多发性硬化周围神经损伤的病理与临床分析

目的：报道12例多发性硬化（MS）患者周围神经病理检查的异常改变，从中证实MS患者存在周围神经的节段性脱髓鞘病损。方法：12例经肌电图检查发现存在周围神经异常改变的患者行腓肠神经活检及病理学观察。结果：11例标本形态上以脱髓鞘为主，8例可见有髓纤维减少，电镜下显示髓鞘失，有髓纤维再生，形成空泡；神经膜细胞增殖生形成葱头改变；7例可见髓鞘板层松解现象，结论：MS患者不但出现CNS的脱髓鞘病理，而且部分患者同时存在周围神经系统的脱髓鞘病损。     

Quantitative, histological and ultrastructural studies of peripheral nerve in arteriosclerotic non-diabetic patients

The superficial peroneal nerve was taken from 12 arteriosclerotic non-diabetic patients just after amputation of a leg. Preparations of teased fibers were performed in 8 cases. Specimens were studied by light and electron microscopy in all cases. Histograms of myelinated fibers in transverse semi-thin sections showed that depletion of myelinated fibers varied from case to case, with no selective vulnerability in either the large or the small diameter group. There was a dramatic loss of myelinated fibers in only one case. No real nerve infarct was observed. In most cases, regions of Wallerian-like degeneration were prevalent; however, myelino-axonal changes were severe only in a few cases. Axons with organelle aggregates were seen in some cases. Figures of segmental demyelination were not numerous in this series. Unmyelinated fibers were also damaged, and the degree of involvement differed from case to case. Pathological changes observed in this study confirm the relative resistance of peripheral nerve to ischemia.     

Guillain-Barré syndrome: an ultrastructural study of peripheral nerve in 65 patients

65 biopsies of peripheral nerve from patients suffering from Guillain-Barré syndrome were studied by electron microscopy. In 48 cases there was macrophagic invasion of the Schwann cells of certain myelinated fibers, and in 32 of these cases some myelin sheaths were stripped away by an elongated macrophagic process. Vesicular disruption of the myelin sheath was observed in only 8 cases and in less than 1% of the myelinated fibers. Uncompacted myelin lamellae were observed in a few myelinated fibers. These ultrastructural lesions are analysed and commented on with a view to selecting patients who are to undergo plasma exchange.     

Quantitative histologic study of the sural nerve in Lesch-Nyhan syndrome

The sural nerve of a 31-year-old man with Lesch-Nyhan syndrome obtained at autopsy was studied histologically. Large, myelinated nerve fibers were reduced in number and no myelinated nerve fibers larger than 5 microns were seen. Diameter distribution of myelinated nerve fibers did not demonstrate a bimodal pattern. The density of myelinated nerve fibers was 5,530/mm2 and was decreased as compared to the controls. On electron microscopic examination, lipid-like inclusions were observed in the cytoplasm of some Schwann cells. The role of these inclusions could not be elucidated, but reduction of larger myelinated nerve fibers suggests a peripheral nervous disorder in patients with this syndrome; therefore, patients with Lesch-Nyhan syndrome must be reappraised for disorders of the peripheral nervous system.     

Abnormalities of peripheral nerve in patients with human immunodeficiency virus infection

The purpose of this study was to assess systematically morphology of peripheral nerves from patients with human immunodeficiency virus infection (acquired immunodeficiency syndrome [AIDS] and AIDS-related complex) examined at autopsy. Sural nerve specimens were taken from 25 patients (mean age 44 years) and evaluated by routine procedures used in our laboratory. In 13 cases no detectable abnormality was seen. Twelve patients (48%) showed loss of myelinated fibers with disproportionately greater loss of large myelinated fibers. Three of these patients showed severe myelinated fiber loss; 2 had no documented symptoms and no other known predisposing factors for a peripheral neuropathy. Changes suggestive of wallerian degeneration were occasionally seen, as were epineurial and endoneurial inflammatory infiltrates. Segmental demyelination was not identified in any nerve examined. Electron microscopy revealed thickened basement membranes around small blood vessels, Schwann cells, and fibroblasts. Peripheral nerve abnormalities in patients with AIDS or ARC are frequent and their pathogenesis remains unclear.     

Evaluation of dermal myelinated nerve fibers in diabetes mellitus

Skin biopsies have primarily been used to study the non‐myelinated nerve fibers of the epidermis in a variety of neuropathies. In this study, we have expanded the skin biopsy technique to glabrous, non‐hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n = 9; Type II, n = 11) and 16 age‐matched healthy controls (age 29–73) underwent skin biopsy of the index finger, nerve conduction studies (NCS), and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MCs) and their afferent myelinated nerve fibers (p = 0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in NCS. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN.     

Peripheral nerves injury of electrophysiology and pathology in MS

OBJECTIVE We report the EMG and pathological features of sural nerve biopsy of 12 patients with MS. The pathological of thesel 1 patients demonstrated demyelination injury of peripheral nerves.METHODS Twelve cases abnomaly are screened with EMG from60 cases MS. Sural nerve biopsy were analyzed by HE AND loyez, and electron microscopy. RESULTS EMG showed slow of MCV in 9 patients and SCV in 7 patients. Myelinated fibers was the presence in 8 sural nerve biopsy patients and most striking demyelinating fibers, regeneration of myelinated fibers. CONCLUSION Ms is characterized by demyelinating disorder limited to the CNS.There are,howeve ,the results of this study sugee that combine with PNS demyelinating injury in MS may be more frequent than is generally assumed.     

A clinicopathologic study of acrodystrophic neuropathies

Sixteen patients presenting with trophic changes associated with a peripheral neuropathy were investigated. Muscle power was normal in all patients, but neurogenic muscle atrophy was demonstrated in 4 of the 7 patients who had a muscle biopsy. Alcoholism was responsible for the neuropathy in 11 patients. In the other patients, one had primary hemochromatosis without diabetes and another a dominantly inherited primary hypertrophic neuropathy. Qualitative and quantitative light and electron microscopic studies, including teased nerve fiber preparations, showed axonal loss as the most salient feature. In the alcoholic patients, the large myelinated fibers were primarily involved, followed by small myelinated and unmyelinated fibers. The lesions were predominant distally as shown in patients who had a sural nerve biopsy at both calf and ankle levels. A mechanism of dying-back degeneration of the longest sensory fibers is the most plausible explanation for neurological and pathological abnormalities. In alcoholic neuropathy with trophic changes, loss of sensory fibers is more important than in alcoholic neuropathy without trophic changes. In familial and sporadic cases, axonal loss is more severe and unmyelinated fibers are more severely affected than in alcoholic acrodystrophic neuropathy. Patients with peripheral neuropathies who present with loss of pain sensation but have preserved muscle power are especially exposed to the development of trophic changes induced by usual trauma in insensitive tissues.     

Xeroderma pigmentosum: neurological, neurophysiological and morphological studies

In 3 cases of xeroderma pigmentosum showing signs of peripheral neuropathy, electrophysiological studies were made. In one of them, a sural nerve biopsy was performed. MCV obtained from the lower limbs were moderately reduced in all cases, and SCV could be obtained in only 1 case from the median nerve. Auditory brain stem responses were not obtainable in all cases. Sural nerve biopsy revealed a marked decrease of myelinated fibers and also suggested severe damage in both myelinated and unmyelinated fibers. Teased fiber study showed myelin ovoids and indicated axonal degeneration. Sensory nerves including the acoustic nerve may suffer damage earlier than the motor nerve. In all cases CT scans revealed brain atrophy and thickening of the skull.     

Peripheral neuropathy in two children with mitochondrial encephalomyopathy]

Peripheral neuropathy (PN) associated with mitochondrial encephalomyopathy (MEM) has been reported in adult patients, while children with both conditions are rare. Electrophysiological and pathological studies disclosed evidence of PN in a 3-year-old girl and an 8-year-old boy with MEM. In both patients, peripheral nerve conduction velocities were reduced, while amplitudes of evoked potentials were normal. No ragged red fibers were found in the biopsy muscle, while most of the muscle fibers showed poor activity with histochemical staining for cytochrome c oxidase (CCO). Biochemical studies revealed deficiency of CCO in both cases. In the latter patient, CCO activity was also absent in the intramuscular peripheral nerve using CCO staining, and histopathological studies of the sural nerve revealed a marked decrease in the number of large myelinated fibers and an unusual accumulation of the mitochondria in the Schwann cell cytoplasm. These results may support the hypothesis that a common pathogenesis exists in both peripheral nerve and muscle due to mitochondrial dysfunction.     

Spatial distribution of nerve fiber pathology and vasculitis in microscopic polyangiitis-associated neuropathy

We analyzed the 3-dimensional distribution of pathologic findings in 8 autopsied cases of neuropathy associated with microscopic polyangiitis. Necrotizing vasculitis was commonly and diffusely present in the epineurium of the sciatic/tibial and median nerves. Although findings of vasculitis were distributed diffusely in proximal to distal segments of the nerve trunks, marked loss of myelinated fibers occurred only from the middle to distal segments of these nerves. Neurons of the sensory and sympathetic ganglia were well preserved, as were myelinated fibers of the anterior and posterior spinal roots. Central fascicular nerve fiber degeneration, suggesting direct ischemic damage, occurred in restricted segments of the proximal-middle portion of the sciatic/tibial and median nerve trunks. Vasculitis was also seen in various visceral organs in all patients, but its distribution differed among individual patients; the severity of vasculitis in the other organs did not correlate with that in the peripheral nerves. The distinct spatial distribution pattern of nerve fiber degeneration, in contrast to the ubiquitous presence of vasculitis, suggested that the ischemic zone that directly damages nerve fibers is present in the proximal-middle portion of peripheral nerve trunks in microscopic polyangiitis.     

The neuropathy of Charlevoix-Saguenay ataxia: an electrophysiological and pathological study.

Two female patients aged 30 and 40 years with the Charlevoix-Saguenay ataxia were studied. Both had absent sensory action potentials in upper and lower extremities but, unlike typical cases of Friedreich's ataxia, they displayed a marked slowing of motor conduction velocities. Sural nerve biopsies taken from calf and ankle revealed a severe loss of large myelinated axons contrasting with a normal myelinated fiber density. Evidence for active axonal degeneration was scarce, with no indication of axonal regeneration. Teased myelinated fibers revealed an increased variability of internodal length but no evidence for myelin breakdown. These findings support, as a primary defect, a developmental abnormality of peripheral nerve, namely a lack of maturation of large myelinated axons and possibly a faulty myelination of nerve fibers. We think it is unlikely to represent a progressive axonal atrophic or dystrophic process, as suggested in Friedreich's ataxia.     

Alcoholic neuropathy: Clinical,electrophysiological, and biopsy findings

Nerve conduction and biopsy findings from the sural nerve in 37 patients with alcohokic neuropathy were compared with findings in 6 patients who had neuropathy associated with postgastrectomy malnutrition. Half the patients with alcoholic neuropathy had both muscle weakness and sensory loss, half had only sensory impairment, but all had electromyographic signs of denervation. Only half the patients, with or without muscle weakness, had signs of malnutrition. In alcoholics, sural nerve conduction velocity was slowed to at most 60% of normal, correlating with loss of large fibers. These findings, together with a marked reduction in amplitude of the sensory potentials, are consistent with axonal loss. Myelinated fiber counts showed loss of small and large fibers in most nerves, retaining a bimodal distribution. Signs of regeneration were rare. Segmental demyelination was found in only 0.3% of teased fibers. Electron microscopy confirmed axonal degeneration of myelinated and unmyelinated fibers. Neuropathy after gastrectomy malnutrition was clinically similar to alcoholic neuropathy. Conduction velocities were slower than expected from the diameter of the largest myelinated fibers, however, and teased fibers showed segmental demyelination. The findings are against alcoholic neuropathy being due to malnutrition and suggest a toxic action on peripheral nerve.     

Morphometry of the degenerative process in the hypoglossal nerves in amyotrophic lateral sclerosis

Summary The peripheral hypoglossal nerves in 13 cases of amyotrophic lateral sclerosis (ALS) and five control cases were examined using morphometrical methods to demonstrate the degenerative process of motor nerve degeneration. The total number of myelinated fibers and their histograms were analyzed according to the degree of severity of the degeneration. Reduction of the total number of myelinated fibers in ALS hypoglossal nerves were graded in three groups: mild 65%–75%, moderate 50%–65% and severe 30%–50% of the myelinated fibers in controls. Each histogram of the remaining myelinated fibers showed different patterns corresponding to the degree of the degeneration and disclosed that the progressive reduction of large myelinated fibers was the fundamental change. Small myelinated fibers were not reduced, but increased, especially in the group with a moderate grade of degeneration. In plastic section, there were clusters of regenerated myelinated fibers. The transient increase of small myelinated fibers may be a reflexion of myelinated fiber regeneration during the progressive degenerative process of the motor neurons. The correlation between the degree of severity of the hypoglossal nerve degeneration and the atrophy of the tongue muscle and the duration of bulbar symptoms was examined and discussed.Supported by grant from the Ministry of Health and Welfare of Japan (Research project of progressive degenerative neurological disease)     

Epidemic neuropathy in Cuba: Morphological characterization of peripheral nerve lesions in sural nerve biopsies

More than 50 000 patients were affected in Cuba during an epidemic outbreak of peripheral neuropathy from January 1992 until September 1993. The disease presented as either a retrobulbar optic neuropathy, a predominantly sensory peripheral neuropathy, a dorsolateral myeloneuropathy, or as mixed forms. The morphological findings in sural nerve biopsies from 34 patients with various forms of the disease are presented here. Frozen, paraffin and semi-thin sections were prepared for light and electron microscopy, immunohistochemistry and morphometric analysis. Every case presented morphological alterations ranging from mild axonal dystrophy (9 cases, or 27%) to moderate and severe axonal damage (25 cases, or 73%). In 6 cases (18%), axonal damage was accompanied by perineural fibrosis and vascular abnormalities. Axonal regeneration was noted in 8 cases (23%) and remyelination in 9 (26%). Morphometric analysis showed a predominant loss of myelinated fibers in 92% of the patients. Quantification of myelinated fiber loss in 11 patients revealed a remarkable decrease in large caliber fibers. Scarce mononuclear cells were observed in 17 cases. No virus-like elements were seen. The morphological features found in this study indicate that, regardless of the clinical presentation, peripheral nerve lesions of the epidemic neuropathy in Cuba correspond to an axonal neuropathy. These lesions are compatible with nutritional, toxic, or metabolic etiologies. An inflammatory etiology would be unusual with these lesions.     

Neuropathy caused by cisplatin. Clinical, electrophysiological and morphological study

Seven patients with cancer presented a sensory peripheral neuropathy induced by cisplatinum. This drug was used alone in 1 case and, in 6 other cases it was associated with drugs without any toxicity for the peripheral nervous system. Every patient had an electromyogram and motor and sensory nerve conduction studies. A sural nerve biopsy was performed in 5 cases for light and electron microscopic studies as well as for teasing and quantitative studies. Electromyograms and motor nerve conductions were normal. Sensory nerve conductions were slowed with very low amplitude sensory action potentials. Such results suggested axonal changes. Nerve biopsies showed typical axonopathic changes with secondary demyelination. Morphometric studies confirmed a loss of myelinated fibers affecting the large fibers in all cases, according to the slowed sensory nerve conductions. This study confirmed that the cisplatinum-induced neuropathy is a new form of toxic distal axonal neuropathy. The hypothesis of a primary demyelination of peripheral nerves, which has been proposed, could not be retained.     

Congenital insensitivity to pain with anhydrosis. Report of two unrelated cases

Two unrelated female cases of congenital insensitivity to pain with anhydrosis are presented. The first case was born from consanguineous parents. In both cases, onset of manifestation was observed in infancy with automutilation and recurrent fever. Both were mentally retarded. They underwent a peripheral nerve biopsy respectively at 3 and 33 years. A dramatic loss of unmyelinated fibers was observed in both cases. Myelinated fibers were also moderately reduced in number, especially those of smallest diameter; this loss was more marked in the second patient who was adult when the peripheral nerve was studied. Clusters of regenerating myelinated fibers were seen in both cases. Such histological observations might suggest a slowly progressive disorder. The cases are discussed together with previous reports dealing with congenital insensitivity to pain.     

Peripheral nerve morphometry in stroke patients

Sural nerve biopsy specimens from affected and non-affected limbs of stroke patients were examined morphometrically. Two principle abnormalities of peripheral nerve were found in hemiparetic and hemiplegic limbs. First, the frequency of abnormal teased nerve fibers was significantly increased with abnormal internodes frequently "clustered" and showing a 50% or more reduction in myelin thickness. Second, the mean diameter of myelinated nerve fibers was reduced. These results suggest a primary atrophy of peripheral nerve fibers in the affected limbs of stroke patients with secondary demyelination. Possible aetiological factors include disuse, transynaptic degeneration, ischemia, pressure effect, and decreased axoplasmic flow. It would seem that the structural integrity of peripheral nerve is frequently compromised following a cerebral lesion.     

Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies

OBJECTIVE: To study intraepidermal nerve fiber (IENF) density in distal leg skin biopsies, sural nerve morphometry, electrophysiology, and clinical features in patients with peripheral neuropathies. METHODS: We studied 26 patients with neuropathic complaints who had undergone clinical evaluation, nerve conduction studies, distal leg skin biopsy, and sural nerve biopsy. We quantified densities of IENF and of myelinated and unmyelinated fibers in the sural nerve. Associations among skin and sural nerve morphometric measures and sensory nerve action potential (SNAP) amplitudes were examined nonparametrically. Morphometric measures were examined with respect to diagnostic category of neuropathy. RESULTS: IENF density correlated with the densities of sural nerve total myelinated (r = 0.57, p = 0.0011), small myelinated (r = 0.53, p = 0.0029), and large myelinated fibers (r = 0.49, p = 0.0054). There was a trend toward an association between IENF and sural nerve unmyelinated fiber densities (r = 0.32, p = 0.054). Sural SNAP amplitude and large myelinated fiber densities were highly correlated (r = 0.87, p < 0.0001). IENF density and sural nerve small fiber measures were concordant in 73% of patients. Reduced IENF density was the only indicator of small fiber depletion in 23% of cases. It was usually normal in acquired demyelinating neuropathies and where clinical suspicion for neuropathy was low. CONCLUSIONS: Distal leg Intraepidermal nerve (IENF) density may be more sensitive than sural nerve biopsy in identifying small fiber sensory neuropathies. Assessments of IENF density and large fiber measures on biopsy and electrophysiology are both useful for characterizing sensory and sensorimotor neuropathies.     

Anti-MAG IgM penetration into myelinated fibers correlates with the extent of myelin widening.

The purpose of this study was to evaluate the relationship between immunoglobulin M (IgM) antibodies penetration into myelinated peripheral nerve fibers and the widening of the peripheral myelin sheaths in anti-myelin-associated glycoprotein (anti-MAG) demyelinating IgM monoclonal polyneuropathy. Demyelinating polyneuropathy with monoclonal IgM is often associated with anti-MAG autoantibodies, which are thought to initiate the disease with IgM deposits usually present on the myelin sheaths. We analyzed nerve biopsies from 12 patients with an anti-MAG demyelinating neuropathy by confocal and electron microscopy. The total number of nerve fibers and the proportion of IgM-associated fibers were quantified after immunohistochemical staining. The affinities of IgM were examined by analyzing the binding pattern of serum IgM on normal peripheral nerve sections. Ultrastructural examinations of the biopsies showed a good correlation between in situ widened myelin sheaths and the IgM penetration level into myelinated fibers. The terminal complement complex appears not be involved in the penetration of IgM into the myelinated fibers. Our findings suggest a causative role of the IgM anti-MAG antibodies in the ultrastructural modifications of the myelin sheaths. The basement membrane and myelin components appear to be the major targets of the IgM monoclonal antibodies. However, the pathogenic mechanism whereby IgM antibodies reach their targets and induce nerve damage are still unclear.