IgG anti-ganglioside antibodies and their subclass distribution in two patients with acute and chronic motor neuropathy.

IgG anti-ganglioside antibodies were found in two patients with motor neuropathy. The first patient had a chronic axonal neuropathy with persistently elevated anti-GM1 antibodies. The second patient had an acute axonal neuropathy with anti-GM1, GD1b and asialoGM1 antibodies. In both, the IgG subclass study showed that the antibodies belonged to the IgG1 subclass. An enzyme-linked immunosorbent assay (ELISA) for light chains revealed anti-ganglioside antibodies of the lambda type.     

Bickerstaff's brainstem encephalitis associated with IgM antibodies to GM1b and GalNAc-GD1a

This is the first report of a case of Bickerstaff's brainstem encephalitis (BBE) associated with IgM antibodies to GM1b and GalNAc-GD1a. Subsequent to Campylobacter jejuni enteritis, the patient rapidly developed consciousness disturbance and hyperreflexia in addition to external ophthalmoplegia and cerebellar-like ataxia. EEG showed transient 7 Hz monorhythmic theta activities, predominantly in the front-central area. He received high doses of immunoglobulin intravenously and had completely recovered 3 months later. High anti-GM1b and anti-GalNAc-GD1a IgM antibody titers present during the acute phase decreased with his clinical improvement. An absorption study showed the anti-GM1b and anti-GalNAc-GD1a IgM antibodies to be cross-reactive. Anti-GM1b and anti-GalNAc-GD1a antibodies have been detected in some patients who developed Guillain-Barré syndrome after C. jejuni enteritis, whereas the anti-GQ1b IgG antibody is associated with BBE. Infection by C. jejuni bearing a GM1b-like or GalNAc-GD1a-like lipooligosaccharide may trigger the production of anti-GalNAc-GD1a and anti-GM1b IgM antibodies. It is not clear why our patient developed BBE rather than Guillain-Barré syndrome. These antibodies may, however, prove useful serological markers for identifying BBE patients who do not have the anti-GQ1b IgG antibody.     

Bickerstaff's brainstem encephalitis and Fisher syndrome: their relationship and treatment]

The nosological position of Bickerstaff's brainstem encephalitis (BBE) was not eatablished, and its etiology was not clear until 1993. Because anti-GQ1b IgG antibody frequently occurs in patients with Fisher syndrome (FS) and there are clinical similarities between FS and BBE, we investigated anti-ganglioside antibodies in sera from three patients with BBE. High anti-GQ1b IgG antibody titers were present in their sera, but decreased with the clinical course of the illness. The findings that BBE and FS shared common autoantibody suggest that autoimmune mechanism common to FS is likely in BBE, and that both conditions form a continuous spectrum. To clarify the clinical features of BBE, we reviewed detailed clinical profiles and laboratory findings for 62 cases of BBE diagnosed by the strict criteria of progressive, relatively symmetric external ophthalmoplegia and ataxia by 4 weeks, and disturbance of consciousness or hyperreflexia. A striking feature was the association with flaccid symmetric tetraparesis seen in 60%. Limb weakness in the BBE cases studied was considered the result of overlap by the axonal subtype of Guillain-Barré syndrome. These indicates that the two disorders are closely related and form a continuous spectrum, and that treatment for Guillain-Barré syndrome should be applied for BBE.     

Autoantibodies to GM1b and GalNAc-GD1a: relationship to Campylobacter jejuni infection and acute motor axonal neuropathy in China.

IgG antibodies to the minor gangliosides GM1b and GalNAc-GD1a frequently are present in sera of Japanese patients with Guillain-Barré syndrome. The relationship between these autoantibodies and Campylobacter jejuni infection, the type of disease (acute motor axonal neuropathy [AMAN], or acute inflammatory demyelinating polyneuropathy [AIDP]) has yet to be established. Sera samples were obtained from 55 Chinese patients with clinically defined Guillain-Barré syndrome. An electrophysiology study showed nine AIDP, 28 had AMAN, and 18 unclassified. C. jejuni serology was positively correlated with anti-GM1b and anti-GalNAc-GD1a IgG antibodies (respective P values, 0.007 and 0.02). The frequencies of positive anti-GM1b and anti-GalNAc-GD1a serology were greater in AMAN (32 and 21%) than in AIDP (11 and 0%), but the differences were not significant. Infection by C. jejuni may induce IgG anti-GM1b antibody in some patients and IgG anti-GalNAc-GD1a antibody in others. A larger population of patients must be studied to show whether there is a definite correlation.     

Axonal Guillain-Barré syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan

To clarify the relations of the axonal form of Guillain-Barré syndrome (GBS) to anti-ganglioside antibodies and Campylobacter jejuni infection, 86 consecutive Japanese GBS patients were studied. Electrodiagnostic criteria showed acute inflammatory demyelinating polyneuropathy in 36% of the patients and acute motor axonal neuropathy (AMAN) in 38%. Frequent anti-ganglioside antibodies were of the IgG class and against GM1 (40%), GD1a (30%), GalNAc-GD1a (17%), and GD1b (21%). Identified infections were C. jejuni (23%), cytomegalovirus (10%), Mycoplasma pneumoniae (6%), and Epstein-Barr virus (3%). There was a strong association between AMAN and IgG antibodies against GM1, GD1a, GalNAc-GD1a, or GD1b. Almost all the patients with at least one of these antibodies had the AMAN pattern or rapid resolution of conduction slowing/block possibly because of early-reversible changes on the axolemma. C. jejuni infection was frequently associated with AMAN or anti-ganglioside antibodies, but more than half of the patients with AMAN or anti-ganglioside antibodies were C. jejuni-negative. These findings suggest that the three phenomena "axonal dysfunctions (AMAN or early-reversible conduction failure)," "IgG antibodies against GM1, GD1a, GalNAc-GD1a, or GD1b," and "C. jejuni infection" are closely associated but that microorganisms other than C. jejuni frequently trigger an anti-ganglioside response and elicit axonal GBS.     

High-dose intravenous immunoglobulin therapy in a child case of Bickerstaff's brainstem encephalitis

We report an 11-year-old boy with Bickerstaff's brainstem encephalitis (BBE). He had gait disturbance, disturbed consciousness, and diplopia after upper respiratory tract infection. On admission, he showed multiple cranial nerve palsy, muscle weakness of arms, cerebeller ataxia and generalized areflexia. The cerebrospinal fluid on day 7 revealed albuminocytologic dissociation. IgG antibodies against GQ1b and GT1a were detected in the serum. Immunoglobulin was administered intravenously from day 11, and then his symptoms gradually diminished. When he was discharged on day 27, he had neither conscious disturbance nor limb weakness. There still were mild ophthalmoparesis and diminished deep tendon reflexes, but they disappeared by 10 months after the onset. Effective therapy for BBE has yet to be established. Our case had features of Guillain-Barré syndrome (GBS) and Miller Fisher syndrome, such as an acute monophasic course, limb weakness with areflexia, albuminocytologic dissociation in the cerebrospinal fluid, detection of serum anti-ganglioside antibodies and efficacy of intravenous immunoglobulin, indicating that BBE and GBS are closely related. Our case suggested that intravenous immunoglobulin therapy, an established treatment for GBS, should be considered in some patients with BBE.     

Guillain–Barré syndrome–like–onset neurosarcoidosis positive for immunoglobulin G anti-N-acetylgalactosaminyl-GD1a antibody

Anti-ganglioside antibodies have been reported in various peripheral neuropathies, including Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, Fisher syndrome, monoclonal gammopathy-associated neuropathy, and other idiopathic neuropathies. To our knowledge, there has been no report of anti-ganglioside-positive sarcoidosis. We report a 62-year-old man with acute weakness of the limbs and sensory disturbance of the right arm and trunk resembling GBS. Soluble interleukin-2 receptor and angiotensin-converting enzyme levels were elevated. Anti-ganglioside antibodies (immunoglobulin G anti-N-acetylgalactosaminyl-GD1a antibody [IgG anti-GalNAc-GD1a antibody]) were detected. Neurophysiological examination demonstrated axonal neuropathy. Bilateral hilar lymphadenopathy was demonstrated on a chest CT scan, and abnormal uptake of ⁶⁷Gallium was detected by scintigraphy. The ratio of CD4 to CD8 was elevated in bronchoalveolar lavage fluid. Noncaseating epithelioid cell granulomas were detected in a specimen obtained via transbronchial lung biopsy. Because intravenous immunoglobulin did not improve the symptoms, we commenced steroid pulse therapy followed by oral prednisolone therapy. After steroid therapy, he recovered fully. Because the findings in our patient fulfilled the criteria for neurosarcoidosis, we diagnosed his illness as probable neurosarcoidosis. To the best of our knowledge, this is the first patient with GBS–like–onset neurosarcoidosis positive for anti-IgG anti-GalNAc-GD1a antibody.     

Ganglioside mimicry and peripheral nerve disease

Four criteria must be satisfied to conclude that a given microorganism causes Guillain-Barré (GBS) or Fisher (FS) syndrome associated with anti-ganglioside antibodies: (1) an epidemiological association between the infecting microbe and GBS or FS; (2) isolation in the acute progressive phase of illness of that microorganism from GBS or FS patients with associated anti-ganglioside IgG antibodies; (3) identification of a microbial ganglioside mimic; and (4) a GBS or FS with associated anti-ganglioside antibodies model produced by sensitization with the microbe itself or its component, as well as with ganglioside. Campylobacter jejuni is a definitive causative microorganism of acute motor axonal neuropathy and may cause FS and related conditions. Haemophilus influenzae and Mycoplasma pneumoniae are possible causative microorganisms of acute motor axonal neuropathy or FS. Acute and chronic inflammatory demyelinating polyneuropathies may be produced by mechanisms other than ganglioside mimicry.     

An anti-ganglioside antibody-secreting hybridoma induces neuropathy in mice

Immune responses against gangliosides are strongly implicated in the pathogenesis of some variants of Guillain-Barré syndrome (GBS). For example, IgG antibodies against GM1, GD1a, and related gangliosides are frequently present in patients with post-Campylobacter acute motor axonal neuropathy (AMAN) variant of GBS, and immunization of rabbits with GM1 has produced a model of AMAN. However, the role of anti-ganglioside antibodies in GBS continues to be debated because of lack of a passive transfer model. We recently have raised several monoclonal IgG anti-ganglioside antibodies. We passively transfer these antibodies by intraperitoneal hybridoma implantation and by systemic administration of purified anti-ganglioside antibodies in mice. Approximately half the animals implanted with an intraperitoneal clone of anti-ganglioside antibody-secreting hybridoma developed a patchy, predominantly axonal neuropathy affecting a small proportion of nerve fibers. In contrast to hybridoma implantation, passive transfer with systemically administered anti-ganglioside antibodies did not cause nerve fiber degeneration despite high titre circulating antibodies. Blood-nerve barrier studies indicate that animals implanted with hybridoma had leaky blood-nerve barrier compared to mice that received systemically administered anti-ganglioside antibodies. Our findings suggest that in addition to circulating antibodies, factors such as antibody accessibility and nerve fiber resistance to antibody-mediated injury play a role in the development of neuropathy.     

Detection of anti-ganglioside antibodies in Guillain-Barré syndrome and its variants by the agglutination assay

Sera from 40 patients with Guillain-Barré syndrome (GBS), including the subtypes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS) were examined for the presence of anti-ganglioside antibodies using the ganglioside agglutination assay, and the enzyme-linked immunosorbent assay (ELISA). In the ELISA system, sera were tested for IgM and IgG antibodies to GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides. Antibodies to gangliosides were detected in 21 (53%) of the GBS patients by agglutination assay and in 17 (43%) of the patients by ELISA. Some of the sera reacted with more than one ganglioside. Antibodies were not found in the control sera that were studied. The agglutination assay may be useful for rapid screening of GBS sera for antibodies to multiple gangliosides.     

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. Ann Neurol 1999;45:168–173     

Cerebellar ataxia and acute motor axonal neuropathy associated with Anti GD1b and Anti GM1 antibodies.

The anti-GD1b antibody is known to bind to the cerebellar granular layer or spinocerebellar Ia fibers. A few cases of anti-GD1b positive acute inflammatory demyelinating polyneuropathy with prominent cerebellar ataxia were reported. Recently, we encountered a middle-aged woman with Guillain Barré syndrome (GBS) with severe cerebellar ataxia and relatively mild motor weakness. Anti-GD1b Ig G antibody and anti-GM1 Ig G antibody titers were markedly elevated in her serum. She was diagnosed with acute motor axonal neuropathy (AMAN) with prominent cerebellar ataxia based on the results of the serial nerve conduction study suggesting axonal neuropathy. This case presents the clinico-pathogenic role of autoantibodies to the GD1b and the GM1 in acute inflammatory neuropathy.     

Anti-ganglioside antibody and neuropathy: review of our research

Some patients developed Guillain-Barré syndrome (GBS) after the administration of bovine gangliosides. Patients with GBS subsequent to Campylobacter jejuni enteritis frequently have IgG antibody to GM1 ganglioside. Fisher's syndrome (FS), a variant of GBS, is associated with IgG antibody to GQ1b ganglioside. We showed the existence of molecular mimicry between GM1 and lipopolysaccharide (LPS) of C. jejuni isolated from a GBS patient, and that between GQ1b and C. jejuni LPSs from FS patients. Several lines of evidence suggest a pathogenic role for anti-ganglioside antibodies. Some patients developed sensorimotor polyneuropathy after anti-GD2 antibody administration. Anti-GM1 antibody can block motor nerve conduction. The molecular mimicry between infectious agents and gangliosides may function in the production of anti-ganglioside antibodies and the development of GBS and FS. Anti-GQ1b IgG antibody is detected also in Bickerstaff's brainstem encephalitis and acute ophthalmoparesis, which suggests that these conditions are categorized as autoimmune diseases related to FS. Since a tryptophan-immobilized column effectively adsorb anti-GQ1b IgG antibody, immunoadsorption with the column should be considered as an alternative form of plasmapheresis for the anti-GQ1b IgG antibody syndrome.     

Ganglioside mimicry as a cause of Guillain-Barré syndrome

Guillain-Barré syndrome (GBS), characterized by acute progressive limb weakness and areflexia, is the prototype of postinfectious autoimmune diseases. Campylobacter jejuni is the most frequently identified agent of infection in GBS patients, often preceding acute motor axonal neuropathy (AMAN), a variant of GBS. Anti-GM1, anti-GM1b, anti-GD1a, and anti-GalNAc-GD1a IgG antibodies are associated with AMAN. Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] was seen between the lipo-oligosaccharide of C. jejuni isolated from an AMAN patient and human GM1 ganglioside. Sensitization with the lipo-oligosaccharide of C. jejuni induces AMAN in rabbits as does sensitization with GM1 ganglioside. Paralyzed rabbits have pathological changes in their peripheral nerves identical to changes seen in human GBS. C. jejuni infection may induce anti-ganglioside antibodies by molecular mimicry, eliciting AMAN. This is the first verification of the causative mechanism of molecular mimicry in an autoimmune disease. To express ganglioside mimics, C. jejuni requires specific gene combinations that function in sialic acid biosynthesis or transfer. The knockout mutants of these landmark genes of GBS show reduced reactivity with GBS patients' sera, and fail to induce an anti-ganglioside antibody response in mice. These genes are crucial for the induction of neuropathogenic cross-reactive antibodies. An approach for evaluating intravenous immune globulin, a treatment for GBS, based on our animal model of AMAN is also discussed in this review, and recent advances made in this field are described.     

Rapidly progressive, predominantly motor Guillain-Barré syndrome with anti-GalNAc-GD1a antibodies

OBJECTIVE: To investigate the presence of anti-GalNAc-GD1a antibodies in patients with Guillain-Barré syndrome (GBS) and to determine the relation of anti-ganglioside antibodies with clinical features. BACKGROUND: The GBS is heterogeneous with regard to clinical manifestations, antecedent infections, and the presence and specificity of anti-ganglioside antibodies. Recently, antibodies to minor gangliosides have been identified in serum from GBS patients. METHODS: The authors used ELISA to detect anti-ganglioside antibodies in 132 GBS patients and then correlated results with a database containing information on antecedent infections and clinical parameters. RESULTS: Anti-GalNAc-GD1a antibodies could be detected in 19 (14%) GBS patients. The presence of anti-GalNAc-GD1a antibodies was related to antecedent Campylobacter jejuni infection (p<0.001). GBS patients with anti-GalNAc-GD1a antibodies had a rapidly progressive, more severe, and predominantly distal weakness. Furthermore, they had less sensory loss, paresthesia, and cranial nerve involvement. In most patients, this reactivity was independent of reactivity to GM1. Dividing patients into separate groups based on their reactivity to GalNAc-GD1a and GM1 enabled the authors to delineate more homogeneous subgroups with regard to clinical features. CONCLUSIONS: This study provides further evidence for the hypothesis that antecedent infections and the specificity of subsequent anti-neural antibody responses determine the clinical manifestations in GBS patients.     

Clinical phenotype of patients with neuropathy associated with monoclonal gammopathy: a comparative study and a review of the literature

The objective of this study was to investigate if the clinical and electrophysiological phenotype of patients with polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is related to the presence of antibodies against gangliosides or myelin-associated glycoprotein (MAG). We compared clinical and nerve conduction study (NCS) characteristics of 11 IgM-PNP patients with antibodies against asialo-GM1 or gangliosides (GM1, GD1a, GD1b, GM2 or GQ1b) to 11 consecutive IgM-PNP patients with anti-MAG neuropathy and to 9 IgM-PNP patients without antibodies against either MAG or gangliosides. Patients with anti-ganglioside antibodies could not be differentiated from those with anti-MAG antibodies based on clinical characteristics. However, within the group of anti-ganglioside antibody positive patients, antibodies against GD1b and GQ1b were associated with a purely sensory neuropathy (p = 0.002), while asymmetric weakness with symmetric sensory loss was associated with anti-asialo-GM1 antibodies. In conclusion, polyneuropathy associated with IgM monoclonal gammopathy and anti-ganglioside antibodies clinically resembles anti-MAG neuropathy. Pure sensory neuropathy and marked asymmetry may suggest the presence of anti-ganglioside rather than anti-MAG antibodies.     

Motor nerve damage is associated with anti-ganglioside antibodies in diabetes

Few reports exist on the association between the humoral immune response to glycolipids and neuropathic findings in diabetes. To address this issue, we assayed serum anti-GM1, GD1b, GD1a, and sulfatides IgG and IgM in a group of 85 non-selected diabetic patients, and correlated these antibodies to clinical and electrophysiological findings. Diabetic patients had higher mean titers of anti-GM1 (IgM), GD1b, GD1a, and sulfatide (IgG) antibodies when compared to healthy controls. Patients with a positive titer of anti-ganglioside antibodies had significant alterations of motor conduction parameters. The statistical significance increased when considering those patients with both anti-ganglioside reactivity and a high value for glycosylated hemoglobin. Production of antibodies to ganglioside may follow the exposure of hidden motor nerve epitopes in damaged motor nerves and contribute to the neuropathy.     

Nationwide survey of childhood Guillain-Barré syndrome,Fisher syndrome,and Bickerstaff brainstem encephalitis in Japan

ObjectiveGuillain-Barré syndrome (GBS), Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE) are immune-mediated neuropathies presenting with symptoms such as weakness, ophthalmoplegia, ataxia, and consciousness disturbances. Although the epidemiology of GBS and BBE in patients of all ages has been reported, childhood data have not been well-investigated. We aimed to determine the clinical features, therapeutics, and prognoses of childhood GBS, FS, and BBE in Japan.MethodsWe sent questionnaires to 1068 pediatric neurologists in Japan from 2014 to 2016 to determine the number of children less than 15 years old with GBS, FS, or BBE and their age and sex. We subsequently performed a secondary survey to investigate the clinical features, laboratory data, treatment, and prognosis.ResultsFive-hundred thirty-eight pediatric neurology specialists (50.4%) responded to the first survey. The total number of children with GBS, FS, and BBE in Japan from 2014 to 2016 were 87, 10, and 6, respectively. GBS was classified as acute inflammatory demyelinating neuropathy (35.6%), acute motor axonal neuropathy (20.7%), or acute motor-sensory axonal neuropathy (10.3%), with a male-to-female ratio of 1.29:1.0 and a wide distribution of onset ages. The disease severities of GBS, FS, and BBE were variable, but all children could walk within one year.ConclusionThe prognoses of childhood GBS, FS, and BBE were generally favorable, as long as the patient was promptly treated with either intravenous immunoglobulin or plasma exchange.     

Anti-ganglioside antibodies alter presynaptic release and calcium influx

Acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome is often associated with IgG anti-GM1 and -GD1a antibodies. The pathophysiological basis of antibody-mediated selective motor nerve dysfunction remains unclear. We investigated the effects of IgG anti-GM1 and -GD1a monoclonal antibodies (mAbs) on neuromuscular transmission and calcium influx in hemidiaphragm preparations and in cultured neurons, respectively, to elucidate mechanisms of Ab-mediated muscle weakness. Anti-GM1 and -GD1a mAbs depressed evoked quantal release to a significant yet different extent, without affecting postsynaptic currents. At equivalent concentrations, anti-GD1b, -GT1b, or sham mAbs did not affect neuromuscular transmission. At fourfold higher concentration, an anti-GD1b mAb (specificity described in immune sensory neuropathies) induced completely reversible blockade. In neuronal cultures, anti-GM1 and -GD1a mAbs significantly reduced depolarization-induced calcium influx. In conclusion, different anti-ganglioside mAbs induce distinct effects on presynaptic transmitter release by reducing calcium influx, suggesting that this is one mechanism of antibody-mediated muscle weakness in AMAN.     

A case of anti-GM1 antibody positive HTLV-I associated myelopathy (HAM) with polyneuropathy]

We report a case of HTLV-I associated myelopathy (HAM) with polyneuropathy. A 59-year old man suffering from progressive paraparesis associated with subclinical polyneuropathy was admitted to our hospital. HTLV-I antibodies in the serum and CSF were positive, and a diagnosis of HAM was made. His laboratory investigation revealed elevated serum IgG and IgM anti GM-1 antibodies. The nerve conduction study showed a mild reduction in motor and sensory conduction velocity in all extremities. A sural nerve biopsy revealed active demyelination and globule-like changes, which are specific for HAM neuropathy. Anti-GM1 antibodies are frequently present in autoimmune motor neuropathy. They are thought to inflict a damage on both the myelin and axons of the peripheral nerves. Ours is believed to be the first case of HAM associated with anti-GM1 antibodies, although polyneuropathy is often associated with HAM. While it is not clear whether the lesion observed in HAM neuropathy results from the direct cytopathic effect of the virus or from the immune response, some immune-mediated reactions are thought to play an important role. This case suggests that a case of HAM with polyneuropathy should be examined for the presence of the anti-ganglioside antibodies. More investigations are needed to fully understand the mechanism of the HAM neuropathy.