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PubMed1985

Electron microscopic findings of the peripheral nerve lesions of nude mice inoculated with M. leprae.

Peripheral nerve lesions of nude mice inoculated with Mycobacterium leprae were examined from 1 year to 1 year and 8 months post-inoculation. Leprosy bacilli and intracytoplasmic foamy structures were found in the perineurial cells, endothelial cells of capillaries, Schwann cells, and axons of the myelinated nerve fibers inside the lepromas of foot pads. In the proximal portion of the sciatic nerve, bacilli were found chiefly in the macrophages of the endoneurial space. Bacilli were not found in the perineurial cells of the sciatic nerves. Marked fibrosis, hypertrophy or degeneration of Schwann cells, demyelination, axonal damage or irreversible destruction of nerve architecture were not observed clearly. Therefore, it is thought that nude mice inoculated with M. leprae are suitable models for the study of the early peripheral nerve lesions of lepromatous leprosy.

Animals↗
PubMed2002

Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors.

CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma. OBJECTIVE: To determine the specificity of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6 melanotic), 13 malignant peripheral nerve sheath tumors; 10 schwannomas (1 pigmented), 12 neurofibromas (4 pigmented), and 20 fibrohistiocytic tumors (10 dermatofibrosarcoma protuberans and 10 dermatofibromas). Microwave-based antigen retrieval was performed in 10mM citrate buffer, pH 6.0, for 20 minutes at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45. CONCLUSIONS: Our results support the sensitivity of tyrosinase expression and demonstrate the relative specificity of tyrosinase as a marker for melanocytic lesions, including desmoplastic melanoma, although pigmented peripheral nerve tumors may demonstrate focal positive staining. Immunoreactivity for tyrosinase and HMB-45 may have been enhanced by the microwave-based antigen-retrieval technique used in this study.

Antigens, CD34↗
PubMed2003

Schwann cells synthesize alpha7beta1 integrin which is dispensable for peripheral nerve development and myelination.

Defects in laminins or laminin receptors are responsible for various neuromuscular disorders, including peripheral neuropathies. Interactions between Schwann cells and their basal lamina are fundamental to peripheral nerve development and successful myelination. Selected laminins are expressed in the endoneurium, and their receptors are developmentally regulated during peripheral nerve formation. Loss-of-function mutations have confirmed the importance and the role of some of these molecules. Here we show for the first time that another laminin receptor, alpha7beta1 integrin, previously described only in neurons, is also expressed in Schwann cells. The expression of alpha7 appears postnatally, such that alpha7beta1 is the last laminin receptor expressed by differentiating Schwann cells. Genetic inactivation of the alpha7 subunit in mice does not affect peripheral nerve formation or the expression of other laminin receptors. Of note, alpha7beta1 is not necessary for basal lamina formation and myelination. Nonetheless, these data taken together with the previous demonstration of impaired axonal regrowth in alpha7-null mice suggest a possible Schwann cell-autonomous role for alpha7 in nerve regeneration.

Animals↗
PubMed1994

Brachial plexus repair by peripheral nerve grafts directly into the spinal cord in rats. Behavioral and anatomical evidence of functional recovery.

Over the years, peripheral nerve grafts, a favorable environment for the support of axonal elongation, have attracted interest as a possible means of promoting spinal cord repair. In the experiments described here, rats underwent an avulsion injury of the brachial plexus, and the musculocutaneous nerve was repaired by direct insertion of peripheral nerve grafts into the spinal cord. After varying postoperative periods, the rats were submitted to a series of behavioral tests to evaluate forelimb and hindlimb function. They also underwent retrograde double-labeling studies. Nerve grafts were harvested and processed for electronic microscopy. The biceps muscle was removed and weighed and its histology studied. After surgery, central axons effectively regenerated about 65 mm along the peripheral nerve grafts, restoring normal active elbow flexion. Forelimb movements were well coordinated in both voluntary and automatic activities. Clinical investigations showed that there were no side effects in the ipsilateral forepaw, contralateral forelimb, or either hindlimb. Regenerating axons stemmed from original motoneurons, foreign motoneurons, and even antagonist motoneurons, but this did not impair function. Ganglionic neurons from adjacent roots also sent processes to the peripheral nerve grafts.

Animals↗
PubMed2000

Effective gene transfer into regenerating sciatic nerves by adenoviral vectors: potentials for gene therapy of peripheral nerve injury.

Replication defective adenoviral vectors have been demonstrated as an effective method for delivering genes into a variety of cell types and tissues both in vivo and in vitro. Transfecting genes into neuronal cells has proven to be difficult because of their lack of cell division. Since the major problem in neurological disease is the degeneration of the terminally differentiated neuronal cells, the adenoviral vector's ability to transfer genes into differentiated post-mitotic cells makes them advantageous for a gene delivery system for the nervous system. Here we showed that a replication defective recombinant adenovirus carrying the lacZ gene could infect the neuronal stem cells and even the differentiated neuronal cells derived from the central nervous system. The lacZ gene delivered into the neuronal cells was expressed efficiently. In addition, the recombinant virus also infected Schwann cells in intact and injured nerves in vivo. The expression of the lacZ gene lasted for 5 weeks, within which nerve regeneration is accomplished in the rat. Adenoviral vectors might thus be used to modulate Schwann cell gene expression for treating peripheral nerve injury or peripheral neuropathy.

Adenoviridae↗
PubMed1995

Late radiation injury to muscle and peripheral nerves.

Late radiation injury to muscles and peripheral nerves is infrequently observed. However, the success of radiation oncology has led to longer patient survival, providing a greater opportunity for late effects to develop, increase in severity and, possibly, impact the quality of life of the patient. In addition, when radiation therapy is combined with surgery and/or chemotherapy, the risk of late complications is likely to increase. It is clear that the incidence of complications involving muscles and nerves increases with time following radiation. The influence of volume has yet to be determined; however, an increased volume is likely to increase the risk of injury to muscles and nerves. Experimental and clinical studies have indicated that the alpha/beta ratio for muscle is approximately 4 Gy and, possibly, 2 Gy for peripheral nerve, indicating the great influence of fractionation on response of these tissues. This is of concern for intraoperative radiation therapy, and for high dose rate brachytherapy. This review of clinical and experimental data discusses the response of muscle and nerves late after radiation therapy. A grading system has been proposed and endpoints suggested.

Humans↗
PubMed2002

Training of residents in peripheral nerve blocks during anesthesiology residency.

STUDY OBJECTIVE: To survey American anesthesiology residency program directors to determine the availability and extent of training in peripheral nerve block techniques. DESIGN: Survey questionnaire was mailed and faxed to 132 American anesthesiology residency program directors and followed up 4 weeks later with another mailing to nonresponders. SETTING: University medical center. MEASUREMENTS AND MAIN RESULTS: Of the 132 American anesthesiology residency program directors surveyed, 69 (52%) responded. Of the responders, 40 (58%) offered a specific peripheral nerve block rotation. The rotation was of 1 month's duration in 61% of these programs. Formal instruction was administered during the rotation in 69%. The regional instruction approach consisted of a nerve stimulator (98%), paresthesia (75%), and transarterial (85%). Multimedia, mannequins, and cadaver dissection were used infrequently (13-25%). During the rotation, residents performed a variety of blocks, but the number of each block varied from 2 (supraclavicular) to 10 (axillary). These blocks were performed in the operating room in 48% of programs. Finally, in the programs with a specific peripheral nerve block rotation, residents were evaluated. CONCLUSIONS: Specific peripheral nerve block rotations are not always included in anesthesiology residents' curriculum. In addition, residents in programs with a specific nerve block rotation are exposed to a greater number of peripheral nerve block techniques than those who do not have such a rotation included in their curriculum.

Academic Medical Centers↗
PubMed2004

Inhibitory effect of cyclosporin A on p-glycoprotein function in peripheral nerves of mice treated with doxorubicin and vinblastine.

OBJECTIVE: To investigate the inhibitory effect of cyclosporin A on p-glycoprotein function in peripheral nerves (VIIth, VIIIth and sciatic nerves). MATERIAL AND METHODS: Male mdr1a(-/-) and mdr1a(+/+) FVB mice were used. Doxorubicin (30 mg/kg) was administered intravenously with or without i.p. administration of cyclosporin A (200 mg/kg). Vinblastine (5 mg/kg) was also administered intravenously with or without i.p. administration of cyclosporin A (200 mg/kg). RESULTS: Tissue concentrations of doxorubicin and vinblastine in peripheral nerves of the mdr1a(+/+) mice pretreated with 200 mg/kg cyclosporin A were significantly higher than those in the mdr1a(+/+) mice administered doxorubicin or vinblastine alone, suggesting that cyclosporin A inhibited the efflux pump function of p-glycoprotein in the peripheral nerves. In the mdr1a(-/-) mice, tissue concentrations of doxorubicin and vinblastine in peripheral nerves were also significantly higher than those in the mdr1a(+/+) mice administered doxorubicin or vinblastine alone. Based on these results, it is suggested that p-glycoprotein plays an important role in blood-nerve barrier function by preventing side-effects induced by neurotoxic drugs. CONCLUSION: When doxorubicin and vinblastine are co-administered with cyclosporin A, the patient should be carefully monitored because peripheral nerve disorders may be induced.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1975

Myxoedematous polyneuropathy: a light and electron microscopic study of the peripheral nerve and muscle.

Histopathological findings of biopsied peripheral nerve and muscle were studied in a case with myxoedematous polyneuropathy. The most striking findings in the sural nerve were segmental demyelination and onion bulb formation with scanty mucinous deposits in addition to marked loss of large myelinated nerve fibres. The peroneus brevis muscle revealed the association of neuropathic and myopathic changes. It is suggested that myxoedematous polyneuropathy might be intrinsic neuropathy due to metabolic disorder of Schwann cells related to hypothyroidism, resulting in segmental demyelination, not merely compressive neuropathy due to mucinous deposits in the peripheral nerves.

Aged↗
PubMed2004

Radiotherapy-induced malignant peripheral nerve sheath tumor of the cauda equina.

STUDY DESIGN: Case report. OBJECTIVES: To report a rare case of radiation-induced malignant peripheral nerve sheath tumor of the cauda equina 10 years after treatment for testicular seminoma. SUMMARY OF BACKGROUND DATA: Development of malignant peripheral nerve sheath tumor after irradiation is well recognized and often associated with a dismal prognosis. There have been isolated reports of malignant peripheral nerve sheath tumor developing in sites of previous irradiation for testicular seminoma. METHODS: Retrospective review of case records and imaging. RESULTS: A 38-year-old man presented with signs of cauda equina syndrome. Ten years previously, he had undergone right radical inguinal orchidectomy and adjuvant para-aortic radiotherapy as treatment for Stage I testicular seminoma. Magnetic resonance imaging demonstrated an inoperable intra- and extradural tumor leading to significant cauda equina compression. CT-guided biopsy revealed a diagnosis of malignant peripheral nerve sheath tumor, most likely due to previous radiotherapy. His clinical condition did not improve, and he underwent a course of palliative chemotherapy. CONCLUSIONS: Postirradiation malignant peripheral nerve sheath tumors are rare and occur in a population at high risk of developing second malignancies. The authors report the fourth case resulting from adjuvant radiotherapy for testicular seminoma, with the present report being the first report of extensive intradural tumor leading to cauda equina syndrome.

Accidental Falls↗
PubMed2006

Reduced peripheral nerve function is related to lower hip BMD and calcaneal QUS in older white and black adults: the Health, Aging, and Body Composition Study.

UNLABELLED: Bone tissue is innervated, and peripheral nerve function may impact BMD. Older black and white men and women (N = 2200) in the Health, Aging, and Body Composition Study with worse sensory and motor peripheral nerve function had lower hip BMD and calcaneal BUA independent of lean mass, strength, physical ability, and diabetes. Poor peripheral nerve function may directly affect bone. INTRODUCTION: Bone tissue is innervated, yet little is known about the impact of nerve function on BMD. Poor peripheral nerve function may contribute to lower BMD and higher fracture risk, particularly in those with diabetic neuropathy. MATERIALS AND METHODS: The Health, Aging, and Body Composition (Health ABC) Study included annual exams in white and black men and women 70-79 years of age recruited from Pittsburgh and Memphis. Nerve function in legs/feet was assessed by 1.4- and 10-g monofilament detection, vibration threshold, and peroneal motor nerve conduction velocity (NCV) and amplitude (CMAP). Total hip BMD, heel broadband ultrasound attenuation (BUA), and total fat and lean mass were measured 1 year later (QDR 4500A, Sahara QUS; Hologic). RESULTS: Participants (N = 2200) were 48% men and 37% black. Poor nerve function (lower monofilament detection, higher vibration threshold, lower CMAP, lower NCV) was associated with 1.4-5.7% lower BUA and significant for all but NCV, adjusted for demographics, diabetes, body composition, and physical ability. Results were similar for adjusted hip BMD, with 1.0-2.9% lower BMD, significant for monofilament and CMAP testing. When considering the components of BMD, total hip area was 1.8-4.9% higher in those with the worst nerve function, although BMC showed little difference. Lower monofilament detection and CMAP were independently associated with lower heel BUA (p < 0.01), and monofilament detection was associated with lower hip BMD (p < 0.05) in regression additionally adjusted for lifestyle factors, bone-active medications, and diabetes-related complications. CONCLUSIONS: Poor peripheral nerve function may directly related to lower BMD, likely through an increase in bone area in older adults, independent of lean mass, strength, physical ability, and diabetes. Whether those with impaired nerve function are at higher risk for fracture independent of falls needs to be studied.

Aged↗
PubMed1970

The role of diffusion barriers in determining the excitability of peripheral nerve.

The excitability changes occurring in normal isolated peripheral nerves of rats have been studied during exposure to hypoxic and anoxic conditions before and after the administration of insulin. The changes observed have been explained in terms of the dynamics of K' equilibrium in the periaxonal spaces, and attention is drawn to the importance of the relative impermeability of the periaxonal diffusion barrier in determining this equilibrium. Isolated peripheral nerves from alloxan-diabetic rats, studied under similar conditions, show significant differences in the sequence of their excitability changes. It has been shown that the rate of change of excitability in these nerves is slower than those of control nerves. These results have now been interpreted in terms of the K' changes in the periaxonal space. It is concluded that these slower excitability changes are due to an increase in the permeability of the diffusion barrier of the diabetic nerve to potassium.

Animals↗
PubMed2002

Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized by the occurrence of bilateral vestibular schwannomas, various brain and spinal tumours as well as peripheral nerve tumours, cutaneous tumours and juvenile posterior lenticular opacity. NF2 is caused by mutations in both alleles of a tumour suppressor gene coding for a protein called schwannomin or merlin. It is suggested that the development of NF2 tumours is caused by complete inactivation of the merlin/schwannomin gene. Interestingly, in a NF2 mouse model, peripheral nerve pathology was more frequently described than schwannomas. However, review of the literature shows that patients suffering from NF2 seldom have unexplained clinical features of peripheral nerve lesion unrelated to tumour masses. Single case reports describe sural nerve biopsies, which histologically show onion-bulb-like formations, seemingly originating from Schwann cells. We have conducted a systematic investigation to determine the occurrence and aetiology of peripheral nerve involvement in NF2 patients. We investigated 15 patients with definite NF2 and in 10 of these found electrophysiological evidence of neuropathy. In this study we present the classification of neuropathy, correlation to clinical findings, and histological findings of a sural nerve biopsy. We conclude that peripheral neuropathy, mostly of axonal type, is a common clinical finding in NF2. We hypothesize that the aetiology of this frequent peripheral neuropathy syndrome in NF2 is caused by compression effects of multiple tumourlets, originating along the length of the peripheral nerves on adjacent nerve fibres, by local influences of the endoneurial pathological cells on adjacent nerve fibres and/or the inability of these cells to properly adhere to, or ensheath, the axon.

Adult↗
PubMed1998

Effects of prelesioned peripheral nerve graft on nerve regeneration in the rat spinal cord.

OBJECTIVE: The aim of this study was to examine the effects of prelesioned peripheral nerve grafts on central nerve regeneration compared with the freshly transected peripheral nerve grafts in the dorsal funiculus of the rat spinal cord. METHODS: The experimental paradigm consisted of ligating the common peroneal nerve at the midthigh level for 7 days, while the adjacent tibial nerve was left intact. Numerous Schwann cells appeared accompanying regenerating axons in the proximal stump of the ligated nerve. The proximal stumps of the ligated (prelesioned) common peroneal nerve and the intact (untreated) tibial nerve were excised as one tissue block and autografted into the dorsal funiculi of the upper cervical cord. The graft was placed so that the prelesioned common peroneal nerve was positioned on the left dorsal funiculus and the untreated tibial nerve was positioned to the right of the midsagittal plane. Nerve regeneration was examined by light and transmission electron microscopy 1 to 16 weeks after grafting, comparing the effectiveness of prelesioned and untreated nerve grafts. RESULTS: Numerous regenerating axons were observed in the caudal border of both grafts 1 to 2 weeks after grafting. Astrocyte proliferation was suppressed in the prelesioned grafts compared to the untreated grafts. Four to 16 weeks later, the number of regenerating axons was approximately 10-fold as large in the prelesioned grafts as in the untreated grafts. The regenerating axons were myelinated by Schwann cells. Astrocytic glial scar formation was inconspicuous in the prelesioned grafts, whereas it was prominent in the untreated grafts. Schwann cells were contiguous with astrocytes along regenerating axons, forming a continuous conduit from the central to peripheral nerve microenvironments for the outgrowth of regenerating axons. CONCLUSION: The prelesioned peripheral nerve graft is more effective than the untreated graft in suppressing astrocytic scar formation and in supporting the outgrowth of regenerating axons in the dorsal funiculus of rat spinal cord.

Animals↗
PubMed1994

Cytogenetic analysis of soft tissue sarcomas. Recurrent chromosome abnormalities in malignant peripheral nerve sheath tumors (MPNST).

Malignant peripheral nerve sheath tumors (MPNST) are known to develop in patients with neurofibromatosis 1 (NF1), thus providing an excellent model for the study of multistep carcinogenesis in genetically predisposed individuals. To determine the sites of gene(s) involved in such a process, we have performed cytogenetic analysis on 10 tumors. The patients were five males and five females ranging in age from 15 to 77 years. Nine patients had NF1. Karyotypic analysis of these tumors exhibited complex clonal abnormalities of several chromosomes. Recurrent abnormalities (numerical as well as structural) of chromosomes 1, 11, 12, 14, 17, and 22 occurred in a substantial proportion of tumors studied. Although abnormalities of these chromosomes have been seen in a variety of other tumors, the aberrations of chromosomes 17 and 22 are of particular interest; chromosomes 17 and 22 carry the genes for NF1 and NF2, respectively. In addition to other clonal aberrations, six tumors had abnormalities of both chromosomes 17 and 22, while three tumors only had an abnormality of chromosome 17. In eight tumors a structural abnormality of chromosome 17 included deletion or a relative deficiency of 17p; in four of the tumors there was also either deletion or rearrangement of the NF1 locus at the cytogenetic level. One tumor had monosomy of chromosome 17. The abnormality of chromosome 22 was deletion of 22q11.2-->qter. This study suggests that the germline mutation in one of the copies accompanied by loss or inactivation of the second copy of the NF1 gene and tumor suppressor gene(s) on 17p and 22q may be associated with the neoplastic transformation; abnormalities of other chromosomes may be related to progression of MPNST. Although the role of the p53 gene in carcinogenesis is well documented in several tumor types, the role of the NF2 gene or other unidentified tumor suppressor gene(s) on chromosomes 22q, 1p, 11, 12, 14 remains to be seen.

Adolescent↗
PubMed1976

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.

Action Potentials↗
PubMed1992

The reaction of mesencephalic trigeminal neurons to peripheral nerve transection in the adult rat.

The effects of peripheral nerve transection on mesencephalic trigeminal (MeV) neurons have been studied qualitatively and quantitatively in the rat. In the qualitative part of the study the brain stem was studied in Fink-Heimer stained sections 3-30 days after a masseteric nerve transection. Degeneration argyrophilia was observed both in the MeV tract and in the supratrigeminal and trigeminal motor nuclei, as well as in the lateral part of the brain stem reticular formation. The first signs of transganglionic degeneration (TGD) were seen 7 days postoperatively, and the amount of degeneration increased considerably with longer survival times. A quantitative analysis of the MeV nucleus was made 60 days after transection of the left masseteric nerve. This analysis showed a 10.5-22.7% reduction of cells on the side that had undergone masseteric nerve transection. The mean difference (left vs right side) was -2.4% in animals that had not been operated on. These findings show that mesencephalic trigeminal neurons with proprioceptive functions are very sensitive to peripheral nerve injury with a substantial cell loss and TGD as the result.

Animals↗
PubMed2006

Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation (malignant triton tumor).

Malignant peripheral nerve sheath tumors arise from Schwann cells or within existing neurofibromas and have a strong association with type 1 neurofibromatosis. These tumors are histologically diverse and may contain malignant areas of divergent mesenchymal differentiation, the most common of which is skeletal muscle (rhabdomyosarcoma). Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation is also known as malignant triton tumor. Malignant triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does, and the correct diagnosis requires attention to the clinical history and knowledge of the complexities regarding its differential diagnosis. In this review we discuss the clinical, histopathological, immunohistochemical, and prognostic features of this rare neoplasm.

Biomarkers, Tumor↗