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  • Peripheral neuropathy  (9)
  • Thalidomide  (3)
  • 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.
    Type of Medium: Electronic Resource
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  • 4
    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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  • 5
    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.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Thalidomide ; Wallerian degeneration ; Schwann cell proliferation ; Immune inhibition ; Endoneurial edema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In addition to the well-known teratogenic effect of thalidomide, previous studies have revealed mild immunosuppressive properties and, more recently, and antiangiogenic activity. To find out more about the specificity of these effects we studied the influence of orally administered thalidomide on Wallerian degeneration in rats. Wallerian degeneration is a potent experimental model for studying reproducible cell proliferation in vivo. Examination of distal nerve segments of transected sciatic nerves from rats that had been treated with thalidomide (2×250 mg/kg per day) revealed a significant reduction of endoneurial cell counts at 10–15 days after surgery compared to that seen in controls. This effect was not statistically significant, at a very early stage of Wallerian degeneration, i.e., at 5 days after transection of the nerve. Subperineurial edema and phagocytosis was also reduced, although this was not statistically significant. This apparently nonspecific inhibitory effect of thalidomide during early Wallerian degeneration shown in the present study should be investigated further for its possible relationship to other previously established inhibitory activities of thalidomide, especially its immunosuppressive effect in man.
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  • 7
    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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  • 8
    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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  • 9
    ISSN: 1432-0533
    Keywords: Unmyelinated axons ; Sensory neuropathy ; Thalidomide ; Aging ; Senile peripheral nerves
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sural nerve biopsies of four patients, aged 54–76 years, with a predominantly sensory type of neuropathy following high dosages of thalidomide were examined by light and electron microscopy. The present study includes a qualitative and quantitative evaluation of unmyelinated nerve fibers. Despite severe neuropathy, increased numbers of small unmyelinated axons per endoncurial area were noted in all patients. This numerical increase appeared to be independent of aging, since it was not seen in two senile controls, studied at the age of 83 and 88 years. The increase in the endoneurial density of unmyelinated axons, especially of small sized fibers, is likely to be related to regeneration following degeneration of unmyelinated axons although endoneurial shrinkage secondary to loss of large myelinated fibers could have caused an additional increase in the number of axons per endoneurial area. Axonal sprouting, despite degeneration of large numbers of myelinated and unmyelinated fibers, appears to be consistent with some of the characteristic clinical features of thalidomide neuropathy such as paresthesias, hyperesthesia for pain and temperature, and disturbances of autonomic functions. On the other hand, a variable number of empty Schwann cells (bands of Büngner) and pockets at the surface of many Schwann cells noted in the four patients with neuropathy were also seen in both senile controls with no signs of neuropathy. Thus, it is obvious that pockets and empty Schwann cells may be related to aging or other causes of slow axonal wasting with Schwann cell proliferation and are not necessarily associated with clinically manifest neuropathy.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 65 (1985), S. 285-292 
    ISSN: 1432-0533
    Keywords: Thalidomide ; Neuropathy ; Conduction velocity ; Myelin sheath
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphological studies of experimental thalidomide neuropathy have thus far failed to show any significant structural changes. The present investigation was performed on sural nerves of female New Zealand white rabbits showing a reduction of sensory conduction velocity after oral treatment with thalidomide (100 mg/kg b.wt. per day) for a period of 33 weeks. Rabbits of the same strain and equal sex, weight, and number served as controls. Very few nerve fibers were undergoing Wallerian degeneration in both groups, experimental animals and controls. Morphometry, however, revealed a statistically significant reduction of the mean myelin thickness of sural nerve fibers in the thalidomide group of rabbits as compared to controls. The mean myelin thickness of the largest nerve fibers was also significantly smaller than in the control group. On the other hand, axonal diameters were not significantly altered. The association between the decrease of the sensory conduction velocity, the reduction of the myelin sheath thickness, and the chronic thalidomide application is discussed.
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