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  • Peripheral neuropathy  (9)
  • Mitochondria  (5)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 432 (1998), S. 199-205 
    ISSN: 1432-2307
    Keywords: Key words Nerve biopsy ; Sural nerve ; Peripheral neuropathy ; Skin biopsy ; Fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Peripheral nerve biopsy is now an established, valuable investigative procedure, but as it can give rise to significant residual symptoms it should only be undertaken after careful consideration of the indications and with informed consent from the patient. Nerve biopsies should only be processed and evaluated in a laboratory with the relevant particular expertise. It is generally recommended that a sural nerve biopsy be performed in combination with a muscle biopsy but not vice versa (muscle biopsies together with a nerve biopsy). Nerve biopsy is not the only means of sampling peripheral nerve tissue to study the peripheral nervous system. Examination of the innervation of the skin may be informative. The same is likely to be true for motor point muscle biopsy. Nerve biopsy is mainly used for morphology although molecular genetic techniques using fresh or archival nerve biopsies are increasingly available. Chemical analysis is undertaken mainly for research purposes.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 83 (1992), S. 120-133 
    ISSN: 1432-0533
    Keywords: Sural nerve ; Schmidt-Lanterman incisures ; Myelinated nerve fibers ; Peripheral neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fine structural alterations of Schmidt-Lanterman incisures (SLI) were investigated in a series of 242 unselected sural nerve biopsies that had been examined for diagnostic purposes. The series included cases with Friedreich's ataxia, HSAN I, HMSN I-III, HMSN VI, tomaculous neuropathy, metachromatic leukodystrophy, ceroidlipofuscinosis, dysproteinemic neuropathies, and myotonic dystrophy, in addition to several neuropathies less-specifically classified as either of a predominantly demyelinating, axonal, or neuronal type. The following classification of SLI alterations is proposed: (A) abnormal inclusions: (B) changes in shape and dimension; and (C) modes of disintegration. Abnormal inclusions comprised membranous whorls, uniform and pleomorphous lysosome-like bodies, and accumulation of granular substances at the site of the major dense line, or granular deposits at the site of the intraperiod line of the myelin sheath. Variations of incisural shape and dimension included folding, dilatation, and pocket formation (compartmentalization). Disintegration at incisures comprised a fine, vesicular and a gross, vacuolar type. Various combinations of these changes were observed. The most frequent change consisted of membranous whorls, detected in SLI of 89 biopsies. They were most prominent in chloroquine neuropathy where they occurred in SLI as well as in the adaxonal and abaxonal cytoplasm of Schwann cells. Compartmentalization of the myelin sheath at incisures associated with formation of myelin loops was a frequent feature in myotonic dystrophy. It is concluded, that changes of incisural ultrastructure are sensitive indicators of human neuropathies offering clues to the type of the underlying pathomechanism.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 81 (1991), S. 680-685 
    ISSN: 1432-0533
    Keywords: Endoneurial fibroblasts ; Peripheral neuropathy ; Connective tissue disease ; Vasculitis ; Cell necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 42 human sural nerve biopsies degeneration of endoneurial cells was evaluated semiquantitatively at the electronmicroscopic level. These cells were of non-Schwannian origin since they were not surrounded by a basement membrane. Most of the degenerating cells resembled endoneurial fibroblasts: their remaining cytoplasmic processes were quite extensive, not finger-like as in macrophages, and their cytoplasm did not contain conspicuous lysosomes or phagolysosomes that would identify them as degenerating macrophages. Criteria for regarding these cells as degenerating were defects of the cytoplasmic surface membrane with extracellularly situated organelles. The ratio between normal and degenerating endoneurial cells in five different groups of peripheral neuropathies was compared to a group of normal controls. No degenerating endoncurial cells were found in the latter. The largest proportion of degenerating endoneurial cells was noted in patients with panarteritis nodosa (30% of the endoneurial cells evaluated). Between 9% and 18% of the evaluated endoneurial cells were seen degenerating in hereditary motor and sensory neuropathies, in neuropathies associated with IgG or IgM gammopathy, and in chronic demyelinating inflammatory polyradiculoneuropathy. These findings suggest that degeneration of endoneurial cells is a nonspecific sign of peripheral neuropathy occurring in various types of neuropathy, although vasculitis represents the most frequent cause. Thus, degeneration of endoneurial cells can be added to the growing list of changes that possibly indicate an inflammatory disorder, even during the intervening stage when apparent inflammatory cell infiltrates are lacking.
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  • 4
    ISSN: 1432-0533
    Keywords: Key words Zidovudine ; Myopathy ; Nucleus ; Mitochondria ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term zidovudine (also termed azidothymidine, AZT) treatment of AIDS patients may cause severe myopathy characterized by conspicuous mitochondrial and nuclear changes. The mitochondrial changes are attributed to an inhibitory effect of AZT on the mitochondrial γ-polymerase in a variety of cells. Inhibition of the nuclear α-polymerase is another well-known side effect of AZT, whereas the (nuclear) β-polymerase appears to be rather insensitive. The nuclear changes seen in AIDS patients are usually considered secondary to the human immunodeficiency virus infection. To eliminate the influence of the virus on the nuclei, we studied the effect of AZT on non-infected, organotypic co-cultures of spinal ganglia, spinal cord, and skeletal muscle from fetal rats. We noted significant changes not only in the mitochondria but also in the nuclei of spinal ganglia, spinal cord, and muscle cells, which depended more on the duration of AZT application (1, 3, 5, and 8 days) than on the concentration (0.1, 1, 10, 100 and 1000 μM). The alterations of the mitochondria consisted mainly of swelling, loss of cristae and, finally, disappearance. The nuclei showed nucleolar segregation, marginal condensation of heterochromatin, formation of interchromatin and perichromatin granules, nuclear protrusions and pseudoinclusions and, finally, disintegration. The changes were not as pleomorphic as those seen in biopsy specimens from AIDS patients who had received long-term treatment with AZT. However, this difference can easily be attributed to the short duration of drug application in tissue culture compared to the long-term medication in patients.
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  • 5
    ISSN: 1432-0533
    Keywords: Mitochondrial myopathies ; Peripheral neuropathy ; Hereditary motor and sensory neuropathy ; Schwann cells ; Arterioles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fifteen cases of mitochondrial myopathy, three cases of hereditary motor and sensory neuropathy (HMSN) VI, and 280 cases of neuropathies of different etiologies were examined by electron microscopy for the presence of mitochondrial abnormalities in the sural nerve. Altered mitochondria were found in most cases of mitochondrial myopathy, in all cases of HMSN VI, and in 25 cases out of the series of unselected neuropathies. The mitochondrial changes comprised enlargement with an amorphous matrix and distorted cristae, with hexagonal paracrystalline inclusions, and with prominent cristae containing oblique striations, and a variety of rare changes. Most mitochondrial abnormalities were found in Schwann cells. An increase of the number of mitochondria was noted in smooth muscle and endothelial cells of epineurial arterioles of two cases with mitochondrial encephalomyopathy. Neuropathy was present in all cases of mitochondrial myopathy according to morphometrical analysis. Whether neuropathy is caused directly by mitochondrial dysfunction or by other pathogenetic mechanisms remains to be determined.
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  • 6
    ISSN: 1432-0533
    Keywords: Zidovudine ; Myopathy ; Nucleus ; Mitochondria ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Zidovudine (formerly azidothymidine) is a potent inhibitor of the human immunodeficiency virus (HIV) reverse transcriptase and represents the first approved drug showing clinical efficacy in HIV-associated diseases. However, considerable toxicity causing macrocytic anemia, neutropenia, and myopathy has been reported, with severe mitochondrial alterations as a special feature of this myopathy. The mitochondrial changes are consistent with the fact that zidovudine acts as an inhibitor of the mitochondrial gamma-polymerase. Electron microscopically, we could confirm the presence of severely altered mitochondria in a 32-year-old male, who developed a necrotizing myopathy after daily administration of 1,000 mg zidovudine over a period of 15 months. In addition, there were even more severe nuclear changes that, for the most part, have not been documented electron microscopically in HIV-related myopathy either with or without zidovudine treatment, especially in non-necrotic and non-regenerating fibers. Since various in vitro studies have shown interference of zidovudine with nuclear DNA metabolism even in human cell lines, we assume that the nuclear changes that we observed are at least in part related to zidovudine treatment.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Key words Cerebral autosomal dominant arteriopathy ; Immunoglobulin deposits ; Peripheral neuropathy ; Sural ; nerve biopsy ; Small vessel disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy' (CADASIL) has recently been identified as a hereditary disorder with characteristic fine structural changes of small intracerebral arteries and arterioles. Electron microscopically there are characteristic perivascular deposits of granular electron-dense material resembling immunoglobulin deposits. The present case from a family with four affected members in three successive generations shows that similar vascular changes as described in the central nervous system are present in blood vessels of the sural nerve, although less pronounced and, therefore, affording electron microscopy for their unequivocal detection. Nevertheless it has been shown for the first time that the diagnosis of CADASIL can be verified by a sural nerve biopsy. Occasional focal accumulation of pinocytotic vesicles opposite the granular deposits suggests exocytosis as one of the possible pathomechanisms for their production.
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  • 8
    ISSN: 1432-0533
    Keywords: Cerebral autosomal dominant arteriopathy Immunoglobulin deposits ; Peripheral neuropathy ; Sural nerve biopsy ; Small vessel disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy' (CADASIL) has recently been identified as a hereditary disorder with characteristic fine structural changes of small intracerebral arteries and arterioles. Electron microscopically there are characteristic perivascular deposits of granular electron-dense material resembling immunoglobulin deposits. The present case from a family with four affected members in three successive generations shows that similar vascular changes as described in the central nervous system are present in blood vessels of the sural nerve, although less pronounced and, therefore, affording electron microscopy for their unequivocal detection. Nevertheless it has been shown for the first time that the diagnosis of CADASIL can be verified by a sural nerve biopsy. Occasional focal accumulation of pinocytotic vesicles opposite the granular deposits suggests exocytosis as one of the possible pathomechanisms for their production.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 72 (1986), S. 29-37 
    ISSN: 1432-0533
    Keywords: Peripheral neuropathy ; Angiopathic neuropathy ; Vasculitis ; Smooth muscle cells ; Blood vessels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Proliferation of epineurial capillaries and smooth muscle cells in human sural nerves has been documented. These are basically independant changes, although both can occur in the same nerve. Proliferated epineurial capillaries were seen in association with arterial stenosis or occlusion with or without granulating or granulomatous inflammatory reactions. Although non-specific they appear to be of considerable diagnostic value indicating compensatory hypervascularisation subsequent to peripheral focal ischemia. Separation and numerical increase of epineurial smooth muscle cells, on the other hand, was also recognised as a significant though non-specific alteration occurring in various inflammatory, immunogenetic, or other, non-inflammatory angiopathies. The youngest (1.3 years) and the oldest individual (104 years) studied, as well as many other documented and non-documented cases, did not show this type of change. Smooth muscle cells may survive isolated or focally separated from adjacent vessel walls in the epineurium.
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  • 10
    ISSN: 1432-0533
    Keywords: Muscle spindle ; Denervation ; Reinnervation ; Muscle fiber atrophy ; Mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fine structure of normal, denervated, and reinnervated muscle spindles in lower lumbrical muscles of rats was studied morphometrically at time intervals ranging from 3–14 months. In control spindles, the mean transverse area of mitochondria was estimated to be more than twice as large in nuclear chain than in typical nuclear bag fibers. Following denervation, there was a severe decrease of the mean number and transverse area of mitochondria, and a moderate, but statistically significant decrease of the mean transverse area of intrafusal muscle fibers (IMFs) despite an increase of the number of IMFs. At 12–14 months of reinnervation, changes of the transverse areas of IMFs were statistically insignificant, but the mean values for the mitochondria were incompletely restored. At 4×3 months, after fourfold repeated crush injuries to the nerve, most of the values estimated (transverse area of mitochondria; number, shape, and transverse area of IMFs and nuclei) tended to approach those in denervated rather than in reinnervated IMFs. The differences of the reactions of intra- and extrafusal muscle fibers following complete motor and sensory denervation appeared to be in accordance with their normal dimensional dissimilarities.
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