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The fan-wise split preparation method for quantitation of peripheral nerve injuries.

The applicability of the fan-wise split preparation method to the analysis of peripheral nerve injuries was explored in an experimental compression injury of the mouse sciatic nerve. The preservation of myelin sheaths was sufficient to enumerate the damaged myelinated fibers. Because of the simplicity and relative ease of the technique, this method could be a useful adjunct for the assessment of therapeutic modalities using experimental animals.

Animals↗

Spatiotemporal pattern of macrophage recruitment after chronic nerve compression injury.

The contribution of macrophages to the pathogenesis of chronic nerve compression (CNC) injuries is presently unclear. We examined the time course and spatial localization of macrophage invasion from 24 hours to 28 days post-CNC injury with immunohistochemistry (IHC) and electron microscopy (EM). To clarify the differences in macrophage activity between different peripheral nerve injuries, we compared CNC injury to a nerve crush (CR) injury at similar time points. Entire counts of macrophages with ED1-immunoreactivity (IR) showed a slow, gradual increase in macrophage number from 24 hours to 28 days post-operatively in compressed sections. ED1-IR was greatest at the site of compression and in distal nerve segments with minimal immunostaining in proximal and normal sections. Quantitative analysis of ED1-IR after crush injury demonstrated a rapid time course of macrophage recruitment with ED1-IR peaking at 48 hours and declining to normal values as early as 21 days post-CR injury. Ultrastructural analysis with EM 14 days post-CNC injury revealed greater macrophage localization in the inner one-third region of normal nerves relative to the outer region. Differences in macrophage localization within inner and outer regions of compressed sections were negligible, as macrophages were found diffusely throughout the endoneurium by day 14. Our findings suggest that macrophage recruitment is dependent upon proximity to neural vasculature with relative macrophage density highest specifically around endoneurial blood vessels in both normal and compressed sections. Taken together, our results detail the unique spatiotemporal dynamics of macrophage recruitment early after CNC injury as distinct from a crush injury.

Animals↗

Age-related differences in measures of upper extremity impairment.

BACKGROUND: Upper extremity cumulative trauma disorders (CTDs) are among the most prevalent and costly occupational injuries. These disorders include nerve compression syndromes, tenosynovitis, epicondylitis, tendinitis, and arthritis. These have been related in the past to repetitive use of the upper extremity. The expected increase in the age of the American work force and the assumption that older workers are more susceptible to the disorders prompted this investigation of the relationship of age to signs and symptoms of upper extremity impairment. METHODS: A battery measuring seven objective signs and four reported symptoms of upper extremity cumulative trauma disorders was administered to two stratified random samples of workers. One group (n = 157) processed cooked poultry and the second group (n = 118) performed data entry at VDT terminals. Workers were separated into three age groups (younger: 20-35 years, middle-aged: 36-50 years, and older: 51-71 years). RESULTS: A series of analyses of variance were computed to determine whether the older workers were more impaired. No significant age differences were found for sign, symptom, or total scores in either sample, and no significant Age x Gender interaction was present. Older workers were more impaired for vibratory sensation, cutaneous pressure, and motor latency. CONCLUSIONS: The results support the hiring of older workers for general tasks in the workplace without significant worry of increased susceptibility to CTDs.

Adolescent↗

Musculoskeletal ultrasound--a state of the art review in rheumatology. Part 2: Clinical indications for musculoskeletal ultrasound in rheumatology.

Rheumatologists remain divided on whether they should introduce musculoskeletal ultrasound (MSUS) into their clinical practice. A central issue in the application of MSUS in clinical rheumatology is the need for proof of clinical relevance and improved patient care. There is now accumulating evidence that MSUS improves clinical diagnosis and intervention skills. High-resolution ultrasound is superior to clinical examination in the diagnosis and localization of joint and bursal effusion and synovitis. MSUS is the imaging modality of choice for the diagnosis of tendon pathology. MSUS is seven times more sensitive than plain radiography in the detection of rheumatoid erosions, allowing earlier diagnosis of progressive rheumatoid arthritis. Ligament, muscle, peripheral nerve and cartilage pathology can also be readily demonstrated by MSUS. There is exciting evidence that MSUS may potentially be used by rheumatologists to non-invasively diagnose and monitor not just joint and muscle disease but also nerve compression syndromes, scleroderma, vasculitis and Sjögren's syndrome. Joint aspiration and injection accuracy can be improved by MSUS, with initial evidence confirming improved efficacy. As the number of rheumatologists performing MSUS increases and the technical capabilities of MSUS improve, there is likely to be a growing number of proven clinical indications for the application of MSUS in rheumatology practice. This paper reviews the evidence for the application of MSUS in rheumatology.

Bone and Bones↗

Management of Paget's disease of bone.

Paget's disease of bone is a common condition with a strong genetic component, characterized by focal increases in bone turnover, affecting one or more bones throughout the skeleton. Paget's disease can be asymptomatic but is frequently associated with bone pain, bone deformity, pathological fracture, secondary osteoarthritis and deafness. Inhibitors of osteoclastic bone resorption, such as bisphosphonates and calcitonin, suppress bone turnover and improve bone pain in Paget's disease. Many patients also require therapy with analgesics and anti-inflammatory agents, since pain in Paget's disease can arise not only from increased bone turnover but also from complications such as osteoarthritis and nerve compression syndromes, which do not respond well to antiresorptive therapy. Comparative studies have shown that second- and third-generation bisphosphonates, such as tiludronate, alendronate and risedronate, are more effective than etidronate at inhibiting bone turnover in Paget's disease but they have not been found to be significantly more effective in controlling bone pain. Importantly, none of the treatments that are currently available for Paget's disease have been shown to prevent complications such as deafness, fracture or bone deformity, or to alter the natural history of the disease. More research is required to define the long-term effects of antiresorptive treatment on clinical outcomes in Paget's disease, so that clinicians and their patients can make better-informed choices about the risks and benefits of treatment.

Biomarkers↗

Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement.

Bone metastases represents a common cause of morbidity in patients suffering many types of cancer: breast, lung, kidney, prostate, and multiple myeloma. Osteolytic metastases often cause severe pain, pathologic fractures, hypercalcemia, spinal cord compression, and other nerve-compression syndromes. Osteoclasts (OCs), cells deriving from granulocitic-macrophagic lineage, are responsible for osteolysis, which may be reduced by inhibiting both OCs formation and activity. By studying bone osteolytic metastases mechanism in solid tumors, we report here our findings that cancer patients with bone involvement display an increase in osteoclasts precursors, compared with both healthy controls and cancer patients without bone metastases. Peripheral blood mononuclear cells (PBMCs) from patients with osteolytic lesions show osteoclastogenesis without adding M-CSF, RANKL, or TNF-alpha. However, these factors are necessary to generate OCs from healthy donors, non-osteolytic patient PBMCs and T-cell depleted PBMCs. OCs derived from cancer patients show more resorption pits than OCs from healthy donors and express genes involved in osteoclastogenesis. Our data show that a spontaneous osteoclastogenesis occurs in patients affected by osteolytic lesions and may be supported by factors released by T lymphocytes. These factors could give a priming to osteoclast precursors and promote osteoclastogenesis. In fact, T-cell depleted PBMCs do not differentiate into OCs without adding M-CSF and RANKL. Moreover, we do not obtain a higher number of OCs by increasing RANKL doses in cultures, and OCs and T lymphocytes mRNA level are detected for TNF-alpha but not for RANKL. The addition of OPG to PBMCs cultures do not modify spontaneous osteoclastogenesis. A neutralizing anti-TNF-alpha antibody in unstimulated PBMC cultures of osteolytic cancer patients induces an inhibition of osteoclastogenesis. These data suggest that TNF-alpha may be responsible for osteoclastogenesis in these tumors.

Aged↗

C-terminal flanking peptide of neuropeptide Y in DRG following nerve compression.

The C-terminal flanking peptide of neuropeptide Y (CPON) was studied in dorsal root ganglia (DRG) by immunocytochemistry after different recovery periods (3, 6,14 and 28 days) following tourniquet compression of the rat hindlimb (sciatic nerve; 150 or 300 mmHg; 2 h). Compression induced a transient increase in the number of CPON-positive DRG-neurons (the contralateral uninjured side was devoid of CPON-positive cells). The compression-induced increase in CPON was less than that observed in separate rats subjected to sciatic nerve transection. The results show that compression induces regenerative changes in peripheral neurons and that such an injury of the nerve trunk is not limited to the site of the compression but results in the activation of the entire neuron.

Animals↗

Experimental nerve compression and upregulation of CPON in DRG.

Expression of C-terminal flanking peptide of neuropeptide Y (CPON) in DRG and cell proliferation (incorporation of BrdU) in sciatic nerve of rats following chronic nerve compression (silicone tubes with different internal diameters) was studied by immunocytochemistry. An increased number of CPON-positive neurons and cells incorporating BrdU was induced on the compressed side, most pronounced when a tight tube was used, while no cells expressed CPON or BrdU in intact nerves. The increase was transient and declined with time. Nerve compression induces transient cell proliferation in the nerve and expression of CPON in nerve cell bodies, but this is of a lesser magnitude than those following nerve transection.

Animals↗

Surgical treatment of the radial nerve lesions associated with fractures of the humerus.

Twelve patients who were surgically treated for radical nerve injuries associated with fractures of the humerus are reviewed. The average follow-up was 6 years (range 1-10). The mean time to full recovery was 19 months (range 12-40). Three fractures were open, and nine were closed. Seven of the fractures were located in the distal third of the humerus; two were in the middle third; two were segmental, involving both the middle and the distal thirds of the shaft; and one was supracondylar. All patients received initial treatment of the fracture in other medical units. The mean interval between the lesion and surgical treatment of the nerve injury was 6 months (range 25 days to 15 months). Perineural fibrosis at the lesion site was observed in four patients. Three nerves were found entrapped in the callus. In two cases the nerve was found to be partially divided, and in three cases a total section was observed. The techniques employed were microsurgical reconstruction with interfascicular grafting using sural nerve in six patients, neurolysis in five cases, and tendon transfers in one case. Excellent and good results were obtained in 91% of cases. In the case with a poor result, tendon transfers were made, with an acceptable functional result.

Adolescent↗

Surgical decompression without transposition for ulnar neuropathy: factors determining outcome.

Fifty-one surgical decompressions without nerve transposition for ulnar neuropathy were performed in 46 patients. All of the patients were men with an average age of 59 years at the time of surgery. The follow-up range was between 5 and 32 months (average, 17.8 months). The disease involved the nondominant arm in 24 patients (52%) and was bilateral in 5 (11%). In 23 cases (50%), no predisposing condition could be identified, whereas 15 patients (33%) abused alcohol and 8 patients (17%) had diabetes mellitus. Fifty-seven percent of the patients helped by surgery had symptoms for less than 1 year, whereas only 30% of patients with symptoms for more than 1 year had symptomatic improvement. The relative magnitude of the slowing of ulnar nerve conduction velocity across the elbow was not significantly correlated with the success of decompression in relieving symptoms. Ulnar nerve conduction velocities across the elbow were 36.13 +/- 11.76 m/s in those responding to surgery and 38.97 +/- 13.91 m/s in those not responding (c = 0.06, dF = 50, P less than 0.3). A total of 37 patients showed symptomatic improvement after decompression. Simple decompression of the ulnar nerve was performed under local anesthesia without transposition of the nerve. In all of these cases, compression of the nerve occurred predominantly in the epicondylar groove. Narrowing of the nerve in the groove was present in 28 cases (55%); scar tissue was found adhering to the nerve in 21 cases (41%); and two pseudoneuromas were found (4%). Forty-one operations (80%) resulted in symptomatic improvement, typically noted by the patient within the first month postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intraoperative mapping of the trigeminal nerve root: technique and application in the surgical management of facial pain.

A method for intraoperative topographic mapping of the trigeminal nerve root using electrophysiological methods is described. A series of 15 patients under general anesthesia during microvascular decompression and selective posterior fossa trigeminal rhizotomy was studied. This method was used to study the localization of fibers of individual subdivisions of the intradural portion of the trigeminal nerve and as a guide for performing physiologically controlled, selective, microsurgical trigeminal rhizotomy.

Action Potentials↗

Double crush syndrome.

Nerve entrapment conditions and peripheral neuropathies are sometimes related to injurious events, toxicosis, and repetitive microtrauma to soft tissue and nerve structures. An interesting theory concerning peripheral entrapment neuropathy has been discussed in the literature. This theory is called the double crush syndrome. This article briefly discusses the biologic/metabolic, structural, toxicogenic, and vasculopathic rationale for the pathogenesis of double crush syndrome.

Acute Disease↗

Pathoanatomy and pathophysiology of nerve root compression.

The anatomy and physiology of the nerve root complex in the lumbar spine are reviewed, with special reference to the effects of mechanical deformation of nerve roots in association with intervertebral disc herniation and spinal stenosis. Biomechanical aspects of nerve root deformation induced by compression are discussed. The functional changes induced by compression can be caused by mechanical nerve fiber deformation but also may be a consequence of changes in nerve root microcirculation, leading to ischemia and formation of intraneural edema. Nerve root compression can, by different neurophysiologic mechanisms, induce motor weakness and altered sensibility or pain. Intraneural edema and demyelination seem to be critical factors for the production of pain in association with nerve root compression.

Capillary Permeability↗

Morphologic and quantitative changes in neurotransmitters in the lumbar spinal cord after acute or chronic mechanical compression of the cauda equina.

Changes in the neurotransmitters associated with pain transmission and regulation in the lumbar spinal cord were studied after acute or chronic mechanical compression of the cauda equina in rats. Using glyoxylic acid histofluorescence and immunohistochemical methods, it was morphologically apparent that substance P-containing nerve ending were decreased after chronic compression of the cauda equina. Somatostatin nerve terminals were reduced, and aminergic fibers and serotonin were enhanced after both acute and chronic mechanical compressions. In addition, quantitative analysis revealed that the levels of norepinephrine and serotonin remained elevated after mechanical compression of the cauda equina. It is suggested that pain in the lower back and extremities after mechanical compression of the cauda equina is controlled by these complicated changes of neurotransmitters in the lumbar spinal cord.

Animals↗