g(m2)-ganglioside and Motor-Neuron-Disease

The authors describe the clinical phenotypes of hexosaminidase deficiencies (GM2 gangliosidosis). The symptoms, differently combined, include cerebellar ataxia, motor neuron disease, dystonia, psychosis, neurovegetative troubles with different severity. Morphological changes are evident in rectal, muscle or nerve biopsies. Minor clinical changes are described in carriers from a family. A chronic GM2 gangliosidosis has to be suspected in any atypical case with the above-mentioned symptoms with autosomal-recessive inheritance.

Topics: Adolescent; Adult; beta-N-Acetylhexosaminidases; Biopsy; Cerebellar Ataxia; Child; Diagnosis, Differential; Dystonia; Electrodiagnosis; G(M2) Ganglioside; Gangliosidoses; Genes, Recessive; Genetic Carrier Screening; Humans; Motor Neuron Disease; Neurocognitive Disorders; Pedigree; Phenotype; Radiography; Sandhoff Disease; Tay-Sachs Disease

to explore the experiences of people with Motor Neurone Disease (MND), current and bereaved carers in the final stages of the disease and bereavement period.. a qualitative study using narrative interviews was used to elicit accounts from 24 people with MND and 18 current family carers and 10 former family carers.. the needs of patients and carers are not being adequately met in the final stages of MND and there appears a need for increased, co-ordinated support from palliative care services. The use of advance care planning tools is regarded as beneficial for patients and carers, but health professionals demonstrate a limited understanding of them. Anxiety and distress in patients, carers and bereaved carers is heightened during this period. Carer burden is excessive and may exacerbate patient distress and desire for hastening death.. this study has identified a number of issues people with MND and their carers face in the final stages of the illness, indicating some ways in which health, social and palliative care services could be improved or co-operate more effectively in order to better meet their needs.

Topics: Adult; Advance Care Planning; Aged; Aged, 80 and over; Attitude to Death; Bereavement; Caregivers; Cost of Illness; Delivery of Health Care, Integrated; Euthanasia; Female; G(M2) Ganglioside; Health Services Needs and Demand; Humans; Male; Middle Aged; Motor Neuron Disease; Patient Education as Topic; Qualitative Research; Stress, Psychological; Terminal Care

Anti-GM2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome. To determine whether these antibodies can induce complement-dependent cytolysis we performed a cytotoxicity assay on neuroblastoma cells with sera from seven patients with demyelinating dysimmune neuropathies and high titers of anti-GM2 IgM. As controls we used sera from seven patients with other anti-neural reactivities, six with the same neuropathies but no anti-GM2 or other anti-neural reactivity and from eight normal subjects. Of the seven positive sera tested, six induced complement-mediated cytotoxicity, while none of the controls had any relevant effect on neuroblastoma cells. Preincubation of positive sera with purified GM2 removed cytotoxic activity. Affinity purified anti-GM2 IgM had the same cytotoxic anti-GM2 effect of whole serum while serum or complement alone did not have any effect. In four anti-GM2-positive patients the percentage of cell lysis correlated with anti-GM2 titers and with IgM staining of neuroblastoma cells while in two the cytotoxic effect was higher than expected from antibody titers. Complement-mediated cell lysis induced by anti-GM2 IgM antibodies may be a possible mechanism of neural damage in patients with dysimmune neuropathy and high titers of anti-GM2 IgM antibodies.

Topics: Chromatography, Affinity; Complement Activation; G(M2) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin M; Motor Neuron Disease; Neuroblastoma; Tumor Cells, Cultured

GM2 ganglioside is a potential peripheral nerve antigen for neuropathy-associated autoantibodies. However little data are available on their pathogenic effects, if any. In this study we have screened both neuropathy-associated and control sera for anti-GM2 antibodies and subsequently used high titre sera for immunohistological and complement mediated cytotoxicity studies. We identified abnormally elevated anti-GM2 antisera in the normal population, as well as in patients with peripheral neuropathies and other neurological diseases. GM2 antibodies were either mono-reactive, cross-reactive with GM1a, or cross-reactive with GalNAc-GM1b and/or GalNAc-GD1a. All GM2 antisera from neuropathy subjects and normal controls bound to, and were capable of complement-mediated lysis of the NSC-34 cell line which expresses high levels of membrane-associated GM2. However, in immunohistological studies on human and rodent peripheral nervous system tissues, no specific binding was seen with GM2 antisera, either cross-reactive with GalNAc-GM1b and GalNAc-GDla, or with GM1a. These data indicate that although GM2 antisera can lyse neural membranes containing GM2, this antigen(s) is not detectable by standard immunohistological techniques in human or rodent peripheral nerve. This raises doubts about their pathophysiological significance in human autoimmune neuropathy.

Topics: Adolescent; Adult; Amyotrophic Lateral Sclerosis; Autoantibodies; Case-Control Studies; Cell Line; Cross Reactions; Cytotoxicity, Immunologic; G(M2) Ganglioside; Guillain-Barre Syndrome; Humans; Immunohistochemistry; Middle Aged; Motor Neuron Disease; Peripheral Nervous System Diseases

Anti-GM2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome, in whom they were often associated with a concomitant reactivity with GM1. To investigate the possible clinical and pathogenetic relevance of these antibodies we measured serum anti-GM2 IgM titers by ELISA in 224 patients with different neuropathies and motor neuron disease and examined their binding to SK-N-SH neuroblastoma cells by indirect immunofluorescence (IIF). High titers of anti-GM2 IgM antibodies were found in eight patients with dysimmune neuropathies including two with multifocal motor neuropathy (MMN), two with purely motor demyelinating neuropathy without conduction block (MN) and four with Guillain-Barré syndrome (GBS). In two MMN patients reactivity with GM2 was associated with anti-GM1 reactivity and in one MN patient with anti-GM1, -GD1a and -GD1b reactivity. All but one patient had a concomitant reactivity with GalNAc-GD1a. Serum IgM from all positive patients intensely stained by IIF the surface of SK-N-SH neuroblastoma cells. This reactivity was blocked by serum pre-incubation with GM2, was not observed with sera from patients without anti-GM2 antibodies including those with high anti-GM1 or other anti-glycolipid antibodies, and correlated with the presence of GM2 in the SK-N-SH neuroblastoma cells. These findings indicate that anti-GM2 antibodies, though infrequent, are strictly associated with dysimmune neuropathies and suggest that SK-N-SH neuroblastoma cells can be a suitable in vitro model to study the functional and biological effects of these antibodies.

Topics: Adolescent; Adult; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; G(M2) Ganglioside; Humans; Immunoblotting; Immunoglobulin M; Male; Middle Aged; Motor Neuron Disease; Myelin Sheath; Neuroblastoma; Polyradiculoneuropathy; Sural Nerve; Tumor Cells, Cultured

An 11-year-old girl died of a neuronal storage disorder that clinically was characterized by failure to thrive and muscular hypotonia from birth, with the subsequent evolution of motor neuron disease, epilepsy, and dementia. A wide range of metabolic disorders, including all forms of GM2 gangliosidosis, could be excluded. Electron microscopy demonstrated neuronal zebra body inclusions, and immunohistochemistry demonstrated that GM2 ganglioside was a major constituent of the storage material. We suggest that the patient died of a lysosomal storage disease that is clinically and biochemically different from Tay-Sachs disease, Sandhoff disease, and other GM2 gangliosidoses described previously. This case also further demonstrates that significant accumulation of GM2 ganglioside, which is crucial for dendritic formation, may occur in neuronal storage diseases lacking known defects in ganglioside catabolism.

Topics: Child; Dementia; Epilepsy, Tonic-Clonic; Failure to Thrive; Female; G(M2) Ganglioside; Humans; Immunohistochemistry; Lysosomal Storage Diseases; Microscopy, Electron; Motor Neuron Disease; Muscle Hypotonia

We describe the first two European cases of acute axonal motor neuropathy with both IgG and IgA anti-GD1a antibodies following Campylobacter enteritis. Both patients acutely developed severe weakness without sensory involvement, had antibodies to Campylobacter jejuni and polyclonal IgG and IgA titers > or = 12,800 to GD1a at onset, which decreased during follow-up. Serial electrophysiologic studies showed: 1, normal or only slightly slowed motor conductions; 2, evidence of a progressive loss of excitability and conduction failure in nerve fibers undergoing axonal degeneration in intermediate nerve segments and evidence of distal axonal involvement in one nerve; 3, normal sensory conductions, sensory potential amplitudes and somatosensory evoked potentials. Although we cannot exclude that axonal degeneration followed demyelination, we think that anti-GD1a antibodies account for the axonal involvement because GD1a is present in the axolemma and exposed at the node of Ranvier and in nerve terminals. The exclusive motor involvement could be explained by the fact that GD1a has a different internal structure in motor and sensory fibers.

Topics: Adult; Aged; Antibodies, Bacterial; Autoantibodies; Axons; Campylobacter Infections; Campylobacter jejuni; Europe; Evoked Potentials, Motor; Evoked Potentials, Somatosensory; Female; G(M1) Ganglioside; G(M2) Ganglioside; Gangliosides; Humans; Immunoglobulin A; Immunoglobulin G; Male; Median Nerve; Motor Neuron Disease; Neural Conduction; Polyradiculoneuropathy; Ulnar Nerve