anti-GM1 IgM Research Articles

Multifocal motor neuropathy

To determine the prevalence and specificity of antibodies against single gangliosides and ganglioside complexes in serum from 88 patients with multifocal motor neuropathy (MMN) and to study the association with clinical features. ELISA was used to detect immunoglobulin (Ig)M, IgG, and IgA antibodies against GM1, GM2, GD1a, GD1b, GM1b, GT1a, GT1b, GQ1b, GalNAc-GD1a, and the glycolipid SGPG; absorption studies were performed to study cross-reactivity. Presence of antibodies against ganglioside complexes consisting of any of combinations of GM1, GM2, GD1a, GD1b, GT1b, and GQ1b was also tested. Anti-GM1 IgM, IgG, and IgA antibodies were detected in serum from 43%, 1%, and 5% of patients with MMN. Anti-GM2 IgM antibodies were detected in 6% and anti-GD1b IgM antibodies in 9% of patients. Patients with MMN with anti-GM1 IgM antibodies had more severe weakness (p < 0.01), more disability (p < 0.01), and more axon loss (p = 0.05) than patients without anti-GM1 IgM antibodies. Anti-GM1 IgM antibody titers correlated with Medical Research Council scores (correlation coefficient = 0.43; p < 0.0001). Anti-GD1b IgM antibody activity was associated with reduced vibration sense (p < 0.01). Absorption studies showed that anti-GD1b and anti-GM2 IgM antibodies cross-reacted with GM1. Antibodies against ganglioside complexes were not detected. Complexes containing GD1a, GD1b, GT1b, or GQ1b with GM1 lowered antibody activity against GM1. Anti-ganglioside IgM antibodies in MMN display limited specificity and are associated with severity and clinical characteristics. Results of this study suggest that anti-GM1 IgM antibodies may play a role in MMN pathogenesis.

Non-classical binding of a polyreactive α-type anti-idiotypic antibody to B cells

Detailed information on the immunological relevance of α-type anti-idiotypic antibodies is lacking after more than 30 years since Jerne postulated his Idiotypic Network Theory. The B7Y33 mutant is a mouse-human chimeric version of the B7 MAb, a polyreactive α-type anti-idiotypic antibody, generated against an anti-GM2 ganglioside IgM Ab1 antibody. It retained the unusual self-binding activity and multispecificity of the parental murine antibody, being able to recognize several anti-ganglioside IgM antibodies as well as non-immunoglobulin antigens. Previous work with the murine B7 MAb suggested that this antibody might have immunoregulatory properties, and therefore we investigated the possible interaction of B7Y33 with immune cells. We found that B7Y33 binds to human and murine B lymphocytes. Inhibition assays using flow cytometry indicated that this antibody is capable of binding the Fc γ receptor II (FcγRII). The recognition of FcγRII-expressing K562, Raji and Daudi human cell lines, together with the capability of inhibiting the binding of an anti-human FcγRII antibody to these cells, suggest that B7Y33 interacts with both the FcγRIIa and FcγRIIb isoforms. We evaluated the contribution to the binding of different surface-exposed residues at the top of the heavy chain variable region (VH) CDR loops through the construction of mutants with substitutions in the three conventional VH CDRs (HCDRs) and the “HCDR4”, located in the framework 3 (HFR3). In addition, we assessed the involvement of the Fc region by performing key mutations in the CH2 domain. Furthermore, chimeric hybrid molecules were obtained by combining the B7Y33 heavy chain with unrelated light chains. Our results indicate that the multispecificity and self-binding properties of B7Y33 are not linked to its recognition of B lineage cells, and that this phenomenon occurs in a non-classical way with the participation of both the variable and constant regions of the antibody. Two possible models for this interaction are proposed, with B7Y33 binding to two FcγRIIb molecules through the Fc and Fv regions, or simultaneously to FcγRIIb and another unknown antigen on B cells. The FcγRIIb has recently received great attention as an attractive target for therapies directed to B lymphocytes. The recognition of peripheral B lymphocytes from B cell chronic lymphocytic leukemia (B-CLL) patients by B7Y33 suggests its potential application for the treatment of B cell malignancies.

IVIg inhibits classical pathway activity and anti-GM1 IgM-mediated complement deposition in MMN

The effects of intravenous immunoglobulins (IVIg) on anti-GM1 IgM titer and function, classical complement pathway activity, and antibody–complement interaction were investigated in 62 patients with multifocal motor neuropathy (MMN). In vitro, IVIg decreased complement deposition by anti-GM1 IgM antibodies. First IVIg treatment (2 g/kg) decreased C1q and C4 concentrations and classical pathway activity in serum. In sera from patients receiving IVIg maintenance therapy (0.4 g/kg) C4 concentrations and classical pathway activity were generally lower at higher IgG concentrations. The beneficial effects of IVIg in MMN may be explained by reduced antibody-mediated complement deposition in nerves amplified by a systemically attenuated classical pathway.

IVIG blocks complement deposition mediated by anti-GM1 antibodies in multifocal motor neuropathy

BackgroundThe pathogenesis of multifocal motor neuropathy (MMN) has yet to be established. MMN patients often carry anti-GM1 IgM antibodies, suggesting an autoimmune process involving complement. Intravenous immunoglobulin (IVIG) is the...

Motor neuropathies and serum IgM binding to NS6S heparin disaccharide or GM1 ganglioside

BackgroundSerum IgM binding to GM1 ganglioside (GM1) is often associated with chronic acquired motor neuropathies. This study compared the frequency and clinical associations of serum IgM binding to a different...

Abstract 2418: Low dose antibody against GM2 ganglioside results in accelerated tumor growth

Abstract A variety of monoclonal antibodies have demonstrated prolongation of disease free and overall survival in preclinical studies and in the clinic when the tumors were known to be strongly positive for the target antigen. This includes monoclonal antibodies against gangliosides GD2, GD3 and GM2. On the other hand, randomized trials with the antibody inducing GM2-KLH vaccine in melanoma patients have demonstrated either no benefit (Kirkwood, JCO 19(9): 2370, 2001) or a decrease in overall survival (Eggermont, JCO 26 (abstract 9004), 2008). The predominant antibodies induced by the GM2-KLH conjugate vaccine are anti-GM2 IgM antibodies. While GM2 is present on essentially all melanomas, it is expressed at only low levels in the great majority of these cases. We hypothesized therefore that 1) induction of high titers of antibodies against GM2 results in only a low level of cell surface binding antibodies against GM2 because of the low level GM2 expression, and 2) that this results in low level inflammation and angiogenesis, and tumor cell activation, as has been described for sub-lytic levels of cell surface complement activation in other settings. To address these hypotheses, we explored the impact of a range of doses of PGNX, an anti-GM2 IgM monoclonal antibody, on growth of the luciferase transduced neuroblastoma cell line CHLA-136luc in vitro and in vivo. We incubated 10,000 CHLA-136luc cells with different amounts of PGNX (0.01, 0.05, 2 and 5µg) and 5 µl human complement in 0.1ml medium overnight and measured cell growth using the Wst-1 assay. Increased cell growth was seen at PGNX doses of 0.01 and 0.05 µg (P&amp;lt;0.05 vs. control). The 5µg PGNX dose decreased cell growth (P&amp;lt;0.05 vs. control) and this was confirmed by the Calcein-AM dye release cytotoxicity assay which showed 50% complement mediated lysis. SCID mice were injected intravenously with 0.5 million CHLA-136-luc neuroblastoma cells and treated with 1µg, 5µg or 50µg of PGNX intraperitoneally on days 1 and 14 after tumor challenge. The 50µg dose resulted in strikingly delayed tumor growth, prolonged survival and apparent cure in 10%-40% of mice. This protection from tumor challenge was inhibited by depletion of complement (treatment with cobra venom factor) and depletion of polymorphonucleocytes (treatment with mAb RB), but not by NK cell depletion (mAb NK1.1). Treatment with 5µg or 1µg of PGNX had the opposite effect. The 5µg dose resulted in accelerated tumor growth when measured prior to day 40, but survival was not significantly impacted. At the 1µg PGNX dose, tumor growth was more dramatically accelerated and survival was significantly diminished compared to the no treatment control groups. Supported by a grants from the NIH PO1 CA 052477 and from The Breast Cancer Research Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2418.

A Guillain-Barré syndrome variant with prominent facial diplegia

To determine the clinical features of a Guillain-Barré syndrome variant with prominent facial diplegia, we retrospectively reviewed approximately 8,600 cases referred to our neuroimmunological laboratory for serological tests during the past seven years. Patients' histories, neurological signs, and laboratory and electrophysiological data were clarified based on their clinical records. Sera obtained during the acute phase were tested for prior infectious serology and anti-ganglioside antibodies. In 22 patients, clinical signs such as acute progressive bifacial weakness, paresthesias in the distal dominant limbs, and hypo- or areflexia, were compatible with a Guillain-Barré syndrome variant, facial diplegia and paresthesias. Other cranial nerve involvements, limb weakness, and ataxia were absent or minimal. Clinical courses were monophasic, the nadir being reached within four weeks. Eighteen patients (86%) had had infectious symptoms within the four weeks preceding the onset of neurological illness. In the infection serology tests, anti-cytomegalovirus IgM antibodies were the most frequent (35%). All the patients had cerebrospinal fluid albuminocytologic dissociation. In nerve conduction studies, 14 (64%) showed demyelination in their limbs. Anti-GM2 IgM antibodies were detected in four patients who had anti-cytomegalovirus IgM antibodies. Patients with conditions similar to facial diplegia and paresthesias, but lacking either distal paresthesias or hyporeflexia, were regarded as having marginal facial diplegia and paresthesias, because they also frequently had features of Guillain-Barré syndrome, such as an antecedent infection or cerebrospinal fluid albuminocytologic dissociation. Our findings are further evidence of a facial variant of Guillain-Barré syndrome and provide important information essential for its diagnosis.

Different antiganglioside antibody pattern between relapsing-remitting and progressive multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder, but an unique antigen has not been found. Antiganglioside antibodies (AGA) have been reported in MS, nevertheless, a clinical significance of AGA in MS has not been established. The aims of this study were to study AGA in sera of MS patients and to investigate relationships between AGA and clinical course of MS. 42 patients with MS who fulfilled the criteria of clinically definite disease (59% RRMS, 21% SPMS, 20% PPMS), 89 patients with systemic lupus erythematosus and 36 healthy controls were studied. A modification of previously described ELISA techniques was used to estimate serum IgG and IgM anti-GM1, asialoGM1 and anti-GD1a antibodies. 47.6% of the patients showed AGA reactivity. Anti-GM1 was found in 38% of MS patients, anti-asialoGM1 in 23.8% and anti-GD1a in 33.3%. IgG was the isotype more commonly found. A correlation between presence of AGA and progressive disease and between anti-GD1a and PPMS was found. The presence of AGA in MS patients is elevated. In contrast with the results of others authors, a strong correlation between AGA and progressive disease is showed in our study.

Sensory loss in multifocal motor neuropathy: A clinical and electrophysiological study

Some patients fulfilling the criteria for the diagnosis of multifocal motor neuropathy with conduction block (MMN-CB) at the onset of disease may subsequently develop a sensory loss associated with electrophysiological sensory abnormalities. The latter could represent an overlap between MMN-CB and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. The objective was to specify the features of MMN-CB with sensory loss (MMN-CB-Se). Five patients in a series of 11 consecutive patients who fulfilled the criteria of the American Association of Neuromuscular and Electrodiagnostic Medicine for MMN-CB at the first examination and were treated periodically with intravenous immunoglobulin (IVIg) developed sensory loss in the course of the disease. In these five patients we compared the clinical, laboratory, and electrophysiological features found after the development of sensory loss with those at the first examination. The mean time to appearance of objective sensory signs was 7.2 years. In three of the five patients the sensory loss was preceded by intermittent paresthesias in the same nerve territories as the motor involvement. The most frequent electrophysiological abnormality was amplitude reduction of sensory nerve action potentials. There were no bilateral or symmetrical clinical and electrophysiological sensory abnormalities. Anti-GM1 IgM antibodies were positive in four patients. MMN-CB-Se could be an overlap between MMN-CB and MADSAM. It shares the distribution of the sensory disorders encountered in MADSAM, but it is closer to MMN-CB on clinical and therapeutic levels. Study of more patients would be useful to classify this subgroup more accurately.

Asymmetrical Weakness Associated with Central Nervous System Involvement in a Patient with Guillain-Barrè Syndrome

Guillain-Barrè syndrome (GBS) is usually associated with symmetrical weakness, and therefore asymmetrical weakness may confuse diagnosis. We report on a patient with GBS subsequent to Campylobacter jejuni enteritis who had asymmetrical weakness with CNS involvement. The patient tested positive for anti-ganglioside antibodies, including anti-GM1 IgM, anti-GD1b IgG, and anti-GT1a IgG. Patients with GBS can manifest asymmetrical signs and symptoms attributable to CNS involvement. Prompt, accurate diagnosis and treatment of post-C. jejuni GBS is especially important because its prognosis is relatively poor.

STD-NMR Used To Elucidate the Fine Binding Specificity of Pathogenic Anti-Ganglioside Antibodies Directly in Patient Serum

High-resolution binding profiles were elucidated for anti-GM1 IgM autoantibodies from two patients with a progressive form of paraproteinemic polyneuropathy. Antibody-ligand interaction was characterized by generating STD-NMR signals in target ganglio-oligosaccharides added directly to patient sera, without the requirement of antibody fractionation. Both immunoglobulins were found to have similar binding modalities, with interaction confined to two distinct spatially separated regions of GM1: the terminal betaGal(1-3)betaGalNAc disaccharide unit and the sialic acid residue. We describe a unique and powerful biophysical technique applied to define the molecular interaction between autoimmune disease-causing antibodies and their ganglioside targets.

Diagnosis and treatment of multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a unique disease mimicking motor neuron disease, but it is treatable with intravenous immunoglobulins. Anti-GM1 IgM antibody titers are not sensitive enough to predict the outcome. Electrodiagnosis is essential for the diagnosis of MMN. Conduction block has been suggested as the best diagnostic marker, but it is not found in all treatable cases. Activity-dependent conduction changes, as revealed by comparing conduction before and after maximal voluntary contraction of the muscle, are a convenient and promising tool. Treatment options include various immunosuppressants (including cyclophosphamide), but there has not been ample evidence in favor of any of these agents in randomized controlled trials. Intravenous immunoglobulins remain the mainstay for treating MMN.

How useful are anti-neural IgM antibodies in the diagnosis of chronic immune-mediated neuropathies?

Antibodies against several neural antigens have been associated with different chronic immune-mediated neuropathies but their practical clinical relevance remains unclear. To determine the possible diagnostic usefulness of these antibodies we reviewed the clinical correlate of IgM antibodies to the myelin-associated glycoprotein (MAG), sulfatide, the gangliosides GM1, GM2, GD1a and GD1b in 539 consecutive patients examined for neuropathy or related diseases in our Neuropathy Clinics and tested for these antibodies in our laboratory since 1985. 302 patients (56%) had an established diagnosis of definite or possible chronic immune-mediated neuropathy while 237 had a neuropathy of non-immune-mediated origin or of unknown aetiology or a closely related disease. Antibodies to one or more antigen were more frequent ( χ 2 = 63.32; p < 0.00001) in patients with chronic immune-mediated neuropathy (37.7%) than with other neuropathy or related diseases (7.2%) and their presence was associated in 87% of the patients with an immune-mediated neuropathy, incrementing by 31% the probability of having this form. Testing for MAG permitted to identify 24.8% of patients with an immune-mediated neuropathy, GM1 an additional 9.9%, while GM2, GD1b, GD1a and sulfatide altogether an additional 3% of the patients. Concerning clinical correlations, all 75 patients with anti-MAG IgM had neuropathy and IgM monoclonal gammopathy (PN + IgM) with a positive predictive value for this neuropathy of 100%. A similarly high predictive value for neuropathy (91.4%) was observed among 269 patients with IgM monoclonal gammopathy including 103 patients without neuropathy. Anti-sulfatide IgM, though rare, were also significantly and constantly associated with PN +IgM and permitted to identify few patients not bearing anti-MAG IgM. Anti-GM1 IgM were significantly associated with multifocal motor neuropathy (MMN) (29.2%) but where also found in a few patients with other immune or non-immune neuropathies or related diseases with a positive predictive value for MMN of 25.5%. Anti-GM2 IgM were also significantly associated with MMN and increased the sensitivity (36.2%) for MMN obtained with anti-GM1 IgM only, without affecting its specificity and positive predictive value. Anti-GD1a, GD1b, though not significantly more frequent in patients with immune-mediated neuropathy, were associated in 80 to 100% of patients with these neuropathies. In conclusion anti-neural IgM antibodies may help in identifying patients with a chronic immune-mediated neuropathy, even if only anti-MAG and anti-sulfatide IgM appear to be strictly associated with a definite clinical syndrome.

Mycophenolate mofetil as adjunctive therapy for MMN patients: a randomized, controlled trial

Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterized by slowly progressive asymmetrical limb weakness. Treatment with immunoglobulins (IVIg) leads to improvement of muscle strength. Anecdotal evidence suggests that immunosuppressive drugs as adjunctive therapy may be beneficial. Mycophenolate mofetil (MMF) is a potent and safe immunosuppressant. Safety and efficacy of MMF as adjunctive therapy for MMN patients receiving IVIg maintenance treatment were evaluated in a randomized controlled trial. MMN patients responding to IVIg treatment were eligible for randomization. Muscle strength and functional status were assessed at monthly intervals for 1 year. Three months after the start of MMF or placebo treatment, IVIg doses were reduced stepwise, until a deterioration of functioning or decline in muscle strength could be observed. An IVIg dose reduction of 50% during adjunctive treatment was defined as a primary endpoint. Secondary outcome measures were improvement in muscle strength and functional status after 3 months and reduction of anti GM1-IgM titres after 12 months of MMF treatment. Twenty-eight patients were randomized. One patient allocated to MMF reached the primary endpoint of 50% IVIg dose reduction. After 12 months IVIg reduction did not differ significantly between the two treatment groups. Patients did not experience drug toxicity and none of the patients showed significant disease progression after 12 months. Muscle strength and functional scores after 3 months and anti GM1-IgM titres after 12 months did not change. Adjunctive treatment of MMN patients with MMF at a dose of 1 g twice daily is safe but does not alter disease course or allow significant reduction of IVIg doses.

Persistent multifocal conduction block in vasculitic neuropathy with IgM anti‐gangliosides

A 30-year-old man with essential cryoglobulinemia presented with an axonal neuropathy and was found to have vasculitis at nerve biopsy. After 44 months, in accord with clinical deterioration, motor conduction studies showed excessive temporal dispersion multifocally, with partial conduction block persisting for 3 years. Antibody testing showed the presence of IgM anti-GM1, anti-GD1a, and anti-GM2 antibodies. Transitory conduction block has been reported occasionally in patients with vasculitis. The persistent multifocal conduction abnormalities found in this patient were more likely due to a superimposed immunomediated demyelination rather than to chronic nerve ischemia secondary to vasculitis.

Neuropathies motrices multifocales avec blocs de conduction, profil évolutif sous immunoglobulines intraveineuses

Multifocal motor neuropathy with conduction block is an immune-mediated motor neuropathy, which usually responds to intravenous immunoglobulin. However, efficacy of long-term intravenous immunoglobulin is controversial. Our aim was to establish the long-term effects of intravenous immunoglobulin therapy on clinical and neurophysiological outcome measures and to determine the criteria predicting a good response to long-term intravenous immunoglobulin treatment. We retrospectively included all multifocal motor neuropathy with conduction blocks patients followed for at least 4 years who received intravenous immunoglobulin therapy. We compared clinical data, MRC sumscores and electrophysiological data between the first and the last examination in the department. Seventeen patients were followed for an average of 8 years (range 4 to 18 years). At last examination, weakness remained asymmetric, predominant in the upper limbs, with a peripheral nerve distribution. At last examination, 3 patterns of evolution was seen: 6/17 patients had muscle strength improvement and need no more intravenous immunoglobulin therapy, 6/17 had initial improvement but became intravenous immunoglobulin dependent and 5/17 did not respond to intravenous immunoglobulin. MRC sumscores, number of conduction blocks and distal compound muscle action potential amplitudes were comparable between the first and the last examination (p>0.05). Improvement of MRC sumscores was not correlated with the clinical, biological and electrophysiological data that we analysed: age, gender, duration of disease, time from onset to intravenous immunoglobulin therapy, number of involved nerves, number of affected limbs, presence of muscle atrophy, MRC sumscores at diagnosis, number of conduction blocks, mean amplitude of the motor evoked potentials, presence of anti-GM1 antibodies, titers and IgM or IgG type of anti-GM1 antibodies. In this study, one third of multifocal motor neuropathy with conduction blocks patients have clinical improvement at last examination and need no more treatment, one third are intravenous immunoglobulin dependent and one third have never responded to intravenous immunoglobulin. Electrophysiological data are comparable between the first and the last examination. No predictive factor has been disclosed for long-term response to intravenous immunoglobulin.

Anti-ganglioside antibodies in coeliac disease with neurological disorders

BackgroundAnti-ganglioside antibodies have been described in sera of coeliac patients with peripheral neuropathy and cerebellar ataxia. AimsTo investigate the correlation between anti-ganglioside antibodies and neurological involvement in coeliac disease before and after gluten-free diet. Patients and methodsTwenty-two untreated coeliac patients with neurological dysfunction and 30 untreated coeliacs without neurological dysfunction, 20 patients with neurological disorders, 50 autoimmune disease and 20 blood donors were tested for anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked immunosorbent assay. ResultsIgG antibodies to at least one of the three antigens tested were positive in 64% of coeliac patients with neurological symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02), 50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet determined anti-ganglioside antibody disappearance in about half of coeliacs. ConclusionsA significant correlation between anti-ganglioside antibodies and neurological disorders in patients with an underlying coeliac disease has been found. Anti-ganglioside antibodies may represent a new immunological marker to identify neurological impairment in patients with coeliac disease.

Prévalence et caractéristiques des syndromes de Guillain-Barré associés à Campylobacter jejuni et au cytomégalovirus en région parisienne

Aim of the study. – We aimed to study prevalence and features of Campylobacter jejuni and cytomegalovirus (CMV)-associated Guillain-Barré syndromes (GBS) in a French care unit. Patients and methods. – We studied 264 patients with GBS admitted at Raymond Poincaré hospital (Garches) between 1996 and 2001. Clinical data were obtained prospectively. Sera were collected at patients entry and tested retrospectively for anti- C. jejuni, anti-CMV and antigangliosides GM1 et GM2 antibodies. Results. – GBS associated with a serological evidence for a recent C. jejuni infection were the more frequent (58/264, 22%); they affected predominantly men of mature years (mean age: 51.3 years; sex-ratio M/F: 1.76), mostly after a gastrointestinal illness (52%); they were often pure motor forms (57%), were severe (mechanical ventilation: 40%) and associated to an anti-GM1 IgG and/or IgM response (44%). GBS cases involving a primary CMV infection were less frequent (40/264, 15%), but were severe too (mechanical ventilation: 37.5%); they occurred preferentially in young women (mean age: 35.9 years; sex-ratio MF: 0.82), often after respiratory tract symptoms (28%) or an influenza-like syndrome (15%) and were frequently associated with sensory loss (73%) and with an anti-GM2 IgM response (47%). Conclusion. – C. jejuni and CMV proved to be major triggering agents of GBS in France. They are associated with distinct presentations, which are both severe.

Multifocal motor neuropathy: Current concepts and controversies

Multifocal motor neuropathy (MMN) is now a well-defined purely motor multineuropathy characterized by the presence of multifocal partial motor conduction blocks (CB), frequent association with anti-GM1 IgM antibodies, and usually a good response to high-dose intravenous immunoglobulin (IVIg) therapy. However, several issues remain to be clarified in the diagnosis, pathogenesis, and therapy of this condition including its nosological position and its relation to other chronic dysimmune neuropathies; the degree of CB necessary for the diagnosis of MMN; the existence of an axonal form of MMN; the pathophysiological basis of CB; the pathogenetic role of antiganglioside antibodies; the mechanism of action of IVIg treatments in MMN and the most effective regimen; and the treatment to be used in unresponsive patients. These issues are addressed in this review of the main clinical, electrophysiological, immunological, and therapeutic features of this neuropathy.

Lewis-Sumner syndrome and multifocal motor neuropathy

We compared the clinical, electrophysiological, laboratory, and pathological features of 13 patients with Lewis-Sumner syndrome (LSS) with those of 20 patients with multifocal motor neuropathy (MMN). LSS and MMN patients have several common clinical features: age at onset, weakness in the distribution of individual peripheral nerves, mild wasting, cramps and fasciculations, partial areflexia, and frequent stepwise disease course. Cerebrospinal fluid protein level was normal or slightly elevated, but always less than 100 mg/dl. Conduction blocks are the electrophysiological hallmarks of these two neuropathies, and no differences in distribution and number of blocks were found. Contrary to MMN, lower-limb involvement at onset was frequent in LSS but extension to the upper limbs was a frequent later feature of the disease. Cranial nerve involvement was noted in 4 LSS patients during relapses and absent in all MMN patients. The major distinguishing features were the clinical and electrophysiological sensory involvement in LSS, and the lack of anti-GM1 antibodies in LSS, whereas IgM anti-GM1 were found in 40% of MMN patients. Some LSS patients responded to steroid therapy, whereas this was ineffective in MMN. From these features, LSS can be considered an entity distinct from MMN, with its own clinical, laboratory, and electrophysiological characteristics, and as an intermediate link between chronic inflammatory demyelinating polyneuropathy and MMN.