1,721,163 research outputs found
Diagnostic role of anti-neural antibodies in dysimmune neuropathies
No full textAntibodies against several neural antigens have been associated with neuropathies (PN), including anti-myelin-associated glycoprotein (MAG) IgM in predominantly sensory demyelinating PN associated with IgM monoclonal gammopathy (PN+IgM), anti-sulfatide IgM in predominantly sensory axonal PN or demyelinating PN+IgM, anti-GM1 or -GD1a IgM in motor neuropathies with (MMN) or without conduction block (MN), anti-GM1 or GD1a IgG in Guillain-Barré syndrome (GBS), anti-GM2 IgM in MMN, MN and GBS, anti-GQ1b IgM in sensory PN+IgM, anti-GQ1b IgG in Fisher syndrome (FS) or ophthalmoplegic GBS, and anti-Hu IgG in paraneoplastic subacute sensory neuropathy (SSN). There is, however, an open debate not only on the pathogenetic relevance of these antibodies but also on their possible diagnostic usefulness. To determine the diagnostic role of these antibodies we reviewed the diagnosis of positive patients among the over 2500 patients tested in our laboratory from 1985 through 1998. Among the 710 patients tested for anti-MAG IgM by immunoblot, all those with titers >1/100,000 and 95% of those with titers >1/6400 but only 25% of those with titers 1/8000 had chronic inflammatory demyelinating polyneuropathy (CIDP) or demyelinating PN+IgM; all those with anti-GD1a >1/5120 had demyelinating PN+IgM (IgM antibodies) or GBS (IgG); and all those with anti-GM2 IgM >1/640 had GBS, MMN or MN. Lower titers were not associated with specific clinical forms. Of the over 1500 sera tested by ELISA for anti-GM1 antibodies, 88% of those with anti-GM1 IgG >1/640 had GBS, while only 62% of those with anti-GM1 IgM >1/320 had a dysimmune neuropathy, including GBS, CIDP, PN+IgM and MN. The sensitivity and specificity for a positive anti-GM1 IgM test was identical using a recently proposed Covalink ELISA technique. Among the 308 patients tested for anti-GQ1b antibodies by ELISA, only titers >1/100 were always associated with FS or ophthalmoplegic GBS in the case of IgG and with PN+IgM in that of IgM. Of the 333 tested for anti-Hu IgG by immunoblot only those with titers >1/6400 always had SSN/limbic encephalitis associated with lung carcinoma. These data show that the diagnostic value of anti-neural antibodies strictly depends on their titers and that while antiMAG, -sulfatide, -GD1a and -GQ1b IgM, and anti-GM1, -GD1a, -GQ1b and -Hu IgG are highly predictive for specific neuropathies, anti-GM1 and anti-GM2 IgM are more generically predictive for a dysimmune PN rather than for MMN or MN
Neuropathy and monoclonal gammopathy
No full textThe association of neuropathy with monoclonal gammopathy has been known for several years, even if the nosological position of these neuropathies is still debated. Similarly unsettled is the pathogenetic role and diagnostic relevance in clinical practice of the antineural antibodies frequently associated with monoclonal gammopathies of undetermined significance of IgM isotype, as well as the most effective therapy (if any) to be used in these patients. Over the past 12 months these issues have been addressed in several papers whose results will be critically reviewed here
Are there immunologically treatable motor neuron diseases?
No full textSeveral studies have addressed the issue of a possible immunological involvement in the pathogenesis of amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), particularly when the disease was associated with cancer, lymphoma or other monoclonal gammopathies or with the presence of serum antibodies to neural antigens. The hypothesis of the existence of immunologically treatable MND was reinforced by the occasional report of MND patients responding to immune or cytostatic therapies and by the identification among those with a purely lower motor neuron syndrome (LMNS) of a motor neuropathy, presently known as multifocal motor neuropathy (MMN), which almost invariably responded to immune therapies. These observations have led to several attempts to treat patients with MND or LMNS, either idiopathic or associated with the above mentioned conditions, with a number of immune or cytostatic therapies. The aim of this review is to verify whether the available data provide enough evidence to support the concept of dysimmune MND and to justify the use in these patients of potentially harmful immune cytostatic therapies
Clinical relevance of anti-GM1 IgM antibodies
No full textAnti-GM1 IgM antibodies were found in 23% of 56 patients with motor neuron disease (MND), in 19% of 69 patients with neuropathy and in 7% of 107 controls with other neurological and non-neurological diseases. Most patients had anti-GM1 IgM titers of 1:80 or less, while slightly higher titers (up to 1:640) were found in 1 patient with MND and 2 with neuropathy, and very high titers (1:20,480) were restricted to a patient with MND and an IgMk M-protein reacting with GM1, GD1b and asialo-GM1. Anti-GM1 IgM antibodies may be a normal constituent of the human antibody repertoire but their frequency and, at times, their levels are higher in patients with MND or neuropathy. The possible pathogenetic role of these antibodies remain to be established
Anti-GM1 antibodies in CSF of patients with the Guillain Barre' Syndrome and motor neuropathy
No full textGangliosides. Their role in clinical neurology
No full textGangliosides are normal constituent of mammalian vertebrate cell membranes and are particularly abundant in the central and peripheral nervous systems. The biological effects of exogenously administered gangliosides have been extensively investigated in vitro and in experimental animal models where they have neuronotrophic and neuritogenic properties. Despite these findings there is still little evidence that treatment with parenteral gangliosides in humans can be effective in peripheral neuropathies or other neuromuscular diseases. The initial preliminary reports on the positive effects of GM1 in cerebrovascular diseases and spinal cord injury need to be confirmed in larger controlled trials. At the same time the occasional development of an acute motor neuropathy clinically presenting as the Guillain-Barré syndrome and associated with high titres of anti-ganglioside antibodies highlights the risks of their widespread use before more consistent data on their efficacy become available
The anti-oligosaccharide antibodies present in sera from patients with motor neuron disease and neuropathy recognize the N-glycolylneuraminic acid containing gangliotetrahexosyl oligosaccharide
No full textWe found that serum antibodies present in the serum of patients with motor neuron disease and neuropathy, which were previously shown to react with the oligosaccharide chain of ganglioside GM1(Neu5Ac), can be recognized and titred using the N-glycolylneuraminic acid containing monosialo-gangliotetrahexosylceramide, GM1(Neu5Gc), which is not a component of normal human cells. The antibody-antigen reaction was abolished by immunoabsorption with the free oligosaccharide chain. This result, together with the knowledge that these antibodies recognize several glycoconjugates, supports the conviction that these antibodies are non-specific for a gangliosidic structure
Treatment of multifocal motor neuropathy
No full textMultifocal motor neuropathy (MMN) is a purely motor multineuropathy characterized by multifocal conduction blocks on motor nerves. The pathogenesis of MMN is not known but its frequent association with anti-ganglioside antibodies and the improvement after immune therapies support an immune pathogenesis. Patients with MMN do not respond to steroids or plasma exchange, which may occasionally even worsen the symptoms, while the efficacy of other immune suppressive therapies is controversial. More than 80% of MMN patients rapidly and consistently improve with highdose intravenous immunoglobulin (IVIg), the efficacy of which has been confirmed in four controlled studies. In most patients, however, the effects of this therapy only last a few weeks and improvement has to be maintained with periodic infusions for long periods of time, if not indefinitely
- …
