Positive neuropathic sensory symptoms as endpoints in diabetic neuropathy trials.
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Clinical Trials as Topic↗
Biomedical subjects
A K Asbury
Publications and source records attributed to A K Asbury.
Molecular population genetic analysis of Campylobacter jejuni HS:19 associated with Guillain-Barré syndrome and gastroenteritis.
Infection with Campylobacter jejuni serotype HS:19 is associated with the development of Guillain-Barré syndrome (GBS). To determine whether a particular HS:19 clone is associated with GBS, multilocus enzyme electrophoresis (MLEE) was used to analyze a worldwide collection of isolates. There were 34 electropherotypes (ETs) in 3 phylogenetic clusters among 83 C. jejuni isolates. Cluster I contained all HS:19 strains, and a single ET (ET4) accounted for most HS:19 strains. HS:19 strains did not occur in any of the other clusters. ET4 contained isolates from different geographic locations, indicating global spread of this clone. Furthermore, ET4 contained isolates from patients with uncomplicated enteritis and GBS, as well as isolates from animal sources. The results of this study show that HS:19 strains comprise a clonal, although not monomorphic, population, which is distinct from non-HS:19 strains within C. jejuni. A unique clone associated with GBS was not identified by use of MLEE.
Campylobacter Infections↗
Physiologic-pathologic correlation in Guillain-Barré syndrome in children.
OBJECTIVE: To correlate electrophysiologic patterns with sural nerve pathology in children with Guillain-Barré syndrome (GBS). BACKGROUND: Based on electrophysiologic and pathologic observations, GBS has been divided into demyelinating and axonal subtypes. The acute motor axonal neuropathy (AMAN) involves predominantly motor nerve fibers with a physiologic pattern suggesting axonal damage, whereas the acute inflammatory demyelinating polyneuropathy (AIDP) involves both motor and sensory nerve fibers with a physiologic pattern suggesting demyelination. In this study, we sought to confirm these observations by correlating sural nerve pathology with electrophysiologic findings in GBS patients. METHODS: Biopsies of sural nerve from 29 of 50 prospectively studied GBS patients were obtained. Nerves were examined by light and electron microscopy, and with immunocytochemistry for macrophages, lymphocytes, and complement activation products. RESULTS: Sural nerves from AMAN patients were normal or had only a few (0.1% to 0.7%) degenerating fibers without lymphocytic infiltration or complement activation. One patient with reduced sural sensory nerve action potential classified as acute motor sensory axonal neuropathy (AMSAN) had many degenerating fibers (2.3%) in the sural nerve. All three AIDP patients displayed active demyelination, and in two patients, lymphocytic infiltration and complement activation products were observed on the abaxonal Schwann cell surface. CONCLUSION: Classification of Guillain-Barré syndrome subtypes based on motor conduction studies correlates closely with pathologic changes seen in sural nerve. In acute motor axonal neuropathy cases, the sural nerve is almost completely spared pathologically. In acute inflammatory demyelinating polyneuropathy cases, macrophage-mediated demyelination and lymphocytic infiltration are common in the biopsies of sural nerves.
Action Potentials↗
New concepts of Guillain-Barré syndrome.
Guillain-Barré syndrome is an acute autoimmune polyradiculoneuropathy with a clinical presentation of flaccid paralysis with areflexia, variable sensory disturbance, and elevated cerebrospinal fluid protein without pleocytosis. Although Guillain-Barré syndrome previously had been viewed as a unitary disorder with variations, it currently is viewed as a group of syndromes with several distinctive subtypes. These include the principal subtype prevalent in the Western world (acute inflammatory demyelinating polyradiculoneuropathy, and others, each with distinctive electrodiagnostic and pathologic features, including acute motor axonal neuropathy), acute motor-sensory axonal neuropathy, Miller Fisher syndrome, and perhaps others. The clinical and pathologic features of these Guillain-Barré syndrome subtypes are reviewed, and the role of antecedent infections, particularly Campylobacter jejuni gastroenteritis, and the role of antiganglioside antibody responses are reviewed with respect to pathogenesis. Treatment of Guillain-Barré syndrome includes both important supportive measures and immunotherapies, specifically high-dose intravenous immunoglobulin and plasma exchange.
Autoantibodies↗
Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barré syndrome.
Immunopathological studies suggest that the target of immune attack is different in the subtypes of Guillain-Barré syndrome (GBS). In acute motor axonal neuropathy (AMAN), the attack appears directed against the axolemma and nodes of Ranvier. In acute inflammatory demyelinating polyneuropathy (AIDP), the attack appears directed against a component of the Schwann cell. However, the nature of the antigenic targets is still not clear. We prospectively studied 138 Chinese GBS patients and found that IgG anti-GD1a antibodies were closely associated with AMAN but not AIDP. With a cutoff titer of greater than 1:100, 60% of AMAN versus 4% of AIDP patients had IgG anti-GD1a antibodies; with a cutoff titer of greater than 1:1,000, 24% of AMAN patients and none of the AIDP patients had IgG anti-GD1a antibodies. In contrast, low levels of IgG anti-GM1 antibodies (> 1:100) were detected in both the AMAN and the AIDP forms (57% vs 35%, NS). High titers of IgG anti-GM1 (>1:1,000) were more common in the AMAN form (24% vs 8%, NS). Serological evidence of recent Campylobacter infection was detected in 81% of AMAN and 50% of AIDP patients, and anti-ganglioside antibodies were common in both Campylobacter-infected and noninfected patients. Our results suggest that IgG anti-GD1a antibodies may be involved in the pathogenesis of AMAN.
Adolescent↗
Ganglioside GM1 mimicry in Campylobacter strains from sporadic infections in the United States.
To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillain-Barré syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 random enteritis-associated isolates of Campylobacter jejuni were analyzed. To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillan-Barre syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 enteritis-associated isolates, randomly collected in the United States, were analyzed using a cholera-toxin binding assay [corrected]. Overall, 26.2% of the isolates were positive for the GM1-like epitope. Of the 36 different O serotypes in the sample, 21 (58.3%) contained no strains positive for GM1, whereas in 6 serotypes (16.7%), >50% of isolates were positive for GM1. GBS-associated serotypes were more likely to contain strains positive for GM1 than were non-GBS-associated serotypes (37.8% vs. 15.1%, P=.0116). The results suggest that humans are frequently exposed to strains exhibiting GM1-like mimicry and, while certain serotypes may be more likely to possess GM1-like epitopes, the presence of GM1-like epitopes on Campylobacter strains does not itself trigger GBS.
Campylobacter Infections↗
Molecular mimicry in Guillain-Barré syndrome.
Guillain-Barré syndrome (GBS) is the commonest cause of acute flaccid paralysis worldwide. Recent pathological and electrodiagnostic studies indicated that there are different patterns within this syndrome. The demyelinating pattern predominates in North America and Europe, whereas axonal variants of GBS occur more frequently in Northern China. Infection with Campylobacter jejuni is one of the most frequently recognized antecedent events in all variants of GBS. The lipopolysaccharides of these organisms share ganglioside-like epitopes with peripheral nerves, and patients with GBS have antiganglioside antibodies. These observations have given rise to the hypothesis that "molecular mimicry" is the immunopathogenic mechanism of injury to peripheral nerve fibers. With this hypothesis in view, we summarize our experience of GBS as it occurs in Northern China. To explore the role of molecular mimicry in this cohort we sought evidence of preceding Campylobacter infection and correlated this with clinical characteristics and antiganglioside serology. Based on our results we propose a sequence of pathogenic events leading to peripheral nerve injury in GBS.
Adolescent↗
Campylobacter jejuni lipopolysaccharides in Guillain-Barré syndrome: molecular mimicry and host susceptibility.
OBJECTIVE: This study was designed to determine if the presence of specific ganglioside-like moieties in Campylobacter lipopolysaccharides (LPSs) is related to the development of Guillain-Barré syndrome (GBS), and to discover how frequently such moieties, including GM1, are present in these LPSs. METHODS: We studied Campylobacter isolates and sera from seven patients with GBS (five acute motor axonal neuropathy, one acute inflammatory demyelinating polyneuropathy, and one Fisher's syndrome), and compared them with similar specimens from patients with Campylobacter enteritis alone. RESULTS: All GBS patients had antiganglioside antibodies. Anti-GM1 and anti-GD1a titers were significantly elevated in post-Campylobacter GBS, both axonal and demyelinating, compared with normal control subjects or those with uncomplicated Campylobacter diarrhea. Campylobacter isolated from patients with GBS and with enteritis alone had similar ganglioside-like moieties. CONCLUSIONS: These results indicate that patients who develop GBS respond differently to the ganglioside-like epitopes on Campylobacter than do non-GBS diarrhea patients. Our findings support a role for host susceptibility as a determinant for the outcome following Campylobacter infection. These findings have important implications for the development of vaccines against Campylobacter jejuni.
Adult↗
Pupil-involving third-nerve palsy and carotid stenosis: rapid recovery following endarterectomy.
We report a patient who presented with a painful pupil-involving third-nerve palsy. Cerebral angiography revealed a high-grade stenosis of the ipsilateral internal carotid artery with a 4-cm intraluminal thrombus. Following emergent carotid endarterectomy, the patient's partial third-nerve palsy resolved in 1 hour. A pupil-involving third-nerve palsy may be an unusual presentation of impending carotid occlusion.
Carotid Stenosis↗
Changing views of Guillain-Barré syndrome.
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Adolescent↗
Patterns of recovery in the Guillain-Barre syndromes.
Clinical, electrodiagnostic, and pathologic studies indicate that the Guillain-Barre syndromes (GBSs) include both primary demyelinating and primary axonal forms. The axonal forms are usually thought to have a poorer prognosis, with less chance for rapid or complete recovery. In northern China, epidemics of one axonal form, acute motor axonal neuropathy (AMAN), occur annually in the summer. Autopsy studies in some fatal cases have demonstrated wallerian-like degeneration of motor roots and motor fibers in the peripheral nerves. Recovery of such patients would require axonal regeneration along the entire length of the nerve fiber. In a 2-year prospective study of GBS at a single hospital in northern China, 42 patients were classified as having either AMAN (32 patients), acute inflammatory demyelinating polyneuropathy (AIDP) (8 patients), or as undetermined (2 patients) by electrodiagnostic criteria. Their recoveries were monitored clinically. The recovery times of AMAN and AIDP patients were similar: the median time to regain the ability to walk 5 meters with assistance was 31 days for patients classified as having AMAN and 32 days for those classified as having AIDP. These rapid recovery times are incompatible with severe wallerian degeneration of the ventral roots and motor nerve fibers. The rapid recoveries observed in AMAN patients could be explained by relatively quickly reversible immune-mediated changes at nodes of Ranvier in motor fibers, by degeneration and regeneration of intramuscular motor nerve terminals, or both.
Adolescent↗
Pathology of the motor-sensory axonal Guillain-Barré syndrome.
The concept of a severe motor-sensory neuropathy of acute onset caused by an immune attack on the axon ("axonal" Guillain-Barré syndrome) has been advanced primarily based on electrodiagnostic and limited pathological data, but remains controversial. At autopsy some cases demonstrate unusually severe inflammatory demyelinating neuropathy. There are conflicting data about whether antecedent Campylobacter jejuni infection is associated with "axonal" Guillain-Barré syndrome. We report 4 individuals from Hebei Province, China, who died 7, 7, 18, and 60 days after onset of a syndrome diagnosed clinically as Guillain-Barré syndrome. High titers of antibodies recognizing C. jejuni, consistent with recent infection, were found in the 2 patients tested. At autopsy the 3 with early disease had ongoing wallerian-like degeneration of fibers in the ventral and dorsal roots and in the peripheral nerves, with only minimal demyelination or lymphocytic infiltration. All 3 had numerous macrophages in the periaxonal space of myelinated internodes, and rare intraaxonal macrophages as well. Examination of the patient having the syndrome for 60 days confirmed the extensive loss of large fibers in the spinal roots and nerves, and the paucity of demyelination and remyelination. These observations confirm predictions that some patients with severe motor-sensory Guillain-Barré syndrome, as defined clinically, have predominantly axonal lesions of both motor and sensory fibers, even in the early stages of the disease, and that axonal Guillain-Barré syndrome can follow C. jejuni infection. The pathology supports the possibility that such cases of motor-sensory axonal Guillain-Barré syndrome represent the most severe end of a spectrum of immune attack directed toward epitopes on the axon.
Acute Disease↗
Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy.
The localization, mode of action, and roles of complement in the Guillain-Barre syndrome have been controversial. We used high-resolution immunocytochemistry to localize complement activation products in early stages of the acute inflammatory demyelinating polyneuropathy (AIDP) pattern of Guillain-Barre syndrome. Three AIDP subjects who were autopsied had had symptoms for 3 to 9 days at the time of death. Immunocytochemistry was performed on etched, epoxy resin-embedded sections, and the next thin section was compared by electron microscopy (thick/thin sections). Many fibers had a rim of the complement activation marker C3d and the terminal complement complex neoantigen C5b-9 along the outer surface of the Schwann cells. Ultrastructural analysis of these C3d-positive fibers showed mild vesicular changes of the outermost myelin lamellae. Vesicular degeneration was seen before the invasion of macrophages into the myelin, and was the predominant change in the subject with symptoms for 3 days. C3d staining was not found on myelin membranes. The results suggest that at least some forms of AIDP are complement mediated. We speculate that complement is activated by antibody bound to epitopes on the outer surface of the Schwann cell and that the resulting complement activation initiates the vesiculation of myelin.
Acute Disease↗
Acute motor axonal neuropathy: an antibody-mediated attack on axolemma.
The acute motor axonal neuropathy (AMAN) form of the Guillain-Barre syndrome is a paralytic disorder of abrupt onset characterized pathologically by motor nerve fiber degeneration of variable severity and by sparing of sensory fibers. There is little demyelination or lymphocytic inflammation. Most cases have antecedent infection with Campylobacter jejuni and many have antibodies directed toward GM1 ganglioside-like epitopes, but the mechanism of nerve-fiber injury has not been defined. In 7 fatal cases of AMAN, immunocytochemistry demonstrated the presence of IgG and the complement activation product C3d bound to the axolemma of motor fibers. The most frequently involved site was the nodal axolemma, but in more severe cases IgG and C3d were found within the periaxonal space of the myelinated internodes, bound to the outer surface of the motor axon. These results suggest that AMAN is a novel disorder caused by an antibody- and complement-mediated attack on the axolemma of motor fibers.
Acute Disease↗
Early nodal changes in the acute motor axonal neuropathy pattern of the Guillain-Barré syndrome.
The axonal patterns of Guillain-Barré syndrome, associated in many cases with antecedent Campylobacter jejuni infection, are now recognized as frequent causes of acute flaccid paralysis in some regions of the world. This study examined ultrastructurally the PNS of seven cases of the acute motor axonal neuropathy form of Guillain-Barré syndrome. In this disorder previous studies of advanced cases have found Wallerian-like degeneration of motor fibres in the spinal roots and peripheral nerves, with little lymphocytic inflammation or demyelination. The present study was focused on identifying early changes and establishing the sequence of changes. By electron microscopy the earliest and mildest changes consisted of lengthening of the node of Ranvier with distortion of the paranodal myelin, and in some instances with breakdown of the outermost myelin terminal loops. At this stage many nodes had overlying macrophages which extended their processes through the Schwann cell basal lamina covering the node and apposed the axolemma. Macrophage processes then extended beneath the myelin terminal loops, and the whole macrophage entered the periaxonal space at the paranode. Macrophage processes dissected the axon from the adaxonal Schwann cell plasmalemma and the macrophages advanced into the internodal periaxonal space, where they typically surrounded a condensed-appearing axon. At this stage the adaxonal Schwann cell cytoplasm regularly degenerated and disappeared, so that the periaxonal space was bounded by the innermost myelin lamella, and the axolemma of many fibres could not be seen. The internodal myelin sheath and the abaxonal Schwann cell cytoplasm remained normal. This arrangement appeared to be stable for some time, but in many fibres the axon subsequently underwent Wallerian-like degeneration. By interfering with impulse conduction, these nodal and periaxonal changes may explain paralysis in some pathologically mild cases. In addition, at early stages, these changes may be reversible, thus explaining the rapid recovery of some patients who become paralysed with acute motor axonal neuropathy. These observations, taken together with previous studies, suggest that acute motor axonal neuropathy is an antibody- and complement-mediated disorder in which the relevant epitopes are present on the nodal and internodal axolemma.
Adolescent↗
Guillain-Barré syndrome in northern China. Relationship to Campylobacter jejuni infection and anti-glycolipid antibodies.
Guillain-Barré syndrome has been considered to be primarily an acute inflammatory demyelinating polyneuropathy (AIDP). Our experience with Guillain-Barré syndrome in northern China differs from the traditional concept. Electrophysiologically and pathologically, most of our patients have motor axonal degeneration with minimal cellular inflammation, which we have termed 'acute motor axonal neuropathy' (AMAN). The current studies were undertaken to characterize prospectively the clinical, electrophysiological, and serological features of Guillain-Barré syndrome, defined clinically, in northern China. In 1991 and 1992, we characterized by electrodiagnostic criteria 129 Chinese patients with Guillain-Barré syndrome. The AMAN form was present in 65% of patients, the AIDP form in 24% and 11% were unclassifiable. For the 38 patients who presented from January to October, 1992, we performed serological assays for antibodies to Campylobacter jejuni and to glycolipids. Of these 38 patients, 55% had AMAN, 32% had AIDP and 13% were unclassifiable. Sixty-six percent of the 38 had serological evidence of recent C. jejuni infection as compared with 16% of village controls (P = 0.001). Seventy-six percent of AMAN patients and 42% of AIDP patients were seropositive. IgG anti-GM1 antibodies were more frequent in Guillain-Barré syndrome patients compared with village controls (42% versus 6%; P < 0.01). However, no statistically significant correlations were found between the pattern of disease, AMAN or AIDP, anti-glycolipid antibodies, or C. jejuni antibodies. Based on electrophysiological criteria, Guillain-Barré syndrome in northern China can be divided into two predominant forms: AIDP and AMAN. The AMAN form is more common and predominates in the yearly summer outbreaks of Guillain-Barré syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Gangliosides and peripheral neuropathies: an overview.
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Gangliosides↗
New horizons in neurology. The twentieth century.
Neurology in the twentieth century has undergone extraordinary change, particularly in the past 40 years. We trace the major trends, including the growth of the field, the technological advances, the revolution in neuroscience, the emergence of neurology as a free-standing specialty, the rise of child neurology, and the development of neurological subspecialization. Subsequent articles in this series will expand on these subjects.
History, 20th Century↗