myelin is only 50 to 70%, from which we can conclude that the selection of fibres carried out in some studies wishing to eliminate abnormal fibres is somewhat exaggerated. By analysing the fibres using various methods significant differences appear, some due to the fact that distinct methods may be used to calculate the same parameters in a different way. The most reliable parameters would appear to be those which do not depend on the shape of the fibres and those which automatic or semiautomatic methods can calculate directly such as areas and perimeters. In any case quantifying methods seem hardly discriminatory and the differences between methods disappear if analyses are carried out using random samples. Preselection of fibres appears unnecessary in this context as in no case are the results altered. Finally we suggest finishing quantitative analyses with qualitative studies which would permit getting more information especially useful in cases of ageing, regeneration or pathological studies.

Aging↗

[Effects of transforming growth factor-beta 1 on the peripheral nerve regeneration of rats].

OBJECTIVE: To explore the effects of exogenous transforming growth factor-beta 1 (TGFbeta1) on peripheral nerve regeneration after the peripheral nerve injury and if TGFbeta1 regulates the expression of basic fibroblast growth factor (bFGF) in the anterior horn motoneurons of spinal cord during regeneration. METHODS: Forty-eight rats were crushed on the right sciatic nerve and then randomly divided into 2 groups: TGFbeta1 group and NS group. In TGFbeta1 group, TGFbeta1 50 microL (0.1 microg/mL) was injected into the proximal nerve near to the crushed nerve and after the operation the injured leg was injected with equal TGFbeta1 whereas the NS was replaced in the NS group. The rats of each group survived for 3, 7, 14 and 21 days after the lesion. The bFGF expression in the anterior horn motoneurons of spinal cord was detected by immunohistochemistry (IHC). Semi-thin section and Fast Blue retrograde tracing were also performed with the rats surviving for 21 days to observe the regeneration of distal end in the injured right sciatic nerve. RESULTS: The number of bFGF immunoreactive positive motoneurons in TGFbeta1 group was obviously higher than that of the NS group (P < 0.05). In the distal sciatic nerve of the rats treated with TGFbeta1, the number and diameter of regenerating myelinated axons and the thickness of myelinated sheath were more than those of the NS group (P < 0.05). The number of motoneurons in spinal cord and neurons in dorsol root ganglia (DRG) labelled with Fast Blue in the NS group was obviously lower than in the TGFbeta1 group (P < 0.01). CONCLUSION: Exogenous TGFbeta1 plays an important role in promoting the peripheral nerve regeneration; TGFbeta1 up-regulates the bFGF expression in the anterior horn motoneurons of spinal cord during the peripheral nerve regeneration.

Animals↗